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• How to Write a Literature Review | Guide, Examples, & Templates

How to Write a Literature Review | Guide, Examples, & Templates

Published on January 2, 2023 by Shona McCombes . Revised on September 11, 2023.

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 that you can later apply to your paper, thesis, or dissertation topic .

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 summarize sources—it analyzes, synthesizes , and critically evaluates to give a clear picture of the state of knowledge on the subject.

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Table of contents

What is the purpose of 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, free lecture slides, other interesting articles, frequently asked questions, introduction.

• Quick Run-through
• Step 1 & 2

When you write a thesis , dissertation , or research paper , you will likely 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 its scholarly context
• Develop a theoretical framework and methodology for your research
• Position your work in relation to other researchers and theorists
• Show how your research addresses a gap or contributes to a debate
• Evaluate the current state of research and demonstrate your knowledge of the scholarly debates around your topic.

Writing literature reviews is a particularly important skill if you want to apply for graduate school or pursue a career in research. 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 problem and questions .

Make a list of keywords

Start by creating a list of keywords related to your research question. 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 as 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 useful 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 also use boolean operators to help narrow down your search.

Make sure to 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.

You likely won’t be able to read absolutely everything that has been written on your topic, so it will be necessary to evaluate which sources are most relevant to your research question.

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?
• 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 use our template to summarize and evaluate sources you’re thinking about using. Click on either button below to download.

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 is important to keep track of your sources with citations to avoid plagiarism . It can be helpful to make an annotated bibliography , where you compile full citation 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.

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To begin organizing your literature review’s argument and structure, be sure you 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 organizing the body of a literature review. 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 summarizing sources in order.

Try to analyze 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 organize 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.

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, you can follow these tips:

• 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 sentences to draw connections, comparisons and contrasts

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

When you’ve finished writing and revising your literature review, don’t forget to proofread thoroughly before submitting. Not a language expert? Check out Scribbr’s professional proofreading services !

This article has been adapted into lecture slides that you can use to teach your students about writing a literature review.

Scribbr slides are free to use, customize, and distribute for educational purposes.

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

• Sampling methods
• Simple random sampling
• Stratified sampling
• Cluster sampling
• Likert scales
• Reproducibility

 Statistics

• Null hypothesis
• Statistical power
• Probability distribution
• Effect size
• Poisson distribution

Research bias

• Optimism bias
• Cognitive bias
• Implicit bias
• Hawthorne effect
• Anchoring bias
• Explicit bias

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

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

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

• To familiarize 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 thesis or dissertation . After the introduction , it grounds your research in a scholarly field and leads directly to your theoretical framework or methodology .

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

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

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Literature Reviews: systematic searching at various levels

• for assignments
• for dissertations / theses
• Search strategy and searching
• Boolean Operators
• Search strategy template
• Screening & critiquing
• Citation Searching
• Google Scholar (with Lean Library)
• Resources for literature reviews
• Adding a referencing style to EndNote
• Exporting from different databases

PRISMA Flow Diagram

• Grey Literature
• What is the PRISMA Flow Diagram?
• How should I use it?
• When should I use it?
• PRISMA Links

The PRISMA Flow Diagram is a tool that can be used to record different stages of the literature search process--across multiple resources--and clearly show how a researcher went from, 'These are the databases I searched for my terms', to, 'These are the papers I'm going to talk about'.

PRISMA is not inflexible; it can be modified to suit the research needs of different people and, indeed, if you did a Google images search for the flow diagram you would see many different versions of the diagram being used. It's a good idea to have a look at a couple of those examples, and also to have a look at a couple of the articles on the PRISMA website to see how it has--and can--be used.

The PRISMA 2020 Statement was published in 2021. It consists of a  checklist  and a  flow diagram , and is intended to be accompanied by the PRISMA 2020 Explanation and Elaboration document.

In order to encourage dissemination of the PRISMA 2020 Statement, it has been published in several journals.

• How to use the PRISMA Flow Diagram for literature reviews A PDF [3.81MB] of the PowerPoint used to create the video. Each slide that has notes has a callout icon on the top right of the page which can be toggled on or off to make the notes visible.

There is also a PowerPoint version of the document but the file size is too large to upload here.

If you would like a copy, please email the Academic Librarians' mailbox from your university account to ask for it to be sent to you.

This is an example of how you  could  fill in the PRISMA flow diagram when conducting a new review. It is not a hard and fast rule but it should give you an idea of how you can use it.

For more detailed information, please have a look at this article:

Page, M.J., McKenzie, J.E., Bossuyt, P.M., Boutron, I., Hoffmann, T.C., Mulrow, C.D., Shamseer, L., Tetzlaff, J.M., Akl, E.A., Brennan, S.E., Chou, R., Glanville, J., Grimshaw, J.M., Hróbjartsson, A., Lalu, M.M., Li, T., Loder, E.W., Mayo-Wilson, E., McDonald, S., McGuinness, L.A., Stewart, L.A., Thomas, J., Tricco, A.C., Welch, V.A., Whiting,P. & Moher, D. (2021) 'The PRISMA 2020 statement: an updated guideline for reporting systematic reviews',  BMJ 372:(71). doi: 10.1136/bmj.n71 .

• Example of PRISMA 2020 diagram This is an example of *one* of the PRISMA 2020 flow diagrams you can use when reporting on your research process. There is more than one form that you can use so for other forms and advice please look at the PRISMA website for full details.

Start using the flow diagram as you start searching the databases you've decided upon. 

Make sure that you record the number of results that you found per database (before removing any duplicates) as per the filled in example. You can also do a Google images search for the PRISMA flow diagram to see the different ways in which people have used them to express their search processes.

• Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) PRISMA is an evidence-based minimum set of items for reporting in systematic reviews and meta-analyses. PRISMA focuses on the reporting of reviews evaluating randomized trials, but can also be used as a basis for reporting systematic reviews of other types of research, particularly evaluations of interventions.
• Prisma Flow Diagram This link will take you to downloadable Word and PDF copies of the flow diagram. These are modifiable and act as a starting point for you to record the process you engaged in from first search to the papers you ultimately discuss in your work. more... less... Do an image search on the internet for the flow diagram and you will be able to see all the different ways that people have modified the diagram to suit their personal research needs.

You can access the various checklists via the Equator website and the articles explaining PRISMA and its various extensions are available via PubMed.

Page, M.J., McKenzie, J.E., Bossuyt, P.M., Boutron, I., Hoffmann, T.C., Mulrow, C.D., Shamseer, L., Tetzlaff, J.M., Akl, E.A., Brennan, S.E., Chou, R., Glanville, J., Grimshaw, J.M., Hróbjartsson, A., Lalu, M.M., Li, T., Loder, E.W., Mayo-Wilson, E., McDonald, S., McGuinness, L.A., Stewart, L.A., Thomas, J., Tricco, A.C., Welch, V.A., Whiting, P., & Moher, D. (2021) ' The PRISMA 2020 statement: an updated guideline for reporting systematic reviews,'  BMJ .  Mar 29; 372:n71. doi: 10.1136/bmj.n71 .

Page, M.J., Moher, D., Bossuyt, P.M., Boutron, I., Hoffmann, T.C., Mulrow, C.D., Shamseer, L., Tetzlaff, J.M., Akl, E.A., Brennan, S.E., Chou, R., Glanville, J., Grimshaw, J.M., Hróbjartsson, A., Lalu, M.M., Li, T., Loder, E.W., Mayo-Wilson, E., McDonald, S., McGuinness, L.A., Stewart, L.A., Thomas, J., Tricco, A.C., Welch, V.A., Whiting, P., & McKenzie, J.E. (2021)  'PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews',  BMJ, Mar 29; 372:n160. doi: 10.1136/bmj.n160 .

Page, M.J., McKenzie, J.E., Bossuyt, P.M., Boutron, I., Hoffmann, T.C., Mulrow, C.D., Shamseer, L., Tetzlaff, J.M., Akl, E.A., Brennan, S.E., Chou, R., Glanville, J., Grimshaw, J.M., Hróbjartsson, A., Lalu, M.M., Li, T., Loder, E.W., Mayo-Wilson, E., McDonald, S., McGuinness, L.A., Stewart, L.A., Thomas, J., Tricco, A.C., Welch, V.A., Whiting, P., & Moher, D. (2021) ' The PRISMA 2020 statement: An updated guideline for reporting systematic reviews,'  Journal of Clinical Epidemiology, June; 134:178-189. doi: 10.1016/j.jclinepi.2021.03.001 . 

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The PRISMA 2020 statement: an updated guideline for reporting systematic reviews

PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews

• Related content
• Peer review
• Matthew J Page , senior research fellow 1 ,
• Joanne E McKenzie , associate professor 1 ,
• Patrick M Bossuyt , professor 2 ,
• Isabelle Boutron , professor 3 ,
• Tammy C Hoffmann , professor 4 ,
• Cynthia D Mulrow , professor 5 ,
• Larissa Shamseer , doctoral student 6 ,
• Jennifer M Tetzlaff , research product specialist 7 ,
• Elie A Akl , professor 8 ,
• Sue E Brennan , senior research fellow 1 ,
• Roger Chou , professor 9 ,
• Julie Glanville , associate director 10 ,
• Jeremy M Grimshaw , professor 11 ,
• Asbjørn Hróbjartsson , professor 12 ,
• Manoj M Lalu , associate scientist and assistant professor 13 ,
• Tianjing Li , associate professor 14 ,
• Elizabeth W Loder , professor 15 ,
• Evan Mayo-Wilson , associate professor 16 ,
• Steve McDonald , senior research fellow 1 ,
• Luke A McGuinness , research associate 17 ,
• Lesley A Stewart , professor and director 18 ,
• James Thomas , professor 19 ,
• Andrea C Tricco , scientist and associate professor 20 ,
• Vivian A Welch , associate professor 21 ,
• Penny Whiting , associate professor 17 ,
• David Moher , director and professor 22
• 1 School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
• 2 Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, Netherlands
• 3 Université de Paris, Centre of Epidemiology and Statistics (CRESS), Inserm, F 75004 Paris, France
• 4 Institute for Evidence-Based Healthcare, Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Australia
• 5 University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA; Annals of Internal Medicine
• 6 Knowledge Translation Program, Li Ka Shing Knowledge Institute, Toronto, Canada; School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, Canada
• 7 Evidence Partners, Ottawa, Canada
• 8 Clinical Research Institute, American University of Beirut, Beirut, Lebanon; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada
• 9 Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, Oregon, USA
• 10 York Health Economics Consortium (YHEC Ltd), University of York, York, UK
• 11 Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada; School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada; Department of Medicine, University of Ottawa, Ottawa, Canada
• 12 Centre for Evidence-Based Medicine Odense (CEBMO) and Cochrane Denmark, Department of Clinical Research, University of Southern Denmark, Odense, Denmark; Open Patient data Exploratory Network (OPEN), Odense University Hospital, Odense, Denmark
• 13 Department of Anesthesiology and Pain Medicine, The Ottawa Hospital, Ottawa, Canada; Clinical Epidemiology Program, Blueprint Translational Research Group, Ottawa Hospital Research Institute, Ottawa, Canada; Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Canada
• 14 Department of Ophthalmology, School of Medicine, University of Colorado Denver, Denver, Colorado, United States; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
• 15 Division of Headache, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Head of Research, The BMJ , London, UK
• 16 Department of Epidemiology and Biostatistics, Indiana University School of Public Health-Bloomington, Bloomington, Indiana, USA
• 17 Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
• 18 Centre for Reviews and Dissemination, University of York, York, UK
• 19 EPPI-Centre, UCL Social Research Institute, University College London, London, UK
• 20 Li Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, Toronto, Canada; Epidemiology Division of the Dalla Lana School of Public Health and the Institute of Health Management, Policy, and Evaluation, University of Toronto, Toronto, Canada; Queen's Collaboration for Health Care Quality Joanna Briggs Institute Centre of Excellence, Queen's University, Kingston, Canada
• 21 Methods Centre, Bruyère Research Institute, Ottawa, Ontario, Canada; School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, Canada
• 22 Centre for Journalology, Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada; School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, Canada
• Correspondence to: M J Page matthew.page{at}monash.edu
• Accepted 4 January 2021

The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found. Over the past decade, advances in systematic review methodology and terminology have necessitated an update to the guideline. The PRISMA 2020 statement replaces the 2009 statement and includes new reporting guidance that reflects advances in methods to identify, select, appraise, and synthesise studies. The structure and presentation of the items have been modified to facilitate implementation. In this article, we present the PRISMA 2020 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and the revised flow diagrams for original and updated reviews.

Systematic reviews serve many critical roles. They can provide syntheses of the state of knowledge in a field, from which future research priorities can be identified; they can address questions that otherwise could not be answered by individual studies; they can identify problems in primary research that should be rectified in future studies; and they can generate or evaluate theories about how or why phenomena occur. Systematic reviews therefore generate various types of knowledge for different users of reviews (such as patients, healthcare providers, researchers, and policy makers). 1 2 To ensure a systematic review is valuable to users, authors should prepare a transparent, complete, and accurate account of why the review was done, what they did (such as how studies were identified and selected) and what they found (such as characteristics of contributing studies and results of meta-analyses). Up-to-date reporting guidance facilitates authors achieving this. 3

The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement published in 2009 (hereafter referred to as PRISMA 2009) 4 5 6 7 8 9 10 is a reporting guideline designed to address poor reporting of systematic reviews. 11 The PRISMA 2009 statement comprised a checklist of 27 items recommended for reporting in systematic reviews and an “explanation and elaboration” paper 12 13 14 15 16 providing additional reporting guidance for each item, along with exemplars of reporting. The recommendations have been widely endorsed and adopted, as evidenced by its co-publication in multiple journals, citation in over 60 000 reports (Scopus, August 2020), endorsement from almost 200 journals and systematic review organisations, and adoption in various disciplines. Evidence from observational studies suggests that use of the PRISMA 2009 statement is associated with more complete reporting of systematic reviews, 17 18 19 20 although more could be done to improve adherence to the guideline. 21

Many innovations in the conduct of systematic reviews have occurred since publication of the PRISMA 2009 statement. For example, technological advances have enabled the use of natural language processing and machine learning to identify relevant evidence, 22 23 24 methods have been proposed to synthesise and present findings when meta-analysis is not possible or appropriate, 25 26 27 and new methods have been developed to assess the risk of bias in results of included studies. 28 29 Evidence on sources of bias in systematic reviews has accrued, culminating in the development of new tools to appraise the conduct of systematic reviews. 30 31 Terminology used to describe particular review processes has also evolved, as in the shift from assessing “quality” to assessing “certainty” in the body of evidence. 32 In addition, the publishing landscape has transformed, with multiple avenues now available for registering and disseminating systematic review protocols, 33 34 disseminating reports of systematic reviews, and sharing data and materials, such as preprint servers and publicly accessible repositories. To capture these advances in the reporting of systematic reviews necessitated an update to the PRISMA 2009 statement.

Summary points

To ensure a systematic review is valuable to users, authors should prepare a transparent, complete, and accurate account of why the review was done, what they did, and what they found

The PRISMA 2020 statement provides updated reporting guidance for systematic reviews that reflects advances in methods to identify, select, appraise, and synthesise studies

The PRISMA 2020 statement consists of a 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and revised flow diagrams for original and updated reviews

We anticipate that the PRISMA 2020 statement will benefit authors, editors, and peer reviewers of systematic reviews, and different users of reviews, including guideline developers, policy makers, healthcare providers, patients, and other stakeholders

Development of PRISMA 2020

A complete description of the methods used to develop PRISMA 2020 is available elsewhere. 35 We identified PRISMA 2009 items that were often reported incompletely by examining the results of studies investigating the transparency of reporting of published reviews. 17 21 36 37 We identified possible modifications to the PRISMA 2009 statement by reviewing 60 documents providing reporting guidance for systematic reviews (including reporting guidelines, handbooks, tools, and meta-research studies). 38 These reviews of the literature were used to inform the content of a survey with suggested possible modifications to the 27 items in PRISMA 2009 and possible additional items. Respondents were asked whether they believed we should keep each PRISMA 2009 item as is, modify it, or remove it, and whether we should add each additional item. Systematic review methodologists and journal editors were invited to complete the online survey (110 of 220 invited responded). We discussed proposed content and wording of the PRISMA 2020 statement, as informed by the review and survey results, at a 21-member, two-day, in-person meeting in September 2018 in Edinburgh, Scotland. Throughout 2019 and 2020, we circulated an initial draft and five revisions of the checklist and explanation and elaboration paper to co-authors for feedback. In April 2020, we invited 22 systematic reviewers who had expressed interest in providing feedback on the PRISMA 2020 checklist to share their views (via an online survey) on the layout and terminology used in a preliminary version of the checklist. Feedback was received from 15 individuals and considered by the first author, and any revisions deemed necessary were incorporated before the final version was approved and endorsed by all co-authors.

The PRISMA 2020 statement

Scope of the guideline.

The PRISMA 2020 statement has been designed primarily for systematic reviews of studies that evaluate the effects of health interventions, irrespective of the design of the included studies. However, the checklist items are applicable to reports of systematic reviews evaluating other interventions (such as social or educational interventions), and many items are applicable to systematic reviews with objectives other than evaluating interventions (such as evaluating aetiology, prevalence, or prognosis). PRISMA 2020 is intended for use in systematic reviews that include synthesis (such as pairwise meta-analysis or other statistical synthesis methods) or do not include synthesis (for example, because only one eligible study is identified). The PRISMA 2020 items are relevant for mixed-methods systematic reviews (which include quantitative and qualitative studies), but reporting guidelines addressing the presentation and synthesis of qualitative data should also be consulted. 39 40 PRISMA 2020 can be used for original systematic reviews, updated systematic reviews, or continually updated (“living”) systematic reviews. However, for updated and living systematic reviews, there may be some additional considerations that need to be addressed. Where there is relevant content from other reporting guidelines, we reference these guidelines within the items in the explanation and elaboration paper 41 (such as PRISMA-Search 42 in items 6 and 7, Synthesis without meta-analysis (SWiM) reporting guideline 27 in item 13d). Box 1 includes a glossary of terms used throughout the PRISMA 2020 statement.

Glossary of terms

Systematic review —A review that uses explicit, systematic methods to collate and synthesise findings of studies that address a clearly formulated question 43

Statistical synthesis —The combination of quantitative results of two or more studies. This encompasses meta-analysis of effect estimates (described below) and other methods, such as combining P values, calculating the range and distribution of observed effects, and vote counting based on the direction of effect (see McKenzie and Brennan 25 for a description of each method)

Meta-analysis of effect estimates —A statistical technique used to synthesise results when study effect estimates and their variances are available, yielding a quantitative summary of results 25

Outcome —An event or measurement collected for participants in a study (such as quality of life, mortality)

Result —The combination of a point estimate (such as a mean difference, risk ratio, or proportion) and a measure of its precision (such as a confidence/credible interval) for a particular outcome

Report —A document (paper or electronic) supplying information about a particular study. It could be a journal article, preprint, conference abstract, study register entry, clinical study report, dissertation, unpublished manuscript, government report, or any other document providing relevant information

Record —The title or abstract (or both) of a report indexed in a database or website (such as a title or abstract for an article indexed in Medline). Records that refer to the same report (such as the same journal article) are “duplicates”; however, records that refer to reports that are merely similar (such as a similar abstract submitted to two different conferences) should be considered unique.

Study —An investigation, such as a clinical trial, that includes a defined group of participants and one or more interventions and outcomes. A “study” might have multiple reports. For example, reports could include the protocol, statistical analysis plan, baseline characteristics, results for the primary outcome, results for harms, results for secondary outcomes, and results for additional mediator and moderator analyses

PRISMA 2020 is not intended to guide systematic review conduct, for which comprehensive resources are available. 43 44 45 46 However, familiarity with PRISMA 2020 is useful when planning and conducting systematic reviews to ensure that all recommended information is captured. PRISMA 2020 should not be used to assess the conduct or methodological quality of systematic reviews; other tools exist for this purpose. 30 31 Furthermore, PRISMA 2020 is not intended to inform the reporting of systematic review protocols, for which a separate statement is available (PRISMA for Protocols (PRISMA-P) 2015 statement 47 48 ). Finally, extensions to the PRISMA 2009 statement have been developed to guide reporting of network meta-analyses, 49 meta-analyses of individual participant data, 50 systematic reviews of harms, 51 systematic reviews of diagnostic test accuracy studies, 52 and scoping reviews 53 ; for these types of reviews we recommend authors report their review in accordance with the recommendations in PRISMA 2020 along with the guidance specific to the extension.

How to use PRISMA 2020

The PRISMA 2020 statement (including the checklists, explanation and elaboration, and flow diagram) replaces the PRISMA 2009 statement, which should no longer be used. Box 2 summarises noteworthy changes from the PRISMA 2009 statement. The PRISMA 2020 checklist includes seven sections with 27 items, some of which include sub-items ( table 1 ). A checklist for journal and conference abstracts for systematic reviews is included in PRISMA 2020. This abstract checklist is an update of the 2013 PRISMA for Abstracts statement, 54 reflecting new and modified content in PRISMA 2020 ( table 2 ). A template PRISMA flow diagram is provided, which can be modified depending on whether the systematic review is original or updated ( fig 1 ).

Noteworthy changes to the PRISMA 2009 statement

Inclusion of the abstract reporting checklist within PRISMA 2020 (see item #2 and table 2 ).

Movement of the ‘Protocol and registration’ item from the start of the Methods section of the checklist to a new Other section, with addition of a sub-item recommending authors describe amendments to information provided at registration or in the protocol (see item #24a-24c).

Modification of the ‘Search’ item to recommend authors present full search strategies for all databases, registers and websites searched, not just at least one database (see item #7).

Modification of the ‘Study selection’ item in the Methods section to emphasise the reporting of how many reviewers screened each record and each report retrieved, whether they worked independently, and if applicable, details of automation tools used in the process (see item #8).

Addition of a sub-item to the ‘Data items’ item recommending authors report how outcomes were defined, which results were sought, and methods for selecting a subset of results from included studies (see item #10a).

Splitting of the ‘Synthesis of results’ item in the Methods section into six sub-items recommending authors describe: the processes used to decide which studies were eligible for each synthesis; any methods required to prepare the data for synthesis; any methods used to tabulate or visually display results of individual studies and syntheses; any methods used to synthesise results; any methods used to explore possible causes of heterogeneity among study results (such as subgroup analysis, meta-regression); and any sensitivity analyses used to assess robustness of the synthesised results (see item #13a-13f).

Addition of a sub-item to the ‘Study selection’ item in the Results section recommending authors cite studies that might appear to meet the inclusion criteria, but which were excluded, and explain why they were excluded (see item #16b).

Splitting of the ‘Synthesis of results’ item in the Results section into four sub-items recommending authors: briefly summarise the characteristics and risk of bias among studies contributing to the synthesis; present results of all statistical syntheses conducted; present results of any investigations of possible causes of heterogeneity among study results; and present results of any sensitivity analyses (see item #20a-20d).

Addition of new items recommending authors report methods for and results of an assessment of certainty (or confidence) in the body of evidence for an outcome (see items #15 and #22).

Addition of a new item recommending authors declare any competing interests (see item #26).

Addition of a new item recommending authors indicate whether data, analytic code and other materials used in the review are publicly available and if so, where they can be found (see item #27).

PRISMA 2020 item checklist

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PRISMA 2020 for Abstracts checklist*

PRISMA 2020 flow diagram template for systematic reviews. The new design is adapted from flow diagrams proposed by Boers, 55 Mayo-Wilson et al. 56 and Stovold et al. 57 The boxes in grey should only be completed if applicable; otherwise they should be removed from the flow diagram. Note that a “report” could be a journal article, preprint, conference abstract, study register entry, clinical study report, dissertation, unpublished manuscript, government report or any other document providing relevant information.

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We recommend authors refer to PRISMA 2020 early in the writing process, because prospective consideration of the items may help to ensure that all the items are addressed. To help keep track of which items have been reported, the PRISMA statement website ( http://www.prisma-statement.org/ ) includes fillable templates of the checklists to download and complete (also available in the data supplement on bmj.com). We have also created a web application that allows users to complete the checklist via a user-friendly interface 58 (available at https://prisma.shinyapps.io/checklist/ and adapted from the Transparency Checklist app 59 ). The completed checklist can be exported to Word or PDF. Editable templates of the flow diagram can also be downloaded from the PRISMA statement website.

We have prepared an updated explanation and elaboration paper, in which we explain why reporting of each item is recommended and present bullet points that detail the reporting recommendations (which we refer to as elements). 41 The bullet-point structure is new to PRISMA 2020 and has been adopted to facilitate implementation of the guidance. 60 61 An expanded checklist, which comprises an abridged version of the elements presented in the explanation and elaboration paper, with references and some examples removed, is available in the data supplement on bmj.com. Consulting the explanation and elaboration paper is recommended if further clarity or information is required.

Journals and publishers might impose word and section limits, and limits on the number of tables and figures allowed in the main report. In such cases, if the relevant information for some items already appears in a publicly accessible review protocol, referring to the protocol may suffice. Alternatively, placing detailed descriptions of the methods used or additional results (such as for less critical outcomes) in supplementary files is recommended. Ideally, supplementary files should be deposited to a general-purpose or institutional open-access repository that provides free and permanent access to the material (such as Open Science Framework, Dryad, figshare). A reference or link to the additional information should be included in the main report. Finally, although PRISMA 2020 provides a template for where information might be located, the suggested location should not be seen as prescriptive; the guiding principle is to ensure the information is reported.

Use of PRISMA 2020 has the potential to benefit many stakeholders. Complete reporting allows readers to assess the appropriateness of the methods, and therefore the trustworthiness of the findings. Presenting and summarising characteristics of studies contributing to a synthesis allows healthcare providers and policy makers to evaluate the applicability of the findings to their setting. Describing the certainty in the body of evidence for an outcome and the implications of findings should help policy makers, managers, and other decision makers formulate appropriate recommendations for practice or policy. Complete reporting of all PRISMA 2020 items also facilitates replication and review updates, as well as inclusion of systematic reviews in overviews (of systematic reviews) and guidelines, so teams can leverage work that is already done and decrease research waste. 36 62 63

We updated the PRISMA 2009 statement by adapting the EQUATOR Network’s guidance for developing health research reporting guidelines. 64 We evaluated the reporting completeness of published systematic reviews, 17 21 36 37 reviewed the items included in other documents providing guidance for systematic reviews, 38 surveyed systematic review methodologists and journal editors for their views on how to revise the original PRISMA statement, 35 discussed the findings at an in-person meeting, and prepared this document through an iterative process. Our recommendations are informed by the reviews and survey conducted before the in-person meeting, theoretical considerations about which items facilitate replication and help users assess the risk of bias and applicability of systematic reviews, and co-authors’ experience with authoring and using systematic reviews.

Various strategies to increase the use of reporting guidelines and improve reporting have been proposed. They include educators introducing reporting guidelines into graduate curricula to promote good reporting habits of early career scientists 65 ; journal editors and regulators endorsing use of reporting guidelines 18 ; peer reviewers evaluating adherence to reporting guidelines 61 66 ; journals requiring authors to indicate where in their manuscript they have adhered to each reporting item 67 ; and authors using online writing tools that prompt complete reporting at the writing stage. 60 Multi-pronged interventions, where more than one of these strategies are combined, may be more effective (such as completion of checklists coupled with editorial checks). 68 However, of 31 interventions proposed to increase adherence to reporting guidelines, the effects of only 11 have been evaluated, mostly in observational studies at high risk of bias due to confounding. 69 It is therefore unclear which strategies should be used. Future research might explore barriers and facilitators to the use of PRISMA 2020 by authors, editors, and peer reviewers, designing interventions that address the identified barriers, and evaluating those interventions using randomised trials. To inform possible revisions to the guideline, it would also be valuable to conduct think-aloud studies 70 to understand how systematic reviewers interpret the items, and reliability studies to identify items where there is varied interpretation of the items.

We encourage readers to submit evidence that informs any of the recommendations in PRISMA 2020 (via the PRISMA statement website: http://www.prisma-statement.org/ ). To enhance accessibility of PRISMA 2020, several translations of the guideline are under way (see available translations at the PRISMA statement website). We encourage journal editors and publishers to raise awareness of PRISMA 2020 (for example, by referring to it in journal “Instructions to authors”), endorsing its use, advising editors and peer reviewers to evaluate submitted systematic reviews against the PRISMA 2020 checklists, and making changes to journal policies to accommodate the new reporting recommendations. We recommend existing PRISMA extensions 47 49 50 51 52 53 71 72 be updated to reflect PRISMA 2020 and advise developers of new PRISMA extensions to use PRISMA 2020 as the foundation document.

We anticipate that the PRISMA 2020 statement will benefit authors, editors, and peer reviewers of systematic reviews, and different users of reviews, including guideline developers, policy makers, healthcare providers, patients, and other stakeholders. Ultimately, we hope that uptake of the guideline will lead to more transparent, complete, and accurate reporting of systematic reviews, thus facilitating evidence based decision making.

Acknowledgments

We dedicate this paper to the late Douglas G Altman and Alessandro Liberati, whose contributions were fundamental to the development and implementation of the original PRISMA statement.

We thank the following contributors who completed the survey to inform discussions at the development meeting: Xavier Armoiry, Edoardo Aromataris, Ana Patricia Ayala, Ethan M Balk, Virginia Barbour, Elaine Beller, Jesse A Berlin, Lisa Bero, Zhao-Xiang Bian, Jean Joel Bigna, Ferrán Catalá-López, Anna Chaimani, Mike Clarke, Tammy Clifford, Ioana A Cristea, Miranda Cumpston, Sofia Dias, Corinna Dressler, Ivan D Florez, Joel J Gagnier, Chantelle Garritty, Long Ge, Davina Ghersi, Sean Grant, Gordon Guyatt, Neal R Haddaway, Julian PT Higgins, Sally Hopewell, Brian Hutton, Jamie J Kirkham, Jos Kleijnen, Julia Koricheva, Joey SW Kwong, Toby J Lasserson, Julia H Littell, Yoon K Loke, Malcolm R Macleod, Chris G Maher, Ana Marušic, Dimitris Mavridis, Jessie McGowan, Matthew DF McInnes, Philippa Middleton, Karel G Moons, Zachary Munn, Jane Noyes, Barbara Nußbaumer-Streit, Donald L Patrick, Tatiana Pereira-Cenci, Ba’ Pham, Bob Phillips, Dawid Pieper, Michelle Pollock, Daniel S Quintana, Drummond Rennie, Melissa L Rethlefsen, Hannah R Rothstein, Maroeska M Rovers, Rebecca Ryan, Georgia Salanti, Ian J Saldanha, Margaret Sampson, Nancy Santesso, Rafael Sarkis-Onofre, Jelena Savović, Christopher H Schmid, Kenneth F Schulz, Guido Schwarzer, Beverley J Shea, Paul G Shekelle, Farhad Shokraneh, Mark Simmonds, Nicole Skoetz, Sharon E Straus, Anneliese Synnot, Emily E Tanner-Smith, Brett D Thombs, Hilary Thomson, Alexander Tsertsvadze, Peter Tugwell, Tari Turner, Lesley Uttley, Jeffrey C Valentine, Matt Vassar, Areti Angeliki Veroniki, Meera Viswanathan, Cole Wayant, Paul Whaley, and Kehu Yang. We thank the following contributors who provided feedback on a preliminary version of the PRISMA 2020 checklist: Jo Abbott, Fionn Büttner, Patricia Correia-Santos, Victoria Freeman, Emily A Hennessy, Rakibul Islam, Amalia (Emily) Karahalios, Kasper Krommes, Andreas Lundh, Dafne Port Nascimento, Davina Robson, Catherine Schenck-Yglesias, Mary M Scott, Sarah Tanveer and Pavel Zhelnov. We thank Abigail H Goben, Melissa L Rethlefsen, Tanja Rombey, Anna Scott, and Farhad Shokraneh for their helpful comments on the preprints of the PRISMA 2020 papers. We thank Edoardo Aromataris, Stephanie Chang, Toby Lasserson and David Schriger for their helpful peer review comments on the PRISMA 2020 papers.

Contributors: JEM and DM are joint senior authors. MJP, JEM, PMB, IB, TCH, CDM, LS, and DM conceived this paper and designed the literature review and survey conducted to inform the guideline content. MJP conducted the literature review, administered the survey and analysed the data for both. MJP prepared all materials for the development meeting. MJP and JEM presented proposals at the development meeting. All authors except for TCH, JMT, EAA, SEB, and LAM attended the development meeting. MJP and JEM took and consolidated notes from the development meeting. MJP and JEM led the drafting and editing of the article. JEM, PMB, IB, TCH, LS, JMT, EAA, SEB, RC, JG, AH, TL, EMW, SM, LAM, LAS, JT, ACT, PW, and DM drafted particular sections of the article. All authors were involved in revising the article critically for important intellectual content. All authors approved the final version of the article. MJP is the guarantor of this work. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.

Funding: There was no direct funding for this research. MJP is supported by an Australian Research Council Discovery Early Career Researcher Award (DE200101618) and was previously supported by an Australian National Health and Medical Research Council (NHMRC) Early Career Fellowship (1088535) during the conduct of this research. JEM is supported by an Australian NHMRC Career Development Fellowship (1143429). TCH is supported by an Australian NHMRC Senior Research Fellowship (1154607). JMT is supported by Evidence Partners Inc. JMG is supported by a Tier 1 Canada Research Chair in Health Knowledge Transfer and Uptake. MML is supported by The Ottawa Hospital Anaesthesia Alternate Funds Association and a Faculty of Medicine Junior Research Chair. TL is supported by funding from the National Eye Institute (UG1EY020522), National Institutes of Health, United States. LAM is supported by a National Institute for Health Research Doctoral Research Fellowship (DRF-2018-11-ST2-048). ACT is supported by a Tier 2 Canada Research Chair in Knowledge Synthesis. DM is supported in part by a University Research Chair, University of Ottawa. The funders had no role in considering the study design or in the collection, analysis, interpretation of data, writing of the report, or decision to submit the article for publication.

Competing interests: All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/conflicts-of-interest/ and declare: EL is head of research for the BMJ ; MJP is an editorial board member for PLOS Medicine ; ACT is an associate editor and MJP, TL, EMW, and DM are editorial board members for the Journal of Clinical Epidemiology ; DM and LAS were editors in chief, LS, JMT, and ACT are associate editors, and JG is an editorial board member for Systematic Reviews . None of these authors were involved in the peer review process or decision to publish. TCH has received personal fees from Elsevier outside the submitted work. EMW has received personal fees from the American Journal for Public Health , for which he is the editor for systematic reviews. VW is editor in chief of the Campbell Collaboration, which produces systematic reviews, and co-convenor of the Campbell and Cochrane equity methods group. DM is chair of the EQUATOR Network, IB is adjunct director of the French EQUATOR Centre and TCH is co-director of the Australasian EQUATOR Centre, which advocates for the use of reporting guidelines to improve the quality of reporting in research articles. JMT received salary from Evidence Partners, creator of DistillerSR software for systematic reviews; Evidence Partners was not involved in the design or outcomes of the statement, and the views expressed solely represent those of the author.

Provenance and peer review: Not commissioned; externally peer reviewed.

Patient and public involvement: Patients and the public were not involved in this methodological research. We plan to disseminate the research widely, including to community participants in evidence synthesis organisations.

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/ .

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YSN Doctoral Programs: Steps in Conducting a Literature Review

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• Steps in Conducting a Literature Review

What is a literature review?

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

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

Why is it important?

A literature review is important because it:

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

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1. Choose a topic. Define your research question.

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

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

2. Decide on the scope of your review

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

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

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

Make a list of the databases you will search. 

Where to find databases:

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

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

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

Review the literature

Some questions to help you analyze the research:

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

Tips: 

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

You Might Also Like:

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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• UNC Libraries
• HSL Academic Process
• Systematic Reviews
• Step 8: Write the Review

Systematic Reviews: Step 8: Write the Review

Created by health science librarians.

• Step 1: Complete Pre-Review Tasks
• Step 2: Develop a Protocol
• Step 3: Conduct Literature Searches
• Step 4: Manage Citations
• Step 5: Screen Citations
• Step 6: Assess Quality of Included Studies
• Step 7: Extract Data from Included Studies

About Step 8: Write the Review

Write your review, report your review with prisma, review sections, plain language summaries for systematic reviews, writing the review- webinars.

• Writing the Review FAQs

  Check our FAQ's

   Email us

   Call (919) 962-0800

   Make an appointment with a librarian

  Request a systematic or scoping review consultation

Search the FAQs

In Step 8, you will write an article or a paper about your systematic review.  It will likely have five sections: introduction, methods, results, discussion, and conclusion.  You will: 

• Review the reporting standards you will use, such as PRISMA. 
• Gather your completed data tables and PRISMA chart. 
• Write the Introduction to the topic and your study, Methods of your research, Results of your research, and Discussion of your results.
• Write an Abstract describing your study and a Conclusion summarizing your paper. 
• Cite the studies included in your systematic review and any other articles you may have used in your paper. 
• If you wish to publish your work, choose a target journal for your article.

The PRISMA Checklist will help you report the details of your systematic review. Your paper will also include a PRISMA chart that is an image of your research process. 

Click an item below to see how it applies to Step 8: Write the Review.

Reporting your review with PRISMA

To write your review, you will need the data from your PRISMA flow diagram .  Review the PRISMA checklist to see which items you should report in your methods section.

Managing your review with Covidence

When you screen in Covidence, it will record the numbers you need for your PRISMA flow diagram from duplicate removal through inclusion of studies.  You may need to add additional information, such as the number of references from each database, citations you find through grey literature or other searching methods, or the number of studies found in your previous work if you are updating a systematic review.

How a librarian can help with Step 8

A librarian can advise you on the process of organizing and writing up your systematic review, including: 

• Applying the PRISMA reporting templates and the level of detail to include for each element
• How to report a systematic review search strategy and your review methodology in the completed review
• How to use prior published reviews to guide you in organizing your manuscript 

Reporting standards & guidelines

Be sure to reference reporting standards when writing your review. This helps ensure that you communicate essential components of your methods, results, and conclusions. There are a number of tools that can be used to ensure compliance with reporting guidelines. A few review-writing resources are listed below.

• Cochrane Handbook - Chapter 15: Interpreting results and drawing conclusions
• JBI Manual for Evidence Synthesis - Chapter 12.3 The systematic review
• PRISMA 2020 (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) The aim of the PRISMA Statement is to help authors improve the reporting of systematic reviews and meta-analyses.

Tools for writing your review

• RevMan (Cochrane Training)
• Methods Wizard (Systematic Review Accelerator) The Methods Wizard is part of the Systematic Review Accelerator created by Bond University and the Institute for Evidence-Based Healthcare.
• UNC HSL Systematic Review Manuscript Template Systematic review manuscript template(.doc) adapted from the PRISMA 2020 checklist. This document provides authors with template for writing about their systematic review. Each table contains a PRISMA checklist item that should be written about in that section, the matching PRISMA Item number, and a box where authors can indicate if an item has been completed. Once text has been added, delete any remaining instructions and the PRISMA checklist tables from the end of each section.
• The PRISMA 2020 statement: an updated guideline for reporting systematic reviews The PRISMA 2020 statement replaces the 2009 statement and includes new reporting guidance that reflects advances in methods to identify, select, appraise, and synthesise studies.
• PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews This document is intended to enhance the use, understanding and dissemination of the PRISMA 2020 Statement. Through examples and explanations, the meaning and rationale for each checklist item are presented.

The PRISMA checklist

The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) is a 27-item checklist used to improve transparency in systematic reviews. These items cover all aspects of the manuscript, including title, abstract, introduction, methods, results, discussion, and funding. The PRISMA checklist can be downloaded in PDF or Word files.

• PRISMA 2020 Checklists Download the 2020 PRISMA Checklists in Word or PDF formats or download the expanded checklist (PDF).

The PRISMA flow diagram

The PRISMA Flow Diagram visually depicts the flow of studies through each phase of the review process. The PRISMA Flow Diagram can be downloaded in Word files.

• PRISMA 2020 Flow Diagrams The flow diagram depicts the flow of information through the different phases of a systematic review. It maps out the number of records identified, included and excluded, and the reasons for exclusions. Different templates are available depending on the type of review (new or updated) and sources used to identify studies.

Documenting grey literature and/or hand searches

If you have also searched additional sources, such as professional organization websites, cited or citing references, etc., document your grey literature search using the flow diagram template version 1 PRISMA 2020 flow diagram for new systematic reviews which included searches of databases, registers and other sources or the version 2 PRISMA 2020 flow diagram for updated systematic reviews which included searches of databases, registers and other sources . 

Complete the boxes documenting your database searches,  Identification of studies via databases and registers, according to the PRISMA flow diagram instructions.  Complete the boxes documenting your grey literature and/or hand searches on the right side of the template, Identification of studies via other methods, using the steps below.

Need help completing the PRISMA flow diagram?

There are different PRISMA flow diagram templates for new and updated reviews, as well as different templates for reviews with and without grey literature searches. Be sure you download the correct template to match your review methods, then follow the steps below for each portion of the diagram you have available.

View the step-by-step explanation of the PRISMA flow diagram

Step 1: Preparation Download the flow diagram template version 1 PRISMA 2020 flow diagram for new systematic reviews which included searches of databases and registers only or the version 2 PRISMA 2020 flow diagram for updated systematic reviews which included searches of databases and registers only . 

View the step-by-step explanation of the grey literature & hand searching portion of the PRISMA flow diagram

Step 1: Preparation Download the flow diagram template version 1 PRISMA 2020 flow diagram for new systematic reviews which included searches of databases, registers and other sources or the version 2 PRISMA 2020 flow diagram for updated systematic reviews which included searches of databases, registers and other sources . 

View the step-by-step explanation of review update portion of the PRISMA flow diagram

Step 1: Preparation Download the flow diagram template version 2 PRISMA 2020 flow diagram for updated systematic reviews which included searches of databases and registers only or the version 2 PRISMA 2020 flow diagram for updated systematic reviews which included searches of databases, registers and other sources . 

For more information about updating your systematic review, see the box Updating Your Review? on the Step 3: Conduct Literature Searches page of the guide.

Sections of a Scientific Manuscript

Scientific articles often follow the IMRaD format: Introduction, Methods, Results, and Discussion.  You will also need a title and an abstract to summarize your research.

You can read more about scientific writing through the library guides below.

• Structure of Scholarly Articles & Peer Review • Explains the standard parts of a medical research article • Compares scholarly journals, professional trade journals, and magazines • Explains peer review and how to find peer reviewed articles and journals
• Writing in the Health Sciences (For Students and Instructors)
• Citing & Writing Tools & Guides Includes links to guides for popular citation managers such as EndNote, Sciwheel, Zotero; copyright basics; APA & AMA Style guides; Plagiarism & Citing Sources; Citing & Writing: How to Write Scientific Papers

Sections of a Systematic Review Manuscript

Systematic reviews follow the same structure as original research articles, but you will need to report on your search instead of on details like the participants or sampling. Sections of your manuscript are shown as bold headings in the PRISMA checklist.

Refer to the PRISMA checklist for more information.

Consider including a Plain Language Summary (PLS) when you publish your systematic review. Like an abstract, a PLS gives an overview of your study, but is specifically written and formatted to be easy for non-experts to understand. 

Tips for writing a PLS:

• Use clear headings e.g. "why did we do this study?"; "what did we do?"; "what did we find?"
• Use active voice e.g. "we searched for articles in 5 databases instead of "5 databases were searched"
• Consider need-to-know vs. nice-to-know: what is most important for readers to understand about your study? Be sure to provide the most important points without misrepresenting your study or misleading the reader. 
• Keep it short: Many journals recommend keeping your plain language summary less than 250 words. 
• Check journal guidelines: Your journal may have specific guidelines about the format of your plain language summary and when you can publish it. Look at journal guidelines before submitting your article. 

Learn more about Plain Language Summaries: 

• Rosenberg, A., Baróniková, S., & Feighery, L. (2021). Open Pharma recommendations for plain language summaries of peer-reviewed medical journal publications. Current Medical Research and Opinion, 37(11), 2015–2016.  https://doi.org/10.1080/03007995.2021.1971185
• Lobban, D., Gardner, J., & Matheis, R. (2021). Plain language summaries of publications of company-sponsored medical research: what key questions do we need to address? Current Medical Research and Opinion, 1–12. https://doi.org/10.1080/03007995.2021.1997221
• Cochrane Community. (2022, March 21). Updated template and guidance for writing Plain Language Summaries in Cochrane Reviews now available. https://community.cochrane.org/news/updated-template-and-guidance-writing-plain-language-summaries-cochrane-reviews-now-available
• You can also look at our Health Literacy LibGuide:  https://guides.lib.unc.edu/healthliteracy 

How to Approach Writing a Background Section

What Makes a Good Discussion Section

Writing Up Risk of Bias

Developing Your Implications for Research Section

• << Previous: Step 7: Extract Data from Included Studies
• Next: FAQs >>
• Last Updated: May 16, 2024 3:24 PM
• URL: https://guides.lib.unc.edu/systematic-reviews

• University of Texas Libraries

Literature Reviews

Steps in the literature review process.

• What is a literature review?
• Define your research question
• Determine inclusion and exclusion criteria
• Choose databases and search
• Review Results
• Synthesize Results
• Analyze Results
• Librarian Support
• You may need to some exploratory searching of the literature to get a sense of scope, to determine whether you need to narrow or broaden your focus
• Identify databases that provide the most relevant sources, and identify relevant terms (controlled vocabularies) to add to your search strategy
• Finalize your research question
• Think about relevant dates, geographies (and languages), methods, and conflicting points of view
• Conduct searches in the published literature via the identified databases
• Check to see if this topic has been covered in other discipline's databases
• Examine the citations of on-point articles for keywords, authors, and previous research (via references) and cited reference searching.
• Save your search results in a citation management tool (such as Zotero, Mendeley or EndNote)
• De-duplicate your search results
• Make sure that you've found the seminal pieces -- they have been cited many times, and their work is considered foundational 
• Check with your professor or a librarian to make sure your search has been comprehensive
• Evaluate the strengths and weaknesses of individual sources and evaluate for bias, methodologies, and thoroughness
• Group your results in to an organizational structure that will support why your research needs to be done, or that provides the answer to your research question  
• Develop your conclusions
• Are there gaps in the literature?
• Where has significant research taken place, and who has done it?
• Is there consensus or debate on this topic?
• Which methodological approaches work best?
• For example: Background, Current Practices, Critics and Proponents, Where/How this study will fit in 
• Organize your citations and focus on your research question and pertinent studies
• Compile your bibliography

Note: The first four steps are the best points at which to contact a librarian. Your librarian can help you determine the best databases to use for your topic, assess scope, and formulate a search strategy.

Videos Tutorials about Literature Reviews

This 4.5 minute video from Academic Education Materials has a Creative Commons License and a British narrator.

Recommended Reading

• Last Updated: Oct 26, 2022 2:49 PM
• URL: https://guides.lib.utexas.edu/literaturereviews

Harvey Cushing/John Hay Whitney Medical Library

Evidence synthesis & literature reviews education, what do you want to learn about, selected training, review types, evidence synthesis process, selected protocols, guidelines, & tools.

Training for Getting Started

This module series helps users gain a more in-depth understanding of the process of conducting a systematic review. Make sure you are connected to the VPN before registering for a free account.

This series covers the fundamental concepts and general procedure of searching the health science literature to ensure your search is comprehensive, methodical, transparent and reproducible.

Need more help?

Fill out our form to get personalized advice about review methodologies appropriate for your project.

Our librarians have co-authored hundreds of evidence synthesis articles. Our staff is continually trained on new search methodologies and processes.

We adhere to the requirements for authorship and contributorship of the International Committee of Medical Journal Editors (ICMJE).

Title: "What type of Review Could You Write"

Top of chart begins Q: "How big is your team?"

• If "Yes" to robust methodology, then "Rapid Review"
• If "No to robust methodology, then "Narrative Review"
• If "Yes", then "Systematic Review and Meta-analysis"
• If "Open", then "Scoping Review"

Build your evidence synthesis team [preparation stage]

Review reporting guidelines, best practice handbooks, and training modules [preparation stage]

Formulate question and decide on review type [preparation stage]

Search for previous published literature and protocols [preparation stage]

Develop and register a protocol [write-up stage]

Develop and test search strategies [preparation stage]

Peer review of search strategies [preparation stage]

Execute search [retrieval stage]

De-duplicate results [retrieval stage]

Screen title and abstracts [screening stage]

Retrieve full-text articles [retrieval stage]

Screen articles in full-text [screening stage]

Search for grey literature [retrieval stage]

Quality assessment and data extraction [synthesis stage]

Citation chasing [retrieval stage]

Update database searches [retrieval stage]

Synthesize data [synthesis stage]

Manuscript development [write-up stage]

View this process as a graphic

Protocols & Reporting Guidelines

• PRISMA  (Preferred Reporting Items for Systematic Reviews and Meta-Analyses)
• MOOSE  (Meta-analyisis of Observational Studies in Epidemiology) 
• ENTREQ  (Enhancing Transparency in Reporting the Synthesis of Qualitative Research)

Protocol Registries

• PROSPERO  (International Prospective Register of Systematic Reviews)
• Open Science Framework: Registries

Quality Assessment Instruments

• CATevaluation : a listing of Critical Appraisal Tools assessed for validity and/or reliability
• GRADE: Grading of Recommendations Assessment, Development and Evaluation
• Critical Appraisal Skills Program (CASP) Checklist
• JBI Critical Appraisal Tools
• Risk of bias tools in systematic reviews of health interventions: an analysis of PROSPERO-registered protocols  (article)
• Critical appraisal of nonrandomized studies: a review of recommended and commonly used tools  (article)

Best Practices

• Cochrane Handbook for Systematic Reviews of Interventions
• CRDs Guidance for Undertaking Reviews in Health Care
• JBI Best Practices  (Joanna Briggs Institute)
• MECIR  (Methodological Expectations for Cochrane Intervention Reviews)
• Publications on systematic review / evidence synthesis methodology (EPPI-Centre)
• Methods Guide for Effectiveness and Comparative Effectiveness Reviews (Agency for Healthcare Research and Quality)
• Yale MeSH Analyzer  - helps identify the problems in your search strategy
• Covidence  - manage bibliographic data, PDFs, forms for risk of bias, and data extraction
• EndNote  - citation management software
• What Review Is Right For You? Interactive Edition  - guidance for conducting and reporting evidence synthesis
• An Introduction to Systematic Reviews  edited by David Gough, Sandy Oliver, James Thomas  
• Systematic Reviews and Meta-Analysis  by Jacqueline Corcoran; Vijayan Pillai; Julia H. Littell
• The Handbook of Research Synthesis and Meta-Analysis  edited by Harris Cooper, Larry V. Hedges, Jeffrey C. Valentine
• Searching the Grey Literature: A handbook for Searching Reports, Working Papers, and other Unpublished Research  by Sarah Bonato

Systematic Review Flow Charts

Free, interactive flow charts for your systematic review, interactive flow charts for communcating review methods.

Interactivity allows the charts to be embedded in a website, linking the reader instantly with more information on the methods used and the results found. Static versions can be used for documents.

The flow charts have been designed to be clear and concise ways to communicate a review or map's methods, whilst providing links to more detailed information.

Versions are provided in several formats: 1) either combining title and abstract screening together, or separately as title then abstract level assessments; 2) for systematic mapping or systematic review, depending on which method is used; 3) in live, editable HTML format for web-based editing, or in .Rhtml format for those comfortable with basic coding in R.

The flow charts

Choose your format, systematic map flow charts, html, css and javascript versions (no coding knowledge necessary), systematic map .rhtml version - for people comfortable with r (basic knowledge only), instructions for use:.

• Select the right file (save the target file that opens in a new window, but remove the added .txt file extension):
• Title and abstract screening combined
• Enter data manually
• Load data from a .csv file
• Title and abstract screening conducted separately
• Open the file in R studio

• The output will be saved as an HTML file
• Embed the html in an <iframe> on your own website

Systematic review .Rhtml version - for people comfortable with R (basic knowledge only)

Like this project, it's been put together by me, neal haddaway.

Haddaway, NR. 2020. SRflowdiagram: flow charts for systematic reviews and maps. doi: 10.5281/zenodo.4134795.

• Activity Diagram (UML)
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• Chemical Chart
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• Class Diagram (UML)
• Collaboration Diagram (UML)
• Compare & Contrast Diagram
• Component Diagram (UML)
• Concept Diagram
• Cycle Diagram
• Data Flow Diagram
• Data Flow Diagrams (YC)
• Database Diagram
• Deployment Diagram (UML)
• Entity Relationship Diagram
• Family Tree
• Fishbone / Ishikawa Diagram
• Gantt Chart
• Infographics
• iOS Mockups
• Network Diagram
• Object Diagram (UML)
• Object Process Model
• Organizational Chart
• Sequence Diagram (UML)
• Spider Diagram
• State Chart Diagram (UML)
• Story Board
• SWOT Diagram
• TQM - Total Quality Management
• Use Case Diagram (UML)
• Value Stream Mapping
• Venn Diagram
• Web Mockups
• Work Breakdown Structure

Literature Review Flowchart

You can easily edit this template using Creately. You can export it in multiple formats like JPEG, PNG and SVG and easily add it to Word documents, Powerpoint (PPT) presentations, Excel or any other documents. You can export it as a PDF for high-quality printouts.

• Flowchart Templates
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• WBS Templates
• Family Tree Templates
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• Data Flow Diagram Templates
• Network Diagram Templates
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• Activity Diagram Templates
• Amazon Web Services Templates
• Android Mockups Templates
• Block Diagram Templates
• Business Process Management Templates
• Chemical Chart Templates
• Cisco Network Diagram Templates
• Class Diagram Templates
• Collaboration Diagram Templates
• Compare & Contrast Diagram Templates
• Component Diagram Templates
• Concept Diagram Templates
• Cycle Diagram Templates
• Data Flow Diagrams(YC) Templates
• Database Diagram Templates
• Deployment Diagram Templates
• Entity Relationship Diagram Templates
• Fishbone Diagram Templates
• Gantt Chart Templates
• Infographic Templates
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• Open access
• Published: 29 March 2021

The PRISMA 2020 statement: an updated guideline for reporting systematic reviews

• Matthew J. Page   ORCID: orcid.org/0000-0002-4242-7526 1 ,
• Joanne E. McKenzie 1 ,
• Patrick M. Bossuyt 2 ,
• Isabelle Boutron 3 ,
• Tammy C. Hoffmann 4 ,
• Cynthia D. Mulrow 5 ,
• Larissa Shamseer 6 ,
• Jennifer M. Tetzlaff 7 ,
• Elie A. Akl 8 ,
• Sue E. Brennan 1 ,
• Roger Chou 9 ,
• Julie Glanville 10 ,
• Jeremy M. Grimshaw 11 ,
• Asbjørn Hróbjartsson 12 ,
• Manoj M. Lalu 13 ,
• Tianjing Li 14 ,
• Elizabeth W. Loder 15 ,
• Evan Mayo-Wilson 16 ,
• Steve McDonald 1 ,
• Luke A. McGuinness 17 ,
• Lesley A. Stewart 18 ,
• James Thomas 19 ,
• Andrea C. Tricco 20 ,
• Vivian A. Welch 21 ,
• Penny Whiting 17 &
• David Moher 22  

Systematic Reviews volume  10 , Article number:  89 ( 2021 ) Cite this article

317k Accesses

3565 Citations

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Metrics details

An Editorial to this article was published on 19 April 2021

The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found. Over the past decade, advances in systematic review methodology and terminology have necessitated an update to the guideline. The PRISMA 2020 statement replaces the 2009 statement and includes new reporting guidance that reflects advances in methods to identify, select, appraise, and synthesise studies. The structure and presentation of the items have been modified to facilitate implementation. In this article, we present the PRISMA 2020 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and the revised flow diagrams for original and updated reviews. In order to encourage its wide dissemination this article is freely accessible on BMJ, PLOS Medicine, Journal of Clinical Epidemiology and International Journal of Surgery journal websites.

Systematic reviews serve many critical roles. They can provide syntheses of the state of knowledge in a field, from which future research priorities can be identified; they can address questions that otherwise could not be answered by individual studies; they can identify problems in primary research that should be rectified in future studies; and they can generate or evaluate theories about how or why phenomena occur. Systematic reviews therefore generate various types of knowledge for different users of reviews (such as patients, healthcare providers, researchers, and policy makers) [ 1 , 2 ]. To ensure a systematic review is valuable to users, authors should prepare a transparent, complete, and accurate account of why the review was done, what they did (such as how studies were identified and selected) and what they found (such as characteristics of contributing studies and results of meta-analyses). Up-to-date reporting guidance facilitates authors achieving this [ 3 ].

The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement published in 2009 (hereafter referred to as PRISMA 2009) [ 4 , 5 , 6 , 7 , 8 , 9 , 10 ] is a reporting guideline designed to address poor reporting of systematic reviews [ 11 ]. The PRISMA 2009 statement comprised a checklist of 27 items recommended for reporting in systematic reviews and an “explanation and elaboration” paper [ 12 , 13 , 14 , 15 , 16 ] providing additional reporting guidance for each item, along with exemplars of reporting. The recommendations have been widely endorsed and adopted, as evidenced by its co-publication in multiple journals, citation in over 60,000 reports (Scopus, August 2020), endorsement from almost 200 journals and systematic review organisations, and adoption in various disciplines. Evidence from observational studies suggests that use of the PRISMA 2009 statement is associated with more complete reporting of systematic reviews [ 17 , 18 , 19 , 20 ], although more could be done to improve adherence to the guideline [ 21 ].

Many innovations in the conduct of systematic reviews have occurred since publication of the PRISMA 2009 statement. For example, technological advances have enabled the use of natural language processing and machine learning to identify relevant evidence [ 22 , 23 , 24 ], methods have been proposed to synthesise and present findings when meta-analysis is not possible or appropriate [ 25 , 26 , 27 ], and new methods have been developed to assess the risk of bias in results of included studies [ 28 , 29 ]. Evidence on sources of bias in systematic reviews has accrued, culminating in the development of new tools to appraise the conduct of systematic reviews [ 30 , 31 ]. Terminology used to describe particular review processes has also evolved, as in the shift from assessing “quality” to assessing “certainty” in the body of evidence [ 32 ]. In addition, the publishing landscape has transformed, with multiple avenues now available for registering and disseminating systematic review protocols [ 33 , 34 ], disseminating reports of systematic reviews, and sharing data and materials, such as preprint servers and publicly accessible repositories. To capture these advances in the reporting of systematic reviews necessitated an update to the PRISMA 2009 statement.

Development of PRISMA 2020

A complete description of the methods used to develop PRISMA 2020 is available elsewhere [ 35 ]. We identified PRISMA 2009 items that were often reported incompletely by examining the results of studies investigating the transparency of reporting of published reviews [ 17 , 21 , 36 , 37 ]. We identified possible modifications to the PRISMA 2009 statement by reviewing 60 documents providing reporting guidance for systematic reviews (including reporting guidelines, handbooks, tools, and meta-research studies) [ 38 ]. These reviews of the literature were used to inform the content of a survey with suggested possible modifications to the 27 items in PRISMA 2009 and possible additional items. Respondents were asked whether they believed we should keep each PRISMA 2009 item as is, modify it, or remove it, and whether we should add each additional item. Systematic review methodologists and journal editors were invited to complete the online survey (110 of 220 invited responded). We discussed proposed content and wording of the PRISMA 2020 statement, as informed by the review and survey results, at a 21-member, two-day, in-person meeting in September 2018 in Edinburgh, Scotland. Throughout 2019 and 2020, we circulated an initial draft and five revisions of the checklist and explanation and elaboration paper to co-authors for feedback. In April 2020, we invited 22 systematic reviewers who had expressed interest in providing feedback on the PRISMA 2020 checklist to share their views (via an online survey) on the layout and terminology used in a preliminary version of the checklist. Feedback was received from 15 individuals and considered by the first author, and any revisions deemed necessary were incorporated before the final version was approved and endorsed by all co-authors.

The PRISMA 2020 statement

Scope of the guideline.

The PRISMA 2020 statement has been designed primarily for systematic reviews of studies that evaluate the effects of health interventions, irrespective of the design of the included studies. However, the checklist items are applicable to reports of systematic reviews evaluating other interventions (such as social or educational interventions), and many items are applicable to systematic reviews with objectives other than evaluating interventions (such as evaluating aetiology, prevalence, or prognosis). PRISMA 2020 is intended for use in systematic reviews that include synthesis (such as pairwise meta-analysis or other statistical synthesis methods) or do not include synthesis (for example, because only one eligible study is identified). The PRISMA 2020 items are relevant for mixed-methods systematic reviews (which include quantitative and qualitative studies), but reporting guidelines addressing the presentation and synthesis of qualitative data should also be consulted [ 39 , 40 ]. PRISMA 2020 can be used for original systematic reviews, updated systematic reviews, or continually updated (“living”) systematic reviews. However, for updated and living systematic reviews, there may be some additional considerations that need to be addressed. Where there is relevant content from other reporting guidelines, we reference these guidelines within the items in the explanation and elaboration paper [ 41 ] (such as PRISMA-Search [ 42 ] in items 6 and 7, Synthesis without meta-analysis (SWiM) reporting guideline [ 27 ] in item 13d). Box 1 includes a glossary of terms used throughout the PRISMA 2020 statement.

PRISMA 2020 is not intended to guide systematic review conduct, for which comprehensive resources are available [ 43 , 44 , 45 , 46 ]. However, familiarity with PRISMA 2020 is useful when planning and conducting systematic reviews to ensure that all recommended information is captured. PRISMA 2020 should not be used to assess the conduct or methodological quality of systematic reviews; other tools exist for this purpose [ 30 , 31 ]. Furthermore, PRISMA 2020 is not intended to inform the reporting of systematic review protocols, for which a separate statement is available (PRISMA for Protocols (PRISMA-P) 2015 statement [ 47 , 48 ]). Finally, extensions to the PRISMA 2009 statement have been developed to guide reporting of network meta-analyses [ 49 ], meta-analyses of individual participant data [ 50 ], systematic reviews of harms [ 51 ], systematic reviews of diagnostic test accuracy studies [ 52 ], and scoping reviews [ 53 ]; for these types of reviews we recommend authors report their review in accordance with the recommendations in PRISMA 2020 along with the guidance specific to the extension.

How to use PRISMA 2020

The PRISMA 2020 statement (including the checklists, explanation and elaboration, and flow diagram) replaces the PRISMA 2009 statement, which should no longer be used. Box  2 summarises noteworthy changes from the PRISMA 2009 statement. The PRISMA 2020 checklist includes seven sections with 27 items, some of which include sub-items (Table  1 ). A checklist for journal and conference abstracts for systematic reviews is included in PRISMA 2020. This abstract checklist is an update of the 2013 PRISMA for Abstracts statement [ 54 ], reflecting new and modified content in PRISMA 2020 (Table  2 ). A template PRISMA flow diagram is provided, which can be modified depending on whether the systematic review is original or updated (Fig.  1 ).

 PRISMA 2020 flow diagram template for systematic reviews. The new design is adapted from flow diagrams proposed by Boers [ 55 ], Mayo-Wilson et al. [ 56 ] and Stovold et al. [ 57 ] The boxes in grey should only be completed if applicable; otherwise they should be removed from the flow diagram. Note that a “report” could be a journal article, preprint, conference abstract, study register entry, clinical study report, dissertation, unpublished manuscript, government report or any other document providing relevant information

We recommend authors refer to PRISMA 2020 early in the writing process, because prospective consideration of the items may help to ensure that all the items are addressed. To help keep track of which items have been reported, the PRISMA statement website ( http://www.prisma-statement.org/ ) includes fillable templates of the checklists to download and complete (also available in Additional file 1 ). We have also created a web application that allows users to complete the checklist via a user-friendly interface [ 58 ] (available at https://prisma.shinyapps.io/checklist/ and adapted from the Transparency Checklist app [ 59 ]). The completed checklist can be exported to Word or PDF. Editable templates of the flow diagram can also be downloaded from the PRISMA statement website.

We have prepared an updated explanation and elaboration paper, in which we explain why reporting of each item is recommended and present bullet points that detail the reporting recommendations (which we refer to as elements) [ 41 ]. The bullet-point structure is new to PRISMA 2020 and has been adopted to facilitate implementation of the guidance [ 60 , 61 ]. An expanded checklist, which comprises an abridged version of the elements presented in the explanation and elaboration paper, with references and some examples removed, is available in Additional file 2 . Consulting the explanation and elaboration paper is recommended if further clarity or information is required.

Journals and publishers might impose word and section limits, and limits on the number of tables and figures allowed in the main report. In such cases, if the relevant information for some items already appears in a publicly accessible review protocol, referring to the protocol may suffice. Alternatively, placing detailed descriptions of the methods used or additional results (such as for less critical outcomes) in supplementary files is recommended. Ideally, supplementary files should be deposited to a general-purpose or institutional open-access repository that provides free and permanent access to the material (such as Open Science Framework, Dryad, figshare). A reference or link to the additional information should be included in the main report. Finally, although PRISMA 2020 provides a template for where information might be located, the suggested location should not be seen as prescriptive; the guiding principle is to ensure the information is reported.

Use of PRISMA 2020 has the potential to benefit many stakeholders. Complete reporting allows readers to assess the appropriateness of the methods, and therefore the trustworthiness of the findings. Presenting and summarising characteristics of studies contributing to a synthesis allows healthcare providers and policy makers to evaluate the applicability of the findings to their setting. Describing the certainty in the body of evidence for an outcome and the implications of findings should help policy makers, managers, and other decision makers formulate appropriate recommendations for practice or policy. Complete reporting of all PRISMA 2020 items also facilitates replication and review updates, as well as inclusion of systematic reviews in overviews (of systematic reviews) and guidelines, so teams can leverage work that is already done and decrease research waste [ 36 , 62 , 63 ].

We updated the PRISMA 2009 statement by adapting the EQUATOR Network’s guidance for developing health research reporting guidelines [ 64 ]. We evaluated the reporting completeness of published systematic reviews [ 17 , 21 , 36 , 37 ], reviewed the items included in other documents providing guidance for systematic reviews [ 38 ], surveyed systematic review methodologists and journal editors for their views on how to revise the original PRISMA statement [ 35 ], discussed the findings at an in-person meeting, and prepared this document through an iterative process. Our recommendations are informed by the reviews and survey conducted before the in-person meeting, theoretical considerations about which items facilitate replication and help users assess the risk of bias and applicability of systematic reviews, and co-authors’ experience with authoring and using systematic reviews.

Various strategies to increase the use of reporting guidelines and improve reporting have been proposed. They include educators introducing reporting guidelines into graduate curricula to promote good reporting habits of early career scientists [ 65 ]; journal editors and regulators endorsing use of reporting guidelines [ 18 ]; peer reviewers evaluating adherence to reporting guidelines [ 61 , 66 ]; journals requiring authors to indicate where in their manuscript they have adhered to each reporting item [ 67 ]; and authors using online writing tools that prompt complete reporting at the writing stage [ 60 ]. Multi-pronged interventions, where more than one of these strategies are combined, may be more effective (such as completion of checklists coupled with editorial checks) [ 68 ]. However, of 31 interventions proposed to increase adherence to reporting guidelines, the effects of only 11 have been evaluated, mostly in observational studies at high risk of bias due to confounding [ 69 ]. It is therefore unclear which strategies should be used. Future research might explore barriers and facilitators to the use of PRISMA 2020 by authors, editors, and peer reviewers, designing interventions that address the identified barriers, and evaluating those interventions using randomised trials. To inform possible revisions to the guideline, it would also be valuable to conduct think-aloud studies [ 70 ] to understand how systematic reviewers interpret the items, and reliability studies to identify items where there is varied interpretation of the items.

We encourage readers to submit evidence that informs any of the recommendations in PRISMA 2020 (via the PRISMA statement website: http://www.prisma-statement.org/ ). To enhance accessibility of PRISMA 2020, several translations of the guideline are under way (see available translations at the PRISMA statement website). We encourage journal editors and publishers to raise awareness of PRISMA 2020 (for example, by referring to it in journal “Instructions to authors”), endorsing its use, advising editors and peer reviewers to evaluate submitted systematic reviews against the PRISMA 2020 checklists, and making changes to journal policies to accommodate the new reporting recommendations. We recommend existing PRISMA extensions [ 47 , 49 , 50 , 51 , 52 , 53 , 71 , 72 ] be updated to reflect PRISMA 2020 and advise developers of new PRISMA extensions to use PRISMA 2020 as the foundation document.

We anticipate that the PRISMA 2020 statement will benefit authors, editors, and peer reviewers of systematic reviews, and different users of reviews, including guideline developers, policy makers, healthcare providers, patients, and other stakeholders. Ultimately, we hope that uptake of the guideline will lead to more transparent, complete, and accurate reporting of systematic reviews, thus facilitating evidence based decision making.

Box 1 Glossary of terms

Systematic review —A review that uses explicit, systematic methods to collate and synthesise findings of studies that address a clearly formulated question [ 43 ]

Statistical synthesis —The combination of quantitative results of two or more studies. This encompasses meta-analysis of effect estimates (described below) and other methods, such as combining P values, calculating the range and distribution of observed effects, and vote counting based on the direction of effect (see McKenzie and Brennan [ 25 ] for a description of each method)

Meta-analysis of effect estimates —A statistical technique used to synthesise results when study effect estimates and their variances are available, yielding a quantitative summary of results [ 25 ]

Outcome —An event or measurement collected for participants in a study (such as quality of life, mortality)

Result —The combination of a point estimate (such as a mean difference, risk ratio, or proportion) and a measure of its precision (such as a confidence/credible interval) for a particular outcome

Report —A document (paper or electronic) supplying information about a particular study. It could be a journal article, preprint, conference abstract, study register entry, clinical study report, dissertation, unpublished manuscript, government report, or any other document providing relevant information

Record —The title or abstract (or both) of a report indexed in a database or website (such as a title or abstract for an article indexed in Medline). Records that refer to the same report (such as the same journal article) are “duplicates”; however, records that refer to reports that are merely similar (such as a similar abstract submitted to two different conferences) should be considered unique.

Study —An investigation, such as a clinical trial, that includes a defined group of participants and one or more interventions and outcomes. A “study” might have multiple reports. For example, reports could include the protocol, statistical analysis plan, baseline characteristics, results for the primary outcome, results for harms, results for secondary outcomes, and results for additional mediator and moderator analyses

Box 2 Noteworthy changes to the PRISMA 2009 statement

• Inclusion of the abstract reporting checklist within PRISMA 2020 (see item #2 and Box 2 ).

• Movement of the ‘Protocol and registration’ item from the start of the Methods section of the checklist to a new Other section, with addition of a sub-item recommending authors describe amendments to information provided at registration or in the protocol (see item #24a-24c).

• Modification of the ‘Search’ item to recommend authors present full search strategies for all databases, registers and websites searched, not just at least one database (see item #7).

• Modification of the ‘Study selection’ item in the Methods section to emphasise the reporting of how many reviewers screened each record and each report retrieved, whether they worked independently, and if applicable, details of automation tools used in the process (see item #8).

• Addition of a sub-item to the ‘Data items’ item recommending authors report how outcomes were defined, which results were sought, and methods for selecting a subset of results from included studies (see item #10a).

• Splitting of the ‘Synthesis of results’ item in the Methods section into six sub-items recommending authors describe: the processes used to decide which studies were eligible for each synthesis; any methods required to prepare the data for synthesis; any methods used to tabulate or visually display results of individual studies and syntheses; any methods used to synthesise results; any methods used to explore possible causes of heterogeneity among study results (such as subgroup analysis, meta-regression); and any sensitivity analyses used to assess robustness of the synthesised results (see item #13a-13f).

• Addition of a sub-item to the ‘Study selection’ item in the Results section recommending authors cite studies that might appear to meet the inclusion criteria, but which were excluded, and explain why they were excluded (see item #16b).

• Splitting of the ‘Synthesis of results’ item in the Results section into four sub-items recommending authors: briefly summarise the characteristics and risk of bias among studies contributing to the synthesis; present results of all statistical syntheses conducted; present results of any investigations of possible causes of heterogeneity among study results; and present results of any sensitivity analyses (see item #20a-20d).

• Addition of new items recommending authors report methods for and results of an assessment of certainty (or confidence) in the body of evidence for an outcome (see items #15 and #22).

• Addition of a new item recommending authors declare any competing interests (see item #26).

• Addition of a new item recommending authors indicate whether data, analytic code and other materials used in the review are publicly available and if so, where they can be found (see item #27).

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Acknowledgements

We dedicate this paper to the late Douglas G Altman and Alessandro Liberati, whose contributions were fundamental to the development and implementation of the original PRISMA statement.

We thank the following contributors who completed the survey to inform discussions at the development meeting: Xavier Armoiry, Edoardo Aromataris, Ana Patricia Ayala, Ethan M Balk, Virginia Barbour, Elaine Beller, Jesse A Berlin, Lisa Bero, Zhao-Xiang Bian, Jean Joel Bigna, Ferrán Catalá-López, Anna Chaimani, Mike Clarke, Tammy Clifford, Ioana A Cristea, Miranda Cumpston, Sofia Dias, Corinna Dressler, Ivan D Florez, Joel J Gagnier, Chantelle Garritty, Long Ge, Davina Ghersi, Sean Grant, Gordon Guyatt, Neal R Haddaway, Julian PT Higgins, Sally Hopewell, Brian Hutton, Jamie J Kirkham, Jos Kleijnen, Julia Koricheva, Joey SW Kwong, Toby J Lasserson, Julia H Littell, Yoon K Loke, Malcolm R Macleod, Chris G Maher, Ana Marušic, Dimitris Mavridis, Jessie McGowan, Matthew DF McInnes, Philippa Middleton, Karel G Moons, Zachary Munn, Jane Noyes, Barbara Nußbaumer-Streit, Donald L Patrick, Tatiana Pereira-Cenci, Ba′ Pham, Bob Phillips, Dawid Pieper, Michelle Pollock, Daniel S Quintana, Drummond Rennie, Melissa L Rethlefsen, Hannah R Rothstein, Maroeska M Rovers, Rebecca Ryan, Georgia Salanti, Ian J Saldanha, Margaret Sampson, Nancy Santesso, Rafael Sarkis-Onofre, Jelena Savović, Christopher H Schmid, Kenneth F Schulz, Guido Schwarzer, Beverley J Shea, Paul G Shekelle, Farhad Shokraneh, Mark Simmonds, Nicole Skoetz, Sharon E Straus, Anneliese Synnot, Emily E Tanner-Smith, Brett D Thombs, Hilary Thomson, Alexander Tsertsvadze, Peter Tugwell, Tari Turner, Lesley Uttley, Jeffrey C Valentine, Matt Vassar, Areti Angeliki Veroniki, Meera Viswanathan, Cole Wayant, Paul Whaley, and Kehu Yang. We thank the following contributors who provided feedback on a preliminary version of the PRISMA 2020 checklist: Jo Abbott, Fionn Büttner, Patricia Correia-Santos, Victoria Freeman, Emily A Hennessy, Rakibul Islam, Amalia (Emily) Karahalios, Kasper Krommes, Andreas Lundh, Dafne Port Nascimento, Davina Robson, Catherine Schenck-Yglesias, Mary M Scott, Sarah Tanveer and Pavel Zhelnov. We thank Abigail H Goben, Melissa L Rethlefsen, Tanja Rombey, Anna Scott, and Farhad Shokraneh for their helpful comments on the preprints of the PRISMA 2020 papers. We thank Edoardo Aromataris, Stephanie Chang, Toby Lasserson and David Schriger for their helpful peer review comments on the PRISMA 2020 papers.

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Patient and public involvement

Patients and the public were not involved in this methodological research. We plan to disseminate the research widely, including to community participants in evidence synthesis organisations.

There was no direct funding for this research. MJP is supported by an Australian Research Council Discovery Early Career Researcher Award (DE200101618) and was previously supported by an Australian National Health and Medical Research Council (NHMRC) Early Career Fellowship (1088535) during the conduct of this research. JEM is supported by an Australian NHMRC Career Development Fellowship (1143429). TCH is supported by an Australian NHMRC Senior Research Fellowship (1154607). JMT is supported by Evidence Partners Inc. JMG is supported by a Tier 1 Canada Research Chair in Health Knowledge Transfer and Uptake. MML is supported by The Ottawa Hospital Anaesthesia Alternate Funds Association and a Faculty of Medicine Junior Research Chair. TL is supported by funding from the National Eye Institute (UG1EY020522), National Institutes of Health, United States. LAM is supported by a National Institute for Health Research Doctoral Research Fellowship (DRF-2018-11-ST2–048). ACT is supported by a Tier 2 Canada Research Chair in Knowledge Synthesis. DM is supported in part by a University Research Chair, University of Ottawa. The funders had no role in considering the study design or in the collection, analysis, interpretation of data, writing of the report, or decision to submit the article for publication.

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JEM and DM are joint senior authors. MJP, JEM, PMB, IB, TCH, CDM, LS, and DM conceived this paper and designed the literature review and survey conducted to inform the guideline content. MJP conducted the literature review, administered the survey and analysed the data for both. MJP prepared all materials for the development meeting. MJP and JEM presented proposals at the development meeting. All authors except for TCH, JMT, EAA, SEB, and LAM attended the development meeting. MJP and JEM took and consolidated notes from the development meeting. MJP and JEM led the drafting and editing of the article. JEM, PMB, IB, TCH, LS, JMT, EAA, SEB, RC, JG, AH, TL, EMW, SM, LAM, LAS, JT, ACT, PW, and DM drafted particular sections of the article. All authors were involved in revising the article critically for important intellectual content. All authors approved the final version of the article. MJP is the guarantor of this work. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.

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All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/conflicts-of-interest/ and declare: EL is head of research for the BMJ ; MJP is an editorial board member for PLOS Medicine ; ACT is an associate editor and MJP, TL, EMW, and DM are editorial board members for the Journal of Clinical Epidemiology ; DM and LAS were editors in chief, LS, JMT, and ACT are associate editors, and JG is an editorial board member for Systematic Reviews . None of these authors were involved in the peer review process or decision to publish. TCH has received personal fees from Elsevier outside the submitted work. EMW has received personal fees from the American Journal for Public Health , for which he is the editor for systematic reviews. VW is editor in chief of the Campbell Collaboration, which produces systematic reviews, and co-convenor of the Campbell and Cochrane equity methods group. DM is chair of the EQUATOR Network, IB is adjunct director of the French EQUATOR Centre and TCH is co-director of the Australasian EQUATOR Centre, which advocates for the use of reporting guidelines to improve the quality of reporting in research articles. JMT received salary from Evidence Partners, creator of DistillerSR software for systematic reviews; Evidence Partners was not involved in the design or outcomes of the statement, and the views expressed solely represent those of the author.

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PRISMA 2020 checklist.

Additional file 2.

PRISMA 2020 expanded checklist.

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Page, M.J., McKenzie, J.E., Bossuyt, P.M. et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Syst Rev 10 , 89 (2021). https://doi.org/10.1186/s13643-021-01626-4

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Research Article

Clinical outcomes of chikungunya: A systematic literature review and meta-analysis

Roles Data curation, Formal analysis, Methodology, Software, Visualization, Writing – original draft

* E-mail: [email protected]

Affiliation Asc Academics B.V., Groningen, Netherlands

Roles Conceptualization, Writing – original draft

Affiliations Valneva Austria GmbH, Vienna, Austria, Department of Health Sciences, University Medical Center Groningen, Groningen, Netherlands

Roles Conceptualization, Data curation, Methodology, Project administration, Writing – review & editing

Affiliations Asc Academics B.V., Groningen, Netherlands, Department of Health Sciences, University Medical Center Groningen, Groningen, Netherlands

Roles Investigation, Project administration

Roles Data curation, Investigation

Roles Conceptualization, Supervision

Affiliation Valneva Austria GmbH, Vienna, Austria

Roles Supervision

Affiliations Department of Health Sciences, University Medical Center Groningen, Groningen, Netherlands, Department of Economics, Econometrics & Finance, University of Groningen, Faculty of Economics & Business, Groningen, The Netherlands, Center of Excellence for Pharmaceutical Care Innovation, Universitas Padjadjaran, Bandung, Indonesia, Division of Pharmacology and Therapy, Faculty of Medicine Universitas Airlangga, Surabaya, Indonesia

Affiliations Asc Academics B.V., Groningen, Netherlands, Department of Health Sciences, University Medical Center Groningen, Groningen, Netherlands, Department of Health Technology and Services Research, University of Twente, Enschede, The Netherlands

• Kris Rama, 
• Adrianne M. de Roo, 
• Timon Louwsma, 
• Hinko S. Hofstra, 
• Gabriel S. Gurgel do Amaral, 
• Gerard T. Vondeling, 
• Maarten J. Postma, 
• Roel D. Freriks

• Published: June 7, 2024
• https://doi.org/10.1371/journal.pntd.0012254
• Peer Review
• Reader Comments

This is an uncorrected proof.

Chikungunya is a viral disease caused by a mosquito-borne alphavirus. The acute phase of the disease includes symptoms such as fever and arthralgia and lasts 7–10 days. However, debilitating symptoms can persist for months or years. Despite the substantial impact of this disease, a comprehensive assessment of its clinical picture is currently lacking.

We conducted a systematic literature review on the clinical manifestations of chikungunya, their prevalence and duration, and related hospitalization. Embase and MEDLINE were searched with no time restrictions. Subsequently, meta-analyses were conducted to quantify pooled estimates on clinical outcomes, the symptomatic rate, the mortality rate, and the hospitalization rate. The pooling of effects was conducted using the inverse-variance weighting methods and generalized linear mixed effects models, with measures of heterogeneity reported.

The systematic literature review identified 316 articles. Out of the 28 outcomes of interest, we were able to conduct 11 meta-analyses. The most prevalent symptoms during the acute phase included arthralgia in 90% of cases (95% CI: 83–94%), and fever in 88% of cases (95% CI: 85–90%). Upon employing broader inclusion criteria, the overall symptomatic rate was 75% (95% CI: 63–84%), the chronicity rate was 44% (95% CI: 31–57%), and the mortality rate was 0.3% (95% CI: 0.1–0.7%). The heterogeneity between subpopulations was more than 92% for most outcomes. We were not able to estimate all predefined outcomes, highlighting the existing data gap.

Chikungunya is an emerging public health concern. Consequently, a thorough understanding of the clinical burden of this disease is necessary. Our study highlighted the substantial clinical burden of chikungunya in the acute phase and a potentially long-lasting chronic phase. Understanding this enables health authorities and healthcare professionals to effectively recognize and address the associated symptoms and raise awareness in society.

Author summary

Chikungunya disease is an emerging public health concern. The disease is transmitted by mosquitoes and characterized by arthralgia and fever in the acute phase, lasting 7–10 days. Additionally, some individuals experience chronic symptoms such as arthralgia and tiredness that can last from months to years. Chikungunya is mainly present in the Americas and Asian countries, but the mosquitoes transmitting the disease are spreading to other regions due to climate change, amongst others. This increased disease threat highlights the importance of understanding chikungunya symptoms. However, there are currently no precise estimates on the prevalence of chikungunya symptoms. Therefore, we analysed the available literature on the clinical manifestations of chikungunya. We found that 75% of infected people develop symptoms, primarily characterized by arthralgia in 90% and fever in 88% of cases. Chronic symptoms affect 44% of symptomatic people, and 0.3% of patients with chikungunya die. Unfortunately, we were not able to estimate all predefined outcomes of interest because we did not find enough studies publishing on some of these, demonstrating that there is still much unknown around the clinical manifestations of chikungunya. However, the results can help healthcare workers early identifying chikungunya and raise awareness of this debilitating disease.

Citation: Rama K, de Roo AM, Louwsma T, Hofstra HS, S. Gurgel do Amaral G, Vondeling GT, et al. (2024) Clinical outcomes of chikungunya: A systematic literature review and meta-analysis. PLoS Negl Trop Dis 18(6): e0012254. https://doi.org/10.1371/journal.pntd.0012254

Editor: Richard A. Bowen, Colorado State University, UNITED STATES

Received: February 26, 2024; Accepted: May 28, 2024; Published: June 7, 2024

Copyright: © 2024 Rama et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript and its Supporting information files.

Funding: This paper was funded by Valneva Austria GmbH. AMR and GTV are Valneva employees. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: KR, TL, HSH, and GSG are employees of Asc Academics. Asc Academics has received consultancy fees for this project from Valneva Austria GmbH. AMR and GTV are Valneva employees and own stock options of Valneva. MJP reports grants and honoraria from various pharmaceutical companies, including those developing, producing, and marketing vaccines. He holds stocks in Health-Ecore (Zeist, Netherlands) and PAG BV (Groningen, Netherlands), and advises ASC Academics (Groningen, Netherlands). These competing interest will not alter adherence to PLOS policies on sharing data and materials.

Introduction

Chikungunya is a viral disease caused by a mosquito-borne alphavirus, the chikungunya virus (CHIKV) [ 1 ]. The infection is characterized by an acute phase with symptoms including fever, arthralgia, and myalgia. While most infected individuals fully recover after the acute phase of the disease, between 30–40% of patients develop persistent symptoms, such as chronic arthritis, fatigue, stiffness, depression, and sleep and neurological disorders, which can last from months to several years [ 2 , 3 ]. Long-term effects lead to significant limitations in daily activities and reduce the patients’ overall quality of life [ 4 – 6 ]. Nevertheless, despite the negative impact of the disease on the quality of life, the awareness and societal understanding of chikungunya remain limited, even among the afflicted populations and healthcare workers [ 7 ]. Chikungunya has been identified as a public health threat based on several records of CHIKV outbreaks worldwide, with a risk of exacerbation in the future due to the global spread of CHIKV [ 8 ]. The distribution of the CHIKV vectors ( Aedes aegypti and Aedes albopictus ) is one of the main factors contributing to the disease’s dissemination. This expansion is attributed to globalization and climate change, allowing the Aedes mosquitos to survive in areas previously considered unsuitable [ 9 , 10 ]. Prevention against the disease consists predominantly of mosquito population control [ 11 ]. Recently, the FDA approved the first chikungunya vaccine, presenting a new tool to fight the disease and potentially alleviate the associated economic and health burdens [ 12 ]. Despite the increasing interest in CHIKV and the recent announcement of a vaccine, uncertainties persist regarding the clinical burden of chikungunya. Although multiple studies have explored one or more health outcomes associated with chikungunya [ 3 , 13 , 14 ], to the best of our knowledge, no extensive meta-analysis was performed to quantify pooled estimates on the clinical presentation of chikungunya. To address this gap, we conducted a comprehensive systematic literature review (SLR) on the clinical manifestations of chikungunya, and proceeded with a robust yet flexible meta-analysis. This approach allowed us to provide estimates on a broad spectrum of endpoints on the health outcomes of chikungunya. We paid particular attention to the symptomatic, mortality, and chronicity rates for a comprehensive understanding of the disease in both acute and chronic phases. Our study aims to contribute valuable insights into the overall clinical outcomes of chikungunya. This, in turn, can inform public health intervention strategies and enhance global surveillance by enabling earlier detection of outbreaks.

Literature search and study selection

The SLR adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 (PRISMA 2020) guidelines, with searches conducted on MEDLINE In-Process via PubMed.com, and Embase via Embase.com without time limits. Grey literature searches were performed for the years 2019–2023 to capture data that may not have yet been included in the databases. The search string included terms related to chikungunya and study design. Eligibility criteria were developed using a Population, Intervention, Comparator, Outcomes, Study (PICOS) framework. The inclusion criteria focused on the clinical manifestations of chikungunya, their prevalence and duration, and related hospitalization, and excluded in vitro/preclinical studies, reviews, and non-English articles. Specifics can be found in S1 Text .

Screening and data extraction

All retrieved articles were deduplicated and titles and abstracts were screened against the PICOS criteria using Rayyan. From the selected articles, full texts were examined for eligibility, followed by detailed data extraction organized by study design, patient characteristics, and outcomes of interest. The whole screening process was conducted by two independent reviewers (GG, HH), resolving conflicts through consensus. An exhaustive feasibility assessment ensured the inclusion of studies with explicit criteria and comparable reporting methods, reducing heterogeneity and potential outlier influence. The risk of bias was determined using a modified Downs and Black checklist [ 15 ] and NIH quality assessment tool for observational studies [ 16 ], see S2 Text . Discrepancies were resolved by consensus. No protocol for this systematic review and meta-analysis was registered.

Population and data analysis

The meta-analysis was performed using the meta package of the R statistical software to create a pooled estimate of the most important clinical outcomes of chikungunya. The outcomes of interest were the overall symptomatic, chronicity, and mortality rates, the underreporting factor, the duration of the acute and chronic phase, the hospitalization and outpatient rate (acute and chronic), the mortality rate per region, and the rate and duration of the following symptoms: arthralgia, arthritis, fatigue, fever, headache, joint swelling, myalgia, nausea, rash, and vomiting. The distinction between arthralgia and arthritis was made based on the definition used in the original study.

Both fixed-effects and random-effects models with logit transformation were estimated, where a random-effects model was chosen in case of high heterogeneity. Fixed-effects meta-analyses employed inverse-variance weighting, while random-effects accounted for between-study heterogeneity and are better suited to account for the larger variations in outcomes reported. Heterogeneity was assessed using Cochran’s Q , I 2 , H 2 statistics, and τ 2 estimation. Outlier analyses employed the leave-one-out method, Baujat plots, and statistical distance measures. All results were visually represented using forest plots, providing a clear and concise graphical representation of the individual study findings and the overall meta-analysis result.

Our study utilized subpopulations—subsets of the original populations defined by particular demographic and clinical features. These features correspond to the data reported in the studies we analyzed and the segmentation into subpopulations was based on the inclusion or exclusion criteria set forth in the original research papers. This approach allowed us to perform a more granular analysis. The clinical outcomes of interest were analyzed for a target population to ensure comparability among included studies, which excluded children under 15, individuals with comorbidities or concurrent infections, and pregnant women. Additionally, we excluded unconfirmed CHIKV cases and studies involving chronic patients reporting on the acute phase due to recall bias. Lastly, retrospective studies focusing on mortality were excluded as they exhibited evidence of selection bias. Meta-analyses were performed when an endpoint was reported at least five times for a given subpopulation.

A preliminary search indicated that data on chronicity, mortality, and symptomatic cases was predominantly reported for a more general population, including individuals under the age of 15 and chronic patients. Therefore, we decided to apply less strict criteria on the studies reporting these outcomes, allowing us to estimate these endpoints. Additionally, to detail the development of chronic symptoms, we estimated the chronic rate at various points from disease onset by dividing studies reporting on chronicity rates following a CHIKV infection into subgroups based on time intervals (three, six, and 12 months). The inclusion criteria for each subgroup were to fall within the time windows created by consecutive intervals (e.g., 90–180 days for three months). We excluded studies extending beyond 24 months to avoid a selection bias, as these already focused on patients with pre-existing chronic conditions.

For the mortality rates, we separated the groups that reported outcomes for high-risk populations from those dealing with the general population with lower risk. This stratification allowed us to account for potential confounding variables. Older age and comorbidities have been identified to increase the risk for mortality [ 2 , 17 ]. Therefore, we classify as high-risk of mortality the groups with a minimum age over 65 (or median above 70 when missing), and previous conditions that induced prior intensive care exceeding 24 hours.

To estimate the overall symptomatic rate, we included studies that explicitly reported symptomatic rates based on one or more of the symptoms commonly associated with the disease. Symptomatic patients were often an implicit inclusion criteria, or a precondition for laboratory testing, making most of the studies reporting on the symptomatic rate unusable. We excluded the studies that had a 100% symptomatic rate to prevent selection bias, as including those would lead to a skewed perspective due to symptoms being part of their inclusion criteria.

Literature search

The SLR was conducted on 4 July 2023 and yielded 16,308 hits. After removing 6,285 duplicates, 10,023 studies were screened by titles and abstracts. From these, a total of 316 articles were deemed suitable for inclusion. The process of the SLR is detailed in Fig 1 , which illustrates the PRISMA diagram of the included studies. The complete PRISMA checklist is provided in S3 Text . The quality assessment of included studies can be found in S1 Table .

• PPT PowerPoint slide
• PNG larger image
• TIFF original image

https://doi.org/10.1371/journal.pntd.0012254.g001

Study characteristics

The categorization of study designs in the included articles was made with careful consideration, taking into account the diversity in how these studies defined their methodologies. The judgment used in categorizing these studies was guided by the definitions provided within the paper itself. When a study described its design in a way that matched more than one predefined category, the predominant one was chosen. This approach aimed to respect the original terminology used by the study authors while also creating a coherent framework for analysis.

Of the 316 articles included, 231 studies were observational, 11 were experimental, and for 74 studies this was not reported. Of the observational studies, 106 were cross-sectional, 35 were cohort, 29 were longitudinal, 25 were retrospective, 23 were prospective, and 13 were case-control or case-series studies. Of the experimental studies, there were 6 trials from phase I to III with double and single-blind designs. Goals ranged from assessing treatments like chloroquine and vaccines’ effectiveness to exploring seroprevalence and chronic CHIKV effects. Two trials investigated new mRNA treatment mechanisms. The focus was solely on CHIKV, not on coinfections.

The study location varied: Southern Asia was the most represented with 78 articles, followed by South America, with 67. There were 41 articles from The Caribbean region, 41 from Eastern Africa, 28 from South-Eastern Asia, 14 from Central America. Eight, six, five, four, and three articles were from Western Europe, Northern America, Southern Europe, Middle Africa, and Western Africa, respectively. Two or one articles were from Eastern Asia, Micronesia, Northern Europe, or Southern Africa. A total of 193 studies reported mean or median age. Data on co-infection with Zika and/or dengue were reported in 11 studies. An overview of the study characteristics, including details on the experimental studies, can be found in S2 Table .

The most commonly reported symptom was fever, reported in 57.9% of the studies (N = 183), followed by rash in 54.1% (N = 171), headache in 51.3% (N = 162), and arthralgia in 47.8% (N = 151). Most studies reported high rates (70% to 100%) of fever. Among the 151 studies reporting arthralgia rates, the symptom prevalence ranged from 1% to 100%, as studies presented heterogeneous settings, including, for example, recovered patients, patients in the acute phase, or chronic patients. Duration of symptoms was reported in 22 studies. Taking all symptoms into account, the mean duration of symptoms ranged from two days (fever) to 342 days (arthralgia). It is important to note that the studies presented heterogeneous groups of patients when reporting on the duration of symptoms, which could explain the wide range reported in literature. The hospitalization rate was reported by 53 studies. The hospitalization rate varied between 0%, reported by five different studies [ 18 – 22 ], and 93% in a study by Reller and colleagues [ 23 ].

The development of chronic disease after CHIKV infection was reported in 68 studies. Most studies defined chronic CHIKV infection as the presence of symptoms three months after the infection. Arthralgia was reported as a chronic symptom in 67 studies, joint swelling was reported in 11 studies, myalgia was reported in eight studies, stiffness, especially in the morning, was reported in six studies, and arthritis was reported in four studies. The percentage of patients developing chronic disease ranged from 16% in a study conducted during an outbreak in Chennai, India [ 24 ] to 100% in two other studies [ 25 , 26 ]. Fifty of the included studies reported data on mortality, of which 22 reported no deaths in the study population. The highest reported mortality rate was 36.67%, or 36,670 per 100,000 population, reported by Gupta and colleagues. This study population consisted of chikungunya patients who had been admitted to the intensive care [ 27 ].

Meta-analyses feasibility and results

From the 316 articles retrieved from the SLR, we extracted 756 distinct subpopulations. Each subpopulation corresponds to a group defined by a unique set of inclusion and exclusion criteria as per the definitions provided in each original study. Out of the 756 subpopulations, 335 were used for the analysis of the general population, while 52 where used for the target population. From the 28 selected clinical outcomes, we were able to conduct 11 meta-analyses for the target population, see Fig 2 . The number of studies and subpopulations available for each endpoint is shown in Table 1 . The forest plots from the individual meta-analyses can be found in S1 Fig , and the outlier analysis for each endpoint with the Baujat plot is presented in S2 Fig . No studies or subpopulations were excluded based on outlier analyses. Below, we present the 11 estimates from the meta-analyses on the target population, followed by the results of the analysis on mortality, chronicity, and overall symptomatic rates in the general population.

https://doi.org/10.1371/journal.pntd.0012254.g002

Presented are the number of studies and number of subpopulations reporting on the specific outcomes, the pooled estimates, confidence intervals and I 2 of the estimated endpoints. CI: confidence interval. I 2 : I-squared statistic of heterogeneity.

https://doi.org/10.1371/journal.pntd.0012254.t001

Chikungunya symptoms estimates in the target population.

The prevalence of arthralgia in symptomatic adults with confirmed chikungunya was estimated at 89.7%, while arthritis was less frequent at 17.6%. Fatigue was observed in 56% of patients, fever in 87.8%, and headache affected 49.5% of the population. Joint swelling was reported in 50% of patients, myalgia in 62.9%, nausea in 34.7%, rash in 44.3%, and vomiting in 17.1%. The hospitalization rate during the acute phase of chikungunya was reported by nine subpopulations and estimated at 17%. All results are presented in Table 1 , showing the pooled effect estimate for each symptom, reflecting the average rate of occurrence in the studied populations within specified confidence intervals. Each symptom analysis showed substantial heterogeneity between subpopulations, indicated by high I 2 statistics.

Chronicity, mortality, and overall symptomatic rate.

The meta-analysis for chronicity rate showed declining rates over time: 43.89% at three months, 34.39% at six months, and 31.87% at twelve months, see Fig 3 . Notably, persistent high heterogeneity was observed across subgroups ( I 2 between 96–97%). Mortality rates were estimated at 0.32% (320 per 100,000 population), for normal-risk populations and 15.34% (15,340 per 100,000 population) for high-risk populations, see Fig 4 . The latter displayed higher heterogeneity ( I 2 = 97%) compared to the normal risk ( I 2 = 87%). The meta-analysis estimates that 74.9% of the general population with CHIKV infection were symptomatic, with a 95% confidence interval from 63% to 84%, see Fig 5 . A total of eight studies with corresponding eight subgroups were included in this analysis. I 2 statistics showed a heterogeneity of 91%. Results of the outlier and influential cases analysis can be found in S2 Fig .

https://doi.org/10.1371/journal.pntd.0012254.g003

https://doi.org/10.1371/journal.pntd.0012254.g004

https://doi.org/10.1371/journal.pntd.0012254.g005

Chikungunya poses an emerging global health threat; however, uncertainties around the health burden of this infectious disease persist. This SLR and meta-analyses aim to consolidate existing research on the clinical manifestations of chikungunya. The objective of this study was to provide accurate estimates on the symptomatology of this disease, with a specific focus on the chronicity, mortality, and overall symptomatic rates. Overall, our findings emphasize the substantial disease burden associated with a CHIKV infection.

Arthralgia, fever, and myalgia were the most prevalent symptoms, affecting 89.7%, 87.8%, and 62.9% of symptomatic adults, respectively. These symptoms are also described in previous literature as most common for chikungunya [ 17 , 28 ]. It’s important to note that these symptoms were often implicitly used when initially detecting suspected cases. Although we removed all explicit inclusion criteria, these estimates are likely affected by selection bias. The hospitalization rate of 17% underscores the challenges for healthcare systems during outbreaks. The disease burden related to these symptoms makes chikungunya a significant burden for local healthcare systems, highly influencing the quality of life of infected individuals [ 6 ].

The number of studies that provided data on mortality, chronicity, and overall symptomatic rate was limited for the target adult population. Thus, we decided to use less restrictive population criteria for these specific outcomes. Within this broader general population, we found a 0.32% (320 per 100,000 population) mortality rate in the low-risk group. This is slightly higher than the common reported case-fatality rate of 0.1% (100 per 100,000 population), although reports on mortality rated may vary [ 2 , 6 ]. To our knowledge, no previous meta-analysis on mortality rates has been performed. Therefore, we argue that 0.32% (320 per 100,000 population) is a realistic estimate for the general population. While this percentage is still relatively low compared to other arboviruses [ 29 ], mortality rates can be drastically higher in high-risk groups. Our meta-analysis revealed a mortality rate of 15.34% (15,340 per 100,000 population) in elderly and individuals with previous emergency department or intensive care admissions.

In defining the high-risk group for mortality, we included hospitalized patients who are typically older. As a result, the average age within this group was higher and advanced age is a recognized risk factor for increased mortality from CHIKV infection [ 30 ]. The task of separating the effects of comorbid conditions from the direct impact of CHIKV on mortality rates is complex. These factors often interact with each other, complicating the attribution of cause of death to CHIKV alone—particularly when our analysis could not conclusively establish the causes listed on death certificates. Furthermore, we recognize the possibility of publication bias in existing research on severe CHIKV cases. There may be an overrepresentation of studies focusing on severe outcomes and elevated mortality rates among individuals with underlying health complications or atypical presentations of CHIKV. Such a bias could lead to an overestimation of the mortality risk associated with the virus. Nonetheless, our SLR showed mortality rates up to 36.67% (36,670 per 100,000 population) in specific populations, demonstrating that despite its low rates in the general population, the impact of mortality should not be overlooked [ 27 ].

The chronic phase of chikungunya can be debilitating and long-lasting, leading to a significant health burden for individuals affected. Results from our meta-analysis showed a chronicity rate of 43.89% at three months, 34.39% at six months, and 31.87% at 12 months post-infection, indicating the lasting health burden. A meta-analysis conducted by Paixao and colleagues on the chronicity rate of chikungunya showed similar outcomes, with an overall no-recovery rate of 43% after three months [ 3 ]. One notable difference, possibly due to variations in methodologies, is that Paixao and colleagues reported slightly lower rates over time. Both studies indicate a stabilization over time, but more research is needed to comprehensively map the progression of the chronic phase. In conclusion, long-term chronic illness majorly impacts the quality of life of chikungunya patients [ 4 , 6 ], making these results alarming, especially in light of the potential growing spread of the disease [ 9 , 10 ].

The significant disease burden related to chikungunya was further underlined by an overall symptomatic rate of 74.9% in the general population. The symptomatic rate of chikungunya was estimated between 72% and 97% by the CDC Yellow Book, showing that our estimate could be on the low end [ 17 ]. A reason for this could be the various definitions of symptomatic manifestations across studies, which posed a challenge in deriving a precise estimate for this outcome. Additionally, estimates in the literature are mainly based on patients showing healthcare-seeking behaviour, leaving out asymptomatic patients. Therefore, these estimates are likely to be overestimated. Because we created our estimate based on the total general population, we expect them to provide a better reflection of reality.

Two studies identified in the SLR were designed to investigate treatment options for Chikungunya and therefore included control groups. However, we excluded control populations without confirmed CHIKV from our analysis because our focus was on populations with confirmed CHIKV. In instances where multiple treatment options were assessed among confirmed CHIKV populations, these groups were included in the analysis as we aimed to understand the symptomatology of the disease at presentation in its acute phase. It should be noted that the inclusion of these populations did not significantly influence the outcomes of our study since the primary interest was in the manifestation of symptoms rather than treatment efficacy.

Although we obtained estimates for 11 of the 28 predefined endpoints, estimation for several endpoints proved infeasible due to their infrequent reporting as identified in the SLR. We did not obtain estimates for the underreporting factor, the length of the acute and the chronic phase, the duration of the different symptoms, and the frequencies of hospitalization and outpatient care. Even considering the subpopulation analysis method used, we could not estimate more endpoints. The limited number of studies reflects the uncertainty and novelty associated with chikungunya and the need for more research in this field.

In cases where meta-analyses were feasible for the endpoints, we encountered challenges due to poor data quality or absent data. This is attributable to two main reasons: firstly, the reporting of several endpoints varied inconsistently across studies, preventing their combination in a meta-analysis; and secondly, some studies that reported the desired endpoint did not meet the inclusion criteria, resulting in sparse data that hindered meaningful analysis. As a result, significant knowledge gaps persist regarding various aspects of chikungunya. Further research is necessary to fill these gaps and enhance our understanding of this disease. Additionally, consistent and strict reporting criteria on the clinical picture of chikungunya are needed to help create more comprehensive estimates. Enhanced quality and quantity of data could facilitate the possibility to study potential differences in symptomatology for the different CHIKV subtypes. Furthermore, it could enable investigations into the pathogenicity of CHIKV over the years by comparing data from previous outbreaks.

A strength of our study is the use of subpopulation analyses. We discovered that extracting subpopulations from individual studies allows more endpoints to be estimated, offering comparable populations that limit heterogeneity. The use of subgroups could be useful for future research and mitigate some of the data discrepancies detected in the SLR.

The main limitation of our study is the significant presence of heterogeneity indicated by an average I 2 statistic of 92%. This reflects substantial differences in the inclusion criteria among the studies, a tendency inherent in the disease area of CHIKV as shown by other meta-analyses reporting similar, or even higher, levels of heterogeneity [ 3 ]. There are several reasons for this high heterogeneity. First, data collection on chikungunya is conducted mostly during the outbreaks which limits the possibility of establishing strict scientific protocols as researchers must adapt to the dynamic nature of the event. Secondly, a standardized methodology for reporting endpoints is lacking, making it challenging to compare studies in a meta-analysis. Thirdly, we noticed that including older individuals affected our results, by showing lower symptomatic rates but higher mortality and hospitalization rates. Future studies might exclude this demographic for more precise age-related outcomes. Additionally, other, less known, symptoms might have influenced the disease estimates. An example of this is depressive symptoms related to chikungunya. A study included in our analysis has potentially skewed our meta-analysis results with inflated estimates for fatigue, headache, and rash because they investigated depressive symptoms during the CHIKV infection [ 31 ]. This highlights how undisclosed factors that increase the population’s vulnerability to chikungunya symptoms can potentially impact the research. Another limitation is the potential for confounding factors contributing to symptom prevalence, which we were unable control for in our study. There’s an implicit assumption that the symptoms described have a causal association with Chikungunya; however, some symptoms such as myalgia and fatigue are commonly prevalent in the population and may not be causally related to CHIKV infection. The difficulty in establishing a direct causal relationship between these symptoms and CHIKV should be taken into consideration when interpreting the results. We acknowledge that this could affect the precision of the associations drawn in our analysis and suggest that future research should aim to discern the specific attributable risk of CHIKV for these symptoms. Lastly, outbreaks often occur in locations with limited surveillance systems, leading to lacking or less accurate data from these areas. The high heterogeneity shows the need for additional research in the fields, as well as standardized methodologies in studying chikungunya. Additionally, it emphasizes the importance of meta-analyses like these to come to accurate estimates.

Chikungunya is recognized as a global public health threat, and the disease is expected to spread further due to globalization and climate change. At the same time, vector control and surveillance systems remain limited. Consequently, a thorough understanding of the clinical burden of chikungunya is important to inform public health intervention strategies and improve global surveillance. Our study showed that chikungunya poses a significant health burden, with 74.9% of infected individuals experiencing symptomatic disease. Chronic symptoms are found in 43.4% of patients and can be debilitating and long-lasting. We were not able to create pooled estimates on all endpoints, highlighting the still existing data gap in literature here. Nevertheless, the outcomes determined add to the growing body of evidence underlining the debilitating consequences of chikungunya. With the growing threat of chikungunya, health authorities and healthcare professionals must be prepared to adequately diagnose patients affected by the disease and consider public health interventions to limit its burden. Our findings contribute to the comprehension of chikungunya’s clinical outcomes, essential for improving global surveillance and detecting potential outbreaks.

Supporting information

S1 text. literature search and study selection..

Containing the search strategy and PICOs of the studies included in the SLR.

https://doi.org/10.1371/journal.pntd.0012254.s001

S2 Text. Quality assessment tools.

Modified Downs & Black checklist and the NIH quality assessment tool.

https://doi.org/10.1371/journal.pntd.0012254.s002

S3 Text. PRISMA 2020 checklist.

https://doi.org/10.1371/journal.pntd.0012254.s003

S1 Table. Quality assessment of included studies.

https://doi.org/10.1371/journal.pntd.0012254.s004

S2 Table. Summary of study characteristics.

https://doi.org/10.1371/journal.pntd.0012254.s005

S1 Fig. Forest plots of the clinical outcomes of chikungunya.

https://doi.org/10.1371/journal.pntd.0012254.s006

S2 Fig. Influential case and outlier analysis with Baujat plots.

https://doi.org/10.1371/journal.pntd.0012254.s007

Acknowledgments

We would like to thank the internal teams of Asc Academics who helped during the data extraction phase of the SLR, as well as Roma Kwiatkiewicz from Asc Academics for providing medical writing support.

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Obstructive sleep apnea and acute lower respiratory tract infections: a narrative literature review.

1. Introduction

2. literature search strategy, 3. obstructive sleep apnea and community-acquired pneumonia, 4. obstructive sleep apnea and influenza pneumonia, 5. obstructive sleep apnea and covid-19 pneumonia, 6. obstructive sleep apnea and lower respiratory tract infections: pathophysiology, 6.1. altered immunity, 6.2. risk of aspiration, 6.3. the role of obesity and other comorbidities, 7. obstructive sleep apnea and lower respiratory tract infections: treatment, 7.1. settings of care and empiric antibiotics, 7.2. specific risks guiding empiric antibiotic therapy, 7.3. antibiotic pharmacokinetics, side effects, and resistance, 8. discussion, 9. conclusions, supplementary materials, author contributions, institutional review board statement, informed consent statement, data availability statement, acknowledgments, conflicts of interest.

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Share and Cite

Nemet, M.; Vukoja, M. Obstructive Sleep Apnea and Acute Lower Respiratory Tract Infections: A Narrative Literature Review. Antibiotics 2024 , 13 , 532. https://doi.org/10.3390/antibiotics13060532

Nemet M, Vukoja M. Obstructive Sleep Apnea and Acute Lower Respiratory Tract Infections: A Narrative Literature Review. Antibiotics . 2024; 13(6):532. https://doi.org/10.3390/antibiotics13060532

Nemet, Marko, and Marija Vukoja. 2024. "Obstructive Sleep Apnea and Acute Lower Respiratory Tract Infections: A Narrative Literature Review" Antibiotics 13, no. 6: 532. https://doi.org/10.3390/antibiotics13060532

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Effects of Oral Collagen for Skin Anti-Aging: A Systematic Review and Meta-Analysis

1 School of Medicine, College of Medicine, Taipei Medical University, Taipei City 110, Taiwan; wt.ude.umt@740011101b

Ya-Li Huang

2 Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei City 11031, Taiwan; wt.ude.umt@gnauhly

Chi-Ming Pu

3 Division of Plastic Surgery, Department of Surgery, Cathay General Hospital, Taipei City 106, Taiwan; moc.nsm@5339namkp

4 School of Medicine, College of Life Science and Medicine, National Tsing Hua University, Hsinchu City 300, Taiwan

5 Cochrane Taiwan, Taipei Medical University, Taipei City 110, Taiwan; moc.liamg@dacanyk (Y.-N.K.); wt.ude.umt@nisheek (K.-H.C.)

6 Evidence-Based Medicine Center, Wan Fang Hospital, Taipei Medical University, Taipei City 116, Taiwan

7 Research Center of Big Data and Meta-Analysis, Wan Fang Hospital, Taipei Medical University, Taipei City 116079, Taiwan

8 Institute of Health Policy and Management, College of Public Health, National Taiwan University, Taipei City 100, Taiwan

Khanh Dinh Hoang

9 Department of Histopathology, Hai Phong University of Medicine and Pharmacy, Hai Phong 04254, Vietnam; nv.ude.umph@hnahkdh

Kee-Hsin Chen

10 Post-Baccalaureate Program in Nursing, College of Nursing, Taipei Medical University, Taipei City 11031, Taiwan

11 Department of Nursing, Wan Fang Hospital, Taipei Medical University, Taipei City 11696, Taiwan

12 Research Center in Nursing Clinical Practice, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan

13 Evidence-Based Knowledge Translation Center, Wan Fang Hospital, Taipei Medical University, Taipei City 11696, Taiwan

14 School of Medicine, Faculty of Health and Medical Sciences, Taylor’s University, Selangor 47500, Malaysia

Chiehfeng Chen

15 Division of Plastic Surgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, Taipei City 116, Taiwan

Associated Data

Data will be made available on reasonable request.

This paper presents a systematic review and meta-analysis of 26 randomized controlled trials (RCTs) involving 1721 patients to assess the effects of hydrolyzed collagen (HC) supplementation on skin hydration and elasticity. The results showed that HC supplementation significantly improved skin hydration (test for overall effect: Z = 4.94, p < 0.00001) and elasticity (test for overall effect: Z = 4.49, p < 0.00001) compared to the placebo group. Subgroup analyses demonstrated that the effects of HC supplementation on skin hydration varied based on the source of collagen and the duration of supplementation. However, there were no significant differences in the effects of different sources ( p = 0.21) of collagen or corresponding measurements ( p = 0.06) on skin elasticity. The study also identified several biases in the included RCTs. Overall, the findings suggest that HC supplementation can have positive effects on skin health, but further large-scale randomized control trials are necessary to confirm these findings.

1. Introduction

The skin, the largest organ of the body exposed to the external environment, is affected by both intrinsic and extrinsic factors in the aging process [ 1 ]. Skin aging is characterized by dehydration, a loss of skin elasticity, and the presence of wrinkles [ 2 ]. Skin aging has attracted considerable attention because of the increasingly high beauty standards. Because many countries are becoming aging societies, the psychosocial effects of skin aging increases the need for effective interventions [ 3 ]. In this context, the use of nutraceuticals as supplements has increased in recent years [ 4 ].

Collagen is the main protein structure of various connective tissues, which constitutes 80% of the dry weight of human skin [ 5 ]. Collagen is characterized by a triple helix structure formed by the repetition of glycine every third residue, and particularly by proline and hydroxyproline in the other residues [ 6 ]. Collagen, the most prevalent component of extracellular matrix, provides mechanical support and directs tissue development [ 7 ].

Aging induces a decline in the enzymes involved in the post-translational processing of collagen, reducing the number of fibroblasts that synthesize collagen and vessels that supply the skin [ 8 ]. The decline in skin quality with age is characterized by a reduction in collagen synthesis and a decrease in skin vascularity, leading to decreased elasticity and the formation of wrinkles [ 9 ]. These changes are due to the decline in fibroblast activity and a decrease in the number of blood vessels in the skin [ 10 ]. Therefore, the skin undergoes regressive changes with age such as dehydration, a loss of elasticity, and a reduction in epidermal thickness [ 11 ]. Various nutrients and supplements are used to improve skin health and maintain a youthful skin appearance [ 12 ]. These strategies include topical creams, injectable fillers, and collagen supplements. Topical creams contain collagen as one of the ingredients, and they are designed to enhance skin hydration and firmness [ 13 ]. However, topical creams have limited ability to penetrate the skin, which can reduce their effectiveness [ 13 ]. Injectable fillers such as hyaluronic acid fillers, stimulate collagen production and provide immediate results by plumping the skin [ 14 ]. However, they can be expensive and come with the risk of adverse events such as bruising, swelling, and infection [ 14 ]. On the other hand, collagen supplements, particularly those containing hydrolyzed collagen peptides, have been shown to be safe and cost-effective compared to other collagen-based strategies. Furthermore, collagen supplements have the advantage of being taken orally, making them easy to incorporate into daily routines [ 15 ].

Among these supplements, hydrolyzed collagen (HC) is the most popular and promising skin anti-aging nutraceutical [ 16 ]. Other studies have indicated that alanine–hydroxyproline–glycine and serine–hydroxyproline–glycine can be detected in human blood 1 h after the oral ingestion of HC [ 17 , 18 ] and deposited on the skin [ 19 ].

A recent study demonstrated that HC improves skin hydration and elasticity [ 16 ]. Nevertheless, not all sources of HC have the same efficacy. Even at the same dose and duration of administration, some specific sources of collagens are more effective than others [ 20 ]. Therefore, studies are required to determine the proper source and therapeutic duration of HC against skin aging.

Because an increasing number of clinical studies on collagen supplements have been conducted globally, their results must be summarized in a systematic review and meta-analysis. Therefore, this systematic review and meta-analysis investigated the effects of collagen supplementation on skin hydration and elasticity.

2. Materials and Methods

2.1. search strategy, inclusion criteria, and exclusion criteria.

We performed a literature search in the Embase, PubMed, and Cochrane Library databases by using the following search terms from Medical Subject Headings with no restrictions applied: (collagen OR hydrolyzed collagen) AND (anti-aging). Relevant studies published before December 2022 were identified. We included studies that met the following criteria: (1) applying a randomized clinical trial (RCT) design; (2) including healthy adults (aged ≥ 18 years); (3) including patients who received HC; (4) being full-text articles written in English. We excluded studies that (1) assessed the combined effect of collagen supplement with another supplement or (2) were RCTs that were not written in English. We extracted raw data from the graphs in articles using WebPlotDigitizer [ 21 ].

2.2. Data Extraction

Two independent reviewers (S-YP, CC) extracted the basic information of the included studies. The following types of information were extracted: study meta-data (i.e., first author, publication year, and study design) and information on the study sample (i.e., number of patients, gender, mean age, and baseline characteristics of the treatment and placebo groups), intervention (i.e., the dose of collagen supplement and form), and outcomes (i.e., hydration and elasticity). Continuous outcomes are presented in terms of the mean ± standard deviation (SD), and discrete data are presented in terms of percentage.

2.3. Statistical Analysis, Sensitivity Analysis and Bias Assessment

We used a random-effects model to calculate the SD and mean difference of the identified studies. A p value of <0.05 indicated statistical significance. The levels of heterogeneity among the included studies were determined using Hedge’s I 2 tests, and forest plots were generated for each included study. Moreover, I 2 ≥ 50% indicated high heterogeneity [ 22 ]. The general effect test result was reported as a z-value, which supported the inference of the 95% confidence interval (CI). A sensitivity analysis was performed to negate the effect of potentially influential studies. Each study was classified in accordance with the Cochrane Handbook for Systematic Reviews of Interventions [ 23 ]. The Cochrane risk of bias (RoB) 2.0 tool was used to assess the risk of bias in the included RCTs. Five domains of bias were evaluated (selection, performance, detection, attrition, and reporting bias) [ 24 ]. In this meta-analysis, all outcomes were analyzed using RevMan software (version 5.4).

3.1. Research Results and Study Characteristics

Figure 1 shows the flowchart of the literature search process performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines [ 25 ]. We identified 1135 studies in our initial search. After removing duplicates and screening titles or abstracts of related articles, we assessed the full-text articles of the remaining 37 studies. Of these studies, 26 articles were included in this systematic review and meta-analysis.

Flowchart of the systematic review and meta-analysis according to the PRISMA guidelines.

3.2. Study Characteristics

A total of 26 RCTs involving 1721 patients were included in this meta-analysis. The duration of the HC supplementation of the included studies ranged from 2 to 12 weeks. Among the included RCTs, 14 focused on collagens extracted from fish, one focused on collagens extracted from bovine, one focused on collagens extracted from chicken, two focused on collagens extracted from porcine, and nine lacked information regarding the source of collagen. The study characteristics of the included RCTs are presented in Table 1 .

The measurement of skin hydration levels is commonly conducted using a non-invasive tool called a corneometer. This instrument emits a high-frequency electric current into the skin’s surface and measures the amount of water present in the top layer, expressed in corneometry units. The corneometer is widely used in evaluating the effectiveness of topical products and assessing overall skin health by providing valuable insights into the skin’s moisture barrier. Therefore, it is considered as a valuable tool in measuring the skin hydration levels and assessing the efficacy of skincare products [ 18 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. On the other hand, the measurement of skin elasticity is often conducted using cutometry, a non-invasive technique that provides valuable insights into skin health. It works by applying a controlled negative pressure to a small area of the skin and measuring the resulting deformation, which is directly proportional to the skin’s elasticity. Cutometry is widely used in research and clinical settings to assess the skin elasticity levels and monitor changes in the skin over time. Overall, it is a safe and reliable tool for evaluating skin health [ 18 , 26 , 27 , 29 , 32 , 33 , 34 , 35 , 36 , 37 ].

Characteristics of the patients in the included studies.

3.3. Meta-Analysis Results

3.3.1. pooled analysis of selected studies.

Some articles were excluded from the research due to various reasons. Studies conducted by Campos, Czajka, Genovese, and Sangsuwan were not considered as they did not measure the hydration levels, which was a key parameter of interest. Similarly, the Asserin study did not measure elasticity, so its results could not be used to evaluate the impact of elasticity on the outcome measures. The Bianchi and Ping study was excluded due to the lack of standard deviation data for the placebo group, which was necessary for the statistical analysis. The Laing study did not provide sufficient direct data on moisture and elasticity, the primary outcomes of interest, and the provided microscopic observations and questionnaires were insufficient for the research. Finally, the Proksch study did not provide data for the placebo group, making it impossible to compare the results with those of the intervention group. Therefore, these studies did not meet the necessary criteria for inclusion in the research.

All included RCTs divided the patients into two groups according to the collagen measurement and skin hydration or elasticity, and then subjected to a meta-analysis. The standard mean difference (SMD) of 18 studies on the effects of HC and the placebo on skin hydration are shown in Figure 2 . The overall pooled effect size of 0.63 (95% CI 0.38, 0.88) indicated that HC supplementation significantly improved skin hydration (z = 4.94, p < 0.00001). Figure 3 shows the forest plot of the meta-analysis of 19 studies on the effects of HC on skin elasticity; the results indicate that HC supplementation significantly improved skin elasticity (z = 4.49, p < 0.00001) compared with the placebo group at a pooled effect size of 0.72 (95% CI 0.40, 1.03).

Forest plot of the included studies evaluating skin hydration in patients supplemented with HC and patients in the placebo group [ 26 , 27 , 28 , 30 , 31 , 32 , 33 , 34 , 35 , 39 , 40 , 43 , 44 , 46 , 47 , 48 , 49 , 50 ]. (HC: hydrolyzed collagen, CI: confidence intervals, SD: standard deviation, I 2 : heterogeneity).

Forest plot of the included studies evaluating skin elasticity in patients supplemented with HC and patients in the placebo group [ 26 , 27 , 28 , 29 , 31 , 32 , 33 , 34 , 35 , 37 , 39 , 40 , 41 , 42 , 43 , 44 , 47 , 48 , 49 ]. (HC: hydrolyzed collagen, CI: confidence intervals, SD: standard deviation, I 2 : heterogeneity).

3.3.2. Subgroup Analysis

Collagen supplements are available in various forms including gels, liquids, and capsules. The type of collagen used in these supplements can vary depending on the source, with some of the most common types including fish, porcine, chicken, and bovine collagen. A subgroup analysis was performed to determine the effects of multiple sources of HC supplements and duration on skin hydration. The results showed that the supplementation with HC originating from fish, bovine, chicken, porcine, and unknown source significantly improved skin hydration ( Figure 4 , p < 0.00001). Of these sources, HC originating from chicken had the weakest effect (−0.03, 95% CI −0.40, 0.34) on skin hydration. In addition, we performed subgroup analyses on the duration of HC supplementation for 2, 4, 6, 8, and 12 weeks. The forest plot analysis revealed that the effects of HC supplementation during 4 ( p = 0.002), 6 ( p = 0.04), 8 ( p < 0.00001), and 12 weeks ( p = 0.001) significantly differed, as shown in Figure 5 . In addition, the effects of the long-term use (>8 weeks) of HC (0.59, 95% CI 0.35, 0.83) were more favorable than that of the short-term use (<8 weeks) of HC (0.39, 95% CI 0.15, 0.63, Figure 6 ).

Forest plot for the subgroup analysis of skin hydration expressed as HC originating from fish, bovine, chicken, porcine, and unknown source in patients supplemented with HC and patients in the placebo group [ 26 , 27 , 28 , 30 , 31 , 32 , 33 , 34 , 35 , 40 , 43 , 44 , 46 , 47 , 48 , 49 , 50 ]. (HC: hydrolyzed collagen, CI: confidence intervals, SD: standard deviation, I 2 : heterogeneity).

Forest plot for the subgroup analysis of skin hydration expressed as 2, 4, 6, 8, and 12 weeks in patients supplemented with HC and patients in the placebo group [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 39 , 40 , 43 , 44 , 46 , 47 , 48 , 49 , 50 ]. (HC: hydrolyzed collagen, CI: confidence intervals, SD: standard deviation, I 2 : heterogeneity).

Forest plot for the subgroup analysis of skin hydration expressed as long-term (>8 weeks) and short-term (<8 weeks) in patients supplemented with HC and patients in the placebo group [ 26 , 27 , 28 , 30 , 31 , 32 , 33 , 34 , 35 , 39 , 40 , 43 , 44 , 46 , 47 , 48 , 49 , 50 ]. (HC: hydrolyzed collagen, CI: confidence intervals, SD: standard deviation, I 2 : heterogeneity).

In addition, three subgroup analyses of the effects of sources of HC, corresponding measurements (R2: Gross elasticity, R5: Net elasticity; elastic portion of relaxation/elastic portion of suction, R7: Elastic portion; elastic portion of relaxation/first maximum amplitude after suction and mm by cutometer) and the duration of HC supplementation on skin elasticity were performed. The subgroup analyses indicated no significant differences in the effects of various sources of HC ( p = 0.21, Figure 7 ) and the corresponding measurements ( p = 0.06, Figure 8 ) on skin elasticity. The subgroup analysis on the duration revealed that 6 weeks of HC supplementation showed no positive effect on skin elasticity ( p = 0.05, Figure 9 ). Furthermore, the effect of the long-term use (>8 weeks) of HC (0.73, 95% CI 0.41, 1.06) was more favorable than that of the short-term use (<8 weeks) of HC (0.67, 95% CI 0.33, 1.00) on skin elasticity. The results of the subgroup analyses are presented in Figure 10 .

Forest plot for the subgroup analysis of skin elasticity expressed as HC originating from fish, bovine, chicken, porcine, and unknown source in patients supplemented with HC and patients in the placebo group [ 26 , 27 , 28 , 29 , 31 , 32 , 33 , 34 , 35 , 37 , 39 , 40 , 41 , 42 , 43 , 44 , 47 , 48 , 49 ]. (HC: hydrolyzed collagen, CI: confidence intervals, SD: standard deviation, I 2 : heterogeneity).

Forest plot for the subgroup analysis of skin elasticity expressed as R2 (Gross elasticity), R5 (Net elasticity; elastic portion of relaxation/elastic portion of suction), R7 (Elastic portion; elastic portion of relaxation/first maximum amplitude after suction), and mm in patients supplemented with hydrolyzed collagen (HC) and patients in the placebo group [ 26 , 28 , 29 , 31 , 33 , 34 , 35 , 37 , 39 , 41 , 43 , 48 , 49 ]. (HC: hydrolyzed collagen, CI: confidence intervals, SD: standard deviation, I 2 : heterogeneity).

Forest plot for the subgroup analysis of skin elasticity expressed as 2, 4, 6, 8, and 12 weeks in patients supplemented with HC and patients in the placebo group [ 26 , 27 , 28 , 29 , 31 , 32 , 33 , 34 , 35 , 37 , 39 , 40 , 41 , 42 , 43 , 44 , 47 , 48 , 49 ]. (HC: hydrolyzed collagen, CI: confidence intervals, SD: standard deviation, I 2 : heterogeneity).

Forest plot for the subgroup analysis of skin elasticity expressed as long-term (>8 weeks) and short-term (<8 weeks) in patients supplemented with HC and patients in the placebo group [ 26 , 27 , 28 , 29 , 31 , 32 , 33 , 34 , 35 , 37 , 39 , 40 , 41 , 42 , 43 , 44 , 47 , 48 , 49 ]. (HC: hydrolyzed collagen, CI: confidence intervals, SD: standard deviation, I 2 : heterogeneity).

In conducting systematic reviews and meta-analyses, it is important to examine the quality of research studies and potential biases. One common method for assessing bias is through the use of RoB (Risk of Bias). RoB evaluates various aspects of a study that could lead to bias such as incomplete outcome data and selective outcome reporting. Each aspect is evaluated based on predefined criteria, and an overall assessment of the study’s risk of bias is made. The goal of RoB is to provide an impartial evaluation of the study’s design, implementation, and reporting to aid in determining the study’s reliability and suitability for inclusion in systematic reviews or meta-analyses [ 24 ]. At the study level, we found an RoB in the bias arising from the randomization process in one study [ 33 ], bias due to deviations from intended intervention in seven studies [ 27 , 30 , 31 , 33 , 35 , 44 , 48 ], bias due to missing outcome data in thirteen studies [ 18 , 27 , 28 , 30 , 31 , 33 , 34 , 35 , 37 , 44 , 47 , 48 , 51 ], and bias in the selection of the reported results in two studies [ 18 , 51 ]. Figure 11 provides additional details on the RoB assessment results for the included RCTs.

Risk of bias [ 18 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 ]. * D1: Randomization process; D2: Deviations from the intended interventions; D3: Missing outcome data; D4: Measurement of outcome; D5: Selection of the reported result.

4. Discussion

To evaluate the effects of collagen supplements on skin aging, we analyzed 26 RCTs to assess the efficacy of oral collagen supplements on skin hydration and elasticity, both of which characterize skin aging. The trials measured skin hydration and elasticity on various areas of the body including the cheek, forearm, and forehead. By analyzing these parameters, our findings revealed that oral collagen supplements improved skin hydration and elasticity. The beneficial effects were significant after 8 weeks or more of HC supplementation.

4.1. Hydration

The key molecule involved in skin moisture is hyaluronic acid, a glycosaminoglycan with a unique capacity to retain water molecules [ 52 ]. The most striking histochemical change observed in aging skin is the gradual loss of epidermal hyaluronic acid [ 53 ]. Oral administration of collagen hydrolysates include rich proline-hydroxyproline, which stimulates hyaluronic acid production in the dermal fibroblast cells [ 54 ].

Our study findings revealed that supplementation with oral collagens improved skin hydration, which is consistent with previous findings. Cao et al. reported that the concentration of moisture in the skin of mice treated with collagen peptides (CPs) was significantly higher compared with that of the control mice ( p < 0.05) [ 55 ]. Sun et al. revealed that collagen as a single supplement showed remarkable effects on skin hydration, with an SMD of 0.77 (95% CI 0.60, 0.94; p < 0.00001) compared with a placebo [ 56 ].

Our findings revealed that fish was the optimal source of collagen for improving skin hydration. A previous study indicated that collagens sourced from fish skins have diverse amino acid compositions than mammalian collagens [ 57 ]. Another study estimated that the yields of collagen derived from fish skin were 50%, collagen derived from fish bones were 40%, and collagen derived from fish fin were 36.4% [ 58 ]. Notably, marine collagen and collagen peptides have high bioavailability, potency, and a favorable safety profile [ 59 ].

In our investigations, only one study by Schwartz (2019) investigated the effect of collagen sourced from chicken, which was the least among all included studies. However, in the study by Cao et al. on the effects of the oral intake of CPs derived from chicken bones in mice showed that the concentration of moisture in the skin of mice treated with CPs was significantly higher compared with that of the control mice ( p < 0.05) [ 55 ]. Schwastz et al. administered 1 g of collagen from hydrolyzed chicken sternal cartilage daily for 12 weeks to all human participants. The skin hydration of the participants significantly increased by 12.5% ( p = 0.003) between weeks 6 and 12 [ 36 ]. Additionally, it is unclear whether the results can be generalized to the wider population, as the studies were conducted on mice and humans with different characteristics and may not reflect the general population.

4.2. Elasticity

Fibril-forming type I collagen is the major collagen in the skin, comprising 90% of the total collagen, and plays a role in structural organization, integrity, and strength and skin [ 60 ]. The elastic fiber network imparts elasticity and resilience to the tissues and comprises elastin and microfibrils, which are composed of various proteins [ 61 ]. The elasticity of the skin depends on the function of the network, and its formation is a complex process involving many factors. One study showed that the intake of HC downregulated placenta growth factor-2, insulin-like growth factor binding protein 2, insulin-like growth factor binding protein 3, platelet factor 4, serpin E1, and transforming growth factor β-1, and increased type I collagen mRNA and protein levels [ 62 ].

Our findings revealed that supplementation with oral collagen improves skin elasticity, which are consistent with previous findings. De Luca et al. found that patients taking marine collagen peptides significantly improved skin elasticity ( p < 0.0001) [ 63 ]. Maia Campos et al. demonstrated that a group treated with oral collagen showed significant differences in the mechanical properties of the skin compared with the baseline and placebo groups after 90 days of treatment only in the net elasticity parameter in the periorbital region [ 64 ]. Lee et al. showed that 12 weeks of oral collagen film consumption significantly increased the elasticity of the skin surface (R2), yielding 0.66 ± 0.05 before use to 0.75 ± 0.04 after 12 weeks ( p < 0.05) [ 65 ]. The study conducted by Sone et al. (2018) was conducted on chronologically aged mice, which showed that oral administration of collagen peptides derived from bovine bone can improve the laxity of chronologically aged skin in mice by increasing the skin collagen content and ratio of type I to type III collagen. The study also suggested that collagen peptides may increase antioxidant properties in the body, and proline intake can improve the elasticity of chronologically aged skin in mice [ 66 ].

Among the included studies, Yoon et al. showed that in humans, 12 weeks of supplementation with oral collagen significantly improved skin elasticity (3.25, 95% CI 2.33, 4.18) compared with other durations. This finding is consistent with that of an open, blinded, and noncomparative study, which showed 38.31% of improvement in elasticity after consuming oral collagen for 3 months [ 67 ]. Another study examined obvious characteristics of skin aging in nude mice after combining treatment with D-galactose and ultraviolet radiation. However, after the oral administration of CP, the concentrations of skin collagen and elastin increased [ 68 ]. While studies suggest that oral collagen supplementation may improve skin elasticity, it is important to consider the limitations of the research. The studies used different durations and forms of collagen supplementation, making it difficult to compare the results. Furthermore, the sample sizes of the studies were relatively small, and the human studies relied on self-reported measures of skin elasticity. Additionally, the study on nude mice may not accurately reflect the effects of oral collagen supplementation in humans.

4.3. Mechanism

Protein hydrolysates are easier to digest and absorb than intact proteins, which increase the production of amino acids after meals [ 69 ]. An in vivo mouse model study found transient increases in the Gly-Pro-Hyp levels in the blood of both humans and mice and that other collagen peptides were also transported to the skin after the ingestion of HC [ 70 ]. Kamiyama et al. used [14C] Gly-Pro-Hyp as a tracer for the tripeptide and compared its absorption with 14C-labeled proline in rats. At 14 days after the administration of [14C] Gly-Pro-Hyp, almost all radioactivity disappeared from the organs, except for the skin, with a radioactivity of 70% observed after 6 h [ 71 ]. Another similar study observed radioactivity after a single administration of [14C] Gly-Pro-Hyp in the connective tissues including the bones and skin within 24 h [ 72 ].

4.4. Sensitivity Analysis

In this study, two included RCTs, namely Campos et al. [ 29 ] (2.17, 95% CI 1.52, 2.81) Choi et al. [ 32 ] (1.61, 95% CI 0.44, 2.78), yielded favorable effects of oral collagen supplementation on skin elasticity. Campos (2015) used a mixture of 10 g of collagen and vitamin A, C, E, zinc as well as excipients, which had beneficial effects, possibly because of its synergism with collagen. A study found that vitamin C triggers a considerable thickening of the epidermis, induces the production of collagen and the formation of elastic microfibrils [ 73 ]. By contrast, vitamin A maintains the health of the epithelial cells on the surface of the skin and increases the production of collagen and the extracellular matrix [ 74 , 75 ]. However, because Choi (2014) enrolled participants aged 30–48 years, which were younger than the participants in the other included studies, it is possible that this study yielded better results due to factors such as a potentially lower prevalence of underlying health conditions or greater overall health among the younger participants. This might thus explain why this study yielded better results. A clinical study that contributed that the composition of the basement membrane changed with age showed that the concentrations of collagen IV, collagen IV, and collagen XII decreased over time [ 76 ]. Thus, a sensitivity analysis was performed to assess the influence of these two studies, and the results of the corresponding forest plots are provided in the Supplementary Materials . The exclusion of this study resulted in no significant change, and the effects of collagen supplementation remained favorable.

4.5. Limitations

This study had several limitations. First, the interventions used in the included studies exhibited some heterogeneity, primarily because of the distinct measurement units and composition of the supplementation. Second, the number of patients included in some studies was less than 40. Therefore, a small sample size may have resulted in a slight RoB. Third, the patients’ lifestyle habits were not included in the analysis. For example, HC supplementation in patients with healthier lifestyle habits could have presented more evident results in improving the appearance of the skin. Thus, additional studies, specifically large clinical trials, are needed.

5. Conclusions

The findings of this study revealed that HC supplementation can improve skin hydration and elasticity. In addition, the long-term use of collagen yields more favorable effects on skin hydration and elasticity than the short-term use of collagen. Nevertheless, large-scale randomized control trials are required to examine the clinical benefits of oral collagen supplements.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/nu15092080/s1 , Figure S1. Elasticity-sensitivity analysis; Figure S2. Hydration-sensitivity analysis.

Funding Statement

This research was funded by Taipei Municipal Wanfang Hospital (managed by Taipei Medical University), grant number 111TMU-WFH-06.

Author Contributions

Conceptualization: S.-Y.P.; Data curation: S.-Y.P. and Y.-N.K.; Formal analysis: S.-Y.P. and C.C.; Funding acquisition: Y.-L.H.; Investigation: C.C.; Methodology: S.-Y.P., Y.-L.H., C.-M.P. and C.C.; Project administration: C.-M.P., Y.-N.K., K.-H.C. and C.C.; Software: C.-M.P., Y.-N.K. and C.C.; Supervision: C.C. and C.-M.P.; Validation: S.-Y.P., Y.-L.H., C.-M.P. and C.C.; Visualization: S.-Y.P.; Writing—original draft: S.-Y.P., C.-M.P. and Y.-L.H.; Writing—review & editing: K.D.H., K.-H.C. and C.C. All authors have read and agreed to the published version of the manuscript.

Institutional Review Board Statement

This study did not require ethical approval.

Informed Consent Statement

This study did not involve humans.

Data Availability Statement

Conflicts of interest.

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

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Risk Factors for Acute Postsurgical Pain: A Narrative Review

Affiliations.

• 1 Department of Anesthesiology, Xishan People's Hospital of Wuxi City, Wuxi, 214105, People's Republic of China.
• 2 Department of Anesthesiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, People's Republic of China.
• 3 Department of Anesthesiology, The Second Affiliated Hospital, Nanjing Medical University, Nanjing, 210011, People's Republic of China.
• 4 Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, People's Republic of China.
• PMID: 38799277
• PMCID: PMC11122256
• DOI: 10.2147/JPR.S462112

Acute postsurgical pain (APSP) has received growing attention as a surgical outcome. When poorly controlled, APSP can affect short- and long-term outcomes in patients. Despite the steady increase in awareness about postoperative pain and standardization of pain prevention and treatment strategies, moderate-to-severe APSP is frequently reported in clinical practice. This is possibly because pain varies widely among individuals and is influenced by distinct factors, such as demographic, perioperative, psychological, and genetic factors. This review investigates the risk factors for APSP, including gender, age, obesity, smoking history, preoperative pain history, pain sensitivity, preoperative anxiety, depression, pain catastrophizing, expected postoperative pain, surgical fear, and genetic polymorphisms. By identifying patients having an increased risk of moderate-to-severe APSP at an early stage, clinicians can more effectively manage individualized analgesic treatment protocols with a combination of pharmacological and non-pharmacological interventions. This would alleviate the transition from APSP to chronic pain and reduce the severity of APSP-induced chronic physical disability and social psychological distress.

Keywords: acute postoperative pain; acute postsurgical pain; predictors; risk factors.

© 2024 Liu et al.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Flowchart of study selection.

Risk factors for acute postsurgical…

Risk factors for acute postsurgical pain.

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