the components of literature review

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The Research Proposal

83 Components of the Literature Review

Krathwohl (2005) suggests and describes a variety of components to include in a research proposal.  The following sections present these components in a suggested template for you to follow in the preparation of your research proposal.

Introduction

The introduction sets the tone for what follows in your research proposal – treat it as the initial pitch of your idea.  After reading the introduction your reader should:

• Understand what it is you want to do;
• Have a sense of your passion for the topic;
• Be excited about the study´s possible outcomes.

As you begin writing your research proposal it is helpful to think of the introduction as a narrative of what it is you want to do, written in one to three paragraphs.  Within those one to three paragraphs, it is important to briefly answer the following questions:

• What is the central research problem?
• How is the topic of your research proposal related to the problem?
• What methods will you utilize to analyze the research problem?
• Why is it important to undertake this research? What is the significance of your proposed research?  Why are the outcomes of your proposed research important, and to whom or to what are they important?

Note : You may be asked by your instructor to include an abstract with your research proposal.  In such cases, an abstract should provide an overview of what it is you plan to study, your main research question, a brief explanation of your methods to answer the research question, and your expected findings. All of this information must be carefully crafted in 150 to 250 words.  A word of advice is to save the writing of your abstract until the very end of your research proposal preparation.  If you are asked to provide an abstract, you should include 5-7 key words that are of most relevance to your study. List these in order of relevance.

Background and significance

The purpose of this section is to explain the context of your proposal and to describe, in detail, why it is important to undertake this research. Assume that the person or people who will read your research proposal know nothing or very little about the research problem.  While you do not need to include all knowledge you have learned about your topic in this section, it is important to ensure that you include the most relevant material that will help to explain the goals of your research.

While there are no hard and fast rules, you should attempt to address some or all of the following key points:

• State the research problem and provide a more thorough explanation about the purpose of the study than what you stated in the introduction.
• Present the rationale for the proposed research study. Clearly indicate why this research is worth doing.  Answer the “so what?” question.
• Describe the major issues or problems to be addressed by your research. Do not forget to explain how and in what ways your proposed research builds upon previous related research.
• Explain how you plan to go about conducting your research.
• Clearly identify the key or most relevant sources of research you intend to use and explain how they will contribute to your analysis of the topic.
• Set the boundaries of your proposed research, in order to provide a clear focus. Where appropriate, state not only what you will study, but what will be excluded from your study.
• Provide clear definitions of key concepts and terms. As key concepts and terms often have numerous definitions, make sure you state which definition you will be utilizing in your research.

Literature Review

This is the most time-consuming aspect in the preparation of your research proposal and it is a key component of the research proposal. As described in Chapter 5 , the literature review provides the background to your study and demonstrates the significance of the proposed research. Specifically, it is a review and synthesis of prior research that is related to the problem you are setting forth to investigate.  Essentially, your goal in the literature review is to place your research study within the larger whole of what has been studied in the past, while demonstrating to your reader that your work is original, innovative, and adds to the larger whole.

As the literature review is information dense, it is essential that this section be intelligently structured to enable your reader to grasp the key arguments underpinning your study. However, this can be easier to state and harder to do, simply due to the fact there is usually a plethora of related research to sift through. Consequently, a good strategy for writing the literature review is to break the literature into conceptual categories or themes, rather than attempting to describe various groups of literature you reviewed.  Chapter V, “ The Literature Review ,” describes a variety of methods to help you organize the themes.

Here are some suggestions on how to approach the writing of your literature review:

• Think about what questions other researchers have asked, what methods they used, what they found, and what they recommended based upon their findings.
• Do not be afraid to challenge previous related research findings and/or conclusions.
• Assess what you believe to be missing from previous research and explain how your research fills in this gap and/or extends previous research

It is important to note that a significant challenge related to undertaking a literature review is knowing when to stop.  As such, it is important to know how to know when you have uncovered the key conceptual categories underlying your research topic.  Generally, when you start to see repetition in the conclusions or recommendations, you can have confidence that you have covered all of the significant conceptual categories in your literature review.  However, it is also important to acknowledge that researchers often find themselves returning to the literature as they collect and analyze their data.  For example, an unexpected finding may develop as one collects and/or analyzes the data and it is important to take the time to step back and review the literature again, to ensure that no other researchers have found a similar finding.  This may include looking to research outside your field.

This situation occurred with one of the authors of this textbook´s research related to community resilience.  During the interviews, the researchers heard many participants discuss individual resilience factors and how they believed these individual factors helped make the community more resilient, overall.  Sheppard and Williams (2016) had not discovered these individual factors in their original literature review on community and environmental resilience. However, when they returned to the literature to search for individual resilience factors, they discovered a small body of literature in the child and youth psychology field. Consequently, Sheppard and Williams had to go back and add a new section to their literature review on individual resilience factors. Interestingly, their research appeared to be the first research to link individual resilience factors with community resilience factors.

Research design and methods

The objective of this section of the research proposal is to convince the reader that your overall research design and methods of analysis will enable you to solve the research problem you have identified and also enable you to accurately and effectively interpret the results of your research. Consequently, it is critical that the research design and methods section is well-written, clear, and logically organized.  This demonstrates to your reader that you know what you are going to do and how you are going to do it.  Overall, you want to leave your reader feeling confident that you have what it takes to get this research study completed in a timely fashion.

Essentially, this section of the research proposal should be clearly tied to the specific objectives of your study; however, it is also important to draw upon and include examples from the literature review that relate to your design and intended methods.  In other words, you must clearly demonstrate how your study utilizes and builds upon past studies, as it relates to the research design and intended methods.  For example, what methods have been used by other researchers in similar studies?

While it is important to consider the methods that other researchers have employed, it is equally important, if not more so, to consider what methods have not been employed but could be.  Remember, the methods section is not simply a list of tasks to be undertaken. It is also an argument as to why and how the tasks you have outlined will help you investigate the research problem and answer your research question(s).

Tips for writing the research design and methods section:

• Specify the methodological approaches you intend to employ to obtain information and the techniques you will use to analyze the data.
• Specify the research operations you will undertake and he way you will interpret the results of those operations in relation to the research problem.
• Go beyond stating what you hope to achieve through the methods you have chosen. State how you will actually do the methods (i.e. coding interview text, running regression analysis, etc.).
• Anticipate and acknowledge any potential barriers you may encounter when undertaking your research and describe how you will address these barriers.
• Explain where you believe you will find challenges related to data collection, including access to participants and information.

Preliminary suppositions and implications

The purpose of this section is to argue how and in what ways you anticipate that your research will refine, revise, or extend existing knowledge in the area of your study. Depending upon the aims and objectives of your study, you should also discuss how your anticipated findings may impact future research.  For example, is it possible that your research may lead to a new policy, new theoretical understanding, or a new method for analyzing data?  How might your study influence future studies?  What might your study mean for future practitioners working in the field?  Who or what may benefit from your study?  How might your study contribute to social, economic, environmental issues?  While it is important to think about and discuss possibilities such as these, it is equally important to be realistic in stating your anticipated findings.  In other words, you do not want to delve into idle speculation.  Rather, the purpose here is to reflect upon gaps in the current body of literature and to describe how and in what ways you anticipate your research will begin to fill in some or all of those gaps.

The conclusion reiterates the importance and significance of your research proposal and it provides a brief summary of the entire proposed study.  Essentially, this section should only be one or two paragraphs in length. Here is a potential outline for your conclusion:

• Discuss why the study should be done. Specifically discuss how you expect your study will advance existing knowledge and how your study is unique.
• Explain the specific purpose of the study and the research questions that the study will answer.
• Explain why the research design and methods chosen for this study are appropriate, and why other design and methods were not chosen.
• State the potential implications you expect to emerge from your proposed study,
• Provide a sense of how your study fits within the broader scholarship currently in existence related to the research problem.

As with any scholarly research paper, you must cite the sources you used in composing your research proposal.  In a research proposal, this can take two forms: a reference list or a bibliography.  A reference list does what the name suggests, it lists the literature you referenced in the body of your research proposal.  All references in the reference list, must appear in the body of the research proposal.  Remember, it is not acceptable to say “as cited in …”  As a researcher you must always go to the original source and check it for yourself.  Many errors are made in referencing, even by top researchers, and so it is important not to perpetuate an error made by someone else. While this can be time consuming, it is the proper way to undertake a literature review.

In contrast, a bibliography , is a list of everything you used or cited in your research proposal, with additional citations to any key sources relevant to understanding the research problem.  In other words, sources cited in your bibliography may not necessarily appear in the body of your research proposal.  Make sure you check with your instructor to see which of the two you are expected to produce.

Overall, your list of citations should be a testament to the fact that you have done a sufficient level of preliminary research to ensure that your project will complement, but not duplicate, previous research efforts. For social sciences, the reference list or bibliography should be prepared in American Psychological Association (APA) referencing format. Usually, the reference list (or bibliography) is not included in the word count of the research proposal. Again, make sure you check with your instructor to confirm.

An Introduction to Research Methods in Sociology Copyright © 2019 by Valerie A. Sheppard is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License , except where otherwise noted.

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Writing a Literature Review

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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.

Literature Reviews

What this handout is about.

This handout will explain what literature reviews are and offer insights into the form and construction of literature reviews in the humanities, social sciences, and sciences.

Introduction

OK. You’ve got to write a literature review. You dust off a novel and a book of poetry, settle down in your chair, and get ready to issue a “thumbs up” or “thumbs down” as you leaf through the pages. “Literature review” done. Right?

Wrong! The “literature” of a literature review refers to any collection of materials on a topic, not necessarily the great literary texts of the world. “Literature” could be anything from a set of government pamphlets on British colonial methods in Africa to scholarly articles on the treatment of a torn ACL. And a review does not necessarily mean that your reader wants you to give your personal opinion on whether or not you liked these sources.

What is a literature review, then?

A literature review discusses published information in a particular subject area, and sometimes information in a particular subject area within a certain time period.

A literature review can be just a simple summary of the sources, but it usually has an organizational pattern and combines both summary and synthesis. A summary is a recap of the important information of the source, but a synthesis is a re-organization, or a reshuffling, of that information. It might give a new interpretation of old material or combine new with old interpretations. Or it might trace the intellectual progression of the field, including major debates. And depending on the situation, the literature review may evaluate the sources and advise the reader on the most pertinent or relevant.

But how is a literature review different from an academic research paper?

The main focus of an academic research paper is to develop a new argument, and a research paper is likely to contain a literature review as one of its parts. In a research paper, you use the literature as a foundation and as support for a new insight that you contribute. The focus of a literature review, however, is to summarize and synthesize the arguments and ideas of others without adding new contributions.

Why do we write literature reviews?

Literature reviews provide you with a handy guide to a particular topic. If you have limited time to conduct research, literature reviews can give you an overview or act as a stepping stone. For professionals, they are useful reports that keep them up to date with what is current in the field. For scholars, the depth and breadth of the literature review emphasizes the credibility of the writer in his or her field. Literature reviews also provide a solid background for a research paper’s investigation. Comprehensive knowledge of the literature of the field is essential to most research papers.

Who writes these things, anyway?

Literature reviews are written occasionally in the humanities, but mostly in the sciences and social sciences; in experiment and lab reports, they constitute a section of the paper. Sometimes a literature review is written as a paper in itself.

Let’s get to it! What should I do before writing the literature review?

If your assignment is not very specific, seek clarification from your instructor:

• Roughly how many sources should you include?
• What types of sources (books, journal articles, websites)?
• Should you summarize, synthesize, or critique your sources by discussing a common theme or issue?
• Should you evaluate your sources?
• Should you provide subheadings and other background information, such as definitions and/or a history?

Find models

Look for other literature reviews in your area of interest or in the discipline and read them to get a sense of the types of themes you might want to look for in your own research or ways to organize your final review. You can simply put the word “review” in your search engine along with your other topic terms to find articles of this type on the Internet or in an electronic database. The bibliography or reference section of sources you’ve already read are also excellent entry points into your own research.

Narrow your topic

There are hundreds or even thousands of articles and books on most areas of study. The narrower your topic, the easier it will be to limit the number of sources you need to read in order to get a good survey of the material. Your instructor will probably not expect you to read everything that’s out there on the topic, but you’ll make your job easier if you first limit your scope.

Keep in mind that UNC Libraries have research guides and to databases relevant to many fields of study. You can reach out to the subject librarian for a consultation: https://library.unc.edu/support/consultations/ .

And don’t forget to tap into your professor’s (or other professors’) knowledge in the field. Ask your professor questions such as: “If you had to read only one book from the 90’s on topic X, what would it be?” Questions such as this help you to find and determine quickly the most seminal pieces in the field.

Consider whether your sources are current

Some disciplines require that you use information that is as current as possible. In the sciences, for instance, treatments for medical problems are constantly changing according to the latest studies. Information even two years old could be obsolete. However, if you are writing a review in the humanities, history, or social sciences, a survey of the history of the literature may be what is needed, because what is important is how perspectives have changed through the years or within a certain time period. Try sorting through some other current bibliographies or literature reviews in the field to get a sense of what your discipline expects. You can also use this method to consider what is currently of interest to scholars in this field and what is not.

Strategies for writing the literature review

Find a focus.

A literature review, like a term paper, is usually organized around ideas, not the sources themselves as an annotated bibliography would be organized. This means that you will not just simply list your sources and go into detail about each one of them, one at a time. No. As you read widely but selectively in your topic area, consider instead what themes or issues connect your sources together. Do they present one or different solutions? Is there an aspect of the field that is missing? How well do they present the material and do they portray it according to an appropriate theory? Do they reveal a trend in the field? A raging debate? Pick one of these themes to focus the organization of your review.

Convey it to your reader

A literature review may not have a traditional thesis statement (one that makes an argument), but you do need to tell readers what to expect. Try writing a simple statement that lets the reader know what is your main organizing principle. Here are a couple of examples:

The current trend in treatment for congestive heart failure combines surgery and medicine. More and more cultural studies scholars are accepting popular media as a subject worthy of academic consideration.

Consider organization

You’ve got a focus, and you’ve stated it clearly and directly. Now what is the most effective way of presenting the information? What are the most important topics, subtopics, etc., that your review needs to include? And in what order should you present them? Develop an organization for your review at both a global and local level:

First, cover the basic categories

Just like most academic papers, literature reviews also must contain at least three basic elements: an introduction or background information section; the body of the review containing the discussion of sources; and, finally, a conclusion and/or recommendations section to end the paper. The following provides a brief description of the content of each:

• Introduction: Gives a quick idea of the topic of the literature review, such as the central theme or organizational pattern.
• Body: Contains your discussion of sources and is organized either chronologically, thematically, or methodologically (see below for more information on each).
• Conclusions/Recommendations: Discuss what you have drawn from reviewing literature so far. Where might the discussion proceed?

Organizing the body

Once you have the basic categories in place, then you must consider how you will present the sources themselves within the body of your paper. Create an organizational method to focus this section even further.

To help you come up with an overall organizational framework for your review, consider the following scenario:

You’ve decided to focus your literature review on materials dealing with sperm whales. This is because you’ve just finished reading Moby Dick, and you wonder if that whale’s portrayal is really real. You start with some articles about the physiology of sperm whales in biology journals written in the 1980’s. But these articles refer to some British biological studies performed on whales in the early 18th century. So you check those out. Then you look up a book written in 1968 with information on how sperm whales have been portrayed in other forms of art, such as in Alaskan poetry, in French painting, or on whale bone, as the whale hunters in the late 19th century used to do. This makes you wonder about American whaling methods during the time portrayed in Moby Dick, so you find some academic articles published in the last five years on how accurately Herman Melville portrayed the whaling scene in his novel.

Now consider some typical ways of organizing the sources into a review:

• Chronological: If your review follows the chronological method, you could write about the materials above according to when they were published. For instance, first you would talk about the British biological studies of the 18th century, then about Moby Dick, published in 1851, then the book on sperm whales in other art (1968), and finally the biology articles (1980s) and the recent articles on American whaling of the 19th century. But there is relatively no continuity among subjects here. And notice that even though the sources on sperm whales in other art and on American whaling are written recently, they are about other subjects/objects that were created much earlier. Thus, the review loses its chronological focus.
• By publication: Order your sources by publication chronology, then, only if the order demonstrates a more important trend. For instance, you could order a review of literature on biological studies of sperm whales if the progression revealed a change in dissection practices of the researchers who wrote and/or conducted the studies.
• By trend: A better way to organize the above sources chronologically is to examine the sources under another trend, such as the history of whaling. Then your review would have subsections according to eras within this period. For instance, the review might examine whaling from pre-1600-1699, 1700-1799, and 1800-1899. Under this method, you would combine the recent studies on American whaling in the 19th century with Moby Dick itself in the 1800-1899 category, even though the authors wrote a century apart.
• Thematic: Thematic reviews of literature are organized around a topic or issue, rather than the progression of time. However, progression of time may still be an important factor in a thematic review. For instance, the sperm whale review could focus on the development of the harpoon for whale hunting. While the study focuses on one topic, harpoon technology, it will still be organized chronologically. The only difference here between a “chronological” and a “thematic” approach is what is emphasized the most: the development of the harpoon or the harpoon technology.But more authentic thematic reviews tend to break away from chronological order. For instance, a thematic review of material on sperm whales might examine how they are portrayed as “evil” in cultural documents. The subsections might include how they are personified, how their proportions are exaggerated, and their behaviors misunderstood. A review organized in this manner would shift between time periods within each section according to the point made.
• Methodological: A methodological approach differs from the two above in that the focusing factor usually does not have to do with the content of the material. Instead, it focuses on the “methods” of the researcher or writer. For the sperm whale project, one methodological approach would be to look at cultural differences between the portrayal of whales in American, British, and French art work. Or the review might focus on the economic impact of whaling on a community. A methodological scope will influence either the types of documents in the review or the way in which these documents are discussed. Once you’ve decided on the organizational method for the body of the review, the sections you need to include in the paper should be easy to figure out. They should arise out of your organizational strategy. In other words, a chronological review would have subsections for each vital time period. A thematic review would have subtopics based upon factors that relate to the theme or issue.

Sometimes, though, you might need to add additional sections that are necessary for your study, but do not fit in the organizational strategy of the body. What other sections you include in the body is up to you. Put in only what is necessary. Here are a few other sections you might want to consider:

• Current Situation: Information necessary to understand the topic or focus of the literature review.
• History: The chronological progression of the field, the literature, or an idea that is necessary to understand the literature review, if the body of the literature review is not already a chronology.
• Methods and/or Standards: The criteria you used to select the sources in your literature review or the way in which you present your information. For instance, you might explain that your review includes only peer-reviewed articles and journals.

Questions for Further Research: What questions about the field has the review sparked? How will you further your research as a result of the review?

Begin composing

Once you’ve settled on a general pattern of organization, you’re ready to write each section. There are a few guidelines you should follow during the writing stage as well. Here is a sample paragraph from a literature review about sexism and language to illuminate the following discussion:

However, other studies have shown that even gender-neutral antecedents are more likely to produce masculine images than feminine ones (Gastil, 1990). Hamilton (1988) asked students to complete sentences that required them to fill in pronouns that agreed with gender-neutral antecedents such as “writer,” “pedestrian,” and “persons.” The students were asked to describe any image they had when writing the sentence. Hamilton found that people imagined 3.3 men to each woman in the masculine “generic” condition and 1.5 men per woman in the unbiased condition. Thus, while ambient sexism accounted for some of the masculine bias, sexist language amplified the effect. (Source: Erika Falk and Jordan Mills, “Why Sexist Language Affects Persuasion: The Role of Homophily, Intended Audience, and Offense,” Women and Language19:2).

Use evidence

In the example above, the writers refer to several other sources when making their point. A literature review in this sense is just like any other academic research paper. Your interpretation of the available sources must be backed up with evidence to show that what you are saying is valid.

Be selective

Select only the most important points in each source to highlight in the review. The type of information you choose to mention should relate directly to the review’s focus, whether it is thematic, methodological, or chronological.

Use quotes sparingly

Falk and Mills do not use any direct quotes. That is because the survey nature of the literature review does not allow for in-depth discussion or detailed quotes from the text. Some short quotes here and there are okay, though, if you want to emphasize a point, or if what the author said just cannot be rewritten in your own words. Notice that Falk and Mills do quote certain terms that were coined by the author, not common knowledge, or taken directly from the study. But if you find yourself wanting to put in more quotes, check with your instructor.

Summarize and synthesize

Remember to summarize and synthesize your sources within each paragraph as well as throughout the review. The authors here recapitulate important features of Hamilton’s study, but then synthesize it by rephrasing the study’s significance and relating it to their own work.

Keep your own voice

While the literature review presents others’ ideas, your voice (the writer’s) should remain front and center. Notice that Falk and Mills weave references to other sources into their own text, but they still maintain their own voice by starting and ending the paragraph with their own ideas and their own words. The sources support what Falk and Mills are saying.

Use caution when paraphrasing

When paraphrasing a source that is not your own, be sure to represent the author’s information or opinions accurately and in your own words. In the preceding example, Falk and Mills either directly refer in the text to the author of their source, such as Hamilton, or they provide ample notation in the text when the ideas they are mentioning are not their own, for example, Gastil’s. For more information, please see our handout on plagiarism .

Revise, revise, revise

Draft in hand? Now you’re ready to revise. Spending a lot of time revising is a wise idea, because your main objective is to present the material, not the argument. So check over your review again to make sure it follows the assignment and/or your outline. Then, just as you would for most other academic forms of writing, rewrite or rework the language of your review so that you’ve presented your information in the most concise manner possible. Be sure to use terminology familiar to your audience; get rid of unnecessary jargon or slang. Finally, double check that you’ve documented your sources and formatted the review appropriately for your discipline. For tips on the revising and editing process, see our handout on revising drafts .

Works consulted

We consulted these works while writing this handout. This is not a comprehensive list of resources on the handout’s topic, and we encourage you to do your own research to find additional publications. Please do not use this list as a model for the format of your own reference list, as it may not match the citation style you are using. For guidance on formatting citations, please see the UNC Libraries citation tutorial . We revise these tips periodically and welcome feedback.

Anson, Chris M., and Robert A. Schwegler. 2010. The Longman Handbook for Writers and Readers , 6th ed. New York: Longman.

Jones, Robert, Patrick Bizzaro, and Cynthia Selfe. 1997. The Harcourt Brace Guide to Writing in the Disciplines . New York: Harcourt Brace.

Lamb, Sandra E. 1998. How to Write It: A Complete Guide to Everything You’ll Ever Write . Berkeley: Ten Speed Press.

Rosen, Leonard J., and Laurence Behrens. 2003. The Allyn & Bacon Handbook , 5th ed. New York: Longman.

Troyka, Lynn Quittman, and Doug Hesse. 2016. Simon and Schuster Handbook for Writers , 11th ed. London: Pearson.

You may reproduce it for non-commercial use if you use the entire handout and attribute the source: The Writing Center, University of North Carolina at Chapel Hill

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• 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
• << Previous: Getting Started
• Next: How to Pick a Topic >>
• Last Updated: Sep 21, 2022 2:16 PM
• URL: https://guides.lib.uconn.edu/literaturereview

How to Write a Literature Review

What is a literature review.

• What Is the Literature
• Writing the Review

A literature review is much more than an annotated bibliography or a list of separate reviews of articles and books. It is a critical, analytical summary and synthesis of the current knowledge of a topic. Thus it should compare and relate different theories, findings, etc, rather than just summarize them individually. In addition, it should have a particular focus or theme to organize the review. It does not have to be an exhaustive account of everything published on the topic, but it should discuss all the significant academic literature and other relevant sources important for that focus.

This is meant to be a general guide to writing a literature review: ways to structure one, what to include, how it supplements other research. For more specific help on writing a review, and especially for help on finding the literature to review, sign up for a Personal Research Session .

The specific organization of a literature review depends on the type and purpose of the review, as well as on the specific field or topic being reviewed. But in general, it is a relatively brief but thorough exploration of past and current work on a topic. Rather than a chronological listing of previous work, though, literature reviews are usually organized thematically, such as different theoretical approaches, methodologies, or specific issues or concepts involved in the topic. A thematic organization makes it much easier to examine contrasting perspectives, theoretical approaches, methodologies, findings, etc, and to analyze the strengths and weaknesses of, and point out any gaps in, previous research. And this is the heart of what a literature review is about. A literature review may offer new interpretations, theoretical approaches, or other ideas; if it is part of a research proposal or report it should demonstrate the relationship of the proposed or reported research to others' work; but whatever else it does, it must provide a critical overview of the current state of research efforts. 

Literature reviews are common and very important in the sciences and social sciences. They are less common and have a less important role in the humanities, but they do have a place, especially stand-alone reviews.

Types of Literature Reviews

There are different types of literature reviews, and different purposes for writing a review, but the most common are:

• Stand-alone literature review articles . These provide an overview and analysis of the current state of research on a topic or question. The goal is to evaluate and compare previous research on a topic to provide an analysis of what is currently known, and also to reveal controversies, weaknesses, and gaps in current work, thus pointing to directions for future research. You can find examples published in any number of academic journals, but there is a series of Annual Reviews of *Subject* which are specifically devoted to literature review articles. Writing a stand-alone review is often an effective way to get a good handle on a topic and to develop ideas for your own research program. For example, contrasting theoretical approaches or conflicting interpretations of findings can be the basis of your research project: can you find evidence supporting one interpretation against another, or can you propose an alternative interpretation that overcomes their limitations?
• Part of a research proposal . This could be a proposal for a PhD dissertation, a senior thesis, or a class project. It could also be a submission for a grant. The literature review, by pointing out the current issues and questions concerning a topic, is a crucial part of demonstrating how your proposed research will contribute to the field, and thus of convincing your thesis committee to allow you to pursue the topic of your interest or a funding agency to pay for your research efforts.
• Part of a research report . When you finish your research and write your thesis or paper to present your findings, it should include a literature review to provide the context to which your work is a contribution. Your report, in addition to detailing the methods, results, etc. of your research, should show how your work relates to others' work.

A literature review for a research report is often a revision of the review for a research proposal, which can be a revision of a stand-alone review. Each revision should be a fairly extensive revision. With the increased knowledge of and experience in the topic as you proceed, your understanding of the topic will increase. Thus, you will be in a better position to analyze and critique the literature. In addition, your focus will change as you proceed in your research. Some areas of the literature you initially reviewed will be marginal or irrelevant for your eventual research, and you will need to explore other areas more thoroughly. 

Examples of Literature Reviews

See the series of Annual Reviews of *Subject* which are specifically devoted to literature review articles to find many examples of stand-alone literature reviews in the biomedical, physical, and social sciences. 

Research report articles vary in how they are organized, but a common general structure is to have sections such as:

• Abstract - Brief summary of the contents of the article
• Introduction - A explanation of the purpose of the study, a statement of the research question(s) the study intends to address
• Literature review - A critical assessment of the work done so far on this topic, to show how the current study relates to what has already been done
• Methods - How the study was carried out (e.g. instruments or equipment, procedures, methods to gather and analyze data)
• Results - What was found in the course of the study
• Discussion - What do the results mean
• Conclusion - State the conclusions and implications of the results, and discuss how it relates to the work reviewed in the literature review; also, point to directions for further work in the area

Here are some articles that illustrate variations on this theme. There is no need to read the entire articles (unless the contents interest you); just quickly browse through to see the sections, and see how each section is introduced and what is contained in them.

The Determinants of Undergraduate Grade Point Average: The Relative Importance of Family Background, High School Resources, and Peer Group Effects , in The Journal of Human Resources , v. 34 no. 2 (Spring 1999), p. 268-293.

This article has a standard breakdown of sections:

• Introduction
• Literature Review
• Some discussion sections

First Encounters of the Bureaucratic Kind: Early Freshman Experiences with a Campus Bureaucracy , in The Journal of Higher Education , v. 67 no. 6 (Nov-Dec 1996), p. 660-691.

This one does not have a section specifically labeled as a "literature review" or "review of the literature," but the first few sections cite a long list of other sources discussing previous research in the area before the authors present their own study they are reporting.

• Next: What Is the Literature >>
• Last Updated: Jan 11, 2024 9:48 AM
• URL: https://libguides.wesleyan.edu/litreview

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• What is a Literature Review? | Guide, Template, & Examples

What is a Literature Review? | Guide, Template, & Examples

Published on 22 February 2022 by Shona McCombes . Revised on 7 June 2022.

What is a literature review? A literature review is a survey of scholarly sources on a specific topic. It provides an overview of current knowledge, allowing you to identify relevant theories, methods, and gaps in the existing research.

There are five key steps to writing a literature review:

• Search for relevant literature
• Evaluate sources
• Identify themes, debates and gaps
• Outline the structure
• Write your literature review

A good literature review doesn’t just summarise sources – it analyses, synthesises, and critically evaluates to give a clear picture of the state of knowledge on the subject.

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Table of contents

Why write a literature review, examples of literature reviews, step 1: search for relevant literature, step 2: evaluate and select sources, step 3: identify themes, debates and gaps, step 4: outline your literature review’s structure, step 5: write your literature review, frequently asked questions about literature reviews, introduction.

• Quick Run-through
• Step 1 & 2

When you write a dissertation or thesis, you will have to conduct a literature review to situate your research within existing knowledge. The literature review gives you a chance to:

• Demonstrate your familiarity with the topic and scholarly context
• Develop a theoretical framework and methodology for your research
• Position yourself in relation to other researchers and theorists
• Show how your dissertation addresses a gap or contributes to a debate

You might also have to write a literature review as a stand-alone assignment. In this case, the purpose is to evaluate the current state of research and demonstrate your knowledge of scholarly debates around a topic.

The content will look slightly different in each case, but the process of conducting a literature review follows the same steps. We’ve written a step-by-step guide that you can follow below.

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Writing literature reviews can be quite challenging! A good starting point could be to look at some examples, depending on what kind of literature review you’d like to write.

• Example literature review #1: “Why Do People Migrate? A Review of the Theoretical Literature” ( Theoretical literature review about the development of economic migration theory from the 1950s to today.)
• Example literature review #2: “Literature review as a research methodology: An overview and guidelines” ( Methodological literature review about interdisciplinary knowledge acquisition and production.)
• Example literature review #3: “The Use of Technology in English Language Learning: A Literature Review” ( Thematic literature review about the effects of technology on language acquisition.)
• Example literature review #4: “Learners’ Listening Comprehension Difficulties in English Language Learning: A Literature Review” ( Chronological literature review about how the concept of listening skills has changed over time.)

You can also check out our templates with literature review examples and sample outlines at the links below.

Download Word doc Download Google doc

Before you begin searching for literature, you need a clearly defined topic .

If you are writing the literature review section of a dissertation or research paper, you will search for literature related to your research objectives and questions .

If you are writing a literature review as a stand-alone assignment, you will have to choose a focus and develop a central question to direct your search. Unlike a dissertation research question, this question has to be answerable without collecting original data. You should be able to answer it based only on a review of existing publications.

Make a list of keywords

Start by creating a list of keywords related to your research topic. Include each of the key concepts or variables you’re interested in, and list any synonyms and related terms. You can add to this list if you discover new keywords in the process of your literature search.

• Social media, Facebook, Instagram, Twitter, Snapchat, TikTok
• Body image, self-perception, self-esteem, mental health
• Generation Z, teenagers, adolescents, youth

Search for relevant sources

Use your keywords to begin searching for sources. Some databases to search for journals and articles include:

• Your university’s library catalogue
• Google Scholar
• Project Muse (humanities and social sciences)
• Medline (life sciences and biomedicine)
• EconLit (economics)
• Inspec (physics, engineering and computer science)

You can use boolean operators to help narrow down your search:

Read the abstract to find out whether an article is relevant to your question. When you find a useful book or article, you can check the bibliography to find other relevant sources.

To identify the most important publications on your topic, take note of recurring citations. If the same authors, books or articles keep appearing in your reading, make sure to seek them out.

You probably won’t be able to read absolutely everything that has been written on the topic – you’ll have to evaluate which sources are most relevant to your questions.

For each publication, ask yourself:

• What question or problem is the author addressing?
• What are the key concepts and how are they defined?
• What are the key theories, models and methods? Does the research use established frameworks or take an innovative approach?
• What are the results and conclusions of the study?
• How does the publication relate to other literature in the field? Does it confirm, add to, or challenge established knowledge?
• How does the publication contribute to your understanding of the topic? What are its key insights and arguments?
• What are the strengths and weaknesses of the research?

Make sure the sources you use are credible, and make sure you read any landmark studies and major theories in your field of research.

You can find out how many times an article has been cited on Google Scholar – a high citation count means the article has been influential in the field, and should certainly be included in your literature review.

The scope of your review will depend on your topic and discipline: in the sciences you usually only review recent literature, but in the humanities you might take a long historical perspective (for example, to trace how a concept has changed in meaning over time).

Remember that you can use our template to summarise and evaluate sources you’re thinking about using!

Take notes and cite your sources

As you read, you should also begin the writing process. Take notes that you can later incorporate into the text of your literature review.

It’s important to keep track of your sources with references to avoid plagiarism . It can be helpful to make an annotated bibliography, where you compile full reference information and write a paragraph of summary and analysis for each source. This helps you remember what you read and saves time later in the process.

You can use our free APA Reference Generator for quick, correct, consistent citations.

To begin organising your literature review’s argument and structure, you need to understand the connections and relationships between the sources you’ve read. Based on your reading and notes, you can look for:

• Trends and patterns (in theory, method or results): do certain approaches become more or less popular over time?
• Themes: what questions or concepts recur across the literature?
• Debates, conflicts and contradictions: where do sources disagree?
• Pivotal publications: are there any influential theories or studies that changed the direction of the field?
• Gaps: what is missing from the literature? Are there weaknesses that need to be addressed?

This step will help you work out the structure of your literature review and (if applicable) show how your own research will contribute to existing knowledge.

• Most research has focused on young women.
• There is an increasing interest in the visual aspects of social media.
• But there is still a lack of robust research on highly-visual platforms like Instagram and Snapchat – this is a gap that you could address in your own research.

There are various approaches to organising the body of a literature review. You should have a rough idea of your strategy before you start writing.

Depending on the length of your literature review, you can combine several of these strategies (for example, your overall structure might be thematic, but each theme is discussed chronologically).

Chronological

The simplest approach is to trace the development of the topic over time. However, if you choose this strategy, be careful to avoid simply listing and summarising sources in order.

Try to analyse patterns, turning points and key debates that have shaped the direction of the field. Give your interpretation of how and why certain developments occurred.

If you have found some recurring central themes, you can organise your literature review into subsections that address different aspects of the topic.

For example, if you are reviewing literature about inequalities in migrant health outcomes, key themes might include healthcare policy, language barriers, cultural attitudes, legal status, and economic access.

Methodological

If you draw your sources from different disciplines or fields that use a variety of research methods , you might want to compare the results and conclusions that emerge from different approaches. For example:

• Look at what results have emerged in qualitative versus quantitative research
• Discuss how the topic has been approached by empirical versus theoretical scholarship
• Divide the literature into sociological, historical, and cultural sources

Theoretical

A literature review is often the foundation for a theoretical framework . You can use it to discuss various theories, models, and definitions of key concepts.

You might argue for the relevance of a specific theoretical approach, or combine various theoretical concepts to create a framework for your research.

Like any other academic text, your literature review should have an introduction , a main body, and a conclusion . What you include in each depends on the objective of your literature review.

The introduction should clearly establish the focus and purpose of the literature review.

If you are writing the literature review as part of your dissertation or thesis, reiterate your central problem or research question and give a brief summary of the scholarly context. You can emphasise the timeliness of the topic (“many recent studies have focused on the problem of x”) or highlight a gap in the literature (“while there has been much research on x, few researchers have taken y into consideration”).

Depending on the length of your literature review, you might want to divide the body into subsections. You can use a subheading for each theme, time period, or methodological approach.

As you write, make sure to follow these tips:

• Summarise and synthesise: give an overview of the main points of each source and combine them into a coherent whole.
• Analyse and interpret: don’t just paraphrase other researchers – add your own interpretations, 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 transitions and topic sentences to draw connections, comparisons and contrasts.

In the conclusion, you should summarise the key findings you have taken from the literature and emphasise their significance.

If the literature review is part of your dissertation or thesis, reiterate how your research addresses gaps and contributes new knowledge, or discuss how you have drawn on existing theories and methods to build a framework for your research. This can lead directly into your methodology section.

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 dissertation , thesis, research paper , or proposal .

There are several reasons to conduct a literature review at the beginning of a research project:

• To familiarise yourself with the current state of knowledge on your topic
• To ensure that you’re not just repeating what others have already done
• To identify gaps in knowledge and unresolved problems that your research can address
• To develop your theoretical framework and methodology
• To provide an overview of the key findings and debates on the topic

Writing the literature review shows your reader how your work relates to existing research and what new insights it will contribute.

The literature review usually comes near the beginning of your  dissertation . After the introduction , it grounds your research in a scholarly field and leads directly to your theoretical framework or methodology .

Cite this Scribbr article

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Write a literature review.

• Examples and Further Information

1. Introduction

Not to be confused with a book review, a literature review surveys scholarly articles, books and other sources (e.g. dissertations, conference proceedings) relevant to a particular issue, area of research, or theory, providing a description, summary, and critical evaluation of each work. The purpose is to offer an overview of significant literature published on a topic.

2. Components

Similar to primary research, development of the literature review requires four stages:

• Problem formulation—which topic or field is being examined and what are its component issues?
• Literature search—finding materials relevant to the subject being explored
• Data evaluation—determining which literature makes a significant contribution to the understanding of the topic
• Analysis and interpretation—discussing the findings and conclusions of pertinent literature

Literature reviews should comprise the following elements:

• An overview of the subject, issue or theory under consideration, along with the objectives of the literature review
• Division of works under review into categories (e.g. those in support of a particular position, those against, and those offering alternative theses entirely)
• Explanation of how each work is similar to and how it varies from the others
• Conclusions as to 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 their area of research

In assessing each piece, consideration should be given to:

• Provenance—What are the author's credentials? Are the author's arguments supported by evidence (e.g. primary historical material, case studies, narratives, statistics, recent scientific findings)?
• Objectivity—Is the author's perspective even-handed or prejudicial? Is contrary data considered or is certain pertinent information ignored to prove the author's point?
• Persuasiveness—Which of the author's theses are most/least convincing?
• Value—Are the author's arguments and conclusions convincing? Does the work ultimately contribute in any significant way to an understanding of the subject?

3. Definition and Use/Purpose

A literature review may constitute an essential chapter of a thesis or dissertation, or may be a self-contained review of writings on a subject. In either case, its purpose is to:

• Place each work in the context of its contribution to the understanding of the subject under review
• Describe the relationship of each work to the others under consideration
• Identify new ways to interpret, and shed light on any gaps in, previous research
• Resolve conflicts amongst seemingly contradictory previous studies
• Identify areas of prior scholarship to prevent duplication of effort
• Point the way forward for further research
• Place one's original work (in the case of theses or dissertations) in the context of existing literature

The literature review itself, however, does not present new primary scholarship.

• Next: Examples and Further Information >>

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Land Acknowledgement

The land on which we gather is the unceded territory of the Awaswas-speaking Uypi Tribe. The Amah Mutsun Tribal Band, comprised of the descendants of indigenous people taken to missions Santa Cruz and San Juan Bautista during Spanish colonization of the Central Coast, is today working hard to restore traditional stewardship practices on these lands and heal from historical trauma.

The land acknowledgement used at UC Santa Cruz was developed in partnership with the Amah Mutsun Tribal Band Chairman and the Amah Mutsun Relearning Program at the UCSC Arboretum .

How To Structure Your Literature Review

3 options to help structure your chapter.

By: Amy Rommelspacher (PhD) | Reviewer: Dr Eunice Rautenbach | November 2020 (Updated May 2023)

Writing the literature review chapter can seem pretty daunting when you’re piecing together your dissertation or thesis. As  we’ve discussed before , a good literature review needs to achieve a few very important objectives – it should:

• Demonstrate your knowledge of the research topic
• Identify the gaps in the literature and show how your research links to these
• Provide the foundation for your conceptual framework (if you have one)
• Inform your own  methodology and research design

To achieve this, your literature review needs a well-thought-out structure . Get the structure of your literature review chapter wrong and you’ll struggle to achieve these objectives. Don’t worry though – in this post, we’ll look at how to structure your literature review for maximum impact (and marks!).

But wait – is this the right time?

Deciding on the structure of your literature review should come towards the end of the literature review process – after you have collected and digested the literature, but before you start writing the chapter. 

In other words, you need to first develop a rich understanding of the literature before you even attempt to map out a structure. There’s no use trying to develop a structure before you’ve fully wrapped your head around the existing research.

Equally importantly, you need to have a structure in place before you start writing , or your literature review will most likely end up a rambling, disjointed mess. 

Importantly, don’t feel that once you’ve defined a structure you can’t iterate on it. It’s perfectly natural to adjust as you engage in the writing process. As we’ve discussed before , writing is a way of developing your thinking, so it’s quite common for your thinking to change – and therefore, for your chapter structure to change – as you write. 

Need a helping hand?

Like any other chapter in your thesis or dissertation, your literature review needs to have a clear, logical structure. At a minimum, it should have three essential components – an  introduction , a  body   and a  conclusion . 

Let’s take a closer look at each of these.

1: The Introduction Section

Just like any good introduction, the introduction section of your literature review should introduce the purpose and layout (organisation) of the chapter. In other words, your introduction needs to give the reader a taste of what’s to come, and how you’re going to lay that out. Essentially, you should provide the reader with a high-level roadmap of your chapter to give them a taste of the journey that lies ahead.

Here’s an example of the layout visualised in a literature review introduction:

Your introduction should also outline your topic (including any tricky terminology or jargon) and provide an explanation of the scope of your literature review – in other words, what you  will   and  won’t   be covering (the delimitations ). This helps ringfence your review and achieve a clear focus . The clearer and narrower your focus, the deeper you can dive into the topic (which is typically where the magic lies). 

Depending on the nature of your project, you could also present your stance or point of view at this stage. In other words, after grappling with the literature you’ll have an opinion about what the trends and concerns are in the field as well as what’s lacking. The introduction section can then present these ideas so that it is clear to examiners that you’re aware of how your research connects with existing knowledge .

2: The Body Section

The body of your literature review is the centre of your work. This is where you’ll present, analyse, evaluate and synthesise the existing research. In other words, this is where you’re going to earn (or lose) the most marks. Therefore, it’s important to carefully think about how you will organise your discussion to present it in a clear way. 

The body of your literature review should do just as the description of this chapter suggests. It should “review” the literature – in other words, identify, analyse, and synthesise it. So, when thinking about structuring your literature review, you need to think about which structural approach will provide the best “review” for your specific type of research and objectives (we’ll get to this shortly).

There are (broadly speaking)  three options  for organising your literature review.

Option 1: Chronological (according to date)

Organising the literature chronologically is one of the simplest ways to structure your literature review. You start with what was published first and work your way through the literature until you reach the work published most recently. Pretty straightforward.

The benefit of this option is that it makes it easy to discuss the developments and debates in the field as they emerged over time. Organising your literature chronologically also allows you to highlight how specific articles or pieces of work might have changed the course of the field – in other words, which research has had the most impact . Therefore, this approach is very useful when your research is aimed at understanding how the topic has unfolded over time and is often used by scholars in the field of history. That said, this approach can be utilised by anyone that wants to explore change over time .

For example , if a student of politics is investigating how the understanding of democracy has evolved over time, they could use the chronological approach to provide a narrative that demonstrates how this understanding has changed through the ages.

Here are some questions you can ask yourself to help you structure your literature review chronologically.

• What is the earliest literature published relating to this topic?
• How has the field changed over time? Why?
• What are the most recent discoveries/theories?

In some ways, chronology plays a part whichever way you decide to structure your literature review, because you will always, to a certain extent, be analysing how the literature has developed. However, with the chronological approach, the emphasis is very firmly on how the discussion has evolved over time , as opposed to how all the literature links together (which we’ll discuss next ).

Option 2: Thematic (grouped by theme)

The thematic approach to structuring a literature review means organising your literature by theme or category – for example, by independent variables (i.e. factors that have an impact on a specific outcome).

As you’ve been collecting and synthesising literature , you’ll likely have started seeing some themes or patterns emerging. You can then use these themes or patterns as a structure for your body discussion. The thematic approach is the most common approach and is useful for structuring literature reviews in most fields.

For example, if you were researching which factors contributed towards people trusting an organisation, you might find themes such as consumers’ perceptions of an organisation’s competence, benevolence and integrity. Structuring your literature review thematically would mean structuring your literature review’s body section to discuss each of these themes, one section at a time.

Here are some questions to ask yourself when structuring your literature review by themes:

• Are there any patterns that have come to light in the literature?
• What are the central themes and categories used by the researchers?
• Do I have enough evidence of these themes?

PS – you can see an example of a thematically structured literature review in our literature review sample walkthrough video here.

Option 3: Methodological

The methodological option is a way of structuring your literature review by the research methodologies used . In other words, organising your discussion based on the angle from which each piece of research was approached – for example, qualitative , quantitative or mixed  methodologies.

Structuring your literature review by methodology can be useful if you are drawing research from a variety of disciplines and are critiquing different methodologies. The point of this approach is to question  how  existing research has been conducted, as opposed to  what  the conclusions and/or findings the research were.

For example, a sociologist might centre their research around critiquing specific fieldwork practices. Their literature review will then be a summary of the fieldwork methodologies used by different studies.

Here are some questions you can ask yourself when structuring your literature review according to methodology:

• Which methodologies have been utilised in this field?
• Which methodology is the most popular (and why)?
• What are the strengths and weaknesses of the various methodologies?
• How can the existing methodologies inform my own methodology?

3: The Conclusion Section

Once you’ve completed the body section of your literature review using one of the structural approaches we discussed above, you’ll need to “wrap up” your literature review and pull all the pieces together to set the direction for the rest of your dissertation or thesis.

The conclusion is where you’ll present the key findings of your literature review. In this section, you should emphasise the research that is especially important to your research questions and highlight the gaps that exist in the literature. Based on this, you need to make it clear what you will add to the literature – in other words, justify your own research by showing how it will help fill one or more of the gaps you just identified.

Last but not least, if it’s your intention to develop a conceptual framework for your dissertation or thesis, the conclusion section is a good place to present this.

Example: Thematically Structured Review

In the video below, we unpack a literature review chapter so that you can see an example of a thematically structure review in practice.

Let’s Recap

In this article, we’ve  discussed how to structure your literature review for maximum impact. Here’s a quick recap of what  you need to keep in mind when deciding on your literature review structure:

• Just like other chapters, your literature review needs a clear introduction , body and conclusion .
• The introduction section should provide an overview of what you will discuss in your literature review.
• The body section of your literature review can be organised by chronology , theme or methodology . The right structural approach depends on what you’re trying to achieve with your research.
• The conclusion section should draw together the key findings of your literature review and link them to your research questions.

If you’re ready to get started, be sure to download our free literature review template to fast-track your chapter outline.

Psst… there’s more!

This post is an extract from our bestselling short course, Literature Review Bootcamp . If you want to work smart, you don't want to miss this .

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27 Comments

Great work. This is exactly what I was looking for and helps a lot together with your previous post on literature review. One last thing is missing: a link to a great literature chapter of an journal article (maybe with comments of the different sections in this review chapter). Do you know any great literature review chapters?

I agree with you Marin… A great piece

I agree with Marin. This would be quite helpful if you annotate a nicely structured literature from previously published research articles.

Awesome article for my research.

I thank you immensely for this wonderful guide

It is indeed thought and supportive work for the futurist researcher and students

Very educative and good time to get guide. Thank you

Great work, very insightful. Thank you.

Thanks for this wonderful presentation. My question is that do I put all the variables into a single conceptual framework or each hypothesis will have it own conceptual framework?

Thank you very much, very helpful

This is very educative and precise . Thank you very much for dropping this kind of write up .

Pheeww, so damn helpful, thank you for this informative piece.

I’m doing a research project topic ; stool analysis for parasitic worm (enteric) worm, how do I structure it, thanks.

comprehensive explanation. Help us by pasting the URL of some good “literature review” for better understanding.

great piece. thanks for the awesome explanation. it is really worth sharing. I have a little question, if anyone can help me out, which of the options in the body of literature can be best fit if you are writing an architectural thesis that deals with design?

I am doing a research on nanofluids how can l structure it?

Beautifully clear.nThank you!

Lucid! Thankyou!

Brilliant work, well understood, many thanks

I like how this was so clear with simple language 😊😊 thank you so much 😊 for these information 😊

Insightful. I was struggling to come up with a sensible literature review but this has been really helpful. Thank you!

You have given thought-provoking information about the review of the literature.

Thank you. It has made my own research better and to impart your work to students I teach

I learnt a lot from this teaching. It’s a great piece.

I am doing research on EFL teacher motivation for his/her job. How Can I structure it? Is there any detailed template, additional to this?

You are so cool! I do not think I’ve read through something like this before. So nice to find somebody with some genuine thoughts on this issue. Seriously.. thank you for starting this up. This site is one thing that is required on the internet, someone with a little originality!

I’m asked to do conceptual, theoretical and empirical literature, and i just don’t know how to structure it

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Literature Review

• What is a Literature Review?
• What is a good literature review?
• Types of Literature Reviews
• What are the parts of a Literature Review?
• What is the difference between a Systematic Review and a Literature Review?

Parts of a Literature Review

Introduction      .

• To explain the focus and establish the importance of the subject
• provide the framework, selection criteria, or parameters of your literature review
• provide background or history
• outline what kind of work has been done on the topic
• briefly identify any controversies within the field or any recent research that has raised questions about earlier assumptions
• In a stand-alone literature review, this statement will sum up and evaluate the current state of this field of research
• In a review that is an introduction or preparatory to a thesis or research report, it will suggest how the review findings will lead to the research the writer proposes to undertake.
• To summarize and evaluate the current state of knowledge in the field
• To note major themes or topics, the most important trends, and any findings about which researchers agree or disagree
• Often divided by headings/subheadings
• If the review is preliminary to your own thesis or research project, its purpose is to make an argument that will justify your proposed research. Therefore, the literature review will discuss only that research which leads directly to your own project.
• To summarize the evidence presented and show its significance
• Rather than restating your thesis or purpose statement, explain what your review tells you about the current state of the field
• If the review is an introduction to your own research, the conclusion highlights gaps and indicates how previous research leads to your own research project and chosen methodology. 
• If the review is a stand-alone assignment for a course, the conclusion should suggest any practical applications of the research as well as the implications and possibilities for future research.
• Find out what style guide you are required to follow (e.g., APA, MLA, ASA)
• Follow the guidelines to format citations and create a reference list or bibliography
• Cite Your Sources

This work is licensed under a  Creative Commons Attribution-NonCommercial-ShareAlike 4.0  International License. adapted from UofG,McLaughlin Library

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Academic Writing

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How to Build a Literature Review

• PRISMA - Systematic reviews & meta-analyses
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• What is a Lit Review?
• Why Write a Lit Review?

Structure of a Literature Review

Preliminary steps for literature review.

• Basic Example
• More Examples

What is a Literature Review?

A literature review is a comprehensive summary and analysis of previously published research on a particular topic. Literature reviews should give the reader an overview of the important theories and themes that have previously been discussed on the topic, as well as any important researchers who have contributed to the discourse. This review should connect the established conclusions to the hypothesis being presented in the rest of the paper.

What a Literature Review Is Not:

• Annotated Bibliography: An annotated bibliography summarizes and assesses each resource individually and separately. A literature review explores the connections between different articles to illustrate important themes/theories/research trends within a larger research area. 
• Timeline: While a literature review can be organized chronologically, they are not simple timelines of previous events. They should not be a list of any kind. Individual examples or events should be combined to illustrate larger ideas or concepts.
• Argumentative Paper: Literature reviews are not meant to be making an argument. They are explorations of a concept to give the audience an understanding of what has already been written and researched about an idea. As many perspectives as possible should be included in a literature review in order to give the reader as comprehensive understanding of a topic as possible.

Why Write a Literature Review?

After reading the literature review, the reader should have a basic understanding of the topic. A reader should be able to come into your paper without really knowing anything about an idea, and after reading the literature, feel more confident about the important points.

A literature review should also help the reader understand the focus the rest of the paper will take within the larger topic. If the reader knows what has already been studied, they will be better prepared for the novel argument that is about to be made.

A literature review should help the reader understand the important history, themes, events, and ideas about a particular topic. Connections between ideas/themes should also explored. Part of the importance of a literature review is to prove to experts who do read your paper that you are knowledgeable enough to contribute to the academic discussion. You have to have done your homework.

A literature review should also identify the gaps in research to show the reader what hasn't yet been explored. Your thesis should ideally address one of the gaps identified in the research. Scholarly articles are meant to push academic conversations forward with new ideas and arguments. Before knowing where the gaps are in a topic, you need to have read what others have written.

As mentioned in other tabs, literature reviews should discuss the big ideas that make up a topic. Each literature review should be broken up into different subtopics. Each subtopic should use groups of articles as evidence to support the ideas. There are several different ways of organizing a literature review. It will depend on the patterns one sees in the groups of articles as to which strategy should be used. Here are a few examples of how to organize your review:

Chronological

If there are clear trends that change over time, a chronological approach could be used to organize a literature review. For example, one might argue that in the 1970s, the predominant theories and themes argued something. However, in the 1980s, the theories evolved to something else. Then, in the 1990s, theories evolved further. Each decade is a subtopic, and articles should be used as examples. 

Themes/Theories

There may also be clear distinctions between schools of thought within a topic, a theoretical breakdown may be most appropriate. Each theory could be a subtopic, and articles supporting the theme should be included as evidence for each one. 

If researchers mainly differ in the way they went about conducting research, literature reviews can be organized by methodology. Each type of method could be a subtopic,  and articles using the method should be included as evidence for each one.

• Define your research question
• Compile a list of initial keywords to use for searching based on question
• Search for literature that discusses the topics surrounding your research question
• Assess and organize your literature into logical groups
• Identify gaps in research and conduct secondary searches (if necessary)
• Reassess and reorganize literature again (if necessary)
• Write review

Here is an example of a literature review, taken from the beginning of a research article. You can find other examples within most scholarly research articles. The majority of published scholarship includes a literature review section, and you can use those to become more familiar with these reviews.

Source:  Perceptions of the Police by LGBT Communities

There are many books and internet resources about literature reviews though most are long on how to search and gather the literature. How to literally organize the information is another matter.

Some pro tips:

• Be thoughtful in naming the folders, sub-folders, and sub, sub-folders.  Doing so really helps your thinking and concepts within your research topic.
• Be disciplined to add keywords under the tabs as this will help you search for ALL the items on your concepts/topics.
• Use the notes tab to add reminders, write bibliography/annotated bibliography
• Your literature review easily flows from your statement of purpose (SoP).  Therefore, does your SoP say clearly and exactly the intent of your research?  Your research assumption and argument is obvious?
• Begin with a topic outline that traces your argument. pg99: "First establish the line of argumentation you will follow (the thesis), whether it is an assertion, a contention, or a proposition.
• This means that you should have formed judgments about the topic based on the analysis and synthesis of the literature you are reviewing."
• Keep filling it in; flushing it out more deeply with your references

Other Resources/Examples

• ISU Writing Assistance The Julia N. Visor Academic Center provides one-on-one writing assistance for any course or need. By focusing on the writing process instead of merely on grammar and editing, we are committed to making you a better writer.
• University of Toronto: The Literature Review Written by Dena Taylor, Health Sciences Writing Centre
• Purdue OWL - Writing a Lit Review Goes over the basic steps
• UW Madison Writing Center - Review of Literature A description of what each piece of a literature review should entail.
• USC Libraries - Literature Reviews Offers detailed guidance on how to develop, organize, and write a college-level research paper in the social and behavioral sciences.
• Creating the literature review: integrating research questions and arguments Blog post with very helpful overview for how to organize and build/integrate arguments in a literature review
• Understanding, Selecting, and Integrating a Theoretical Framework in Dissertation Research: Creating the Blueprint for Your “House” Article focusing on constructing a literature review for a dissertation. Still very relevant for literature reviews in other types of content.

A note that many of these examples will be far longer and in-depth than what's required for your assignment. However, they will give you an idea of the general structure and components of a literature review. Additionally, most scholarly articles will include a literature review section. Looking over the articles you have been assigned in classes will also help you.

• Understanding, Selecting, and Integrating a Theoretical Framework in Dissertation Research: Creating the Blueprint for Your “House” Excellent article detailing how to construct your literature review.
• Sample Literature Review (Univ. of Florida) This guide will provide research and writing tips to help students complete a literature review assignment.
• Sociology Literature Review (Univ. of Hawaii) Written in ASA citation style - don't follow this format.
• Sample Lit Review - Univ. of Vermont Includes an example with tips in the footnotes.

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

• Planning the Review
• The Research Question
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• 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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Literature review.

• What is a Literature Review?
• What is Its Purpose?
• 1. Select a Topic
• 2. Set the Topic in Context
• 3. Types of Information Sources
• 4. Use Information Sources
• 5. Get the Information
• 6. Organize / Manage the Information
• 7. Position the Literature Review
• 8. Write the Literature Review

A literature review is a comprehensive summary of previous research on a topic. The literature review surveys scholarly articles, books, and other sources relevant to a particular area of research.  The review should enumerate, describe, summarize, objectively evaluate and clarify this previous research.  It should give a theoretical base for the research and help you (the author) determine the nature of your research.  The literature review acknowledges the work of previous researchers, and in so doing, assures the reader that your work has been well conceived.  It is assumed that by mentioning a previous work in the field of study, that the author has read, evaluated, and assimiliated that work into the work at hand.

A literature review creates a "landscape" for the reader, giving her or him a full understanding of the developments in the field.  This landscape informs the reader that the author has indeed assimilated all (or the vast majority of) previous, significant works in the field into her or his research. 

 "In writing the literature review, the purpose is to convey to the reader what knowledge and ideas have been established on a topic, and what their strengths and weaknesses are. The literature review must be defined by a guiding concept (eg. 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.( http://www.writing.utoronto.ca/advice/specific-types-of-writing/literature-review )

Recommended Reading

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Essential Components of a Literature Review

Get knowledgeable about all the components of a literature review. Dive into this comprehensive guide to achieve a successful one.

The literature review is the cornerstone of academic research due to the fact that it offers a thorough overview and critical analysis of the content of previously published scholarly works on a certain subject. As scholars set out on their intellectual journeys, it becomes increasingly important to comprehend the key components that are involved in creating an effective and compelling literature review.

The essential components of a literature review will be explored in depth in this article. Researchers can improve the quality and credibility of their work, significantly add value to current knowledge, and build a strong base for future research by having a thorough understanding of these components.

What is a Literature Review?

A literature review is a critical and thorough examination of all previously published academic works that are pertinent to a certain research topic or question, including books, journals, dissertations, and conference papers. It serves as a knowledge synthesis, giving an overview and assessment of the existing literature in a certain field or subject area.

The main goal of a literature review is to identify, examine, and summarize the most important conclusions, concepts, theories, methods, and controversies that have been made in existing literature. It tries to determine the existing level of knowledge, identify any gaps or inconsistencies, and point out areas that require additional research. 

A thorough search for relevant sources, a critical assessment of their value, and creating an organized and coherent synthesis of the data are all components of a well-conducted literature review. It helps researchers situate their own work within the broader academic context, identify research questions or gaps to address, and build on existing knowledge.

Researchers may additionally demonstrate their expertise with the subject, showing their comprehension of the pertinent theories and concepts, and provide the groundwork for the theoretical framework of their own research through the literature review. It can be used to critically engage with already published works, assess other perspectives, and add to the intellectual debate within a given topic.

Purpose of a Literature Review

The purpose of a literature review is to provide an in-depth overview and analysis of existing knowledge, research, and scholarly literature on a specific topic. It fulfills a number of essential purposes in academic and research contexts, including:

• Sets the context by summarizing current knowledge and identifying gaps.
• Identifies areas needing further investigation.
• Evaluates the quality of existing research.
• Prevents duplication and plagiarism by ensuring novelty.
• Supports theoretical frameworks and hypotheses.
• Synthesizes and summarizes many sources of existing knowledge.
• Informs research methodology decisions.
• Guides the direction of the research study.

Examples of Literature Reviews

Here are some examples of literature reviews:

Posttransplantation Diabetes: A Systematic Literature Review

The goal of this systematic literature review is to offer a thorough examination of the body of literature on posttransplantation diabetes (PTD) at this time. The review’s main objectives are to examine the best management practices and comprehensively assess the incidence of PTD, as well as its risk factors and prognostic implications. This review seeks to advance knowledge of PTD and improve patient treatment in transplant settings by integrating and evaluating pertinent studies.

Child Well-being: A Systematic Review of the Literature

This systematic literature review provides a comprehensive assessment of the current state of child well-being research by examining the existing literature in English. The review addresses key research questions, including the definition of child well-being, the domains that contribute to child well-being, the indicators used to measure child well-being, and the methodologies employed for measuring child well-being. The findings of this review contribute to a deeper understanding of child well-being and can inform policies and interventions aimed at promoting positive outcomes for children.

Psychological Safety: A Systematic Review of the Literature

This systematic literature review aims to provide a comprehensive analysis of the empirical research on psychological safety, including its antecedents, outcomes, and moderators at various levels of analysis. With a growing body of empirical evidence in this field, a systematic review is necessary to synthesize the existing literature. In addition to reviewing empirical studies, this study identifies gaps and it emphasizes the importance of integrating key theoretical perspectives to enhance our understanding of how psychological safety develops and influences work outcomes across different levels of analysis. Furthermore, the review provides suggestions for future empirical studies to advance our knowledge of psychological safety. 

Types of Literature Reviews

There are different types of literature reviews that researchers can employ based on their research objectives and the nature of the topic. Here is a brief description of each type:

Chronological

Organizes research in chronological order to illustrate the historical development of ideas and theories over time.

Focuses on common themes or topics across studies to provide a comprehensive analysis of the subject matter.

Methodological

Evaluates research methodologies used in previous studies, highlighting strengths, weaknesses, and analytical techniques.

Theoretical

Analyzes and synthesizes theoretical frameworks and models utilized in research to establish their relevance and applicability.

Integrative

Goes beyond summarizing studies by identifying patterns, relationships, and connections between different studies to provide a cohesive understanding of the topic. 

Employs a rigorous and predefined methodology to select, evaluate, and synthesize relevant research studies. It involves predefined search criteria, inclusion/exclusion criteria, and systematic data extraction to minimize bias and ensure a thorough analysis of the literature.

Maps the existing literature on a broad research topic, identifying key concepts and areas for further investigation. Scoping reviews are particularly useful when the research area is complex or lacks a clear focus.

Meta-Analysis

Quantitatively synthesizes data from multiple studies using statistical analysis to generate pooled effect sizes and draw robust conclusions.

5 Steps to Writing a Literature Review

A literature review should not be a mere summary of sources. It should demonstrate critical thinking, analysis, and the ability to synthesize information from various sources to support your research objective. Here are the steps to writing a literature review:

1. Define your goal

Clarify the purpose of your literature review. Determine if you are aiming to provide an overview, identify research gaps, support a hypothesis, or offer a critical analysis.

2. Do your research

Conduct a comprehensive search of relevant scholarly literature using databases, academic journals, books, and other reputable sources. Select articles, studies, and sources that are directly related to your research topic.

3. Ground summary in relevance

Summarize and synthesize the key findings, arguments, and methodologies of the selected sources. Ensure that your summary directly relates to your research goal and provides meaningful insights.

4. Develop review logically

Organize the literature review in a logical manner. You can choose to structure it chronologically, thematically, or based on other relevant categories. Clearly present the main points and subtopics, and establish connections and relationships between the sources.

5. Include references/works cited list

Properly cite all the sources you have used in your literature review. Follow the appropriate citation style (such as APA, MLA, or Harvard) and provide complete and accurate information for each source in your references or works cited list.

Difference Between a Literature Review and An Annotated Bibliography

A literature review and an annotated bibliography are two distinct academic writing assignments that serve different purposes. 

A literature review aims to provide a comprehensive and critical analysis of the existing literature on a specific research topic. It involves summarizing, evaluating, and synthesizing the key findings, theories, and methodologies of relevant scholarly sources.

Annotated bibliographies, on the other hand, concentrate on giving a concise overview and evaluation (annotation) of each cited source. It tries to educate the reader about the sources’ quality, relevancy, and content. 

For more information on annotated bibliographies, you can visit the article here which provides a detailed explanation of what an annotated bibliography is and how to create one. 

While a literature review covers a broader range of literature and requires a deeper analysis, an annotated bibliography focuses on a narrower selection of sources and provides concise annotations for each entry.

By following the essential components of a literature review discussed in this article, researchers can ensure a high-quality review. Thorough planning, systematic searching, critical evaluation, organization, synthesis, analysis, and effective communication are key. Mastering these components enables researchers to contribute valuable insights and advance knowledge in their field. A well-executed literature review serves as the foundation for robust research and facilitates new discoveries.

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Jessica Abbadia is a lawyer that has been working in Digital Marketing since 2020, improving organic performance for apps and websites in various regions through ASO and SEO. Currently developing scientific and intellectual knowledge for the community's benefit. Jessica is an animal rights activist who enjoys reading and drinking strong coffee.

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How to write a literature review

What is a literature review.

The literature review is a written overview of major writings and other sources on a selected topic. Sources covered in the review may include scholarly journal articles, books, government reports, Web sites, etc. The literature review provides a description, summary and evaluation of each source. It is usually presented as a distinct section of a graduate thesis or dissertation.

Purpose of the literature review

The purpose of the literature review is to provide a critical written account of the current state of research on a selected topic:

• Identifies areas of prior scholarship
• Places each source in the context of its contribution to the understanding of the specific issue, area of research, or theory under review.
• Describes the relationship of each source to the others that you have selected
• Identifies new ways to interpret, and shed light on any gaps in, previous research
• Points the way forward for further research.

Components of the literature review

The literature review should include the following:

• Objective of the literature review
• Overview of the subject under consideration.
• particular position, those opposed, and those offering completely different arguments.
• Discussion of both the distinctiveness of each source and its similarities with the others.

Steps in the literature review process

Preparation of a literature review may be divided into four steps:

• Define your subject and the scope of the review.
• Search the library catalogue, subject specific databases and other search tools to find sources that are relevant to your topic.
• Read and evaluate the sources and to determine their suitability to the understanding of topic at hand (see the Evaluating sources section).
• Analyse, interpret and discuss the findings and conclusions of the sources you selected.

Evaluating sources

In assessing each source, consideration should be given to:

• What is the author's expertise in this particular field of study (credentials)?
• Are the author's arguments supported by empirical evidence (e.g. quantitative/qualitative studies)?
• Is the author's perspective too biased in one direction or are opposing studies and viewpoints also considered?
• Does the selected source contribute to a more profound understanding of the subject?

Examples of a published literature review

Literature reviews are often published as scholarly articles, books, and reports. Here is an example of a recent literature review published as a scholarly journal article:

Ledesma, M. C., & Calderón, D. (2015). Critical race theory in education: A review of past literature and a look to the future. Qualitative Inquiry, 21(3), 206-222. Link to the article

Additional sources on writing literature reviews

Further information on the literature review process may be found below:

• Booth, A., Papaioannou, D., & Sutton, A. (2012). Systematic approaches to a successful literature review
• Fink, A. (2010). Conducting research literature reviews: From the Internet to paper
• Galvin, J. (2006). Writing literature reviews: A guide for students of the social and behavioral sciences
• Machi, L. A., & McEvoy, B. T. (2012). The literature review: Six steps to success

Adapted with permission and thanks from How to Write a Literature Review originally created by Kenneth Lyons, McHenry Library, University of California, Santa Cruz.

Literature Reviews

• What is a Literature Review?
• Six Steps to Writing a Literature Review
• Finding Articles
• Try A Citation Manager
• Avoiding Plagiarism

Selecting a Research Topic 

The first step in the process involves exploring and selecting a topic. You may revise the topic/scope of your research as you learn more from the literature. Be sure to select a topic that you are willing to work with for a considerable amount of time.

When thinking about a topic, it is important to consider the following: 

Does the topic interest you?

Working on something that doesn’t excite you will make the process tedious. The research content should reflect your passion for research so it is essential to research in your area of interest rather than choosing a topic that interests someone else. While developing your research topic, broaden your thinking and creativity to determine what works best for you. Consider an area of high importance to your profession, or identify a gap in the research. It may take some time to narrow down on a topic and get started, but it’s worth the effort.

Is the Topic Relevant?

Be sure your subject meets the assignment/research requirements. When in doubt, review the guidelines and seek clarification from your professor. 

What is the Scope and Purpose?

Sometimes your chosen topic may be too broad. To find direction, try limiting the scope and purpose of the research by identifying the concepts you wish to explore. Once this is accomplished, you can fine-tune your topic by experimenting with keyword searches our  A-Z Databases  until you are satisfied with your retrieval results.

Are there Enough Resources to Support Your Research? 

If the topic is too narrow, you may not be able to provide the depth of results needed. When selecting a topic make sure you have adequate material to help with the research. Explore a variety of resources: journals, books, and online information. 

Adapted from https://jgateplus.com/home/2018/10/11/the-dos-of-choosing-a-research-topic-part-1/

Why use keywords to search? 

• Library databases work differently than Google. Library databases work best when you search for concepts and keywords.
• For your research, you will want to brainstorm keywords related to your research question. These keywords can lead you to relevant sources that you can use to start your research project.
• Identify those terms relevant to your research and add 2-3 in the search box. 

Now its time to decide whether or not to incorporate what you have found into your literature review.  E valuate  your resources to make sure they contain information that is authoritative, reliable, relevant and the most useful in supporting your research.

Remember to be:

• Objective : keep an open mind
• Unbiased : Consider all viewpoints, and include all sides of an argument,  even ones that don't support your own

Criteria for Evaluating Research Publications

Significance and Contribution to the Field

• What is the author’s aim?

• To what extent has this aim been achieved?

• What does this text add to the body of knowledge? (theory, data and/or practical application)

• What relationship does it bear to other works in the field?

• What is missing/not stated?

• Is this a problem?

Methodology or Approach (Formal, research-based texts)

• What approach was used for the research? (eg; quantitative or qualitative, analysis/review of theory or current practice, comparative, case study, personal reflection etc…)

• How objective/biased is the approach?

• Are the results valid and reliable?

• What analytical framework is used to discuss the results?

Argument and Use of Evidence

• Is there a clear problem, statement or hypothesis?

• What claims are made?

• Is the argument consistent?

• What kinds of evidence does the text rely on?

• How valid and reliable is the evidence?

• How effective is the evidence in supporting the argument?

• What conclusions are drawn?

• Are these conclusions justified?

Writing Style and Text Structure

• Does the writing style suit the intended audience? (eg; expert/non-expert, academic/non- academic)

• What is the organizing principle of the text?

• Could it be better organized?

Prepared by Pam Mort, Lyn Hallion and Tracey Lee Downey, The Learning Centre © April 2005 The University of New South Wales. 

Analysis: the Starting Point for Further Analysis & Inquiry

After evaluating your retrieved sources you will be ready to explore both what has been  found  and what is  missing . Analysis involves breaking the study into parts,  understanding  each part, assessing the  strength  of evidence, and drawing  conclusions  about its relationship to your topic. 

Read through the information sources you have selected and try to analyze, understand and critique what you read.  Critically  review each source's methods, procedures, data validity/reliability, and other themes of interest.  Consider  how each source approaches your topic in addition to their collective points of  intersection  and  separation .  Offer an appraisal of past and current thinking, ideas, policies, and practices, identify gaps within the research, and place your current work and research within this wider discussion by considering how your research supports, contradicts, or departs from other scholars’ research and offer recommendations for future research.

Top 10 Tips for Analyzing the Research

• Define key terms
• Note key statistics 
• Determine emphasis, strengths & weaknesses
• Critique research methodologies used in the studies
• Distinguish between author opinion and actual results
• Identify major trends, patterns, categories, relationships, and inconsistencies
• Recognize specific aspects in the study that relate to your topic
• Disclose any gaps in the literature
• Stay focused on your topic
• Excluding landmark studies, use current, up-to-date sources

Prepared by the fine librarians at California State University Sacramento. 

Synthesis vs Summary

Your literature review should not simply be a summary of the articles, books, and other scholarly writings you find on your topic. It should synthesize the various ideas from your sources with your own observations to create a map of the scholarly conversation taking place about your research topics along with gaps or areas for further research.

Bringing together your review results is called synthesis. Synthesis relies heavily on pattern recognition and relationships or similarities between different phenomena. Recognizing these patterns and relatedness helps you make  creative connections  between previously unrelated research and identify any gaps.

As you read, you'll encounter various ideas, disagreements, methods, and perspectives which can be hard to organize in a meaningful way.  A  synthesis matrix  also known as a Literature Review Matrix is an effective and efficient method to organize your literature by recording the main points of each source and documenting how sources relate to each other. If you know how to make an Excel spreadsheet, you can create your own synthesis matrix, or use one of the templates below. 

Because a literature review is NOT a summary of these different sources, it can be very difficult to keep your research organized. It is especially difficult to organize the information in a way that makes the writing process simpler. One way that seems particularly helpful in organizing literature reviews is the synthesis matrix. Click on the link below for a short tutorial and synthesis matrix spreadsheet.

• Literature Review and Synthesis
• Lit Review Synthesis Matrix
• Synthesis Matrix Example

A literature review must include a thesis statement, which is your perception of the information found in the literature. 

A literature review: 

• Demonstrates your thorough  investigation  of and acquaintance with sources related to your topic
• Is not a simple listing, but a  critical discussion
• Must  compare  and  contrast  opinions
• Must  relate  your study to previous studies
• Must show  gaps  in research
• Can  focus  on a research question or a thesis
• Includes a  compilation  of the primary questions and subject areas involved
• Identifies  sources

https://custom-writing.org/blog/best-literature-review

Organizing Your Literature Review

The structure of the review is divided into three main parts—an introduction, body, and the conclusion.

Introduction

Discuss what is already known about your topic and what readers need to know in order to understand your literature review. 

• Scope, Method, Framework: ​ Explain your selection criteria and similarities between your sources. Be sure to mention any consistent methods, theoretical frameworks, or approaches.  
• Research Question or Problem Statement:  State the problem you are addressing and why it is important. Try to write your research question as a statement. 
• Thesis : Address the connections between your sources, current state of knowledge in the field, and consistent approaches to your topic. 
• Format:  Describe your literature review’s organization and adhere to it throughout.   

​ Body 

The discussion of your research and its importance to the literature should be presented in a logical structure.

• Chronological: Structure your discussion by the literature’s publication date moving from the oldest to the newest research. Discuss how your research relates to the literature and highlight any breakthroughs and any gaps in the research.
• Historical: Similar to the chronological structure, the historical structure allows for a discussion of concepts or themes and how they have evolved over time.
• Thematic: Identify and discuss the different themes present within the research. Make sure that you relate the themes to each other and to your research.
• Methodological: This type of structure is used to discuss not so much what is found but how. For example, an methodological approach could provide an analysis of research approaches, data collection or and analysis techniques.

Provide a concise summary of your review and provide suggestions for future research.

Writing for Your Audience 

Writing within your discipline means learning:

• the  specialized vocabulary  your discipline uses
• the rhetorical conventions and  discourse  of your discipline
• the research  methodologies  which are employed

Learn how to write in your discipline by  familiarizing  yourself with the journals and trade publications professionals, researchers, and scholars use. 

Use our Databases by Title  to access:

• The best journals
• The most widely circulated trade publications
• The additional ways professionals and researchers communicate, such as conferences, newsletters, or symposiums.
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Components of a Literature Review

Edg 501 literature review: components of a literature review.

• Structure of a Literature Review
• Writing the Literature Review
• Databases and Searching Tips
• Examples/Writing Helps

Talk to a Librarian

Library links.

• Library Home
• Research Databases

Reference Desk 610.902.8537

The works that make up the literature review fall into three categories:  

General theoretical literature

• This literature establishes the importance of your topic/research.  define abstract concepts, discuss the relationships between abstract concepts, and include statistics about the problem being investigated.  Landmark and classic articles are also included.
• Encyclopedia of Education
• Encyclopedia of Curriculum Studies
• Encyclopedia of Educational Psychology
• 21st Century Education

Literature on related topic areas

• These sources identify general themes that run throughout the literature.   For example,  a  search on the topic of high stakes testing will find articles on high stakes testing and gender, socioeconomic status, inclusive education, cheating, and academic achievement.  

Resources for this literature (see below) : 

• Academic Search Complete This link opens in a new window
• PsycARTICLES This link opens in a new window
• PsycINFO This link opens in a new window

Literature specific to your research focus

• This literature is highly relevant.  The sources isolate the issues and highlight the findings you expected when you articulated your research question or formulated your hypothesis.    

Next Step: See  Writing the Literature Review

Qualitative and Quantitative Research

Qualitative research methods are tools for gathering information that does not take a numerical form that can be counted and otherwise manipulated mathematically. If I live with a group of women and men and observe that males tend to dominate conversations, for example, my results consist of an interpretation based on a set of observations that I summarize in an overall impression. As such, it is a qualitative assessment of what is going on. By contrast, if I systematically count how often men and women interact and then compare the totals, my method is quantitative, because it produces numerical results.

Qualitative methods are most closely associated with  participant observation ,  historical sociology ,  ethnomethodology ,  ethnography and ethnology . Quantitative methods are most closely associated with  surveys ,  experiments , and other forms of numerical  data  gathering. Although quantitative methods are often considered superior to socalled "soft" qualitative methods, most sociologists appreciate that each provides unique and valuable insights into the workings of social life that are beyond the reach of the other.

Qualitative and quantitative research methods. (2000). In A. G. Johnson, 

The Blackwell dictionary of sociology  (2nd ed.). Oxford, UK: Blackwell

Publishers. Retrieved from Credo Reference.

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Literature Reviews

• Introduction

Problem formulation

Conducting your literature review, evaluating the data, analysing the material.

• Resources on writing and research
• Citing and referencing
• You should think about your research topic and identify central areas and issues.
• Next you should compile a list of keywords to help you when searching for materials on your topic.

This involves sourcing the literature pertinent to your research topic. Material could be in any format such as books, journals, websites, multimedia sources etc. It is at this stage that the library will be most useful to you.

There are a number of library resources that might be useful to you when conducting your search:

• The library catalogue  – You can search the catalogue to find materials (books, journals etc) that are available in the library.
• Library Search - simultaneously searches the library catalogue PLUS online databases, online journals, ebooks, articles, and material freely available online. The library recommends that you use this comprehensive discovery search tool.
• Online databases– the library subscribes to a number of online databases covering a variety of subjects. These can be accessed through the library website on  Databases A-Z
• Journals. Journals in print format covering a number of subject disciplines are shelved to the left of the entrance to the library.
• Journals in electronic format and print can be searched for online by logging on to Publication Finder .   You can search by journal title, search within a particular journal for your topic, or browse by discipline.
• Library PC’s– there are a number of PC’s on the mezzanine level of the library where you can access the internet and look at web resources related to your topic.
• Library laptops are available to borrow for three hours within the library.

The resources that you find in the library or electronically could help you to find more material on your topic. Make sure to consult the bibliographies in books, journal article references and links pages on websites which will point you towards other useful material.

Before including any material that you have found in your literature review you must evaluate your results to ensure that the information you have found is relevant, accurate, reliable and current. There are a number of criteria you can use to decide this:

• what is the content of the source? ( look at contents pages, indexes, abstracts etc.)
• who are the intended audience? (books aimed at the general public may not be specific enough)
• Who is the author?
• What is the edition and publication date? (i.e. is the information recent)
• Is the source from a well regarded journal?
• Has the work been reviewed and what do they say?

You need to carefully evaluate web sources as they are not always reliable or accurate. Some other things to keep in mind when evaluating web sources are:

• what is the domain of the site? (i.e. is it an educational or government site or just someone’s home page),
• when was it last updated?
• Have reputable sites got links to this site?

At this stage you must read, interpret and structure the data that you have gathered and finally you must write the review. The review must consist of:

• An Introduction– here the topic should be specified, overall trends and conflicts in the literature should be outlined and gaps in previous research identified. It is also very important at this point to justify your reasons for writing the review.
• A body– this will be the bulk of the review and here you will discuss each piece of literature in turn. Research studies should be presented in a logical order e.g. chronological, thematically etc. Previous studies should be summarised and critically evaluated.
• A conclusion– discuss which studies have made the greatest contribution to the subject. Evaluate the current general state of research in this area and finally discuss the research opportunities in this area.
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• J Grad Med Educ
• v.8(3); 2016 Jul

The Literature Review: A Foundation for High-Quality Medical Education Research

a  These are subscription resources. Researchers should check with their librarian to determine their access rights.

Despite a surge in published scholarship in medical education 1 and rapid growth in journals that publish educational research, manuscript acceptance rates continue to fall. 2 Failure to conduct a thorough, accurate, and up-to-date literature review identifying an important problem and placing the study in context is consistently identified as one of the top reasons for rejection. 3 , 4 The purpose of this editorial is to provide a road map and practical recommendations for planning a literature review. By understanding the goals of a literature review and following a few basic processes, authors can enhance both the quality of their educational research and the likelihood of publication in the Journal of Graduate Medical Education ( JGME ) and in other journals.

The Literature Review Defined

In medical education, no organization has articulated a formal definition of a literature review for a research paper; thus, a literature review can take a number of forms. Depending on the type of article, target journal, and specific topic, these forms will vary in methodology, rigor, and depth. Several organizations have published guidelines for conducting an intensive literature search intended for formal systematic reviews, both broadly (eg, PRISMA) 5 and within medical education, 6 and there are excellent commentaries to guide authors of systematic reviews. 7 , 8

• A literature review forms the basis for high-quality medical education research and helps maximize relevance, originality, generalizability, and impact.
• A literature review provides context, informs methodology, maximizes innovation, avoids duplicative research, and ensures that professional standards are met.
• Literature reviews take time, are iterative, and should continue throughout the research process.
• Researchers should maximize the use of human resources (librarians, colleagues), search tools (databases/search engines), and existing literature (related articles).
• Keeping organized is critical.

Such work is outside the scope of this article, which focuses on literature reviews to inform reports of original medical education research. We define such a literature review as a synthetic review and summary of what is known and unknown regarding the topic of a scholarly body of work, including the current work's place within the existing knowledge . While this type of literature review may not require the intensive search processes mandated by systematic reviews, it merits a thoughtful and rigorous approach.

Purpose and Importance of the Literature Review

An understanding of the current literature is critical for all phases of a research study. Lingard 9 recently invoked the “journal-as-conversation” metaphor as a way of understanding how one's research fits into the larger medical education conversation. As she described it: “Imagine yourself joining a conversation at a social event. After you hang about eavesdropping to get the drift of what's being said (the conversational equivalent of the literature review), you join the conversation with a contribution that signals your shared interest in the topic, your knowledge of what's already been said, and your intention.” 9

The literature review helps any researcher “join the conversation” by providing context, informing methodology, identifying innovation, minimizing duplicative research, and ensuring that professional standards are met. Understanding the current literature also promotes scholarship, as proposed by Boyer, 10 by contributing to 5 of the 6 standards by which scholarly work should be evaluated. 11 Specifically, the review helps the researcher (1) articulate clear goals, (2) show evidence of adequate preparation, (3) select appropriate methods, (4) communicate relevant results, and (5) engage in reflective critique.

Failure to conduct a high-quality literature review is associated with several problems identified in the medical education literature, including studies that are repetitive, not grounded in theory, methodologically weak, and fail to expand knowledge beyond a single setting. 12 Indeed, medical education scholars complain that many studies repeat work already published and contribute little new knowledge—a likely cause of which is failure to conduct a proper literature review. 3 , 4

Likewise, studies that lack theoretical grounding or a conceptual framework make study design and interpretation difficult. 13 When theory is used in medical education studies, it is often invoked at a superficial level. As Norman 14 noted, when theory is used appropriately, it helps articulate variables that might be linked together and why, and it allows the researcher to make hypotheses and define a study's context and scope. Ultimately, a proper literature review is a first critical step toward identifying relevant conceptual frameworks.

Another problem is that many medical education studies are methodologically weak. 12 Good research requires trained investigators who can articulate relevant research questions, operationally define variables of interest, and choose the best method for specific research questions. Conducting a proper literature review helps both novice and experienced researchers select rigorous research methodologies.

Finally, many studies in medical education are “one-offs,” that is, single studies undertaken because the opportunity presented itself locally. Such studies frequently are not oriented toward progressive knowledge building and generalization to other settings. A firm grasp of the literature can encourage a programmatic approach to research.

Approaching the Literature Review

Considering these issues, journals have a responsibility to demand from authors a thoughtful synthesis of their study's position within the field, and it is the authors' responsibility to provide such a synthesis, based on a literature review. The aforementioned purposes of the literature review mandate that the review occurs throughout all phases of a study, from conception and design, to implementation and analysis, to manuscript preparation and submission.

Planning the literature review requires understanding of journal requirements, which vary greatly by journal ( table 1 ). Authors are advised to take note of common problems with reporting results of the literature review. Table 2 lists the most common problems that we have encountered as authors, reviewers, and editors.

Sample of Journals' Author Instructions for Literature Reviews Conducted as Part of Original Research Article a

Common Problem Areas for Reporting Literature Reviews in the Context of Scholarly Articles

Locating and Organizing the Literature

Three resources may facilitate identifying relevant literature: human resources, search tools, and related literature. As the process requires time, it is important to begin searching for literature early in the process (ie, the study design phase). Identifying and understanding relevant studies will increase the likelihood of designing a relevant, adaptable, generalizable, and novel study that is based on educational or learning theory and can maximize impact.

Human Resources

A medical librarian can help translate research interests into an effective search strategy, familiarize researchers with available information resources, provide information on organizing information, and introduce strategies for keeping current with emerging research. Often, librarians are also aware of research across their institutions and may be able to connect researchers with similar interests. Reaching out to colleagues for suggestions may help researchers quickly locate resources that would not otherwise be on their radar.

During this process, researchers will likely identify other researchers writing on aspects of their topic. Researchers should consider searching for the publications of these relevant researchers (see table 3 for search strategies). Additionally, institutional websites may include curriculum vitae of such relevant faculty with access to their entire publication record, including difficult to locate publications, such as book chapters, dissertations, and technical reports.

Strategies for Finding Related Researcher Publications in Databases and Search Engines

Search Tools and Related Literature

Researchers will locate the majority of needed information using databases and search engines. Excellent resources are available to guide researchers in the mechanics of literature searches. 15 , 16

Because medical education research draws on a variety of disciplines, researchers should include search tools with coverage beyond medicine (eg, psychology, nursing, education, and anthropology) and that cover several publication types, such as reports, standards, conference abstracts, and book chapters (see the box for several information resources). Many search tools include options for viewing citations of selected articles. Examining cited references provides additional articles for review and a sense of the influence of the selected article on its field.

Box Information Resources

• Web of Science a
• Education Resource Information Center (ERIC)
• Cumulative Index of Nursing & Allied Health (CINAHL) a
• Google Scholar

Once relevant articles are located, it is useful to mine those articles for additional citations. One strategy is to examine references of key articles, especially review articles, for relevant citations.

Getting Organized

As the aforementioned resources will likely provide a tremendous amount of information, organization is crucial. Researchers should determine which details are most important to their study (eg, participants, setting, methods, and outcomes) and generate a strategy for keeping those details organized and accessible. Increasingly, researchers utilize digital tools, such as Evernote, to capture such information, which enables accessibility across digital workspaces and search capabilities. Use of citation managers can also be helpful as they store citations and, in some cases, can generate bibliographies ( table 4 ).

Citation Managers

Knowing When to Say When

Researchers often ask how to know when they have located enough citations. Unfortunately, there is no magic or ideal number of citations to collect. One strategy for checking coverage of the literature is to inspect references of relevant articles. As researchers review references they will start noticing a repetition of the same articles with few new articles appearing. This can indicate that the researcher has covered the literature base on a particular topic.

Putting It All Together

In preparing to write a research paper, it is important to consider which citations to include and how they will inform the introduction and discussion sections. The “Instructions to Authors” for the targeted journal will often provide guidance on structuring the literature review (or introduction) and the number of total citations permitted for each article category. Reviewing articles of similar type published in the targeted journal can also provide guidance regarding structure and average lengths of the introduction and discussion sections.

When selecting references for the introduction consider those that illustrate core background theoretical and methodological concepts, as well as recent relevant studies. The introduction should be brief and present references not as a laundry list or narrative of available literature, but rather as a synthesized summary to provide context for the current study and to identify the gap in the literature that the study intends to fill. For the discussion, citations should be thoughtfully selected to compare and contrast the present study's findings with the current literature and to indicate how the present study moves the field forward.

To facilitate writing a literature review, journals are increasingly providing helpful features to guide authors. For example, the resources available through JGME include several articles on writing. 17 The journal Perspectives on Medical Education recently launched “The Writer's Craft,” which is intended to help medical educators improve their writing. Additionally, many institutions have writing centers that provide web-based materials on writing a literature review, and some even have writing coaches.

The literature review is a vital part of medical education research and should occur throughout the research process to help researchers design a strong study and effectively communicate study results and importance. To achieve these goals, researchers are advised to plan and execute the literature review carefully. The guidance in this editorial provides considerations and recommendations that may improve the quality of literature reviews.

• Open access
• Published: 26 June 2024

WHO, WHEN, HOW: a scoping review on flexible at-home respite for informal caregivers of older adults

• Maude Viens 1 , 2 ,
• Alexandra Éthier 1 , 2 ,
• Véronique Provencher 1 , 2 &
• Annie Carrier 1 , 2  

BMC Health Services Research volume  24 , Article number:  767 ( 2024 ) Cite this article

122 Accesses

Metrics details

As the world population is aging, considerable efforts need to be put towards developing and maintaining evidenced-based care for older adults. Respite services are part of the selection of homecare offered to informal caregivers. Although current best practices around respite are rooted in person centeredness, there is no integrated synthesis of its flexible components. Such a synthesis could offer a better understanding of key characteristics of flexible respite and, as such, support its implementation and use.

To map the literature around the characteristics of flexible at-home respite for informal caregivers of older adults, a scoping study was conducted. Qualitative data from the review was analyzed using content analysis. The characterization of flexible at-home respite was built on three dimensions: WHO , WHEN and HOW . To triangulate the scoping results, an online questionnaire was distributed to homecare providers and informal caregivers of older adults.

A total of 42 documents were included in the review. The questionnaire was completed by 105 participants. The results summarize the characteristics of flexible at-home respite found in the literature. Flexibility in respite can be understood through three dimensions: (1) WHO is tendering it, (2) WHEN it is tendered and (3) HOW it is tendered. Firstly, human resources ( WHO ) must be compatible with the homecare sector as well as being trained and qualified to offer respite to informal caregivers of older adults. Secondly, flexible respite includes considerations of time, duration, frequency, and predictability ( WHEN ). Lastly, flexible at-home respite exhibits approachability, appropriateness, affordability, availability, and acceptability ( HOW ). Overall, flexible at-home respite adjusts to the needs of the informal caregiver and care recipient in terms of WHO , WHEN , and HOW .

This review is a step towards a more precise definition of flexible at-home respite. Flexibility of homecare, in particular respite, must be considered when designing, implementing and evaluating services.

Peer Review reports

It is an undeniable fact that the world population is aging [ 1 ]. The World Health Organization [ 1 ] estimates that from 2015 to 2050, the percentage of people over 60 years of age will nearly double (from 12 to 22%). Governments must therefore put in place policies, laws and funding infrastructures to provide evidence-based social services and healthcare that are in line with best practices to allow people to age in place [ 2 ]. Aging in place refers to “the ability to live in one’s own home and community safely, independently, and comfortably, regardless of age, income, or ability level” [ 3 ]. Relevant literature indicates that people do not want to age or end their lives in institutionalized care; most wish to receive care in their home and remain in their community with their informal caregivers [ 4 ].

There is then a need to adequately support informal caregivers (caregiver) in the crucial role that they have in allowing older adults to age in their own home. A caregiver is “a person who provides some type of unpaid, ongoing assistance with activities of daily living or instrumental activities of daily living” [ 5 ]. In their duties, caregivers of older adults are responsible for a considerable amount of homecare [ 6 ]: Transportation, management of appointments and bills, domestic chores, etc. Private and public organizations offer a plethora of services to support caregivers of older adults (e.g., support groups, housekeeping, etc.), including respite. Respite is a service for caregivers consisting in “the temporary provision of care for a person, at home or in an institution, by people other than the primary caregiver” [ 7 ]. Maayan and collaborators [ 7 ] characterize all respite services according to three dimensions: (1) WHERE : The place; in a private home, a daycare centre or a residential setting, (2) WHEN : The duration and planning; ranging from a couple of hours to a number of weeks, planned or unplanned, and finally, (3) WHO : The person providing the service; this may be trained or untrained individuals, paid staff or volunteers. Respite is widely recognized as necessary to support caregivers of older adults [ 8 , 9 ]. Indeed, a large number of studies identify the need and use for respite [ 9 , 10 , 11 , 12 ]. For example, Dal Santo and colleagues (2007) found that caregivers of older adults ( n  = 1643) used respite to manage stressful caregiving situations, but also to have a “time away”, without having to worry about their caregiving role [ 13 ]. At-home respite seems to be favoured over other forms of respite, even with the perceived drawbacks, such as the privacy breach of having a care worker in one’s home [ 14 , 15 ].

Studies suggest that caregivers of older adults seek flexibility as a main component of respite [ 16 , 17 , 18 ]. Flexibility, in line with person-centered care, allows respite that addresses their needs, rather than being services that are prescribed according to other criteria [ 16 , 17 ]. Thus, flexibility, both in accessing and in the respite itself, is essential [ 19 , 20 , 21 , 22 , 23 ]. Although there seems to be a consensus around the broader definition of respite, there is no literature reviewing the characteristics of flexible at-home respite. Some studies and reports from organizations and governments document the flexible characteristics of their models, but there are few literature reviews that address them, specifically [ 18 , 22 , 24 ]. Both reviews by Shaw et al. [ 18 ] and Neville et al. [ 19 ] concede that an operational definition of respite ( WHEN , WHERE , WHO ) is not clear. Neville et al. [ 19 ] conclude that “respite has the potential to be delivered in flexible and positive ways”, without addressing these ways. The absence of a unified definition for flexible at-home respite contributes to the challenges of implementing and evaluating services, as well as measuring their effect. Although respite services are deemed necessary, they are seldom used [ 19 , 25 , 26 , 27 ]; as little as 6% of all caregivers receiving any kind support services in Canada actually use them. In scientific literature, the under-usage of respite services is a shared reality around the world [ 28 ]. One of the main reasons for this under-usage is the overall lack of flexibility in both obtaining and using respite [ 29 , 30 ]. Synthesizing the characteristics of flexible at-home respite services is the first steppingstone to a common operational definition. This could contribute to increasing respite use through the implementation or enrichment of programs in ways that answer the dyad’s (caregiver and older adult) needs.

Consequently, to support the implementation and evaluation of homecare programs, the objective of this study was to synthesize the knowledge on the characteristics of flexible at-home respite services offered to caregivers of older adults.

A scoping review [ 32 , 33 , 34 ] was conducted, as part of a larger multi-method participatory research known as the AMORA project [ 31 ] to characterize flexible at-home respite. Scoping reviews allow to map the extent of literature on a specific topic [ 32 , 34 ]. The six steps proposed by Levac et al. [ 32 ] were followed: [ 1 ] Identifying the research question; [ 2 ] searching and [ 3 ] selecting pertinent documents; [ 4 ] extracting ( or charting ) relevant data; [ 5 ] collating, summarizing and reporting findings; [ 6 ] consultation with stakeholders. The sixth step is optional.

Identifying the research question

The research question was: “What are the characteristics of flexible at-home respite services offered to caregivers of older adults?” As the research was conducted, this question was divided into three sub-questions:

WHO is tendering flexible respite?

WHEN is flexible respite tendered?

HOW is flexible respite tendered?

Identifying relevant documents

The search strategy consisted of two methods. First, the key words (1) respite (2) informal caregivers (3) older adults in the title or abstract allowed to identify relevant documents (Table  1 ). Initially included, the term “ flexib *” was removed from the search, given the low number generated (60 versus 1,179 documents without). The first author and a librarian specialized in health sciences research documentation conducted the literature research in July of 2021 and updated it in December of 2022 in 6 databases ( Ageline , Cochrane , CINAHL , Medline , PsychInfo , and Abstracts in Social Gerontology ). The expanded research strategy then consisted of the identification of relevant documents from the selected bibliography and one article that was found by searching for unavailable references (alternative article).

Study selection

To review the most recent literature on flexible at-home respite service characteristics, the research team focused on writings within a 20-year span, as have other reviews (e.g., [ 35 , 36 ]); documents thus had to be published between 2001 and 2022. The research team selected documents written in French or English, only. Included documents had to come from either (1) scientific literature (i.e., articles in an academic journal presenting an empirical study or reviews) or (2) reports and briefs from government, homecare organizations or research centres. All study designs were included. The research team convened that at-home respite is an (1) individual (i.e., not in a group) service (although, theoretically, two persons living in the same household could receive it) from (2) a professional or a volunteer that occurs (3) in the home and that (4) it requires no transport for the dyad. To select documents related to flexible at-home respite, the research team identified those in which the respite displayed an ability to adapt to the dyad’s needs on at least one characteristic of the service, as presented by Maayan and collaborators ( WHERE [Not relevant to this review, as it focuses on at-home respite] , WHO , WHEN ). The team concluded that these three dimensions lacked the precision to globally characterize the service. Indeed, they did not describe access to or activities occurring during respite, or, as the team called it, the HOW (Fig.  1 ). Excluded documents were those covering several services at once, preventing the differentiation of elements that were specific to at-home respite services. As this is a scoping review, the research team did not include a critical appraisal of individual sources of evidence [ 32 , 34 ].

Following the step-by-step Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMAScR) guidelines [ 37 ], the research team met to define the selection strategy. First, they screened the documents by their titles and abstracts, before determining their eligibility, based on their full text. Considering the limited human and financial resources, at each step of the PRISMAScR, a second team member assessed 10% of the documents independently to co-validate the selection; the goal was to reach 80% of agreement between both team members regarding document inclusion or exclusion. If an agreement was not reached, they would meet to obtain a consensus. The research team used Zotero reference management software to store documents as well as a cloud-based website to collaborate on the selection.

Conceptual mapping of results: HOW , WHEN , WHO

Charting the data

The first author charted (or extracted) both quantitative and qualitative data. To quantitatively characterize documents, contextual data (country of origin, year of publication, type of documents, etc.) was extracted in a Microsoft Excel table. For the qualitative data, the research team created an extraction table in Microsoft Word that included the three dimensions of respite ( WHO , WHEN and HOW) and one “ other ” dimension, as to not force any excerpts under the three dimensions. To co-validate the data charting, the second and third authors replicated 10% of the process. Expressly, the first author extracted elements related to a flexible characteristic of the at-home respite ( WHO , WHEN , HOW or other ). Considering limited resources, the third and second authors both co-validated the extraction of 10% of the documents. Authors met to reach a consensus where a disagreement arose.

Collating, summarizing, and reporting the results

The research team used content analysis to “attain a condensed and broad description of the phenomenon” [ 38 ]. To do so, data was prepared (familiarization with the data and extraction of pertinent excerpts) and organized (classification of excerpts) to build a characterization of flexible at-home respite. In this scoping review, a deductive content analysis began with three main categories ( WHO , WHEN , HOW ), with the addition of the temporary “ other ” category. Content analysis aimed to divide these categories into several generic categories, which subdivided into sub-categories (Fig.  2 ), inductively. This allowed to define the three main categories. While the WHO and the WHEN categories describe the service itself (time, duration, qualified staff, etc.), the HOW category is specific to the interface between the organization offering respite and the dyad (assessing the needs of the dyad, coordinating care, etc.). An interface is a situation where two “subjects” interact and affect each other [ 39 ]. In the context of homecare services, Levesque, Harris and Russell (2013) have defined that interface as access [ 40 ]. Therefore, to define the generic categories of the HOW , the team used the five dimensions of their access to care framework: Approachability, appropriateness, affordability, availability and acceptability [ 40 ]. Approachability relates to users recognizing the existence and accessibility of a service [ 40 ]. Appropriateness encompasses the alignment between services and users’ needs, considering timeliness and assessment of needs [ 40 ]. Affordability pertains to users’ economic capacity to allocate resources for accessing suitable services [ 40 ]. Availability signifies that services can be reached, both physically and in a timely manner [ 40 ]. Acceptability involves cultural and social factors influencing users’ willingness to accept services [ 40 ]. In other words, the HOW category focuses on the organizational or professional aspects of the service and how they can be adapted to the dyad.

To co-validate the classification, the research team met until they were all satisfied with the categorization. The first author then completed the classification. After classifying 20% of the documents, the second author would comment the classification. When the authors reached an agreement, the first author would move on to the classification of another 20%. First and second authors would meet when disagreements about classification and categories arose, to confer and adjust. Finally, all categories were discussed with the third author, until a consensus was reached. Once categorization was achieved, the team prepared a synthesis report. In this report, the team defined the main categories ( WHO , WHEN, HOW , other ) and their generic and sub-categories (Fig.  2 ) with pertinent excerpts from the reviewed literature. In summary, the results of the scoping review characterize flexible at-home respite under three attributes: WHO , WHEN and HOW .

Content analysis: Types of categories according to Elo and Kyngäs (2007) ( with examples from results )

Consultation

Rather than conducting a focus group as suggested by Levac and collaborators [ 32 ], the team chose to triangulate the results with those from a survey as a consultation strategy. Specifically, the research team took advantage of a survey being conducted with relevant stakeholders in the larger study (AMORA project), as it allowed to respect the scoping review’s allocated resources. The survey aimed to define flexible at-home respite and the factors affecting its implementation and delivery. A committee including a researcher, a doctoral student and a representative of an organization funding homecare services in Québec (Canada), developed the survey following the three stages proposed by Corbière and Fraccaroli [ 41 ]. It originally included a total of 21 items: Thirteen [ 13 ] close-ended and 8 open-ended questions. Of these 8, 2 addressed the characteristics of an ideal at-home service and suggestions regarding respite and were used here for triangulation purposes. The questionnaire was published online, in French, on the Microsoft Forms ® platform in the summer of 2020. Recruitment of participants (caregivers and people from the homecare sector) was done via email, by contacting regional organizations (Eastern Townships, Québec, Canada). In addition, the 18 senior consultation tables spread throughout the territory of the province of Québec were solicited; working in collaboration with governmental instances in charge of services to older adults and caregivers, these tables bring together representatives for associations, groups or organizations concerned with their living conditions.

The goal was to triangulate the scoping review’s results, i.e., to identify what was common between the literature and real-world experiences, and, as such, to bring contextual value to the results. Accordingly, the team analyzed data using mixed categorization [ 42 ]. The categories from the scoping review served as a starting point (closed categorization), leaving room to create new categories, as the analysis progressed (open categorization). Once all the data (scoping and survey) was categorized, the team identified the characteristics according to sources. To do so, the team tabulated the reoccurrence of each category in the survey, in the scoping review, or in both. They then integrated the results to provide one unified categorization of flexible at-home respite. The AMORA project was approved by the research ethics committee of the Integrated University Health and Social Services Centre (CIUSSS) of the Eastern Townships (project number: 2021–3703).

Of the 1,301 papers retrieved through the database searches, 1,146 were not eligible based on title and abstract, while 116 were excluded after reading their full texts, resulting in 39 included documents (Fig.  3 ). Documents were mainly excluded because they did not provide details about the respite service and its flexibility. The expanded search yielded three additional documents, resulting in a total of 42 documents, included in this scoping review. This section details (1) the characteristics of the selected documents and (2) the characterization of flexible at-home respite.

Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMAScR) flow chart of the scoping review process [ 37 ]

Characteristics of selected documents

The majority (86%) of the documents in the review (Table  2 ) are from after 2005, with only 14% of the documents published before 2005, and are from 9 countries; United States ( n  = 18; 42%), United Kingdom ( n  = 11; 26%), Australia ( n  = 4; 10%), Canada ( n  = 2; 5%), Ireland ( n  = 2; 5%), France ( n  = 2; 5%), Belgium ( n  = 2; 5%), Germany ( n  = 1; 2%), New Zealand ( n  = 1). The types of documents were diverse: 68% ( n  = 28) were empirical studies, 31% ( n  = 13) theoretical papers and 1% ( n  = 2) government briefs. Most ( n  = 23; 56%) of the documents did not specify their research approach, while 10 and 9 took, respectively, a qualitative (23%) or quantitative approach (21%). Most documents address respite in the context of caregiving for someone living with Alzheimer’s disease or other neurocognitive disorders ( n  = 25; 60%), while some targeted older adults in general ( n  = 14; 34%), people in palliative care ( n  = 4; 9%) or other older adult populations (for example, veterans) ( n  = 3; 1%). Respite was usually tendered by community organizations specialized in homecare ( n  = 32; 78%). Although the majority of the documents ( n  = 31; 75%) did not address the type of region (rural, urban, or mixed) surrounding the caregivers, those who did ( n  = 11; 26%) mainly reported being in a mixed environment ( n  = 9; 21%).

Characteristics of survey participants

Although all 100 participants completed the questionnaire, 71 participants answered at least 1 of the 2 open-ended questions: Each question had 66 and 41 answers. Of those 71 participants, most of them were women ( n  = 60; 85%). All participants were aged on average 55 years old (SD = 15). They were mostly from the Eastern Townships area ( n  = 56; 79%). Most participants were either caregivers ( n  = 24; 34%) or homecare workers ( n  = 28; 39%), while some were service administrators ( n  = 11; 15%), and some reported being both caregivers as well as working in the formal caregiving sector ( n  = 7; 10%). Only one person reported themselves as an older adult having a caregiver.

Characterization of flexible at-home respite

The characterization of flexible at-home respite will be presented below in three main categories which are WHO , WHEN , and HOW . Of note, 10 (24%) of the included documents had three categories of flexible components, 16 (38%) had 2 categories and 1 category. Almost all documents discussed the HOW of flexible at-home respite ( n  = 40, 95%). Out of the 33 categories constructed with the scoping review, only 6 (18%) were not reported in the questionnaire: (1) planned respite ( WHEN ), (2) screening of dyads ( HOW ), (3) determining frequency of respite ( HOW ), (4) coordination of care ( HOW ), (5) voucher approach ( HOW ) and (6) acceptability to low-income households ( HOW ). Moreover, the questionnaire added three characteristics that were not present in the scoping review: (1) respite needs to be approachable, (2) the organization must be prompt** and adhocratic** and (3) able to deliver respite regardless of the season** (availability). Generic or sub-categories present only in the scoping review are identified with 1 asterisk (*), while those present only in the questionnaire have 2 (**).

In the selected documents, the WHO dimension of flexible at-home respite services can be broken down into three qualifiers: (1) Compatible , (2) qualified and (3) trained (Table  3 ). This dimension includes all human resources contributing to homecare (administrative staff, governing bodies, paid and volunteer care workers). First, the workforce behind flexible respite is compatible , meaning it has personal characteristics and profiles relevant to homecare for caregivers of older adults [ 17 , 53 , 62 , 63 , 68 ]. Gendron and Adam explain this by describing how the role of the care worker in Baluchon Alzheimer™ goes beyond training: “The nature of their work with [Baluchon Alzheimer™] requires particular human and professional qualities that are quite as important as academic credentials” [ 53 ]. Personal characteristics such as flexibility [ 53 , 62 , 63 , 68 ], empathy and patience [ 17 , 53 , 62 ] are deemed essential attributes. Secondly, the workforce is qualified : It has the necessary skills, abilities and knowledge from past professional [ 14 , 45 , 62 , 70 ] and personal experience [ 62 ] to work, or volunteer, with caregivers of older adults. For a program like Baluchon Alzheimer™, “the backgrounds of the baluchonneuses vary […]; all have experience in gerontology” [ 53 ]. Other areas of qualification in the included documents are a nursing background [ 18 , 45 ] or knowledge related to dementia [ 69 ]. Finally, flexible at-home respite requires a trained workforce engaged in the process of acquiring knowledge and learning the skills to provide respite services to caregivers of older adults. For example, homecare organizations can offer specific training on various topics, depending on their target clientele: Dementia [ 44 ], palliative care [ 59 ], or homecare in general [ 44 ].

The WHEN dimension of flexible at-home respite contains 4 temporal features: (1) Time , (2) duration , (3) frequency and (4) predictability (Table  4 ). First, flexible respite is available on a wide range of possible time slots. For example, the service is “available 24 hours, but typically from 9 am to 10 pm” [ 64 ]. Secondly, flexible respite is accessible on a wide range of possible durations . The Community Dementia Support Service (CDSS) is an example of flexibility in duration by “[being] totally flexible, being available from 2 to 15 hours per week” [ 69 ]. Thirdly, the service is offered in different frequencies : It can be either recurrent or occasional, or a combination of both [ 18 , 64 , 66 ]. The last feature of the WHEN dimension is flexibility in predictability ; the respite service can be planned* or not. A study on respite services in South Australia found that most providers (93%) planned the respite care with the dyad, but that emergency or crisis services were still offered by 35% of them [ 50 ].

At-home respite is flexible when it demonstrates approachability : Caregivers can identify that some form of respite exists and can be reached (Table  5 ). For the respite service to be approachable, the organization needs to be reaching out to dyads; it proactively makes sure that caregivers of older adults have information on services, know of their existence and that they can be used. For example, the El Portal program put in place “advisory groups that included the local clergy, representatives from businesses, caregivers, and service providers who were used for outreach work” [ 66 ]. The organization also screens* dyads to assess their eligibility for respite, as well as for other services from the same program or organization. For example, the North Carolina (U.S.A.) Project C.A.R.E. has an initial assessment that considers the range of homecare services available, rather than just assessing for eligibility for a program [ 57 ]. In addition, flexible respite requires the organization to set attainable and inclusive requirements for eligibility, as to not discourage use [ 24 , 57 , 61 , 66 ]. Finally, the organization communicates consistently with the dyad. As Shanley explains in their literature review, “there are clear and open ways for carers to express concerns about the service, and an open mechanism is available for dealing with these concerns constructively” [ 17 ]. In addition, the survey participants discussed two other characteristics. First, for respite to be approachable, the organization is prompt**, respecting a reasonable delay between the request and the beginning of the service (wait list). Second, it is adhocratic**, meaning the organization does not depend on complex systems of rules and procedures to operate i.e., bureaucracy.

The second access dimension of flexible at-home respite is appropriateness (Table  6 ): The fit between respite services and the dyad’s needs, its timeliness, the amount of care spent in assessing their needs and determining the correct respite service. For the respite service to be appropriate, the organization assesses needs by collecting details about the dyad’s needs; this can include, but is not limited to, clinical, psychological, or social evaluation. The organization then proposes respite services from a wide range of options or packages: A multi-respite package, as presented by Arksey et al., can simply be the combination of at least two different respite services [ 44 ]. For the service to be appropriate, the organization also paces the respite. Apprehension towards service appropriateness can be mitigated by a gradual introduction to homecare, for example when the respite is presented as a trial [ 68 ]. The organization determines the service with the dyad and defines its different characteristics ( WHEN * , WHO ) so interventions correspond to their needs. The organization then determines the appropriate activities to do with the dyad during the respite. For example, the caregiver of older adults can be encouraged to use respite time for leisure (sleep, physical activity, etc.) [ 45 ], while the care worker supports the beneficiary in engaging in an activity such as a walk or a board game [ 14 ]. Furthermore, the organization coordinates* the services for the dyad and acts as a “respite broker” to arrange all aspects of care; this is especially relevant for programs that include a “care budget” that can be used at the caregivers’ discretion [ 58 ]. Finally, for the respite to be appropriate, the organization assures that it is in continuity with other health services, by connecting the dyads to pertinent resources. As described by Shaw, respite should be “embedded in a context that includes assessment, carer education, case management and counselling” [ 18 ].

The third access dimension of flexible at-home respite is affordability , referring to the economic capacity of the dyad to spend resources to use appropriate respite services (Table  7 ). The included documents only explored the direct cost of respite: The amount of money a dyad must pay to receive services. For the respite to be affordable, its direct cost is either (1) adapted, where the cost is modulated according to the dyad’s financial resources, for example on a sliding scale, based on income or (2) nonexistent [ 44 ].

Next, flexible at-home respite must demonstrate availability (Table  8 ): Services can be reached both physically and in a timely manner. Firstly, the organization offers respite in the dyads’ geographic area. Shanley described an at-home mobile respite program designed to reach rural and remote areas, where two care workers visit different locations for set periods of time [ 17 ]. Moreover, one sub-characteristic identified exclusively by the survey participants was seasonality. Indeed, the dyad has access to respite, regardless of the season**. Thus, the geography category is broken down between the access to service (1) in rural or remote areas and (2) notwithstanding the season. Flexibility in availability also requires that the dyads have access to unlimited respite time; the organization does not assign a finite bank of hours. Finally, the organization proposes diverse payment methods to the dyads. The consumer-directed approach is a way that homecare organizations offer flexibility. A care budget is allocated to the caregiver to purchase hours from homecare agencies or to hire their own respite workers. This includes payments to family members or friends to provide respite care [ 79 ]. An example of a type of consumer-directed approach is the use of vouchers*: Credit notes or coupons to purchase service hours from homecare agencies [ 44 ].

Finally, access to flexible at-home respite also relates to acceptability (Table  9 ): The cultural and social factors determining the possibility for the dyad to accept respite and the perception of the appropriateness of seeking services. For the respite to be acceptable, the organization targets and caters to the cultural diversity represented in their local population. The organization is also able to identify and to accommodate underserved groups. In the included documents, underserved groups lacked access to respite for two reasons: (1) Geographic isolation or (2) the requirements to be eligible to “traditional homecare” does not apply to them, for example, for younger people with dementia and people with HIV/AIDS [ 17 ]. The organization can target and cater to low-income households*. Rosenthal Gelman and his collaborators detail a program where, after realizing that low-income caregivers have greater unmet needs, special funds were set aside for respite care vouchers to be distributed [ 70 ].

This scoping review conducted with Levac and colleagues’ method [ 32 ] synthesized the knowledge on the characteristics of flexible at-home respite services offered to caregivers of older adults, from 42 documents. The results provide a synthesis of the characteristics of flexible at-home respite discussed in the literature. The three dimensions of flexibility in respite relate to (1) WHO is tendering it, (2) WHEN it is tendered and (3) HOW it is tendered. First, human resources ( WHO ) must be compatible with the homecare sector as well as being trained and qualified to offer respite to caregivers of older adults. The second feature of flexible respite is temporality ( WHEN ): The time, duration, frequency, and predictability of the service. The last dimension, access ( HOW ), refers to the interface between the respite and the users. Flexible at-home respite exhibits approachability, appropriateness, affordability, availability, and acceptability. In the light of what we learned, flexible at-home respite could be characterized as a service that has the ability to adjust to the needs of the dyad on all three dimensions ( W HO , WHEN , HOW ). However, this seems to be more of an ideal than a reflection of reality.

The survey provided complementary results to the review; the concordance between the two is strong (27/33 = 82%). Six [ 6 ] characteristics were missing from the survey results, including planned respite and the voucher approach ( HOW ). Moreover, the survey added three elements to the review results: The organization’s adhocracy ( HOW ) and promptness ( HOW ) as well as its ability to offer services, regardless of the season ( HOW ). These mismatches might reflect the Québec (and possibly Canadian) landscape of homecare. For example, in the Québec homecare system, respite is mostly planned, it is therefore not surprising that people only mention that unplanned respite is lacking. The “voucher system” was not mentioned in the survey, probably in part because it does not exist in the province of Québec. Additionally, navigating the healthcare system to have free or affordable homecare can be treacherous [ 80 ]. In short, older adults have to go through (1) evaluation(s) by a social worker from a hospital or another public healthcare organization and (2) various administrative tasks ( adhocratic ) [ 2 ], before possibly being put on a waiting list ( prompt ) [ 81 ]. In addition, Canada can experience harsh winters ( seasonality ) that can make transport, which is an integral part of homecare, particularly laborious. Although those categories could reflect the particularity of homecare in Canada, a promising follow up on this review would be to compare the characteristics of flexible respite from one territory to another. It would contribute to providing a more operational definition of flexible at-home respite.

The remainder of this discussion will focus on two main points before touching on the limitations and strengths of this review. First, flexibility in at-home respite seems exceptional. Second, respite care workers are as skilled as they are underappreciated.

This review, in coherence with the literature, highlights the fact that respite services generally lack flexibility: This is the conclusion of several studies on respite [ 7 , 64 , 82 ]. A pattern seems to emerge in the countries represented in the review: Community organizations specialized in homecare (public and/or privately funded) offer respite on predetermined time slots, usually prescribed between traditional office hours (9 AM to 6 PM) [ 50 ]. This lack of flexibility could be explained in part by the rigidity of the structure of homecare services and the fact that its funding does not allow for customizable and punctual services [ 17 , 62 , 73 ]. Nevertheless, there were some examples of flexible respite models, such as Baluchon Alzheimer™ and consumer-directed approaches. Baluchon Alzheimer™ offers long-term at-home respite (4 to 14 days) by qualified and trained baluchonneuses . Prior to the relay of the caregivers, the baluchonneuse takes the time to learn about the dyad, including their environment and routine [ 53 , 62 ]. Caregivers report feeling refreshed upon their return and appreciate the diaries (or logbooks) that the baluchonneuse meticulously fills out [ 53 ]. Another example would be consumer-directed approaches, where caregivers are attributed a budget to hire their own care worker. Allowing caregivers to choose their care worker (either from a self-employed carer or family and friends) can increase the quality of care and satisfaction, while providing relatively affordable care, especially in a situation of labour shortage [ 51 , 79 ]. Even though these two models are a demonstration of how respite can be adapted to the caregiver-senior dyad, for the most part, flexibility is lacking on all three dimensions of respite ( WHO , WHEN , HOW ).

Secondly, the results from the scoping review highlight how homecare as a profession is often overlooked. Indeed, the reviewed documents state the necessary set of skills to offer respite; the level described is one of highly specialized care professionals with important liability. These skills must also transcend advanced knowledge and qualifications, to include interpersonal capabilities [ 17 , 53 , 62 , 63 , 68 ]. Furthermore, care workers must also be flexible to offer a wide range of service time and duration, in addition to being ready to provide “on-the-go” respite [ 53 , 68 ]. Yet, the occupation of homecare worker is an underappreciated and underpaid position [ 83 ]. Community care, like respite, is generally not a priority for social and healthcare funding [ 24 ]. This can be explained in part by the neoliberal approach to care in which the target is to minimize spending and maximize (measurable) outcomes [ 84 ]. Homecare outcomes are often overlooked in favour of service delivery evaluation, in part because they are difficult to measure [ 44 ]. This approach can also lead to prioritizing third party contracting instead of including respite in the range of public services, as to save on expenses related to employment (insurance and other benefits) [ 85 ]. Another contributor is that funding is used for service administration and not to adequately provide services or remunerate care workers [ 86 ]. Finally, care workers are mostly women, known for doing the invisible work that is at the heart of respite care (emotional support, etc.) [ 87 ]. A telling example from the reviewed documents is that Baluchon Alzheimer™ refers to their care workers as baluchonneuses (feminine form) and not baluchoneurs (masculine form) [ 53 ]. Consequently, the homecare sector is faced with recruitment and retention challenges [ 44 , 64 , 88 ]. Authors of the documents included in the review addressed the fact that flexibility in service meant that service providers had to function with excess capacity; for example, by building an “employee bank” to cover all the hours of the day and emergency calls [ 44 ]. Ultimately, staff turnover and shortage caused in part by the work being underappreciated could create a vicious cycle, leading to inflexibility in respite. In short, overlooking and underestimating the crucial and specialized work of homecare workers can contribute to staff turnover, which in turn could result in a lack of flexibility of at-home respite.

Limitations and strengths

The review’s methodological approach has some limitations and strengths. First, according to Levac, Colquhoun and O’Brien [ 32 ], research teams could conduct a sixth step in their scoping study, consisting in consulting experts through a focus group or workshop. This last phase aims at providing further insight into the review’s results and to begin the knowledge translation process. The team did not conduct a traditional consultation phase. Instead, they triangulated the review’s results through a questionnaire. This method was of interest, because of the natural concordance between the results and the considerable number of participants ( n  = 100). The survey still allowed to refine the characterization of respite, but further knowledge transfer to homecare actors and caregivers is necessary. Although innovative, there is a need to further investigate the validity of this approach as a consultation phase. Secondly, the theme of flexible at-home respite may have narrowed the search and identification of relevant documentation, and therefore caused the team to overlook some of the literature. Empirical studies and reviews on respite seldom include a detailed description of services [ 89 , 90 , 91 ]. This made it challenging to understand what services are like, operationally, for the dyad and to judge their flexibility. In addition, it complexified the extraction of relevant data, as descriptions were sparse and scattered throughout the documents. The team worked to mitigate these limitations in the documentation research and data charting phase. To begin, they sorted through all the literature on at-home respite for caregivers of older adults. In other words, the team not only searched for, but also included any explicit mention of flexibility. After selection, the extraction tables allowed enough versatility to include all the flexible characteristics of service, regardless of their placement in the text (introduction, methodology or discussion) or length. Another limitation is that, due to resource constraints, only 10% of the document selection and extraction was assessed by two reviewers, although a minimum of 80% of agreement was met and discussions were used to reach consensus where a disagreement arose. To conclude, strengths of this review include the extensiveness and diversity of the documents and its rigorous methodology, co-validated by a peer and an experienced researcher, with assistance from a specialized librarian.

This review has both scientific and practical implications. From a scientific point of view, the results contribute to the body of knowledge on flexible respite service models for caregivers of seniors, an under-documented topic. To our knowledge, this is the first review that aims to characterize flexible at-home respite. Our results suggest the relevance of further documenting the factors influencing the implementation and delivery of flexible respite services, as well as the consequences of the lack of flexibility in respite services, which may lead to service underuse. Moreover, researchers could focus on documenting respite programs in countries that are not represented in this review. There were notably no documents from the continents of Asia and Africa. Unfortunately, good practices can go unreported in peer-reviewed publications; therefore, a review focusing on government reports and publications aimed at professionals could shed some light on promising respite models. From a practical point of view, this review serves as a starting point for the implementation of flexible home respite that is tailored to the caregivers’ and older adults’ needs. Our characterization of flexible at-home respite can be used to guide the improvement of existing respite services and to design new resources that reflect best practices in homecare, ultimately contributing to successful aging in place for older adults.

Data availability

The data supporting this study’s findings are available from the corresponding author, upon reasonable request.

Abbreviations

Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews

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Acknowledgements

The team thanks the Université de Sherbrooke’s library and archives service for their support. The team also want to thank everyone who participated in the survey.

This article describes a part of a larger study on flexible respite funded by the Fonds de la recherche du Québec (#309508) – Santé and the Conseil de recherches en sciences humaines du Canada (#892-2019-3075). Annie Carrier and Véronique Provencher are Fonds de recherche du Québec – Santé Junior 1 and Junior 2 researchers (#296437 and #297008, respectively). Alexandra Éthier is a Canadian Institutes of Health Research - Research Graduate Scholarships – Doctoral Program recipient (#476590 − 71729).

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MV conducted the review and co-wrote the article with AE. AE co-validated the study selection and co-wrote the article. AC co-validated the study selection, data charting and reviewed the article. VP reviewed the article. All authors read and approved the final manuscript.

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Viens, M., Éthier, A., Provencher, V. et al. WHO, WHEN, HOW: a scoping review on flexible at-home respite for informal caregivers of older adults. BMC Health Serv Res 24 , 767 (2024). https://doi.org/10.1186/s12913-024-11058-0

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CASE REPORT article

Clinical and imaging features of pulmonary mixed squamous cell and glandular papilloma: a case report and literature review.

• Affiliated Hospital of Zunyi Medical University, Zunyi, China

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Pulmonary mixed squamous cell and glandular papilloma (MSGP) is a rare benign lung tumor with both squamous and glandular epithelial components. Reports on primary lung MSGP are few and the aim of this study is to describe the imaging including computed tomography (CT) and positron emission tomography (PET) findings, histopathological characteristics of a case of MSGP in our hospital. A 53-year-old woman with no smoking history who underwent a chest CT scan revealed a nodule in the upper lobe of the left lung.The solid nodule showed no lobulation or spiculation but demonstrated significant enhancement on contrast-enhanced CT and increased fluorine-18 fluorodeoxyglucose ( 18 F-FDG) uptake on PET. Moreover, a literature review identified 19 cases of lung MSGP involving imaging findings including CT or/and PET imaging. Except for one patient with ground glass nodule, the rest were solid, and ranged in size from 0.7 to 8.2 cm, which can present as a mildly to significantly increased 18 F-FDG uptake on PET. MSGP is a rare benign tumor entity, and understanding its imaging findings and pathological immunohistochemical 2 characteristics will help to improve the accurate diagnosis of MSGP, so as to avoid unnecessary lobectomy and mediastinal lymph node dissection.

Keywords: Mixed squamous cell and glandular papilloma, Lung, lung cancer, PET/CT, CT

Received: 24 May 2024; Accepted: 03 Jul 2024.

Copyright: © 2024 Hu, Zhao, Li, Wang and Cai. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Wei Zhao, Affiliated Hospital of Zunyi Medical University, Zunyi, China Fangming Li, Affiliated Hospital of Zunyi Medical University, Zunyi, China Pan Wang, Affiliated Hospital of Zunyi Medical University, Zunyi, China Jiong Cai, Affiliated Hospital of Zunyi Medical University, Zunyi, China

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

• Open access
• Published: 27 June 2024

The double whammy of ER-retention and dominant-negative effects in numerous autosomal dominant diseases: significance in disease mechanisms and therapy

• Nesrin Gariballa 1 ,
• Feda Mohamed 1 , 2 ,
• Sally Badawi 1 &
• Bassam R. Ali 1 , 2  

Journal of Biomedical Science volume  31 , Article number:  64 ( 2024 ) Cite this article

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The endoplasmic reticulum (ER) employs stringent quality control mechanisms to ensure the integrity of protein folding, allowing only properly folded, processed and assembled proteins to exit the ER and reach their functional destinations. Mutant proteins unable to attain their correct tertiary conformation or form complexes with their partners are retained in the ER and subsequently degraded through ER-associated protein degradation (ERAD) and associated mechanisms. ER retention contributes to a spectrum of monogenic diseases with diverse modes of inheritance and molecular mechanisms. In autosomal dominant diseases, when mutant proteins get retained in the ER, they can interact with their wild-type counterparts. This interaction may lead to the formation of mixed dimers or aberrant complexes, disrupting their normal trafficking and function in a dominant-negative manner. The combination of ER retention and dominant-negative effects has been frequently documented to cause a significant loss of functional proteins, thereby exacerbating disease severity. This review aims to examine existing literature and provide insights into the impact of dominant-negative effects exerted by mutant proteins retained in the ER in a range of autosomal dominant diseases including skeletal and connective tissue disorders, vascular disorders, neurological disorders, eye disorders and serpinopathies. Most crucially, we aim to emphasize the importance of this area of research, offering substantial potential for understanding the factors influencing phenotypic variability associated with genetic variants. Furthermore, we highlight current and prospective therapeutic approaches targeted at ameliorating the effects of mutations exhibiting dominant-negative effects. These approaches encompass experimental studies exploring treatments and their translation into clinical practice.

The exploration of molecular and cellular mechanisms underlying many genetic diseases typically starts by evaluating the early stages of the protein biogenesis as well as its subsequent processes including trafficking, interactions, the execution of its biological function and even its disposal. A detailed understanding of defects and aberrations in these processes provides key insights into the molecular foundation of the pathogenesis of genetic diseases and the consequent manifestations of the pathological phenotypes. In eukaryotic cells, secretory and endomembrane proteins destined for many cellular organelles typically enter the endoplasmic reticulum (ER) in their unfolded states, where they undergo their initial and crucial processes to acquire their proper tertiary conformations [ 1 , 2 ]. In particular, this is where these ER-targeted proteins undergo essential post-translational modifications including glycosylation, proline isomerization, lipidation and disulfide bond formation, which are often crucial for guiding proper folding, stability and the performance of their biological functions [ 3 , 4 ]. To ensure efficiency and fidelity, cells have adapted extensive ER quality control (ERQC) mechanisms that allow only properly folded proteins to reach their functional destination [ 5 ]. Due to the extensive and rigorous cellular mechanisms dedicated to maintaining protein fidelity and proper conformation, it is estimated that 12–15% of newly synthesized proteins do not successfully attain their intended conformation, leading to their subsequent elimination via one or more of the cellular degradation pathways within the secretory pathway [ 6 , 7 ]. This percentage is significantly increased when proteins harbor mutations that lead to their mis- or mal-folding, and often the removal of the mutant protein quantitatively [ 8 ]. Disease-causing mutations, including point mutations, insertions, deletions and repeat expansions impact protein structure and function in diverse ways, leading to three primary disease cellular mechanisms: loss-of-function, gain-of-function or dominant-negative effects [ 9 ]. Loss-of-function mutations may cause decreased or total loss of protein function that consequently leads to failure or reduction in performing its normal physiological function [ 10 ]. Conversely, gain-of-function mutations occur when the mutant protein acquires a new or abnormal function such as increased or uncontrolled activities leading to dysregulation in the normal cellular activities [ 11 ]. In autosomal dominant diseases where one allele expresses the mutant protein, while the other allele preserves its WT expression, a range of disease mechanisms can be demonstrated including loss-of-function of one allele (haploinsufficiency), gain-of-function, dominant-negative effects or a combination of two mechanisms [ 11 ]. The dominant-negative effects exerted by the mutant protein on the WT protein may exacerbate the haploinsufficiency state in autosomal dominant diseases [ 12 ]. This occurs through interference with the function or trafficking of the normally functioning protein. It is common for proteins to function as homodimers, oligomers or part of multi-subunit complexes. As a consequence, when a mutant protein is expressed from the mutant allele, this can lead to the formation of abnormal dimers, heteromers or multi-subunit complexes that often negatively impact the function or stability of their functioning unit. Numerous studies, including our own, indicate that ER-targeted mutant proteins that are unable to attain their correct conformation, often experience defective trafficking, leading to their entrapment in the ER and subsequent degradation via the ER-associated protein degradation (ERAD) and other associated mechanisms [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. Therefore, exploring whether certain ER-retained mutant proteins exert dominant-negative effects on their WT counterparts, or their complexes has become crucial. Such effects may exacerbate the disease pathological state, potentially explaining some of the broad and variable spectrum of phenotypic expressivity observed for many monogenic diseases [ 12 ]. Despite extensive research efforts directed towards comprehending loss of function and gain of function mutations in dominant conditions, there has been relatively limited exploration into the involvement of dominant-negative effects mechanisms. ERAD is a complex mechanism that plays a crucial role in protein quality control in the secretory pathway, involving the recognition of mutant, orphaned and misfolded proteins then targeting them for re-translocation for degradation by the proteasomal or lysosomal machineries. This mechanism has been implicated in the pathology of numerus human genetic condition and the number is expected to keep rising due to the central importance of this quality control mechanism in the monitoring almost a third of the cellular proteins [ 21 , 22 , 23 ].

In this manuscript, we aim to review the literature and include our perspectives on the impact of various dominant-negative effects implicated in the pathology of a spectrum of autosomal dominant diseases caused by mutations in secretory and membrane proteins (Table  1 ). We will focus on both the currently acknowledged and potential dominant-negative effects displayed by mutant variants retained in the ER as a result of the ER quality control (ERQC) mechanisms. In addition, we will also highlight existing and potential therapeutic interventions aimed at mitigating the impact of mutations exhibiting dominant-negative effects, spanning from experimental research on therapies to their application in patient care.

The dominant-negative effects: Concept and mechanisms

Dominant-negative mutations have been defined in 1987 by Ira Herskovitz as “those leading to mutant polypeptides that disrupt the activity of the WT gene when overexpressed” [ 83 , 84 ]. This current review is focused on the combinational mechanism of ER retention and dominant-negative effects exerted by the mutant proteins on their WT counterpart, resulting in the entrapment and defective trafficking of WT proteins from the ER to their functional destinations. `It is crucial, however, to recognize that dominant-negative mechanisms extend far beyond those caused by ER-retained mutants. Here is an overview of some of these mechanisms:

Altered protein trafficking: Mutant proteins might alter the trafficking of the WT proteins causing their entrapment in cellular compartments, thus preventing their trafficking to their functional destination. For example, some ER-retained endoglin mutants associated with hereditary haemorrhagic telangiectasia type 1(HHT1) form heterodimers with WT endoglin in the ER and thus preventing its trafficking to the plasma membrane [ 47 ]

The formation of inactive protein complexes: Trafficking-competent mutant proteins can form heterodimers with their WT counterpart expressed by the unaffected allele or with other WT partner proteins expressed by different genes, which renders the heterodimeric complex inactive [ 85 ]. This type of dominant-negative effect is best represented in collagen disorders such as Osteogenesis Imperfecta (OI), in which a mutant collagen protein forms inactive complexes with its WT partners negatively impacting the function of the whole collagen matrix [ 39 ].

Competitive binding inhibition: In this case, the mutant proteins compete with the WT counterparts for binding to shared substrates or ligands, thereby limiting proper binding interactions, leading to a potential inhibitory effect. For example, Von Willebrand disease (VWD) is a bleeding disease caused by mutants von Willebrand factor (VWF), a glycoprotein expressed by endothelial cells [ 86 ]. Mutants VWF interfere with the binding of WT protein to platelets and sub-endothelium in a dominant-negative manner, resulting in reduced clotting function and increased risk of bleeding [ 87 ].

Protein destabilizing effect: The dominant-negative effect exerted by the mutant protein results in WT reduced stability or even premature degradation. Certain p53 tumor suppressor mutant proteins adversely affect the stability of WT p53, leading to its reduced function and effectiveness [ 88 ].

Conformational effects: Secreted misfolded mutant proteins with structural defects may give rise to conformational defects in the WT protein complex, impeding its physiological function. For example, mutant fibrillin-1 proteins encoded by FBN1 gene, associated with Marfan disease exhibit a dominant-negative effect on the WT protein via disruption of the normal assembly of the extracellular matrix [ 89 ].

Protein quality control mechanisms in the early secretory pathway: Components and involvement in human diseases

Newly synthesized secretory and membrane proteins are transported to the ER where they undergo various interactions, posttranslational modifications and assembly to generate mature proteins in fully folded three-dimensional states. While protein folding can occur co- or posttranslationally, its accuracy and efficiency are important factors for the protein’s functionality and cellular homeostasis. Protein folding in the ER is mediated via a complex ER-resident chaperoning and folding machineries, consisting of the heat shock protein (Hsp) chaperones and the calnexin/calreticulin (CNX/CRT) lectin-like chaperones [ 90 ]. Among the major molecular chaperones involved in preventing protein aggregations and incorrect folding is the Hsp70 chaperone; BiP (Fig.  1 ) [ 91 , 92 ]. Dysfunction in the chaperoning machinery contributes to various diseases, including Alzheimer's and Parkinson diseases [ 93 ].

Protein synthesis and quality control mechanisms in the ER. Newly synthesized proteins in the ER undergo quality control checks to ensure correct folding. Misfolded proteins form aggregates in the ER lumen and activate the UPR response that leads to transcriptional activation of various ER stress genes and are degraded via the proteasomal ERAD machinery based on their lesioned domain

In addition to the failure of the chaperoning systems, several other factors contribute to defective protein folding in the ER, including transcriptional or translational errors, abnormal chemical protein modifications, oxidative stress, and genetic mutations [ 18 , 94 ]. Consequently, incorrect protein folding results in defective trafficking of the proteins to their destination associated with ER retention and the formation of protein aggregates in the ER lumen. Accumulation of misfolded proteins in the ER triggers an ER stress signaling cascade known as the unfolded protein response (UPR). The UPR employs cytoprotective strategies aimed at preserving ER homeostasis, thereby alleviating ER stress caused by the burden of misfolded proteins. This is accomplished by activating downstream ER quality control activities. The UPR cascade is induced by three established arms: protein kinase RNA like endoplasmic reticulum kinase (PERK), inositol requiring enzyme 1 (IRE1), and activating transcription factor 6 (ATF6) (Fig.  1 ) [ 20 , 95 ]. The coordinated activation of the three UPR arms collectively targets the attenuation of protein synthesis within the ER, induction of molecular chaperones’ gene expression aiding in protein folding, and ultimately the removal of misfolded proteins via ERAD mechanism [ 96 ]. ER stress and the disruption of the UPR have been linked to the development of various diseases, spanning neurodegenerative conditions like Alzheimer's and Parkinson's diseases [ 97 ], metabolic disorders such as diabetes and obesity [ 98 , 99 , 100 ], inflammatory diseases [ 101 ], cancer [ 102 , 103 ], and rare genetic disorders like cystic fibrosis (CF) [ 104 ], Gaucher disease [ 105 , 106 ], Acromesomelic Dysplasia 1, Maroteaux type [ 18 ] and many others [ 107 , 108 , 109 , 110 ]. Understanding the mechanisms underlying ER stress and the UPR activation is crucial for elucidating disease pathogenesis and developing therapeutic strategies. CF has been recognized as a pioneering disease in the field of ER stress research due to its well-defined genetic basis, thoroughly investigated pathophysiology, and the availability of animal models and cell culture systems for studying disease mechanisms [ 111 ]. CF is an autosomal recessive disorder caused by mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene, which encodes a chloride channel primarily found in the apical membrane of epithelial cells [ 112 ]. Mutations in CFTR result in defective chloride ion transport across cell membranes, leading to sticky mucus production in the lungs and digestive system. Studies have revealed that most CF disease-causing mutations, including the most common CF variant (F508del), result in defective protein folding and trafficking, leading to ER retention and degradation of misfolded CFTR protein [ 113 , 114 , 115 , 116 , 117 ]. This accumulation of misfolded CFTR protein in the ER triggers ER stress and activates the the UPR mechanism aimed at restoring ER homeostasis [ 118 ].

In eukaryotic cells, nascently synthesized proteins are subjected to unique quality control assessments. This step involves the UDP-glucose: glycoprotein glucosyltransferase (UGGT) interaction with partially or misfolded proteins providing a further folding attempt mediated by the CNX/CRT chaperones cycle [ 119 ]. Proteins failing to meet the stringent quality checks are destined for degradation via various pathways including the ERAD machinery. Misfolded proteins are recognized and processed by distinct ERAD sub-pathways: ERAD-L, ERAD-M, and ERAD-C, based on the site of the defective domain within the protein—luminal (ERAD-L), membrane-bound (ERAD-M), or cytosolic (ERAD-C) (Fig.  1 ) [ 120 ]. ERAD substrates are exported and tagged with ubiquitin that serves as a degradation signal. These proteins are retrotranslocated to the cytosol for degradation by the large protein complex, the proteasome or the lysosomes, via a pathway known as the ER-to-lysosome associated degradation (ERLAD) [ 121 ]. Moreover, some ER retained mutants might escape the ERQC mechanism and avoid being degraded. These mutants might form aggregates in the ER lumen or interact in a dominant-negative manner with their WT counterparts and possibly affect their normal physiological function. These mechanisms and indeed defects in their components have been implicated in numerous human conditions, which is the focus of this review.

ER-retained mutant proteins exhibit dominant-negative effects in a range of autosomal dominant disorders

As indicated earlier, the entrapment of secretory proteins may result in a spectrum of monogenic diseases with varied modes of inheritance and molecular mechanisms. These encompass a range from loss of function, gain of function, dominant-negative effects, or combinations thereof. Here, we emphasize the dominant-negative effects demonstrated or predicted to play significant roles in the pathology of numerous autosomal dominant diseases. In these conditions, both the WT and mutant variants are expressed and anticipated to interact during the initial stages of the protein biogenesis and assembly within the ER, particularly in cases where the protein functions as a dimer, oligomer or part of a multi-subunit complex (Fig.  2 ). The broad spectrum of phenotypic severity observed across various autosomal dominant diseases constitutes a significant area of ambiguity and concern in biomedical research. The exploration of mechanisms, or combinations thereof, that cause phenotypic heterogeneity among affected individuals is essential in understanding the complex genotype–phenotype interplay. Extensive literature highlights examples of dominant-negative effects instigated by mutant variants, wherein these mutants impair the function of the WT counterpart at the functional location. In this review, we specifically explore the dominant-negative effects exerted by ER-retained mutants on the WT proteins, thereby initiating a double effect that entails dominant-negative effects on top of haploinsufficiency leading to the entrapment and possibly premature degradation of WT protein. Consequently, this combinatorial mechanism causes an excessive loss of protein function, thereby exacerbating the severity of disease phenotypes for some mutants exhibiting ER retention. It is important to note that our aim in this review is not to exhaustively cover every condition exhibiting dominant-negative effects within the field, but rather to highlight the widespread involvement of these mechanisms in disease pathogenesis in some autosomal dominant conditions.

Dominant-negative effects exerted by ER-retained mutant on the WT protein expressed by the functional allele. Monomeric Plasma membrane proteins or secretory proteins that fail to attain their normal conformation get targeted by the ERAD machinery for proteasomal degradation. In the case of dimeric or oligomeric proteins, ER-retained mutants are likely to interfere with the WT counterpart via a formation of hetero dimers/oligomers complexes. This interreference causes the entrapment of the WT within these complexes impeding its normal trafficking and leading to premature degradation through the ERAD mechanism

Skeletal and connective tissue disorders

Marfan Syndrome (MFS, MIM #154700) is an autosomal dominant genetic disease caused by heterozygous mutations in the FBN1 gene that encodes Fibrillin-1, a crucial protein component in the extracellular matrix (ECM) [ 122 ]. The disease is broadly classified as a connective tissue disorder with clinical manifestations impacting various organs including the heart, the blood vessels and the eyes [ 123 ]. The most distinctives features include a long face, high-arched palate, elongated limbs, tall and slender physique, chest deformities, lens dislocation, aortic root dilation and potential aneurysms [ 122 ]. MFS is characterized by a wide spectrum of phenotypic variabilities among affected individuals, including those carrying different genetic variants or even those with the same variant [ 123 ]. Fibrillin family of proteins encompasses three main types of fibrillin, fibrillin-1, 2 and 3. Fibrillin-2 and 3 are predominantly expressed during development, whereas fbrillin-1 is expressed throughout adulthood, as it provides strength and elasticity to connective tissues in major organs [ 124 ]. Fibrillin-1 is a 250 kDa glycoprotein characterized by multi-modular organization and is considered as the major structural component of the connective tissues microfibrils [ 24 ]. However, the mechanism by which fibrillin-1 assembles into microfibrils, remains to be fully elucidated. The majority of disease-causing variants in FBN-1 involve the substitution of cysteine amino acids, which play a critical role in forming disulphide bridges and maintaining proper protein conformation. For instance, severely misfolded variants like C1117Y and C1129Y, where cysteine is replaced by tyrosine, exhibit defective trafficking and become trapped and accumulate in the ER [ 24 ]. Conversely, the disease-causing variant G1127S is secreted normally, similar to the WT. These conclusions were drawn by examining their glycosylation profiles. Variants C1117Y and C1129Y exhibit a simple N-linked glycosylation pattern characteristic of ER acquisition. On the other hand, they lack the complex N-glycosylation typical of Golgi apparatus processing, resulting in a lower molecular weight presentation on SDS-PAGE, confirming their retention in the ER. In contrast, variant G1127S appears in a mature, fully glycosylated form, mirroring WT fibrillin-1 [ 24 ]. As a result, it was proposed that normally-trafficked fibrillin-1 mutants such as G1127S are likely to exert dominant-negative effects via misincorporation into the normal microfibril, however, no clear evidence was presented. In addition, intracellular dominant-negative was postulated as a probable disease mechanism attributed to the ER-retained variants such as C1117Y and C1129Y in addition to haploinsufficiency. This occurs because ER-retained mutants are prone to interact with WT fibrillin-1, forming heterodimers during the initial stages of protein dimerization within the ER. This interaction hampers the trafficking and secretion of fibrillin-1 to the cell surface [ 24 ]. The concept of a dominant-negative effect was previously proposed by Dietz and colleagues , supported by their demonstration that patients expressing the least amount of the nonsense mutant variants of fibrillin-1 exhibited the mildest disease phenotype. Conversely, patients with fully expressed variants exhibited the usual moderate to severe manifestation of the diseases [ 25 ].

Recent advances in high-throughput genomic analysis have revealed that idiopathic short stature (ISS, MIM # 300582) in children is linked to various genes that regulate growth plate function, including heterozygous mutations in NPR2 [ 29 ]. NPR-B encoded by NPR2 functions as a homodimer that catalyzes the conversion of GTP to cGMP upon binding of its ligand, C-type natriuretic peptide (CNP) [ 30 ]. Recently, co-immunoprecipitation assays have revealed that diseases-causing heterozygous missense NPR-B variants (R110C, R495C and Y598N) identified in ISS subjects exhibit dominant-negative effects on the WT receptor [ 29 , 31 ]. These studies have demonstrated that intracellular cGMP levels significantly increase upon cell transfection with the WT NPR-B. On the other hand, a significant decrease is observed when a mutant variant is co-expressed with the WT receptor. Notably, a prior investigation has also identified variant R110C as an ISS-causing mutation. This study demonstrated that this particular variant displays defective trafficking from the ER to the Golgi apparatus, evidenced by an immature glycosylation profile characteristic of ER-retained mutants [ 28 ]. Conversely, variant Q417E, also identified in the same study, trafficked normally to the plasma membrane. Interestingly, both variants exhibited dominant-negative effects, as evidenced by a decrease in cGMP production capacities. Specifically, R110C showed a negligible cGMP response, while Q417E displayed a significantly reduced response. These findings underscore the importance of further investigating the implications of dominant-negative effects and ER retention across a broader spectrum of variants. This approach will enable researchers to gain a more comprehensive understanding of the molecular pathology associated with variable variants.

Autosomal dominant Limb-girdle Muscular Dystrophy (LGMD-1CI, MIM # 609115) is a specific subtype of LGMD that is associated with mutations in CAV3 gene. The disorder is characterized by progressive muscle weakness primarily affecting the shoulders and hips muscles [ 125 ]. Caveolin-3 encoded by CAV3 is a member of the caveolin integral membrane proteins and a key structural protein of caveolar membrane in muscle cells [ 126 ]. Up to date ten LGMD-1C-disease causing variants of CAV3 have been identified according to the Human Genome Mutation Database (HGMD) ( https://www.hgmd.cf.ac.uk/ac/index.php ). Amongst the most studied variants are P104L, ΔTFT/63–65 (deletion of amino acids 63 to 65) and A45T. Minetti, Sotgia, Lisanti, and colleagues were the first to report the disease causing variants P104L, ΔTFT/63–65 in LGMD-1C patients [ 127 ]. In vitro characterization and immunofluorescence staining experiments have shown that the two variants fail to reach the plasma membrane. Instead, they are retained at the Golgi complex level and subsequently degraded through proteasomal degradation, along with partial degradation of the WT protein [ 128 ]. These findings suggest a dominant-negative effect of these two variants on the WT protein, leading to its entrapment in mixed WT/mutant oligomers, which ultimately results in proteasomal degradation, as evidenced by ER-localization. The same research group later demonstrated that treatment with the proteasomal inhibitor (MG-132) significantly enhanced the trafficking of WT protein entrapped at the Golgi complex to the plasma membrane in cells expressing both the WT and mutant variants [ 34 ]. Similarly Herrmann and colleagues have demonstrated that disease-causing variant A45T exhibit defective trafficking and also prevent the normal localization of WT caveolin-3 in a dominant-negative manner [ 129 ].

Collagen-related mutations in connective tissue disorders

The intricacy of collagen structures and their assembly plays a pivotal role in the diverse phenotypic manifestations observed in individuals with mutant collagen genes. Collagen, being the most abundant protein in the human body and a fundamental component of connective tissues, contributes significantly to the structural integrity of various tissues in the body such as skin, cartilage, and blood vessels [ 130 ]. The variability in collagen types and their interactions within heterotypic fibrils adds a layer of complexity to the assembly process. Mutations in collagen genes can disrupt this intricate network, leading to a spectrum of phenotypes broadly known as collagenopathies or connective tissue disorders [ 131 ].

A collagen molecule is most characterized by its triple-helical α-domain, which constitutes up to 95% of the molecule in some classes of collagen (reviewed in [ 132 , 133 ]. Several collagen-related genetic disorders are caused by a dominant inheritance of glycine substitution to a larger amino acid in the triple helical domain of the protein, which structurally affect collagen folding and assembly [ 131 ].

Mutations in collagen type VII alpha 1 encoded by the gene COL7A1 cause dystrophic epidermolysis bullosa (DEB, MIM # 131750), a genetic disorder characterized by skin blistering in response to minor trauma or friction [ 134 ]. It has long been established that certain disease-causing variants involving glycine substitutions accumulate intracellularly in the endoplasmic reticulum (ER) and fail to undergo proper extracellular secretion [ 135 ]. This failure to secrete results in a haploinsufficiency state, contributing to the manifestation of the disease. The same group has later shown that secreted mutant α1(VII) chains exert a dominant-negative effect by interacting with the WT protein forming heterotrimeric triple helix complex, leading to a destabilizing effect on collagen VII structure [ 131 ].

Heterozygous mutations in collagen VI genes ( COL6A1, COL6A2  and  COL6A3 ) are associated with Bethlem myopathy disorder (BMD, MIM # 158810), which is a milder form of Ullrich congenital muscular dystrophy (UCMD, MIM # 254090) also associated with homozygous mutations in the same genes. Bethlem myopathy is mainly characterized by proximal muscle weakness and joint contracture that progressively affect mobility and flexibility [ 136 ]. However, distinction between the two diseases in terms of their mode of inheritance was revised when patients with heterozygous mutations exhibited a severe form of the disease that is typical of UCMD. This finding has given rise to rigorous protein synthesis studies in order to provide an explanation for the consequences of severe mutations in the extremely complex structure of collagen VI [ 37 , 137 ]. The three alpha chains α1, α2 and α3 that characterize collagen VI fold into triple helical heterotrimeric monomer in the ER, which are then transported to the cell surface via the Golgi apparatus [ 133 ]. When these procollagen monomers reach the cell surface, they align in a staggered fashion to form dimers that are bonded via a disulfide bond, then dimers are aligned laterally to form a tetrameric complex in the extracellular matrix (ECM) [ 138 ]. It has been demonstrated that large amino acid deletion at the N terminal of the triple helical domain resulted in the secretion of mutant heterotetramers. The tetrameric stoichiometry of collagen VI means that mutations in any of the three alpha chains would result in only 1/16 normal tetramer [ 37 , 137 ]. This finding unequivocally illustrates the dominant-negative impact exerted by the mutant chain on the overall structural assembly of collagen VI. As a result, the collective effect resembles the complete loss of collagen VI observed in individuals with the homozygous mutation in UCMD. On the other hand, patients carrying heterozygous, in-frame amino acid deletions downstream of the triple-helical domain, which removes cysteines required for dimerization, exhibit a milder form of the disease. This deletion prevents the formation of WT/mutant dimers and consequently reduces the dominant-negative impact on the WT protein [ 137 ].

Osteogenesis imperfecta (OI) has served as a classic example for dominant-negative effects of structural proteins [ 41 ]. The disease, also known as brittle bone disease, is characterized mainly by bone fragility, short stature, loose joints and other variable skeletal deformities [ 139 ]. Classical OI types I to IV are caused by autosomal inherited mutations in COL1A1  or  COL1A2 genes that encode α1 and α2 subunits of collagen 1, respectively. Type I collagen is a heterotrimeric complex that consists of two α1 and one α2 chains, synthesized in the ER and assembled via a recognition sequence at the C terminal, along with the formation of disulfide bondings, prior to being transported to the Golgi apparatus [ 39 , 140 ]. The variability in the phenotype of this disease, coupled with a limited understanding of its underlying mechanisms, has prompted researchers to identify additional collagen-related genes involved in the regulation of collagen metabolism and assembly. Most of these genes have been linked to autosomal recessive pattern of inheritance. Nonetheless, mutations in Collagen1 genes still account for the majority of OI cases [ 141 ].

Molecular mechanisms attributed to the manifestation of autosomal dominant OI include decreased transcript due to nonsense mutation, decreased collagen secretion due to ER retention, and disrupted pro-collagen chains assembly and processing [ 41 , 142 , 143 , 144 ]. ER retention of glycine-substitution mutant variants of α1 and α2 subunits of collagen 1 was observed through transmission electron microscopy analysis of OI fibroblasts, revealing the presence of an enlarged ER indicative of ER stress [ 145 ]. Apoptotic cellular death was also demonstrated to be triggered despite autophagic activation through the UPR in an attempt to salvage the cells. Severe forms of OI that involve glycine substitution are associated with pathogenic variants that exert a dominant-negative effect, disrupting the assembly of the triple helix and collagen fibril. This disruption results in severe structural damage to the bone matrix [ 41 , 146 , 147 ].

Ehlers-Danlos syndromes (EDS) represent a group of genetically heterogenous conditions that are caused by pathogenic variants in up to 19 genes, mostly encode collagens or collage-related proteins [ 148 ]. Classic EDS (cEDS, MIM # 130000) is mainly associated with mutations in COL5A1 or COL5A2 genes encoding α1 and α2 chains of the collagen 5. Patients of this class of EDS present with joint hypermobility, skin hyper-elasticity and a tendency to develop atrophic scars [ 149 ]. Despite the limited number of clinically well described cEDS associated with mutations in COL5A2,  the majority manifest severe phenotypes and have an impact on the structural integrity of collagen V. These mutations exhibit a dominant-negative effects that disrupt the formation of heterotypic fibrils and the interactions between collagen 5 and other constituents of the extracellular matrix [ 43 , 150 ].

Pathogenic variants of COL2A1 and COL11A1 genes encoding collagen II α1 and collagen XI α2 chains have been associated with Stickler syndrome type 1 and 2, (ST1, MIM # 108300 and STL2, MIM # 604841), respectively. The α1 chain from COL11A1 combines with the α2 chain from COL11A2 and the α1 chain from COL2A1 to create heterotrimeric type XI collagen [ 46 ]. Stickler syndromes are a group of heterogenous connective tissue disorders characterized by distinctive facial feature, ocular abnormalities and joint anomalies. Splice site mutations in COL11A2 are the primary disease-causing mutations reported thus far. However, mutant mRNA does not undergo nonsense-mediated decay (NMD), allowing mutant chains to be expressed and associate with other α chains, leading to the formation of mutant collagen XI trimers in a dominant-negative manner [ 46 , 151 ]. Conversely, patients with mutations that lead to unexpressed protein due to targeting by the NMD mechanism tend to exhibit a milder form of the disease, and this mechanism is considered haploinsufficiency only [ 152 ].

Akawi and colleagues have argued that homozygous misfolding mutations in COL11A are more severe than bi-allelic null mutations as a result of the possible interference of the misfolded COL11A with its other collagen partners, presumably as a result of dominant-negative effects, and hence disrupting the function of the whole complex more severely [ 153 , 154 ]. On the other hand, pathogenic variants of COL2A1 , associated with Stickler syndrome type1, are believed to manifest the disease phenotype through only haploinsufficiency [ 46 ]. Several misfolded variants of both types of collagens were reported to be retained in the ER, followed by proteasomal degradation [ 45 ]. Nonetheless, to our knowledge, whether ER-retained mutants exert dominant-negative effects by interfering with the WT in heterotrimeric complexes remains largely unexplored.

The preceding discussion highlights how the complexity of collagen structure magnifies the dominant-negative effect of mutant subunits by exacerbating the disruption in the intricate network of collagen assembly. Mutant collagen subunits, with their altered structures, not only compromise the functionality of individual molecules but also introduce a destabilizing influence during fibril formation. These effects ultimately contribute to the diverse phenotypic outcomes observed in collagen-related genetic disorders. It’s important to note that there has been limited research dedicated to investigating the dominant-negative effect exerted by mutant collagen subunits when trapped in the ER, potentially affecting their trafficking. The ER serves as a crucial site for proper folding and post-translational modifications of collagen molecules before they are transported to their functional destinations. The presence of mutant subunits in the ER may disrupt these processes, leading to the accumulation of misfolded or improperly modified collagen. This lack of in-depth exploration into the consequences of such entrapment hinders a comprehensive understanding of how trafficking abnormalities contribute to the overall pathogenesis of collagen-related genetic disorders.

Vascular monogenic disorders

Hereditary haemorrhagic telangiectasia (HHT) is a vascular genetic disorder characterized by vascular dysplasia inherited in an autosomal dominant manner. Its spectrum of phenotypes varies from occasional nasal bleeds to internal organ hemorrhages affecting the gastrointestinal tracts (GI), kidneys, liver, and brain [ 155 ].The disease has been classified into four types according to the causative gene: HHT1, HHT2, HHT5 and (JPH) Juvenile polyposis and HHT, associated with mutations in ENG, ACVLR1, GDF2 and SMAD4 genes, respectively [ 156 , 157 , 158 , 159 ]. These genes encode proteins that are components of the transforming growth factor beta (TGFβ) signaling pathway, which regulates various cellular processes [ 109 , 160 , 161 ]. Hereditary haemorrhagic telangiectasia type 1 (HHT1, MIM # 187300) is associated with mutations in the gene ENG that encodes endoglin, a dimeric glycoprotein that functions as a co-receptor on the plasma membrane. It is predominantly expressed in vascular endothelial cells of various tissues and organs throughout the body and it is therefore essential for the normal structure of the blood vessels [ 162 ]. In earlier work, we have utilized glycosylation profiling assays and immunofluorescence microscopy to demonstrate that several disease-causing missense endoglin variants get trapped in the ER by the machinery of the ERQC mechanism and fail to traffic to the plasma membrane, where they function [ 13 ]. Subsequently, we have also demonstrated the implication of ERAD in the degradation of ER-retained missense mutant variants P165L and V105D using HRD1-knockout HEK293 invitro cellular model [ 163 ]. Protein elimination leads to a haploinsufficiency state, ultimately contributing to the manifestation of the disease phenotype. Given that endoglin is a homodimeric protein synthesized in the ER, it was logical to explore whether mutant variants expressed by the affected allele would interact with WT endoglin, potentially leading to a dominant-negative effect. Interestingly, our co-immunoprecipitation assays have clearly demonstrated that ER-retained endoglin variants (L32R, V105D, P165L, I271N and C363Y) heterodimerize with WT endoglin in a dominant-negative manner impairing its trafficking to the plasma membrane [ 47 ]. This mechanism is likely to exacerbates the disease state, resulting in a scenario where 50% of the protein is lost due to the loss of one allele leading to haploinsufficiency, coupled with a possible additional ~ 25% loss attributed to the dominant-negative effects exerted by the mutant ER-retained protein on its WT counterpart. Our findings were consistent with two prior studies that briefly illustrated the formation of mixed dimers of endoglin WT and mutant variants [ 164 , 165 ].

Hereditary haemorrhagic telangiectasia type 2 (HHT2, MIM # 600376) is associated with mutations in ACVRL1 gene, encoding activin receptor-like kinase, also denoted as ALK1, a type 1 receptor in the TGFβ signaling pathway [ 166 ]. Both HHT1 and HHT2 are presented with similar phenotypes, as both endoglin and ALK1 play a crucial role in endothelial cells differentiation during capillary development leading to vascular malformation phenotypes in both disorders [ 167 ]. Similar to endoglin, both our research and other studies have shown that several missense mutant variants located at the intracellular kinase domain of ALK1 receptor become entrapped in the ER and fail to traffic to the plasma membrane where they normally perform their functional role in TGFβ signaling cascade [ 16 , 164 , 168 ]. Currently, haploinsufficiency has been accepted as the primary disease mechanism [ 158 , 169 ]. However, the homodimeric nature of the ALK1 receptor raises a strong possibility that some of these ER-retained mutants may form heterodimeric complexes with the WT, thereby hijacking it and impairing its trafficking to the plasma membrane in a dominant-negative manner. Recently, variants of ALK1 that exhibit a normal trafficking to the plasma membrane were also proposed to exert a dominant-negative effect on the WT via forming dysfunctional heterodimers on the plasma membrane, which further impedes the 50% functionality of WT expressed by the unaffected allele [ 49 ]. These findings further consolidate the prediction that some ER-retained mutants may exhibit a dominant-negative effect on the WT protein through heterodimerization between the mutant and WT alleles.

Pulmonary arterial hypertension (PAH, # 178600) is another hereditary vascular disease associated with heterozygous mutations in BMPR2 gene, encoding yet another type 2 receptor; bone morphogenetic protein receptor 2 [ 170 ]. Considerable research efforts have been carried out to understand the molecular mechanisms that may contribute to the wide spectrum of the disease phenotypes as well as the reduced penetrance rate, (reviewed in [ 171 ]. In an effort to understand the mechanisms by which missense mutant variants lose their functionality, we investigated the trafficking of various disease-causing variants spanning all receptor’s domains. Our findings revealed that some variants that harbor mutations at the ligand binding domain are entirely or partially trapped in the ER, ultimately leading to premature degradation through, most likely, the ERAD mechanism [ 15 ]. Retention of disease-causing missense variants of BMPR2 and the consequential defective trafficking of the receptor to the plasma membrane, which also has also been reported by others, further consolidates the implication of the ERQC mechanism in the pathogenesis of PAH [ 50 , 172 ]. Furthermore, evidence of a dominant-negative effect exerted by BMPR2 missense variants on a type 1 receptor has also been reported [ 50 ]. Remarkably, there has been no exploration into whether those ER-retained mutants would exert a dominant-negative effect on WT BMPR2 expressed from the unaffected allele. Like endoglin and ALK1, BMPR2 is a homodimeric protein. This characteristic raises the possibility that heterodimerization between WT and dominant-negative ER-retained mutants may occur during the early stages of protein biogenesis in the ER, impairing its trafficking to the plasma membrane.

Loeys-Dietz Syndrome (LDS, MIM # 609192) is a rare genetic disorder inherited in an autosomal dominant manner [ 173 ]. It is characterized by multisystemic phenotypic presentations including aortic/arterial aneurysms in addition to craniofacial, osteoarticular, musculoskeletal, and cutaneous malformations [ 173 , 174 ]. Up to date, mutations in six genes (TGFBR1, TGFBR2, SMAD2, SMAD3, TGFB2, and TGFB3) that encode TGFβ signaling components have been associated with LDS [ 174 , 175 ]. Functional assays have demonstrated that mutated TGFBR1 interfere with the endogenously expressed WT receptor, reducing its activity in a dominant-negative manner [ 52 ]. These findings open the doors for further investigation into the molecular mechanisms that lead to the loss of function of these major components in the signaling pathway. A possible dominant-negative effect exerted by the mutant allele on the WT may also represent logical contributor to an aggravated haploinsufficiency state in LDS. Furthermore, considering that LDS is associated with several mutant variants of components functioning along the same signaling pathway, it is worthwhile to investigate whether some of these mutant components might interfere with the function of multiple components within the signaling pathway, potentially contributing to the observed heterogeneity in LDS phenotypes.

It is crucial to highlight that the majority of TGFβ signaling pathways involve dimeric proteins, whether secretory or membrane-bound. As illustrated in a prior review, through an extensive literature search, we have shown that these proteins are implicated in around 25 monogenic human diseases [ 109 ]. However, the disease mechanisms of these conditions remain underexplored in terms of possible implication of ERQC mechanism and also the potential existence of dominant-negative effects. Further investigation into these aspects is warranted to enhance our understanding of the pathogenesis associated with TGFβ signaling-related monogenic diseases.

Long QT syndromes (LQTS) are a group of autosomal inherited arrhythmogenic disorders characterized by abnormal cardiac activity presented by prolonged QT intervals, leading to a type of arrhythmia known as torsades de pointes [ 176 ]. Irregularities in the heartbeat have the potential to result in fainting, seizures, or sudden cardiac arrest. LQTS is classified into three primary types based on the causative genes: LQTS1, MIM # 192500, LQST2, MIM # 613688, and LQTS3, MIM # 603830 encoded by the genes ( KCNQ1 ), ( KCNH2 ) and ( SCN5A ), respectively. These genes encode ion channels essential for cardiac repolarization [ 177 ]. Nonetheless, each type has distinct triggers, clinical manifestations, severity and penetrance profile, suggesting variable molecular mechanisms involved, in addition to environmental factors, age and gender [ 178 ]. LQTS2 is associated with KCNH2 , a gene that encodes the voltage-gated K + channel α-subunit (Kv11.1), which function as tetrameric complex that consists of four Kv11.1 α-subunit [ 179 ].

Ficker and colleagues reported through immunoprecipitation analysis that Kv11.1 disease-causing variants R752W and G601S show defective trafficking, evidenced by their strong association with molecular chaperones Hsp90 and Hsp70 in the ER. Defective trafficking results in ER-retention of misfolded Kv11.1variants, followed by premature degradation through the ERAD mechanism. Conversely, the non-functional G628S variant displayed transient associations with the molecular chaperones before being released to the plasma membrane, similar to WT Kv11.1 [ 54 ]. Characterizing the physiological properties of Kv11.1 disease-causing variants harboring the missense mutation (E637K) situated in the pore-S6 loop of the channel, using a Xenopus oocyte heterologous expression system, revealed intriguing findings. Coexpression of WT (WT) and E637K variants resulted in a peak tail current significantly lower than the current peaks anticipated from the WT alone. These findings suggest that this mutation exerts a dominant-negative effect on the WT Kv11.1 channel and highlights the significance of the pore-S6 loop in the channel's function [ 180 , 181 ]. Therefore, if a dominant-negative effect can occur on the plasma membrane through the formation of the WT/mutant tetrameric complexes, then it follows logically that ER-retained mutants may also form similar tetrameric complexes in the ER, that impede the trafficking of the WT ion channel to the plasma membrane, employing a similar dominant-negative mechanism.

Neurological disorders

The spectrum of molecular mechanisms underlying monogenic neurological disorders with autosomal dominant inheritance is diverse, reflecting the wide array of genes and protein variants involved. Nonetheless, protein misfolding and aggregation are recurrent themes, leading to cellular death and permanent neurological dysfunction. Phenotypic traits can be further aggravated by dominant-negative variants that interfere with the remaining 50% functionality of the WT protein.

Heterozygous mutations in the GABAA receptor gamma2 subunit encoded by the gene GABRG2 have been associated with generalized epilepsy with febrile seizures plus (GEFS + , MIM # 607681) [ 59 , 182 ]. The GABAA receptor, a pentameric ligand-gated ion channels serving as a receptor for the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), is typically composed of two α subunits, two β subunits, and one γ2 subunit [ 183 ]. The molecular mechanisms associated with disease-causing variants were identified to involve haploinsufficiency attributable to the mutant allele, along with the exertion of a dominant-negative effect by the mutated γ2 subunit. Kang and colleagues have demonstrated, using in vitro cellular models, that the pathogenic variant γ2(Q351X) associated with GEFS exhibits defective trafficking to the plasma membrane, leading to proteasomal degradation through ERAD. Additionally, γ2(Q351X) was shown to exert a dominant-negative effect on WT receptors, reducing their assembly, trafficking, and surface expression ( 59). This effect likely arises from the oligomerization of mutant and other WT subunits that form the full pentameric receptor complex, resulting in ER retention of both WT and mutant subunits followed by premature degradation through ERAD. Pulse-chase experiments revealed that coexpression of the γ2 subunit mutation, Q351X, with other WT subunits reduced GABAA function to a level lower than the predicted 50% level for heterozygous carriers. Therefore, the combined mechanism of ER retention and dominant-negative effect exerted by the mutant γ2 subunit on partnering subunits is predicted to be the most likely mechanism for the manifestation of GEFS + associated with this mutation.

A combination of haploinsufficiency and dominant-negative effect mechanisms has also been identified as the underlying mechanism for severe cases of Neurofibromatosis type 1 (NF1, MIM # 162200), a rare genetic disorder characterized by the development of tumors on nerve tissues throughout the body [ 61 ]. Neurofibromin, encoded by NF1 gene, is a tumor suppressor and a GTPase activating proteins that regulates RAS signaling cascade in various cell types including neuronal cells [ 184 ]. In invitro cellular models, it has been demonstrated that misfolded neurofibromins, encoded by variants in codons 844 to 848, exert a destabilizing effect on the WT protein through protein dimerization in the ER. Heterodimeric complexes are recognized by the ERQC mechanism and marked for degradation via ERAD mechanism. This interaction results in a complete reduction of neurofibromin levels, surpassing the threshold observed in haploinsufficiency alone [ 185 ].

In genetic disorders, dominant-negative effect might also occur when a mutated protein disrupts the function of another protein it unexpectedly interacts with, leading to the manifestation of disease symptoms. This phenomenon is best demonstrated by missense variants of voltage-gated potassium channel (Kv3.3) associated with autosomal dominant spinocerebellar ataxias 13 (SCA13, MIM #176264), encoded by the gene KCNC3 [ 186 ]. These misfolded variants display impaired trafficking, resulting in entrapment within endosomal vesicles and a failure to reach their designated functional location at the plasma membrane [ 60 ]. Intriguingly, they also intracellularly engage with the human epidermal growth factor receptor (EGFR) through an unknown mechanism, implying a pivotal role for EGFR in cerebellum development and, consequently, highlighting its involvement in the pathology of SCA13.

DYT1, also known as early onset torsion dystonia, is an autosomal dominant neurological disease characterized by involuntary muscle contractions (dystonic movements) affecting several parts of the body, resulting in severe disability [ 187 ]. The disease typically begins in childhood or adolescence and represents the most common and severe type of dystonias. DYT1 dystonia is caused by a specific mutation in the TOR1A gene, which involves the deletion of three base pairs (GAG), resulting in the loss of a single glutamic acid residue in the torsinA protein at position 302 (ΔE-torsinA) [ 63 ]. The torsinA protein is an ER-resident glycoprotein and a member of the AAA + (ATPases Associated with diverse cellular Activities) protein family that play key roles in cellular functions related to protein folding, trafficking, and/or degradation [ 188 ]. Oligomerization is a conserved feature of members of the AAA +  family of ATPases, however, unlike WT-torsinA, mutant ΔE-torsinA is mislocalized and forms perinuclear aggregates [ 63 ]. Furthermore, through coimmunoprecipitation assays, it has been shown that WT torsinA interacts with the mutant protein, resulting in a dominant-negative effect by sequestering WT protein to the perinuclear region, where they form multimeric protein complexes [ 64 ]. The number of remaining functional WT-torsinA multimers would depend on the expression ratio of WT-torsinA: ΔE-torsinA. Interestingly, investigations into the degradation pathways of WT and mutant ΔE torsinA proteins have revealed divergent degradation pathways for each. WT-torsinA was found to degrade through autophagy, while ΔE-torsinA, which exhibited a significantly shorter half-life, was selectively and efficiently degraded via the proteasome through ERAD, rendering it a potential target for interventional rescue [ 64 ].

Eye disorders

Retinitis pigmentosa (RP, MIM # 613731) is a genetic degenerative eye disorder that is associated with mutations in numerous genes, which contribute to the heterogeneity of the disease. Mutations in rhodopsin gene ( RHO ) have been identified as one of the most common causes of autosomal dominant PR [ 189 ]. Rhodopsin is a light-sensitive receptor protein that plays a crucial role in the conversion of light signals into electrical signals in rod photoreceptor cells of the retina. RHO mutations have been categorized into seven categories according to their effect on the protein’s structure and function, reviewed in [ 67 ]. Rhodopsin has a high ability to form dimeric and higher order oligomers which is believed to play a key role in the photoreceptor function [ 190 ]. The most common disease-causing misfolded rhodopsin variants P23H and K296E were found to form ER-retained aggregates followed by proteasomal degradation. But if degradation was not complete, mutant rhodopsin can accumulate in photoreceptor cells, leading to cell degeneration and contributing to the development of the disease phenotypes [ 66 ]. In addition, It was demonstrated using fluorescence microscopy and immunoblot analysis that co-expression of variants P23H or G188R, together with the WT rhodopsin has resulted in the entrapment of WT rhodopsin in the ER. Misfolded dimers aggregate with the WT Rhodopsin exerting a dominant-negative effect through hetero-oligomerization [ 68 , 69 ].

Primary open angle glaucoma (POAG, # 137750), has also been identified as a leading cause for irreversible blindness due to damaged optic nerve [ 191 ]. Mutations in the myocilin gene ( MYOC ) have been associated with the disorder in several families with early onset of visual impairment. Total loss of myocilin in samples of patients harboring heterozygous mutations has been attributed to a combinational mechanism of haploinsufficiency and dominant-negative effects exerted by the entrapped mutant myocilin on the WT expressed from the functional allele [ 72 ].

Furthermore, Wolfram syndrome (WS, MIM # 222300) is a multisystemic syndrome that is characterized primarily by diabetes mellitus, optic atrophy which represent a major feature affecting nearly all reported patients, in addition to sensorineural deafness, neurodegeneration and psychological imbalances [ 192 ]. The autosomal dominant form of the disease is caused by heterozygous mutations in the WFS1 gene that encodes wolframin, a transmembrane protein that regulates calcium homeostasis within the ER. In contrast to homozygous mutants, It has been reported by many that some heterozygous misfolded wolframin exhibit a dominant-negative effect on the WT as it aggregates in the ER lumen causing ER stress and cellular toxicity [ 75 , 193 , 194 ].

Serpinopathies

Serpins are a large group of serine protease inhibitors that play a key role in regulating proteases activities across various organs [ 195 ]. Mutations in these genes result in the aggregation of mutant proteins, inducing cellular dysfunction and giving rise to a spectrum of monogenic disorders collectively termed serpinopathies. Serpins are inherently unstable, and this is mainly due to their mechanism of action, as they alternate between folded and unfolded state in order to perform their inhibitory function. Mutations that lead to unfolded proteins destabilize this fine balance and promote protein aggregate formation [ 196 ]. Heterozygous mutations in SERPINC1, SERPINA1and SERPING1 have been associated with autosomal dominant antithrombin deficiency (MIM #107300), Alpha-1-antitrypsin deficiency (A1ATD, MIM # 613490) and hereditary angioedema type 1 (HAE1,MIM # 106100), respectively. Dominant-negative variants of these three genes have been associated with the formation of mutant/WT protein aggregates in the ER, resulting in significant reduced plasma levels of the respective proteins and correlating with severe disease phenotypes [ 78 , 79 , 81 ].

Therapeutic challenges and emerging strategies in dominant-negative disorders

Treating conditions that include dominant-negative effect as a contributing mechanism can be a difficult task for medical professionals, as it presents a significant therapeutic challenge. Simply increasing protein levels is not always an effective strategy because as highlighted earlier, the mutant protein may interfere with the function of its WT counterpart [ 197 ]. This combination of the "poisoning" effect and potential ER retention and aggregation, resulting from the ER machinery involvement, requires alternative therapeutic approaches. Strategies designed to address the pathological consequences of some dominant-negative mutations fall into three main categories, utilizing diverse tools and techniques summarized in (Fig.  3 ).

Therapeutic Strategies for Dominant-negative Disorders. A Genetic modulation directly tackles the faulty gene through diverse techniques by introducing a functional copy, eliminating the mutated allele, combining both approaches, or even editing the mutation itself using advanced tools like CRISPR/Cas9 and base editing techniques B ) Post-translational modulation mainly targets correcting the underlying folding or structural deformity through chemical and pharmacological chaperones, or through directly manipulating specific components of the ER quality control machinery. For some diseases, recombinant proteins are administered to compensate for the loss of the WT protein C ) Pharmacological bypass therapy uses drugs or different pharmacological compounds to mimic the function of the WT protein or compensate for its absence, even without repairing the gene, to relieve the underlying clinical symptoms by targeting downstream pathways affected by the mutation

Therapeutic interventions aimed at counteracting dominant-negative effects may show promise for disorders characterized by ER-retention dominant-negative mechanisms. However, their efficacy depends on factors such as the nature of the disorder, the specific genetic mutation involved, and the mechanism of action of the intervention.

Genetic modulation

The straightforward approach in genetic modulation that comes to mind is to introduce a functional copy of the defective gene into the diseased cell. Therapeutic approaches aimed at increasing the amount of WT protein in autosomal dominant diseases caused by dominant-negative variants can also be effective for variants exhibiting the combinational mechanism of ER retention and dominant-negative effects. The underlying principle is the same: enhancing the availability of functional WT protein to compensate for the defective mutant protein. By boosting the levels of WT protein, these therapies can mitigate the impact of the dominant-negative mutant, regardless of whether the mutation leads to ER retention or other misfolding issues. This strategy holds promise for improving cellular function and alleviating disease symptoms across a range of genetic disorders with similar pathogenic mechanisms. In RP disorder for example, increasing WT rhodopsin to three-fold its normal level in the eyes of transgenic mice carrying the P23H ER-retained/dominant-negative variant has been shown to protects the retina, suggesting gene therapies that carefully boost rhodopsin levels could alleviate such diseases [ 198 ]. Delivering a normal copy of the RHO gene via adeno-associated virus serotype 5 (AAV) vector prevented retinal degeneration in P23H transgenic mice through the increased expression of WT rhodopsin. This aims to increase the WT to mutant protein ratio, potentially out-competing the mutant protein and subsequently restoring some function [ 199 ]. Similarly, the introduction of a WT copy of the GABRG2 gene into transgenic mice carrying the dominant-negative Q390X variant (Gabrg2 + /Q390X) associated with Dravet syndrome (epileptic encephalopathy) significantly rescued their underlying seizures [ 58 ]. However, mutated proteins with dominant-negative effects may still exert detrimental effects even with increased WT protein expression. Therefore, treating such conditions might necessitates targeting the mutant allele at the DNA or RNA levels [ 200 ]. AAV vectors have been employed to selectively disrupt the expression of the dominant-negative allele in the COL1A1 gene through the insertion of a neomycin resistance cassette to the first exon of the gene in mesenchymal stem cells (MSCs) derived from patients presented with OI, successfully demonstrating targeted gene modification in adult human stem cells [ 201 ]. Alternatively, various methodologies can be used to silence the mutated allele at the transcription level via antisense oligodeoxyribonucleotides (ODNs), short interfering RNA (siRNA), and hammerhead ribozymes. In this context, highly specific siRNA has been designed to selectively suppress the mutant torsin A protein, the primary causative factor in the most common form of primary generalized dystonia [ 202 ]. It efficiently suppressed the mutant torsin A in cells mimicking the heterozygous state without affecting the WT allele.

Given the limitations of each approach individually in effectively bypassing the underlying defect, especially for cells sensitive to haploinsufficiency, their synergistic application emerges as a viable solution. Dotzler SM and colleagues presented a therapeutic solution by incorporating a suppression-and-replacement genetic approach for LQT1 syndrome that utilizes a two-component strategy [ 203 ]. The first component is based on the use of a short hairpin RNA (shRNA) to specifically suppress the expression of the patient's endogenous, mutated KCNQ1 gene. Secondly, the introduction of a codon-altered, shRNA-immune copy of KCNQ1 , thereby achieving functional replacement of the defective allele. This dual-pronged approach demonstrates promising preclinical efficacy, as evidenced by the successful restoration of normal function in induced pluripotent stem cell-derived cardiomyocytes harboring diverse LQT1-causing KCNQ1 variants. Furthermore, it represents a feasible therapeutic strategy that can effectively address the double whammy of ER-retention and dominant negative effects by specifically silencing the mutant allele, which prevents the production of the defective protein, thereby reducing its detrimental interactions with the WT protein. Additionally, it helps in mitigating issues related to ER retention, as fewer mutant proteins are available to be retained in the ER. Consequently, more WT proteins can function correctly, improving cellular function and potentially ameliorate disease symptoms.

Fueled by the discovery of CRISPR/Cas9 technology, genetic tools have been developed to directly correct the disease-causing variant in different genetic diseases [ 204 ]. CRISPR/Cas9-mediated gene correction has been implemented in OI patients’ derived iPSCs which were differentiated to Osteoblast cells with recovered type I collagen levels [ 205 ]. Besides that, Huang et al. leveraged cutting-edge base editing technology to precisely repair a disease-causing mutation (FBN1; T7498C) in MFS, demonstrating the potential of this approach for gene therapy in MFS and other genetic disorders [ 26 ]. Unlike CRISPR/Cas9 base editing technology, the proposed technology is more precise with minimal risk of unintended mutations as it does not require the generation of a double-strand break to correct the intended nucleotide [ 206 ].

Post-translational modulation

Instead of genetically manipulating the affected gene, administration of exogenous WT proteins through protein replacement therapy has shown successful outcomes in a few diseases with dominant-negative pathophysiology. Although not universally applicable to dominant-negative disorders, the clinical success of recombinant intravenous (IV) C1INH formulations in hereditary angioedema patients underscores the therapeutic potential of protein replacement therapy for this class of diseases [ 207 ]. It demonstrates its ability to mitigate the pathological protein misfolding and abnormal ER aggregation caused by the underlying heterozygous SERPING1 variations. It's important to recognize that protein replacement therapy, despite its success in some dominant-negative diseases, may not be feasible for all due to technological limitations and individual patient factors.

Interventions that promote proper folding and prevent aggregation of the mutated protein show promise in rescuing the WT protein from ER entrapment. Pharmacological chaperones (Pcs) have been used in this context to specifically bind to the mutated protein promoting its proper folding and stabilization which will subsequently prevent its retention and premature degradation along with its WT counterpart [ 208 ]. Therefore, the application of Pcs presents a compelling strategy for targeting the combinational mechanism of dominant negative effects exerted by ER-retained mutant variants. Several studies have demonstrated the potential of retinoid analogs to act as specific PC compounds for the P23H mutation in rhodopsin, which causes RP [ 209 ]. These chaperones enhance the folding of the mutant protein and reduce its dominant-negative effect on the processing of the WT form [ 69 ]. Similarly, the IN3 PC compound corrects folding errors of several GnRH receptor (GnRHR) mutants; causative of hypogonadotropic hypogonadism, and promotes its correct intracellular trafficking along with its interacting WT subunits [ 210 ]. Unlike the targeted approach of PCs, chemical chaperones exhibit a broad-spectrum effect stabilizing various proteins and preventing aggregation in a non-specific manner [ 211 ]. For example, 4-phenylbutyrate (4-PBA) is a clinically approved medication for urea cycle disorders that showed its potential to prevent P23H rhodopsin aggregation and reduce the associated ER stress in RP [ 67 ]. In addition, protein rescue may also involve targeting specific components of ERAD and the ER machinery. Proteasomal inhibitors such as MG-132, MG-115, lactacystin, or proteasome inhibitor I prevented the premature degradation of ER-tagged caveolin-3 mutants, rescuing their interacting WT forms in a LGMD-1C cellular model [ 34 ]. Moreover, targeting the abberent activation of the UPR pathway due to ER stress in cells with accumulated misfolded proteins may offer a potential therapeutic approach in dominant-negative diseases. In a mouse model of RP, knocking out ATF4 in mice expressing the dominant-negative T17M rhodopsin mutation halted retinal degeneration. Blocking ATF4 expression lead to the downregulation of multiple UPR components like pEIF2α, ATF6, and CHOP, ultimately blocking the activation of cell death pathways [ 212 ]. Overall, addressing distinct elements within the ER machinery, aiming to mitigate the dominant-negative consequences caused by misfolded proteins and restore the WT from the underlying damage, signifies an innovative and promising frontier where cell biology intersects with medicine.

Pharmacological bypass therapy

Besides, several therapeutic interventions have been utilized to bypass the need to directly manipulate the underlying defect with various agents or pharmacological medications, often referred to as phenotypic correctors, that resemble the downstream effects of the WT protein. In ISS therapy, long-term growth hormone (GH) treatment can increase the height in childhood and adult life of familial and nonfamilial ISS cases including patients carrying heterozygous variants in the NPR2 gene showing dominant-negative effects [ 213 ]. Despite the response variability towards GH therapy, several NPR2 cases showed promising responses in height correction, especially with earlier (before puberty) and long-term administration [ 32 , 214 ]. On the other hand, myoblast cultures derived from patients with UCMD, caused by mutations in COL6A1, COL6A2, or COL6A3 genes, displayed increased cellular apoptosis. Oral treatment with cyclosporine A (an immunosuppressive drug; CsA) for one month significantly reduced apoptosis through the normalization of the mitochondrial membrane potential of the tested muscle cells [ 215 ]. The overall conclusion from this pilot study is that long-term CsA treatment influences myofiber regeneration and ameliorates muscle cell performance in treated patients. HAE1, characterized by uncontrolled plasma kallikrein due to C1INH deficiency even with heterozygous carriers, shows enhanced treatment response to drugs inhibiting kallikrein, leading to significant clinical improvement [ 207 ].

Future perspectives and conclusions

The dominant-negative effects exerted by mutant proteins on either their WT allele or interacting partners represent a major mechanism underlying various autosomal dominant genetic diseases and may contribute significantly to their wide spectrum of phenotypic clinical manifestations. Furthermore, an additional combined mechanism emerges when ER-retained mutant proteins form mixed complexes with WT counterparts or multi-subunit partners, resulting in the mis-localization and premature degradation of these WT partners. As a consequence, an additional loss of functional protein occurs, further compromising cellular function and exacerbating disease phenotypes. Thus, the dual additive impact of the dominant-negative effects and ERAD-mediated degradation is playing a pivotal role in the complexity of disease pathogenesis in numerous autosomal genetic disorders. Notably and surprisingly, this specific and highly damaging combinatorial mechanism remains relatively understudied and underappreciated in the field. This review represents an initial effort to illuminate and highlight this aspect of research, presenting significant potential for elucidating the factors influencing variant-associated phenotypic variability and detailed disease pathogenesis in numerous conditions. By highlighting these complex interactions, this review aims to promote further exploration and potentially uncover novel avenues for understanding and addressing mechanisms underlying autosomal dominant diseases. Furthermore, understanding these intricate mechanisms may offer insights into potential novel therapeutic strategies aimed at mitigating clinical presentations in these diseases including ameliorating their severity.

Availability of data and materials

All dataset was incorporated in this manuscript.

Abbreviations

4-Phenylbutyrate

Activating transcription factor 6

Bethlem myopathy disorder

Cystic fibrosis transmembrane conductance regulator

C-type natriuretic peptide

Calnexin/calreticulin

Dystrophic epidermolysis bullosa

Extracellular matrix

Ehlers-Danlos syndrome

Epidermal growth factor receptor

Endoplasmic reticulum

ER-associated protein degradation

ER quality control

Gamma-aminobutyric acid

Febrile seizures plus

Growth hormone

GnRH receptor

Hereditary haemorrhagic telangiectasia type 1

Hereditary haemorrhagic telangiectasia type 2

Heat shock proteins

Inositol requiring enzyme 1

Idiopathic short stature

Intravenous

Loeys-Dietz Syndrome

Limb-girdle muscular dystrophy

LQT syndromes

Marfan syndrome

Mesenchymal stem cells

Myocilin gene

Nonsense-mediated decay

Neurofibromatosis Type 1

Oligodeoxyribo nucleotides

Osteogenesis imperfecta

Pulmonary arterial hypertension

Pharmacological chaperones

Protein kinase RNA like endoplasmic reticulum kinase

Primary open angle glaucoma

Rhodopsin gene

Retinitis pigmentosa

Short hairpin RNA

Short interfering RNA

Stickler syndrome type1

Stickler syndrome type 2

Transforming growth factor beta

Ullrich congenital muscular dystrophy

UDP-glucose: glycoprotein glucosyltransferase

Unfolded protein response

Von Willebrand disease

Von Willebrand factor

Wolfram syndrome

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This work was supported by ASPIRE, the technology program management pillar of Abu Dhabi’s Advanced Technology Research Council (ATRC), via individual grant AARE19-086 and the ASPIRE Precision Medicine Research Institute grant VRI-20–10.

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Gariballa, N., Mohamed, F., Badawi, S. et al. The double whammy of ER-retention and dominant-negative effects in numerous autosomal dominant diseases: significance in disease mechanisms and therapy. J Biomed Sci 31 , 64 (2024). https://doi.org/10.1186/s12929-024-01054-1

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Published on 3.7.2024 in Vol 26 (2024)

Design of Digital Mental Health Platforms for Family Member Cocompletion: Scoping Review

Authors of this article:

• Ellen T Welsh 1 , BSc, MEng   ; 
• Jennifer E McIntosh 1 , PhD   ; 
• An Vuong 1 , BPsy (Hons)   ; 
• Zoe C G Cloud 1 , PhD   ; 
• Eliza Hartley 1 , DPsych   ; 
• James H Boyd 2 , PhD  

1 The Bouverie Centre, School of Psychology and Public Health, La Trobe University, Brunswick, Australia

2 School of Psychology and Public Health, La Trobe University, Bundoora, Australia

Corresponding Author:

Ellen T Welsh, BSc, MEng

The Bouverie Centre

School of Psychology and Public Health

La Trobe University

8 Gardiner Street

Brunswick, 3056

Phone: 61 384814800

Email: [email protected]

Background: The COVID-19 pandemic placed an additional mental health burden on individuals and families, resulting in widespread service access problems. Digital mental health interventions suggest promise for improved accessibility. Recent reviews have shown emerging evidence for individual use and early evidence for multiusers. However, attrition rates remain high for digital mental health interventions, and additional complexities exist when engaging multiple family members together.

Objective: As such, this scoping review aims to detail the reported evidence for digital mental health interventions designed for family use with a focus on the build and design characteristics that promote accessibility and engagement and enable cocompletion by families.

Methods: A systematic literature search of MEDLINE, Embase, PsycINFO, Web of Science, and CINAHL databases was conducted for articles published in the English language from January 2002 to March 2024. Eligible records included empirical studies of digital platforms containing some elements designed for cocompletion by related people as well as some components intended to be completed without therapist engagement. Platforms were included in cases in which clinical evidence had been documented.

Results: Of the 9527 papers reviewed, 85 (0.89%) met the eligibility criteria. A total of 24 unique platforms designed for co-use by related parties were identified. Relationships between participants included couples, parent-child dyads, family caregiver–care recipient dyads, and families. Common platform features included the delivery of content via structured interventions with no to minimal tailoring or personalization offered. Some interventions provided live contact with therapists. User engagement indicators and findings varied and included user experience, satisfaction, completion rates, and feasibility. Our findings are more remarkable for what was absent in the literature than what was present. Contrary to expectations, few studies reported any design and build characteristics that enabled coparticipation. No studies reported on platform features for enabling cocompletion or considerations for ensuring individual privacy and safety. None examined platform build or design characteristics as moderators of intervention effect, and none offered a formative evaluation of the platform itself.

Conclusions: In this early era of digital mental health platform design, this novel review demonstrates a striking absence of information about design elements associated with the successful engagement of multiple related users in any aspect of a therapeutic process. There remains a large gap in the literature detailing and evaluating platform design, highlighting a significant opportunity for future cross-disciplinary research. This review details the incentive for undertaking such research; suggests design considerations when building digital mental health platforms for use by families; and offers recommendations for future development, including platform co-design and formative evaluation.

Introduction

Family mental health.

Normatively, mental health disorders impacted >1 billion people worldwide in 2016 [ 1 ]. The COVID-19 pandemic brought further substantial impact on mental health, placing increased demand on mental health services [ 2 ]. Mental health is inherently relational [ 3 , 4 ], and family members and partners are inevitably impacted by an individual’s mental health challenges [ 5 ]. During the COVID-19 pandemic, markers of heightened family stress included rising rates of family violence [ 6 ]; increased parenting stress [ 7 ]; and observed rates of maladaptive parenting practices, including neglectful, harsh, and coercive parenting [ 8 - 10 ].

There is a strong evidence base for family and systemic interventions for child- and adult-focused mental health challenges. Family participation supports members of the family to safely contribute to individual recovery and improved relationships [ 11 - 13 ] and can be more beneficial than individual work [ 14 - 16 ] and family educational interventions [ 17 ]. In addition, parent involvement in interventions for childhood behavioral [ 18 ] and adolescent anxiety disorders [ 19 ] has been shown to be beneficial and contributes to positive long-term outcomes.

Digital Mental Health

The World Health Organization has emphasized the significant potential of digital mental health interventions (DMHIs) in expanding reach and access to services [ 20 ]. Such DMHIs have shown promise in reaching underserved populations [ 21 ], leading to improved management of symptoms in individuals [ 22 ], particularly youth aged <25 years [ 23 , 24 ]. There is growing meta-analytic evidence for positive mental health outcomes of digitally delivered versus in-person individual treatment, for example, in the field of cognitive behavioral interventions [ 25 ]. With rapid developments in technology, research interest is expanding, with most of the literature so far focused on DMHIs for individuals. For example, a review of systematic reviews of digital interventions for mental health and well-being (with no limitations placed on population) conducted in 2021 identified 246 systematic reviews published between 2016 and 2021, all of which reviewed digitally delivered mental health interventions for individuals [ 26 ].

Beyond DMHIs designed for individuals, 2 first-generation reviews of dyadic (caregiver and care recipient) [ 27 ] and couple-targeted DMHIs [ 28 ] suggest that DMHIs can decrease barriers and improve timely access and outcomes for distressed relationships. However, research into DMHIs for families to access together is as yet undeveloped.

Despite growing evidence, and regardless of the population targeted, retention rates for DMHIs remain low, limiting their ultimate impact [ 29 - 32 ]. Among other factors, interface ease of use has been identified as a barrier to DMHI retention and engagement by individuals [ 25 , 33 ]. It is likely that similar (or possibly even greater) barriers for family engagement in the digital mental health space exist. Given the fundamental differences in the approach and focus for family and relational interventions when compared to interventions designed for individuals [ 3 , 34 ], it is likely that there are unique factors to consider when designing DMHIs for use by families. This might include considerations for individual user privacy and ways in which the platform allows multiple people to contribute to and especially cocomplete activities, such as shared goal setting. Thus, it would be ill-founded to extrapolate results from studies on DMHIs designed for use by individuals and assume similar platform interaction values for families. The need for further research specific to the design of DMHIs for family use is clear.

Design of DMHIs for Families

Therefore, the question arises about what an effective DMHI for family use might look like. Given that computers and tablets are designed for use by individuals, DMHIs intended for cocompletion by family members may use different platform and interface features to support and sustain family engagement. No review to date has examined evidence for design and build characteristics that promote cocompletion usability, including improved engagement and accessibility.

In that light, this review aimed to synthesize the available evidence regarding the build and design characteristics that enable cocompletion and discuss reported indicators of user engagement with platforms designed for such use, namely, usability, satisfaction, acceptability, and feasibility. In the digital mental health literature, these user engagement indicators measure the ability of a platform to engage and sustain users. However, there is a notable lack of agreement on both the definition and measurement of the construct of engagement , which can lead to inappropriate selection, presentation, and interpretation of user engagement indicators across studies [ 35 ]. As such, a scoping review was conducted, and we adopted the definition of user engagement as outlined by Perski et al [ 36 ]: “ Engagement with [Digital Behaviour Change Interventions] is (1) the extent (e.g. amount, frequency, duration, depth) of usage and (2) a subjective experience characterised by attention, interest and affect.”

In this scoping review, we differentiate the term “platform” from the term “intervention.” We define “platform” as the tools, infrastructure, and technical foundation behind the delivery of an intervention, including interface characteristics such as the design, layout, and delivery mode. We define “intervention” as the mental health–related content that is delivered via the platform. This review sought to understand (1) the design and functionality characteristics that enable the effective engagement with and cocompletion of a family-oriented DMHI and (2) whether these elements moderate the effect of the intervention on mental health or relational outcomes. To distinguish effective platform contributors to engagement from elements pertaining to intervention content, we selected only those platforms housing interventions of established clinical efficacy (which we defined as any intervention that had at least one study reporting a significant improvement in a mental health or relational outcome). In addition, it is expected that build characteristics may vary by population, and given that there is no uniform family composition, this review scoped platforms designed for cocompletion by any family relationship type, including couples, family subsystems, and whole families.

Search Strategy

To identify studies reviewing platforms delivering clinical interventions designed for cocompletion by families, a systematic search was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines [ 37 ]. A comprehensive electronic literature search for articles published in English was conducted in the following databases: MEDLINE, Embase, and PsycINFO via the Ovid platform; CINAHL via the EBSCOhost platform, and Web of Science. In line with developments in digital technology, studies were included if they were published in or since 2002. The search was first conducted on June 24, 2022, and additional searches were conducted on November 24, 2022; April 21, 2023; and March 15, 2024.

Eligibility Criteria

As advised by the Joanna Briggs Institute’s guidelines for conducting scoping reviews [ 38 ], the population, concept, and context framework was used to define eligibility. Textbox 1 shows the inclusion and exclusion criteria in line with the population, concept, and context framework and contains additional study elements relevant to the eligibility criteria.

Studies were not excluded when platforms contained additional components involving practitioner (sometimes referred to in the studies as a coach, professional, therapist, or staff member) engagement. Further to the inclusion and exclusion criteria outlined in Textbox 1 , platforms offering interventions that had no evidence of clinical efficacy (ie, no identified studies that reported any significant improvements in mental health or relational outcomes) were excluded. Provided that at least 1 identified study established clinical efficacy for that platform, all studies on that intervention were then included regardless of whether they reported on clinical outcomes. Platforms that met all the other inclusion criteria but without established clinical efficacy are presented in Multimedia Appendix 1 .

Inclusion criteria

• Population: Digital mental health interventions (DMHIs) designed for completion by at least 2 related people together
• Concept: Platform design elements of DMHIs (via a web or smartphone interface) containing some component that was intended to be completed without therapist or human intervention (ie, was self-directed by participants)
• Context: Open and included all care settings (eg, primary care and community) and all jurisdictions and geographic locations
• Study type and design: Empirical studies
• Publication date: from January 1, 2002, to March 15, 2024
• Publication language: English

Exclusion criteria

• Population: DMHIs designed for completion by individuals or designed for use by related people but with no activities completed together (ie, completed separately) and DMHIs where children were the focus and the parent’s role was only in assisting their child to participate
• Concept: DMHIs in which the target condition was physical illness, physical activity, and weight management and programs delivered through virtual reality devices, wearable devices, DVD, or other non–web-based approaches
• Study type and design: Nonempirical studies and gray literature (ie, non–peer-reviewed or unpublished manuscripts)

Search and Data Extraction Methodology

A total of 3 key search constructs addressed the different elements of the research question: digital intervention, mental or relational health, and population. Results were combined using Boolean operators. The search strategies for each database can be found in Multimedia Appendix 2 . The reference lists of relevant reviews were also screened for potentially relevant studies. Data extraction was completed by 2 researchers trained in systematic search methodology using a standardized template, and discrepancies were resolved through discussion between the 2 researchers. In cases in which it appeared that there could be cocompletion but it was not directly specified, the study authors were contacted, and websites were searched.

Screening and Selection Process

Search results were downloaded into EndNote (Clarivate Analytics) [ 39 ] and imported into Covidence (Veritas Health Innovation) [ 40 ]. Duplicates were first removed in EndNote and again following import into Covidence. In total, 2 researchers screened the identified studies at the title and abstract level, with 20% being double screened. Disagreements were resolved through discussion. A total of 2 researchers screened the articles at the full-text level with 20% double screening to determine eligibility against the inclusion criteria outlined previously. Reasons for exclusion at the full-text level were recorded.

Data Synthesis

Data were synthesized using a narrative approach. Due to high variability in the reporting of outcomes and measurements across studies, a systematic or meta-analytic approach was not possible.

The included articles were grouped by the digital platform used. Information regarding the authors, the year of publication, the country where the study took place, the population, and associated user engagement indicators was extracted. Significant differences in mental health or relational outcomes following the DMHI were indicated. Details about the platforms were extracted into a separate table. Also detailed were the intervention target; the relationship between the participants; components designed to be completed in a self-paced manner, together, individually, or with a professional; tailored components; and any additional key features. Results were categorized and synthesized based on the targeted relationship for the intervention (eg, couples or families).

The combined searches yielded 17,765 results. Following removal of 46.37% (8238/17,765) of duplicates in EndNote and Covidence, 9527 papers were screened at the title and abstract level, resulting in 9184 (96.4%) exclusions. A total of 343 full-text articles were reviewed for inclusion, with 263 (76.7%) exclusions. Reasons for exclusion included the platform being designed for use by individuals (154/263, 58.6%), nonempirical studies (55/263, 20.9%), the platform not containing any self-guided components (36/263, 13.7%), or wrong indication (eg, weight loss intervention; 18/263, 6.8%). A total of 80 studies were included for data extraction. An additional 5 studies were identified through reference scanning and included in data extraction, resulting in a total of 85 studies included in this review. Figure 1 shows the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) diagram [ 37 ].

The following sections first summarize the studies identified and then report on characteristics of and findings related to the included platforms.

Included Studies

Table 1 details the characteristics of the 85 studies, including study type, their population and sample size, usability measures and findings, and an indication of clinical efficacy based on significant improvement in mental health or relational outcomes following completion of the intervention. Among the 85 included studies, data were collected during randomized controlled trials (n=63, 74%), pilot feasibility studies (n=14, 16%), single-arm studies (n=7, 8%), and nonrandomized quasi-experimental studies (n=1, 1%).

A total of 74% (63/85) of the studies were conducted in the United States; 12% (10/85) were conducted in Canada; 5% (4/85) were conducted in Australia; 2% (2/85) were conducted in the United Kingdom; 2% (2/85) were conducted in China; and 1% (1/85) were conducted each in the Netherlands, Sweden, Japan, and Korea. In total, 52% (44/85) of the included studies were published between January 2019 and March 2024, whereas 5% (4/85) of the studies were published in the first 5 years of the search period (2002-2006 inclusive) and the remainder (37/85, 43%) were published in between these periods.

a 4Cs:CRC: Caring for Couples Coping With Colorectal Cancer.

b RCT: randomized controlled trial.

c Indicates significance, or that the intervention was superior to the comparator, at the postintervention time point for the outcome measure.

d CA-CIFFTA: Computer-Assisted, Culturally Informed, and Flexible Family-Based Treatment for Adolescents.

e C-MBI: couple mindfulness-based intervention.

f YBCS: young breast cancer survivor.

g MBI: mindfulness-based intervention.

h I-MBI: mindfulness-based intervention for individuals.

i HOPES: Helping Overcome Posttraumatic Stress Disorder and Enhance Satisfaction.

j PTSD: posttraumatic stress disorder.

k QoL: quality of life.

l AOD: alcohol and other drug.

m CSQ: Client Satisfaction Questionnaire.

n TSQ: Treatment Satisfaction Questionnaire.

o eMB: mothers and babies online course.

p CSQ-8: 8-item Client Satisfaction Questionnaire.

q ePREP: computer-based Prevention and Relationship Enhancement Program.

r IRC: internet resource comparison.

s FOCUS: family involvement, optimistic outlook, coping effectiveness, uncertainty reduction, and symptom management.

t iCBT: internet-delivered cognitive behavioral therapy.

u MR: Mission Reconnect.

v PREP: Prevention and Relationship Enhancement Program.

w OFPS: Online Family Problem-Solving Therapy.

x TBI: traumatic brain injury.

y WEQ: Website Evaluation Questionnaire.

z OSS: Online Satisfaction Survey.

aa SES: socioeconomic status.

ab CAPS: counselor-assisted problem-solving.

ac F-PST: family-problem-solving therapy.

ad TOPS: teen online problem-solving.

ae LI-IPV: low-intensity intimate partner violence.

af OR: odds ratio.

ag PACT: Parenting Acceptance and Commitment Therapy.

ah PERC: Prostate Cancer Education and Resources for Couples.

ai WiWi: Was It Worth It questionnaire.

The Platforms

A total of 24 unique platforms were identified from the 85 studies. Table 2 shows the characteristics of the 24 platforms, including the intervention target; relationship targeted; duration of intervention participation; components designed for cocompletion, individual completion, and therapist engagement; any tailoring offered; and additional reported features.

Most interventions (14/24, 58%) were designed for cocompletion by couples, with some identified interventions for parent-child dyads (6/24, 25%), families (2/24, 8%), and caregiver–care recipient dyads (2/24, 8%). Given that it was expected that build characteristics might differ according to the population (eg, number of participating family members and their ages), platform results are grouped and reported by the relationship structure targeted by the platform (ie, couples, parent-child dyads, families, and caregiver–care recipient dyads).

Data from Table 2 are synthesized based on the features of the platforms and detail reported user engagement indicators. As platforms were included only in cases in which at least one study had demonstrated clinical efficacy of the intervention, mental health and relational outcomes are not reported in this table (and are, instead, indicated in Table 1 ).

b CA-CIFFTA: Computer-Assisted, Culturally Informed, and Flexible Family-Based Treatment for Adolescents.

c CBT: cognitive behavioral therapy.

d C-MBI: couple mindfulness-based intervention.

e YBCS: young breast cancer survivor.

f HOPES: Helping Overcome Posttraumatic Stress Disorder and Enhance Satisfaction.

g PTSD: posttraumatic stress disorder.

h eMB: mothers and babies online course.

i ePREP: computer-based Prevention and Relationship Enhancement Program.

j FOCUS: family involvement, optimistic outlook, coping effectiveness, uncertainty reduction, and symptom management.

k iCBT: internet-delivered cognitive behavioral therapy.

l MR: Mission Reconnect.

m OFPS: Online Family Problem-Solving Therapy.

n CAPS: counselor-assisted problem-solving.

o TOPS: teen online problem-solving.

p TBI: traumatic brain injury.

q OR: OurRelationship.

r PACT: Parenting Acceptance and Commitment Therapy.

s PERC: Prostate Cancer Education and Resources for Couples.

t PREP: Prevention and Relationship Enhancement Program.

Features of Platforms for Couples

Of the platforms requiring cocompletion, platforms designed for couples were the most common. A total of 58% (14/24) of the identified platforms were for couples. The intervention targets included relationship distress when a member has a cancer diagnosis (2/14, 14%); relationship functioning when a member has a cancer diagnosis (2/14, 14%), has posttraumatic stress disorder (1/14, 7%), or is a veteran (1/14, 7%); parenting-focused interventions, including a father-inclusive parenting intervention (1/14, 7%), education for foster and adoptive parents (1/14, 7%), and an intervention for military couples transitioning to parenthood (1/14, 7%); partnership support interventions for cases in which the male partner is undergoing treatment for infertility (1/14, 7%) or a member is pregnant (1/14, 7%); general relational distress (1/14, 7%); and preventative interventions to enhance relationship satisfaction and mental health (1/14, 7%) and reduce vulnerability to middle adulthood depression (1/14, 7%).

Structure and Duration of Engagement

Duration of participation varied from 1 to 16 weeks, with the most common duration being 8 weeks (5/14, 36%) followed by 6 weeks (4/14, 29%), including 1 intervention described as taking 5 to 7 weeks. The intended duration of 7% (1/14) of the interventions was not specified. One intervention offered a brief version that was completed by couples in 2 weeks as opposed to the 6-week full version. As per the inclusion criteria for this review, all interventions involved some web-based self-paced component completed on the platform. Most appeared to require at least weekly engagement, although it was not always specified or prescribed. One platform was designed such that participants could complete the intervention modules in any order but advised participants to access 1 module per week and complete all modules. For all the remaining interventions, it appeared that intervention content or modules were designed to be completed in a defined order and over a specified period.

Coparticipation and Contact With Practitioners

A total of 43% (6/14) of the interventions contained elements that were intended for individual completion (ranging from completing assessments to completion of entire sections of content), 50% (7/14) of the interventions required couples to cocomplete the whole intervention, and 7% (1/14) of the interventions gave participants the choice to complete some or all of the intervention together. In total, 57% (8/14) of the interventions included an element of practitioner engagement, including asynchronous platform-based messaging or scheduled synchronous counseling sessions.

Tailoring and Additional Features

Beyond personalization through contact with practitioners, 29% (4/14) of the platforms provided tailored content or options for personalization. A total of 14% (2/14) of the platforms provided supplementary content that could be accessed based on need, and 14% (2/14) of the platforms provided personalized feedback and reporting based on responses to questionnaires. In total, 29% (4/14) of the platforms specified that they were formatted for both web and mobile or tablet use, and 7% (1/14) of the platforms allowed participants to select either audio-enhanced or text-based presentation of content. Finally, 7% (1/14) of the platforms included an automated graph depicting reported symptom change over time and a progress bar to incentivize participation.

Reported User Engagement Indicators of Platforms for Couples

A total of 56% (48/85) of the studies examined the 14 couple-focused platforms. Of those 48 studies, 30 (62%) reported on user engagement indicators, including 23 (77%) studies that reported on satisfaction, feedback, usability, participant evaluation, feasibility, and acceptability and 18 (60%) that reported on completion rates and website use. The remaining 38% (18/48) of the studies did not report on any user engagement data or findings.

Measures used to collect participant satisfaction, feedback, usability, and evaluation varied. A total of 10% (5/48) of the studies administered the Client Evaluation of Services Questionnaire [ 126 ], and 15% (7/48) used the Client Satisfaction Questionnaire [ 127 ]. The remaining studies reported on satisfaction, feedback, and participant evaluation through nonvalidated measures. Satisfaction ratings were generally high across all studies.

The impact of video content on user engagement appeared mixed. Participants in 8% (4/48) of the studies provided feedback that the content and examples presented in the videos were helpful; however, in another 4% (2/48) of the studies, participants reported that the videos were unhelpful or that they negatively impacted engagement as they were not relatable, overly dramatized, or appeared outdated. In addition, participant qualitative feedback reported in another study suggested that outdated imagery and low-technology visualizations also negatively impacted engagement. Other factors that were reported to be important based on qualitative feedback included one study that reported on the structured nature of the intervention and reminder calls and another where participants reported that they were more likely to access audio-enhanced slides than text-based content. Feedback provided by participants in one study also noted that the flexibility of the web-based format facilitated engagement. However, in general, satisfaction, feedback, usability, and evaluation data were reported as average values on rating scales.

Reporting of completion rates and website use rates varied. They were reported as combinations of the following: the average number of participants who completed the entire intervention, the average number of modules or sessions completed by individuals or couples, the average time to completion, the number of discrete log-ins or page views, and the amount of time spent accessing the platform. Feasibility and acceptability data were reported similarly, with completion statistics often used as an indication of an intervention’s feasibility or acceptability. In addition, 5 studies reported on predictors of noncompletion, including 3 (60%) studies that reported higher levels of support from a practitioner as predictors of completion. The remaining 40% (2/5) of the studies reported on participant baseline characteristics as predictors of noncompletion.

Finally, 4% (2/48) of the studies on the same platform identified different couple “types” with regard to their enthusiasm and engagement (eg, “keen completers” or “stragglers”) and therapists’ role in engagement promotion. One study reported that higher levels of engagement (measured using participants’ correct responses to quiz questions) led to greater intervention effect on a number of clinical outcomes, and another found that those with the shortest time frame between commencement and completion (ie, completed the intervention faster) were more likely to be classified as “treatment responders” (identified by significant improvement on outcomes) at the postintervention assessment.

No studies of couple-based platforms identified build or design characteristics as moderators of intervention effect. No studies performed a formative evaluation of the platforms, and no studies reported design and build characteristics that enabled coparticipation beyond participant qualitative feedback.

Parent-Child Dyads

Features of platforms for parent-child dyads.

Platforms designed for co-use by parent-child dyads were the second most common, accounting for 25% (6/24) of the platforms identified in this review. The intervention targets included behavioral problems and conflict in young minority adolescents and their families (1/6, 17%), emotional development and parental responses to child behavior (1/6, 17%), mother-daughter relationship quality and risk of underage drinking (1/6, 17%), adolescent male domestic violence prevention (1/6, 17%), emotional availability and parent-child adjustment when a child has cerebral palsy (1/6, 17%), and anxiety management skills and psychoeducation for parents and children (1/6, 17%). A total of 67% (4/6) of the platforms were developed for adolescents and a parent, 17% (1/6) were for young children aged 2 to 7 years and a parent, and 17% (1/6) were for children aged 7 to 12 years and their parents. In all cases, only 1 parent was asked to participate. In the following sections, we summarize the reported features of the platforms as detailed in the included studies.

Duration of intervention use varied from 4 to 12 weeks, with the most common duration being 10 weeks (3/6, 50%). One intervention of a 10-week duration in total enforced an extended break in the middle of intervention engagement, and another offered a brief version of only 4 weeks (compared with the 10-week full version). Participation varied from once a fortnight to 2 web-based sessions or modules a week. A total of 83% (5/6) of the interventions appeared to involve completion in a structured manner following a predetermined order. One platform presented intervention content in a modular format that allowed participants to select the content that was relevant to their needs and cultural preferences in any order. However, the intended duration and number of modules accessed appeared to be prescribed.

The amount and method of coparticipation varied greatly. A total of 33% (2/6) of the platforms required parents to watch the intervention content or preparatory materials before engaging with their adolescent child. In total, 33% (2/6) of the platforms required the parent to complete explanation videos or additional content following cocompletion with their young child. A total of 17% (1/6) of the platforms involved cocompletion of all intervention modules and independent completion of questions about content, with both the parent and adolescent required to complete these questions before the dyad could progress to the next module. Finally, studies on 17% (1/6) of the platforms reported that “some exercises” were designed for cocompletion but did not specify the extent of cocompletion.

A total of 67% (4/6) of the interventions included contact with a practitioner, whereas 33% (2/6) were entirely self-guided. One of those offering contact with a practitioner only offered this to parents and not the participating child. A total of 33% (2/6) of the interventions included scheduled sessions with a practitioner to discuss content, with 17% (1/6) also supporting asynchronous communication with a practitioner via the platform. Finally, in 17% (1/6) of the interventions, participants could contact practitioners via the platform for technical troubleshooting as required.

In total, 17% (1/6) of the platforms allowed participants to select content based on their clinical and cultural needs. Content was selected from a list of available modules, although the process through which the dyads selected this content was not described. This same platform offered dyads links to external sources of information based on their responses to questionnaires.

Reported User Engagement Indicators of Platforms for Parent-Child Dyads

A total of 14% (12/85) of the studies evaluated 6 different interventions designed for use by parent-child dyads. Of those 12 studies, 5 (42%) reported on user engagement indicators, including completion or fidelity (4/5, 80%) and satisfaction or acceptability (3/5, 60%). The remaining 58% (7/12) of the studies reported on mental health or relational outcomes and did not report on user engagement indicators.

The 33% (4/12) of the studies reporting on completion or fidelity documented the number of participants who completed the entire intervention as prescribed. One study also reported on the average time it took participants to complete the intervention, and another reported on the number of dyads who accessed all sessions and received calls from a practitioner. No studies reported on participants’ interaction with the platform or any predictors of noncompletion.

All studies reporting on satisfaction and acceptability did so using nonvalidated measures. Mean satisfaction ratings were high. One study asked participants to indicate how easily they found time to complete the activities together, with a mean rating of 3.04/5 (SD 0.37) for daughters and a mean rating of 3.24/5 (SD 0.33) for mothers. In no study did the satisfaction and acceptability data distinguish between platform and intervention satisfaction.

No studies on parent-child interventions identified platform build or design characteristics as moderators of intervention effect. No studies performed formative evaluations of the platforms, and no studies reported on design and build characteristics that enabled coparticipation.

Features of Platforms for Families

Among the 24 platforms, 2 (8%) designed for cocompletion by families were identified. The intervention targets included family functioning when a child has an anxiety diagnosis (1/2, 50%) and family functioning when a child, adolescent, or teenager has a traumatic brain injury (1/2, 50%). Both platforms were intended for use by a child, adolescent, or teenager with a presenting clinical concern and any family members, including parents and siblings. Though siblings and other family members were invited to participate, the studies detailed outcomes and engagement for a single parent and child only.

Intervention participation on one platform extended for 10 weeks over 11 web-based chapters, and the other delivered 7 to 11 sessions over 6 months. Both were designed for sequential completion of module content.

One platform asked family members to complete the entire intervention together. The other asked parents to complete sections themselves before working with their children on a small number of modules intended for cocompletion. Both included scheduled telehealth sessions with a practitioner during intervention participation. In addition, one platform also included a platform-based message system for contacting practitioners asynchronously. In this same platform, practitioners also provided reports to participants following exercise completion.

One platform provided no tailoring beyond engagement with and feedback provided by practitioners. The other platform included supplementary sessions that could be completed by families should they wish to. In addition, this platform supported cocompletion by asking family members to select their picture when they were present. The platform would then either prompt individual family members to respond or ask all family members to respond together.

Reported User Engagement Indicators of Platforms for Families

A total of 27% (23/85) of the studies examined the 2 family-based interventions. Of these 23 studies, 16 (70%) reported user engagement indicators including satisfaction and ease of use (n=9, 56%); completion rates, compliance, adherence, and website use (n=13, 81%); and feasibility (n=2, 12%). The remaining 30% (7/23) of the studies did not report on satisfaction, completion, or feasibility data or findings.

Of the 9 studies reporting satisfaction and ease of use, 6 (67%) used an adaptation of the Website Evaluation Questionnaire [ 128 ] to measure participant satisfaction with the intervention. The remaining 33% (3/9) of the studies administered nonvalidated measures developed for the studies. Satisfaction ratings were high across all studies. In 33% (2/6) of the studies in which the Website Evaluation Questionnaire was administered, participants were asked to rate the website’s ease of use, generally reporting that the website was “moderately easy” to “easy” to use. Participants in one study reported a preference for meeting in person. Other than this, satisfaction ratings either were relevant to content or did not distinguish between platform and intervention satisfaction.

Completion rates, compliance, adherence, and website use were all reported as combinations of the following: the number of participants who completed the entire intervention, the average number of modules completed, time spent on the platform, and the number of families who completed supplemental sessions. Feasibility was reported similarly, with one study also reporting that families were able to complete all sessions without practitioner assistance. In addition, one study reported on number of sessions completed as a predictor of symptom change (with inconsistent effect), and another reported on participant characteristics at baseline as predictors of completion.

A total of 13% (3/23) of the studies also measured participants’ technology use and comfort with technology before the commencement of the intervention and examined this as a predictor of intervention effect. Results were inconsistent. In addition, one study identified whether participants’ preference for treatment modality before the intervention, that is, face-to-face, web self-paced, or therapist-guided modality, impacted treatment outcomes. It was found that adolescent treatment preference was significantly related to attrition, but there were no other links with treatment effect or satisfaction.

No studies on family-based platforms identified build or design characteristics as moderators of the intervention effect. No studies performed a formative evaluation of the platforms, and aside from one study describing how participants identified that they were present, no studies reported design and build characteristics that enabled coparticipation.

Caregiver–Care Recipient (Family) Dyads

Features of platforms for caregiver–care recipient dyads.

Among the 24 platforms, 2 (8%) were identified for family caregiver–care recipient dyads. The targets of the interventions on the platforms included dyadic resilience for patients with stroke or brain tumor and their family caregivers (1/2, 50%) and the psychosocial health of patients with cancer and their family caregivers (1/2, 50%).

One of the 2 platforms involved intervention participation over 6 weeks, with 3 sessions delivered sequentially. The other platform contained 4 web-based modules and a participant journal completed over 8 weeks. While not explicitly reported, it appeared that this platform also required sequential completion of intervention content.

Both platforms were designed to be completed by members of the dyad together; however, one had the option of completing the entire intervention independently if desired. One platform contained an asynchronous help function that generated an email to the project director. The other included a telehealth session before commencement of the web-based component.

One platform contained several tailored elements, whereas the other did not offer any personalization. Tailoring included platform-generated messages that provided web links addressing the dyad’s concerns and supplementary activities offered between web sessions. Both were generated from self-reported baseline information.

Reported User Engagement Indicators of Platforms for Caregiver–Care Recipient Dyads

The 2 interventions were each evaluated in 1% (1/85) of the studies. Both studies reported on satisfaction, and one reported on feasibility, with both reporting high satisfaction ratings. One study reported that there were no adverse effects of participants completing the intervention on the web-based platform together, and the other identified the length of the modules and the ability to complete the intervention in the users’ own time as facilitators to use. In one study, participants noted that finding time to complete the intervention as a dyad was sometimes challenging. Where feasibility was reported, the study found lower enrollment rates than those for previous in-person randomized controlled trials but higher retention rates.

Neither study identified build or design characteristics as moderators of intervention effect. No study performed a formative evaluation of the platforms, and neither reported on design nor build characteristics that enabled coparticipation.

Principal Findings

This review details build, design, and user engagement characteristics of platforms that enable cocompletion of clinical interventions by related people. To distinguish effective platform contributors to engagement from elements pertaining to intervention content, we selected only those platforms housing interventions of established clinical efficacy (ie, previously reported significant improvement of at least one mental health or relational outcome). Some common design features were identified; however, in contrast to expected findings, specific design characteristics enabling cocompletion were rarely reported, and evidence for engaging families was underexplored.

Common Platform Features

This review identified platform design features that were common across the included studies. Regardless of the relationship targeted, most platforms delivered a structured intervention that required engagement over a prescribed duration with content completed sequentially. A total of 8% (2/24) of the platforms allowed participants to access content in a nonsequential manner, and a handful (4/24, 17%) offered supplementary content based on identified need. Retention rates remain low for DMHIs [ 29 ], and there are further complexities when family members participate together [ 50 ]. As such, consideration might be given to ways in which families’ time on the platform can be optimized.

Single Session Thinking is one process through which therapists treat each encounter as if it were the sole session, encouraging the participants to make the most of the time [ 129 ]. Adaptation to web delivery of family therapy sessions already holds promise [ 130 ], and digital single-session interventions have been trialed in college student settings with positive preliminary findings [ 131 - 133 ]. Therefore, there is emerging evidence suggesting that Single Session Thinking principles could be readily applied to DMHIs, mimicking single, stand-alone sessions that address the family’s present needs as they identify them. Check-in prompts and invitations to return as needed could be automated from the platform to encourage return visits as required or desired by the family. A platform designed to deliver content in this way would likely reduce the burden on families and provide greater flexibility in how they access content.

Minimal tailoring was offered in 29% (7/24) of the DMHIs identified in this review, providing more or less the same intervention to all participants. A total of 67% (16/24) of the interventions included interaction (either synchronous or asynchronous) with a practitioner. Evidence for personalized mental health care is growing rapidly, acknowledging the complexity and diversity of individuals and families [ 134 , 135 ]. Higher levels of engagement are reported for guided interventions (ie, those where participants have some contact with a practitioner) than for self-guided interventions; however, incorporating human contact can be costly and can limit the flexibility and accessibility associated with DMHIs [ 136 ]. Research suggests that, compared with targeted or generic feedback, personalization can be used to improve engagement and subsidize personal contact and contributes to positive attitudes toward a DMHI [ 134 , 135 ]. Beyond this, several studies included in this review (9/85, 11%) identified baseline characteristics that moderated participants’ responses to the intervention. These included characteristics such as age, relationship status, and previous comfort with technology. Understanding how baseline measures might impact participants’ ability or desire to engage with platforms and providing options for personalization accordingly would likely result in greater engagement. A family-based platform might include tailored design options such as color and font choices, preferences for video- or text-based content, and preferences for receipt of prompts and reminders. In addition, if children are present, families could have the option to access content that has been adapted for younger readers. In a world where artificial intelligence is supporting personalization across the internet, it would be remiss not to consider personalization in family- and relational-based DMHIs.

Platform Features for Enabling Cocompletion

By their nature, computers and mobile devices are designed for use by individuals. Given obvious complexities involved in having multiple people participate in a web-based intervention together, it was expected that platforms designed for such use may contain features for enabling cocompletion across the life span. It was also expected that the way in which participants engage may differ from that in platforms designed for individual use. This could include considerations about privacy of individual participants’ data, methods for encouraging participants to work together, and design choices to allow all participants to contribute to activities. One platform requested participants to select their image when they were in attendance, and this was then used to prompt individuals to respond and participate in activities. Other than this, no study identified platform characteristics that were included to specifically enable cocompletion. In general, studies detailed participants’ engagement with the intervention but not with the platform. Reporting on platform engagement might include details on how participants navigated the interface, how they identified and accessed content, or the modes through which content was delivered. On the other hand, intervention reporting was found to delve into factors such as attrition rate and measurement completion. Crucially, it is important to distinguish between intervention trial attrition (ie, dropout or loss to follow-up) and platform disengagement (ie, nonuse attrition), as recommended in a previous review [ 137 ]. These 2 forms of attrition are influenced by distinct factors [ 138 , 139 ], and failure to differentiate between them could potentially lead to misinterpretation of platform engagement dynamics.

It was also expected that studies would provide insights into the build and design considerations related to individual user privacy and safety within a shared web-based space. This encompasses considerations such as determining when an individual’s information can or should be shared with other members of the family and effectively identifying and responding to safety risks. From our perspective, these design aspects are essential considerations when developing a family-based DMHI. However, none of the studies identified in this review reported or discussed how they tackled or addressed these privacy and safety considerations. To further ensure the adequate addressing of not only these concerns and anticipate other potential considerations, rigorous co-design processes are essential. This co-design strategy would significantly contribute to the refinement of family-based DMHIs, ensuring that they meet the nuanced needs of users.

Engagement With Practitioners

The varied nature of engagement with guided tools (ie, involving interaction with practitioners, structured sessions, and feedback loops) stands in stark contrast to the self-guided use and consistent participation characterizing engagement with tools lacking contact with practitioners. Recognizing challenges intrinsic to self-guided tools, such as user motivation and adherence, becomes paramount, particularly given that the absence of practitioner involvement is likely to make the sustainability of user interest more demanding. The role of technology in promoting engagement with practitioners is multifaceted, encompassing communication facilitation through asynchronous methods and data-driven insights that enhance personalized interactions. Moreover, exploring hybrid models and incorporating periodic check-ins or teletherapy sessions within self-guided platforms presents a promising balance between autonomy and professional support.

Addressing challenges in technology engagement involves prioritizing user-centered design; integrating behavioral science principles; and leveraging feedback mechanisms, either automated or through clinician input, to ensure continuous support and guidance. Looking forward, suggested avenues for future research are many, including the long-term effectiveness of guided and self-guided tools, understanding the impact of different engagement strategies, and developing sophisticated technology-assisted therapeutic approaches.

Evidence for Enabling Cocompletion

We faced constraints in reporting evidence on platform features that engaged and enabled cocompletion by families because no study conducted a direct evaluation of the platform design. This limitation hindered our ability to provide comprehensive insights into the effectiveness of features promoting cocompletion among participating family members. In addition, while several studies (13/85, 15%) evaluated practitioner support, family member coparticipation, population characteristics, and baseline scores on mental health or relational measures as moderators of intervention outcomes, no study evaluated design features as potential moderators of intervention outcomes.

Of the 85 included studies, 66 (78%) reported on user engagement indicators. Of those, most (48/66, 73%) used custom, nonvalidated measures, and the remaining studies used validated measures that were intervention specific and gave no information about platform engagement. Given this measurement heterogeneity, little is possible by way of cross-study comparison. In addition, without evaluation of platform design strategies, no conclusions can be drawn about enabling or disabling features. The capacity for real-world translation and understanding of how to overcome known barriers is constrained.

A Need for Cohesive Platform Evaluation and Reporting

Platform user experience design, including ease of use, navigation, screen layout, readability, gamification, feedback, and attractiveness, plays a large role in a participant’s perception of and engagement with a website and, ultimately, a site’s usability [ 29 , 140 , 141 ]. In addition, individual participant characteristics such as age, literacy level, level of disability, and mental health conditions may impact their engagement with and ability to use a platform as designed. When a family presents on a web-based platform, more than one person’s needs must be catered to.

There is a lack of consensus and shared understanding of how to usefully conceptualize and measure engagement with and accessibility of digital mental health platforms [ 35 , 36 ]. This variability is not unique to the context of family-based mental health platforms, with reviews of engagement in digital mental health reporting similar heterogeneity [ 35 , 134 , 142 ]. Studies tend to report on measures such as completion or attrition rates, usability, user satisfaction, acceptability, and feasibility as indicators of how well the application engaged users. Often, these data are self-reported. Given the high attrition rates for self-guided platforms [ 102 ] and additional complexities involved in requiring family members to cocomplete activities [ 50 ], understanding platform characteristics that enable co-use and promote engagement is vital to informing the future development of such platforms. There is limited direct evidence to support practitioners, developers, and designers in understanding why engagement levels remain low, and there remains a limited understanding of how to design a DMHI to optimize engagement for families.

Assessment of user engagement indicators such as completion data alone is likely insufficient to measure how well a platform engaged its users. For example, reporting on duration of participation and sessions completed neglects factors impacting how families navigate the website, such as interface design and organization, and user characteristics. Analysis of platform use patterns and baseline characteristics in addition to these completion statistics would provide greater insights into how families engage with a platform. Formative as opposed to summative evaluations of usability are conducted to inform the redesign and improvement of a web interface. Formative evaluations consider multiple factors and involve building a deep understanding of user perceptions and use patterns of platforms. In addition to self-reported measures and completion rates, formative evaluations often also consider website analytics such as bounce rate, pages per session, top exit pages, and the pathways that users take to get to pages where they ultimately spend most of their time. It is a recommendation of this review that formative evaluations of web-based mental health platforms become common practice for DMHIs, particularly for novel and complex applications such as family-based platforms.

Finally, a systematic review of evaluations of usability of mobile mental health technologies [ 143 ] recommended closer collaboration between health care and computer science experts when evaluating DMHIs, suggesting that this would increase the quality of interpretation of the evaluation. A summary of learnings from the ParentWorks trial identified an expected benefit of having involved a web agency during the early stages of content translation to optimize user experience [ 144 ]. An interdisciplinary approach might enhance knowledge sharing, too, through detailed reporting of DMHI design decisions and their interactions with platform elements and clinical outcomes.

Clearly, there remains a need for coherent reporting and evaluation practices in the field to inform guidelines and policy on effective strategies for engaging families on the web in mental health–related interventions. Until rigorous co-design with families and an interdisciplinary approach between content experts and user experience designers is taken to formative evaluations, the growth and expansion of efficacious mental health platforms for family use will lag.

Study Strengths, Limitations, and Future Research Directions

This study represents the first of its kind. Using a replicable search strategy over 4 periods, we synthesized in this study the state of the published evidence regarding platform design and build characteristics enabling successful engagement of related parties with digitally delivered mental health interventions. Given that gray literature was not searched for this review, it is possible that emerging evidence for new multiuser digital platforms was missed. Our findings are limited by the technical reporting of the studies. Principally, many studies did not provide details about their platform build or the way in which participants engaged with the platform, including whether coparticipation was expected. Where this information was not provided, the study authors were contacted, and websites were searched to retrieve the relevant information. It is likely that examination of some relevant functionality was precluded when this information was not provided or was insufficient.

Many studies (24/85, 28%) explicitly excluded participants when those other than the identified person had a mental illness. Whether through caregiving burden, stigma, or familial shared conditions, it is rare for a family presenting for therapy to have only 1 member experiencing mental health stress or significant challenges [ 145 , 146 ]. Given the potential of these platforms to aid family therapy, further research with families in which multiple members experience stress or mental health challenges is needed. Until then, it is difficult to generalize the evidence reported in this review to the real-world experience of families who may present for family therapy.

In addition, diversity in populations was limited, with most studies including White, heterosexual, and middle-class participants. There was a lack of evidence from low- and middle-income countries (LMICs), with all studies conducted in more high-income countries. The technological experiences and needs of families in LMICs will likely vary significantly from those in more high-income countries given, among other factors, the varying degree of ease of access to technology. Digital interventions have the potential to expand reach and access to services; however, until participants from LMICs are included in studies of digital platforms for families, findings cannot be generalized to these populations and ultimate reach will be limited.

As this is a new and novel field, language and terminology are still being defined, and means of measuring and defining engagement and feasibility are not well established [ 29 ]. Of the included studies, 52% (44/85) were published in the last 5 years, reflecting rapid developments in technology and associated applications.

Conclusions

While there is emerging evidence suggesting that DMHIs are clinically effective, there remains a large evidence gap in the literature on the extent to which platform-specific design and build elements may also contribute to timely access, user experience, safe cocompletion by family members, and clinical outcomes. In the service of improved mental and relational health outcomes, our findings point to a significant opportunity for meaningful cross-disciplinary research, development, and evaluation of family-based mental health platforms. Findings from the next era of research will be central to enabling policy and practice advancements in equitable access to effective mental health care support for families.

Data Availability

All data generated or analyzed during this study are included in this published article (and its supplementary information files).

Conflicts of Interest

None declared.

Excluded studies and platforms.

Search strategies.

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Abbreviations

Edited by A Mavragani; submitted 29.05.23; peer-reviewed by M Ali, M Loades, F Tong; comments to author 01.12.23; revised version received 13.12.23; accepted 04.05.24; published 03.07.24.

©Ellen T Welsh, Jennifer E McIntosh, An Vuong, Zoe C G Cloud, Eliza Hartley, James H Boyd. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 03.07.2024.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in the Journal of Medical Internet Research (ISSN 1438-8871), is properly cited. The complete bibliographic information, a link to the original publication on https://www.jmir.org/, as well as this copyright and license information must be included.