what type of methodology is a literature review

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Types of Literature Review — A Guide for Researchers

Table of Contents

Researchers often face challenges when choosing the appropriate type of literature review for their study. Regardless of the type of research design and the topic of a research problem , they encounter numerous queries, including:

What is the right type of literature review my study demands?

• How do we gather the data?
• How to conduct one?
• How reliable are the review findings?
• How do we employ them in our research? And the list goes on.

If you’re also dealing with such a hefty questionnaire, this article is of help. Read through this piece of guide to get an exhaustive understanding of the different types of literature reviews and their step-by-step methodologies along with a dash of pros and cons discussed.

Heading from scratch!

What is a Literature Review?

A literature review provides a comprehensive overview of existing knowledge on a particular topic, which is quintessential to any research project. Researchers employ various literature reviews based on their research goals and methodologies. The review process involves assembling, critically evaluating, and synthesizing existing scientific publications relevant to the research question at hand. It serves multiple purposes, including identifying gaps in existing literature, providing theoretical background, and supporting the rationale for a research study.

What is the importance of a Literature review in research?

Literature review in research serves several key purposes, including:

• Background of the study: Provides proper context for the research. It helps researchers understand the historical development, theoretical perspectives, and key debates related to their research topic.
• Identification of research gaps: By reviewing existing literature, researchers can identify gaps or inconsistencies in knowledge, paving the way for new research questions and hypotheses relevant to their study.
• Theoretical framework development: Facilitates the development of theoretical frameworks by cultivating diverse perspectives and empirical findings. It helps researchers refine their conceptualizations and theoretical models.
• Methodological guidance: Offers methodological guidance by highlighting the documented research methods and techniques used in previous studies. It assists researchers in selecting appropriate research designs, data collection methods, and analytical tools.
• Quality assurance and upholding academic integrity: Conducting a thorough literature review demonstrates the rigor and scholarly integrity of the research. It ensures that researchers are aware of relevant studies and can accurately attribute ideas and findings to their original sources.

Types of Literature Review

Literature review plays a crucial role in guiding the research process , from providing the background of the study to research dissemination and contributing to the synthesis of the latest theoretical literature review findings in academia.

However, not all types of literature reviews are the same; they vary in terms of methodology, approach, and purpose. Let's have a look at the various types of literature reviews to gain a deeper understanding of their applications.

1. Narrative Literature Review

A narrative literature review, also known as a traditional literature review, involves analyzing and summarizing existing literature without adhering to a structured methodology. It typically provides a descriptive overview of key concepts, theories, and relevant findings of the research topic.

Unlike other types of literature reviews, narrative reviews reinforce a more traditional approach, emphasizing the interpretation and discussion of the research findings rather than strict adherence to methodological review criteria. It helps researchers explore diverse perspectives and insights based on the research topic and acts as preliminary work for further investigation.

Steps to Conduct a Narrative Literature Review

Source:- https://www.researchgate.net/figure/Steps-of-writing-a-narrative-review_fig1_354466408

Define the research question or topic:

The first step in conducting a narrative literature review is to clearly define the research question or topic of interest. Defining the scope and purpose of the review includes — What specific aspect of the topic do you want to explore? What are the main objectives of the research? Refine your research question based on the specific area you want to explore.

Conduct a thorough literature search

Once the research question is defined, you can conduct a comprehensive literature search. Explore and use relevant databases and search engines like SciSpace Discover to identify credible and pertinent, scholarly articles and publications.

Select relevant studies

Before choosing the right set of studies, it’s vital to determine inclusion (studies that should possess the required factors) and exclusion criteria for the literature and then carefully select papers. For example — Which studies or sources will be included based on relevance, quality, and publication date?

*Important (applies to all the reviews): Inclusion criteria are the factors a study must include (For example: Include only peer-reviewed articles published between 2022-2023, etc.). Exclusion criteria are the factors that wouldn’t be required for your search strategy (Example: exclude irrelevant papers, preprints, written in non-English, etc.)

Critically analyze the literature

Once the relevant studies are shortlisted, evaluate the methodology, findings, and limitations of each source and jot down key themes, patterns, and contradictions. You can use efficient AI tools to conduct a thorough literature review and analyze all the required information.

Synthesize and integrate the findings

Now, you can weave together the reviewed studies, underscoring significant findings such that new frameworks, contrasting viewpoints, and identifying knowledge gaps.

Discussion and conclusion

This is an important step before crafting a narrative review — summarize the main findings of the review and discuss their implications in the relevant field. For example — What are the practical implications for practitioners? What are the directions for future research for them?

Write a cohesive narrative review

Organize the review into coherent sections and structure your review logically, guiding the reader through the research landscape and offering valuable insights. Use clear and concise language to convey key points effectively.

Structure of Narrative Literature Review

A well-structured, narrative analysis or literature review typically includes the following components:

• Introduction: Provides an overview of the topic, objectives of the study, and rationale for the review.
• Background: Highlights relevant background information and establish the context for the review.
• Main Body: Indexes the literature into thematic sections or categories, discussing key findings, methodologies, and theoretical frameworks.
• Discussion: Analyze and synthesize the findings of the reviewed studies, stressing similarities, differences, and any gaps in the literature.
• Conclusion: Summarizes the main findings of the review, identifies implications for future research, and offers concluding remarks.

Pros and Cons of Narrative Literature Review

• Flexibility in methodology and doesn’t necessarily rely on structured methodologies
• Follows traditional approach and provides valuable and contextualized insights
• Suitable for exploring complex or interdisciplinary topics. For example — Climate change and human health, Cybersecurity and privacy in the digital age, and more
• Subjectivity in data selection and interpretation
• Potential for bias in the review process
• Lack of rigor compared to systematic reviews

Example of Well-Executed Narrative Literature Reviews

Paper title:  Examining Moral Injury in Clinical Practice: A Narrative Literature Review

Source: SciSpace

While narrative reviews offer flexibility, academic integrity remains paramount. So, ensure proper citation of all sources and maintain a transparent and factual approach throughout your critical narrative review, itself.

2. Systematic Review

A systematic literature review is one of the comprehensive types of literature review that follows a structured approach to assembling, analyzing, and synthesizing existing research relevant to a particular topic or question. It involves clearly defined criteria for exploring and choosing studies, as well as rigorous methods for evaluating the quality of relevant studies.

It plays a prominent role in evidence-based practice and decision-making across various domains, including healthcare, social sciences, education, health sciences, and more. By systematically investigating available literature, researchers can identify gaps in knowledge, evaluate the strength of evidence, and report future research directions.

Steps to Conduct Systematic Reviews

Source:- https://www.researchgate.net/figure/Steps-of-Systematic-Literature-Review_fig1_321422320

Here are the key steps involved in conducting a systematic literature review

Formulate a clear and focused research question

Clearly define the research question or objective of the review. It helps to centralize the literature search strategy and determine inclusion criteria for relevant studies.

Develop a thorough literature search strategy

Design a comprehensive search strategy to identify relevant studies. It involves scrutinizing scientific databases and all relevant articles in journals. Plus, seek suggestions from domain experts and review reference lists of relevant review articles.

Screening and selecting studies

Employ predefined inclusion and exclusion criteria to systematically screen the identified studies. This screening process also typically involves multiple reviewers independently assessing the eligibility of each study.

Data extraction

Extract key information from selected studies using standardized forms or protocols. It includes study characteristics, methods, results, and conclusions.

Critical appraisal

Evaluate the methodological quality and potential biases of included studies. Various tools (BMC medical research methodology) and criteria can be implemented for critical evaluation depending on the study design and research quetions .

Data synthesis

Analyze and synthesize review findings from individual studies to draw encompassing conclusions or identify overarching patterns and explore heterogeneity among studies.

Interpretation and conclusion

Interpret the findings about the research question, considering the strengths and limitations of the research evidence. Draw conclusions and implications for further research.

The final step — Report writing

Craft a detailed report of the systematic literature review adhering to the established guidelines of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). This ensures transparency and reproducibility of the review process.

By following these steps, a systematic literature review aims to provide a comprehensive and unbiased summary of existing evidence, help make informed decisions, and advance knowledge in the respective domain or field.

Structure of a systematic literature review

A well-structured systematic literature review typically consists of the following sections:

• Introduction: Provides background information on the research topic, outlines the review objectives, and enunciates the scope of the study.
• Methodology: Describes the literature search strategy, selection criteria, data extraction process, and other methods used for data synthesis, extraction, or other data analysis..
• Results: Presents the review findings, including a summary of the incorporated studies and their key findings.
• Discussion: Interprets the findings in light of the review objectives, discusses their implications, and identifies limitations or promising areas for future research.
• Conclusion: Summarizes the main review findings and provides suggestions based on the evidence presented in depth meta analysis.

*Important (applies to all the reviews): Remember, the specific structure of your literature review may vary depending on your topic, research question, and intended audience. However, adhering to a clear and logical hierarchy ensures your review effectively analyses and synthesizes knowledge and contributes valuable insights for readers.

Pros and Cons of Systematic Literature Review

• Adopts rigorous and transparent methodology
• Minimizes bias and enhances the reliability of the study
• Provides evidence-based insights
• Time and resource-intensive
• High dependency on the quality of available literature (literature research strategy should be accurate)
• Potential for publication bias

Example of Well-Executed Systematic Literature Review

Paper title: Systematic Reviews: Understanding the Best Evidence For Clinical Decision-making in Health Care: Pros and Cons.

Read this detailed article on how to use AI tools to conduct a systematic review for your research!

3. Scoping Literature Review

A scoping literature review is a methodological review type of literature review that adopts an iterative approach to systematically map the existing literature on a particular topic or research area. It involves identifying, selecting, and synthesizing relevant papers to provide an overview of the size and scope of available evidence. Scoping reviews are broader in scope and include a diverse range of study designs and methodologies especially focused on health services research.

The main purpose of a scoping literature review is to examine the extent, range, and nature of existing studies on a topic, thereby identifying gaps in research, inconsistencies, and areas for further investigation. Additionally, scoping reviews can help researchers identify suitable methodologies and formulate clinical recommendations. They also act as the frameworks for future systematic reviews or primary research studies.

Scoping reviews are primarily focused on —

• Emerging or evolving topics — where the research landscape is still growing or budding. Example — Whole Systems Approaches to Diet and Healthy Weight: A Scoping Review of Reviews .
• Broad and complex topics : With a vast amount of existing literature.
• Scenarios where a systematic review is not feasible: Due to limited resources or time constraints.

Steps to Conduct a Scoping Literature Review

While Scoping reviews are not as rigorous as systematic reviews, however, they still follow a structured approach. Here are the steps:

Identify the research question: Define the broad topic you want to explore.

Identify Relevant Studies: Conduct a comprehensive search of relevant literature using appropriate databases, keywords, and search strategies.

Select studies to be included in the review: Based on the inclusion and exclusion criteria, determine the appropriate studies to be included in the review.

Data extraction and charting : Extract relevant information from selected studies, such as year, author, main results, study characteristics, key findings, and methodological approaches.  However, it varies depending on the research question.

Collate, summarize, and report the results: Analyze and summarize the extracted data to identify key themes and trends. Then, present the findings of the scoping review in a clear and structured manner, following established guidelines and frameworks .

Structure of a Scoping Literature Review

A scoping literature review typically follows a structured format similar to a systematic review. It includes the following sections:

• Introduction: Introduce the research topic and objectives of the review, providing the historical context, and rationale for the study.
• Methods : Describe the methods used to conduct the review, including search strategies, study selection criteria, and data extraction procedures.
• Results: Present the findings of the review, including key themes, concepts, and patterns identified in the literature review.
• Discussion: Examine the implications of the findings, including strengths, limitations, and areas for further examination.
• Conclusion: Recapitulate the main findings of the review and their implications for future research, policy, or practice.

Pros and Cons of Scoping Literature Review

• Provides a comprehensive overview of existing literature
• Helps to identify gaps and areas for further research
• Suitable for exploring broad or complex research questions
• Doesn’t provide the depth of analysis offered by systematic reviews
• Subject to researcher bias in study selection and data extraction
• Requires careful consideration of literature search strategies and inclusion criteria to ensure comprehensiveness and validity.

In short, a scoping review helps map the literature on developing or emerging topics and identifying gaps. It might be considered as a step before conducting another type of review, such as a systematic review. Basically, acts as a precursor for other literature reviews.

Example of a Well-Executed Scoping Literature Review

Paper title: Health Chatbots in Africa Literature: A Scoping Review

Check out the key differences between Systematic and Scoping reviews — Evaluating literature review: systematic vs. scoping reviews

4. Integrative Literature Review

Integrative Literature Review (ILR) is a type of literature review that proposes a distinctive way to analyze and synthesize existing literature on a specific topic, providing a thorough understanding of research and identifying potential gaps for future research.

Unlike a systematic review, which emphasizes quantitative studies and follows strict inclusion criteria, an ILR embraces a more pliable approach. It works beyond simply summarizing findings — it critically analyzes, integrates, and interprets research from various methodologies (qualitative, quantitative, mixed methods) to provide a deeper understanding of the research landscape. ILRs provide a holistic and systematic overview of existing research, integrating findings from various methodologies. ILRs are ideal for exploring intricate research issues, examining manifold perspectives, and developing new research questions.

Steps to Conduct an Integrative Literature Review

• Identify the research question: Clearly define the research question or topic of interest as formulating a clear and focused research question is critical to leading the entire review process.
• Literature search strategy: Employ systematic search techniques to locate relevant literature across various databases and sources.
• Evaluate the quality of the included studies : Critically assess the methodology, rigor, and validity of each study by applying inclusion and exclusion criteria to filter and select studies aligned with the research objectives.
• Data Extraction: Extract relevant data from selected studies using a structured approach.
• Synthesize the findings : Thoroughly analyze the selected literature, identify key themes, and synthesize findings to derive noteworthy insights.
• Critical appraisal: Critically evaluate the quality and validity of qualitative research and included studies by using BMC medical research methodology.
• Interpret and present your findings: Discuss the purpose and implications of your analysis, spotlighting key insights and limitations. Organize and present the findings coherently and systematically.

Structure of an Integrative Literature Review

• Introduction : Provide an overview of the research topic and the purpose of the integrative review.
• Methods: Describe the opted literature search strategy, selection criteria, and data extraction process.
• Results: Present the synthesized findings, including key themes, patterns, and contradictions.
• Discussion: Interpret the findings about the research question, emphasizing implications for theory, practice, and prospective research.
• Conclusion: Summarize the main findings, limitations, and contributions of the integrative review.

Pros and Cons of Integrative Literature Review

• Informs evidence-based practice and policy to the relevant stakeholders of the research.
• Contributes to theory development and methodological advancement, especially in the healthcare arena.
• Integrates diverse perspectives and findings
• Time-consuming process due to the extensive literature search and synthesis
• Requires advanced analytical and critical thinking skills
• Potential for bias in study selection and interpretation
• The quality of included studies may vary, affecting the validity of the review

Example of Integrative Literature Reviews

Paper Title: An Integrative Literature Review: The Dual Impact of Technological Tools on Health and Technostress Among Older Workers

5. Rapid Literature Review

A Rapid Literature Review (RLR) is the fastest type of literature review which makes use of a streamlined approach for synthesizing literature summaries, offering a quicker and more focused alternative to traditional systematic reviews. Despite employing identical research methods, it often simplifies or omits specific steps to expedite the process. It allows researchers to gain valuable insights into current research trends and identify key findings within a shorter timeframe, often ranging from a few days to a few weeks — unlike traditional literature reviews, which may take months or even years to complete.

When to Consider a Rapid Literature Review?

• When time impediments demand a swift summary of existing research
• For emerging topics where the latest literature requires quick evaluation
• To report pilot studies or preliminary research before embarking on a comprehensive systematic review

Steps to Conduct a Rapid Literature Review

• Define the research question or topic of interest. A well-defined question guides the search process and helps researchers focus on relevant studies.
• Determine key databases and sources of relevant literature to ensure comprehensive coverage.
• Develop literature search strategies using appropriate keywords and filters to fetch a pool of potential scientific articles.
• Screen search results based on predefined inclusion and exclusion criteria.
• Extract and summarize relevant information from the above-preferred studies.
• Synthesize findings to identify key themes, patterns, or gaps in the literature.
• Prepare a concise report or a summary of the RLR findings.

Structure of a Rapid Literature Review

An effective structure of an RLR typically includes the following sections:

• Introduction: Briefly introduce the research topic and objectives of the RLR.
• Methodology: Describe the search strategy, inclusion and exclusion criteria, and data extraction process.
• Results: Present a summary of the findings, including key themes or patterns identified.
• Discussion: Interpret the findings, discuss implications, and highlight any limitations or areas for further research
• Conclusion: Summarize the key findings and their implications for practice or future research

Pros and Cons of Rapid Literature Review

• RLRs can be completed quickly, authorizing timely decision-making
• RLRs are a cost-effective approach since they require fewer resources compared to traditional literature reviews
• Offers great accessibility as RLRs provide prompt access to synthesized evidence for stakeholders
• RLRs are flexible as they can be easily adapted for various research contexts and objectives
• RLR reports are limited and restricted, not as in-depth as systematic reviews, and do not provide comprehensive coverage of the literature compared to traditional reviews.
• Susceptible to bias because of the expedited nature of RLRs. It would increase the chance of overlooking relevant studies or biases in the selection process.
• Due to time constraints, RLR findings might not be robust enough as compared to systematic reviews.

Example of a Well-Executed Rapid Literature Review

Paper Title: What Is the Impact of ChatGPT on Education? A Rapid Review of the Literature

A Summary of Literature Review Types

Tools and Resources for Conducting Different Types of Literature Reviews

Online scientific databases.

Platforms such as SciSpace , PubMed , Scopus , Elsevier , and Web of Science provide access to a vast array of scholarly literature, facilitating the search and data retrieval process.

Reference management software

Tools like SciSpace Citation Generator , EndNote, Zotero , and Mendeley assist researchers in organizing, annotating, and citing relevant literature, streamlining the review process altogether.

Automate Literature Review with AI tools

Automate the literature review process by using tools like SciSpace literature review which helps you compare and contrast multiple papers all on one screen in an easy-to-read matrix format. You can effortlessly analyze and interpret the review findings tailored to your study. It also supports the review in 75+ languages, making it more manageable even for non-English speakers.

Goes without saying — literature review plays a pivotal role in academic research to identify the current trends and provide insights to pave the way for future research endeavors. Different types of literature review has their own strengths and limitations, making them suitable for different research designs and contexts. Whether conducting a narrative review, systematic review, scoping review, integrative review, or rapid literature review, researchers must cautiously consider the objectives, resources, and the nature of the research topic.

If you’re currently working on a literature review and still adopting a manual and traditional approach, switch to the automated AI literature review workspace and transform your traditional literature review into a rapid one by extracting all the latest and relevant data for your research!

There you go!

Frequently Asked Questions

Narrative reviews give a general overview of a topic based on the author's knowledge. They may lack clear criteria and can be biased. On the other hand, systematic reviews aim to answer specific research questions by following strict methods. They're thorough but time-consuming.

A systematic review collects and analyzes existing research to provide an overview of a topic, while a meta-analysis statistically combines data from multiple studies to draw conclusions about the overall effect of an intervention or relationship between variables.

A systematic review thoroughly analyzes existing research on a specific topic using strict methods. In contrast, a scoping review offers a broader overview of the literature without evaluating individual studies in depth.

A systematic review thoroughly examines existing research using a rigorous process, while a rapid review provides a quicker summary of evidence, often by simplifying some of the systematic review steps to meet shorter timelines.

A systematic review carefully examines many studies on a single topic using specific guidelines. Conversely, an integrative review blends various types of research to provide a more comprehensive understanding of the topic.

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Types of Literature Review

There are many types of literature review. The choice of a specific type depends on your research approach and design. The following types of literature review are the most popular in business studies:

Narrative literature review , also referred to as traditional literature review, critiques literature and summarizes the body of a literature. Narrative review also draws conclusions about the topic and identifies gaps or inconsistencies in a body of knowledge. You need to have a sufficiently focused research question to conduct a narrative literature review

Systematic literature review requires more rigorous and well-defined approach compared to most other types of literature review. Systematic literature review is comprehensive and details the timeframe within which the literature was selected. Systematic literature review can be divided into two categories: meta-analysis and meta-synthesis.

When you conduct meta-analysis you take findings from several studies on the same subject and analyze these using standardized statistical procedures. In meta-analysis patterns and relationships are detected and conclusions are drawn. Meta-analysis is associated with deductive research approach.

Meta-synthesis, on the other hand, is based on non-statistical techniques. This technique integrates, evaluates and interprets findings of multiple qualitative research studies. Meta-synthesis literature review is conducted usually when following inductive research approach.

Scoping literature review , as implied by its name is used to identify the scope or coverage of a body of literature on a given topic. It has been noted that “scoping reviews are useful for examining emerging evidence when it is still unclear what other, more specific questions can be posed and valuably addressed by a more precise systematic review.” [1] The main difference between systematic and scoping types of literature review is that, systematic literature review is conducted to find answer to more specific research questions, whereas scoping literature review is conducted to explore more general research question.

Argumentative literature review , as the name implies, examines literature selectively in order to support or refute an argument, deeply imbedded assumption, or philosophical problem already established in the literature. It should be noted that a potential for bias is a major shortcoming associated with argumentative literature review.

Integrative literature review reviews , critiques, and synthesizes secondary data about research topic in an integrated way such that new frameworks and perspectives on the topic are generated. If your research does not involve primary data collection and data analysis, then using integrative literature review will be your only option.

Theoretical literature review focuses on a pool of theory that has accumulated in regard to an issue, concept, theory, phenomena. Theoretical literature reviews play an instrumental role in establishing what theories already exist, the relationships between them, to what degree existing theories have been investigated, and to develop new hypotheses to be tested.

At the earlier parts of the literature review chapter, you need to specify the type of your literature review your chose and justify your choice. Your choice of a specific type of literature review should be based upon your research area, research problem and research methods.  Also, you can briefly discuss other most popular types of literature review mentioned above, to illustrate your awareness of them.

[1] Munn, A. et. al. (2018) “Systematic review or scoping review? Guidance for authors when choosing between a systematic or scoping review approach” BMC Medical Research Methodology

  John Dudovskiy

• UConn Library
• Literature Review: The What, Why and How-to Guide
• Introduction

Literature Review: The What, Why and How-to Guide — Introduction

• Getting Started
• How to Pick a Topic
• Strategies to Find Sources
• Evaluating Sources & Lit. Reviews
• Tips for Writing Literature Reviews
• Writing Literature Review: Useful Sites
• Citation Resources
• Other Academic Writings

What are Literature Reviews?

So, what is a literature review? "A literature review is an account of what has been published on a topic by accredited scholars and researchers. In writing the literature review, your purpose is to convey to your reader what knowledge and ideas have been established on a topic, and what their strengths and weaknesses are. As a piece of writing, the literature review must be defined by a guiding concept (e.g., your research objective, the problem or issue you are discussing, or your argumentative thesis). It is not just a descriptive list of the material available, or a set of summaries." Taylor, D.  The literature review: A few tips on conducting it . University of Toronto Health Sciences Writing Centre.

Goals of Literature Reviews

What are the goals of creating a Literature Review?  A literature could be written to accomplish different aims:

• To develop a theory or evaluate an existing theory
• To summarize the historical or existing state of a research topic
• Identify a problem in a field of research 

Baumeister, R. F., & Leary, M. R. (1997). Writing narrative literature reviews .  Review of General Psychology , 1 (3), 311-320.

What kinds of sources require a Literature Review?

• A research paper assigned in a course
• A thesis or dissertation
• A grant proposal
• An article intended for publication in a journal

All these instances require you to collect what has been written about your research topic so that you can demonstrate how your own research sheds new light on the topic.

Types of Literature Reviews

What kinds of literature reviews are written?

Narrative review: The purpose of this type of review is to describe the current state of the research on a specific topic/research and to offer a critical analysis of the literature reviewed. Studies are grouped by research/theoretical categories, and themes and trends, strengths and weakness, and gaps are identified. The review ends with a conclusion section which summarizes the findings regarding the state of the research of the specific study, the gaps identify and if applicable, explains how the author's research will address gaps identify in the review and expand the knowledge on the topic reviewed.

• Example : Predictors and Outcomes of U.S. Quality Maternity Leave: A Review and Conceptual Framework:  10.1177/08948453211037398  

Systematic review : "The authors of a systematic review use a specific procedure to search the research literature, select the studies to include in their review, and critically evaluate the studies they find." (p. 139). Nelson, L. K. (2013). Research in Communication Sciences and Disorders . Plural Publishing.

• Example : The effect of leave policies on increasing fertility: a systematic review:  10.1057/s41599-022-01270-w

Meta-analysis : "Meta-analysis is a method of reviewing research findings in a quantitative fashion by transforming the data from individual studies into what is called an effect size and then pooling and analyzing this information. The basic goal in meta-analysis is to explain why different outcomes have occurred in different studies." (p. 197). Roberts, M. C., & Ilardi, S. S. (2003). Handbook of Research Methods in Clinical Psychology . Blackwell Publishing.

• Example : Employment Instability and Fertility in Europe: A Meta-Analysis:  10.1215/00703370-9164737

Meta-synthesis : "Qualitative meta-synthesis is a type of qualitative study that uses as data the findings from other qualitative studies linked by the same or related topic." (p.312). Zimmer, L. (2006). Qualitative meta-synthesis: A question of dialoguing with texts .  Journal of Advanced Nursing , 53 (3), 311-318.

• Example : Women’s perspectives on career successes and barriers: A qualitative meta-synthesis:  10.1177/05390184221113735

Literature Reviews in the Health Sciences

• UConn Health subject guide on systematic reviews Explanation of the different review types used in health sciences literature as well as tools to help you find the right review type
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Literature Review as a Research Methodology: An overview and guidelines

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Lau F, Kuziemsky C, editors. Handbook of eHealth Evaluation: An Evidence-based Approach [Internet]. Victoria (BC): University of Victoria; 2017 Feb 27.

Handbook of eHealth Evaluation: An Evidence-based Approach [Internet].

Chapter 9 methods for literature reviews.

Guy Paré and Spyros Kitsiou .

9.1. Introduction

Literature reviews play a critical role in scholarship because science remains, first and foremost, a cumulative endeavour ( vom Brocke et al., 2009 ). As in any academic discipline, rigorous knowledge syntheses are becoming indispensable in keeping up with an exponentially growing eHealth literature, assisting practitioners, academics, and graduate students in finding, evaluating, and synthesizing the contents of many empirical and conceptual papers. Among other methods, literature reviews are essential for: (a) identifying what has been written on a subject or topic; (b) determining the extent to which a specific research area reveals any interpretable trends or patterns; (c) aggregating empirical findings related to a narrow research question to support evidence-based practice; (d) generating new frameworks and theories; and (e) identifying topics or questions requiring more investigation ( Paré, Trudel, Jaana, & Kitsiou, 2015 ).

Literature reviews can take two major forms. The most prevalent one is the “literature review” or “background” section within a journal paper or a chapter in a graduate thesis. This section synthesizes the extant literature and usually identifies the gaps in knowledge that the empirical study addresses ( Sylvester, Tate, & Johnstone, 2013 ). It may also provide a theoretical foundation for the proposed study, substantiate the presence of the research problem, justify the research as one that contributes something new to the cumulated knowledge, or validate the methods and approaches for the proposed study ( Hart, 1998 ; Levy & Ellis, 2006 ).

The second form of literature review, which is the focus of this chapter, constitutes an original and valuable work of research in and of itself ( Paré et al., 2015 ). Rather than providing a base for a researcher’s own work, it creates a solid starting point for all members of the community interested in a particular area or topic ( Mulrow, 1987 ). The so-called “review article” is a journal-length paper which has an overarching purpose to synthesize the literature in a field, without collecting or analyzing any primary data ( Green, Johnson, & Adams, 2006 ).

When appropriately conducted, review articles represent powerful information sources for practitioners looking for state-of-the art evidence to guide their decision-making and work practices ( Paré et al., 2015 ). Further, high-quality reviews become frequently cited pieces of work which researchers seek out as a first clear outline of the literature when undertaking empirical studies ( Cooper, 1988 ; Rowe, 2014 ). Scholars who track and gauge the impact of articles have found that review papers are cited and downloaded more often than any other type of published article ( Cronin, Ryan, & Coughlan, 2008 ; Montori, Wilczynski, Morgan, Haynes, & Hedges, 2003 ; Patsopoulos, Analatos, & Ioannidis, 2005 ). The reason for their popularity may be the fact that reading the review enables one to have an overview, if not a detailed knowledge of the area in question, as well as references to the most useful primary sources ( Cronin et al., 2008 ). Although they are not easy to conduct, the commitment to complete a review article provides a tremendous service to one’s academic community ( Paré et al., 2015 ; Petticrew & Roberts, 2006 ). Most, if not all, peer-reviewed journals in the fields of medical informatics publish review articles of some type.

The main objectives of this chapter are fourfold: (a) to provide an overview of the major steps and activities involved in conducting a stand-alone literature review; (b) to describe and contrast the different types of review articles that can contribute to the eHealth knowledge base; (c) to illustrate each review type with one or two examples from the eHealth literature; and (d) to provide a series of recommendations for prospective authors of review articles in this domain.

9.2. Overview of the Literature Review Process and Steps

As explained in Templier and Paré (2015) , there are six generic steps involved in conducting a review article:

• formulating the research question(s) and objective(s),
• searching the extant literature,
• screening for inclusion,
• assessing the quality of primary studies,
• extracting data, and
• analyzing data.

Although these steps are presented here in sequential order, one must keep in mind that the review process can be iterative and that many activities can be initiated during the planning stage and later refined during subsequent phases ( Finfgeld-Connett & Johnson, 2013 ; Kitchenham & Charters, 2007 ).

Formulating the research question(s) and objective(s): As a first step, members of the review team must appropriately justify the need for the review itself ( Petticrew & Roberts, 2006 ), identify the review’s main objective(s) ( Okoli & Schabram, 2010 ), and define the concepts or variables at the heart of their synthesis ( Cooper & Hedges, 2009 ; Webster & Watson, 2002 ). Importantly, they also need to articulate the research question(s) they propose to investigate ( Kitchenham & Charters, 2007 ). In this regard, we concur with Jesson, Matheson, and Lacey (2011) that clearly articulated research questions are key ingredients that guide the entire review methodology; they underscore the type of information that is needed, inform the search for and selection of relevant literature, and guide or orient the subsequent analysis. Searching the extant literature: The next step consists of searching the literature and making decisions about the suitability of material to be considered in the review ( Cooper, 1988 ). There exist three main coverage strategies. First, exhaustive coverage means an effort is made to be as comprehensive as possible in order to ensure that all relevant studies, published and unpublished, are included in the review and, thus, conclusions are based on this all-inclusive knowledge base. The second type of coverage consists of presenting materials that are representative of most other works in a given field or area. Often authors who adopt this strategy will search for relevant articles in a small number of top-tier journals in a field ( Paré et al., 2015 ). In the third strategy, the review team concentrates on prior works that have been central or pivotal to a particular topic. This may include empirical studies or conceptual papers that initiated a line of investigation, changed how problems or questions were framed, introduced new methods or concepts, or engendered important debate ( Cooper, 1988 ). Screening for inclusion: The following step consists of evaluating the applicability of the material identified in the preceding step ( Levy & Ellis, 2006 ; vom Brocke et al., 2009 ). Once a group of potential studies has been identified, members of the review team must screen them to determine their relevance ( Petticrew & Roberts, 2006 ). A set of predetermined rules provides a basis for including or excluding certain studies. This exercise requires a significant investment on the part of researchers, who must ensure enhanced objectivity and avoid biases or mistakes. As discussed later in this chapter, for certain types of reviews there must be at least two independent reviewers involved in the screening process and a procedure to resolve disagreements must also be in place ( Liberati et al., 2009 ; Shea et al., 2009 ). Assessing the quality of primary studies: In addition to screening material for inclusion, members of the review team may need to assess the scientific quality of the selected studies, that is, appraise the rigour of the research design and methods. Such formal assessment, which is usually conducted independently by at least two coders, helps members of the review team refine which studies to include in the final sample, determine whether or not the differences in quality may affect their conclusions, or guide how they analyze the data and interpret the findings ( Petticrew & Roberts, 2006 ). Ascribing quality scores to each primary study or considering through domain-based evaluations which study components have or have not been designed and executed appropriately makes it possible to reflect on the extent to which the selected study addresses possible biases and maximizes validity ( Shea et al., 2009 ). Extracting data: The following step involves gathering or extracting applicable information from each primary study included in the sample and deciding what is relevant to the problem of interest ( Cooper & Hedges, 2009 ). Indeed, the type of data that should be recorded mainly depends on the initial research questions ( Okoli & Schabram, 2010 ). However, important information may also be gathered about how, when, where and by whom the primary study was conducted, the research design and methods, or qualitative/quantitative results ( Cooper & Hedges, 2009 ). Analyzing and synthesizing data : As a final step, members of the review team must collate, summarize, aggregate, organize, and compare the evidence extracted from the included studies. The extracted data must be presented in a meaningful way that suggests a new contribution to the extant literature ( Jesson et al., 2011 ). Webster and Watson (2002) warn researchers that literature reviews should be much more than lists of papers and should provide a coherent lens to make sense of extant knowledge on a given topic. There exist several methods and techniques for synthesizing quantitative (e.g., frequency analysis, meta-analysis) and qualitative (e.g., grounded theory, narrative analysis, meta-ethnography) evidence ( Dixon-Woods, Agarwal, Jones, Young, & Sutton, 2005 ; Thomas & Harden, 2008 ).

9.3. Types of Review Articles and Brief Illustrations

EHealth researchers have at their disposal a number of approaches and methods for making sense out of existing literature, all with the purpose of casting current research findings into historical contexts or explaining contradictions that might exist among a set of primary research studies conducted on a particular topic. Our classification scheme is largely inspired from Paré and colleagues’ (2015) typology. Below we present and illustrate those review types that we feel are central to the growth and development of the eHealth domain.

9.3.1. Narrative Reviews

The narrative review is the “traditional” way of reviewing the extant literature and is skewed towards a qualitative interpretation of prior knowledge ( Sylvester et al., 2013 ). Put simply, a narrative review attempts to summarize or synthesize what has been written on a particular topic but does not seek generalization or cumulative knowledge from what is reviewed ( Davies, 2000 ; Green et al., 2006 ). Instead, the review team often undertakes the task of accumulating and synthesizing the literature to demonstrate the value of a particular point of view ( Baumeister & Leary, 1997 ). As such, reviewers may selectively ignore or limit the attention paid to certain studies in order to make a point. In this rather unsystematic approach, the selection of information from primary articles is subjective, lacks explicit criteria for inclusion and can lead to biased interpretations or inferences ( Green et al., 2006 ). There are several narrative reviews in the particular eHealth domain, as in all fields, which follow such an unstructured approach ( Silva et al., 2015 ; Paul et al., 2015 ).

Despite these criticisms, this type of review can be very useful in gathering together a volume of literature in a specific subject area and synthesizing it. As mentioned above, its primary purpose is to provide the reader with a comprehensive background for understanding current knowledge and highlighting the significance of new research ( Cronin et al., 2008 ). Faculty like to use narrative reviews in the classroom because they are often more up to date than textbooks, provide a single source for students to reference, and expose students to peer-reviewed literature ( Green et al., 2006 ). For researchers, narrative reviews can inspire research ideas by identifying gaps or inconsistencies in a body of knowledge, thus helping researchers to determine research questions or formulate hypotheses. Importantly, narrative reviews can also be used as educational articles to bring practitioners up to date with certain topics of issues ( Green et al., 2006 ).

Recently, there have been several efforts to introduce more rigour in narrative reviews that will elucidate common pitfalls and bring changes into their publication standards. Information systems researchers, among others, have contributed to advancing knowledge on how to structure a “traditional” review. For instance, Levy and Ellis (2006) proposed a generic framework for conducting such reviews. Their model follows the systematic data processing approach comprised of three steps, namely: (a) literature search and screening; (b) data extraction and analysis; and (c) writing the literature review. They provide detailed and very helpful instructions on how to conduct each step of the review process. As another methodological contribution, vom Brocke et al. (2009) offered a series of guidelines for conducting literature reviews, with a particular focus on how to search and extract the relevant body of knowledge. Last, Bandara, Miskon, and Fielt (2011) proposed a structured, predefined and tool-supported method to identify primary studies within a feasible scope, extract relevant content from identified articles, synthesize and analyze the findings, and effectively write and present the results of the literature review. We highly recommend that prospective authors of narrative reviews consult these useful sources before embarking on their work.

Darlow and Wen (2015) provide a good example of a highly structured narrative review in the eHealth field. These authors synthesized published articles that describe the development process of mobile health ( m-health ) interventions for patients’ cancer care self-management. As in most narrative reviews, the scope of the research questions being investigated is broad: (a) how development of these systems are carried out; (b) which methods are used to investigate these systems; and (c) what conclusions can be drawn as a result of the development of these systems. To provide clear answers to these questions, a literature search was conducted on six electronic databases and Google Scholar . The search was performed using several terms and free text words, combining them in an appropriate manner. Four inclusion and three exclusion criteria were utilized during the screening process. Both authors independently reviewed each of the identified articles to determine eligibility and extract study information. A flow diagram shows the number of studies identified, screened, and included or excluded at each stage of study selection. In terms of contributions, this review provides a series of practical recommendations for m-health intervention development.

9.3.2. Descriptive or Mapping Reviews

The primary goal of a descriptive review is to determine the extent to which a body of knowledge in a particular research topic reveals any interpretable pattern or trend with respect to pre-existing propositions, theories, methodologies or findings ( King & He, 2005 ; Paré et al., 2015 ). In contrast with narrative reviews, descriptive reviews follow a systematic and transparent procedure, including searching, screening and classifying studies ( Petersen, Vakkalanka, & Kuzniarz, 2015 ). Indeed, structured search methods are used to form a representative sample of a larger group of published works ( Paré et al., 2015 ). Further, authors of descriptive reviews extract from each study certain characteristics of interest, such as publication year, research methods, data collection techniques, and direction or strength of research outcomes (e.g., positive, negative, or non-significant) in the form of frequency analysis to produce quantitative results ( Sylvester et al., 2013 ). In essence, each study included in a descriptive review is treated as the unit of analysis and the published literature as a whole provides a database from which the authors attempt to identify any interpretable trends or draw overall conclusions about the merits of existing conceptualizations, propositions, methods or findings ( Paré et al., 2015 ). In doing so, a descriptive review may claim that its findings represent the state of the art in a particular domain ( King & He, 2005 ).

In the fields of health sciences and medical informatics, reviews that focus on examining the range, nature and evolution of a topic area are described by Anderson, Allen, Peckham, and Goodwin (2008) as mapping reviews . Like descriptive reviews, the research questions are generic and usually relate to publication patterns and trends. There is no preconceived plan to systematically review all of the literature although this can be done. Instead, researchers often present studies that are representative of most works published in a particular area and they consider a specific time frame to be mapped.

An example of this approach in the eHealth domain is offered by DeShazo, Lavallie, and Wolf (2009). The purpose of this descriptive or mapping review was to characterize publication trends in the medical informatics literature over a 20-year period (1987 to 2006). To achieve this ambitious objective, the authors performed a bibliometric analysis of medical informatics citations indexed in medline using publication trends, journal frequencies, impact factors, Medical Subject Headings (MeSH) term frequencies, and characteristics of citations. Findings revealed that there were over 77,000 medical informatics articles published during the covered period in numerous journals and that the average annual growth rate was 12%. The MeSH term analysis also suggested a strong interdisciplinary trend. Finally, average impact scores increased over time with two notable growth periods. Overall, patterns in research outputs that seem to characterize the historic trends and current components of the field of medical informatics suggest it may be a maturing discipline (DeShazo et al., 2009).

9.3.3. Scoping Reviews

Scoping reviews attempt to provide an initial indication of the potential size and nature of the extant literature on an emergent topic (Arksey & O’Malley, 2005; Daudt, van Mossel, & Scott, 2013 ; Levac, Colquhoun, & O’Brien, 2010). A scoping review may be conducted to examine the extent, range and nature of research activities in a particular area, determine the value of undertaking a full systematic review (discussed next), or identify research gaps in the extant literature ( Paré et al., 2015 ). In line with their main objective, scoping reviews usually conclude with the presentation of a detailed research agenda for future works along with potential implications for both practice and research.

Unlike narrative and descriptive reviews, the whole point of scoping the field is to be as comprehensive as possible, including grey literature (Arksey & O’Malley, 2005). Inclusion and exclusion criteria must be established to help researchers eliminate studies that are not aligned with the research questions. It is also recommended that at least two independent coders review abstracts yielded from the search strategy and then the full articles for study selection ( Daudt et al., 2013 ). The synthesized evidence from content or thematic analysis is relatively easy to present in tabular form (Arksey & O’Malley, 2005; Thomas & Harden, 2008 ).

One of the most highly cited scoping reviews in the eHealth domain was published by Archer, Fevrier-Thomas, Lokker, McKibbon, and Straus (2011) . These authors reviewed the existing literature on personal health record ( phr ) systems including design, functionality, implementation, applications, outcomes, and benefits. Seven databases were searched from 1985 to March 2010. Several search terms relating to phr s were used during this process. Two authors independently screened titles and abstracts to determine inclusion status. A second screen of full-text articles, again by two independent members of the research team, ensured that the studies described phr s. All in all, 130 articles met the criteria and their data were extracted manually into a database. The authors concluded that although there is a large amount of survey, observational, cohort/panel, and anecdotal evidence of phr benefits and satisfaction for patients, more research is needed to evaluate the results of phr implementations. Their in-depth analysis of the literature signalled that there is little solid evidence from randomized controlled trials or other studies through the use of phr s. Hence, they suggested that more research is needed that addresses the current lack of understanding of optimal functionality and usability of these systems, and how they can play a beneficial role in supporting patient self-management ( Archer et al., 2011 ).

9.3.4. Forms of Aggregative Reviews

Healthcare providers, practitioners, and policy-makers are nowadays overwhelmed with large volumes of information, including research-based evidence from numerous clinical trials and evaluation studies, assessing the effectiveness of health information technologies and interventions ( Ammenwerth & de Keizer, 2004 ; Deshazo et al., 2009 ). It is unrealistic to expect that all these disparate actors will have the time, skills, and necessary resources to identify the available evidence in the area of their expertise and consider it when making decisions. Systematic reviews that involve the rigorous application of scientific strategies aimed at limiting subjectivity and bias (i.e., systematic and random errors) can respond to this challenge.

Systematic reviews attempt to aggregate, appraise, and synthesize in a single source all empirical evidence that meet a set of previously specified eligibility criteria in order to answer a clearly formulated and often narrow research question on a particular topic of interest to support evidence-based practice ( Liberati et al., 2009 ). They adhere closely to explicit scientific principles ( Liberati et al., 2009 ) and rigorous methodological guidelines (Higgins & Green, 2008) aimed at reducing random and systematic errors that can lead to deviations from the truth in results or inferences. The use of explicit methods allows systematic reviews to aggregate a large body of research evidence, assess whether effects or relationships are in the same direction and of the same general magnitude, explain possible inconsistencies between study results, and determine the strength of the overall evidence for every outcome of interest based on the quality of included studies and the general consistency among them ( Cook, Mulrow, & Haynes, 1997 ). The main procedures of a systematic review involve:

• Formulating a review question and developing a search strategy based on explicit inclusion criteria for the identification of eligible studies (usually described in the context of a detailed review protocol).
• Searching for eligible studies using multiple databases and information sources, including grey literature sources, without any language restrictions.
• Selecting studies, extracting data, and assessing risk of bias in a duplicate manner using two independent reviewers to avoid random or systematic errors in the process.
• Analyzing data using quantitative or qualitative methods.
• Presenting results in summary of findings tables.
• Interpreting results and drawing conclusions.

Many systematic reviews, but not all, use statistical methods to combine the results of independent studies into a single quantitative estimate or summary effect size. Known as meta-analyses , these reviews use specific data extraction and statistical techniques (e.g., network, frequentist, or Bayesian meta-analyses) to calculate from each study by outcome of interest an effect size along with a confidence interval that reflects the degree of uncertainty behind the point estimate of effect ( Borenstein, Hedges, Higgins, & Rothstein, 2009 ; Deeks, Higgins, & Altman, 2008 ). Subsequently, they use fixed or random-effects analysis models to combine the results of the included studies, assess statistical heterogeneity, and calculate a weighted average of the effect estimates from the different studies, taking into account their sample sizes. The summary effect size is a value that reflects the average magnitude of the intervention effect for a particular outcome of interest or, more generally, the strength of a relationship between two variables across all studies included in the systematic review. By statistically combining data from multiple studies, meta-analyses can create more precise and reliable estimates of intervention effects than those derived from individual studies alone, when these are examined independently as discrete sources of information.

The review by Gurol-Urganci, de Jongh, Vodopivec-Jamsek, Atun, and Car (2013) on the effects of mobile phone messaging reminders for attendance at healthcare appointments is an illustrative example of a high-quality systematic review with meta-analysis. Missed appointments are a major cause of inefficiency in healthcare delivery with substantial monetary costs to health systems. These authors sought to assess whether mobile phone-based appointment reminders delivered through Short Message Service ( sms ) or Multimedia Messaging Service ( mms ) are effective in improving rates of patient attendance and reducing overall costs. To this end, they conducted a comprehensive search on multiple databases using highly sensitive search strategies without language or publication-type restrictions to identify all rct s that are eligible for inclusion. In order to minimize the risk of omitting eligible studies not captured by the original search, they supplemented all electronic searches with manual screening of trial registers and references contained in the included studies. Study selection, data extraction, and risk of bias assessments were performed inde­­pen­dently by two coders using standardized methods to ensure consistency and to eliminate potential errors. Findings from eight rct s involving 6,615 participants were pooled into meta-analyses to calculate the magnitude of effects that mobile text message reminders have on the rate of attendance at healthcare appointments compared to no reminders and phone call reminders.

Meta-analyses are regarded as powerful tools for deriving meaningful conclusions. However, there are situations in which it is neither reasonable nor appropriate to pool studies together using meta-analytic methods simply because there is extensive clinical heterogeneity between the included studies or variation in measurement tools, comparisons, or outcomes of interest. In these cases, systematic reviews can use qualitative synthesis methods such as vote counting, content analysis, classification schemes and tabulations, as an alternative approach to narratively synthesize the results of the independent studies included in the review. This form of review is known as qualitative systematic review.

A rigorous example of one such review in the eHealth domain is presented by Mickan, Atherton, Roberts, Heneghan, and Tilson (2014) on the use of handheld computers by healthcare professionals and their impact on access to information and clinical decision-making. In line with the methodological guide­lines for systematic reviews, these authors: (a) developed and registered with prospero ( www.crd.york.ac.uk/ prospero / ) an a priori review protocol; (b) conducted comprehensive searches for eligible studies using multiple databases and other supplementary strategies (e.g., forward searches); and (c) subsequently carried out study selection, data extraction, and risk of bias assessments in a duplicate manner to eliminate potential errors in the review process. Heterogeneity between the included studies in terms of reported outcomes and measures precluded the use of meta-analytic methods. To this end, the authors resorted to using narrative analysis and synthesis to describe the effectiveness of handheld computers on accessing information for clinical knowledge, adherence to safety and clinical quality guidelines, and diagnostic decision-making.

In recent years, the number of systematic reviews in the field of health informatics has increased considerably. Systematic reviews with discordant findings can cause great confusion and make it difficult for decision-makers to interpret the review-level evidence ( Moher, 2013 ). Therefore, there is a growing need for appraisal and synthesis of prior systematic reviews to ensure that decision-making is constantly informed by the best available accumulated evidence. Umbrella reviews , also known as overviews of systematic reviews, are tertiary types of evidence synthesis that aim to accomplish this; that is, they aim to compare and contrast findings from multiple systematic reviews and meta-analyses ( Becker & Oxman, 2008 ). Umbrella reviews generally adhere to the same principles and rigorous methodological guidelines used in systematic reviews. However, the unit of analysis in umbrella reviews is the systematic review rather than the primary study ( Becker & Oxman, 2008 ). Unlike systematic reviews that have a narrow focus of inquiry, umbrella reviews focus on broader research topics for which there are several potential interventions ( Smith, Devane, Begley, & Clarke, 2011 ). A recent umbrella review on the effects of home telemonitoring interventions for patients with heart failure critically appraised, compared, and synthesized evidence from 15 systematic reviews to investigate which types of home telemonitoring technologies and forms of interventions are more effective in reducing mortality and hospital admissions ( Kitsiou, Paré, & Jaana, 2015 ).

9.3.5. Realist Reviews

Realist reviews are theory-driven interpretative reviews developed to inform, enhance, or supplement conventional systematic reviews by making sense of heterogeneous evidence about complex interventions applied in diverse contexts in a way that informs policy decision-making ( Greenhalgh, Wong, Westhorp, & Pawson, 2011 ). They originated from criticisms of positivist systematic reviews which centre on their “simplistic” underlying assumptions ( Oates, 2011 ). As explained above, systematic reviews seek to identify causation. Such logic is appropriate for fields like medicine and education where findings of randomized controlled trials can be aggregated to see whether a new treatment or intervention does improve outcomes. However, many argue that it is not possible to establish such direct causal links between interventions and outcomes in fields such as social policy, management, and information systems where for any intervention there is unlikely to be a regular or consistent outcome ( Oates, 2011 ; Pawson, 2006 ; Rousseau, Manning, & Denyer, 2008 ).

To circumvent these limitations, Pawson, Greenhalgh, Harvey, and Walshe (2005) have proposed a new approach for synthesizing knowledge that seeks to unpack the mechanism of how “complex interventions” work in particular contexts. The basic research question — what works? — which is usually associated with systematic reviews changes to: what is it about this intervention that works, for whom, in what circumstances, in what respects and why? Realist reviews have no particular preference for either quantitative or qualitative evidence. As a theory-building approach, a realist review usually starts by articulating likely underlying mechanisms and then scrutinizes available evidence to find out whether and where these mechanisms are applicable ( Shepperd et al., 2009 ). Primary studies found in the extant literature are viewed as case studies which can test and modify the initial theories ( Rousseau et al., 2008 ).

The main objective pursued in the realist review conducted by Otte-Trojel, de Bont, Rundall, and van de Klundert (2014) was to examine how patient portals contribute to health service delivery and patient outcomes. The specific goals were to investigate how outcomes are produced and, most importantly, how variations in outcomes can be explained. The research team started with an exploratory review of background documents and research studies to identify ways in which patient portals may contribute to health service delivery and patient outcomes. The authors identified six main ways which represent “educated guesses” to be tested against the data in the evaluation studies. These studies were identified through a formal and systematic search in four databases between 2003 and 2013. Two members of the research team selected the articles using a pre-established list of inclusion and exclusion criteria and following a two-step procedure. The authors then extracted data from the selected articles and created several tables, one for each outcome category. They organized information to bring forward those mechanisms where patient portals contribute to outcomes and the variation in outcomes across different contexts.

9.3.6. Critical Reviews

Lastly, critical reviews aim to provide a critical evaluation and interpretive analysis of existing literature on a particular topic of interest to reveal strengths, weaknesses, contradictions, controversies, inconsistencies, and/or other important issues with respect to theories, hypotheses, research methods or results ( Baumeister & Leary, 1997 ; Kirkevold, 1997 ). Unlike other review types, critical reviews attempt to take a reflective account of the research that has been done in a particular area of interest, and assess its credibility by using appraisal instruments or critical interpretive methods. In this way, critical reviews attempt to constructively inform other scholars about the weaknesses of prior research and strengthen knowledge development by giving focus and direction to studies for further improvement ( Kirkevold, 1997 ).

Kitsiou, Paré, and Jaana (2013) provide an example of a critical review that assessed the methodological quality of prior systematic reviews of home telemonitoring studies for chronic patients. The authors conducted a comprehensive search on multiple databases to identify eligible reviews and subsequently used a validated instrument to conduct an in-depth quality appraisal. Results indicate that the majority of systematic reviews in this particular area suffer from important methodological flaws and biases that impair their internal validity and limit their usefulness for clinical and decision-making purposes. To this end, they provide a number of recommendations to strengthen knowledge development towards improving the design and execution of future reviews on home telemonitoring.

9.4. Summary

Table 9.1 outlines the main types of literature reviews that were described in the previous sub-sections and summarizes the main characteristics that distinguish one review type from another. It also includes key references to methodological guidelines and useful sources that can be used by eHealth scholars and researchers for planning and developing reviews.

Typology of Literature Reviews (adapted from Paré et al., 2015).

As shown in Table 9.1 , each review type addresses different kinds of research questions or objectives, which subsequently define and dictate the methods and approaches that need to be used to achieve the overarching goal(s) of the review. For example, in the case of narrative reviews, there is greater flexibility in searching and synthesizing articles ( Green et al., 2006 ). Researchers are often relatively free to use a diversity of approaches to search, identify, and select relevant scientific articles, describe their operational characteristics, present how the individual studies fit together, and formulate conclusions. On the other hand, systematic reviews are characterized by their high level of systematicity, rigour, and use of explicit methods, based on an “a priori” review plan that aims to minimize bias in the analysis and synthesis process (Higgins & Green, 2008). Some reviews are exploratory in nature (e.g., scoping/mapping reviews), whereas others may be conducted to discover patterns (e.g., descriptive reviews) or involve a synthesis approach that may include the critical analysis of prior research ( Paré et al., 2015 ). Hence, in order to select the most appropriate type of review, it is critical to know before embarking on a review project, why the research synthesis is conducted and what type of methods are best aligned with the pursued goals.

9.5. Concluding Remarks

In light of the increased use of evidence-based practice and research generating stronger evidence ( Grady et al., 2011 ; Lyden et al., 2013 ), review articles have become essential tools for summarizing, synthesizing, integrating or critically appraising prior knowledge in the eHealth field. As mentioned earlier, when rigorously conducted review articles represent powerful information sources for eHealth scholars and practitioners looking for state-of-the-art evidence. The typology of literature reviews we used herein will allow eHealth researchers, graduate students and practitioners to gain a better understanding of the similarities and differences between review types.

We must stress that this classification scheme does not privilege any specific type of review as being of higher quality than another ( Paré et al., 2015 ). As explained above, each type of review has its own strengths and limitations. Having said that, we realize that the methodological rigour of any review — be it qualitative, quantitative or mixed — is a critical aspect that should be considered seriously by prospective authors. In the present context, the notion of rigour refers to the reliability and validity of the review process described in section 9.2. For one thing, reliability is related to the reproducibility of the review process and steps, which is facilitated by a comprehensive documentation of the literature search process, extraction, coding and analysis performed in the review. Whether the search is comprehensive or not, whether it involves a methodical approach for data extraction and synthesis or not, it is important that the review documents in an explicit and transparent manner the steps and approach that were used in the process of its development. Next, validity characterizes the degree to which the review process was conducted appropriately. It goes beyond documentation and reflects decisions related to the selection of the sources, the search terms used, the period of time covered, the articles selected in the search, and the application of backward and forward searches ( vom Brocke et al., 2009 ). In short, the rigour of any review article is reflected by the explicitness of its methods (i.e., transparency) and the soundness of the approach used. We refer those interested in the concepts of rigour and quality to the work of Templier and Paré (2015) which offers a detailed set of methodological guidelines for conducting and evaluating various types of review articles.

To conclude, our main objective in this chapter was to demystify the various types of literature reviews that are central to the continuous development of the eHealth field. It is our hope that our descriptive account will serve as a valuable source for those conducting, evaluating or using reviews in this important and growing domain.

• Ammenwerth E., de Keizer N. An inventory of evaluation studies of information technology in health care. Trends in evaluation research, 1982-2002. International Journal of Medical Informatics. 2004; 44 (1):44–56. [ PubMed : 15778794 ]
• Anderson S., Allen P., Peckham S., Goodwin N. Asking the right questions: scoping studies in the commissioning of research on the organisation and delivery of health services. Health Research Policy and Systems. 2008; 6 (7):1–12. [ PMC free article : PMC2500008 ] [ PubMed : 18613961 ] [ CrossRef ]
• Archer N., Fevrier-Thomas U., Lokker C., McKibbon K. A., Straus S.E. Personal health records: a scoping review. Journal of American Medical Informatics Association. 2011; 18 (4):515–522. [ PMC free article : PMC3128401 ] [ PubMed : 21672914 ]
• Arksey H., O’Malley L. Scoping studies: towards a methodological framework. International Journal of Social Research Methodology. 2005; 8 (1):19–32.
• A systematic, tool-supported method for conducting literature reviews in information systems. Paper presented at the Proceedings of the 19th European Conference on Information Systems ( ecis 2011); June 9 to 11; Helsinki, Finland. 2011.
• Baumeister R. F., Leary M.R. Writing narrative literature reviews. Review of General Psychology. 1997; 1 (3):311–320.
• Becker L. A., Oxman A.D. In: Cochrane handbook for systematic reviews of interventions. Higgins J. P. T., Green S., editors. Hoboken, nj : John Wiley & Sons, Ltd; 2008. Overviews of reviews; pp. 607–631.
• Borenstein M., Hedges L., Higgins J., Rothstein H. Introduction to meta-analysis. Hoboken, nj : John Wiley & Sons Inc; 2009.
• Cook D. J., Mulrow C. D., Haynes B. Systematic reviews: Synthesis of best evidence for clinical decisions. Annals of Internal Medicine. 1997; 126 (5):376–380. [ PubMed : 9054282 ]
• Cooper H., Hedges L.V. In: The handbook of research synthesis and meta-analysis. 2nd ed. Cooper H., Hedges L. V., Valentine J. C., editors. New York: Russell Sage Foundation; 2009. Research synthesis as a scientific process; pp. 3–17.
• Cooper H. M. Organizing knowledge syntheses: A taxonomy of literature reviews. Knowledge in Society. 1988; 1 (1):104–126.
• Cronin P., Ryan F., Coughlan M. Undertaking a literature review: a step-by-step approach. British Journal of Nursing. 2008; 17 (1):38–43. [ PubMed : 18399395 ]
• Darlow S., Wen K.Y. Development testing of mobile health interventions for cancer patient self-management: A review. Health Informatics Journal. 2015 (online before print). [ PubMed : 25916831 ] [ CrossRef ]
• Daudt H. M., van Mossel C., Scott S.J. Enhancing the scoping study methodology: a large, inter-professional team’s experience with Arksey and O’Malley’s framework. bmc Medical Research Methodology. 2013; 13 :48. [ PMC free article : PMC3614526 ] [ PubMed : 23522333 ] [ CrossRef ]
• Davies P. The relevance of systematic reviews to educational policy and practice. Oxford Review of Education. 2000; 26 (3-4):365–378.
• Deeks J. J., Higgins J. P. T., Altman D.G. In: Cochrane handbook for systematic reviews of interventions. Higgins J. P. T., Green S., editors. Hoboken, nj : John Wiley & Sons, Ltd; 2008. Analysing data and undertaking meta-analyses; pp. 243–296.
• Deshazo J. P., Lavallie D. L., Wolf F.M. Publication trends in the medical informatics literature: 20 years of “Medical Informatics” in mesh . bmc Medical Informatics and Decision Making. 2009; 9 :7. [ PMC free article : PMC2652453 ] [ PubMed : 19159472 ] [ CrossRef ]
• Dixon-Woods M., Agarwal S., Jones D., Young B., Sutton A. Synthesising qualitative and quantitative evidence: a review of possible methods. Journal of Health Services Research and Policy. 2005; 10 (1):45–53. [ PubMed : 15667704 ]
• Finfgeld-Connett D., Johnson E.D. Literature search strategies for conducting knowledge-building and theory-generating qualitative systematic reviews. Journal of Advanced Nursing. 2013; 69 (1):194–204. [ PMC free article : PMC3424349 ] [ PubMed : 22591030 ]
• Grady B., Myers K. M., Nelson E. L., Belz N., Bennett L., Carnahan L. … Guidelines Working Group. Evidence-based practice for telemental health. Telemedicine Journal and E Health. 2011; 17 (2):131–148. [ PubMed : 21385026 ]
• Green B. N., Johnson C. D., Adams A. Writing narrative literature reviews for peer-reviewed journals: secrets of the trade. Journal of Chiropractic Medicine. 2006; 5 (3):101–117. [ PMC free article : PMC2647067 ] [ PubMed : 19674681 ]
• Greenhalgh T., Wong G., Westhorp G., Pawson R. Protocol–realist and meta-narrative evidence synthesis: evolving standards ( rameses ). bmc Medical Research Methodology. 2011; 11 :115. [ PMC free article : PMC3173389 ] [ PubMed : 21843376 ]
• Gurol-Urganci I., de Jongh T., Vodopivec-Jamsek V., Atun R., Car J. Mobile phone messaging reminders for attendance at healthcare appointments. Cochrane Database System Review. 2013; 12 cd 007458. [ PMC free article : PMC6485985 ] [ PubMed : 24310741 ] [ CrossRef ]
• Hart C. Doing a literature review: Releasing the social science research imagination. London: SAGE Publications; 1998.
• Higgins J. P. T., Green S., editors. Cochrane handbook for systematic reviews of interventions: Cochrane book series. Hoboken, nj : Wiley-Blackwell; 2008.
• Jesson J., Matheson L., Lacey F.M. Doing your literature review: traditional and systematic techniques. Los Angeles & London: SAGE Publications; 2011.
• King W. R., He J. Understanding the role and methods of meta-analysis in IS research. Communications of the Association for Information Systems. 2005; 16 :1.
• Kirkevold M. Integrative nursing research — an important strategy to further the development of nursing science and nursing practice. Journal of Advanced Nursing. 1997; 25 (5):977–984. [ PubMed : 9147203 ]
• Kitchenham B., Charters S. ebse Technical Report Version 2.3. Keele & Durham. uk : Keele University & University of Durham; 2007. Guidelines for performing systematic literature reviews in software engineering.
• Kitsiou S., Paré G., Jaana M. Systematic reviews and meta-analyses of home telemonitoring interventions for patients with chronic diseases: a critical assessment of their methodological quality. Journal of Medical Internet Research. 2013; 15 (7):e150. [ PMC free article : PMC3785977 ] [ PubMed : 23880072 ]
• Kitsiou S., Paré G., Jaana M. Effects of home telemonitoring interventions on patients with chronic heart failure: an overview of systematic reviews. Journal of Medical Internet Research. 2015; 17 (3):e63. [ PMC free article : PMC4376138 ] [ PubMed : 25768664 ]
• Levac D., Colquhoun H., O’Brien K. K. Scoping studies: advancing the methodology. Implementation Science. 2010; 5 (1):69. [ PMC free article : PMC2954944 ] [ PubMed : 20854677 ]
• Levy Y., Ellis T.J. A systems approach to conduct an effective literature review in support of information systems research. Informing Science. 2006; 9 :181–211.
• Liberati A., Altman D. G., Tetzlaff J., Mulrow C., Gøtzsche P. C., Ioannidis J. P. A. et al. Moher D. The prisma statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: Explanation and elaboration. Annals of Internal Medicine. 2009; 151 (4):W-65. [ PubMed : 19622512 ]
• Lyden J. R., Zickmund S. L., Bhargava T. D., Bryce C. L., Conroy M. B., Fischer G. S. et al. McTigue K. M. Implementing health information technology in a patient-centered manner: Patient experiences with an online evidence-based lifestyle intervention. Journal for Healthcare Quality. 2013; 35 (5):47–57. [ PubMed : 24004039 ]
• Mickan S., Atherton H., Roberts N. W., Heneghan C., Tilson J.K. Use of handheld computers in clinical practice: a systematic review. bmc Medical Informatics and Decision Making. 2014; 14 :56. [ PMC free article : PMC4099138 ] [ PubMed : 24998515 ]
• Moher D. The problem of duplicate systematic reviews. British Medical Journal. 2013; 347 (5040) [ PubMed : 23945367 ] [ CrossRef ]
• Montori V. M., Wilczynski N. L., Morgan D., Haynes R. B., Hedges T. Systematic reviews: a cross-sectional study of location and citation counts. bmc Medicine. 2003; 1 :2. [ PMC free article : PMC281591 ] [ PubMed : 14633274 ]
• Mulrow C. D. The medical review article: state of the science. Annals of Internal Medicine. 1987; 106 (3):485–488. [ PubMed : 3813259 ] [ CrossRef ]
• Evidence-based information systems: A decade later. Proceedings of the European Conference on Information Systems ; 2011. Retrieved from http://aisel ​.aisnet.org/cgi/viewcontent ​.cgi?article ​=1221&context ​=ecis2011 .
• Okoli C., Schabram K. A guide to conducting a systematic literature review of information systems research. ssrn Electronic Journal. 2010
• Otte-Trojel T., de Bont A., Rundall T. G., van de Klundert J. How outcomes are achieved through patient portals: a realist review. Journal of American Medical Informatics Association. 2014; 21 (4):751–757. [ PMC free article : PMC4078283 ] [ PubMed : 24503882 ]
• Paré G., Trudel M.-C., Jaana M., Kitsiou S. Synthesizing information systems knowledge: A typology of literature reviews. Information & Management. 2015; 52 (2):183–199.
• Patsopoulos N. A., Analatos A. A., Ioannidis J.P. A. Relative citation impact of various study designs in the health sciences. Journal of the American Medical Association. 2005; 293 (19):2362–2366. [ PubMed : 15900006 ]
• Paul M. M., Greene C. M., Newton-Dame R., Thorpe L. E., Perlman S. E., McVeigh K. H., Gourevitch M.N. The state of population health surveillance using electronic health records: A narrative review. Population Health Management. 2015; 18 (3):209–216. [ PubMed : 25608033 ]
• Pawson R. Evidence-based policy: a realist perspective. London: SAGE Publications; 2006.
• Pawson R., Greenhalgh T., Harvey G., Walshe K. Realist review—a new method of systematic review designed for complex policy interventions. Journal of Health Services Research & Policy. 2005; 10 (Suppl 1):21–34. [ PubMed : 16053581 ]
• Petersen K., Vakkalanka S., Kuzniarz L. Guidelines for conducting systematic mapping studies in software engineering: An update. Information and Software Technology. 2015; 64 :1–18.
• Petticrew M., Roberts H. Systematic reviews in the social sciences: A practical guide. Malden, ma : Blackwell Publishing Co; 2006.
• Rousseau D. M., Manning J., Denyer D. Evidence in management and organizational science: Assembling the field’s full weight of scientific knowledge through syntheses. The Academy of Management Annals. 2008; 2 (1):475–515.
• Rowe F. What literature review is not: diversity, boundaries and recommendations. European Journal of Information Systems. 2014; 23 (3):241–255.
• Shea B. J., Hamel C., Wells G. A., Bouter L. M., Kristjansson E., Grimshaw J. et al. Boers M. amstar is a reliable and valid measurement tool to assess the methodological quality of systematic reviews. Journal of Clinical Epidemiology. 2009; 62 (10):1013–1020. [ PubMed : 19230606 ]
• Shepperd S., Lewin S., Straus S., Clarke M., Eccles M. P., Fitzpatrick R. et al. Sheikh A. Can we systematically review studies that evaluate complex interventions? PLoS Medicine. 2009; 6 (8):e1000086. [ PMC free article : PMC2717209 ] [ PubMed : 19668360 ]
• Silva B. M., Rodrigues J. J., de la Torre Díez I., López-Coronado M., Saleem K. Mobile-health: A review of current state in 2015. Journal of Biomedical Informatics. 2015; 56 :265–272. [ PubMed : 26071682 ]
• Smith V., Devane D., Begley C., Clarke M. Methodology in conducting a systematic review of systematic reviews of healthcare interventions. bmc Medical Research Methodology. 2011; 11 (1):15. [ PMC free article : PMC3039637 ] [ PubMed : 21291558 ]
• Sylvester A., Tate M., Johnstone D. Beyond synthesis: re-presenting heterogeneous research literature. Behaviour & Information Technology. 2013; 32 (12):1199–1215.
• Templier M., Paré G. A framework for guiding and evaluating literature reviews. Communications of the Association for Information Systems. 2015; 37 (6):112–137.
• Thomas J., Harden A. Methods for the thematic synthesis of qualitative research in systematic reviews. bmc Medical Research Methodology. 2008; 8 (1):45. [ PMC free article : PMC2478656 ] [ PubMed : 18616818 ]
• Reconstructing the giant: on the importance of rigour in documenting the literature search process. Paper presented at the Proceedings of the 17th European Conference on Information Systems ( ecis 2009); Verona, Italy. 2009.
• Webster J., Watson R.T. Analyzing the past to prepare for the future: Writing a literature review. Management Information Systems Quarterly. 2002; 26 (2):11.
• Whitlock E. P., Lin J. S., Chou R., Shekelle P., Robinson K.A. Using existing systematic reviews in complex systematic reviews. Annals of Internal Medicine. 2008; 148 (10):776–782. [ PubMed : 18490690 ]

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• Cite this Page Paré G, Kitsiou S. Chapter 9 Methods for Literature Reviews. In: Lau F, Kuziemsky C, editors. Handbook of eHealth Evaluation: An Evidence-based Approach [Internet]. Victoria (BC): University of Victoria; 2017 Feb 27.
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In this Page

• Introduction
• Overview of the Literature Review Process and Steps
• Types of Review Articles and Brief Illustrations
• Concluding Remarks

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Research Methods

• Getting Started
• Literature Review Research
• Research Design
• Research Design By Discipline
• SAGE Research Methods
• Teaching with SAGE Research Methods

Literature Review

• What is a Literature Review?
• What is NOT a Literature Review?
• Purposes of a Literature Review
• Types of Literature Reviews
• Literature Reviews vs. Systematic Reviews
• Systematic vs. Meta-Analysis

Literature Review  is a comprehensive survey of the works published in a particular field of study or line of research, usually over a specific period of time, in the form of an in-depth, critical bibliographic essay or annotated list in which attention is drawn to the most significant works.

Also, we can define a literature review as the collected body of scholarly works related to a topic:

• Summarizes and analyzes previous research relevant to a topic
• Includes scholarly books and articles published in academic journals
• Can be an specific scholarly paper or a section in a research paper

The objective of a Literature Review is to find previous published scholarly works relevant to an specific topic

• Help gather ideas or information
• Keep up to date in current trends and findings
• Help develop new questions

A literature review is important because it:

• Explains the background of research on a topic.
• Demonstrates why a topic is significant to a subject area.
• Helps focus your own research questions or problems
• Discovers relationships between research studies/ideas.
• Suggests unexplored ideas or populations
• Identifies major themes, concepts, and researchers on a topic.
• Tests assumptions; may help counter preconceived ideas and remove unconscious bias.
• Identifies critical gaps, points of disagreement, or potentially flawed methodology or theoretical approaches.
• Indicates potential directions for future research.

All content in this section is from Literature Review Research from Old Dominion University 

Keep in mind the following, a literature review is NOT:

Not an essay 

Not an annotated bibliography  in which you summarize each article that you have reviewed.  A literature review goes beyond basic summarizing to focus on the critical analysis of the reviewed works and their relationship to your research question.

Not a research paper   where you select resources to support one side of an issue versus another.  A lit review should explain and consider all sides of an argument in order to avoid bias, and areas of agreement and disagreement should be highlighted.

A literature review serves several purposes. For example, it

• provides thorough knowledge of previous studies; introduces seminal works.
• helps focus one’s own research topic.
• identifies a conceptual framework for one’s own research questions or problems; indicates potential directions for future research.
• suggests previously unused or underused methodologies, designs, quantitative and qualitative strategies.
• identifies gaps in previous studies; identifies flawed methodologies and/or theoretical approaches; avoids replication of mistakes.
• helps the researcher avoid repetition of earlier research.
• suggests unexplored populations.
• determines whether past studies agree or disagree; identifies controversy in the literature.
• tests assumptions; may help counter preconceived ideas and remove unconscious bias.

As Kennedy (2007) notes*, it is important to think of knowledge in a given field as consisting of three layers. First, there are the primary studies that researchers conduct and publish. Second are the reviews of those studies that summarize and offer new interpretations built from and often extending beyond the original studies. Third, there are the perceptions, conclusions, opinion, and interpretations that are shared informally that become part of the lore of field. In composing a literature review, it is important to note that it is often this third layer of knowledge that is cited as "true" even though it often has only a loose relationship to the primary studies and secondary literature reviews.

Given this, while literature reviews are designed to provide an overview and synthesis of pertinent sources you have explored, there are several approaches to how they can be done, depending upon the type of analysis underpinning your study. Listed below are definitions of types of literature reviews:

Argumentative Review      This form examines literature selectively in order to support or refute an argument, deeply imbedded assumption, or philosophical problem already established in the literature. The purpose is to develop a body of literature that establishes a contrarian viewpoint. Given the value-laden nature of some social science research [e.g., educational reform; immigration control], argumentative approaches to analyzing the literature can be a legitimate and important form of discourse. However, note that they can also introduce problems of bias when they are used to to make summary claims of the sort found in systematic reviews.

Integrative Review      Considered a form of research that reviews, critiques, and synthesizes representative literature on a topic in an integrated way such that new frameworks and perspectives on the topic are generated. The body of literature includes all studies that address related or identical hypotheses. A well-done integrative review meets the same standards as primary research in regard to clarity, rigor, and replication.

Historical Review      Few things rest in isolation from historical precedent. Historical reviews are focused on examining research throughout a period of time, often starting with the first time an issue, concept, theory, phenomena emerged in the literature, then tracing its evolution within the scholarship of a discipline. The purpose is to place research in a historical context to show familiarity with state-of-the-art developments and to identify the likely directions for future research.

Methodological Review      A review does not always focus on what someone said [content], but how they said it [method of analysis]. This approach provides a framework of understanding at different levels (i.e. those of theory, substantive fields, research approaches and data collection and analysis techniques), enables researchers to draw on a wide variety of knowledge ranging from the conceptual level to practical documents for use in fieldwork in the areas of ontological and epistemological consideration, quantitative and qualitative integration, sampling, interviewing, data collection and data analysis, and helps highlight many ethical issues which we should be aware of and consider as we go through our study.

Systematic Review      This form consists of an overview of existing evidence pertinent to a clearly formulated research question, which uses pre-specified and standardized methods to identify and critically appraise relevant research, and to collect, report, and analyse data from the studies that are included in the review. Typically it focuses on a very specific empirical question, often posed in a cause-and-effect form, such as "To what extent does A contribute to B?"

Theoretical Review      The purpose of this form is to concretely examine the corpus of theory that has accumulated in regard to an issue, concept, theory, phenomena. The theoretical literature review help establish what theories already exist, the relationships between them, to what degree the existing theories have been investigated, and to develop new hypotheses to be tested. Often this form is used to help establish a lack of appropriate theories or reveal that current theories are inadequate for explaining new or emerging research problems. The unit of analysis can focus on a theoretical concept or a whole theory or framework.

* Kennedy, Mary M. "Defining a Literature."  Educational Researcher  36 (April 2007): 139-147.

All content in this section is from The Literature Review created by Dr. Robert Larabee USC

Robinson, P. and Lowe, J. (2015),  Literature reviews vs systematic reviews.  Australian and New Zealand Journal of Public Health, 39: 103-103. doi: 10.1111/1753-6405.12393

What's in the name? The difference between a Systematic Review and a Literature Review, and why it matters . By Lynn Kysh from University of Southern California

Systematic review or meta-analysis?

A  systematic review  answers a defined research question by collecting and summarizing all empirical evidence that fits pre-specified eligibility criteria.

A  meta-analysis  is the use of statistical methods to summarize the results of these studies.

Systematic reviews, just like other research articles, can be of varying quality. They are a significant piece of work (the Centre for Reviews and Dissemination at York estimates that a team will take 9-24 months), and to be useful to other researchers and practitioners they should have:

• clearly stated objectives with pre-defined eligibility criteria for studies
• explicit, reproducible methodology
• a systematic search that attempts to identify all studies
• assessment of the validity of the findings of the included studies (e.g. risk of bias)
• systematic presentation, and synthesis, of the characteristics and findings of the included studies

Not all systematic reviews contain meta-analysis. 

Meta-analysis is the use of statistical methods to summarize the results of independent studies. By combining information from all relevant studies, meta-analysis can provide more precise estimates of the effects of health care than those derived from the individual studies included within a review.  More information on meta-analyses can be found in  Cochrane Handbook, Chapter 9 .

A meta-analysis goes beyond critique and integration and conducts secondary statistical analysis on the outcomes of similar studies.  It is a systematic review that uses quantitative methods to synthesize and summarize the results.

An advantage of a meta-analysis is the ability to be completely objective in evaluating research findings.  Not all topics, however, have sufficient research evidence to allow a meta-analysis to be conducted.  In that case, an integrative review is an appropriate strategy. 

Some of the content in this section is from Systematic reviews and meta-analyses: step by step guide created by Kate McAllister.

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Libraries | Research Guides

Literature reviews, what is a literature review, learning more about how to do a literature review.

• Planning the Review
• The Research Question
• Choosing Where to Search
• Organizing the Review
• Writing the Review

A literature review is a review and synthesis of existing research on a topic or research question. A literature review is meant to analyze the scholarly literature, make connections across writings and identify strengths, weaknesses, trends, and missing conversations. A literature review should address different aspects of a topic as it relates to your research question. A literature review goes beyond a description or summary of the literature you have read. 

• Sage Research Methods Core Collection This link opens in a new window SAGE Research Methods supports research at all levels by providing material to guide users through every step of the research process. SAGE Research Methods is the ultimate methods library with more than 1000 books, reference works, journal articles, and instructional videos by world-leading academics from across the social sciences, including the largest collection of qualitative methods books available online from any scholarly publisher. – Publisher

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Which review is that? A guide to review types

• Which review is that?
• Review Comparison Chart
• Decision Tool
• Critical Review
• Integrative Review
• Narrative Review
• State of the Art Review
• Narrative Summary
• Systematic Review
• Meta-analysis
• Comparative Effectiveness Review
• Diagnostic Systematic Review
• Network Meta-analysis
• Prognostic Review
• Psychometric Review
• Review of Economic Evaluations
• Systematic Review of Epidemiology Studies
• Living Systematic Reviews
• Umbrella Review
• Review of Reviews
• Rapid Review
• Rapid Evidence Assessment
• Rapid Realist Review
• Qualitative Evidence Synthesis
• Qualitative Interpretive Meta-synthesis
• Qualitative Meta-synthesis
• Qualitative Research Synthesis
• Framework Synthesis - Best-fit Framework Synthesis
• Meta-aggregation
• Meta-ethnography
• Meta-interpretation
• Meta-narrative Review
• Meta-summary
• Thematic Synthesis
• Mixed Methods Synthesis
• Narrative Synthesis
• Bayesian Meta-analysis
• EPPI-Centre Review
• Critical Interpretive Synthesis
• Realist Synthesis - Realist Review
• Scoping Review
• Mapping Review
• Systematised Review
• Concept Synthesis
• Expert Opinion - Policy Review
• Technology Assessment Review

Methodological Review

• Systematic Search and Review

A methodological review is a type of systematic secondary research (i.e., research synthesis) which focuses on summarising the state-of-the-art methodological practices of research in a substantive field or topic" (Chong et al, 2021).

Methodological reviews "can be performed to examine any methodological issues relating to the design, conduct and review of research studies and also evidence syntheses". Munn et al, 2018)

Further Reading/Resources

Clarke, M., Oxman, A. D., Paulsen, E., Higgins, J. P. T., & Green, S. (2011). Appendix A: Guide to the contents of a Cochrane Methodology protocol and review. Cochrane Handbook for systematic reviews of interventions . Full Text PDF

Aguinis, H., Ramani, R. S., & Alabduljader, N. (2023). Best-Practice Recommendations for Producers, Evaluators, and Users of Methodological Literature Reviews. Organizational Research Methods, 26(1), 46-76. https://doi.org/10.1177/1094428120943281 Full Text

Jha, C. K., & Kolekar, M. H. (2021). Electrocardiogram data compression techniques for cardiac healthcare systems: A methodological review. IRBM . Full Text

References Munn, Z., Stern, C., Aromataris, E., Lockwood, C., & Jordan, Z. (2018). What kind of systematic review should I conduct? A proposed typology and guidance for systematic reviewers in the medical and health sciences. BMC medical research methodology , 18 (1), 1-9. Full Text Chong, S. W., & Reinders, H. (2021). A methodological review of qualitative research syntheses in CALL: The state-of-the-art. System , 103 , 102646. Full Text

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Literature Review: Types of literature reviews

• Traditional or narrative literature reviews
• Scoping Reviews
• Systematic literature reviews
• Annotated bibliography
• Keeping up to date with literature
• Finding a thesis
• Evaluating sources and critical appraisal of literature
• Managing and analysing your literature
• Further reading and resources

Types of literature reviews

The type of literature review you write will depend on your discipline and whether you are a researcher writing your PhD, publishing a study in a journal or completing an assessment task in your undergraduate study.

A literature review for a subject in an undergraduate degree will not be as comprehensive as the literature review required for a PhD thesis.

An undergraduate literature review may be in the form of an annotated bibliography or a narrative review of a small selection of literature, for example ten relevant articles. If you are asked to write a literature review, and you are an undergraduate student, be guided by your subject coordinator or lecturer.

The common types of literature reviews will be explained in the pages of this section.

• Narrative or traditional literature reviews
• Critically Appraised Topic (CAT)
• Scoping reviews
• Annotated bibliographies

These are not the only types of reviews of literature that can be conducted. Often the term "review" and "literature" can be confusing and used in the wrong context. Grant and Booth (2009) attempt to clear up this confusion by discussing 14 review types and the associated methodology, and advantages and disadvantages associated with each review.

Grant, M. J. and Booth, A. (2009), A typology of reviews: an analysis of 14 review types and associated methodologies . Health Information & Libraries Journal, 26 , 91–108. doi:10.1111/j.1471-1842.2009.00848.x

What's the difference between reviews?

Researchers, academics, and librarians all use various terms to describe different types of literature reviews, and there is often inconsistency in the ways the types are discussed. Here are a couple of simple explanations.

• The image below describes common review types in terms of speed, detail, risk of bias, and comprehensiveness:

"Schematic of the main differences between the types of literature review" by Brennan, M. L., Arlt, S. P., Belshaw, Z., Buckley, L., Corah, L., Doit, H., Fajt, V. R., Grindlay, D., Moberly, H. K., Morrow, L. D., Stavisky, J., & White, C. (2020). Critically Appraised Topics (CATs) in veterinary medicine: Applying evidence in clinical practice. Frontiers in Veterinary Science, 7 , 314. https://doi.org/10.3389/fvets.2020.00314 is licensed under CC BY 3.0

• The table below lists four of the most common types of review , as adapted from a widely used typology of fourteen types of reviews (Grant & Booth, 2009).  

Grant, M.J. & Booth, A. (2009).  A typology of reviews: An analysis of 14 review types and associated methodologies. Health Information & Libraries Journal, 26 (2), 91-108. https://doi.org/10.1111/j.1471-1842.2009.00848.x

See also the Library's  Literature Review guide.

Critical Appraised Topic (CAT)

For information on conducting a Critically Appraised Topic or CAT

Callander, J., Anstey, A. V., Ingram, J. R., Limpens, J., Flohr, C., & Spuls, P. I. (2017).  How to write a Critically Appraised Topic: evidence to underpin routine clinical practice.  British Journal of Dermatology (1951), 177(4), 1007-1013. https://doi.org/10.1111/bjd.15873 

Books on Literature Reviews

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Research Methods: Literature Reviews

• Annotated Bibliographies
• Literature Reviews
• Scoping Reviews
• Systematic Reviews
• Scholarship of Teaching and Learning
• Persuasive Arguments
• Subject Specific Methodology

A literature review involves researching, reading, analyzing, evaluating, and summarizing scholarly literature (typically journals and articles) about a specific topic. The results of a literature review may be an entire report or article OR may be part of a article, thesis, dissertation, or grant proposal. A literature review helps the author learn about the history and nature of their topic, and identify research gaps and problems.

Steps & Elements

Problem formulation

• Determine your topic and its components by asking a question
• Research: locate literature related to your topic to identify the gap(s) that can be addressed
• Read: read the articles or other sources of information
• Analyze: assess the findings for relevancy
• Evaluating: determine how the article are relevant to your research and what are the key findings
• Synthesis: write about the key findings and how it is relevant to your research

Elements of a Literature Review

• Summarize subject, issue or theory under consideration, along with objectives of the review
• Divide works under review into categories (e.g. those in support of a particular position, those against, those offering alternative theories entirely)
• Explain how each work is similar to and how it varies from the others
• Conclude which pieces are best considered in their argument, are most convincing of their opinions, and make the greatest contribution to the understanding and development of an area of research

Writing a Literature Review Resources

• How to Write a Literature Review From the Wesleyan University Library
• Write a Literature Review From the University of California Santa Cruz Library. A Brief overview of a literature review, includes a list of stages for writing a lit review.
• Literature Reviews From the University of North Carolina Writing Center. Detailed information about writing a literature review.
• Undertaking a literature review: a step-by-step approach Cronin, P., Ryan, F., & Coughan, M. (2008). Undertaking a literature review: A step-by-step approach. British Journal of Nursing, 17(1), p.38-43

Literature Review Tutorial

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A literature review is a document or section of a document that collects key sources on a topic and discusses those sources in conversation with each other (also called synthesis ). The lit review is an important genre in many disciplines, not just literature (i.e., the study of works of literature such as novels and plays). When we say “literature review” or refer to “the literature,” we are talking about the research ( scholarship ) in a given field. You will often see the terms “the research,” “the scholarship,” and “the literature” used mostly interchangeably.

Where, when, and why would I write a lit review?

There are a number of different situations where you might write a literature review, each with slightly different expectations; different disciplines, too, have field-specific expectations for what a literature review is and does. For instance, in the humanities, authors might include more overt argumentation and interpretation of source material in their literature reviews, whereas in the sciences, authors are more likely to report study designs and results in their literature reviews; these differences reflect these disciplines’ purposes and conventions in scholarship. You should always look at examples from your own discipline and talk to professors or mentors in your field to be sure you understand your discipline’s conventions, for literature reviews as well as for any other genre.

A literature review can be a part of a research paper or scholarly article, usually falling after the introduction and before the research methods sections. In these cases, the lit review just needs to cover scholarship that is important to the issue you are writing about; sometimes it will also cover key sources that informed your research methodology.

Lit reviews can also be standalone pieces, either as assignments in a class or as publications. In a class, a lit review may be assigned to help students familiarize themselves with a topic and with scholarship in their field, get an idea of the other researchers working on the topic they’re interested in, find gaps in existing research in order to propose new projects, and/or develop a theoretical framework and methodology for later research. As a publication, a lit review usually is meant to help make other scholars’ lives easier by collecting and summarizing, synthesizing, and analyzing existing research on a topic. This can be especially helpful for students or scholars getting into a new research area, or for directing an entire community of scholars toward questions that have not yet been answered.

What are the parts of a lit review?

Most lit reviews use a basic introduction-body-conclusion structure; if your lit review is part of a larger paper, the introduction and conclusion pieces may be just a few sentences while you focus most of your attention on the body. If your lit review is a standalone piece, the introduction and conclusion take up more space and give you a place to discuss your goals, research methods, and conclusions separately from where you discuss the literature itself.

Introduction:

• An introductory paragraph that explains what your working topic and thesis is
• A forecast of key topics or texts that will appear in the review
• Potentially, a description of how you found sources and how you analyzed them for inclusion and discussion in the review (more often found in published, standalone literature reviews than in lit review sections in an article or research paper)
• Summarize and synthesize: Give an overview of the main points of each source and combine them into a coherent whole
• Analyze and interpret: Don’t just paraphrase other researchers – add your own interpretations where possible, discussing the significance of findings in relation to the literature as a whole
• Critically Evaluate: Mention the strengths and weaknesses of your sources
• Write in well-structured paragraphs: Use transition words and topic sentence to draw connections, comparisons, and contrasts.

Conclusion:

• Summarize the key findings you have taken from the literature and emphasize their significance
• Connect it back to your primary research question

How should I organize my lit review?

Lit reviews can take many different organizational patterns depending on what you are trying to accomplish with the review. Here are some examples:

• Chronological : The simplest approach is to trace the development of the topic over time, which helps familiarize the audience with the topic (for instance if you are introducing something that is not commonly known in your field). If you choose this strategy, be careful to avoid simply listing and summarizing sources in order. Try to analyze the patterns, turning points, and key debates that have shaped the direction of the field. Give your interpretation of how and why certain developments occurred (as mentioned previously, this may not be appropriate in your discipline — check with a teacher or mentor if you’re unsure).
• Thematic : If you have found some recurring central themes that you will continue working with throughout your piece, you can organize your literature review into subsections that address different aspects of the topic. For example, if you are reviewing literature about women and religion, key themes can include the role of women in churches and the religious attitude towards women.
• Qualitative versus quantitative research
• Empirical versus theoretical scholarship
• Divide the research by sociological, historical, or cultural sources
• Theoretical : In many humanities articles, the literature review is the foundation for the theoretical framework. You can use it to discuss various theories, models, and definitions of key concepts. You can argue for the relevance of a specific theoretical approach or combine various theorical concepts to create a framework for your research.

What are some strategies or tips I can use while writing my lit review?

Any lit review is only as good as the research it discusses; make sure your sources are well-chosen and your research is thorough. Don’t be afraid to do more research if you discover a new thread as you’re writing. More info on the research process is available in our "Conducting Research" resources .

As you’re doing your research, create an annotated bibliography ( see our page on the this type of document ). Much of the information used in an annotated bibliography can be used also in a literature review, so you’ll be not only partially drafting your lit review as you research, but also developing your sense of the larger conversation going on among scholars, professionals, and any other stakeholders in your topic.

Usually you will need to synthesize research rather than just summarizing it. This means drawing connections between sources to create a picture of the scholarly conversation on a topic over time. Many student writers struggle to synthesize because they feel they don’t have anything to add to the scholars they are citing; here are some strategies to help you:

• It often helps to remember that the point of these kinds of syntheses is to show your readers how you understand your research, to help them read the rest of your paper.
• Writing teachers often say synthesis is like hosting a dinner party: imagine all your sources are together in a room, discussing your topic. What are they saying to each other?
• Look at the in-text citations in each paragraph. Are you citing just one source for each paragraph? This usually indicates summary only. When you have multiple sources cited in a paragraph, you are more likely to be synthesizing them (not always, but often
• Read more about synthesis here.

The most interesting literature reviews are often written as arguments (again, as mentioned at the beginning of the page, this is discipline-specific and doesn’t work for all situations). Often, the literature review is where you can establish your research as filling a particular gap or as relevant in a particular way. You have some chance to do this in your introduction in an article, but the literature review section gives a more extended opportunity to establish the conversation in the way you would like your readers to see it. You can choose the intellectual lineage you would like to be part of and whose definitions matter most to your thinking (mostly humanities-specific, but this goes for sciences as well). In addressing these points, you argue for your place in the conversation, which tends to make the lit review more compelling than a simple reporting of other sources.

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Systematic Reviews

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What Makes a Systematic Review Different from Other Types of Reviews?

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Reproduced from Grant, M. J. and Booth, A. (2009), A typology of reviews: an analysis of 14 review types and associated methodologies. Health Information & Libraries Journal, 26: 91–108. doi:10.1111/j.1471-1842.2009.00848.x

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Literature reviews.

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Research methods overview

Finding literature on research methodologies, sage research methods online.

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What are research methods?

Research methodology is the specific strategies, processes, or techniques utilised in the collection of information that is created and analysed.

The methodology section of a research paper, or thesis, enables the reader to critically evaluate the study’s validity and reliability by addressing how the data was collected or generated, and how it was analysed.

Types of research methods

There are three main types of research methods which use different designs for data collection.  

(1) Qualitative research

Qualitative research gathers data about lived experiences, emotions or behaviours, and the meanings individuals attach to them. It assists in enabling researchers to gain a better understanding of complex concepts, social interactions or cultural phenomena. This type of research is useful in the exploration of how or why things have occurred, interpreting events and describing actions.

Examples of qualitative research designs include:

• focus groups
• observations
• document analysis
• oral history or life stories  

(2) Quantitative research

Quantitative research gathers numerical data which can be ranked, measured or categorised through statistical analysis. It assists with uncovering patterns or relationships, and for making generalisations. This type of research is useful for finding out how many, how much, how often, or to what extent.

Examples of quantitative research designs include:

• surveys or questionnaires
• observation
• document screening
• experiments  

(3) Mixed method research

Mixed Methods research integrates both Qualitative research and Quantitative research. It provides a holistic approach combining and analysing the statistical data with deeper contextualised insights. Using Mixed Methods also enables triangulation, or verification, of the data from two or more sources.

Sometimes in your literature review, you might need to discuss and evaluate relevant research methodologies in order to justify your own choice of research methodology.

When searching for literature on research methodologies it is important to search across a range of sources. No single information source will supply all that you need. Selecting appropriate sources will depend upon your research topic.

Developing a robust search strategy will help reduce irrelevant results. It is good practice to plan a strategy before you start to search.

Search tips

(1) free text keywords.

Free text searching is the use of natural language words to conduct your search. Use selective free text keywords such as: phenomenological, "lived experience", "grounded theory", "life experiences", "focus groups", interview, quantitative, survey, validity, variance, correlation and statistical.

To locate books on your desired methodology, try LibrarySearch . Remember to use  refine  options such as books, ebooks, subject, and publication date.  

(2) Subject headings in Databases

Databases categorise their records using subject terms, or a controlled vocabulary (thesaurus). These subject headings may be useful to use, in addition to utilising free text keywords in a database search.

Subject headings will differ across databases, for example, the PubMed database uses 'Qualitative Research' whilst the CINHAL database uses 'Qualitative Studies.'  

(3) Limiting search results

Databases enable sets of results to be limited or filtered by specific fields, look for options such as Publication Type, Article Type, etc. and apply them to your search.  

(4) Browse the Library shelves

To find books on  research methods  browse the Library shelves at call number  001.42

• SAGE Research Methods Online SAGE Research Methods Online (SRMO) is a research tool supported by a newly devised taxonomy that links content and methods terms. It provides the most comprehensive picture available today of research methods (quantitative, qualitative and mixed methods) across the social and behavioural sciences.

SAGE Research Methods Overview  (2:07 min) by SAGE Publishing  ( YouTube ) 

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What is a literature review?

A literature review is an integrated analysis -- not just a summary-- of scholarly writings and other relevant evidence related directly to your research question.  That is, it represents a synthesis of the evidence that provides background information on your topic and shows a association between the evidence and your research question.

A literature review may be a stand alone work or the introduction to a larger research paper, depending on the assignment.  Rely heavily on the guidelines your instructor has given you.

Why is it important?

A literature review is important because it:

• Explains the background of research on a topic.
• Demonstrates why a topic is significant to a subject area.
• Discovers relationships between research studies/ideas.
• Identifies major themes, concepts, and researchers on a topic.
• Identifies critical gaps and points of disagreement.
• Discusses further research questions that logically come out of the previous studies.

APA7 Style resources

APA Style Blog - for those harder to find answers

1. Choose a topic. Define your research question.

Your literature review should be guided by your central research question.  The literature represents background and research developments related to a specific research question, interpreted and analyzed by you in a synthesized way.

• Make sure your research question is not too broad or too narrow.  Is it manageable?
• Begin writing down terms that are related to your question. These will be useful for searches later.
• If you have the opportunity, discuss your topic with your professor and your class mates.

2. Decide on the scope of your review

How many studies do you need to look at? How comprehensive should it be? How many years should it cover? 

• This may depend on your assignment.  How many sources does the assignment require?

3. Select the databases you will use to conduct your searches.

Make a list of the databases you will search. 

Where to find databases:

• use the tabs on this guide
• Find other databases in the Nursing Information Resources web page
• More on the Medical Library web page
• ... and more on the Yale University Library web page

4. Conduct your searches to find the evidence. Keep track of your searches.

• Use the key words in your question, as well as synonyms for those words, as terms in your search. Use the database tutorials for help.
• Save the searches in the databases. This saves time when you want to redo, or modify, the searches. It is also helpful to use as a guide is the searches are not finding any useful results.
• Review the abstracts of research studies carefully. This will save you time.
• Use the bibliographies and references of research studies you find to locate others.
• Check with your professor, or a subject expert in the field, if you are missing any key works in the field.
• Ask your librarian for help at any time.
• Use a citation manager, such as EndNote as the repository for your citations. See the EndNote tutorials for help.

Review the literature

Some questions to help you analyze the research:

• What was the research question of the study you are reviewing? What were the authors trying to discover?
• Was the research funded by a source that could influence the findings?
• What were the research methodologies? Analyze its literature review, the samples and variables used, the results, and the conclusions.
• Does the research seem to be complete? Could it have been conducted more soundly? What further questions does it raise?
• If there are conflicting studies, why do you think that is?
• How are the authors viewed in the field? Has this study been cited? If so, how has it been analyzed?

Tips: 

• Review the abstracts carefully.  
• Keep careful notes so that you may track your thought processes during the research process.
• Create a matrix of the studies for easy analysis, and synthesis, across all of the studies.
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Evidence Synthesis, Systematic Review Services : Literature Review Types, Taxonomies

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Choosing a Literature Review Methodology

Growing interest in evidence-based practice has driven an increase in review methodologies. Your choice of review methodology (or literature review type) will be informed by the intent (purpose, function) of your research project and the time and resources of your team. 

• Decision Tree (What Type of Review is Right for You?) Developed by Cornell University Library staff, this "decision-tree" guides the user to a handful of review guides given time and intent.

Types of Evidence Synthesis*

Critical Review - Aims to demonstrate writer has extensively researched literature and critically evaluated its quality. Goes beyond mere description to include degree of analysis and conceptual innovation. Typically results in hypothesis or model.

Mapping Review (Systematic Map) - Map out and categorize existing literature from which to commission further reviews and/or primary research by identifying gaps in research literature.

Meta-Analysis - Technique that statistically combines the results of quantitative studies to provide a more precise effect of the results.

Mixed Studies Review (Mixed Methods Review) - Refers to any combination of methods where one significant component is a literature review (usually systematic). Within a review context it refers to a combination of review approaches for example combining quantitative with qualitative research or outcome with process studies.

Narrative (Literature) Review - Generic term: published materials that provide examination of recent or current literature. Can cover wide range of subjects at various levels of completeness and comprehensiveness.

Overview - Generic term: summary of the [medical] literature that attempts to survey the literature and describe its characteristics.

Qualitative Systematic Review or Qualitative Evidence Synthesis - Method for integrating or comparing the findings from qualitative studies. It looks for ‘themes’ or ‘constructs’ that lie in or across individual qualitative studies.

Rapid Review - Assessment of what is already known about a policy or practice issue, by using systematic review methods to search and critically appraise existing research.

Scoping Review or Evidence Map - Preliminary assessment of potential size and scope of available research literature. Aims to identify nature and extent of research.

State-of-the-art Review - Tend to address more current matters in contrast to other combined retrospective and current approaches. May offer new perspectives on issue or point out area for further research.

Systematic Review - Seeks to systematically search for, appraise and synthesis research evidence, often adhering to guidelines on the conduct of a review. (An emerging subset includes Living Reviews or Living Systematic Reviews - A [review or] systematic review which is continually updated, incorporating relevant new evidence as it becomes available.)

Systematic Search and Review - Combines strengths of critical review with a comprehensive search process. Typically addresses broad questions to produce ‘best evidence synthesis.’

Umbrella Review - Specifically refers to review compiling evidence from multiple reviews into one accessible and usable document. Focuses on broad condition or problem for which there are competing interventions and highlights reviews that address these interventions and their results.

*These definitions are in Grant & Booth's "A Typology of Reviews: An Analysis of 14 Review Types and Associated Methodologies."

Literature Review Types/Typologies, Taxonomies

Grant, M. J., and A. Booth. "A Typology of Reviews: An Analysis of 14 Review Types and Associated Methodologies."  Health Information and Libraries Journal  26.2 (2009): 91-108.  DOI: 10.1111/j.1471-1842.2009.00848.x  Link

Munn, Zachary, et al. “Systematic Review or Scoping Review? Guidance for Authors When Choosing between a Systematic or Scoping Review Approach.” BMC Medical Research Methodology , vol. 18, no. 1, Nov. 2018, p. 143. DOI: 10.1186/s12874-018-0611-x. Link

Sutton, A., et al. "Meeting the Review Family: Exploring Review Types and Associated Information Retrieval Requirements."  Health Information and Libraries Journal  36.3 (2019): 202-22.  DOI: 10.1111/hir.12276  Link

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Choosing a Review Type

For guidance related to choosing a review type, see:

• "What Type of Review is Right for You?" - Decision Tree (PDF) This decision tree, from Cornell University Library, highlights key difference between narrative, systematic, umbrella, scoping and rapid reviews.
• Reviewing the literature: choosing a review design Noble, H., & Smith, J. (2018). Reviewing the literature: Choosing a review design. Evidence Based Nursing, 21(2), 39–41. https://doi.org/10.1136/eb-2018-102895
• What synthesis methodology should I use? A review and analysis of approaches to research synthesis Schick-Makaroff, K., MacDonald, M., Plummer, M., Burgess, J., & Neander, W. (2016). What synthesis methodology should I use? A review and analysis of approaches to research synthesis. AIMS Public Health, 3 (1), 172-215. doi:10.3934/publichealth.2016.1.172 More information less... ABSTRACT: Our purpose is to present a comprehensive overview and assessment of the main approaches to research synthesis. We use "research synthesis" as a broad overarching term to describe various approaches to combining, integrating, and synthesizing research findings.
• Right Review - Decision Support Tool Not sure of the most suitable review method? Answer a few questions and be guided to suitable knowledge synthesis methods. Updated in 2022 and featured in the Journal of Clinical Epidemiology 10.1016/j.jclinepi.2022.03.004

Types of Evidence Synthesis / Literature Reviews

Literature reviews are comprehensive summaries and syntheses of the previous research on a given topic.  While narrative reviews are common across all academic disciplines, reviews that focus on appraising and synthesizing research evidence are increasingly important in the health and social sciences.  

Most evidence synthesis methods use formal and explicit methods to identify, select and combine results from multiple studies, making evidence synthesis a form of meta-research.  

The review purpose, methods used and the results produced vary among different kinds of literature reviews; some of the common types of literature review are detailed below.

Common Types of Literature Reviews 1

Narrative (literature) review.

• A broad term referring to reviews with a wide scope and non-standardized methodology
• Search strategies, comprehensiveness of literature search, time range covered and method of synthesis will vary and do not follow an established protocol

Integrative Review

• A type of literature review based on a systematic, structured literature search
• Often has a broadly defined purpose or review question
• Seeks to generate or refine and theory or hypothesis and/or develop a holistic understanding of a topic of interest
• Relies on diverse sources of data (e.g. empirical, theoretical or methodological literature; qualitative or quantitative studies)

Systematic Review

• Systematically and transparently collects and categorize existing evidence on a question of scientific, policy or management importance
• Follows a research protocol that is established a priori
• Some sub-types of systematic reviews include: SRs of intervention effectiveness, diagnosis, prognosis, etiology, qualitative evidence, economic evidence, and more.
• Time-intensive and often takes months to a year or more to complete 
• The most commonly referred to type of evidence synthesis; sometimes confused as a blanket term for other types of reviews

Meta-Analysis

• Statistical technique for combining the findings from disparate quantitative studies
• Uses statistical methods to objectively evaluate, synthesize, and summarize results
• Often conducted as part of a systematic review

Scoping Review

• Systematically and transparently collects and categorizes existing evidence on a broad question of scientific, policy or management importance
• Seeks to identify research gaps, identify key concepts and characteristics of the literature and/or examine how research is conducted on a topic of interest
• Useful when the complexity or heterogeneity of the body of literature does not lend itself to a precise systematic review
• Useful if authors do not have a single, precise review question
• May critically evaluate existing evidence, but does not attempt to synthesize the results in the way a systematic review would 
• May take longer than a systematic review

Rapid Review

• Applies a systematic review methodology within a time-constrained setting
• Employs methodological "shortcuts" (e.g., limiting search terms and the scope of the literature search), at the risk of introducing bias
• Useful for addressing issues requiring quick decisions, such as developing policy recommendations

Umbrella Review

• Reviews other systematic reviews on a topic
• Often defines a broader question than is typical of a traditional systematic review
• Most useful when there are competing interventions to consider

1. Adapted from:

Eldermire, E. (2021, November 15). A guide to evidence synthesis: Types of evidence synthesis. Cornell University LibGuides. https://guides.library.cornell.edu/evidence-synthesis/types

Nolfi, D. (2021, October 6). Integrative Review: Systematic vs. Scoping vs. Integrative. Duquesne University LibGuides. https://guides.library.duq.edu/c.php?g=1055475&p=7725920

Delaney, L. (2021, November 24). Systematic reviews: Other review types. UniSA LibGuides. https://guides.library.unisa.edu.au/SystematicReviews/OtherReviewTypes

Further Reading: Exploring Different Types of Literature Reviews

• A typology of reviews: An analysis of 14 review types and associated methodologies Grant, M. J., & Booth, A. (2009). A typology of reviews: An analysis of 14 review types and associated methodologies. Health Information and Libraries Journal, 26 (2), 91-108. doi:10.1111/j.1471-1842.2009.00848.x More information less... ABSTRACT: The expansion of evidence-based practice across sectors has lead to an increasing variety of review types. However, the diversity of terminology used means that the full potential of these review types may be lost amongst a confusion of indistinct and misapplied terms. The objective of this study is to provide descriptive insight into the most common types of reviews, with illustrative examples from health and health information domains.
• Clarifying differences between review designs and methods Gough, D., Thomas, J., & Oliver, S. (2012). Clarifying differences between review designs and methods. Systematic Reviews, 1 , 28. doi:10.1186/2046-4053-1-28 More information less... ABSTRACT: This paper argues that the current proliferation of types of systematic reviews creates challenges for the terminology for describing such reviews....It is therefore proposed that the most useful strategy for the field is to develop terminology for the main dimensions of variation.
• Are we talking the same paradigm? Considering methodological choices in health education systematic review Gordon, M. (2016). Are we talking the same paradigm? Considering methodological choices in health education systematic review. Medical Teacher, 38 (7), 746-750. doi:10.3109/0142159X.2016.1147536 More information less... ABSTRACT: Key items discussed are the positivist synthesis methods meta-analysis and content analysis to address questions in the form of "whether and what" education is effective. These can be juxtaposed with the constructivist aligned thematic analysis and meta-ethnography to address questions in the form of "why." The concept of the realist review is also considered. It is proposed that authors of such work should describe their research alignment and the link between question, alignment and evidence synthesis method selected.
• Meeting the review family: Exploring review types and associated information retrieval requirements Sutton, A., Clowes, M., Preston, L., & Booth, A. (2019). Meeting the review family: Exploring review types and associated information retrieval requirements. Health Information & Libraries Journal, 36(3), 202–222. doi: 10.1111/hir.12276

Integrative Reviews

"The integrative review method is an approach that allows for the inclusion of diverse methodologies (i.e. experimental and non-experimental research)." (Whittemore & Knafl, 2005, p. 547).

• The integrative review: Updated methodology Whittemore, R., & Knafl, K. (2005). The integrative review: Updated methodology. Journal of Advanced Nursing, 52 (5), 546–553. doi:10.1111/j.1365-2648.2005.03621.x More information less... ABSTRACT: The aim of this paper is to distinguish the integrative review method from other review methods and to propose methodological strategies specific to the integrative review method to enhance the rigour of the process....An integrative review is a specific review method that summarizes past empirical or theoretical literature to provide a more comprehensive understanding of a particular phenomenon or healthcare problem....Well-done integrative reviews present the state of the science, contribute to theory development, and have direct applicability to practice and policy.

• Conducting integrative reviews: A guide for novice nursing researchers Dhollande, S., Taylor, A., Meyer, S., & Scott, M. (2021). Conducting integrative reviews: A guide for novice nursing researchers. Journal of Research in Nursing, 26(5), 427–438. https://doi.org/10.1177/1744987121997907
• Rigour in integrative reviews Whittemore, R. (2007). Rigour in integrative reviews. In C. Webb & B. Roe (Eds.), Reviewing Research Evidence for Nursing Practice (pp. 149–156). John Wiley & Sons, Ltd. https://doi.org/10.1002/9780470692127.ch11

Scoping Reviews

Scoping reviews are evidence syntheses that are conducted systematically, but begin with a broader scope of question than traditional systematic reviews, allowing the research to 'map' the relevant literature on a given topic.

• Scoping studies: Towards a methodological framework Arksey, H., & O'Malley, L. (2005). Scoping studies: Towards a methodological framework. International Journal of Social Research Methodology, 8 (1), 19-32. doi:10.1080/1364557032000119616 More information less... ABSTRACT: We distinguish between different types of scoping studies and indicate where these stand in relation to full systematic reviews. We outline a framework for conducting a scoping study based on our recent experiences of reviewing the literature on services for carers for people with mental health problems.
• Scoping studies: Advancing the methodology Levac, D., Colquhoun, H., & O'Brien, K. K. (2010). Scoping studies: Advancing the methodology. Implementation Science, 5 (1), 69. doi:10.1186/1748-5908-5-69 More information less... ABSTRACT: We build upon our experiences conducting three scoping studies using the Arksey and O'Malley methodology to propose recommendations that clarify and enhance each stage of the framework.
• Methodology for JBI scoping reviews Peters, M. D. J., Godfrey, C. M., McInerney, P., Baldini Soares, C., Khalil, H., & Parker, D. (2015). The Joanna Briggs Institute reviewers’ manual: Methodology for JBI scoping reviews [PDF]. Retrieved from The Joanna Briggs Institute website: http://joannabriggs.org/assets/docs/sumari/Reviewers-Manual_Methodology-for-JBI-Scoping-Reviews_2015_v2.pdf More information less... ABSTRACT: Unlike other reviews that address relatively precise questions, such as a systematic review of the effectiveness of a particular intervention based on a precise set of outcomes, scoping reviews can be used to map the key concepts underpinning a research area as well as to clarify working definitions, and/or the conceptual boundaries of a topic. A scoping review may focus on one of these aims or all of them as a set.

Systematic vs. Scoping Reviews: What's the Difference? 

YouTube Video 4 minutes, 45 seconds

Rapid Reviews

Rapid reviews are systematic reviews that are undertaken under a tighter timeframe than traditional systematic reviews. 

• Evidence summaries: The evolution of a rapid review approach Khangura, S., Konnyu, K., Cushman, R., Grimshaw, J., & Moher, D. (2012). Evidence summaries: The evolution of a rapid review approach. Systematic Reviews, 1 (1), 10. doi:10.1186/2046-4053-1-10 More information less... ABSTRACT: Rapid reviews have emerged as a streamlined approach to synthesizing evidence - typically for informing emergent decisions faced by decision makers in health care settings. Although there is growing use of rapid review "methods," and proliferation of rapid review products, there is a dearth of published literature on rapid review methodology. This paper outlines our experience with rapidly producing, publishing and disseminating evidence summaries in the context of our Knowledge to Action (KTA) research program.
• What is a rapid review? A methodological exploration of rapid reviews in Health Technology Assessments Harker, J., & Kleijnen, J. (2012). What is a rapid review? A methodological exploration of rapid reviews in Health Technology Assessments. International Journal of Evidence‐Based Healthcare, 10 (4), 397-410. doi:10.1111/j.1744-1609.2012.00290.x More information less... ABSTRACT: In recent years, there has been an emergence of "rapid reviews" within Health Technology Assessments; however, there is no known published guidance or agreed methodology within recognised systematic review or Health Technology Assessment guidelines. In order to answer the research question "What is a rapid review and is methodology consistent in rapid reviews of Health Technology Assessments?", a study was undertaken in a sample of rapid review Health Technology Assessments from the Health Technology Assessment database within the Cochrane Library and other specialised Health Technology Assessment databases to investigate similarities and/or differences in rapid review methodology utilised.
• Rapid Review Guidebook Dobbins, M. (2017). Rapid review guidebook. Hamilton, ON: National Collaborating Centre for Methods and Tools.
• NCCMT Summary and Tool for Dobbins' Rapid Review Guidebook National Collaborating Centre for Methods and Tools. (2017). Rapid review guidebook. Hamilton, ON: McMaster University. Retrieved from http://www.nccmt.ca/knowledge-repositories/search/308
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Methodology

• Systematic Review | Definition, Example, & Guide

Systematic Review | Definition, Example & Guide

Published on June 15, 2022 by Shaun Turney . Revised on November 20, 2023.

A systematic review is a type of review that uses repeatable methods to find, select, and synthesize all available evidence. It answers a clearly formulated research question and explicitly states the methods used to arrive at the answer.

They answered the question “What is the effectiveness of probiotics in reducing eczema symptoms and improving quality of life in patients with eczema?”

In this context, a probiotic is a health product that contains live microorganisms and is taken by mouth. Eczema is a common skin condition that causes red, itchy skin.

Table of contents

What is a systematic review, systematic review vs. meta-analysis, systematic review vs. literature review, systematic review vs. scoping review, when to conduct a systematic review, pros and cons of systematic reviews, step-by-step example of a systematic review, other interesting articles, frequently asked questions about systematic reviews.

A review is an overview of the research that’s already been completed on a topic.

What makes a systematic review different from other types of reviews is that the research methods are designed to reduce bias . The methods are repeatable, and the approach is formal and systematic:

• Formulate a research question
• Develop a protocol
• Search for all relevant studies
• Apply the selection criteria
• Extract the data
• Synthesize the data
• Write and publish a report

Although multiple sets of guidelines exist, the Cochrane Handbook for Systematic Reviews is among the most widely used. It provides detailed guidelines on how to complete each step of the systematic review process.

Systematic reviews are most commonly used in medical and public health research, but they can also be found in other disciplines.

Systematic reviews typically answer their research question by synthesizing all available evidence and evaluating the quality of the evidence. Synthesizing means bringing together different information to tell a single, cohesive story. The synthesis can be narrative ( qualitative ), quantitative , or both.

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Systematic reviews often quantitatively synthesize the evidence using a meta-analysis . A meta-analysis is a statistical analysis, not a type of review.

A meta-analysis is a technique to synthesize results from multiple studies. It’s a statistical analysis that combines the results of two or more studies, usually to estimate an effect size .

A literature review is a type of review that uses a less systematic and formal approach than a systematic review. Typically, an expert in a topic will qualitatively summarize and evaluate previous work, without using a formal, explicit method.

Although literature reviews are often less time-consuming and can be insightful or helpful, they have a higher risk of bias and are less transparent than systematic reviews.

Similar to a systematic review, a scoping review is a type of review that tries to minimize bias by using transparent and repeatable methods.

However, a scoping review isn’t a type of systematic review. The most important difference is the goal: rather than answering a specific question, a scoping review explores a topic. The researcher tries to identify the main concepts, theories, and evidence, as well as gaps in the current research.

Sometimes scoping reviews are an exploratory preparation step for a systematic review, and sometimes they are a standalone project.

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A systematic review is a good choice of review if you want to answer a question about the effectiveness of an intervention , such as a medical treatment.

To conduct a systematic review, you’ll need the following:

• A precise question , usually about the effectiveness of an intervention. The question needs to be about a topic that’s previously been studied by multiple researchers. If there’s no previous research, there’s nothing to review.
• If you’re doing a systematic review on your own (e.g., for a research paper or thesis ), you should take appropriate measures to ensure the validity and reliability of your research.
• Access to databases and journal archives. Often, your educational institution provides you with access.
• Time. A professional systematic review is a time-consuming process: it will take the lead author about six months of full-time work. If you’re a student, you should narrow the scope of your systematic review and stick to a tight schedule.
• Bibliographic, word-processing, spreadsheet, and statistical software . For example, you could use EndNote, Microsoft Word, Excel, and SPSS.

A systematic review has many pros .

• They minimize research bias by considering all available evidence and evaluating each study for bias.
• Their methods are transparent , so they can be scrutinized by others.
• They’re thorough : they summarize all available evidence.
• They can be replicated and updated by others.

Systematic reviews also have a few cons .

• They’re time-consuming .
• They’re narrow in scope : they only answer the precise research question.

The 7 steps for conducting a systematic review are explained with an example.

Step 1: Formulate a research question

Formulating the research question is probably the most important step of a systematic review. A clear research question will:

• Allow you to more effectively communicate your research to other researchers and practitioners
• Guide your decisions as you plan and conduct your systematic review

A good research question for a systematic review has four components, which you can remember with the acronym PICO :

• Population(s) or problem(s)
• Intervention(s)
• Comparison(s)

You can rearrange these four components to write your research question:

• What is the effectiveness of I versus C for O in P ?

Sometimes, you may want to include a fifth component, the type of study design . In this case, the acronym is PICOT .

• Type of study design(s)
• The population of patients with eczema
• The intervention of probiotics
• In comparison to no treatment, placebo , or non-probiotic treatment
• The outcome of changes in participant-, parent-, and doctor-rated symptoms of eczema and quality of life
• Randomized control trials, a type of study design

Their research question was:

• What is the effectiveness of probiotics versus no treatment, a placebo, or a non-probiotic treatment for reducing eczema symptoms and improving quality of life in patients with eczema?

Step 2: Develop a protocol

A protocol is a document that contains your research plan for the systematic review. This is an important step because having a plan allows you to work more efficiently and reduces bias.

Your protocol should include the following components:

• Background information : Provide the context of the research question, including why it’s important.
• Research objective (s) : Rephrase your research question as an objective.
• Selection criteria: State how you’ll decide which studies to include or exclude from your review.
• Search strategy: Discuss your plan for finding studies.
• Analysis: Explain what information you’ll collect from the studies and how you’ll synthesize the data.

If you’re a professional seeking to publish your review, it’s a good idea to bring together an advisory committee . This is a group of about six people who have experience in the topic you’re researching. They can help you make decisions about your protocol.

It’s highly recommended to register your protocol. Registering your protocol means submitting it to a database such as PROSPERO or ClinicalTrials.gov .

Step 3: Search for all relevant studies

Searching for relevant studies is the most time-consuming step of a systematic review.

To reduce bias, it’s important to search for relevant studies very thoroughly. Your strategy will depend on your field and your research question, but sources generally fall into these four categories:

• Databases: Search multiple databases of peer-reviewed literature, such as PubMed or Scopus . Think carefully about how to phrase your search terms and include multiple synonyms of each word. Use Boolean operators if relevant.
• Handsearching: In addition to searching the primary sources using databases, you’ll also need to search manually. One strategy is to scan relevant journals or conference proceedings. Another strategy is to scan the reference lists of relevant studies.
• Gray literature: Gray literature includes documents produced by governments, universities, and other institutions that aren’t published by traditional publishers. Graduate student theses are an important type of gray literature, which you can search using the Networked Digital Library of Theses and Dissertations (NDLTD) . In medicine, clinical trial registries are another important type of gray literature.
• Experts: Contact experts in the field to ask if they have unpublished studies that should be included in your review.

At this stage of your review, you won’t read the articles yet. Simply save any potentially relevant citations using bibliographic software, such as Scribbr’s APA or MLA Generator .

• Databases: EMBASE, PsycINFO, AMED, LILACS, and ISI Web of Science
• Handsearch: Conference proceedings and reference lists of articles
• Gray literature: The Cochrane Library, the metaRegister of Controlled Trials, and the Ongoing Skin Trials Register
• Experts: Authors of unpublished registered trials, pharmaceutical companies, and manufacturers of probiotics

Step 4: Apply the selection criteria

Applying the selection criteria is a three-person job. Two of you will independently read the studies and decide which to include in your review based on the selection criteria you established in your protocol . The third person’s job is to break any ties.

To increase inter-rater reliability , ensure that everyone thoroughly understands the selection criteria before you begin.

If you’re writing a systematic review as a student for an assignment, you might not have a team. In this case, you’ll have to apply the selection criteria on your own; you can mention this as a limitation in your paper’s discussion.

You should apply the selection criteria in two phases:

• Based on the titles and abstracts : Decide whether each article potentially meets the selection criteria based on the information provided in the abstracts.
• Based on the full texts: Download the articles that weren’t excluded during the first phase. If an article isn’t available online or through your library, you may need to contact the authors to ask for a copy. Read the articles and decide which articles meet the selection criteria.

It’s very important to keep a meticulous record of why you included or excluded each article. When the selection process is complete, you can summarize what you did using a PRISMA flow diagram .

Next, Boyle and colleagues found the full texts for each of the remaining studies. Boyle and Tang read through the articles to decide if any more studies needed to be excluded based on the selection criteria.

When Boyle and Tang disagreed about whether a study should be excluded, they discussed it with Varigos until the three researchers came to an agreement.

Step 5: Extract the data

Extracting the data means collecting information from the selected studies in a systematic way. There are two types of information you need to collect from each study:

• Information about the study’s methods and results . The exact information will depend on your research question, but it might include the year, study design , sample size, context, research findings , and conclusions. If any data are missing, you’ll need to contact the study’s authors.
• Your judgment of the quality of the evidence, including risk of bias .

You should collect this information using forms. You can find sample forms in The Registry of Methods and Tools for Evidence-Informed Decision Making and the Grading of Recommendations, Assessment, Development and Evaluations Working Group .

Extracting the data is also a three-person job. Two people should do this step independently, and the third person will resolve any disagreements.

They also collected data about possible sources of bias, such as how the study participants were randomized into the control and treatment groups.

Step 6: Synthesize the data

Synthesizing the data means bringing together the information you collected into a single, cohesive story. There are two main approaches to synthesizing the data:

• Narrative ( qualitative ): Summarize the information in words. You’ll need to discuss the studies and assess their overall quality.
• Quantitative : Use statistical methods to summarize and compare data from different studies. The most common quantitative approach is a meta-analysis , which allows you to combine results from multiple studies into a summary result.

Generally, you should use both approaches together whenever possible. If you don’t have enough data, or the data from different studies aren’t comparable, then you can take just a narrative approach. However, you should justify why a quantitative approach wasn’t possible.

Boyle and colleagues also divided the studies into subgroups, such as studies about babies, children, and adults, and analyzed the effect sizes within each group.

Step 7: Write and publish a report

The purpose of writing a systematic review article is to share the answer to your research question and explain how you arrived at this answer.

Your article should include the following sections:

• Abstract : A summary of the review
• Introduction : Including the rationale and objectives
• Methods : Including the selection criteria, search method, data extraction method, and synthesis method
• Results : Including results of the search and selection process, study characteristics, risk of bias in the studies, and synthesis results
• Discussion : Including interpretation of the results and limitations of the review
• Conclusion : The answer to your research question and implications for practice, policy, or research

To verify that your report includes everything it needs, you can use the PRISMA checklist .

Once your report is written, you can publish it in a systematic review database, such as the Cochrane Database of Systematic Reviews , and/or in a peer-reviewed journal.

In their report, Boyle and colleagues concluded that probiotics cannot be recommended for reducing eczema symptoms or improving quality of life in patients with eczema. Note Generative AI tools like ChatGPT can be useful at various stages of the writing and research process and can help you to write your systematic review. However, we strongly advise against trying to pass AI-generated text off as your own work.

If you want to know more about statistics , methodology , or research bias , make sure to check out some of our other articles with explanations and examples.

• Student’s  t -distribution
• Normal distribution
• Null and Alternative Hypotheses
• Chi square tests
• Confidence interval
• Quartiles & Quantiles
• Cluster sampling
• Stratified sampling
• Data cleansing
• Reproducibility vs Replicability
• Peer review
• Prospective cohort study

Research bias

• Implicit bias
• Cognitive bias
• Placebo effect
• Hawthorne effect
• Hindsight bias
• Affect heuristic
• Social desirability bias

A literature review is a survey of scholarly sources (such as books, journal articles, and theses) related to a specific topic or research question .

It is often written as part of a thesis, dissertation , or research paper , in order to situate your work in relation to existing knowledge.

A literature review is a survey of credible sources on a topic, often used in dissertations , theses, and research papers . Literature reviews give an overview of knowledge on a subject, helping you identify relevant theories and methods, as well as gaps in existing research. Literature reviews are set up similarly to other  academic texts , with an introduction , a main body, and a conclusion .

An  annotated bibliography is a list of  source references that has a short description (called an annotation ) for each of the sources. It is often assigned as part of the research process for a  paper .  

A systematic review is secondary research because it uses existing research. You don’t collect new data yourself.

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JSmol Viewer

Digital twin—a review of the evolution from concept to technology and its analytical perspectives on applications in various fields.

1. Introduction

2. literature review methodology, 3. digital twin, from concept to architecture model, 3.1. the concept of digital twins.

• High degree of accuracy: From the appearance, functionalities, and content point of view, the DT must be an accurate copy of its physical counterpart. Thus, the higher the precision, the actions and simulation scenarios should achieve the same behavior both in the physical and virtual environment.
• Dynamic: Communication between the physical product and its virtual twin must be continuous and bidirectional, and any change made to one must be reflected in the behavior of the other.
• Self-evolving: Throughout the life cycle, the DT follows the changes along with its physical counterpart. The DT adapts and optimizes with the aid of the data received from the physical counterpart in real time, evolving with it.
• Identifiable: Each real product must have its own DT. During the product life cycle, information and functional models evolve, and based on this, at any point in time, the DT can be identified in a unique mode from its physical twin [ 11 ].

3.2. Classification of Digital Twins

• Digital Twin Prototype (DTP): The DTP is the DT that contains the essential information for creating a physical copy of a virtual version. The product cycle will be initiated upon achievement of the DTP, which undergoes several tests before the physical twin is created. Once the DTP is realized and validated, its physical counterpart can be produced in the real environment. The simulation accuracy determines the physical twin quality.
• Digital Twin Instance (DTI): The DTI originates in the production phase and is a DT that is strongly correlated, throughout its life cycle. After building the physical system, real space data are transmitted to digital space and, reversely, to predict and monitor the system behavior.
• Predictive DT: DT predicts the behavior and performance of its physical counterpart.
• Interrogative DT: The DT is used to query the status of its counterpart.
• Digital Model: The data between the physical and virtual object are manually changed by the user. Any change to the state of the physical object is not reflected in the virtual object, and any change to the state of the virtual object is not reflected in the physical object.
• Digital Shadow: The data of the physical object is automatically transmitted to the virtual object, so there is one-way communication between the two objects.
• Digital Twin: This DT category involves a two-way data transmission between the physical twin and the digital one, and any modification made to both the physical and the digital object will be reflected in the behavior of its counterpart.
• Predictive Digital Twin: Like the normal Digital Twin, it is characterized by continuous, real-time communication between the two components. The novelty brought by the Predictive DT consists of the fact that the digital twin also contains cyber security components and artificial intelligence algorithms that increase the accuracy of the simulation results and allow predictions to be made.
• Product DT: DT is used for prototyping, and various conditions are analyzed, which helps to confirm that the physical product behaves according to the desired standards.
• Production DT: DT is used before actual production and has a role in process validation, simulation and analysis. It also helps develop efficient production methodologies.
• Performance DT: This DT can include both actual product and production performance and is used for decision-making processes by receiving, integrating, and analyzing product data. It also optimizes operations based on resource availability, providing the opportunity to improve product and production DT through a feedback loop.
• Unit level: Represents the smallest unit participating in production and examines the functional, geometric, behavioral, and operational model of the physical counterpart unit level.
• System level: Represents a collaboration of unit-level DTs, and each unit-level DT represents a component of the new system.
• System of Systems (SoSs) level: Represents the connection of multiple system-level DTs to form a system of systems. The system-of-systems DT also includes various phases throughout the life cycle of a product.
• Partial DT: May contain parameters (pressure, temperature, humidity) and is used to determine the DT functionality and connectivity.
• DT Clone: It is used to make prototypes that are made by means of the relevant data about the product/system. The data are contained in this DT.
• Augmented DT: It has the role of making a correlation between current data and past data based on algorithms and analyses.
• Pre-Digital Twin: In this stage, the DT is created before the physical object and is used in the process of decision making, referring to the prototype to reduce the risks that may arise.
• Digital Twin: It represents the second stage, and at its level, the data of the physical product are incorporated. It is applied in the design and development decision-making phases of the product life cycle, and data transfer to it is realized in both senses.
• Adaptive Digital Twin: The DT offers a dynamic interface between the DT itself and the physical object. It has the ability of priority learning and can maintain the human operators preferences with the help of supervised machine learning process. Operation’s real-time decision-making and planning are also noted as advantages.
• Intelligent Digital Twin: Unlike the Adaptive DT, this DT offers unsupervised machine learning functionality, increasing its autonomy. It also provides higher accuracy and efficient system analysis.

3.3. Digital Twin Models, Frameworks, and Architectures

• The integration of different perspectives to achieve a complex framework regarding the use of the Digital Twin in Industry 4.0.
• Addressing requirements according to production paradigms that make the transition from mass production to customized production.
• Decomposition of a process into sub-processes, which can be approached and adapted with respect to the vertical axis.
• Integration of relationships between different levels, which is achieved through the iterative and incremental process.

4. Analyses of the Applications of Digital Twin Models

4.1. manufacturing, 4.1.1. application and adoption of digital twin in manufacturing.

• Remote control and monitoring in real-time: the digital twin can be monitored and controlled at any time from any location.
• Increased safety and efficiency: integrating quantitative data and performing complex analyses in real time.
• Predictive maintenance and planning, achieved by continuously analyzing data and taking measures so that the impact of failures is minimal or eliminated.
• Assessment of risks through simulations to take place at the level of the digital twin and finding methods to mitigate risks highlighted from a primary phase of the life cycle.
• Rapid and continuous customization of products and services according to current trends and customer requirements.

4.1.2. Benefits and Challenges of Digital Twins in Manufacturing

4.2. medicine, 4.2.1. application and adoption of digital twin in medicine, 4.2.2. benefits and challenges of digital twins in medicine, 4.3. digital twin in other domains, benefits and challenges of digital twins in other domains, 6. discussion, 7. conclusions, author contributions, institutional review board statement, informed consent statement, data availability statement, conflicts of interest.

• Qi, Q.; Tao, F.; Hu, T.; Anwer, N.; Liu, A.; Wei, Y.; Wang, L.; Nee, A.Y.C. Enabling technologies and tools for digital twin. J. Manuf. Syst. 2021 , 58 , 3–21. [ Google Scholar ] [ CrossRef ]
• Grieves, M. Digital twin: Manufacturing excellence through virtual factory replication. White Pap. 2014 , 1 , 1–7. [ Google Scholar ]
• Glaessgen, E.; Stargel, D. The digital twin paradigm for future NASA and US Air Force vehicles. In Proceedings of the 53rd AIAA/ASME/ASCE/AHS/ASC Structures, Structural Dynamics and Materials Conference 20th AIAA/ASME/AHS Adaptive Structures Conference 14th AIAA, Honolulu, HI, USA, 23–26 April 2012; p. 1818. [ Google Scholar ]
• Tao, F.; Zhang, M.; Cheng, J.; Qi, Q. Digital twin workshop: A new paradigm for future workshop. Comput. Integr. Manuf. Syst. 2017 , 23 , 1–9. [ Google Scholar ]
• Tao, F.; Liu, W.; Zhang, M.; Hu, T.; Qi, Q.; Zhang, H.; Sui, F.; Wang, T.; Xu, H.; Huang, Z.; et al. Five-dimension digital twin model and its ten applications. Comput. Integr. Manuf. Syst. 2019 , 25 , 1–18. [ Google Scholar ]
• Negri, E.; Fumagalli, L.; Macchi, M. A review of the roles of digital twin in CPS-based production systems. Procedia Manuf. 2017 , 11 , 939–948. [ Google Scholar ] [ CrossRef ]
• Autiosalo, J. Platform for industrial internet and digital twin focused education, research, and innovation: Ilmatar the overhead crane. In Proceedings of the 2018 IEEE 4th World Forum on Internet of Things (WF-IoT), Singapore, 5–8 February 2018; pp. 241–244. [ Google Scholar ]
• Boschert, S.; Rosen, R. Digital twin: The simulation aspect. In Mechatronic Futures ; Springer: Cham, Switzerland, 2016; pp. 59–74. [ Google Scholar ]
• Tao, F.; Zhang, H.; Liu, A.; Nee, A.Y. Digital twin in industry: State-of-the-art. IEEE Trans. Ind. Inform. 2018 , 15 , 2405–2415. [ Google Scholar ] [ CrossRef ]
• Zheng, Y.; Yang, S.; Cheng, H. An application framework of digital twin and its case study. J. Ambient. Intell. Humaniz. Comput. 2019 , 10 , 1141–1153. [ Google Scholar ] [ CrossRef ]
• Singh, M.; Fuenmayor, E.; Hinchy, E.P.; Qiao, Y.; Murray, N.; Devine, D. Digital twin: Origin to future. Appl. Syst. Innov. 2021 , 4 , 36. [ Google Scholar ] [ CrossRef ]
• Grieves, M.; Vickers, J. Digital twin: Mitigating unpredictable, undesirable emergent behavior in complex systems. In Transdisciplinary Perspectives on Complex Systems ; Springer: Cham, Switzerland, 2017; pp. 85–113. [ Google Scholar ]
• Kritzinger, W.; Karner, M.; Traar, G.; Henjes, J.; Sihn, W. Digital Twin in manufacturing: A categorical literature review and classification. IFAC-Pap. 2018 , 51 , 1016–1022. [ Google Scholar ] [ CrossRef ]
• Digital Twin. Available online: https://www.plm.automation.siemens.com/global/en/our-story/glossary/digital-twin/24465 (accessed on 12 October 2020).
• Exosite. The 3 Types of Digital Twin Maturity Models. 2017. Available online: https://blog.exosite.com/3-digital-twin-maturity-models (accessed on 1 May 2022).
• Madni, A.M.; Madni, C.C.; Lucero, S.D. Leveraging digital twin technology in model-based systems engineering. Systems 2019 , 7 , 7. [ Google Scholar ] [ CrossRef ]
• Malakuti, S.; Grüner, S. Architectural aspects of digital twins in IIoT systems. In Proceedings of the 12th European Conference on Software Architecture: Companion Proceedings ECSA Companion, Madrid, Spain, 24–28 September 2018. [ Google Scholar ]
• Lu, Y.; Liu, C.; Kevin, I.; Wang, K.; Huang, H.; Xu, X. Digital Twin-driven smart manufacturing: Connotation, reference model, applications and research issues. Robot. Comput. Integr. Manuf. 2020 , 61 , 101837. [ Google Scholar ] [ CrossRef ]
• Alam, K.M.; El Saddik, A. C2PS: A digital twin architecture reference model for the cloud-based cyber-physical systems. IEEE Access 2017 , 5 , 2050–2062. [ Google Scholar ] [ CrossRef ]
• Bevilacqua, M.; Bottani, E.; Ciarapica, F.E.; Costantino, F.; Di Donato, L.; Ferraro, A.; Mazzuto, G.; Monteriù, A.; Nardini, G.; Ortenzi, M.; et al. Digital twin reference model development to prevent operators’ risk in process plants. Sustainability 2020 , 12 , 1088. [ Google Scholar ] [ CrossRef ]
• Pisching, M.A.; Pessoa, M.A.; Junqueira, F.; dos Santos Filho, D.J.; Miyagi, P.E. An architecture based on RAMI 4.0 to discover equipment to process operations required by products. Comput. Ind. Eng. 2018 , 125 , 574–591. [ Google Scholar ] [ CrossRef ]
• ISO 23247-2:2021 ; Automation Systems and Integration — Digital Twin Framework for Manufacturing — Part 2: Reference Architecture, Edition 1. ISO: Geneva, Switzerland, 2021.
• Aheleroff, S.; Xu, X.; Zhong, R.Y.; Lu, Y. Digital twin as a service (DTaaS) in industry 4.0: An architecture reference model. Adv. Eng. Inform. 2021 , 47 , 101225. [ Google Scholar ] [ CrossRef ]
• Kontar, R.; Shi, N.; Yue, X.; Chung, S.; Byon, E.; Chowdhury, M.; Jin, J.; Kontar, W.; Masoud, N.; Nouiehed, M.; et al. The internet of federated things (IoFT). IEEE Access 2021 , 9 , 156071–156113. [ Google Scholar ] [ CrossRef ]
• Smith, V.; Chiang, C.K.; Sanjabi, M.; Talwalkar, A.S. Federated multi-task learning. In Advances in Neural Information Processing Systems ; Neural Information Processing Systems Foundation, Inc. (NeurIPS): La Jolla, CA, USA, 2017; Volume 30. [ Google Scholar ]
• Snell, J.; Swersky, K.; Zemel, R. Prototypical networks for few-shot learning. In Advances in Neural Information Processing Systems ; Neural Information Processing Systems Foundation, Inc. (NeurIPS): La Jolla, CA, USA, 2017; Volume 30. [ Google Scholar ]
• Liu, M.; Fang, S.; Dong, H.; Xu, C. Review of digital twin about concepts, technologies, and industrial applications. J. Manuf. Syst. 2021 , 58 , 346–361. [ Google Scholar ] [ CrossRef ]
• Rosen, R.; Von Wichert, G.; Lo, G.; Bettenhausen, K.D. About the importance of autonomy and digital twins for the future of manufacturing. IFAC-Pap. 2015 , 48 , 567–572. [ Google Scholar ] [ CrossRef ]
• Park, K.T.; Nam, Y.W.; Lee, H.S.; Im, S.J.; Noh, S.D.; Son, J.Y.; Kim, H. Design and implementation of a digital twin application for a connected micro smart factory. Int. J. Comput. Integr. Manuf. 2019 , 32 , 596–614. [ Google Scholar ] [ CrossRef ]
• Tao, F.; Zhang, M. Digital twin shop-floor: A new shop-floor paradigm towards smart manufacturing. IEEE Access 2017 , 5 , 20418–20427. [ Google Scholar ] [ CrossRef ]
• Bertoni, M.; Bertoni, A. Designing solutions with the product-service systems digital twin: What is now and what is next? Comput. Ind. 2022 , 138 , 103629. [ Google Scholar ] [ CrossRef ]
• Wang, X.; Wang, Y.; Tao, F.; Liu, A. New paradigm of data-driven smart customization through digital twin. J. Manuf. Syst. 2021 , 58 , 270–280. [ Google Scholar ] [ CrossRef ]
• Meierhofer, J.; West, S.; Rapaccini, M.; Barbieri, C. The digital twin as a service enabler: From the service ecosystem to the simulation model. In Exploring Services Science, Proceedings of the 10th International Conference, IESS 2020, Porto, Portugal, 5–7 February 2020 ; Springer: Cham, Switzerland, 2020; pp. 347–359. [ Google Scholar ]
• Li, X.; Wang, Z.; Chen, C.H.; Zheng, P. A data-driven reversible framework for achieving Sustainable Smart product-service systems. J. Clean. Prod. 2021 , 279 , 123618. [ Google Scholar ] [ CrossRef ]
• Kaewunruen, S.; Peng, S.; Phil-Ebosie, O. Digital twin aided sustainability and vulnerability audit for subway stations. Sustainability 2020 , 12 , 7873. [ Google Scholar ] [ CrossRef ]
• Zhang, H.; Ma, L.; Sun, J.; Lin, H.; Thürer, M. Digital twin in services and industrial product service systems: Review and analysis. Procedia CIRP 2019 , 83 , 57–60. [ Google Scholar ] [ CrossRef ]
• Bagozi, A.; Bianchini, D.; De Antonellis, V.; Marini, A.; Ragazzi, D. Interactive data exploration as a service for the smart factory. In Proceedings of the 2017 IEEE International Conference on Web Services (ICWS), Honolulu, HI, USA, 25–30 June 2017; pp. 293–300. [ Google Scholar ]
• Olivotti, D.; Dreyer, S.; Lebek, B.; Breitner, M.H. Creating the foundation for digital twins in the manufacturing industry: An integrated installed base management system. Inf. Syst. Bus. Manag. 2019 , 17 , 89–116. [ Google Scholar ] [ CrossRef ]
• Bonnard, R.; Hascoët, J.Y.; Mognol, P. Data model for additive manufacturing digital thread: State of the art and perspectives. Int. J. Comput. Integr. Manuf. 2019 , 32 , 1170–1191. [ Google Scholar ] [ CrossRef ]
• Minerva, R.; Crespi, N. Digital twins: Properties, software frameworks, and application scenarios. IT Prof. 2021 , 23 , 51–55. [ Google Scholar ] [ CrossRef ]
• Wuest, T.; Hribernik, K.; Thoben, K.D. Accessing servitisation potential of PLM data by applying the product avatar concept. Prod. Plan. Control. 2015 , 26 , 1198–1218. [ Google Scholar ] [ CrossRef ]
• Ströer, F.; Sivasothy, P.; Faißt, K.G.; Apostolov, H.; Eickhoff, T.; Bechev, D.; Bulun, G.; Seewig, J.; Eigner, M.; Sauer, B. Combined development and test of product-service systems in early product development stages for customized, availability-oriented business models in the capital goods industry. Procedia CIRP 2018 , 72 , 714–719. [ Google Scholar ] [ CrossRef ]
• D’Amico, D.; Ekoyuncu, J.; Addepalli, S.; Smith, C.; Keedwell, E.; Sibson, J.; Penver, S. Conceptual framework of a digital twin to evaluate the degradation status of complex engineering systems. Procedia CIRP 2019 , 86 , 61–67. [ Google Scholar ] [ CrossRef ]
• Grijalvo Martín, M.; Pacios Álvarez, A.; Ordieres-Meré, J.; Villalba-Díez, J.; Morales-Alonso, G. New business models from prescriptive maintenance strategies aligned with sustainable development goals. Sustainability 2020 , 13 , 216. [ Google Scholar ] [ CrossRef ]
• Tao, F.; Sui, F.; Liu, A.; Qi, Q.; Zhang, M.; Song, B.; Guo, Z.; Lu, S.C.-Y.; Nee, A.Y. Digital twin-driven product design framework. Int. J. Prod. Res. 2019 , 57 , 3935–3953. [ Google Scholar ] [ CrossRef ]
• Schleich, B.; Anwer, N.; Mathieu, L.; Wartzack, S. Shaping the digital twin for design and production engineering. CIRP Ann. 2017 , 66 , 141–144. [ Google Scholar ] [ CrossRef ]
• Macchi, M.; Roda, I.; Negri, E.; Fumagalli, L. Exploring the role of digital twin for asset lifecycle management. IFAC-Pap. 2018 , 51 , 790–795. [ Google Scholar ] [ CrossRef ]
• Fang, X.; Wang, H.; Liu, G.; Tian, X.; Ding, G.; Zhang, H. Industry application of digital twin: From concept to implementation. Int. J. Adv. Manuf. Technol. 2022 , 121 , 4289–4312. [ Google Scholar ] [ CrossRef ]
• Jia, W.; Wang, W.; Zhang, Z. From simple digital twin to complex digital twin Part I: A novel modeling method for multi-scale and multi-scenario digital twin. Adv. Eng. Inform. 2022 , 53 , 101706. [ Google Scholar ] [ CrossRef ]
• Dumitrache, I. Cyber-Physical Systems (CPS) Factor determinant în economia bazată pe inovare şi cunoştinţe. Rev. Română Infor. Autom. 2013 , 23 , 43–54. [ Google Scholar ]
• Choi, S.H.; Park, K.B.; Roh, D.H.; Lee, J.Y.; Mohammed, M.; Ghasemi, Y.; Jeong, H. An integrated mixed reality system for safety-aware human-robot collaboration using deep learning and digital twin generation. Robot. Comput. Integr. Manuf. 2022 , 73 , 102258. [ Google Scholar ] [ CrossRef ]
• Kousi, N.; Gkournelos, C.; Aivaliotis, S.; Lotsaris, K.; Bavelos, A.C.; Baris, P.; Michalos, G.; Makris, S. Digital twin for designing and reconfiguring human–robot collaborative assembly lines. Appl. Sci. 2021 , 11 , 4620. [ Google Scholar ] [ CrossRef ]
• Bilberg, A.; Malik, A.A. Digital twin driven human–robot collaborative assembly. CIRP Ann. 2019 , 68 , 499–502. [ Google Scholar ] [ CrossRef ]
• Oracle. About the IoT Digital Twin Framework. Available online: https://docs.oracle.com/en/cloud/paas/iot-cloud/iotgs/iot-digital-twin-framework.html (accessed on 17 June 2024).
• Qi, Q.; Tao, F. Digital twin and big data towards smart manufacturing and industry 4.0: 360 degree comparison. IEEE Access 2018 , 6 , 3585–3593. [ Google Scholar ] [ CrossRef ]
• He, B.; Bai, K.J. Digital twin-based sustainable intelligent manufacturing: A review. Adv. Manuf. 2021 , 9 , 1–21. [ Google Scholar ] [ CrossRef ]
• Wang, Y.; Cao, Y.; Wang, F.Y. Anomaly detection in digital twin model. In Proceedings of the 2021 IEEE 1st International Conference on Digital Twins and Parallel Intelligence (DTPI), Beijing, China, 15 July–15 August 2021; pp. 208–211. [ Google Scholar ]
• Augustine, P. The industry use cases for the digital twin idea. In Advances in Computers ; Elsevier: Amsterdan, The Netherlands, 2020; Volume 117, pp. 79–105. [ Google Scholar ]
• Xu, Q.; Ali, S.; Yue, T. Digital twin-based anomaly detection in cyber-physical systems. In Proceedings of the 2021 14th IEEE Conference on Software Testing, Verification and Validation (ICST), Porto de Galinhas, Brazil, 12–16 April 2021; pp. 205–216. [ Google Scholar ]
• Stary, C.; Elstermann, M.; Fleischmann, A.; Schmidt, W. Behavior-centered digital-twin design for dynamic cyber-physical system development. Complex Syst. Inform. Model. Q. 2022 , 30 , 31–52. [ Google Scholar ] [ CrossRef ]
• Steinmetz, C.; Rettberg, A.; Ribeiro, F.G.C.; Schroeder, G.; Pereira, C.E. Internet of things ontology for digital twin in cyber physical systems. In Proceedings of the 2018 VIII Brazilian symposium on computing systems engineering (SBESC), Salvador, Brazil, 5–8 November 2018; pp. 154–159. [ Google Scholar ]
• Son, Y.H.; Park, K.T.; Lee, D.; Jeon, S.W.; Do Noh, S. Digital twin–based cyber-physical system for automotive body production lines. Int. J. Adv. Manuf. Technol. 2021 , 115 , 291–310. [ Google Scholar ] [ CrossRef ]
• Rasheed, A.; San, O.; Kvamsdal, T. Digital twin: Values, challenges and enablers from a modeling perspective. IEEE Access 2020 , 8 , 21980–22012. [ Google Scholar ] [ CrossRef ]
• Bruynseels, K.; Santoni de Sio, F.; Van den Hoven, J. Digital twins in health care: Ethical implications of an emerging engineering paradigm. Front. Genet. 2018 , 9 , 320848. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Zhang, B.; Korolj, A.; Lai, B.F.L.; Radisic, M. Advances in organ-on-a-chip engineering. Nat. Rev. Mater. 2018 , 3 , 257–278. [ Google Scholar ] [ CrossRef ]
• Skardal, A.; Shupe, T.; Atala, A. Organoid-on-a-chip and body-on-a-chip systems for drug screening and disease modeling. Drug Discov. Today 2016 , 21 , 1399–1411. [ Google Scholar ] [ CrossRef ]
• Jimenez, J.I.; Jahankhani, H.; Kendzierskyj, S. Health care in the cyberspace: Medical cyber-physical system and digital twin challenges. In Digital Twin Technologies and Smart Cities ; Springer: Cham, Switzerland, 2020; pp. 79–92. [ Google Scholar ]
• Lee, I.; Sokolsky, O.; Chen, S.; Hatcliff, J.; Jee, E.; Kim, B.; King, A.; Mullen-Fortino, M.; Park, S.; Roederer, A.; et al. Challenges and research directions in medical cyber–physical systems. Proc. IEEE 2011 , 100 , 75–90. [ Google Scholar ]
• Dey, N.; Ashour, A.S.; Shi, F.; Fong, S.J.; Tavares, J.M.R. Medical cyber-physical systems: A survey. J. Med. Syst. 2018 , 42 , 74. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Subramanian, B.; Kim, J.; Maray, M.; Paul, A. Digital Twin Model: A Real-Time Emotion Recognition System for Personalized Healthcare. IEEE Access 2022 , 10 , 81155–81165. [ Google Scholar ] [ CrossRef ]
• Elayan, H.; Aloqaily, M.; Guizani, M. Digital twin for intelligent context-aware IoT healthcare systems. IEEE Internet Things J. 2021 , 8 , 16749–16757. [ Google Scholar ] [ CrossRef ]
• Diaz, V.; Viceconti, M.; Stroetmann, K.; Kalra, D. Roadmap for the Digital Patient ; European Commission: Brussels, Belgium, 2013. [ Google Scholar ]
• van Houten, H. How a Virtual Heart Could Save Your Real One. 2020. Available online: https://www.philips.com/a-w/about/news/archive/blogs/innovation-matters/20181112-how-a-virtual-heart-could-save-your-real-one.html (accessed on 16 June 2024).
• Background Information. Erlang. 2018. Available online: www.siemens-healthineers.com (accessed on 16 June 2024).
• Yakışan, B. Siemens Healthineers sağLıkta Geleceğin Teknolojilerini tanıTtı. Anadolu Ajansı. 2019. Available online: https://www.aa.com.tr/tr/sirkethaberleri/hizmet/siemens-healthineers-saglikta-gelecegin-teknolojilerini-tanitti-/654299 (accessed on 16 June 2024).
• Price, L. Digital Health Hype Cycle 2020. Healthcare Digital. 2020. Available online: https://www.healthcare.digital/single-post/2020/01/29/Digital-Health-Hype-Cycle-2020 (accessed on 16 June 2024).
• University of Amsterdam. Your Digital Twin: Closer Than You Think—Informatics Institute—University of Amsterdam. 2018. Available online: https://ivi.uva.nl/content/news/2018/04/your-digitaltwin.html?1556017299749 (accessed on 16 June 2024).
• Dassault Systèmes’ Living Heart Project Reaches Next Milestones in Mission to Improve Patient Care. Dassault Systèmes. 2017. Available online: https://www.3ds.com/newsroom/press-releases/dassault-systemes-living-heart-project-reaches-next-milestones-mission-improve-patient-care (accessed on 16 June 2024). Dassault Systèmes.
• D’Souza, K. Technology to Transform Lives: The SIMULIA Living Heart Model. 2015. Available online: https://www.fda.gov/downloads/AboutFDA/CentersOffices/OfficeofMedicalProductsandToba (accessed on 16 June 2024).
• Erol, T.; Mendi, A.F.; Doğan, D. The digital twin revolution in healthcare. In Proceedings of the 2020 4th International Symposium on Multidisciplinary Studies and Innovative Technologies (ISMSIT), Istanbul, Turkey, 22–24 October 2020; pp. 1–7. [ Google Scholar ]
• Yuzyılın Saglık Trendleri GE Turkiye Blog. General Electric. 2016. Available online: https://geturkiyeblog.com/21-yuzyilin-saglik-trendleri/ (accessed on 16 June 2024).
• Sooma Sooma TreatmentOutcomes (2018). Sooma. 2018. Available online: https://soomamedical.com/sooma-treatment-outcomes-2018/ (accessed on 16 June 2024).
• Myontec MBody Shorts—Perform Better, Myontec. 2020. Available online: https://performbetter.co.uk/product/myontec-mbody-pro-portable (accessed on 16 June 2024).
• Sun, T.; He, X.; Li, Z. Digital twin in healthcare: Recent updates and challenges. Digit. Health 2023 , 9 , 20552076221149651. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Moztarzadeh, O.; Jamshidi, M.; Sargolzaei, S.; Jamshidi, A.; Baghalipour, N.; Malekzadeh Moghani, M.; Hauer, L. Metaverse and Healthcare: Machine Learning-Enabled Digital Twins of Cancer. Bioengineering 2023 , 10 , 455. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• ISO/IEC 27001:2022 ; Information Security, Cybersecurity and Privacy Protection—Information Security Management Systems—Requirements, Edition 3. ISO: Geneva, Switzerland, 2022.
• Vahdati, A. Cornea digital twins for studying the critical role of mechanics in physiology, pathology and surgical repair. In Digital Human Modeling and Medicine ; Academic Press: Cambridge, MA, USA, 2023; pp. 443–463. [ Google Scholar ]
• Iliuţă, M.E.; Moisescu, M.A.; Caramihai, S.I.; Cernian, A.; Pop, E.; Chiş, D.I.; Mitulescu, T.C. Digital Twin Models for Personalised and Predictive Medicine in Ophthalmology. Technologies 2024 , 12 , 55. [ Google Scholar ] [ CrossRef ]
• Armeni, P.; Polat, I.; De Rossi, L.M.; Diaferia, L.; Visioli, G.; Meregalli, S.; Gatti, A. Digital Twins for Health: Opportunities, Barriers and a Path Forward. In Digital Twin Technology—Fundamentals and Applications ; IntechOpen: Rijeka, Croatia, 2023. [ Google Scholar ]
• Mitrofanova, Y.S.; Sherstobitova, A.A.; Filippova, O.A. Modeling smart learning processes based on educational data mining tools. In Smart Education and e-Learning 2019 ; Springer: Singapore, 2019; pp. 561–571. [ Google Scholar ]
• Abdel-Basset, M.; Manogaran, G.; Mohamed, M.; Rushdy, E. Internet of things in smart education environment: Supportive framework in the decision-making process. Concurr. Comput. Pract. Exp. 2019 , 31 , e4515. [ Google Scholar ] [ CrossRef ]
• Adu, E.K.; Poo, D.C. Smart learning: A new paradigm of learning in the smart age. In Proceedings of the International Conference on Teaching and Learning in Higher Education, Kuching, Malaysia, 11–13 April 2014. [ Google Scholar ]
• Arantes, J. Digital twins and the terminology of “personalization” or “personalized learning” in educational policy: A discussion paper. Policy Futur. Educ. 2024 , 22 , 524–543. [ Google Scholar ] [ CrossRef ]
• Chen, Y.; Zheng, Y.; Xue, T.; Lin, W.; Wen, J.; Chen, G. Harnessing the Synergy of Real Teacher, Digital Twin, and AI in Blended Metaverse Learning Environment: A Catalyst for Medical Education Reforms. 2024. Available online: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4745941 (accessed on 2 March 2024).
• Khana, Z.H.; Mekida, S. Designing Remote Labs in Outcome Based Education using Digital Twin and Metaverse. Available online: https://www.researchgate.net/profile/Zeashan-Khan/publication/377928011_Designing_Remote_Labs_in_Outcome_based_Education_using_Digital_Twin_and_Metaverse/links/65bdd0801bed776ae3276058/Designing-Remote-Labs-in-Outcome-based-Education-using-Digital-Twin-and-Metaverse.pdf (accessed on 16 June 2024).
• Sim, J.K.; Xu, K.W.; Jin, Y.; Lee, Z.Y.; Teo, Y.J.; Mohan, P.; Huang, L.; Xie, Y.; Li, S.; Liang, N.; et al. Designing an Educational Metaverse: A Case Study of NTUniverse. Appl. Sci. 2024 , 14 , 2559. [ Google Scholar ] [ CrossRef ]
• Goodwin, T.; Xu, J.; Celik, N.; Chen, C.H. Real-time digital twin-based optimization with predictive simulation learning. J. Simul. 2024 , 18 , 47–64. [ Google Scholar ] [ CrossRef ]
• Dietz, M.; Pernul, G. Digital twin: Empowering enterprises towards a system-of-systems approach. Bus. Inf. Syst. Eng. 2020 , 62 , 179–184. [ Google Scholar ] [ CrossRef ]
• Priyanka, E.B.; Thangavel, S.; Gao, X.Z.; Sivakumar, N.S. Digital twin for oil pipeline risk estimation using prognostic and machine learning techniques. J. Ind. Inf. Integr. 2022 , 26 , 100272. [ Google Scholar ] [ CrossRef ]
• Lu, H.; Guo, L.; Azimi, M.; Huang, K. Oil and Gas 4.0 era: A systematic review and outlook. Comput. Ind. 2019 , 111 , 68–90. [ Google Scholar ] [ CrossRef ]
• Mohamed, N.; Al-Jaroodi, J.; Lazarova-Molnar, S. Leveraging the capabilities of industry 4.0 for improving energy efficiency in smart factories. IEEE Access 2019 , 7 , 18008–18020. [ Google Scholar ] [ CrossRef ]
• Dong, B.; O’Neill, Z.; Li, Z. A BIM-enabled information infrastructure for building energy Fault Detection and Diagnostics. Autom. Constr. 2014 , 44 , 197–211. [ Google Scholar ] [ CrossRef ]
• Modi, A.S. Review article on deep learning approaches. In Proceedings of the 2018 Second International Conference on Intelligent Computing and Control Systems (ICICCS), Madurai, India, 14–15 June 2018; pp. 1635–1639. [ Google Scholar ]
• Barkwell, K.E.; Cuzzocrea, A.; Leung, C.K.; Ocran, A.A.; Sanderson, J.M.; Stewart, J.A.; Wodi, B.H. Big data visualization and visual analytics for music data mining. In Proceedings of the 2018 22nd International Conference Information Visualization (IV), Salerno, Italy, 10–13 July 2018; pp. 235–240. [ Google Scholar ]
• Bibri, S.E.; Krogstie, J. The core enabling technologies of big data analytics and context-aware computing for smart sustainable cities: A review and synthesis. J. Big Data 2017 , 4 , 1–50. [ Google Scholar ] [ CrossRef ]
• Deng, Z.; Huang, M.; Wan, N.; Zhang, J. The Current Development of Structural Health Monitoring for Bridges: A Review. Buildings 2023 , 13 , 1360. [ Google Scholar ] [ CrossRef ]
• Huang, M.; Ling, Z.; Sun, C.; Lei, Y.; Xiang, C.; Wan, Z.; Gu, J. Two-stage damage identification for bridge bearings based on sailfish optimization and element relative modal strain energy. Struct. Eng. Mech. Int. J. 2023 , 86 , 715–730. [ Google Scholar ]
• Zhang, J.; Huang, M.; Wan, N.; Deng, Z.; He, Z.; Luo, J. Missing measurement data recovery methods in structural health Monitoring: The State, challenges and case study. Measurement 2024 , 231 , 114528. [ Google Scholar ] [ CrossRef ]
• Huang, M.; Zhang, J.; Hu, J.; Ye, Z.; Deng, Z.; Wan, N. Nonlinear modeling of temperature-induced bearing displacement of long-span single-pier rigid frame bridge based on DCNN-LSTM. Case Stud. Therm. Eng. 2024 , 53 , 103897. [ Google Scholar ] [ CrossRef ]
• Xia, H.; Liu, Z.; Maria, E.; Liu, X.; Lin, C. Study on city digital twin technologies for sustainable smart city design: A review and bibliometric analysis of geographic information system and building information modeling integration. Sustain. Cities Soc. 2022 , 84 , 104009. [ Google Scholar ] [ CrossRef ]
• Vuoto, A.; Funari, M.F.; Lourenço, P.B. Shaping digital twin concept for built cultural heritage conservation: A systematic literature review. Int. J. Archit. Herit. 2023 , 1–34. [ Google Scholar ] [ CrossRef ]
• Vuoto, A.; Funari, M.F.; Lourenço, P.B. On the use of the digital twin concept for the structural integrity protection of architectural heritage. Infrastructures 2023 , 8 , 86. [ Google Scholar ] [ CrossRef ]
• Zhang, X.; Shen, J.; Saini, P.K.; Lovati, M.; Han, M.; Huang, P.; Huang, Z. Digital twin for accelerating sustainability in positive energy district: A review of simulation tools and applications. Front. Sustain. Cities 2021 , 3 , 663269. [ Google Scholar ] [ CrossRef ]

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Iliuţă, M.-E.; Moisescu, M.-A.; Pop, E.; Ionita, A.-D.; Caramihai, S.-I.; Mitulescu, T.-C. Digital Twin—A Review of the Evolution from Concept to Technology and Its Analytical Perspectives on Applications in Various Fields. Appl. Sci. 2024 , 14 , 5454. https://doi.org/10.3390/app14135454

Iliuţă M-E, Moisescu M-A, Pop E, Ionita A-D, Caramihai S-I, Mitulescu T-C. Digital Twin—A Review of the Evolution from Concept to Technology and Its Analytical Perspectives on Applications in Various Fields. Applied Sciences . 2024; 14(13):5454. https://doi.org/10.3390/app14135454

Iliuţă, Miruna-Elena, Mihnea-Alexandru Moisescu, Eugen Pop, Anca-Daniela Ionita, Simona-Iuliana Caramihai, and Traian-Costin Mitulescu. 2024. "Digital Twin—A Review of the Evolution from Concept to Technology and Its Analytical Perspectives on Applications in Various Fields" Applied Sciences 14, no. 13: 5454. https://doi.org/10.3390/app14135454

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• Volume 14, Issue 6
• Modelling years of life lost due to acute type A aortic dissection in the German healthcare setting: a predictive study
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• http://orcid.org/0000-0002-0101-0388 Philipp Schiele 1 ,
• Adriana N König 2 ,
• Alexander Meyer 3 , 4 , 5 ,
• Volkmar Falk 3 , 4 , 5 , 6 ,
• Christoph A Nienaber 7 , 8 ,
• http://orcid.org/0000-0003-4666-9511 Stephan D Kurz 3 , 4
• 1 Department of Statistics , Ludwig-Maximilians-Universität München , München , Germany
• 2 Munich School of Management and Munich Center of Health Sciences , Ludwig-Maximilians-Universität München , München , Germany
• 3 Department of Cardiothoracic and Vascular Surgery , Deutsches Herzzentrum der Charité (DHZC) , Berlin , Germany
• 4 Charité-Universitätsmedizin Berlin , Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health , Berlin , Germany
• 5 DZHK (German Centre for Cardiovascular Research), Partner Site Berlin , Berlin , Germany
• 6 Department of Health Sciences and Technology , ETH Zurich , Zurich , Switzerland
• 7 National Heart and Lung Institute , Imperial College London , London , UK
• 8 Cardiology and Aortic Centre , The Royal Brompton & Harefield Hospitals as part of Guys’ and St. Thomas’ NHS Foundation Trust , London , UK
• Correspondence to Dr Stephan D Kurz; stephan.kurz{at}dhzc-charite.de

Objectives This study aimed to develop a patient-centred approach to the burden of acute type A aortic dissection (ATAAD) through modelling. The main objective was to identify potential improvements in managing this life-threatening cardiovascular condition and to provide evidence-based recommendations to optimise outcomes.

Design We developed a predictive model along patient pathways to estimate the burden of ATAAD through the years of life lost (YLLs) metric. The model was created based on a systematic review of the literature and was parameterised using demographic data from the German healthcare environment. The model was designed to allow interactive simulation of different scenarios resulting from changes in key impact factors.

Setting The study was conducted using data from the German healthcare environment and results from the literature review.

Participants The study included a comprehensive modelling of ATAAD cases in Germany but did not directly involve participants.

Interventions There were no specific interventions applied in this study based on the modelling design.

Primary and secondary outcome measures The single outcome measure was the estimation of YLL due to ATAAD in Germany.

Results Our model estimated 102 791 YLL per year for ATAAD in Germany, with 62 432 and 40 359 YLL for men and women, respectively. Modelling an improved care setting yielded 93 191 YLL or 9.3% less YLL compared with the current standard while a worst-case scenario resulted in 113 023 or 10.0% more YLL. The model is accessible at https://acuteaorticdissection.com/ to estimate custom scenarios.

Conclusions Our study provides an evidence-based approach to estimating the burden of ATAAD and identifying potential improvements in the management of pathways. This approach can be used by healthcare decision-makers to inform policy changes aimed at optimising patient outcomes. By considering patient-centred approaches in any healthcare environment, the model has the potential to improve efficient care for patients suffering from ATAAD.

• decision making
• organisation of health services
• patient-centered care
• public health
• cardiothoracic surgery
• accident & emergency medicine

Data availability statement

Data are available in a public, open access repository. All data sources are publicly available. For convenience, the data can also be downloaded from https://acuteaorticdissection.com/ . The code is made available on request. Detailed citations for datasets used are provided in the dataset references section of this manuscript.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:  http://creativecommons.org/licenses/by-nc/4.0/ .

https://doi.org/10.1136/bmjopen-2023-078398

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STRENGTHS AND LIMITATIONS OF THIS STUDY

Used comprehensive modelling to estimate acute type A aortic dissection’s years of life lost in Germany.

Based on systematic review and demographic data analysis.

Assumptions and modelling may not fully capture real-world variability.

Study’s applicability is limited to Germany’s healthcare context.

Future research is needed to incorporate broader data and contexts.

Introduction

Acute type A aortic dissection (ATAAD) is an urgent, life-threatening condition that poses a significant risk of early mortality if not promptly treated. Given the nature of the disease’s pathophysiology and the sudden onset of symptoms, the first point of medical contact is typically through local ambulance services or emergency department staff. However, the initial clinical manifestation can often be ambiguous and challenging, leading to a high rate of misdiagnosis. 1 Epidemiological studies report an incidence rate of approximately 1.85–11.9 cases per 100 000 population annually in Europe, 2–6 whereas data from Berlin emergency departments suggest an estimated incidence of 5.93–24.92 cases per 100 000 patients annually. 7 Remarkably, the clinical diagnosis of ATAAD is likely to be overlooked in up to 78.3% of instances even within the emergency department. 1 8 Although the diagnostic gold standard is an electrocardiogram-triggered CT angiogram, 9 patients with a confirmed diagnosis of acute aortic syndrome are typically transferred either within the hospital to the cardiac surgery department or to a suitable cardiac surgical centre in the vicinity, presenting a common logistical challenge. These critical stages of the care pathway are highly dependent on local circumstances, and reliable data on this process are scarce. To better understand patient pathways, we have segmented the preclinical process into distinct phases, including transfers between different hospitals and the time required for diagnosis. We note that in rare circumstances like multimorbidity, high age or explicit patient will, medical treatment may be applied, reducing the chances of survival significantly. 10 These cases are not considered in detail in this study.

Several factors influence the likelihood of an ATAAD occurrence and the subsequent outcomes, as demonstrated by a systematic review of the literature. Among these are underlying risk factors, 11 the time from the onset of pain to surgical incision (‘pain-to-cut-time’, PCT 1 12 ), and the relationship between surgical volume and outcome. 13 While these factors have been individually investigated, no model currently exists that captures the cumulative impact of these factors, thereby enabling a comprehensive evaluation of the implications of ATAAD. The aim of this study is to model specific conditions in the care of ATAAD to enhance understanding of potential improvements and their impact on the disease burden. A suitable metric for quantifying this burden is the years of life lost (YLLs), which recognises premature mortality and extends the conventional mortality measure with an age-dependent weighting of deaths, making it an appropriate tool for assessing the impact of risk factors and diseases. Adopting a structured approach to modelling the care pathway and assessing outcomes is crucial for gaining a deeper understanding of ATAAD, despite the inherent challenges in capturing its full complexity.

Systematic literature search

A comprehensive literature search in the PubMed database until April 2023 was conducted before starting the modelling process, visualised in figure 1 . The search included articles using the keywords ‘acute type A aortic dissection’ in combination with ‘incidence’, ‘transportation’, ‘delay’, ‘heart surgery’, ‘misdiagnosis’ and ‘volume outcome’. No restrictions were placed on language or publication type using the strategy:

(“acute type A aortic dissection” [Title/Abstract]) AND (“incidence” [Title/Abstract] OR “transportation” [Title/Abstract] OR “delay” [Title/Abstract] OR “heart surgery” [Title/Abstract] OR “misdiagnosis” [Title/Abstract] OR “volume-outcome” [Title/Abstract]).

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Systematic review flow chart. Visual representation of the review methodology.

A total of 300 results were obtained. Additionally, we manually searched the reference lists of relevant articles to identify any additional studies. After removing duplicates, the remaining studies were assessed for inclusion and relevance by at least two independent reviewers using strict criteria. We included studies that offered detailed insights into the incidence, epidemiology, outcomes and treatment efficacy of ATAAD, particularly those providing population-based data and exploring diagnostic and treatment delays. Exclusion criteria targeted case reports, editorial comments, review articles without original data and studies not directly focusing on ATAAD or applicable to a broad healthcare context. Additionally, each study underwent careful evaluation to ensure the reliability and validity of our analysis, with a particular focus on the study populations and measurements. This meticulous selection and evaluation process led to a refined list of studies foundational for our predictive model development, anchoring our analysis in relevant and high-quality research.

Modelling approach

The initial step of the modelling process involved describing the management of pathways during an ATAAD event ( figure 2 ) according to the literature search. This pathway was divided into five segments: the immediate ATAAD event (1), transportation to the primary hospital (2), diagnosis (3), transportation to the hospital of definitive care (4) and surgery (5). For each segment, a standard case was defined based on parameters obtained from published evidence. Additionally, best-case and worst-case scenarios were developed with adjusted parameter values. By calculating the mortality rate for each segment, we could determine the overall mortality of an ATAAD event. Although patient-level data and uncertainty quantifications were lacking for some inputs, the best, standard and worst-case scenarios provided an initial understanding of the results’ variability. Moreover, the model allows for the incorporation of alternative parameterisations, enabling readers to simulate different settings based on the healthcare system of their respective regions.

ATAAD flow chart. Visualisation of the patient flow after ATAAD event through the care segments alongside transition probabilities. ATAAD, acute type A aortic dissection.

Standard-case scenario

According to Howard et al 2 and Landenhed et al , 11 the mortality rate before the first medical contact in a dissection event is estimated to be up to 35.1% (segment I). If left untreated, the mortality rate is 0.5%–2% per hour. 9 14 15 Thus, PCT is a crucial factor influencing ATAAD patient mortality. 1 12 After a correct initial diagnosis, the average PCT is approximately 5.5 hours and reflected in the transportation and diagnosis segments in figure 2 (segments 2–4). However, due to challenges in accurately diagnosing ATAAD, cases are often initially misdiagnosed as acute coronary syndromes, with a clinical misdiagnosis rate of up to 78.3%. 1 8 Initial misdiagnosis not only has an immediate negative impact but also extends the PCT by an average of 3.3 hours to establish a correct diagnosis. 1 Similar findings have been reported by Harris et al 16 using data from the International Registry of Acute Aortic Dissection. This conservative analysis assumed that an increased PCT due to misdiagnosis contributes to mortality (segment III) but excluded any direct negative impact from incorrect medication. The volume of ATAAD surgeries performed by the surgeon at the receiving hospital was identified as another significant factor for mortality (segment V). Reutersberg et al 13 reported in-hospital mortality rates of 22.3% in low-volume hospitals, 19.0% in medium-volume hospitals and 16.5% in high-volume centres. Similar trends were observed by Knipp et al 17 (in the USA) and Benedetto et al 18 (in the UK). The study by Reutersberg et al 13 also highlighted age as an influential factor for in-hospital mortality, with an OR of 1.14 per 5 years of age. This finding was also supported by Fukui et al 19 and Rylski et al . 20 Therefore, we incorporated age as a variable in our mortality model, using the baseline mortality rates for a person of average age (45.1 years) with adjustment based on the OR identified by Reutersberg et al . 13

YLL modelling

To model the YLL due to ATAAD, we obtained the most recent population pyramid of Germany, with detailed information on the national age distribution. 21 Additionally, we acquired conditional life expectancy data, 22 representing the expected remaining years of life for individuals at any age (eg, as of 2020, a woman in Germany who has reached the age of 85 years has an expected remaining life expectancy of 6.5 years). The age structure and conditional life expectancy data by sex are illustrated in online supplemental figure .

Supplemental material

The crude incidence rate of ATAAD was obtained through an analysis of autopsy reports, allowing for the inclusion of mortality data even at the prehospital stage. 3 The estimate was based on the analysis of a substantial sample size of approximately 30 million person-years from the Berlin-Brandenburg region, rendering the dataset suitable and appropriate to serve as a valuable reference. Applying the relative incidence rates per age group according to this distribution ( figure 3 ) to the population data of Germany, we derived an annual incidence rate of 14.5 cases per 100 000 population. The model also allows to select alternative incidence distributions from different data sources or healthcare environments.

Incidence. Distribution of ATAAD incidence by age and sex. ATAAD, acute type A aortic dissection.

Next, we computed the YLL by integrating the previously mentioned data points. For each subgroup defined by age and sex, we determined the absolute number of incidences based on the incidence distribution. Using the mortality rates obtained from the pathway specifications depicted in figure 2 , the absolute number of ATAAD-related deaths within each subgroup was estimated. By considering the expected remaining life expectancy and the mortality resulting from a probability-weighted outcome of the patient pathway the YLL was obtained for each subgroup, ultimately generating the absolute YLL distribution.

In line with standard practice in burden-of-disease studies, future YLLs were discounted at a rate of 3% per year. 23 Additionally, we considered two hypothetical scenarios to assess the potential impact of changes to the standard model.

Best-case scenario

The best-case scenario assumed highly efficient patient transportation and significantly improved diagnostic performance. The PCT in this scenario was set to the first quartile reported by Zaschke et al . 1 Furthermore, in line with the volume-outcome relationship, ATAAD cases were assumed to be treated exclusively in high-volume clinics, leading to a hypothetical in-hospital mortality rate of 14.0% based on the study by Umana-Pizano et al . 24

Worst-case scenario

Conversely, the worst-case scenario simulated a deterioration in patient transportation, with the transport time set to the third quartile reported by Zaschke et al . 1 This scenario also accounted for a decrease in the volume-outcome effect, where ATAAD surgeries were performed only in low-volume centres.

Table 1 presents the parameter values used in our three scenarios.

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Scenario parametrisation

Patient and public involvement

The study was purely modelling-based, using publicly available data. As a result, there was no direct involvement of patients or the public in the research process.

The simulation results for our predefined scenarios are outlined below. All estimates are primarily based on the incidence distribution reported by Kurz et al , 3 which reflects a German population. Alternative results are also provided, based on an incidence distribution presented in Howard et al 2 (originating from Oxfordshire, UK) and presented in parenthesis for comparative purposes.

When assessing the model in the base case, we obtained a mortality rate of 53.6% for any individual of average age, considering immediate mortality as well as transport time and surgical mortalities. Applying the model to entire the population of Germany, we calculated a total of 102 791 (46 178) YLL in 2020. Among these, 62 432 (27 326) YLLs were attributed to males while 40 359 (18 852) YLLs were attributed to females. This accounts for 57.3% (60.6%) of the total expected residual life at the time of diagnosis. Figure 4 provides an overview of the YLL distribution across different age groups and sexes.

YLL due to ATAAD. Age distribution of YLL by sex. ATAAD, acute type A aortic dissection; YLL, years of life lost.

Best-case and worst-case scenarios

In the best-case scenario, the YLL decreased to 93 191 (41,703), representing a reduction of 9.3% (9.7%) compared with the base case, or 9600 (4,475) years. Conversely, the worst-case assumptions resulted in an increase of 10.0% (9.3%) and 113 023 (50,453) YLL. Thus, the overall impact of the different scenarios amounts to 19 832 (8750) YLL. A significant portion of the YLL, 62 916 (26 726), was attributed to immediate mortality from ATAAD before any medical intervention could take place. Excluding these cases, 39 875 (19 452) YLL out of the total 102 791 (46 178) YLL remained, representing the potential impact of patient management on the YLL. Therefore, the 9.3% (9.7%) reduction in total YLL in the best-case scenario corresponds to a notable improvement of 24.1% (23.0%) when excluding cases of immediate death. Conversely, the worst-case scenario indicates an increase of YLL by 25.7% (22.0%) when considering the adjusted metric excluding sudden death.

To enhance the applicability of the model, we developed an interactive dashboard (accessible at https://acuteaorticdissection.com/ for potential users). This dashboard allows users to simulate different scenarios of important parameters as derived from current literature and facilitates the demonstration of the interplay between key factors in the model.

Our analysis devises a data-informed model to estimate the burden of disease subsequent to ATAAD. This methodology introduces a unique analytical angle for evaluating ATAAD, enabling an association between patient outcomes and events throughout the primary care stages from symptom onset to treatment. It facilitates the assessment of the cumulative impact of varied interventions, supporting clinical and administrative decisions in public health. Our study used the German healthcare system as a representative example to quantify YLL. In the year 2020, ATAAD’s immediate effects led to 102 791 YLL, of which 9600 could have been saved through improved care.

Earlier studies had cited 4 040 920 YLL in Germany in 2010 and attributed to a wide range of cardiovascular and circulatory diseases. 25 This suggests that ATAAD’s strain on the healthcare system approximates 2.5% of that of cardiovascular diseases. Comparing the standard care against substandard care or an optimised care scenario, we simulate two hypothetical situations demonstrating significant effects on YLL. The analysis underscores several time-sensitive stages that add up to the total time to definitive care. Furthermore, as the surgical care volume is known to significantly influence outcomes, early diagnosis and prompt transfer to high-volume centres is recommended, even accepting longer transport times to optimise outcomes in ATAAD care.

Impact of delay

Outcomes of ATAAD are highly time-sensitive, with the first 48 hours after symptom onset accounting for the highest risk to patients, many of whom succumb before reaching medical facilities or receiving a diagnosis. With a routine usage of scores such as the Aortic Dissection Detection Score, or a low threshold for CT imaging, a swifter diagnosis is likely. Additionally, ultrasound screening may be used to enhance the diagnosis process even further. Even minor alterations to emergency room procedures or ambulance services could significantly enhance diagnostic accuracy. Important examples include bilateral blood pressure measurement, neurological symptom checks and a thorough check for a personal or family medical history for aortic diseases. Basic implementation of diagnostic algorithms to exclude acute aortic syndrome in chest, back or thoracic pain cases would also be crucial. Classifying patient treatment as an emergency until definitive care is reached can lead to prioritisation in disposition management and thus further reduce treatment time until treatment. 26 The Berlin STEMO concept 27 and the Aortentelefon in Berlin 12 serve as excellent examples of structured approaches to preclinical processes leading to improved patient outcomes, with similar observations noted in the UK. 28 29

Volume factor

Beyond PCT, the quality and expertise of surgical intervention may significantly impact survival. As demonstrated in our best-case and worst-case scenario, patients are likely to benefit from surgical management at high-volume centres specialised in aortic dissection surgery. Particularly high-risk patients, where surgery may be deemed too risky, could benefit from the expertise available at high-volume centres, familiar with risk/benefit estimations and individual prognosis assessments.

Striving for undelayed onsite diagnosis followed by prompt transfer to specialist aortic teams in high-volume centres is recommended and in line with international efforts to manage acute conditions as well. Orchestrated centralised care has been linked with reduced 30-day mortality and improved long-term survival of dissection in the UK. 29 Evidence from Japan suggests that the benefits of high-volume care could potentially offset concerns over prehospital transfer distance. 30 A network of highly specialised centres has proven effective for acute myocardial infarction 31 and is likely to hold true for dissection. Making use of aerial transport can further improve the tradeoff in favour of high-volume centres. 32 The low incidence and more difficult onsite diagnosis of ATAAD need to be addressed by education and awareness, a task supported by the use of our analytical tool.

Limitations

Despite the significance of our findings, there are certain limitations. First, our study relied on modelling techniques and parameterisation using available published evidence, introducing potential biases and uncertainties associated with data quality and reliability. Second, our model incorporated assumptions and simplifications to model the complex pathway of ATAAD, which may not fully capture the heterogeneity and variability of real-world scenarios. Third, the lack of patient-level data and potentially imprecise quantifications for certain input variables required the use of best-case, standard-case and worst-case scenarios, which may not encompass the full range of the clinical spectrum. Furthermore, our study focused on the population of Germany, limiting generalisability and applicability to other regions with different healthcare systems and demographics. Lastly, our model did not consider potential changes in healthcare practices or technological advancements over time, which could impact the mortality and YLL associated with ATAAD. These limitations highlight the need for further research incorporating more comprehensive data and accounting for contextual factors to enhance the accuracy and applicability of future assessments of the ATAAD burden.

In conclusion, this analysis uses a comprehensive modelling approach to assess the burden of ATAAD in the population of Germany. By simulating predefined scenarios and incorporating data from published evidence, valuable insights into the mortality and YLL associated with ATAAD are provided.

Our findings show that ATAAD imposes a substantial burden in terms of mortality and YLL, with a base-case mortality rate of 53.6% and a total of 102 791 YLL in the year 2020. These results highlight the need for better management strategies to improve patient outcomes and reduce the impact of this life-threatening condition.

Furthermore, our analysis demonstrated the potential influence of various scenarios on the YLL, with the best-case scenario showing a 9.3% reduction and the worst-case scenario indicating a 10.0% increase compared with the base case. These findings underscore the importance of accurate early diagnosis, timely interventions, and the significance of specialised high-volume clinics in improving patient outcomes.

We also developed an interactive dashboard to facilitate easy interaction with the model and allow for simulations of various parameters and scenarios. This tool serves as a potential resource for healthcare professionals and strategists to explore the impact of different interventions and regional healthcare systems on the burden of ATAAD.

Overall, this analysis provides important insight into the burden of ATAAD in Germany and offers a foundation for further research and informed decision-making to enhance patient care and outcomes. By addressing the challenges of ATAAD comprehensively, the aim of reducing the mortality and YLL associated with this devastating condition may become more realistic.

Ethics statements

Patient consent for publication.

Not applicable.

Acknowledgments

Philipp Schiele and Adriana König would like to thank their Ph.D. supervisors Professor Stefan Mittnik, Ph.D., and Professor Dr Reiner Leidl for helpful discussions.

• Zaschke L ,
• Habazettl H ,
• Thurau J , et al
• Howard DPJ ,
• Banerjee A ,
• Fairhead JF , et al
• Kempfert J , et al
• Mészáros I ,
• Szlávi J , et al
• Ståhle E , et al
• Di Marco L ,
• Fortuna D , et al
• Wundram M ,
• Eulert-Grehn J-J , et al
• Ormerod OJ ,
• Giannopoulos N , et al
• Vilacosta I ,
• San Román JA ,
• di Bartolomeo R , et al
• Nakamae K ,
• Oshitomi T ,
• Uesugi H , et al
• Landenhed M ,
• Engström G ,
• Gottsäter A , et al
• Zschaler S ,
• Schmidt G ,
• Reutersberg B ,
• Salvermoser M ,
• Trenner M , et al
• Evangelista A ,
• Isselbacher EM ,
• Bossone E , et al
• Harris KM ,
• Strauss CE ,
• Eagle KA , et al
• Prager RL , et al
• Benedetto U ,
• Dimagli A , et al
• Morita S , et al
• Schilling O ,
• Federal Statistical Office (Destatis)
• German Federal Health Monitoring Service
• Murray CJL ,
• Umana-Pizano JB ,
• Nissen AP ,
• Sandhu HK , et al
• Hornberg C , et al
• Buschmann CT , et al
• Ebinger M ,
• Siegerink B ,
• Kunz A , et al
• Field M , et al
• Talukder S ,
• Norkunas M , et al
• Izumisawa Y ,
• Ichihara N , et al
• Cannon CP ,
• Gibson CM ,
• Lambrew CT , et al
• Stroux A , et al

Supplementary materials

Supplementary data.

This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

• Data supplement 1

Contributors PS, ANK and SDK conceptualised the study. PS developed the model, did the formal analysis and was responsible for data visualisation. PS, ANK, CN and SDK determined the model inputs. ANK and AM validated the model. PS and ANK wrote the first draft of the manuscript. AM, VF, CN and SDK edited the manuscript. VF and SDK supervised the research project. All authors had full access to all the data in the study, accepted responsibility to submit for publication and approved the final version of the manuscript. SD serves as the guarantor of the project. AI was used only to improve the wording and flow of our manuscript.

Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

Competing interests AM is a shareholder of x-cardiac and receives consulting fees from Edwards and Pfizer as well as travel grants from Abbott, Edwards, and Medtronic. All other authors declare no competing interests.

Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

Provenance and peer review Not commissioned; externally peer reviewed.

Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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• Open access
• Published: 26 June 2024

iPSCs chondrogenic differentiation for personalized regenerative medicine: a literature review

• Eltahir Abdelrazig Mohamed Ali 1 , 2   na1 ,
• Rana Smaida 3   na1 ,
• Morgane Meyer 2 , 3   na1 ,
• Wenxin Ou 2 , 6 , 7   na1 ,
• Zongjin Li 4 ,
• Zhongchao Han 5 ,
• Nadia Benkirane-Jessel 1 , 2 , 3 ,
• Jacques Eric Gottenberg 2 , 6 &
• Guoqiang Hua   ORCID: orcid.org/0000-0001-7639-5908 1 , 2  

Stem Cell Research & Therapy volume  15 , Article number:  185 ( 2024 ) Cite this article

Metrics details

Cartilage, an important connective tissue, provides structural support to other body tissues, and serves as a cushion against impacts throughout the body. Found at the end of the bones, cartilage decreases friction and averts bone-on-bone contact during joint movement. Therefore, defects of cartilage can result from natural wear and tear, or from traumatic events, such as injuries or sudden changes in direction during sports activities. Overtime, these cartilage defects which do not always produce immediate symptoms, could lead to severe clinical pathologies. The emergence of induced pluripotent stem cells (iPSCs) has revolutionized the field of regenerative medicine, providing a promising platform for generating various cell types for therapeutic applications. Thus, chondrocytes differentiated from iPSCs become a promising avenue for non-invasive clinical interventions for cartilage injuries and diseases. In this review, we aim to highlight the current strategies used for in vitro chondrogenic differentiation of iPSCs and to explore their multifaceted applications in disease modeling, drug screening, and personalized regenerative medicine. Achieving abundant functional iPSC-derived chondrocytes requires optimization of culture conditions, incorporating specific growth factors, and precise temporal control. Continual improvements in differentiation methods and integration of emerging genome editing, organoids, and 3D bioprinting technologies will enhance the translational applications of iPSC-derived chondrocytes. Finally, to unlock the benefits for patients suffering from cartilage diseases through iPSCs-derived technologies in chondrogenesis, automatic cell therapy manufacturing systems will not only reduce human intervention and ensure sterile processes within isolator-like platforms to minimize contamination risks, but also provide customized production processes with enhanced scalability and efficiency.

Graphical abstract

Cartilage is a semi-rigid, load-bearing, avascular connective tissue, formed solely by cells known as chondrocytes. These cells are loosely embedded in an extracellular matrix (ECM) composed predominantly of collagens and, in some cases, elastic fibers, hyaluronan and proteoglycans [ 1 ]. Cartilage formation, also known as chondrogenesis, is a dynamic cellular process of a condensed mesenchyme tissue derived from the mesoderm germ layer during embryogenesis. Cartilage represents the fetal precursor tissue for skeletal development. In adults, it persists at almost all joints between bones and in structures that must be deformable as well as strong such as in the respiratory system. Based on the structure and composition of their ECMs, chondrocytes form three different types of cartilage; namely, hyaline cartilage, fibrocartilage and elastic cartilage [ 2 ].

Cartilage exhibits diverse clinical aspects and relevance to various medical disciplines, including orthopedics, rheumatology, and respiratory medicine. Cartilage defects are associated with various clinical conditions such as osteoarthritis (OA), rheumatoid arthritis, and cartilage dysplasias [ 1 ]. Understanding the clinical significance of cartilage is critical for the development of effective therapeutics and interventions in various healthcare settings. Orthopedic surgeries such as joint arthroplasty and cartilage transplantation are the most commonly used therapeutic interventions for cartilage repair or replacement [ 3 ]. However, these surgical interventions are invasive or minimally invasive, and their ability to restore normal joint function, alleviate pain, and improve the quality of life for individuals with cartilage-related issues is limited.

Therefore, it is crucial to develop other non-invasive therapeutic approaches with high safety and efficacy. Theoretically and due to their ability to repair injured tissues, adult stem cells can be a good source for developing therapies for a large number of diseases [ 4 ]. Mesenchymal stem cells (MSCs) which can be derived from various tissues such as bone marrow, adipose tissu, placenta, umbilical cord blood, and multiple dental tissues, are multipotent cells that have the potential to differentiate into the mesenchymal lineages including osteocytes, chondrocytes, and adipocytes, as well as other non-mesenchymal lineages, such as cardiomyocytes, astrocytes, neural cells, and endothelial cells [ 5 , 6 ]. Therefore, extensive efforts have been spent to develop MSCs-based cell therapies for a broad spectrum of diseases, encompassing cartilage and bone diseases, hematological diseases, inflammatory diseases, and graft-versus-host disease [ 7 ]. It is important to note that different transcription factors regulate the differentiation of MSCs to different lineages. Chondrogenic differentiation is determined by members the SOX (sex determining region Y (SRY)-related HMG-box) family of transcription factors SOX9, SOX5, and SOX6 while regulation of osteoblast differentiation involve the transcription factors runt-related transcription factor 2 (RUNX2), osterix, and β-catenin [ 8 , 9 ]. Among the different sources of MSCs, bone marrow-derived MSCs (BM-MSCs) are the most commonly used MSCs in regenerative medicine, particularly for cartilage and bone regeneration [ 10 ]. Although significant strides have been taken to improve the chondrogenic differentiation from BM-MSCs and other cell sources, several obstacles persist complicating the achievement of consistent and effective chondrocytes required for clinical application [ 11 ]. Several factors may lead to the failure of utilizing BM-MSCs for efficient treatment of cartilage diseases including but not limited to the restricted proliferation capabilities in cultures [ 12 ], donor variations, and immunogenicity triggered during culture and cryopreservation [ 13 ].

These challenges could be addressed by the induced pluripotent stem cell (iPSC) technology. iPSCs are pluripoent cells which have the capacity for self-renewal and differentiation into almost all cell types [ 14 ]. The concept of self-renewal is the ability of the cells to undergo infinite cell divisions without differentiation into other cell types, while pluripotency is the ability of the cells to produce specialized cells of the three embryonic layers: ectoderm, mesoderm, and endoderm [ 15 ]. iPSCs can be generated from any type of cells through non-integrating reprogramming method using specific transcription factors known as Yamanaka factors namely, Octamer binding transcription factor 3/4 (OCT3/4), SOX2, Krüppel-like factor 4 (KLF4), and Cellular-Myelocytomatosis c-MYC [ 15 ]. Simplicity and reproducibility are the attractive features of the iPSC technology and have attracted the biomedical scientists to generate and differentiate iPSCs from numerous normal and disease-specific cell types for disease modeling and drug screening applications [ 16 ]. Syngeneic non-integrated iPSCs and their derivatives have no or minimal immunogenic effect supporting the notion that these cells could be used for cellular therapy without causing harmful immune responses [ 17 ]. Therefore, generation of iPSC-derived chondrocytes has become indispensable to advance our understanding of the mechanisms of cartilage-related disorders and represents an important avenue in regenerative medicine. In the following section, we will summarize different strategies developed to differentiate iPSCs into chondrocytes aiming to recapitulate the in vivo microenvironment that support chondrogenesis, and to generate functional and stable iPSC-derived chondrocytes.

Generation of iPSC-derived chondrocytes

Chondrocytes can be differentiated from iPSCs though different intermediate stages, such as iPSC-derived MSCs (iPSC-MSCs), embryoid bodies (EBs) formation, induction of neural crest cells (NCCs), and primitive streak-mesendoderm and mesodermal lineage. iPSC-MSCs are morphologically highly similar to BM-MSCs and their gene expression profiling is also comparable to that of BM-MSCs [ 18 ], and exhibit traits that encompass features of both iPSCs and MSCs. iPSC-MSCs show reduced immunogenicity as compared to iPSCs [ 19 ], which renders them appropriate for allogeneic transplantation and enables development of off-the-shelf therapies. Moreover, patient-specific iPSC-MSCs open up the potential for developing personalized medicine for autologous transplantation, in vitro disease modeling, and drug screening [ 20 ]. These iPSC-MSCs were reported to differentiate into chondrocytes with growth factors, such as transforming growth factor-beta 3 (TGF-β3) (Fig.  1 A). Another commonly used approach to obtain chondrocytes from iPSCs in vitro is through formation of three-dimensional (3D) aggregates of pluripotent stem cells (PSCs) known as embryoid bodies (EBs) (Fig.  1 B). The EB has the capacity to generate ectodermal, mesodermal and endodermal cells due to its initiation of a process that resembles gastrulation-like events in embryonic development [ 21 ]. Several protocols have been developed under this category with slight variations in the number and concentration of growth factors used, the number of days required and whether an additional step such as differentiation of EBs to MSCs or paraxial mesoderm cells, is needed to differentiate iPSCs to chondrocytes [ 22 ]. NCCs are a multipotent group of transient embryonic cells in the vertebrate. They are derived from the ectoderm and differentiate to the peripheral nervous system cells and several non-neural cell types including pigment cells, and the cranio-facial cartilage and bones [ 23 ]. Taking the advantage of being multipotent, chondrogenic cells could be differentiated from the NCC-derived MSCs [ 24 ] (Fig.  1 C). Chondrocytes were also reported to be differentiated from human embryonic stem cells (hESCs) through primitive streak or mesendoderm to mesoderm [ 25 ]. Cheng et al. followed this method to differentiate iPSCs to chondrocyte in three short stages using different combination of growth factors in each stage [ 26 ] (Fig.  1 D). iPSCs can also be differentiated to chondrocytes by co-culture with primary chondrocytes (Fig.  1 D). This method is based on the fact that the primary chondrocytes secret paracrine factors which may induce chondrogenic differentiation of the stem cells by closely mimicking the in vivo tissue microenvironment for chondrogenesis [ 27 ]. Moreover, co-culture permits crosstalk between the stem cells and the primary chondrocytes influencing chondrocyte development. It facilitates physical contact between different cell types which stabilizes the cellular phenotype and allows for communication of molecular signals involved in chondrogenic differentiation [ 28 ].

Schematic representation of the current strategies for in vitro differentiation of iPSCs to chondrocytes. A Via iPSC-derived MSCs. B Via EBs formation. C Via induction of NCCs. D Via primitive streak-mesendoderm and mesodermal lineage. E Via co-culture with primary chondrocytes. BMP4: bone morphogenetic protein 4; BMP7: bone morphogenetic protein 7; CHIR99021: glycogen synthase kinase 3 (GSK-3) inhibitor; DM: dorsomorphin; EB: embryoid body; EGF: epidermal growth factor; FGF2: fibroblast growth factor 2; GDF5: growth/differentiation factor-5; hESC: human embryonic stem cell; iPSC: induced pluripotent stem cell; MSC: mesenchymal stem cell; NCC: neural crest cell; NT4: neurotrophin-4; PDGF: platelet-derived growth factor; PSC: pluripotent stem cell; SB431542: transforming growth factor-beta receptor inhibitor; TGF-β3: transforming growth factor-beta 3; Wnt3a: Wingless/Int1 family member 3A

The above-mentioned studies showed that cartilage cells differentiated from human iPSCs represent a promising tool for regenerative medicine to treat cartilage-related diseases, however some challenges remain. The variability in the quality and characteristics of different iPSC lines affects the efficiency and consistency of chondrogenic differentiation [ 29 ]. Since the suspension culture promotes the chondrogenic differentiation and enables removal of non-chondrocytic cells, Yamashita and colleagues reported that homogenous chondrogenic nodules derived from iPSCs cultivated in suspension culture has the potential to form scaffold-free hyaline cartilage in animal models [ 30 ]. How to generate homogenous cartilage cells without formation of hypertrophic chondrocytes which have the potential to trigger the process of initiating endochondral ossification in vivo remains the main challenge. Moreover, iPSCs have the potential to form teratomas, therefore it is crucial to ensure complete elimination of undifferentiated iPSCs from chondrogenic cultures to prevent teratoma formation upon transplantation [ 31 ]. Obtaining fully mature chondrocytes from iPSCs with a phenotype comparable to native chondrocytes, is challenging [ 32 ]. In addition, undesired development of chondrogenic hypertrophy and fibrocartilage in vitro may require modification of the growth factors cocktail used [ 33 ]. Due to bovine xenoproteins, use of fetal bovine serum (FBS) in cell culture may induce adverse response in transplant patient upon injection of MSCs [ 34 ]. Additionally, there is a risk of infection because of viral and prion contamination [ 35 ]. Interestingly, MSC induction in xeno-free conditions may tackle these problems and promote the safety and efficiency of iPSC-MSCs for clinical applications [ 36 ].

Genome-edited iPSC-derived chondrocytes

In the last decade, the clustered regularly interspaced short palindromic repeats (CRISPR-Cas9) approach has become an efficient and indispensable tool in biomedical research, and has been extensively explored in bone and cartilage research [ 37 , 38 ]. It has been used to edit genes associated with chondrogenic differentiation to enhance their expression [ 39 ] or to modify signaling pathways involved in chondrogenesis [ 40 ]. For example, chondrogenesis can be regulated by the expression of SOX9 and Stat3 [ 39 ]. Chondrogenic differentiation of MSCs can be promoted by knocking down the RUNX2 , a key transcription factor associated with osteoblast differentiation [ 41 ]. Genomic editing in iPSC-derived chondrocytes has been also reported in disease modeling. Efficient editing of cartilage related genes enables to investigate in depth the mechanisms underlying cartilage disorders and to identify potential therapeutic agents [ 42 ]. An interesting genome editing study showed simultaneous SOX9 activation and peroxisome proliferator-activated receptor gamma (PPAR-γ) repression in rat BM-MSCs, which promoted chondrocytes differentiation and regeneration of calvarial bone [ 43 ]. Various studies have investigated diverse targets for regeneration, paving the way for potential clinical trials in the near future. Genome editing has been employed to boost the regenerative potential of chondrocytes. This may involve editing genes related to ECM production, cell proliferation, or resistance to hypertrophy [ 41 , 44 , 45 ]. Although numerous studies have been reported on the application of genome-edited chondrocytes for in vivo cartilage repair, drug screening, and disease modeling [ 39 , 41 , 43 ], relatively few studies have been conducted specifically on iPSC-derived chondrocytes [ 40 , 46 , 47 ]. It was revealed that mutations in TRPV4 disrupted the bone morphogenetic protein (BMP) signaling pathway in iPSC-derived chondrocytes and blocked formation of hypertrophic chondrocytes providing potential targets for drug development for TRPV4-associated skeletal dysplasias [ 48 ]. The existing methods for chondrogenic differentiation from iPSCs may generate heterogeneous cell populations. To resolve this problem, a collagen, type II, alpha 1- green fluorescent protein (COL2A1-GFP) knock-in reporter allele generated by CRISPR-Cas9 system was used to purify the cells. The purified chondroprogenitors exhibited enhanced chondrogenic potential in comparison to unselected groups [ 40 ].

Transplantation of allogeneic human iPSC-derived cartilage have shown to be more effective than allogeneic BM-MSC-derived cartilage [ 49 ]. However, these cartilage cells can trigger immunological reactions [ 50 ]. To overcome this issue, it is necessary to reduce the immunological reactions. The β2 microglobulin, a component of MHC class I molecules, was knocked down in monkey iPSCs before their differentiation into chondrocytes. As expected, the allogeneic iPSC-derived cartilage transplanted in osteochondral defects in monkey knee joints showed increased proliferation of natural killer cells and leukocytes surrounding the knocked down PSC-derived cartilage. This indicates the intricate processes in the immune response of the transplanted allogeneic cartilage in osteochondral defects in vivo [ 47 ]. These studies highlight the tremendous advantages of the CRISPR-Cas9 system in understanding the pathogenesis, identification of promising drug targets, and development of feasible treatment interventions for cartilage diseases.

Cartilage organoids formed and differentiated from iPSCs

iPSC-derived cartilage organoids are 3D cell clusters that are created by differentiation of iPSCs in vitro. To support formation of cartilage organoids and their ability to self-renewal and self-organization, a number of biocompatible materials are used, such as Matrigel and synthetic hydrogels [ 51 ]. Cartilage organoid technology has been developed to facilitate drug screening through identification of important signaling pathways, recapitulate joint developmental events during embryogenesis and cartilage regeneration. Li and colleagues showed that long-term culturing of hiPSC-derived multi-tissue organoids (MTOs) in E8 medium results in a spontaneous emergence of hyaline cartilage tissues. Moreover, a transcriptome analysis indicated a strong association between the expression of chondrogenic markers in MTOs and fetal lower limb chondrocytes [ 52 ]. Another intriguing research demonstrated that subcutaneous implantation of iPSC-derived cartilage microtissues combined with pre-hypertrophic cartilage organoids in nude mice results in formation of both cartilaginous and bony regions [ 53 ]. Similarly, O’Connor and colleagues established osteochondral organoids using murine iPSCs through time-dependent sequential exposure of TGF-β3 and BMP2, to mimic natural bone development through the process of endochondral ossification. The generated organoids showed dual tissues consisting of cartilaginous and calcified bony regions [ 54 ]. A recent study showed a sequential differentiation process to produce matrix-rich cartilage spheroids from iPSC-MSCs by inducing NCCs in xeno-free environments. Efficient chondrogenic differentiation was induced by a thienoindazole derivative, TD-198946, a small molecule used to enhance differentiation of various human progenitor cells to chondrocytes. No hypertrophy, fibrotic cartilage formation, or dedifferentiation detected in vivo in the generated cartilage spheroids. These chondrogenic spheroids can serve as building blocks for biofabrication of engineered cartilage tissues, as they have the ability to fuse within a short timeframe of a few days [ 24 ]. It is worth mentioning that iPSC-derived cartilage organoids have also been reported to recruit osteogenic precursors for bone repair [ 55 ]. A recent study has revealed that allogeneic iPSC-derived cartilage organoids transplanted in the knee joints of a primate model of chondral defects integrated with articular cartilage of the host and prevented further degeneration of the surrounding cartilage [ 49 ]. These findings open new horizons for development of complex tissue engineered implants to promote zone-specific functionality by using pre-differentiated organoids as building blocks to establish articular cartilage grafts. Even though the research on iPSC-derived cartilage organoids is still in its infancy and creating fully functional cartilage organoids is still challenging, it is evident that they have demonstrated promising applications in drug screening, disease modeling, regeneration, and repair. It is of note that application of 3D bioprinting technology in development of iPSC-derived cartilage organoids can create more complex cartilage organoids and heighten their structural organization [ 56 ].

Therapeutic applications of iPSC-derived chondrocytes

Advanced disease modeling.

iPSC-derived chondrocytes have been utilized to recapitulate cartilage injuries and diseases in vitro (Table  1 ). The pluripotency and unlimited self-renewal capacity of the iPSCs make these cells vitally important for disease modeling, which permit us to investigate the mechanisms of various diseases, screen for potential treatment targets, and test therapeutic agents [ 57 ]. iPSC-derived disease models for both monogenic and complex cartilage diseases have been developed with more focus on single gene cartilage disorders [ 58 ]. Saitta et al. established an iPSC-based in vitro model of skeletal dysplasia to investigate the initial stages of abnormal cartilage formation. Mutations in the calcium channel gene TRPV4 lead to abnormal chondrogenesis during cartilage growth plate differentiation [ 59 ]. Isogenic iPSCs with wild-type or mutant NLRP3 have been generated from patients with neonatal-onset multisystem inflammatory disease. Both in vitro and in vivo chondrogenic differentiation were performed. Furthermore, immunodeficient mice that received mutant cartilaginous pellets in vivo experienced disordered endochondral ossification [ 60 ]. In vitro models of familial osteochondritis dissecans (FOCD) was developed using both patient BM-MSCs and iPSCs derived from patient fibroblasts to delineate the pathogenesis of this disease. The results showed that chondrogenic pellets with a high glycosaminoglycan (GAG) content but a poor structural integrity. Moreover, dysregulation of matrix production and assembly was evident. These findings show that how studying FOCD iPSC-derived chondrocytes can reveal insights into disease phenotype and pathogenesis offering a new in vitro model of OA and cartilage degeneration [ 61 ]. Esseltine et al. [ 62 ] converted fibroblasts from patient with oculodentodigital dysplasia (ODDD) into iPSCs, which provided a useful model for investigation of this disease. In this study, the iPSCs showed mutated Cx43 gene, decreased levels of Cx43 mRNA and protein, resulting in impaired channel function. Furthermore, the subcellular localization of Cx43 changed during the chondrogenic differentiation of ODDD-derived iPSCs. This altered localization may have contributed to the more compact cartilage pellet morphology observed in differentiated ODDD-derived iPSCs. Additionally, other research teams successfully developed iPSC-derived disease models for other genetic and complex multifactorial skeletal disorders including type II collagenopathy , fibrodysplasia ossificans progressive (FOP), OA, hand OA, and early-onset finger OA (efOA) [ 58 ]. Recently, a novel method was introduced to direct iPSC-derived sclerotome through a sequential transformation in a 3D pellet culture. The generated chondroprogenitors can further be differentiated into articular chondrocytes or, alternatively, transformed into hypertrophic chondrocytes capable of transitioning into osteoblasts. Moreover, distinctive gene expression signatures have been identified at critical developmental stages, highlighting the effectiveness of this system in modeling genetic disorders affecting cartilage and bone [ 63 ]. In general, these studies demonstrated that normal chondrogenesis can be recapitulated using an iPSC-derived model, and disease-specific iPSCs exhibit molecular evidence of aberrant chondrogenic developmental processes. These findings may be utilized to develop therapeutic strategies for cartilage-related disorders.

To overcome some limitations of scaffold-based 3D cell culture method, scaffold-free methods showed promising results as well. Nakumora et al. [ 64 ] reported efficient fabrication of unified, self-sufficient, and functional cartilaginous constructs by combining iPSCs and bio-3D printers using a Kenzan needle array technology. This approach may facilitate repairing of articular cartilage defects . Zhang et al. [ 65 ] established a rapid and efficient approach, employing a 3D rotary suspension culture system, to directly guide iPSC differentiation toward the chondrogenic mesoderm lineage. Subsequently, the research group introduced a tetracycline-controlled BMP4 gene regulation system for iPSCs, linking transcriptional activation of BMP4 with heightened chondrogenesis using the piggyBac (PB) transposon-based gene delivery system. Kotaka and associates used magnetically-labeled iPSCs and an external magnetic force to evaluate the safety and efficacy of magnetic field-mediated delivery of iPSCs for articular cartilage repair in nude rats. The results demonstrated the effectiveness and safety of this approach for in vivo cartilage repair [ 66 ] .

Drug screening

Surgical interventions are performed to prevent progressing of focal articular cartilage defects [ 29 ], however, no effective drugs are available for treatment of cartilage regeneration. Using human MSCs for screening of compounds that promote chondrogenesis has limitations due to limited expansion of MSC passages, variations between donors and the high cost [ 67 ]. The development of the iPSC technology and advancement in genome editing approaches provide crucial tools for drug screening by establishing iPSC-derived chondrocytes. Using human iPSCs, a 96-well screening platform was developed to identify chondrogenesis-inducing agents that can be used separately or combined with other techniques for cartilage regeneration and repair. Due to their ability to promote chondrogenesis in vitro and in vivo, AB235 and NB61, two chimeric ligands of Activin/BMP2, were used and tested separately at two different doses for validation of the 96-well chondrogenic screening format. Strikingly, elevated concentrations of each of these two agents resulted in improved chondrogenic differentiation [ 68 ]. Another OA drug screening study was conducted on iPSC-derived or native mouse cartilage samples. The inflammatory environment of OA was induced in these cells by interleukin-1α (IL-1α), and a 96-well plate format was used for screening of OA drug candidates. The high-throughput screening revealed that the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) inhibitor SC514 was the most effective drug candidate to reduce cartilage loss induced by IL-1α [ 69 ]. Increased mineralization in the FOP-derived iPSCs has been detected, a phenomenon that could be mitigated by the use of the BMP inhibitor DMH1 [ 70 ]. It has been demonstrated that statins could effectively rectify the degraded cartilage observed in both chondrogenically differentiated thanatophoric dysplasia type 1 (TD1)- and achondroplasia (ACH)-specific iPSCs [ 71 ]. These studies illustrate the potential of iPSCs to provide a suitable platform to identify novel therapeutic agents for cartilage-related disorders and facilitate development of personalized regenerative medicine.

Preclinical studies

Chondrocytes derived from iPSCs have demonstrated great promise in a variety of regenerative medicine applications, especially in relation to cartilage regeneration and repair [ 49 , 64 , 72 ]. These cells offer regenerative treatments for diseases such as OA and cartilage injuries (Table  1 ). They can be combined with biomaterial scaffolds or scaffold-free methods to create engineered cartilage grafts for transplantation [ 73 ]. Generation of cartilage tissues from patient-specific iPSCs reduces the risk of immunological rejection, thus this personalized strategy has a potential for treating diseases such as OA [ 19 ]. Before their clinical application, preclinical studies of the iPSC-derived chondrocytes are crucial to assess their viability, functionality, and safety [ 74 ]. iPSC-MSCs were used to repair cartilage defects in a rabbit model. Macroscopic and histological assessment revealed more cartilage repair in the experimental group as compared to both the control and scaffold implantation group. Furthermore, no teratoma formation detected in all the three groups indicating the safety and potential of iPSC-MSCs for cartilage regeneration [ 75 ]. Ko et al. [ 76 ] implanted iPSC-derived chondrocytes in osteochondral defects in immunosuppressed rats. The defects exhibited a significantly higher quality of cartilage repair than in the control. In another study, homogenous cartilaginous particles derived from chondrocyte-specific reporter hiPSC lines were transplanted into joint surface defects in immunodeficient rat and immunosuppressed mini-pig models. The neocartilage survived and integrated into native cartilage, and no tumor formation was observed in all the animal models following the transplantation [ 30 ]. The potential of MSC-based therapies is attributed to the release of trophic factors via paracrine signaling, with small extracellular vesicles (sEVs) potentially playing a significant role [ 77 ]. Zhu et al. [ 78 ] investigated the therapeutic efficacy of exosomes derived from synovial membrane MSCs (SM-MSC-Exos) and iPSC-MSCs (iPSC-MSC-Exos) in treatment of OA. The injected exosomes in an OA mouse model showed that iPSC-MSC-Exos exhibit a stronger therapeutic impact on OA compared to SM-MSC-Exos. Similarly, iPSC-MSC-derived sEVs injected in degenerative discs of intervertebral disc degeneration (IVDD) rat models revealed significant improvement in IVDD and senescence of nucleus pulposus cells of the IVD [ 79 ]. Given the poliferative capacity of autologous iPSC-MSCs, these cells ensure a consistent and abundant source of therapeutic sEVs, which could introduce a new therapeutic strategy for OA and IVDD treatment [ 78 , 79 ]. As previousely mentioned, Nejadnik et al. developed an effective method to directly differentiate human iPSCs (hiPSCs) into MSCs and chondrocytes without the need for EBs formation. Transplantation of these cells in OA rat models successfully repaired the osteochondral defects [ 33 ]. However, the traces of fibrocartilage and hypertrophic cartilage detected in the generated chondrocytes in vitro and use of FBS in the chondrogenic medium may prevent their clinical application. Use of Xeno-free media and thorough characterization of hiPSC-derived MSCs and chondrocytes will be essential prior to transplantation [ 33 ]. An intriguing study has demonestrated that chondrogenic spheroids derived from iPSC-MSCs retain cartilage phenotype in vivo comparable to the chondrogenic-like tissues generated from the same cell spheroids in vitro. In contrast to spheroids obtained from iPSC-MSCs, distinct bone-like tissue formation was evident in BM-MSC spheroids. This may prove the capacity of iPSC-MSC-derived chondrogenic spheroids to form cartilage-like tissues without endochondral ossification for treatment of cartilage defects in vivo [ 24 ]. Additionally, due to the ability of chondrogenic spheroids to fuse rapidly within a short timeframe, they can serve as as building blocks for constructing larger cartilage tissues using techniques like the Kenzan bioprinting method [ 56 ]. Current focus tends to shift towards investigating immune reactions in the context of allogeneic cartilage transplantation. Abe and colleagues were the first to conduct allogeneic cartilage transplantation into a primate model using major histocompatibility complex (MHC)-mismatched iPSC-derived cartilage organoids without the need for immunosuppressive drugs [ 49 ]. Remarkably, the transplanted organoids exhibited successful engraftment into chondral defects on the knee joint surface of the primate model, demonstrating survival, integration, and remodeling similar to native cartilage, without any observed immune reactions [ 49 ]. The findings of these preclinical studies demonstrate effective and clinically translatable approaches for regenerating cartilage tissue using hiPSC-derived MSCs and chondrocytes, offering potential enhancements in cartilage regeneration outcomes in cartilage diseases.

Clinical studies

Over the past decade, iPSCs have shown significant advancements, offering new prospects for personalized cell therapy. Patient-derived iPSCs exhibit a lower risk of rejection compared to allogeneic iPSCs. Therefore, some challenges such as tumorigenicity or immunogenicity must be addressed before the iPSCs can be extensively utilized in clinical therapy. To date, 89 clinical trials referenced under “induced pluripotent stem cells” have been registered on the World Health Organization (WHO)-managed main databases ( https://clinicaltrials.gov/ , International Clinical Trials Registry Platform (ICTRP), https://trialsearch.who.int/ ). Several studies from the Japan Primary Registries Network ( https://rctportal.niph.go.jp/en ) can be added to the list since most of their 21 iPSCs trials are not cross-referenced with the WHO’s platforms. Among the total 110 identified clinical trials, 51 trials were registered as interventional and the remaining as observational. Despite the low rejection risk, slow shifting from autologous to allogenic iPSC-derived therapy approach has been crucial due to the time and cost required for characterization and safety testing of each cell line. Furthermore, allogeneic iPSCs approach allow more time for the testing process, and once an approved cell line is established, it can be used to treat multiple patients. Opting for allogeneic cell therapy would result in a readily accessible therapeutic product for interventions [ 80 ].

Until recently, pluripotent cell-derived MSCs were not a popular focus in clinical research, with only a small number of studies exploring this area, despite the wide variety of potential tissues that could be produced. Currently, only three clinical trials involving ESC-derived MSCs [ 81 , 82 , 83 ], and six iPSC-MSCs clinical trials have been reported (Table  2 ) [ 84 , 85 ]. It is important to note that from the six clinical trials, cartilage regeneration through iPSC-MSCs was only addressed in two studies. In 2020, the University of Sydney and Cynata Therapeutics conducted phase 1 clinical trial to evaluate the safety, efficacy, and cost-effectiveness of an allogenic MSCs therapy (Cymerus MSCs) for tibiofemoral knee OA [ 86 ]. Lately, Cynata Therapeutics has reported that 321 subjects were recruited for the phase 3 SCUlpTOR clinical trial which will start in 2024 for 24 months (Trial ID: ACTRN12620000870954). In the foreseeable future, the phase 1 clinical trial sponsored by the Chinese Nuwacell Biotechnology company will investigate the safety and efficacy of the NCR100 allogenic iPSC-MSCs intra-articular injection for treatment of knee OA (Trial ID: NCT06049342). This is the first Chinese iPSC-derived cell product approved to be used in phase 1 clinical trial following six years of research and development, ( https://en.nuwacell.com/news ). It is to be noted that a study tried to directly differentiate allogenic iPSCs into chondrocytes without intermediate MSCs differentiation, to treat knee OA as well (Trial ID: jRCTa050190104). The 2020 Japanese interventional trial from Kyoto University was followed by a second observational trial in 2020 for post-treatment evaluation on the subject’s knees (Trial ID: jRCT1050220051).

As a concluding remark, there have been no results regarding cartilage regeneration through iPSC-derived cell therapy in these trials so far. The scarcity of iPSC-MSCs and cartilage-oriented clinical trials indicates significant potential for further advancement and enhancement. Hopefully with the extensively growing iPSCs research, cartilage regeneration for condition such as OA will receive greater attention.

Limitations of iPSC-derived chondrocyte in vitro models

Throughout this review, numerous studies have demonstrated the tremendous advantages offered by iPSC-derived chondrocytes for cartilage research. However, there are some limitations associated with iPSC-derived chondrocyte in vitro models. The first limitation is that the iPSC-derived chondrocytes may show an immature phenotype, and it is still challenging to obtain iPSC-derived chondrocytes with full maturation and stability [ 87 ]. The second limitation is the possibility to generate diverse cell populations with variation in maturation stages. This heterogeneity might complicate result interpretation and compromise the validity and reproducibility of experimental results [ 22 ]. Due to the potential of iPSCs to form teratomas, residual undifferentiated iPSCs in iPSC-derived cartilage grafts may pose a risk of tumor formation in transplantation studies [ 88 ]. Another main challenge is the variability in the efficiency of chondrogenic differentiation among different iPSC lines and even among clones of the same line [ 31 ]. Moreover, the culture conditions for differentiation of iPSCs to chondrocytes may not fully replicate the complex microenvironment of native cartilage tissue. The artificial culture conditions can influence cellular behavior and might not fully capture the in vivo physiological and mechanical complexity of chondrocytes [ 18 , 24 ]. Even though patient-derived iPSCs can potentially reduce the immunological rejection [ 89 ], the in vitro differentiation and manipulation processes may introduce foreign antigens, raising concerns about the immunogenicity of the generated chondrocytes [ 19 ]. In addition, the ability of iPSC-derived chondrocytes to produce a mature and robust ECM may be limited. The structure and organization of the ECM are essential for the functionality and integrity of cartilage tissue. Therefore, ECM defects may affect the utility of in vitro models [ 90 ]. Last, but not the least, the robustness of cartilage in vitro models may be affected by the technical aspects of iPSC maintenance, differentiation, and characterization, which may introduce variability [ 32 ]. These limitations illuminate the challenges associated with iPSC-derived chondrocyte in vitro models. Improvement and optimization of chondrogenic differentiation protocols may overcome these limitations and ensure reliable and comparable results across various studies.

Scaling-up of iPSC-derived cells

The potential of iPSC-derived technologies in chondrogenesis, offering significant benefits for OA and other medical conditions, is evident. However, unlocking these benefits encounters hurdles such as limited process understanding, outdated manufacturing techniques, and insufficient automation. Manual manufacturing and quality control processes prove labor-intensive and error prone. To address the anticipated demand for iPSC-derived cells, scalable production methods must be developed to uphold clinical-grade yields and immunomodulatory properties. Moreover, research indicates that human iPSCs might present an epigenetic edge compared to adult stem cells in producing chondrocytes on a large scale without a tendency towards hypertrophy. Ko and his team showcased heightened expression of key chondrogenic markers such as SOX9, COL2A1, and aggrecan (ACAN), alongside decreased levels of hypertrophic markers like COL10A1 and RUNX2 in iPSC-derived chondrocytes when compared to BM-MSC pellets [ 76 ].

It is crucial to establish robust protocols for large-scale iPSC production to support tasks like cell banking. Thorough evaluations of iPSC-derived chondrocytes in large-scale production settings are essential for consistent quality outcomes and to tackle the challenge of spontaneous differentiation. Closing the gap between research and clinical application necessitates the development of scaled production technologies spanning from initial seeding to final fill-and-finish stages. Embracing full automation in iPSCs cell therapy manufacturing and quality control is paramount for enhancing both product quality and production efficiency in this rapidly evolving field [ 91 ]. A recent study developed hiPSC-derived limb bud mesenchymal cells (ExpLBM cells) with strong chondrogenic potential and stable proliferation. Using a stirred bioreactor, this method outperformed conventional culture plate methods by yielding significant cartilage tissue with just 1 × 10 6 cells. This produced significant amounts of cartilaginous particles, suggesting a scalable method for cartilage regeneration without immune rejection. This efficient approach requires minimal cell quantities and offers potential scalability through adjustments in medium volume and cell numbers [ 92 ]. Another recent study has introduced GelMA microcarriers developed via step emulsification microfluidic devices as a degradable platform for amplifying iPSC-MSCs in scalable bioreactors, while maintaining typical MSC traits and immune-modulatory capabilities. These GelMA microcarriers, manufactured with efficiency and reproducibility in mind, facilitate substantial expansion of iPSC-MSCs (up to 16 times within 8 days) in vertical wheel bioreactors, with a post-digestion viability exceeding 95%. When compared to monolayer culture, iPSC-MSCs expanded on GelMA microcarriers exhibit at least similar, if not superior, immune-modulatory potential. This approach marks a notable progression in producing immune-modulatory iPSC-MSCs, providing scalability, cost-efficiency, and simplified cell retrieval through direct dissolution of microcarriers, thereby minimizing cell wastage [ 93 ].

A novel, good manufacturing practice (GMP)-compliant scalable manufacturing procedure is introduced for the fabrication of iPSC-MSCs, tackling the aforementioned hurdles. By employing xenogeneic-, serum-, and feeder-free conditions, alongside chemically defined maintenance for iPSCs, the process eliminates the necessity for murine feeders and accomplishes mesoderm induction, resulting in heightened performance of MSCs in immunopotency assessments. The manufacturing process comprises three phases: iPSC banking, iPSC expansion and differentiation into MSCs, and MSC expansion and formulation of the final clinical product. Impressively, one vial of iPSCs can yield an average of 3.2 × 10 10 MSCs, and the complete iPSC bank has the potential to generate 2.9 × 10 15 MSCs, equating to 29 million clinical doses, each containing 1 × 10 8 MSCs. This method presents a promising resolution to the challenges of supply, scalability, and consistency in iPSC-MSC production, paving the way for their utilization in clinical applications with heightened efficacy and safety. This optimized manufacturing process for iPSC-MSCs has been applied in treating steroid-resistant acute graft versus host disease (SR-aGvHD) in a phase 1 clinical trial but could be similarly employed in the iPSC-MSCs-Chondrocyte approach for chondrogenesis [ 84 ].

The aim of automating cell therapy manufacturing is to reduce human intervention, ensuring sterile processes within isolator-like platforms to minimize contamination risks. Despite notable advancements, challenges persist, including difficulties in executing specific biological procedures with robotic assistance, prompting the need for exploring new solutions and standardization. Establishing an automated manufacturing platform requires precise definition of process parameters and configurations through validated standard operating procedures (SOPs). To address these needs, an advanced automated cell manufacturing platform was employed to produce both equine and human iPSC-MSCs via EBs [ 94 ]. These iPSC-MSCs were further demonstrated their ability to differentiate into adipogenic, osteogenic, and chondrogenic lineages proficiently. The main goal of this study was to develop a simplified and uniform procedure for isolating MSCs from peripheral blood under GMP conditions, ensuring their viability and purity. Compared to existing protocols documented in the literature, this approach offers simplicity, scalability and consistently delivering robust cell purity [ 94 ]. Recently, another automatic system was reported to produce iPSC-derived therapies, covering a range of cell types including iPSC-MSCs, iPSC-derived chondrocytes, and extracellular vesicles [ 95 ]. iPSC expansion and differentiation into MSCs and chondrocytes take place in plates, while expansion of iPSC-derived MSCs and production of extracellular vesicles utilize microcarriers within stirred tank bioreactors. The system is designed to oversee iPSC expansion, differentiation, and the fill and finish of the products. Furthermore, this platform including a range of quality control assays such as microscopy, cell counting, viability assessment, qPCR, and endotoxin assays, aims to address these challenges by establishing an automated platform for producing cell therapies specifically targeting OA, and serves as an example of how existing automation technology can be customized and improved to enhance scalability and efficiency.

Conclusions

Genomic abnormalities detected during the reprogramming and subsequent expansion of iPSCs raised serious safety concerns [ 96 ]. Therefore, several factors including starting cell source, method of delivery, reprogramming factor and cell passage, should be taken into consideration for the generation of iPSCs in order to reduce not only genomic instability [ 97 ], but also immunogenicity [ 98 , 99 ].

The field of iPSC-derived cartilages is rapidly evolving, and several approaches and perspectives have been explored to tackle limitations and enhance the potential applications of these cells in regenerative medicine. Development of new or optimization of the current differentiation protocols to improve the maturation and stability of iPSC-derived chondrocytes is critical [ 25 ]. This can be achieved by further research on signaling pathways, culture conditions, and other factors that facilitate the maturation of iPSC-derived chondrocytes. It is significantly important to implement cutting-edge 3D culture systems combined with ink-free bioprinting technique to more closely mimic the in vivo microenvironment of cartilage tissue [ 56 ]. Using bioreactors, biomimetic scaffolds, 3D bioprinting and other advanced technologies can improve the functional characteristics of iPSC-derived chondrocytes for cartilage repair. Generation of heterogeneous cell populations remains one of the major challenges in development of efficient cartilage grafts [ 100 ]. To eliminate undesired cells and promote the homogeneity of iPSC-derived chondrocyte populations, sustained development of precise genome editing tools is quite essential. Moreover, it is necessary to identify the sources of heterogeneity in iPSC-derived chondrocyte populations to reduce variability and improve reproducibility [ 101 ]. Tumorigenicity associated with residual undifferentiated iPSCs can be addressed by advancements in purification methods and genetic modifications to increase the safety of iPSC-derived chondrocytes for clinical applications [ 102 ]. Moreover, scalability and cost-effectiveness of the methods used for generation of iPSC-derived chondrocytes should be improved by simplifying the differentiation protocols, optimizing culture conditions, and utilizing automation technologies [ 95 ]. Additionally, it is very crucial to enhance the development of in vivo models to investigate the safety and efficacy of iPSC-derived chondrocytes in preclinical studies [ 103 ]. Successful preclinical studies should be followed by well-designed clinical trials in patients with cartilage-related disorders. Furthermore, for personalized regenerative medicine, the design of preclinical and clinical trials should focus on the integration of patient-specific iPSCs with advanced gene editing technologies and highly efficient chondrogenic differentiation protocols. These future perspectives reflect the continuous endeavors to harness the full potential of iPSC-derived chondrocytes, opening the door for innovative approaches in cartilage regeneration and repair. Since this field is advancing rapidly, interdisciplinary collaborations and advancement in technologies will play a vital role in shaping the future of iPSC-based cartilage regeneration research.

Abbreviations

Two dimentional

Three dimentional

Achondroplasia

Bone marrow-derived Mesenchymal stem cells

Bone morphogenetic protein 2

Bone morphogenetic protein 4

Umbilical cord blood mononuclear cell

Cellular-Myelocytomatosis

Collagen, type II, alpha 1

Collagen, type II, alpha 1-green fluorescent protein

Clustered regularly interspaced short palindromic repeats

Dorsomorphin homolog 1

Embryoid bodies

Extracellular matrix

Early-onset finger osteoarthritis

Fibrodysplasia ossficans progressive

Good manufacturing practice

Human embryonic stem cells

Human induced pluripotent stem cells

Hand osteoarthritis

Identification number

• Induced pluripotent stem cells

Intervertebral disc degeneration

Krüppel-like factor 4

Knee osteoarthritis

Metaphyseal chondrodysplasia type Schmid

Multiple epiphyseal dysplasia

Mesenchymal stem cell

Not applicable

Neural crest cells

Kappa-light-chain-enhancer of activated B cells

Normal human epidermal keratinocytes

• Osteoarthritis

Octamer binding transcription factor 3/4

Peripheral blood mononuclear cells

Pluripotent stem cells

Runt-related transcription factor 2

Small extracellular vesicles

Standard operating procedures

SRY-related high mobility group box

Sex determining region Y

Thanatophoric dysplasia type 1

Transforming growth factor-beta 3

Krishnan Y, Grodzinsky AJ. Cartilage diseases. Matrix Biol. 2018;71–72:51–69.

Article   PubMed   PubMed Central   Google Scholar  

Sha’ban M. Histology and biomechanics of cartilage. Cartil Tissue Knee Jt Biomech [Internet]. Elsevier; 2024 [cited 2024 Feb 9]. pp. 25–35. Available from: https://linkinghub.elsevier.com/retrieve/pii/B9780323905978000013

Tokgoz E, Levitt S, Sosa D, Carola NA, Patel V. Robotics applications in total knee arthroplasty. Total knee arthroplasty. Cham: Springer Nature Switzerland; 2023. p. 155–74.

Google Scholar  

Trounson A, McDonald C. Stem cell therapies in clinical trials: progress and challenges. Cell Stem Cell. 2015;17:11–22.

Article   CAS   PubMed   Google Scholar  

Pittenger MF, Discher DE, Péault BM, Phinney DG, Hare JM, Caplan AI. Mesenchymal stem cell perspective: cell biology to clinical progress. NPJ Regen Med. 2019;4:22.

Uccelli A, Moretta L, Pistoia V. Mesenchymal stem cells in health and disease. Nat Rev Immunol. 2008;8:726–36.

Squillaro T, Peluso G, Galderisi U. Clinical trials with mesenchymal stem cells: an update. Cell Transpl. 2016;25:829–48.

Article   Google Scholar  

Nakashima K, Zhou X, Kunkel G, Zhang Z, Deng JM, Behringer RR, et al. The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell. 2002;108:17–29.

Yoshida CA, Furuichi T, Fujita T, Fukuyama R, Kanatani N, Kobayashi S, et al. Core-binding factor β interacts with Runx2 and is required for skeletal development. Nat Genet. 2002;32:633–8.

Kangari P, Talaei-Khozani T, Razeghian-Jahromi I, Razmkhah M. Mesenchymal stem cells: amazing remedies for bone and cartilage defects. Stem Cell Res Ther. 2020;11:492.

Somoza RA, Welter JF, Correa D, Caplan AI. Chondrogenic differentiation of mesenchymal stem cells: challenges and unfulfilled expectations. Tissue Eng Part B Rev. 2014;20:596–608.

Kim HJ, Park J-S. Usage of human mesenchymal stem cells in cell-based therapy: advantages and disadvantages. Dev Reprod. 2017;21:1–10.

Galipeau J. The mesenchymal stromal cells dilemma—does a negative phase III trial of random donor mesenchymal stromal cells in steroid-resistant graft-versus-host disease represent a death knell or a bump in the road? Cytotherapy. 2013;15:2–8.

Article   PubMed   Google Scholar  

Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126:663–76.

Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131:861–72.

Karagiannis P, Takahashi K, Saito M, Yoshida Y, Okita K, Watanabe A, et al. Induced pluripotent stem cells and their use in human models of disease and development. Physiol Rev. 2019;99:79–114.

Guha P, Morgan JW, Mostoslavsky G, Rodrigues NP, Boyd AS. Lack of immune response to differentiated cells derived from syngeneic induced pluripotent stem cells. Cell Stem Cell. 2013;12:407–12.

Guzzo RM, Gibson J, Xu R, Lee FY, Drissi H. Efficient differentiation of human iPSC-derived mesenchymal stem cells to chondroprogenitor cells. J Cell Biochem. 2013;114:480–90.

Diekman BO, Christoforou N, Willard VP, Sun H, Sanchez-Adams J, Leong KW, et al. Cartilage tissue engineering using differentiated and purified induced pluripotent stem cells. Proc Natl Acad Sci. 2012;109:19172–7.

Article   CAS   PubMed   PubMed Central   Google Scholar  

Walters-Shumka JP, Sorrentino S, Nygaard HB, Willerth SM. Recent advances in personalized 3D bioprinted tissue models. MRS Bull. 2023;48:632–42.

Article   CAS   Google Scholar  

Schell JP. Spontaneous differentiation of human pluripotent stem cells via embryoid body formation. Hum stem cell man. Elsevier; 2012. p. 363–73.

De Kinderen P, Meester J, Loeys B, Peeters S, Gouze E, Woods S, et al. Differentiation of Induced pluripotent stem cells into chondrocytes: methods and applications for disease modeling and drug discovery. J Bone Miner Res. 2020;37:397–410.

Gammill LS, Bronner-Fraser M. Neural crest specification: migrating into genomics. Nat Rev Neurosci. 2003;4:795–805.

Zujur D, Al-Akashi Z, Nakamura A, Zhao C, Takahashi K, Aritomi S, et al. Enhanced chondrogenic differentiation of iPS cell-derived mesenchymal stem/stromal cells via neural crest cell induction for hyaline cartilage repair. Front Cell Dev Biol. 2023;11:1140717.

Oldershaw RA, Baxter MA, Lowe ET, Bates N, Grady LM, Soncin F, et al. Directed differentiation of human embryonic stem cells toward chondrocytes. Nat Biotechnol. 2010;28:1187–94.

Cheng A, Kapacee Z, Peng J, Lu S, Lucas RJ, Hardingham TE, et al. Cartilage repair using human embryonic stem cell-derived chondroprogenitors. Stem Cells Transl Med. 2014;3:1287–94.

Aung A, Gupta G, Majid G, Varghese S. Osteoarthritic chondrocyte–secreted morphogens induce chondrogenic differentiation of human mesenchymal stem cells. Arthritis Rheum. 2011;63:148–58.

Heng BC, Cao T, Lee EH. Directing stem cell differentiation into the chondrogenic lineage in vitro. Stem Cells. 2004;22:1152–67.

Tsumaki N, Okada M, Yamashita A. iPS cell technologies and cartilage regeneration. Bone. 2015;70:48–54.

Yamashita A, Morioka M, Yahara Y, Okada M, Kobayashi T, Kuriyama S, et al. Generation of scaffoldless hyaline cartilaginous tissue from human iPSCs. Stem Cell Rep. 2015;4:404–18.

Koyama N, Miura M, Nakao K, Kondo E, Fujii T, Taura D, et al. Human induced pluripotent stem cells differentiated into chondrogenic lineage via generation of mesenchymal progenitor cells. Stem Cells Dev. 2013;22:102–13.

Castro-Viñuelas R, Sanjurjo-Rodríguez C, Piñeiro-Ramil M, Hermida-Gómez T, Fuentes-Boquete IM, de Toro-Santos FJ, et al. Induced pluripotent stem cells for cartilage repair: current status and future perspectives. Eur Cell Mater. 2018;36:96–109.

Nejadnik H, Diecke S, Lenkov OD, Chapelin F, Donig J, Tong X, et al. Improved approach for chondrogenic differentiation of human induced pluripotent stem cells. Stem Cell Rev Rep. 2015;11:242–53.

Hemeda H, Giebel B, Wagner W. Evaluation of human platelet lysate versus fetal bovine serum for culture of mesenchymal stromal cells. Cytotherapy. 2014;16:170–80.

Marcus-Sekura C, Richardson JC, Harston RK, Sane N, Sheets RL. Evaluation of the human host range of bovine and porcine viruses that may contaminate bovine serum and porcine trypsin used in the manufacture of biological products. Biologicals. 2011;39:359–69.

Kamiya D, Takenaka-Ninagawa N, Motoike S, Kajiya M, Akaboshi T, Zhao C, et al. Induction of functional xeno-free MSCs from human iPSCs via a neural crest cell lineage. Npj Regen Med. 2022;7:47.

Fitzgerald J. Applications of CRISPR for musculoskeletal research. Bone Jt Res. 2020;9:351–9.

Vlashi R, Zhang X, Li H, Chen G. Potential therapeutic strategies for osteoarthritis via CRISPR/Cas9 mediated gene editing. Rev Endocr Metab Disord. 2023;25:339.

Mochizuki Y, Chiba T, Kataoka K, Yamashita S, Sato T, Kato T, et al. Combinatorial CRISPR/Cas9 approach to elucidate a far-upstream enhancer complex for tissue-specific Sox9 expression. Dev Cell. 2018;46:794-806.e6.

Adkar SS, Wu C-L, Willard VP, Dicks A, Ettyreddy A, Steward N, et al. Step-wise chondrogenesis of human induced pluripotent stem cells and purification via a reporter allele generated by CRISPR-Cas9 genome editing. Stem Cells. 2019;37:65–76.

Kim HJ, Park JM, Lee S, Cho HB, Park J-I, Kim J-H, et al. Efficient CRISPR-Cas9-based knockdown of RUNX2 to induce chondrogenic differentiation of stem cells. Biomater Sci. 2022;10:514–23.

Lilianty J, Bateman JF, Lamandé SR. Generation of a heterozygous COL2A1 (pG1113C) hypochondrogenesis mutation iPSC line, MCRIi019-A-7, using CRISPR/Cas9 gene editing. Stem Cell Res. 2021;56:102515.

Truong VA, Hsu M-N, Kieu Nguyen NT, Lin M-W, Shen C-C, Lin C-Y, et al. CRISPRai for simultaneous gene activation and inhibition to promote stem cell chondrogenesis and calvarial bone regeneration. Nucl Acids Res. 2019;47:e74–e74.

Bonato A, Fisch P, Ponta S, Fercher D, Manninen M, Weber D, et al. Engineering inflammation-resistant cartilage: bridging gene therapy and tissue engineering. Adv Healthc Mater. 2023;12:2202271.

Farhang N, Davis B, Weston J, Ginley-Hidinger M, Gertz J, Bowles RD. Synergistic CRISPRa-regulated chondrogenic extracellular matrix deposition without exogenous growth factors. Tissue Eng Part A. 2020;26:1169–79.

Dicks A, Wu C-L, Steward N, Adkar SS, Gersbach CA, Guilak F. Prospective isolation of chondroprogenitors from human iPSCs based on cell surface markers identified using a CRISPR-Cas9-generated reporter. Stem Cell Res Ther. 2020;11:66.

Okutani Y, Abe K, Yamashita A, Morioka M, Matsuda S, Tsumaki N. Generation of monkey induced pluripotent stem cell-derived cartilage lacking major histocompatibility complex class I molecules on the cell surface. Tissue Eng Part A. 2022;28:94–106.

Dicks AR, Maksaev GI, Harissa Z, Savadipour A, Tang R, Steward N, et al. Skeletal dysplasia-causing TRPV4 mutations suppress the hypertrophic differentiation of human iPSC-derived chondrocytes. Elife. 2023;12:e71154.

Abe K, Yamashita A, Morioka M, Horike N, Takei Y, Koyamatsu S, et al. Engraftment of allogeneic iPS cell-derived cartilage organoid in a primate model of articular cartilage defect. Nat Commun. 2023;14:804.

Kimura T, Yamashita A, Ozono K, Tsumaki N. Limited immunogenicity of human induced pluripotent stem cell-derived cartilages. Tissue Eng Part A. 2016;22:1367–75.

Crispim JF, Ito K. De novo neo-hyaline-cartilage from bovine organoids in viscoelastic hydrogels. Acta Biomater. 2021;128:236–49.

Li M, Abrahante JE, Vegoe A, Chai YW, Lindborg B, Toth F, et al. Self-organized emergence of hyaline cartilage in hiPSC-derived multi-tissue organoids. Cell Biol. 2021;2014:272481. https://doi.org/10.1101/2021.09.21.461213 .

Hall GN, Tam WL, Andrikopoulos KS, Casas-Fraile L, Voyiatzis GA, Geris L, et al. Patterned, organoid-based cartilaginous implants exhibit zone specific functionality forming osteochondral-like tissues in vivo. Biomaterials. 2021;273:120820.

O’Connor SK, Katz DB, Oswald SJ, Groneck L, Guilak F. Formation of osteochondral organoids from murine induced pluripotent stem cells. Tissue Eng Part A. 2021;27:1099–109.

Tam WL, Freitas Mendes L, Chen X, Lesage R, Van Hoven I, Leysen E, et al. Human pluripotent stem cell-derived cartilaginous organoids promote scaffold-free healing of critical size long bone defects. Stem Cell Res Ther. 2021;12:513.

Vignes H, Smaida R, Conzatti G, Hua G, Benkirane-Jessel N. Custom-made meniscus biofabrication. Trends Biotechnol. 2023;41:1467–70.

Singh VK, Kalsan M, Kumar N, Saini A, Chandra R. Induced pluripotent stem cells: applications in regenerative medicine, disease modeling, and drug discovery. Front Cell Dev Biol. 2015. https://doi.org/10.3389/fcell.2015.00002/abstract .

Lach MS, Rosochowicz MA, Richter M, Jagiełło I, Suchorska WM, Trzeciak T. The induced pluripotent stem cells in articular cartilage regeneration and disease modelling: are we ready for their clinical use? Cells. 2022;11:529.

Saitta B, Passarini J, Sareen D, Ornelas L, Sahabian A, Argade S, et al. Patient-derived skeletal dysplasia induced pluripotent stem cells display abnormal chondrogenic marker expression and regulation by BMP2 and TGFβ1 . Stem Cells Dev. 2014;23:1464–78.

Yokoyama K, Ikeya M, Umeda K, Oda H, Nodomi S, Nasu A, et al. Enhanced chondrogenesis of induced pluripotent stem cells from patients with neonatal-onset multisystem inflammatory disease occurs via the caspase 1–independent cAMP/protein kinase A/CREB pathway. Arthritis Rheumatol. 2015;67:302–14.

Xu M, Stattin E-L, Shaw G, Heinegård D, Sullivan G, Wilmut I, et al. Chondrocytes derived from mesenchymal stromal cells and induced pluripotent cells of patients with familial osteochondritis dissecans exhibit an endoplasmic reticulum stress response and defective matrix assembly. Stem Cells Transl Med. 2016;5:1171–81.

Esseltine JL, Shao Q, Brooks C, Sampson J, Betts DH, Séguin CA, et al. Connexin43 mutant patient-derived induced pluripotent stem cells exhibit altered differentiation potential. J Bone Miner Res Off J Am Soc Bone Miner Res. 2017;32:1368–85.

Lamandé SR, Ng ES, Cameron TL, Kung LHW, Sampurno L, Rowley L, et al. Modeling human skeletal development using human pluripotent stem cells. Proc Natl Acad Sci. 2023;120:e2211510120.

Nakamura A, Murata D, Fujimoto R, Tamaki S, Nagata S, Ikeya M, et al. Bio-3D printing iPSC-derived human chondrocytes for articular cartilage regeneration. Biofabrication. 2021;13:044103.

Zhang M, Niibe K, Kondo T, Limraksasin P, Okawa H, Miao X, et al. Rapid and efficient generation of cartilage pellets from mouse induced pluripotent stem cells by transcriptional activation of BMP-4 with shaking culture. J Tissue Eng. 2022;13:20417314221114616.

Kotaka S, Wakitani S, Shimamoto A, Kamei N, Sawa M, Adachi N, et al. Magnetic targeted delivery of induced pluripotent stem cells promotes articular cartilage repair. Stem Cells Int. 2017;2017:9514719.

Siddappa R, Licht R, Van Blitterswijk C, De Boer J. Donor variation and loss of multipotency during in vitro expansion of human mesenchymal stem cells for bone tissue engineering. J Orthop Res. 2007;25:1029–41.

Yang S-L, Harnish E, Leeuw T, Dietz U, Batchelder E, Wright PS, et al. Compound screening platform using human induced pluripotent stem cells to identify small molecules that promote chondrogenesis. Protein Cell. 2012;3:934–42.

Willard VP, Diekman BO, Sanchez-Adams J, Christoforou N, Leong KW, Guilak F. Use of cartilage derived from murine induced pluripotent stem cells for osteoarthritis drug screening. Arthritis Rheumatol. 2014;66:3062–72.

Matsumoto Y, Hayashi Y, Schlieve CR, Ikeya M, Kim H, Nguyen TD, et al. Induced pluripotent stem cells from patients with human fibrodysplasia ossificans progressiva show increased mineralization and cartilage formation. Orphanet J Rare Dis. 2013;8:190.

Yamashita A, Morioka M, Kishi H, Kimura T, Yahara Y, Okada M, et al. Statin treatment rescues FGFR3 skeletal dysplasia phenotypes. Nature. 2014;513:507–11.

Chang Y-H, Wu K-C, Ding D-C. Induced pluripotent stem cell-differentiated chondrocytes repair cartilage defect in a rabbit osteoarthritis model. Stem Cells Int. 2020;2020:1–16.

Lammi M, Piltti J, Prittinen J, Qu C. Challenges in fabrication of tissue-engineered cartilage with correct cellular colonization and extracellular matrix assembly. Int J Mol Sci. 2018;19:2700.

Yamashita A, Tsumaki N. Recent progress of animal transplantation studies for treating articular cartilage damage using pluripotent stem cells. Dev Growth Differ. 2021;63:72–81.

Xu X, Shi D, Liu Y, Yao Y, Dai J, Xu Z, et al. In vivo repair of full-thickness cartilage defect with human iPSC-derived mesenchymal progenitor cells in a rabbit model. Exp Ther Med. 2017;14:239–45.

Ko J-Y, Kim K-I, Park S, Im G-I. In vitro chondrogenesis and in vivo repair of osteochondral defect with human induced pluripotent stem cells. Biomaterials. 2014;35:3571–81.

Liang X, Ding Y, Zhang Y, Tse H-F, Lian Q. Paracrine mechanisms of mesenchymal stem cell-based therapy: current status and perspectives. Cell Transpl. 2014;23:1045–59.

Zhu Y, Wang Y, Zhao B, Niu X, Hu B, Li Q, et al. Comparison of exosomes secreted by induced pluripotent stem cell-derived mesenchymal stem cells and synovial membrane-derived mesenchymal stem cells for the treatment of osteoarthritis. Stem Cell Res Ther. 2017;8:64.

Sun Y, Zhang W, Li X. Induced pluripotent stem cell-derived mesenchymal stem cells deliver exogenous miR-105-5p via small extracellular vesicles to rejuvenate senescent nucleus pulposus cells and attenuate intervertebral disc degeneration. Stem Cell Res Ther. 2021;12:286.

Blair NF, Barker RA. Making it personal: the prospects for autologous pluripotent stem cell-derived therapies. Regen Med. 2016;11:423–5.

Yan L, Wu Y, Li L, Wu J, Zhao F, Gao Z, et al. Clinical analysis of human umbilical cord mesenchymal stem cell allotransplantation in patients with premature ovarian insufficiency. Cell Prolif. 2020;53:e12938.

Shin JH, Ryu C-M, Yu HY, Park J, Kang AR, Shin JM, et al. Safety of human embryonic stem cell-derived mesenchymal stem cells for treating interstitial cystitis: a phase I study. Stem Cells Transl Med. 2022;11:1010–20.

Guo B, Duan Y, Li Z, Tian Y, Cheng X, Liang C, et al. High-strength cell sheets and vigorous hydrogels from mesenchymal stem cells derived from human embryonic stem cells. ACS Appl Mater Interfaces. 2023;15:27586–99.

Bloor AJC, Patel A, Griffin JE, Gilleece MH, Radia R, Yeung DT, et al. Production, safety and efficacy of iPSC-derived mesenchymal stromal cells in acute steroid-resistant graft versus host disease: a phase I, multicenter, open-label, dose-escalation study. Nat Med. 2020;26:1720–5.

Rasko JEJ, Patel A, Griffin JE, Gilleece MH, Radia R, Yeung DT, et al. Results of the first completed clinical trial of an iPSC-derived product: CYP-001 in steroid-resistant acute GvHD. Biol Blood Marrow Transpl. 2019;25:S255–6.

Liu X, Robbins S, Wang X, Virk S, Schuck K, Deveza LA, et al. Efficacy and cost-effectiveness of stem cell injections for symptomatic relief and structural improvement in people with tibiofemoral knee OsteoaRthritis: protocol for a randomised placebo-controlled trial (the SCUlpTOR trial). BMJ Open. 2021;11:e056382.

Graceffa V, Vinatier C, Guicheux J, Stoddart M, Alini M, Zeugolis DI. Chasing chimeras–the elusive stable chondrogenic phenotype. Biomaterials. 2019;192:199–225.

Wang Z. Assessing tumorigenicity in stem cell-derived therapeutic products: a critical step in safeguarding regenerative medicine. Bioengineering. 2023;10:857.

Abe K, Tsumaki N. Regeneration of joint surface defects by transplantation of allogeneic cartilage: application of iPS cell-derived cartilage and immunogenicity. Inflamm Regen. 2023;43:56.

Saito T, Yano F, Mori D, Kawata M, Hoshi K, Takato T, et al. Hyaline cartilage formation and tumorigenesis of implanted tissues derived from human induced pluripotent stem cells. Biomed Res. 2015;36:179–86.

Dupuis V, Oltra E. Methods to produce induced pluripotent stem cell-derived mesenchymal stem cells: Mesenchymal stem cells from induced pluripotent stem cells. World J Stem Cells. 2021;13:1094–111.

Fujisawa Y, Takao T, Yamada D, Takarada T. Development of cartilage tissue using a stirred bioreactor and human iPSC-derived limb bud mesenchymal cells. Biochem Biophys Res Commun. 2023;687:149146.

Rogers RE, Haskell A, White BP, Dalal S, Lopez M, Tahan D, et al. A scalable system for generation of mesenchymal stem cells derived from induced pluripotent cells employing bioreactors and degradable microcarriers. Stem Cells Transl Med. 2021;10:1650–65.

Vieira CP, McCarrel TM, Grant MB. Novel methods to mobilize, isolate, and expand mesenchymal stem cells. Int J Mol Sci. 2021;22:5728.

Herbst L, Groten F, Murphy M, Shaw G, Nießing B, Schmitt RH. Automated production at scale of induced pluripotent stem cell-derived mesenchymal stromal cells, chondrocytes and extracellular vehicles: towards real-time release. Processes. 2023;11:2938.

Pera MF. The dark side of induced pluripotency. Nature. 2011;471:46–7.

Yoshihara M, Hayashizaki Y, Murakawa Y. Genomic Instability of iPSCs: challenges towards their clinical applications. Stem Cell Rev Rep. 2017;13:7–16.

Apostolou E, Hochedlinger K. iPS cells under attack. Nature. 2011;474:165–6.

Liu X, Li W, Fu X, Xu Y. The immunogenicity and immune tolerance of pluripotent stem cell derivatives. Front Immunol. 2017;8:645.

Murphy C, Mobasheri A, Táncos Z, Kobolák J, Dinnyés A. The potency of induced pluripotent stem cells in cartilage regeneration and osteoarthritis treatment. In: Turksen K, editor. Cell biology and translational medicine, vol. 1. Cham: Springer International Publishing; 2017. p. 55–68.

Chapter   Google Scholar  

Kim IG, Park SA, Lee S-H, Choi JS, Cho H, Lee SJ, et al. Transplantation of a 3D-printed tracheal graft combined with iPS cell-derived MSCs and chondrocytes. Sci Rep. 2020;10:4326.

Okita K, Matsumura Y, Sato Y, Okada A, Morizane A, Okamoto S, et al. A more efficient method to generate integration-free human iPS cells. Nat Methods. 2011;8:409–12.

Lo Monaco M, Merckx G, Ratajczak J, Gervois P, Hilkens P, Clegg P, et al. Stem cells for cartilage repair: preclinical studies and insights in translational animal models and outcome measures. Stem Cells Int. 2018;2018:1–22.

Castro-Viñuelas R, Sanjurjo-Rodríguez C, Piñeiro-Ramil M, Hermida-Gómez T, Rodríguez-Fernández S, Oreiro N, et al. Generation and characterization of human induced pluripotent stem cells (iPSCs) from hand osteoarthritis patient-derived fibroblasts. Sci Rep. 2020;10:4272.

Rim YA, Nam Y, Park N, Jung H, Lee K, Lee J, et al. Chondrogenic differentiation from induced pluripotent stem cells using non-viral minicircle vectors. Cells. 2020;9:582.

Ozaki T, Kawamoto T, Iimori Y, Takeshita N, Yamagishi Y, Nakamura H, et al. Evaluation of FGFR inhibitor ASP5878 as a drug candidate for achondroplasia. Sci Rep. 2020;10:20915.

Rim YA, Nam Y, Park N, Lee K, Jung H, Jung SM, et al. Characterization of early-onset finger osteoarthritis-like condition using patient-derived induced pluripotent stem cells. Cells. 2021;10:317.

Pretemer Y, Kawai S, Nagata S, Nishio M, Watanabe M, Tamaki S, et al. Differentiation of hypertrophic chondrocytes from human iPSCs for the in vitro modeling of chondrodysplasias. Stem Cell Rep. 2021;16:610–25.

Kimura T, Bosakova M, Nonaka Y, Hruba E, Yasuda K, Futakawa S, et al. An RNA aptamer restores defective bone growth in FGFR3-related skeletal dysplasia in mice. Sci Transl Med. 2021;13:eaba4226.

Lee SJ, Nam Y, Rim YA, Lee K, Ju JH, Kim DS. Perichondrium-inspired permeable nanofibrous tube well promoting differentiation of hiPSC-derived pellet toward hyaline-like cartilage pellet. Biofabrication. 2021;13:045015.

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Acknowledgements

We thank the support of Institut national de la santé et de la recherche médicale (INSERM), Faculté de médecine et Faculté de chirurgie dentaire de Université de Strasbourg, and Lamina therapeutics. EAMA is financially supported by ANR ARTiTHERA, WO was supported by Chinese Scholarship Council (CSC N° 202309240005). We also thank Servier Medical ART for free medical images.

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Eltahir Abdelrazig Mohamed Ali, Rana Smaida, Morgane Meyer and Wenxin Ou have contributed equally to this work.

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Institut National de la Santé et de la Recherche Médicale (INSERM), UMR 1260, Regenerative NanoMedicine (RNM), 1 Rue Eugène Boeckel, 67000, Strasbourg, France

Eltahir Abdelrazig Mohamed Ali, Nadia Benkirane-Jessel & Guoqiang Hua

Université de Strasbourg, 67000, Strasbourg, France

Eltahir Abdelrazig Mohamed Ali, Morgane Meyer, Wenxin Ou, Nadia Benkirane-Jessel, Jacques Eric Gottenberg & Guoqiang Hua

Lamina Therapeutics, 1 Rue Eugène Boeckel, 67000, Strasbourg, France

Rana Smaida, Morgane Meyer & Nadia Benkirane-Jessel

Nankai University School of Medicine, Tianjin, 300071, China

Beijing Engineering Laboratory of Perinatal Stem Cells, Beijing Institute of Health and Stem Cells, Health & Biotech Co, Beijing, 100176, China

Zhongchao Han

Centre National de Référence des Maladies Auto-Immunes et Systémiques Rares, Est/Sud-Ouest (RESO), Service de Rhumatologie, Centre Hospitalier Universitaire de Strasbourg, 67000, Strasbourg, France

Wenxin Ou & Jacques Eric Gottenberg

Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China

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EAMA, RS, MM and WO wrote the draft of the manuscript. ZL, ZH, NBJ, JEG and GH revised the manuscript. All authors reviewed and approved the final manuscript.

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Correspondence to Nadia Benkirane-Jessel , Jacques Eric Gottenberg or Guoqiang Hua .

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Ali, E.A.M., Smaida, R., Meyer, M. et al. iPSCs chondrogenic differentiation for personalized regenerative medicine: a literature review. Stem Cell Res Ther 15 , 185 (2024). https://doi.org/10.1186/s13287-024-03794-1

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Additive fault diagnosis techniques in rotor systems: a state-of-the-art review

• Published: 27 June 2024
• Volume 49 , article number  207 , ( 2024 )

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• Prabhat Kumar 1 &
• Rajiv Tiwari   ORCID: orcid.org/0000-0003-2111-5918 2  

Faults in rotating systems can cause significant damage to the machinery and can result in downtime and production losses. Hence, the timely detection and diagnosis of faults are very important for the smooth running of machines and the assurance of their safety and reliability. In view of this, a review of the literature has been presented in the article on the types of additive faults and their identification using conventional signal-based techniques and automated artificial intelligence techniques. Through a literature survey, the faulty rigid and flexible rotor systems mounted on rolling element bearings, hydrodynamic bearings, and active magnetic bearings have been studied. The faults incorporated in this article are the additive fault types, in which the process is affected by adding process variables. The rotor unbalances, shaft or bearing misalignment, crack, internal damping, bow in the shaft, rotor-to-stator rub, and mechanical looseness are the classifications of additive faults. Additionally, understanding the rotor response through theoretical and experimental investigations influenced by the additive faults and its detection and diagnosis using vibration and current-induced signals is extremely important, and therefore the present paper briefly discusses this. Following the state of the art in the dynamic analysis and identification of multiple hazardous faults, the general remarks and future directions for further research have been suggested at the end of this article.

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Tiwari R 2017 Rotor Systems: Analysis and Identification. CRC Press, Boca Raton

Google Scholar  

Höfling T and Pfeufer T 1994 Detection of additive and multiplicative faults-parity space vs. parameter estimation. IFAC Proc. 27: 515–520

Isermann R 2004 Model-based fault detection and diagnosis-status and applications. IFAC Proc. 37: 49–60

Muszynska A 1995 Vibrational diagnostics of rotating machinery malfunctions. Int. J. Rotat. Mach. 1: 237–266

Article   Google Scholar  

Tiwari R, Lees A and Friswell M 2004 Identification of dynamic bearing parameters: a review. Shock. Vib. Digest. 36: 99–124

Tiwari R, Manikandan S and Dwivedy S 2005 A review of the experimental estimation of the rotor dynamic parameters of seals. Shock Vib. Digest. 37: 261

Uddin M N and Rahman M M 2015 Online current and vibration signal monitoring based fault detection of bowed rotor induction motor. In: IEEE Energy Conversion Congress and Exposition (ECCE) , pp. 2988–2994

Gangsar P and Tiwari R 2016 Taxonomy of induction-motor mechanical-fault based on time-domain vibration signals by multiclass SVM classifiers. Intell. Ind. Syst. 2: 269–281

Rapur J S and Tiwari R 2018 Automation of multi-fault diagnosing of centrifugal pumps using multi-class support vector machine with vibration and motor current signals in frequency domain. J. Braz. Soc. Mech. Sci. Eng. 40: 1–21

Făgărăşan I and Iliescu S S 2008 Applications of fault detection methods to industrial processes. WSEAS Trans. Syst. 7: 812–821

Walker R, Perinpanayagam S and Jennions I K 2013 Rotordynamic faults: recent advances in diagnosis and prognosis. Int. J. Rotat. Mach. 2013: 856865

Srinivas R S, Tiwari R and Kannababu C 2018 Application of active magnetic bearings in flexible rotordynamic systems—a state-of-the-art review. Mech. Syst. Signal. Process. 106: 537–572

Gayen D, Tiwari R and Chakraborty D 2019 Static and dynamic analyses of cracked functionally graded structural components: a review. Compos. Part B: Eng. 173: 106982

Benbouzid M E H, Vieira M and Theys C 1999 Induction motors’ faults detection and localization using stator current advanced signal processing techniques. IEEE Trans. Power. Electron. 14: 14–22

Lin D, Wiseman M, Banjevic D and Jardine A K 2004 An approach to signal processing and condition-based maintenance for gearboxes subject to tooth failure. Mech. Syst. Signal Process. 18: 993–1007

Liu Z and Zhang L 2020 A review of failure modes, condition monitoring and fault diagnosis methods for large-scale wind turbine bearings. Measurement 149: 107002

Kuo C H, Chuang Y-F and Liang S-H 2022 Failure mode detection and validation of a shaft-bearing system with common sensors. Sensors 22: 6167

Bishop R and Gladwell G 1959 The vibration and balancing of an unbalanced flexible rotor. J. Mech. Eng. Sci. 1: 66–77

Smalley A 1989 The dynamic response of rotors to rubs during startup. J. Vib. Acoust. Stress. Reliab. Des. 111: 226–233

Lees A 2007 Misalignment in rigidly coupled rotors. J. Sound. Vib. 305: 261–271

Chatzisavvas I and Dohnal F 2015 Unbalance identification using the least angle regression technique. Mech. Syst. Signal. Process. 50: 706–717

Shin D, Suh J and Palazzolo A 2022 Parametric study of flexure pivot bearing induced thermal bow-rotor instability (Morton effect). J. Tribol. 144: 071801

Drechslen J 1980 Processing surplus information in computer aided balancing of large flexible rotors. In: International Conference on Vibrations in Rotating Machinery , Cambridge, UK

Morton P 1985 Modal balancing of flexible shafts without trial weights. Proc. Inst. Mech. Eng. Part C: J. Mech. Eng. Sci. 199: 71–78

Krodkiewski J, Ding J and Zhang N 1994 Identification of unbalance change using a non-linear mathematical model for multi-bearing rotor systems. J. Sound Vib. 169: 685–698

Lees A and Friswell M 1997 The evaluation of rotor imbalance in flexibly mounted machines. J. Sound. Vib. 208: 671–683

Shih Y P and Lee A-C 1997 Identification of the unbalance distribution in flexible rotors. Int. J. Mech. Sci. 39: 841–857

Zhou S and Shi J 2001 Active balancing and vibration control of rotating machinery: a survey. Shock Vib. Digest. 33: 361–371

De Queiroz M 2009 An active identification method of rotor unbalance parameters. J. Vib. Control 15: 1365–1374

Article   MathSciNet   Google Scholar  

Nauclér P and Söderström T 2010 Unbalance estimation using linear and nonlinear regression. Automatica 46: 1752–1761

Sudhakar G and Sekhar A 2011 Identification of unbalance in a rotor bearing system. J. Sound. Vib. 330: 2299–2313

De Castro H F, Cavalca K L, De Camargo L W F and Bachschmid N 2010 Identification of unbalance forces by metaheuristic search algorithms. Mech. Syst. Signal. Process. 24: 1785–1798

Menshikov Y 2013 Identification of rotor unbalance as inverse problem of measurement. Adv. Pure Math. 3: 20–25

Pennacchi P, Vania A, Chatterton S, Nistor I, Voinis P, Ricci R et al 2013 Unbalance identification in large steam turbo-generator unit using a model-based method. In: International Design Engineering Technical Conferences & Computers and Information in Engineering Conference V008T13A053

Markert R, Platz R and Seidler M 2001 Model based fault identification in rotor systems by least squares fitting. Int. J. Rotat. Mach. 7: 311–321

Yao J, Liu L, Yang F, Scarpa F and Gao J 2018 Identification and optimization of unbalance parameters in rotor-bearing systems. J. Sound Vib. 431: 54–69

Shrivastava A and Mohanty A R 2019 Identification of unbalance in a rotor system using a joint input-state estimation technique. J. Sound Vib. 442: 414–427

Shrivastava A and Mohanty A R 2020 Identification of unbalance in a rotor-bearing system using Kalman filter–based input estimation technique. J. Vib. Control 26: 1081–1091

Yun X, Pang Z, Jiang G and Mei X 2021 Research on identification of unbalance parameters of rotor with multi-plane using improved particle swarm optimization. J. Braz. Soc. Mech. Sci. Eng. 43: 1–12

Abbasi A, Firouzi B, Sendur P, Ranjan G and Tiwari R 2022 Identification of unbalance characteristics of rotating machinery using a novel optimization-based methodology. Soft Comput. 26: 4831–4862

Lin C-L, Liang J-W, Huang Y-M and Huang S-C 2023 A novel model-based unbalance monitoring and prognostics for rotor-bearing systems. Adv. Mech. Eng. 15: 16878132221148020

Wang Z, Lu C, Ma J and Du S 2023 Identification method of unbalanced fault characteristics of horizontal shaft of rotary table of drilling rig. In: IOP Conference Series: Materials Science and Engineering , p. 012012

Zhang Y, Xie Z, Zhai L and Shao M 2023 Unbalanced vibration suppression of a rotor with Rotating-Frequency faults using signal purification. Mech. Syst. Signal. Process. 190: 110153

Zhong S and Hou L 2023 Numerical and experimental studies on unsupervised deep Lagrangian learning based rotor balancing method. Sci. China Technol. Sci. 66: 1050–1061

Lin K, Li Y, Wu Y, Fu H, Jiang J and Chen Y 2023 A deep learning-based unbalanced force identification of the hypergravity centrifuge. Sensors 23: 3797

Baltazar-Tadeo L A, Colín-Ocampo J, Mendoza-Larios J G, Abúndez-Pliego A, Nango-Blanco M and Blanco-Ortega A et al . 2023 An integrated balancing method for asymmetric rotor-bearing systems: algebraic identification, modal balancing, and active balancing disks. J. Vib. Eng. Tech. 11: 619–645

Davies W and Mayes I 1984 The vibrational behavior of a multi-shaft, multi-bearing system in the presence of a propagating transverse crack. J. Vib Acoust. Stress Reliab. Des. 106: 146–153

Kumar P 2024 Dynamic analysis and identification in a cracked and unbalanced rigid rotor with two offset discs and one middle disc mounted on foil bearings. Int. J. Dyn. Control 12: 2024

Gasch R 1993 A survey of the dynamic behaviour of a simple rotating shaft with a transverse crack. J. Sound. Vib. 160: 313–332

Singh S and Tiwari R 2015 Model-based fatigue crack identification in rotors integrated with active magnetic bearings. J. Vib. Control. 23: 980–1000

Nelson H and Nataraj C 1986 The dynamics of a rotor system with a cracked shaft. J. Vib. Acoust. 108: 189–196

Jun O, Eun H, Earmme Y and Lee C-W 1992 Modelling and vibration analysis of a simple rotor with a breathing crack. J. Sound. Vib. 155: 273–290

Sekhar A and Prasad P B 1997 Dynamic analysis of a rotor system considering a slant crack in the shaft. J. Sound. Vib. 208: 457–474

Sekhar A 1999 Vibration characteristics of a cracked rotor with two open cracks. J. Sound. Vib. 223: 497–512

Zhu C, Robb D A and Ewins D J 2003 The dynamics of a cracked rotor with an active magnetic bearing. J. Sound. Vib. 265: 469–487

Sekhar A 2004 Crack identification in a rotor system: a model-based approach. J. Sound. Vib. 270: 887–902

Sekhar A 2004 Model-based identification of two cracks in a rotor system. Mech. Syst. Signal. Process. 18: 977–983

Dharmaraju N, Tiwari R and Talukdar S 2004 Identification of an open crack model in a beam based on force–response measurements. Comput. Struct. 82: 167–179

Dharmaraju N, Tiwari R and Talukdar S 2005 Development of a novel hybrid reduction scheme for identification of an open crack model in a beam. Mech. Syst. Signal. Process. 19: 633–657

Pennacchi P, Bachschmid N and Vania A 2006 A model-based identification method of transverse cracks in rotating shafts suitable for industrial machines. Mech. Syst. Signal. Process. 20: 2112–2147

Sekhar A 2008 Multiple cracks effects and identification. Mech. Syst. Signal. Process. 22: 845–878

Kumar C and Rastogi V 2009 A brief review on dynamics of a cracked rotor. Int. J. Rotat. Mach. 2009: 1–6

Singh S and Tiwari R 2010 Identification of a multi-crack in a shaft system using transverse frequency response functions. Mech. Mach. Theory 45: 1813–1827

Han Q, Zhao J and Chu F 2012 Dynamic analysis of a geared rotor system considering a slant crack on the shaft. J. Sound. Vib. 331: 5803–5823

Singh S and Tiwari R 2016 Model-based switching-crack identification in a Jeffcott rotor with an offset disk integrated with an active magnetic bearing. J. Dyn. Syst. Meas. Control 138: 031006

Shravankumar C and Tiwari R 2013 Model-based crack identification using full-spectrum. In: ASME 2013 Gas Turbine India Conference , pp. V001T06A011–V001T06A011

Singh S and Tiwari R 2018 Model based identification of crack and bearing dynamic parameters in flexible rotor systems supported with an auxiliary active magnetic bearing. Mech. Mach. Theory 122: 292–307

Gradzki R, Kulesza Z and Bartoszewicz B 2019 Method of shaft crack detection based on squared gain of vibration amplitude. Nonlinear Dyn. 98: 671–690

Joshuva A and Sugumaran V 2019 Crack detection and localization on wind turbine blade using machine learning algorithms: a data mining approach. Struct. Durab. Health Monit. 13: 181

Yang Y, Xia W, Han J, Song Y, Wang J and Dai Y 2019 Vibration analysis for tooth crack detection in a spur gear system with clearance nonlinearity. Int. J. Mech. Sci. 157: 648–661

Chen Z and Shao Y 2011 Dynamic simulation of spur gear with tooth root crack propagating along tooth width and crack depth. Eng. Fail. Anal. 18: 2149–2164

Xiang L, Zhang Y and Hu A 2019 Crack characteristic analysis of multi-fault rotor system based on whirl orbits. Nonlinear Dyn. 95: 2675–2690

Peng H and He Q 2019 The effects of the crack location on the whirl motion of a breathing cracked rotor with rotational damping. Mech. Syst. Signal. Process. 123: 626–647

Aftab H, Baneen U and Israr A 2021 Identification and severity estimation of a breathing crack in a plate via nonlinear dynamics. Nonlinear Dyn. 104: 1973–1989

Mohammed S A, Ghazaly N M and Abdo J 2022 Fault diagnosis of crack on gearbox using vibration-based approaches. Symmetry 14: 417

Zhong X and Ban H 2022 Crack fault diagnosis of rotating machine in nuclear power plant based on ensemble learning. Ann. Nucl. Energy 168: 108909

Qiao Z, Chen K, Zhou C and Ma H 2023 An improved fault model of wind turbine gear drive under multi-stage cracks. Simul. Model. Prac. Theory 122: 102679

Wang C, Zheng Z, Guo D, Liu T, Xie Y and Zhang D 2023 An experimental setup to detect the crack fault of asymmetric rotors based on a deep learning method. Appl. Sci. 13: 1327

Kumar P 2021 Model based analysis and identification of unbalance and misalignment in rotor systems levitated by active magnetic bearings. In: PhD, Mechanical Engineering, Indian Institute of Technology Guwahati , Guwahati

Dewell D and Mitchell L 1984 Detection of a misaligned disk coupling using spectrum analysis. J. Vib. Acoust. Stress Reliab. Des. 106: 9–16

Sekhar A and Prabhu B 1995 Effects of coupling misalignment on vibrations of rotating machinery. J. Sound. Vib. 185: 655–671

Rao A S and Sekhar A 1996 Vibration analysis of rotor-coupling-bearing system with misaligned shafts. In: ASME 1996 International Gas Turbine and Aeroengine Congress and Exhibition , pp. V005T14A001-V005T14A001

Hu W, Miah H, Feng N and Hahn E 2000 A rig for testing lateral misalignment effects in a flexible rotor supported on three or more hydrodynamic journal bearings. Tribol. Int. 33: 197–204

Prabhakar S, Sekhar A and Mohanty A 2001 Vibration analysis of a misaligned rotor-coupling-bearing system passing through the critical speed. Proc. Inst. Mech. Eng Part C: J. Mech. Eng. Sci. 215: 1417–1428

Al-Hussain K 2003 Dynamic stability of two rigid rotors connected by a flexible coupling with angular misalignment. J. Sound. Vib. 266: 217–234

Pennacchi P and Vania A 2005 Diagnosis and model based identification of a coupling misalignment. Shock Vib. 12: 293–308

Patel T H and Darpe A K 2009 Experimental investigations on vibration response of misaligned rotors. Mech. Syst. Signal Process. 23: 2236–2252

Arebi L, Gu F, Hu N and Ball A 2011 Misalignment detection using a wireless sensor mounted on a rotating shaft. In: Proceedings of the 24th International Congress on Condition Monitoring and Diagnostics Engineering Management , Stavanger, Norway

Messaoud N B, Bouaziz S, Fakhfakh T, Maatar M and Haddar M 2011 Dynamic behavior of active magnetic bearings in presence of angular misalignment defect. Int. J. Appl. Mech. 3: 491–505

Lal M 2020 Modeling and estimation of speed dependent bearing and coupling misalignment faults in a turbine generator system. Mech. Syst. Signal Process. 151: 107365

Lal M and Tiwari R 2012 Multi-fault identification in simple rotor-bearing-coupling systems based on forced response measurements. Mech. Mach. Theory 51: 87–109

Lal M and Tiwari R 2013 Quantification of multiple fault parameters in flexible turbo-generator systems with incomplete rundown vibration data. Mech. Syst. Signal Process. 41: 546–563

Lal M and Tiwari R 2018 Experimental identification of shaft misalignment in a turbo-generator system. Sādhanā 43: 80

Verma A K, Sarangi S and Kolekar M 2014 Experimental investigation of misalignment effects on rotor shaft vibration and on stator current signature. J. Fail. Anal. Prev. 14: 125–138

Jang J Y and Khonsari M M 2015 On the characteristics of misaligned journal bearings. Lubricants 3: 27–53

Jang J and Khonsari M 2019 Performance and characterization of dynamically-loaded engine bearings with provision for misalignment. Tribol. Int. 130: 387–399

Sawalhi N, Ganeriwala S and Tóth M 2019 Parallel misalignment modeling and coupling bending stiffness measurement of a rotor-bearing system. Appl. Acoust. 144: 124–141

Srinivas R S, Tiwari R and Babu C K 2020 Modeling, analysis, and identification of parallel and angular misalignments in a coupled rotor-bearing-active magnetic bearing system. J. Dyn. Syst. Meas. Control 143: 011007

Kumar P and Tiwari R 2019 A numerical study on the effect of unbalance and misalignment fault parameters in a rigid rotor levitated by active magnetic bearings. In: ASME 2019 Gas Turbine India Conference , p. V001T05A003

Kumar P, Kumar V, Kumar K and Meena L S 2020 Unbalance and dynamic parameters estimation in a rigid rotor mounted on active magnetic bearings. In: Advances in Applied Mechanical Engineering , pp. 363–371

Kumar P and Tiwari R 2020 Development of a novel approach for quantitative estimation of rotor unbalance and misalignment in a rotor system levitated by active magnetic bearings. Iran. J. Sci. Technol. Trans. Mech. Eng. 45(769–786): 2020

Kumar P and Tiwari R 2020 Dynamic analysis and identification of unbalance and misalignment in a rigid rotor with two offset discs levitated by active magnetic bearings: a novel trial misalignment approach. Propuls. Power Res. 10: 58–82

Kumar P and Tiwari R 2021 Finite element modelling, analysis and identification using novel trial misalignment approach in an unbalanced and misaligned flexible rotor system levitated by active magnetic bearings. Mech. Syst. Signal Process. 152: 107454

Tiwari R and Kumar P 2022 An innovative virtual trial misalignment approach for identification of unbalance, sensor and active magnetic bearing misalignment along with its stiffness parameters in a magnetically levitated flexible rotor system. Mech. Syst. Signal Process. 167: 108540

Kumar R, Singh M, Khan S, Singh J, Sharma S and Kumar H et al . 2023 A state-of-the-art review on the misalignment, failure modes and its detection methods for bearings. MAPAN 38: 265–274

Hu S, Han T, Qi Y, Zhang C, Shi X and Peng Z 2023 Misalignment fault identification of a multi-span rotor system enabled by triboelectric nanogenerators. Nano Energy 109: 108308

Zhang C, Cao P, Zhu R, Chen W and Wang D 2023 Dynamic modeling and analysis of the spline joint-flexible coupling-rotor system with misalignment. J. Sound. Vib. 554: 117696

Kimball A L 1932 Vib. Prevent. Eng . J. Wiley & sons, Incorporated

Ehrich F 1964 Shaft whirl induced by rotor internal damping. J. Appl. Mech. 31: 279–282

Lund J 1974 Stability and damped critical speeds of a flexible rotor in fluid-film bearings. J. Manuf. Sci. Eng. 96: 509–517

Zorzi E and Nelson H 1977 Finite element simulation of rotor-bearing systems with internal damping. J. Eng. Gas Turbines Power 99: 71–76

Chen L-W and Ku D-M 1991 Analysis of whirl speeds of rotor-bearing systems with internal damping by C0 finite elements. Finite Element Anal. Des. 9: 169–176

Ku D M 1998 Finite element analysis of whirl speeds for rotor-bearing systems with internal damping. Mech. Syst. Signal Process. 12: 599–610

Melanson J and Zu J 1998 Free vibration and stability analysis of internally damped rotating shafts with general boundary conditions. J. Vib. Acoust. 120: 776–783

Forrai L 2000 Instability due to internal damping of symmetrical rotor-bearing systems. J. Comput. Appl. Math. 1: 137–147

Genta G 2004 On a persistent misunderstanding of the role of hysteretic damping in rotordynamics. J. Vib. Acoust. 126: 459–461

Dimentberg M 2005 Vibration of a rotating shaft with randomly varying internal damping. J. Sound. Vib. 285: 759–765

Fischer J and Strackeljan J 2006 Stability analysis of high speed lab centrifuges considering internal damping in rotor-shaft joints. Eur. J. Eng. Mech. 26: 131–147

Montagnier O and Hochard C 2007 Dynamic instability of supercritical driveshafts mounted on dissipative supports-effects of viscous and hysteretic internal damping. J. Sound. Vib. 305: 378–400

Kang C, Hsu W, Lee E and Shiau T 2011 Dynamic analysis of gear-rotor system with viscoelastic supports under residual shaft bow effect. Mech. Mach. Theo. 46: 264–275

Samantaray A 2008 Steady-state dynamics of a non-ideal rotor with internal damping and gyroscopic effects. Nonlinear Dyn. 56: 443–451

Vatta F and Vigliani A 2008 Internal damping in rotating shafts. Mech. Mach. Theory 43: 1376–1384

Chouksey M, Dutt J and Modak S 2012 Modal analysis of rotor-shaft system under the influence of rotor-shaft material damping and fluid film forces. Mech. Mach. Theory 48: 81–93

Sarmah N and Tiwari R 2018 Identification of crack and internal damping parameters using full spectrum responses from a Jeffcott rotor incorporated with an active magnetic bearing. In: International Conference on Rotor Dynamics , pp. 34–48

Roy D K and Tiwari R 2019 Experimental identification of rotating and stationary damping in a cracked rotor system with an offset disc. Arch. Mech. Eng. 66: 447–474

Kozioł M and Cupiał P 2020 The influence of the active control of internal damping on the stability of a cantilever rotor with a disc. Mech. Des. Struct. Mach. 50: 1–14

Wang L, Wang A, Jin M, Yin Y, Heng X and Ma P 2021 Nonlinear dynamic response and stability of a rod fastening rotor with internal damping effect. Arch. Appl. Mech. 91: 3851–3867

Sarmah N and Tiwari R 2022 Numerical and experimental study on quantitative assessment of multiple fault parameters in a warped internally damped rotor with a transverse fatigue crack integrated with an active magnetic bearing. Mech. Syst. Signal Process. 174: 109112

Meacham W, Talbert P, Nelson H and Cooperrider N 1988 Complex modal balancing of flexible rotors including residual bow. J. Propul. Power. 4: 245–251

Rao J and Sharma M 2000 Dynamic analysis of bowed rotors. In: Proceedings of the VETOMAC-1 Conference , Bangalore, India

Nelson H D 2002 Steady synchronous response and balancing of rotor systems with residual shaft bow. Int. J. Rotat. Mach. 8: 431–438

Pennacchi P and Vania A 2004 Accuracy in the identification of a generator thermal bow. J. Sound. Vib. 274: 273–295

Song G, Yang Z, Ji C and Wang F 2013 Theoretical-experimental study on a rotor with a residual shaft bow. Mech. Mach. Theory 63: 50–58

Mogal S and Lalwani D 2017 Fault diagnosis of bent shaft in rotor bearing system. J. Mech. Sci. Technol. 31: 1–4

Pereira E, Dedini K and Tuckmantel F 2019 Modeling of shaft bow using finite element of curved beam. Int. J. Eng. Res. Technol. 27: 1–1

Chatterton S, Pennacchi P and Vania A 2022 An unconventional method for the diagnosis and study of generator rotor thermal bows. J. Eng. Gas. Turbines Power 144: 011024

Gautam A K and Tiwari R 2023 Dynamic response characteristics of multiplicative faults in a misaligned-bowed rotor-train system integrated with active magnetic bearings. Int. J. Dyn. Control 12: 1–29

MathSciNet   Google Scholar  

Han Y, Ri K, Yun C, Kim K and Han P 2023 Effect of nonlinearities on response characteristics of rotor systems with residual shaft bow. Nonlinear Dyn. 111: 16003–16019

Chu F and Zhang Z 1997 Periodic, quasi-periodic and chaotic vibrations of a rub-impact rotor system supported on oil film bearings. Int. J. Eng. Sci. 35: 963–973

Chu F and Zhang Z 1998 Bifurcation and chaos in a rub-impact Jeffcott rotor system. J. Sound Vib. 210: 1–18

Al-bedoor B O 2000 Transient torsional and lateral vibrations of unbalanced rotors with rotor-to-stator rubbing. J. Sound Vib. 229: 627–645

Bachschmid N, Pennacchi P, Vania A, Zanetta G and Gregori L 2004 Identification of rub and unbalance in 320-MW turbogenerators. Int. J. Rotat. Mach. 10: 265–281

Wang H, Guan X, Chen G, Gong J, Yu L and Yuan S et al . 2019 Characteristics analysis of rotor-rolling bearing coupled system with fit looseness fault and its verification. J. Mech. Sci. Technol. 33: 29–40

Chang-Jian C-W and Chen C-K 2007 Chaos and bifurcation of a flexible rub-impact rotor supported by oil film bearings with nonlinear suspension. Mech. Mach. Theory 42: 312–333

Abuzaid M A, Eleshaky M E and Zedan M G 2009 Effect of partial rotor-to-stator rub on shaft vibration. J. Mech. Sci. Technol. 23: 170–182

Yungong L, Jinping Z, Liqiang W and Yang C 2011 A fault feature extraction method for rotor rubbing based on load identification and measured impact response. Proc. Eng. 24: 793–797

Ma H, Tai X, Yi H, Lv S and Wen B 2013 Nonlinear dynamic characteristics of a flexible rotor system with local rub-impact. J. Phys. Conf. Ser. 448: 012015

Huang Z 2016 Dynamic analysis on rotor-bearing system with coupling faults of crack and rub-impact. J. Phys. Conf. Ser. 744: 012158

Liang H, Lu H, Feng K, Liu Y, Li J and Meng L 2021 Application of the improved NOFRFs weighted contribution rate based on KL divergence to rotor rub-impact. Nonlinear Dyn. 104: 3937–3954

Prabith K and Krishna I P 2022 Response and stability analysis of a two-spool aero-engine rotor system undergoing multi-disk rub-impact. Int. J. Mech. Sci. 213: 106861

Sozinando D F, Tchomeni B X and Alugongo A A 2023 Experimental study of coupled torsional and lateral vibration of vertical rotor-to-stator contact in an inviscid fluid. Math. Comput. Appl. 28: 44

Paiva A, Moreira R V, Brandão A and Savi M A 2023 Nonlinear dynamics of a rotor–stator system with contacts. Nonlinear Dyn. 111: 11753–11772

Chu F and Tang Y 2001 Stability and non-linear responses of a rotor-bearing system with pedestal looseness. J. Sound Vib. 241: 879–893

Wu T, Chung Y and Liu C 2010 Looseness diagnosis of rotating machinery via vibration analysis through Hilbert–Huang transform approach. J. Vib. Acoust. 132: 031005

Ma H, Huang J, Zhang S and Niu H 2013 Nonlinear vibration characteristics of a rotor system with pedestal looseness fault under different loading conditions. J. Vibroeng. 15: 406–418

Reddy M C S and Sekhar A 2013 Application of artificial neural networks for identification of unbalance and looseness in rotor bearing systems. Int. J. Appl. Sci. Eng. 11: 69–84

Cao Q, Xiang Q and Qin G 2015 Review of mechanical looseness phenomena and failure characteristics study. Noise Vib. Control 35: 1–6

Wang H, Chen G and Song P 2016 Asynchronous vibration response characteristics of aero-engine with support looseness fault. J. Comput. Nonlinear Dyn. 11: 031013

Wang H 2021 Passive vibration reduction of a squeeze film damper for a rotor system with fit looseness between outer ring and housing. J. Low Freq. Noise Vib. Active Control 40: 1473–1492

Lin J, Zhao Y, Wang P, Wang Y, Han Q and Ma H 2021 Nonlinear responses of a rotor-bearing-seal system with pedestal looseness. Shock Vib. 2021: 9937700

Zhang H, Lu K, Zhang W and Fu C 2022 Investigation on dynamic behaviors of rotor system with looseness and nonlinear supporting. Mech. Syst. Signal Process. 166: 108400

Xingrong H, Donglai Y, Kaiwen X and Yi Y 2023 Analysis of dry friction fault caused by rotor elastic support bolt looseness. J. Aerosp. Power 38: 1723–1733

Zhao Y, Lin J, Wang X, Han Q and Liu Y 2023 A novel data-driven feature extraction strategy and its application in looseness detection of rotor-bearing system. Mathematics 11: 2769

Goyal D, Chaudhary A, Dang R K, Pabla B and Dhami S 2018 Condition monitoring of rotating machines: a review. World Sci. News 113: 98–108

Frank P M 1996 Analytical and qualitative model-based fault diagnosis–a survey and some new results. Eur. J. Control 2: 6–28

Zhuge J 2009 Vibration data collector signal analysis. Part of VDC User’s Manual, CRYSTAL instrument

Doebling S W, Farrar C R and Prime M B 1998 A summary review of vibration-based damage identification methods. Shock Vib. Digest 30: 91–105

Giurgiutiu V 2002 Current issues in vibration-based fault diagnostics and prognostics. In: Smart Nondestructive Evaluation for Health Monitoring of Structural and Biological Systems , pp. 101–112

Carden E P and Fanning P 2004 Vibration based condition monitoring: a review. Struct. Health Monit. 3: 355–377

Peng Z K and Chu F 2004 Application of the wavelet transform in machine condition monitoring and fault diagnostics: a review with bibliography. Mech. Syst. Signal Process. 18: 199–221

Nandi S, Toliyat H A and Li X 2005 Condition monitoring and fault diagnosis of electrical motors—a review. IEEE Trans. Energy Convers. 20: 719–729

Lu B, Li Y, Wu X and Yang Z 2009 A review of recent advances in wind turbine condition monitoring and fault diagnosis. In: IEEE Power Electronics and Machines in Wind Applications , pp. 1–7

Do V T and Chong U-P 2011 Signal model-based fault detection and diagnosis for induction motors using features of vibration signal in two-dimension domain. J. Mech. Eng. 57: 655–666

Lei Y, Lin J, Zuo M J and He Z 2014 Condition monitoring and fault diagnosis of planetary gearboxes: a review. Measurement 48: 292–305

Giantomassi A, Ferracuti F, Iarlori S, Ippoliti G and Longhi S 2015 Signal based fault detection and diagnosis for rotating electrical machines: issues and solutions. In: Complex System Modelling and Control Through Intelligent Soft Computations , pp. 275–309

Gao Z, Cecati C and Ding S X 2015 A survey of fault diagnosis and fault-tolerant technique-Part I: fault diagnosis with model-based and signal-based approaches. IEEE Trans. Ind. Elect. 62: 3757–3767

De Azevedo H D M, Araújo A M and Bouchonneau N 2016 A review of wind turbine bearing condition monitoring: state of the art and challenges. Renew. Sustain. Energy Rev. 56: 368–379

Wu C, Guo C, Xie Z, Ni F and Liu H 2018 A signal-based fault detection and tolerance control method of current sensor for PMSM drive. IEEE Trans. Ind. Electron. 65: 9646–9657

Salameh J P, Cauet S, Etien E, Sakout A and Rambault L 2018 Gearbox condition monitoring in wind turbines: a review. Mech. Syst. Signal Process. 111: 251–264

Dai J, Tang J, Huang S and Wang Y 2019 Signal-based intelligent hydraulic fault diagnosis methods: review and prospects. Chin. J. Mech. Eng. 32: 1–22

Park Y-J, Fan S-KS and Hsu C-Y 2020 A review on fault detection and process diagnostics in industrial processes. Processes 8: 1123

Gangsar P and Tiwari R 2020 Signal based condition monitoring techniques for fault detection and diagnosis of induction motors: a state-of-the-art review. Mech. Syst. Signal Process. 144: 106908

Abid A, Khan M T and Iqbal J 2021 A review on fault detection and diagnosis techniques: basics and beyond. Artifi. Intel. Rev. 54: 3639–3664

Kumar R, Ismail M, Zhao W, Noori M, Yadav A R and Chen S et al . 2021 Damage detection of wind turbine system based on signal processing approach: a critical review. Clean Technol. Environ. Policy 23: 561–580

Tiboni M, Remino C, Bussola R and Amici C 2022 A review on vibration-based condition monitoring of rotating machinery. Appl. Sci. 12: 972

Mutra R R, Reddy D M, Srinivas J, Sachin D and Rao K B 2023 Signal-based parameter and fault identification in roller bearings using adaptive neuro-fuzzy inference systems. J. Braz. Soc. Mech. Sci. Eng. 45: 45

Boztas G 2023 Comparison of acoustic signal-based fault detection of mechanical faults in induction motors using image classification models. Trans. Inst. Meas. Control . https://doi.org/10.1177/01423312231171664

Alharbi F, Luo S, Zhang H, Shaukat K, Yang G and Wheeler C A et al . 2023 A brief review of acoustic and vibration signal-based fault detection for belt conveyor idlers using machine learning models. Sensors 23: 1902

Rao B K N 1996 Handbook of Condition Monitoring. Elsevier, USA

Davies A 2012 Handbook of Condition Monitoring: Techniques and Methodology. Springer, Dordrecht

Mohanty A R 2014 Machinery Condition Monitoring: Principles and Practices. CRC Press, Boca Raton

Book   Google Scholar  

Correa J C A J and Guzman A A L 2020 Mechanical Vibrations and Condition Monitoring. Academic Press

Collacott R 2012 Mechanical Fault Diagnosis and Condition Monitoring. Springer, Dordrecht

Sinha J K 2020 Industrial Approaches in Vibration-Based Condition Monitoring. CRC Press, Boca Raton

Rao J 2000 Vibratory Condition Monitoring of Machines. CRC Press, Boca Raton

Randall R B 2021 Vibration-Based Condition Monitoring: Industrial, Automotive and Aerospace Applications. Wiley, Hoboken

Ahmed H and Nandi A K 2020 Condition Monitoring with Vibration Signals: Compressive Sampling and Learning Algorithms for Rotating Machines. Wiley, Hoboken

Beebe R S and Beebe R S 2004 Predictive Maintenance of Pumps using Condition Monitoring. Elsevier, Amsterdam

Tiwari R 2023 Simple Rotor Analysis Through Tutorial Problems. CRC Press, Boca Raton

Marwala T 2012 Condition Monitoring Using Computational Intelligence Methods: Applications in Mechanical and Electrical Systems. Springer, London

Barszcz T 2019 Vibration-Based Condition Monitoring of Wind Turbines. Springer, Cham

Tavner P, Ran L, Penman J and Sedding H 2008 Condition Monitoring of Rotating Electrical Machines. Institution of Engineering and Technology, Stevenage

Bachschmid N and Pennacchi P 2003 Accuracy of fault detection in real rotating machinery using model based diagnostic techniques. JSME Int. J. Ser. C Mech. Syst. Mach. Elements Manuf. 46: 1026–1034

Patton R J 1994 Robust model-based fault diagnosis: the state of the art. IFAC Proc. 27: 1–24

Patton R, Chen J and Nielsen S 1995 Model-based methods for fault diagnosis: some guide-lines. Trans. Inst. Meas. Control 17: 73–83

Simani S, Fantuzzi C and Patton R J 2003 Model-based fault diagnosis techniques. In: Model-based Fault Diagnosis in Dynamic Systems Using Identification Techniques , Springer, pp. 19–60

Kumar P and Tiwari R 2023 A review: multiplicative faults and model-based condition monitoring strategies for fault diagnosis in rotary machines. J. Braz. Soc. Mech. Sci. Eng. 45: 282

Rapur J S and Tiwari R 2017 Experimental time-domain vibration-based fault diagnosis of centrifugal pumps using support vector machine. ASCE ASME J. Risk Uncertain. Eng. Syst. Part B Mech. Eng. 3: 044501

Rapur J S and Tiwari R 2019 On-line time domain vibration and current signals based multi-fault diagnosis of centrifugal pumps using support vector machines. J. Nondestr. Eval. 38: 1–18

Kumar S, Lokesha M, Kumar K and Srinivas K 2018 Vibration based fault diagnosis techniques for rotating mechanical components. In: IOP Conference Series: Materials Science and Engineering , p. 012109

Srilakshmi R and Ratnam C 2019 A review on fault detection, diagnosis and prognosis, in vibration measurement through wavelets on machine elements. Int. J. Appl. Eng. Res. 14: 547–555

Gangsar P and Tiwari R 2019 Diagnostics of mechanical and electrical faults in induction motors using wavelet-based features of vibration and current through support vector machine algorithms for various operating conditions. J. Braz. Soc. Mech. Sci. Eng. 41: 1–25

Gangsar P and Tiwari R 2019 Online diagnostics of mechanical and electrical faults in induction motor using multiclass support vector machine algorithms based on frequency domain vibration and current signals. ASCE ASME J. Risk Uncertain. Eng. Syst. Part B Mech. Eng. 5: 031001

Nasiri S, Khosravani M R and Weinberg K 2017 Fracture mechanics and mechanical fault detection by artificial intelligence methods: a review. Eng. Fail. Anal. 81: 270–293

Liu R, Yang B, Zio E and Chen X 2018 Artificial intelligence for fault diagnosis of rotating machinery: a review. Mech. Syst. Signal Process. 108: 33–47

Wei Y, Li Y, Xu M and Huang W 2019 A review of early fault diagnosis approaches and their applications in rotating machinery. Entropy 21: 409

Lang W, Hu Y, Gong C, Zhang X, Xu H and Deng J 2021 Artificial intelligence-based technique for fault detection and diagnosis of EV motors: a review. IEEE Trans. Transp. Electrifi. 8: 384–406

Saini K, Dhami S and Vanraj 2022 Predictive monitoring of incipient faults in rotating machinery: a systematic review from data acquisition to artificial intelligence. Arch. Comput. Method Eng. 29: 4005–4026

Singh V, Gangsar P, Porwal R and Atulkar A 2023 Artificial intelligence application in fault diagnostics of rotating industrial machines: a state-of-the-art review. J. Intell. Manuf. 34: 931–960

Edwards S, Lees A and Friswell M 2000 Experimental identification of excitation and support parameters of a flexible rotor-bearings-foundation system from a single run-down. J. Sound Vib. 232: 963–992

Alves D S and Cavalca K L 2021 Investigation into the influence of bearings nonlinear forces in unbalance identification. J. Sound Vib. 492: 115807

Nayek B, Das A and Dutt J 2021 Model based estimation of inertial parameters of a rigid rotor having dynamic unbalance on Active Magnetic Bearings in presence of noise. Appl. Math. Model. 97: 701–720

Kumar P, Sanket M, Srivastav S and Madav T D 2023 Vibrational nature of an unbalanced rigid rotor system with three discs secured by two active magnetic bearings. In: Recent Advances in Material: Select Proceedings ICSTE 2023 , Springer, pp. 335–345

Bachschmid N, Pennacchi P, Tanzi E and Vania A 2000 Identification of transverse crack position and depth in rotor systems. Meccanica 35: 563–582

Kumar P, Arambam C, Singh L D and Singh N D 2023 Analysing the dynamic interaction between unbalance and crack responses in a Jeffcott rotor supported by foil bearings: a numerical study. In: Emerging Trends in Mechanical and Industrial Engineering: Select Proceedings ICETMIE 2022 , Springer, pp. 971–980

Hori Y and Uematsu R 1980 Influence of misalignment of support journal bearings on stability of a multi-rotor system. Tribol. Int. 13: 249–252

Xu M and Marangoni R 1994 Vibration analysis of a motor-flexible coupling-rotor system subject to misalignment and unbalance, part II: experimental validation. J. Sound Vib. 176: 681–691

Nejadpak A and Yang C X 2017 Misalignment and unbalance faults detection and identification using KNN analysis. Proc. CANCAM 2017: 1–4

Srinivas R S, Tiwari R and Kannababu C 2019 Model based analysis and identification of multiple fault parameters in coupled rotor systems with offset discs in the presence of angular misalignment and integrated with an active magnetic bearing. J. Sound Vib. 450: 109–140

Kumar P and Tiwari R 2020 Dynamic response analysis of an unbalanced and misaligned rotor supported on active magnetic bearings and touchdown bearings. In: Proceedings of the 6th National Symposium on Rotor Dynamics , pp. 407–418

Kumar P and Tiwari R 2020 Effects of unbalance and AMB misalignment in a rigid rotor with an offset disc levitated by active magnetic bearings: a numerical investigation. In: 12th International Conference on Vibrations in Rotating Machinery , pp. 151–168

Kumar P and Tiwari R 2023 Identification in a magnetically levitated rigid rotor system integrated with misaligned sensors and active magnetic bearings. In: Vibration Engineering and Technology of Machinery: Select Proceedings VETOMAC XVI 2021 vol. 1, Springer, pp 1–24

Shiau T N and Lee E K 1989 The residual shaft bow effect on dynamic response of a simply supported rotor with disk skew and mass unbalances. J. Vib. Acoust. Stress Reliab. Des. 111: 170–178

Shiau T, Lee E, Chen Y and Young T 2006 Dynamic response of a geared rotor-bearing system under residual shaft bow effect. In: Turbo Expo: Power for Land, Sea, and Air , pp. 1225–1231

Yu P, Wang C, Hou L and Chen G 2022 Dynamic characteristics of an aeroengine dual-rotor system with inter-shaft rub-impact. Mech. Syst. Signal Process. 166: 108475

Zhang X, Yang Y, Shi M, Zhang Y and Wang P 2022 An energy track method for early-stage rub-impact fault investigation of rotor system. J. Sound Vib. 516: 116545

Mathew J and Alfredson R 1984 The condition monitoring of rolling element bearings using vibration analysis. J. Vib. Acoust. Stress Reliab. Des. 106: 447–453

Tandon N 1994 A comparison of some vibration parameters for the condition monitoring of rolling element bearings. Measurement 12: 285–289

Tandon N, Yadava G and Ramakrishna A K 2007 A comparison of some condition monitoring techniques for the detection of defect in induction motor ball bearings. Mech. Syst. Signal Process. 21: 244–256

Kim Y-H, Tan A C and Kosse V 2008 Condition monitoring of low-speed bearings—a review. Aus. J. Mech. Eng. 6: 6–68

Craig M, Harvey T, Wood R, Masuda M, Kawabata M and Powrie H 2009 Advanced condition monitoring of tapered roller bearings, Part 1. Tribol. Int. 42: 1846–1856

KiranKumar M, Lokesha M, Kumar S and Kumar A 2018 Review on condition monitoring of bearings using vibration analysis techniques. In IOP Conference Series: Materials Science and Engineering , p. 012110

Abdeljaber O, Sassi S, Avci O, Kiranyaz S, Ibrahim A A and Gabbouj M 2018 Fault detection and severity identification of ball bearings by online condition monitoring. IEEE Trans. Ind. Electron. 66: 8136–8147

Duque-Perez O, Del Pozo-Gallego C, Morinigo-Sotelo D and Fontes Godoy W 2019 Condition monitoring of bearing faults using the stator current and shrinkage methods. Energies 12: 3392

Moshrefzadeh A 2021 Condition monitoring and intelligent diagnosis of rolling element bearings under constant/variable load and speed conditions. Mech. Syst. Signal Process. 149: 107153

Schwendemann S, Amjad Z and Sikora A 2021 A survey of machine-learning techniques for condition monitoring and predictive maintenance of bearings in grinding machines. Comput. Ind. 125: 103380

Kahr M, Kovács G, Loinig M and Brückl H 2022 Condition monitoring of ball bearings based on machine learning with synthetically generated data. Sensors 22: 2490

Euldji R, Bouamhdi M, Rebhi R, Bachene M, Ikumapayi O M, Al-Dujaili A Q, Abdulkareem A I, Humaidi A J and Menni Y 2023 Optimizing condition monitoring of ball bearings: an integrated approach using decision tree and extreme learning machine for effective decision-making. Open Phys. 21: 20220239

Kumar A, Kumar R, Tang H and Xiang J A 2024 comprehensive study on developing an intelligent framework for identification and quantitative evaluation of the bearing defect size. Reliab. Eng. Syst. Saf. 242: 109768

Luo M, André H, Guo Y and Peng Y 2024 Analysis of contact behaviours and vibrations in a defective deep groove ball bearing. J. Sound Vib. 570: 118104

Postlethwaite S, Allen J and Ford D 1999 Machine tool thermal error reduction—an appraisal. Proc. Inst. Mech. Eng. Part B: J. Eng. Manuf. 213: 1–9

Creighton E, Honegger A, Tulsian A and Mukhopadhyay D 2010 Analysis of thermal errors in a high-speed micro-milling spindle. Int. J. Mach. Tool. Manuf. 50: 386–393

Mayr J, Jedrzejewski J, Uhlmann E, Donmez M A, Knapp W, Härtig F, Wendt K, Moriwaki T, Shore P, Schmitt R, Brecher C, Würz T and Wegener K 2012 Thermal issues in machine tools. CIRP Ann. 61: 771–791

Li Y, Zhao W, Lan S, Ni J, Wu W and Lu B 2015 A review on spindle thermal error compensation in machine tools. Int. J. Mach. Tool. Manuf. 95: 20–38

Ma C, Zhao L, Mei X, Shi H and Yang J 2017 Thermal error compensation based on genetic algorithm and artificial neural network of the shaft in the high-speed spindle system. Proc. Inst. Mech. Eng. Part B: J. Eng. Manuf. 231: 753–767

Li Y, Dai Y, Gao Y, Tao X and Wang G 2023 Review on thermal error suppression and modeling compensation methods of high-speed motorized spindle. Recent Patents Eng. 17: 60–76

Haoshuo W, Guangsheng C and Yushan S 2023 Prediction of thermal errors in a motorized spindle in CNC machine tools by applying loads based on heat flux. Proc. Inst. Mech. Eng. Part C: J. Mech. Eng. Sci. 238: 264

Friedrich C, Geist A, Yaqoob M F, Hellmich A and Ihlenfeldt S 2024 Correction of thermal errors in machine tools by a hybrid model approach. Appl. Sci. 14: 671

Kumar P 2023 Condition monitoring of mechanical and electrical faults in stationary and rotating equipments: a review. in Recent Advances in Material: Select Proceedings ICSTE 2023 , Springer, pp. 297–306

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Prabhat Kumar

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Kumar, P., Tiwari, R. Additive fault diagnosis techniques in rotor systems: a state-of-the-art review. Sādhanā 49 , 207 (2024). https://doi.org/10.1007/s12046-024-02543-7

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Received : 28 October 2023

Revised : 06 March 2024

Accepted : 23 March 2024

Published : 27 June 2024

DOI : https://doi.org/10.1007/s12046-024-02543-7

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