systematic literature review write up

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How to write a systematic literature review [9 steps]

What is a systematic literature review?

Where are systematic literature reviews used, what types of systematic literature reviews are there, how to write a systematic literature review, 1. decide on your team, 2. formulate your question, 3. plan your research protocol, 4. search for the literature, 5. screen the literature, 6. assess the quality of the studies, 7. extract the data, 8. analyze the results, 9. interpret and present the results, registering your systematic literature review, frequently asked questions about writing a systematic literature review, related articles.

A systematic literature review is a summary, analysis, and evaluation of all the existing research on a well-formulated and specific question.

Put simply, a systematic review is a study of studies that is popular in medical and healthcare research. In this guide, we will cover:

• the definition of a systematic literature review
• the purpose of a systematic literature review
• the different types of systematic reviews
• how to write a systematic literature review

➡️ Visit our guide to the best research databases for medicine and health to find resources for your systematic review.

Systematic literature reviews can be utilized in various contexts, but they’re often relied on in clinical or healthcare settings.

Medical professionals read systematic literature reviews to stay up-to-date in their field, and granting agencies sometimes need them to make sure there’s justification for further research in an area. They can even be used as the starting point for developing clinical practice guidelines.

A classic systematic literature review can take different approaches:

• Effectiveness reviews assess the extent to which a medical intervention or therapy achieves its intended effect. They’re the most common type of systematic literature review.
• Diagnostic test accuracy reviews produce a summary of diagnostic test performance so that their accuracy can be determined before use by healthcare professionals.
• Experiential (qualitative) reviews analyze human experiences in a cultural or social context. They can be used to assess the effectiveness of an intervention from a person-centric perspective.
• Costs/economics evaluation reviews look at the cost implications of an intervention or procedure, to assess the resources needed to implement it.
• Etiology/risk reviews usually try to determine to what degree a relationship exists between an exposure and a health outcome. This can be used to better inform healthcare planning and resource allocation.
• Psychometric reviews assess the quality of health measurement tools so that the best instrument can be selected for use.
• Prevalence/incidence reviews measure both the proportion of a population who have a disease, and how often the disease occurs.
• Prognostic reviews examine the course of a disease and its potential outcomes.
• Expert opinion/policy reviews are based around expert narrative or policy. They’re often used to complement, or in the absence of, quantitative data.
• Methodology systematic reviews can be carried out to analyze any methodological issues in the design, conduct, or review of research studies.

Writing a systematic literature review can feel like an overwhelming undertaking. After all, they can often take 6 to 18 months to complete. Below we’ve prepared a step-by-step guide on how to write a systematic literature review.

• Decide on your team.
• Formulate your question.
• Plan your research protocol.
• Search for the literature.
• Screen the literature.
• Assess the quality of the studies.
• Extract the data.
• Analyze the results.
• Interpret and present the results.

When carrying out a systematic literature review, you should employ multiple reviewers in order to minimize bias and strengthen analysis. A minimum of two is a good rule of thumb, with a third to serve as a tiebreaker if needed.

You may also need to team up with a librarian to help with the search, literature screeners, a statistician to analyze the data, and the relevant subject experts.

Define your answerable question. Then ask yourself, “has someone written a systematic literature review on my question already?” If so, yours may not be needed. A librarian can help you answer this.

You should formulate a “well-built clinical question.” This is the process of generating a good search question. To do this, run through PICO:

• Patient or Population or Problem/Disease : who or what is the question about? Are there factors about them (e.g. age, race) that could be relevant to the question you’re trying to answer?
• Intervention : which main intervention or treatment are you considering for assessment?
• Comparison(s) or Control : is there an alternative intervention or treatment you’re considering? Your systematic literature review doesn’t have to contain a comparison, but you’ll want to stipulate at this stage, either way.
• Outcome(s) : what are you trying to measure or achieve? What’s the wider goal for the work you’ll be doing?

Now you need a detailed strategy for how you’re going to search for and evaluate the studies relating to your question.

The protocol for your systematic literature review should include:

• the objectives of your project
• the specific methods and processes that you’ll use
• the eligibility criteria of the individual studies
• how you plan to extract data from individual studies
• which analyses you’re going to carry out

For a full guide on how to systematically develop your protocol, take a look at the PRISMA checklist . PRISMA has been designed primarily to improve the reporting of systematic literature reviews and meta-analyses.

When writing a systematic literature review, your goal is to find all of the relevant studies relating to your question, so you need to search thoroughly .

This is where your librarian will come in handy again. They should be able to help you formulate a detailed search strategy, and point you to all of the best databases for your topic.

➡️ Read more on on how to efficiently search research databases .

The places to consider in your search are electronic scientific databases (the most popular are PubMed , MEDLINE , and Embase ), controlled clinical trial registers, non-English literature, raw data from published trials, references listed in primary sources, and unpublished sources known to experts in the field.

➡️ Take a look at our list of the top academic research databases .

Tip: Don’t miss out on “gray literature.” You’ll improve the reliability of your findings by including it.

Don’t miss out on “gray literature” sources: those sources outside of the usual academic publishing environment. They include:

• non-peer-reviewed journals
• pharmaceutical industry files
• conference proceedings
• pharmaceutical company websites
• internal reports

Gray literature sources are more likely to contain negative conclusions, so you’ll improve the reliability of your findings by including it. You should document details such as:

• The databases you search and which years they cover
• The dates you first run the searches, and when they’re updated
• Which strategies you use, including search terms
• The numbers of results obtained

➡️ Read more about gray literature .

This should be performed by your two reviewers, using the criteria documented in your research protocol. The screening is done in two phases:

• Pre-screening of all titles and abstracts, and selecting those appropriate
• Screening of the full-text articles of the selected studies

Make sure reviewers keep a log of which studies they exclude, with reasons why.

➡️ Visit our guide on what is an abstract?

Your reviewers should evaluate the methodological quality of your chosen full-text articles. Make an assessment checklist that closely aligns with your research protocol, including a consistent scoring system, calculations of the quality of each study, and sensitivity analysis.

The kinds of questions you'll come up with are:

• Were the participants really randomly allocated to their groups?
• Were the groups similar in terms of prognostic factors?
• Could the conclusions of the study have been influenced by bias?

Every step of the data extraction must be documented for transparency and replicability. Create a data extraction form and set your reviewers to work extracting data from the qualified studies.

Here’s a free detailed template for recording data extraction, from Dalhousie University. It should be adapted to your specific question.

Establish a standard measure of outcome which can be applied to each study on the basis of its effect size.

Measures of outcome for studies with:

• Binary outcomes (e.g. cured/not cured) are odds ratio and risk ratio
• Continuous outcomes (e.g. blood pressure) are means, difference in means, and standardized difference in means
• Survival or time-to-event data are hazard ratios

Design a table and populate it with your data results. Draw this out into a forest plot , which provides a simple visual representation of variation between the studies.

Then analyze the data for issues. These can include heterogeneity, which is when studies’ lines within the forest plot don’t overlap with any other studies. Again, record any excluded studies here for reference.

Consider different factors when interpreting your results. These include limitations, strength of evidence, biases, applicability, economic effects, and implications for future practice or research.

Apply appropriate grading of your evidence and consider the strength of your recommendations.

It’s best to formulate a detailed plan for how you’ll present your systematic review results. Take a look at these guidelines for interpreting results from the Cochrane Institute.

Before writing your systematic literature review, you can register it with OSF for additional guidance along the way. You could also register your completed work with PROSPERO .

Systematic literature reviews are often found in clinical or healthcare settings. Medical professionals read systematic literature reviews to stay up-to-date in their field and granting agencies sometimes need them to make sure there’s justification for further research in an area.

The first stage in carrying out a systematic literature review is to put together your team. You should employ multiple reviewers in order to minimize bias and strengthen analysis. A minimum of two is a good rule of thumb, with a third to serve as a tiebreaker if needed.

Your systematic review should include the following details:

A literature review simply provides a summary of the literature available on a topic. A systematic review, on the other hand, is more than just a summary. It also includes an analysis and evaluation of existing research. Put simply, it's a study of studies.

The final stage of conducting a systematic literature review is interpreting and presenting the results. It’s best to formulate a detailed plan for how you’ll present your systematic review results, guidelines can be found for example from the Cochrane institute .

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• Knowledge Base

Methodology

• Systematic Review | Definition, Example, & Guide

Systematic Review | Definition, Example & Guide

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

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

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

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

Table of contents

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

A systematic review has many pros .

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

Systematic reviews also have a few cons .

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

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

Step 1: Formulate a research question

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

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

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

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

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

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

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

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

Their research question was:

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

Step 2: Develop a protocol

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

Your protocol should include the following components:

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

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

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

Step 3: Search for all relevant studies

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

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

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

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

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

Step 4: Apply the selection criteria

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

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

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

You should apply the selection criteria in two phases:

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

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

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

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

Step 5: Extract the data

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

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

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

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

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

Step 6: Synthesize the data

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

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

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

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

Step 7: Write and publish a report

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

Your article should include the following sections:

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

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

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

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

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

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

Research bias

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

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

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

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

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

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

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Systematic Review

• Library Help
• What is a Systematic Review (SR)?

Steps of a Systematic Review

• Framing a Research Question
• Developing a Search Strategy
• Searching the Literature
• Managing the Process
• Meta-analysis
• Publishing your Systematic Review

Forms and templates

Image: David Parmenter's Shop

• PICO Template
• Inclusion/Exclusion Criteria
• Database Search Log
• Review Matrix
• Cochrane Tool for Assessing Risk of Bias in Included Studies

   • PRISMA Flow Diagram  - Record the numbers of retrieved references and included/excluded studies. You can use the Create Flow Diagram tool to automate the process.

   •  PRISMA Checklist - Checklist of items to include when reporting a systematic review or meta-analysis

PRISMA 2020 and PRISMA-S: Common Questions on Tracking Records and the Flow Diagram

• PROSPERO Template
• Manuscript Template
• Steps of SR (text)
• Steps of SR (visual)
• Steps of SR (PIECES)

Adapted from  A Guide to Conducting Systematic Reviews: Steps in a Systematic Review by Cornell University Library

Source: Cochrane Consumers and Communications  (infographics are free to use and licensed under Creative Commons )

Check the following visual resources titled " What Are Systematic Reviews?"

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• Last Updated: May 8, 2024 1:44 PM
• URL: https://lib.guides.umd.edu/SR

• A-Z Publications

Annual Review of Psychology

Volume 70, 2019, review article, how to do a systematic review: a best practice guide for conducting and reporting narrative reviews, meta-analyses, and meta-syntheses.

• Andy P. Siddaway 1 , Alex M. Wood 2 , and Larry V. Hedges 3
• View Affiliations Hide Affiliations Affiliations: 1 Behavioural Science Centre, Stirling Management School, University of Stirling, Stirling FK9 4LA, United Kingdom; email: [email protected] 2 Department of Psychological and Behavioural Science, London School of Economics and Political Science, London WC2A 2AE, United Kingdom 3 Department of Statistics, Northwestern University, Evanston, Illinois 60208, USA; email: [email protected]
• Vol. 70:747-770 (Volume publication date January 2019) https://doi.org/10.1146/annurev-psych-010418-102803
• First published as a Review in Advance on August 08, 2018
• Copyright © 2019 by Annual Reviews. All rights reserved

Systematic reviews are characterized by a methodical and replicable methodology and presentation. They involve a comprehensive search to locate all relevant published and unpublished work on a subject; a systematic integration of search results; and a critique of the extent, nature, and quality of evidence in relation to a particular research question. The best reviews synthesize studies to draw broad theoretical conclusions about what a literature means, linking theory to evidence and evidence to theory. This guide describes how to plan, conduct, organize, and present a systematic review of quantitative (meta-analysis) or qualitative (narrative review, meta-synthesis) information. We outline core standards and principles and describe commonly encountered problems. Although this guide targets psychological scientists, its high level of abstraction makes it potentially relevant to any subject area or discipline. We argue that systematic reviews are a key methodology for clarifying whether and how research findings replicate and for explaining possible inconsistencies, and we call for researchers to conduct systematic reviews to help elucidate whether there is a replication crisis.

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• EPPI-Centre methods for conducting systematic reviews The EPPI-Centre develops methods and tools for conducting systematic reviews, including reviews for education, public and social policy.

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• Siddaway AP, Wood AM, Hedges LV. How to Do a Systematic Review: A Best Practice Guide for Conducting and Reporting Narrative Reviews, Meta-Analyses, and Meta-Syntheses. Annu Rev Psychol. 2019 Jan 4;70:747-770. doi: 10.1146/annurev-psych-010418-102803. A resource for psychology systematic reviews, which also covers qualitative meta-syntheses or meta-ethnographies
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• Systematic Reviews and Meta-Analysis — Open & Free (Open Learning Initiative) The course follows guidelines and standards developed by the Campbell Collaboration, based on empirical evidence about how to produce the most comprehensive and accurate reviews of research

• Systematic Reviews by David Gough, Sandy Oliver & James Thomas Publication Date: 2020

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How to write a systematic review

Affiliations.

• 1 The Methodist Orthopedics and Sports Medicine Center, Houston, Texas [email protected].
• 2 Sports Medicine Center, The Ohio State University, Columbus, Ohio Department of Orthopaedic Surgery, The Ohio State University, Columbus, Ohio.
• 3 Department of Orthopaedic Surgery, The Ohio State University, Columbus, Ohio.
• 4 Sports Medicine Center, The Ohio State University, Columbus, Ohio Department of Mechanical and Aerospace Engineering, The Ohio State University, Columbus, Ohio.
• PMID: 23925575
• DOI: 10.1177/0363546513497567

Background: The role of evidence-based medicine in sports medicine and orthopaedic surgery is rapidly growing. Systematic reviews and meta-analyses are also proliferating in the medical literature.

Purpose: To provide the outline necessary for a practitioner to properly understand and/or conduct a systematic review for publication in a sports medicine journal.

Study design: Review.

Methods: The steps of a successful systematic review include the following: identification of an unanswered answerable question; explicit definitions of the investigation's participant(s), intervention(s), comparison(s), and outcome(s); utilization of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines and PROSPERO registration; thorough systematic data extraction; and appropriate grading of the evidence and strength of the recommendations.

Results: An outline to understand and conduct a systematic review is provided, and the difference between meta-analyses and systematic reviews is described. The steps necessary to perform a systematic review are fully explained, including the study purpose, search methodology, data extraction, reporting of results, identification of bias, and reporting of the study's main findings.

Conclusion: Systematic reviews or meta-analyses critically appraise and formally synthesize the best existing evidence to provide a statement of conclusion that answers specific clinical questions. Readers and reviewers, however, must recognize that the quality and strength of recommendations in a review are only as strong as the quality of studies that it analyzes. Thus, great care must be used in the interpretation of bias and extrapolation of the review's findings to translation to clinical practice. Without advanced education on the topic, the reader may follow the steps discussed herein to perform a systematic review.

Keywords: PRISMA; PROSPERO; evidence-based medicine; meta-analysis; systematic review.

© 2013 The Author(s).

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Five steps to conducting a systematic review

Regina kunz.

1 German Cochrane Centre, Freiburg and Department of Nephrology, Charité, Berlin, Germany

Jos Kleijnen

2 Centre for Reviews and Dissemination, York, UK

3 German Cochrane Centre, Freiburg, Germany

Systematic reviews and meta-analyses are a key element of evidence-based healthcare, yet they remain in some ways mysterious. Why did the authors select certain studies and reject others? What did they do to pool results? How did a bunch of insignificant findings suddenly become significant? This paper, along with a book 1 that goes into more detail, demystifies these and other related intrigues.

A review earns the adjective systematic if it is based on a clearly formulated question, identifies relevant studies, appraises their quality and summarizes the evidence by use of explicit methodology. It is the explicit and systematic approach that distinguishes systematic reviews from traditional reviews and commentaries. Whenever we use the term review in this paper it will mean a systematic review . Reviews should never be done in any other way.

In this paper we provide a step-by-step explanation—there are just five steps—of the methods behind reviewing, and the quality elements inherent in each step (Box 1). For purposes of illustration we use a published review concerning the safety of public water fluoridation, but we must emphasize that our subject is review methodology, not fluoridation.

EXAMPLE: SAFETY OF PUBLIC WATER FLUORIDATION

You are a public health professional in a locality that has public water fluoridation. For many years, your colleagues and you have believed that it improves dental health. Recently there has been pressure from various interest groups to consider the safety of this public health intervention because they fear that it is causing cancer. Public health decisions have been based on professional judgment and practical feasibility without explicit consideration of the scientific evidence. (This was yesterday; today the evidence is available in a York review 2 , 3 , identifiable on MEDLINE through the freely accessible PubMed clinical queries interface [ http://www.ncbi.nlm.nib.gov/entrez/query/static/clinical.html ], under ‘systematic reviews’.)

STEP 1: FRAMING THE QUESTION

The research question may initially be stated as a query in free form but reviewers prefer to pose it in a structured and explicit way. The relations between various components of the question and the structure of the research design are shown in Figure 1 . This paper focuses only on the question of safety related to the outcomes described below.

Structured questions for systematic reviews and relations between question components in a comparative study

Box 1 The steps in a systematic review

The problems to be addressed by the review should be specified in the form of clear, unambiguous and structured questions before beginning the review work. Once the review questions have been set, modifications to the protocol should be allowed only if alternative ways of defining the populations, interventions, outcomes or study designs become apparent

The search for studies should be extensive. Multiple resources (both computerized and printed) should be searched without language restrictions. The study selection criteria should flow directly from the review questions and be specified a priori . Reasons for inclusion and exclusion should be recorded

Study quality assessment is relevant to every step of a review. Question formulation (Step 1) and study selection criteria (Step 2) should describe the minimum acceptable level of design. Selected studies should be subjected to a more refined quality assessment by use of general critical appraisal guides and design-based quality checklists (Step 3). These detailed quality assessments will be used for exploring heterogeneity and informing decisions regarding suitability of meta-analysis (Step 4). In addition they help in assessing the strength of inferences and making recommendations for future research (Step 5)

Data synthesis consists of tabulation of study characteristics, quality and effects as well as use of statistical methods for exploring differences between studies and combining their effects (meta-analysis). Exploration of heterogeneity and its sources should be planned in advance (Step 3). If an overall meta-analysis cannot be done, subgroup meta-analysis may be feasible

The issues highlighted in each of the four steps above should be met. The risk of publication bias and related biases should be explored. Exploration for heterogeneity should help determine whether the overall summary can be trusted, and, if not, the effects observed in high-quality studies should be used for generating inferences. Any recommendations should be graded by reference to the strengths and weaknesses of the evidence

Free-form question

Is it safe to provide population-wide drinking water fluoridation to prevent caries?

Structured question

• The populations —Populations receiving drinking water sourced through a public water supply
• The interventions or exposures —Fluoridation of drinking water (natural or artificial) compared with non-fluoridated water
• The outcomes —Cancer is the main outcome of interest for the debate in your health authority
• The study designs —Comparative studies of any design examining the harmful outcomes in at least two population groups, one with fluoridated drinking water and the other without. Harmful outcomes can be rare and they may develop over a long time. There are considerable difficulties in designing and conducting safety studies to capture these outcomes, since a large number of people need to be observed over a long period. These circumstances demand observational, not randomized studies. With this background, systematic reviews on safety have to include evidence from studies with a range of designs.

STEP 2: IDENTIFYING RELEVANT PUBLICATIONS

To capture as many relevant citations as possible, a wide range of medical, environmental and scientific databases were searched to identify primary studies of the effects of water fluoridation. The electronic searches were supplemented by hand searching of Index Medicus and Excerpta Medica back to 1945. Furthermore, various internet engines were searched for web pages that might provide references. This effort resulted in 3246 citations from which relevant studies were selected for the review. Their potential relevance was examined, and 2511 citations were excluded as irrelevant. The full papers of the remaining 735 citations were assessed to select those primary studies in man that directly related to fluoride in drinking water supplies, comparing at least two groups. These criteria excluded 481 studies and left 254 in the review. They came from thirty countries, published in fourteen languages between 1939 and 2000. Of these studies 175 were relevant to the question of safety, of which 26 used cancer as an outcome.

STEP 3: ASSESSING STUDY QUALITY

Design threshold for study selection.

Adequate study design as a marker of quality, is listed as an inclusion criterion in Box 1. This approach is most applicable when the main source of evidence is randomized studies. However, randomized studies are almost impossible to conduct at community level for a public health intervention such as water fluoridation. Thus, systematic reviews assessing the safety of such interventions have to include evidence from a broader range of study designs. Consideration of the type and amount of research likely to be available led to inclusion of comparative studies of any design. In this way, selected studies provided information about the harmful effects of exposure to fluoridated water compared with non-exposure.

Quality assessment of safety studies

After studies of an acceptable design have been selected, their in-depth assessment for the risk of various biases allows us to gauge the quality of the evidence in a more refined way. Biases either exaggerate or underestimate the ‘true’ effect of an exposure. The objective of the included studies was to compare groups exposed to fluoridated drinking water and those without such exposure for rates of undesirable outcomes, without bias. Safety studies should ascertain exposures and outcomes in such a way that the risk of misclassification is minimized. The exposure is likely to be more accurately ascertained if the study was prospective rather than retrospective and if it was started soon after water fluoridation rather than later. The outcomes of those developing cancer (and remaining free of cancer) are likely to be more accurately ascertained if the follow-up was long and if the assessment was blind to exposure status.

When examining how the effect of exposure on outcome was established, reviewers assessed whether the comparison groups were similar in all respects other than their exposure to fluoridated water. This is because the other differences may be related to the outcomes of interest independent of the drinking-water fluoridation, and this would bias the comparison. For example, if the people exposed to fluoridated water had other risk factors that made them more prone to have cancer, the apparent association between exposure and outcome might be explained by the more frequent occurrence of these factors among the exposed group. The technical word for such defects is confounding. In a randomized study, confounding factors are expected to be roughly equally distributed between groups. In observational studies their distribution may be unequal. Primary researchers can statistically adjust for these differences, when estimating the effect of exposure on outcomes, by use of multivariable modelling.

Put simply, use of a prospective design, robust ascertainment of exposure and outcomes, and control for confounding are the generic issues one would look for in quality assessment of studies on safety. Consequently, studies may range from satisfactorily meeting quality criteria, to having some deficiencies, to not meeting the criteria at all, and they can be assigned to one of three prespecified quality categories as shown in Table 1 . A quality hierarchy can then be developed, based on the degree to which studies comply with the criteria. None of the studies on cancer were in the high-quality category, but this was because randomized studies were non-existent and control for confounding was not always ideal in the observational studies. There were 8 studies of moderate quality and 18 of low quality.

Description of quality assessment of studies on safety of public water fluoridation

STEP 4: SUMMARIZING THE EVIDENCE

To summarize the evidence from studies of variable design and quality is not easy. The original review 3 provides details of how the differences between study results were investigated and how they were summarized (with or without meta-analysis). This paper restricts itself to summarizing the findings narratively. The association between exposure to fluoridated water and cancer in general was examined in 26 studies. Of these, 10 examined all-cause cancer incidence or mortality, in 22 analyses. Of these, 11 analyses found a negative association (fewer cancers due to exposure), 9 found a positive one and 2 found no association. Only 2 studies reported statistically significant differences. Thus no clear association between water fluoridation and increased cancer incidence or mortality was apparent. Bone/joint and thyroid cancers were of particular concern because of fluoride uptake by these organs. Neither the 6 studies of osteosarcoma nor the 2 studies of thyroid cancer and water fluoridation revealed significant differences. Overall no association was detected between water fluoridation and mortality from any cancer. These findings were also borne out in the moderate-quality subgroup of studies.

STEP 5: INTERPRETING THE FINDINGS

In the fluoridation example, the focus was on the safety of a community-based public health intervention. The generally low quality of available studies means that the results must be interpreted with caution. However, the elaborate efforts in searching an unusually large number of databases provide some safeguard against missing relevant studies. Thus the evidence summarized in this review is likely to be as good as it will get in the foreseeable future. Cancer was the harmful outcome of most interest in this instance. No association was found between exposure to fluoridated water and specific cancers or all cancers. The interpretation of the results may be generally limited because of the low quality of studies, but the findings for the cancer outcomes are supported by the moderate-quality studies.

After having spent some time reading and understanding the review, you are impressed by the sheer amount of published work relevant to the question of safety. However, you are somewhat disappointed by the poor quality of the primary studies. Of course, examination of safety only makes sense in a context where the intervention has some beneficial effect. Benefit and harm have to be compared to provide the basis for decision making. On the issue of the beneficial effect of public water fluoridation, the review 3 reassures you that the health authority was correct in judging that fluoridation of drinking water prevents caries. From the review you also discovered that dental fluorosis (mottled teeth) was related to concentration of fluoride. When the interest groups raise the issue of safety again, you will be able to declare that there is no evidence to link cancer with drinking-water fluoridation; however, you will have to come clean about the risk of dental fluorosis, which appears to be dose dependent, and you may want to measure the fluoride concentration in the water supply and share this information with the interest groups.

The ability to quantify the safety concerns of your population through a review, albeit from studies of moderate to low quality, allows your health authority, the politicians and the public to consider the balance between beneficial and harmful effects of water fluoridation. Those who see the prevention of caries as of primary importance will favour fluoridation. Others, worried about the disfigurement of mottled teeth, may prefer other means of fluoride administration or even occasional treatment for dental caries. Whatever the opinions on this matter, you are able to reassure all parties that there is no evidence that fluoridation of drinking water increases the risk of cancer.

With increasing focus on generating guidance and recommendations for practice through systematic reviews, healthcare professionals need to understand the principles of preparing such reviews. Here we have provided a brief step-by-step explanation of the principles. Our book 1 describes them in detail.