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Authors: Jack Nunn[a][i]ORCID iD.svg , Steven Chang[a]ORCID iD.svg , et al.

Nunn, J; Chang, S; et al.. 




Abstract

Systematic reviews are a type of literature review that uses systematic methods to collect secondary data, critically appraise research studies, and synthesize findings qualitatively or quantitatively.[1] Systematic reviews formulate research questions that are broad or narrow in scope, and identify and synthesize studies that directly relate to the systematic review question.[2] They are designed to provide a complete, exhaustive summary of current evidence relevant to a research question. For example, systematic reviews of randomized controlled trials are key to the practice of evidence-based medicine,[3] and a review of existing studies is often quicker and cheaper than embarking on a new study.

While systematic reviews are often applied in the biomedical or healthcare context, they can be used in other areas where an assessment of a precisely defined subject would be helpful.[4] Systematic reviews may examine clinical tests, public health interventions, environmental interventions,[5] social interventions, adverse effects, and economic evaluations.[6][7]

An understanding of systematic reviews and how to implement them in practice is highly recommended for professionals involved in the delivery of health care, public health and public policy.

Characteristics[edit]

A systematic review aims to provide an exhaustive summary of current literature relevant to a research question.

Systematic reviews can be used in many areas, such as evidence-based medicine and evidence-based policy and practice[17].

A systematic review uses a rigorous and transparent approach for research synthesis, with the aim of minimizing bias. While many systematic reviews are based on an explicit quantitative meta-analysis of available data, there are also qualitative reviews which adhere to standards for gathering, analyzing and reporting evidence.[11]

Systematic reviews often, but not always, use statistical techniques (meta-analysis) to combine results of eligible studies. Scoring levels are sometimes used to rate the quality of the evidence depending on the methodology used. Multiple people may be consulted to resolve any scoring differences between how evidence is rated.[7]

The EPPI-Centre has been influential in developing methods for combining both qualitative and quantitative research in systematic reviews.[12] The PRISMA statement[13] suggests a standardized way to ensure a transparent and complete reporting of systematic reviews, and is now required for this kind of research by more than 170 medical journals worldwide.[14] A number of specialized PRISMA guideline extensions have been developed to support particular types of studies or aspects of the review process, including PRISMA-P for review protocols[15] and PRISMA-ScR for scoping reviews[16]. A list of PRISMA guideline extensions can be found at the EQUATOR Network entry for PRISMA.

Developments in systematic reviews during the 21st century included realist reviews and the meta-narrative approach, both of which addressed problems of variation in methods and heterogeneity existing on some subjects.[18][19]

Scoping reviews[edit]

Scoping reviews are distinct from systematic reviews in a number of important ways. A scoping review is an attempt to search for concepts, mapping the language which surrounds those concepts and adjusting the search method iteratively.[8] . A scoping review may often be a preliminary stage before a systematic review, which 'scopes' out an area of inquiry and maps the language and key concepts in order to lay the groundwork for a full systematic review. This process is further complicated if it is mapping concepts across multiple languages.

As a scoping review should be systematically conducted and reported (with a repeatable method), some academic publishers categorize them as a kind of 'systematic review', which may cause confusion. Scoping reviews are helpful when it is not possible to carry out a systematic synthesis of research findings, for example, when there are no published clinical trials in the area of inquiry. Scoping reviews are a useful method when an area of inquiry is very broad[9], for example, exploring how the public are involved in all stages systematic reviews.[10]

There is still a lack of clarity when defining the exact method of scoping review as it is both an iterative process and is still relatively new. There have been a number of attempts to improve the standardisation of the method[11][12][13][14], for example via a PRISMA guideline extension for scoping reviews (PRISMA-ScR)[15]. PROSPERO does not permit the submission of protocols of scoping reviews[16], although some journals will publish protocols for scoping reviews.[10]

Stages[edit]

Extraction machine.gif

Figure 1 |  A visualisation of data being 'extracted' and 'combined' in a Cochrane systematic review.[17]

The main stages of a systematic review are:

1. Defining the research question[edit]

Defining an answerable question and agreeing an objective method is required in order to design a useful systematic review.[18] Best practice recommends publishing the protocol of the review before initiating it in order to reduce the risk of unplanned research duplication and to enable consistency between methodology and protocol[19].

2. Searching for relevant data sources[edit]

Planning how the review will search for relevant data from research that matches certain criteria is a decisive stage in developing a rigorous systematic review. Relevant criteria can include only selecting research that is good quality and answers the defined question.[20] The search strategy should be designed to retrieve literature that matches the protocol's specified inclusion and exclusion criteria.

The methodology section of a systematic review should list all of the databases and citation indexes that were searched. The titles and abstracts of identified articles can be checked against pre-determined criteria for eligibility and relevance. Each included study may be assigned an objective assessment of methodological quality, preferably by using methods conforming to the 'Preferred Reporting Items for Systematic Reviews and Meta-Analyses' (PRISMA) statement,[9] or the high-quality standards of Cochrane.[10]

Common information sources used in searches include scholarly databases of peer-reviewed articles such as MEDLINE, Web of Science, Embase, and PubMed as well as sources of unpublished literature such as clinical trial registries and grey literature collections. Key references can also be yielded through additional methods such as citation searching, reference list checking (related to a search method called 'pearl growing'), and directly contacting experts in the field[21].

In order to be systematic, searchers must use a combination of search skills and tools such as database subject headings, keyword searching, Boolean operators, proximity searching, while attempting to balance the sensitivity (systematicity) and precision (accuracy). Inviting and involving an experienced information professional or librarian can notably improve the quality of systematic review search strategies and reporting[22][23][24][25][26].

3. 'Extraction' of relevant data[edit]

Relevant data is 'extracted' from the data sources. Data which can be extracted can include how the research was done (often called the method or 'intervention'), who participated in the research (including how many people), how it was paid for (for example funding sources) and what happened (the outcomes).[17] Figure 1 illustrates relevant data being extracted and 'combined'.

4. Assess the quality of the data[edit]

This stage involves assessing the quality of data by judging it against criteria identified at the first stage.[17] This can include assessing the quality (or certainty) of evidence, using criteria such as GRADE.[27]

5. Analyse and combine the data[edit]

Analysing and combining data can provide an overall result from all of the data (called a meta-analysis). A systematic review may be followed by a meta-analysis (which uses complex statistical methods), although this is not always appropriate. The combination of data from a meta-analysis can be visualised using a blobbogram (also called a forest plot).[17] The diamond in the blobbogram represents the combined results of all the data included. Because this combined result uses data from more sources than just one data set, it's considered more reliable and better evidence, as the more data there is, the more confident we can be of conclusions.[17]

The Cochrane Collaboration logo visually represents how results from some systematic reviews can be explained.[28] The logo is a forest plot of one of the first reviews which showed that corticosteroids given to women who are about to give birth prematurely can save the life of the newborn child.[29]This systematic review 'has probably saved thousands of premature babies'.[30]

Once these stages are complete, the review may be published, disseminated and translated into practice after being adopted as evidence.

Living systematic reviews[edit]

Living systematic reviews are a relatively new kind of high quality, semi-automated, up-to-date online summaries of research which are updated as new research becomes available.[31] The essential difference between 'living systematic review' and conventional systematic review is the publication format. Living systematic reviews are 'dynamic, persistent, online-only evidence summaries, which are updated rapidly and frequently'.[32]

Research fields[edit]

Medicine and biology[edit]

History[edit]

In 1972 Archie Cochrane wrote 'It is surely a great criticism of our profession that we have not organised a critical summary, by specialty or subspecialty, adapted periodically, of all relevant randomised controlled trials'.[33] Critical appraisal and synthesis of research findings in a systematic way emerged in 1975 under the term 'meta analysis'.[34][35] Early syntheses were conducted in broad areas of public policy and social interventions, with systematic research synthesis applied to medicine and health. The Cochrane Collaboration was founded in 1993, building on the work by Iain Chalmers and colleagues in the area of pregnancy and childbirth.[36]

Contemporary[edit]

Named after Archie Cochrane, Cochrane is a group of over 37,000 specialists in healthcare who systematically review randomised trials of the effects of prevention, treatments and rehabilitation as well as health systems interventions. When appropriate, they also include the results of other types of research. Cochrane Reviews are published in The Cochrane Database of Systematic Reviews section of the Cochrane Library. The 2015 impact factor for The Cochrane Database of Systematic Reviews was 6.103, and it was ranked 12th in the “Medicine, General & Internal” category.[37]

There are six types of Cochrane Review:[38][39][40][41]

  1. Intervention reviews assess the benefits and harms of interventions used in healthcare and health policy.
  2. Diagnostic test accuracy reviews assess how well a diagnostic test performs in diagnosing and detecting a particular disease.
  3. Methodology reviews address issues relevant to how systematic reviews and clinical trials are conducted and reported.
  4. Qualitative reviews synthesize qualitative and quantitative evidence to address questions on aspects other than effectiveness.[42]
  5. Prognosis reviews address the probable course or future outcome(s) of people with a health problem.
  6. Overviews of Systematic Reviews (OoRs) are a new type of study in order to compile multiple evidence from systematic reviews into a single document that is accessible and useful to serve as a friendly front end for the Cochrane Collaboration with regard to healthcare decision-making.

The Cochrane Collaboration provides a handbook for systematic reviewers of interventions which "provides guidance to authors for the preparation of Cochrane Intervention reviews."[43] The Cochrane Handbook also outlines the key steps for preparing a systematic review[43] and forms the basis of two sets of standards for the conduct and reporting of Cochrane Intervention Reviews (MECIR - Methodological Expectations of Cochrane Intervention Reviews)[44]

The Cochrane Library is a collection of databases in medicine and other health care specialties provided by Cochrane and other organizations. It is the collection of Cochrane Reviews, a database of systematic review and meta-analyses which summarize and interpret the results of medical research. It was originally published by Update Software and now published by the share-holder owned publisher w:John Wiley & Sons, Ltd. as part of Wiley Online Library. Royalties from sales of the Cochrane Library are the major source of funds for Cochrane (over £6 million in 2017). There are 3.66 billion people around the world who have access to the Library through national licences (for £1.5 billion) or free provision for populations in low- and middle-income countries eligible under the WHO’s HINARI initiative[45].

Authors must pay an additional fee for their review to be truly open access.[46] Cochrane has an annual income of $10m USD.[47]

Public involvement[edit]

Cochrane has a number of tasks that the public or other 'stakeholders' can be involved in doing, associated with producing systematic reviews and other outputs. Tasks can be organised as 'entry level' or higher. Tasks includes:

  • Joining a collaborative volunteer effort to help categorise and summarise healthcare evidence [48]
  • Data extraction and risk of bias assessment
  • Translation of reviews into other languages

A recent systematic review of how people were involved in systematic reviews aimed to document the evidence-base relating to stakeholder involvement in systematic reviews and to use this evidence to describe how stakeholders have been involved in systematic reviews.[49] Thirty percent involved patients and/or carers. The ACTIVE framework provides a way to consistently describe how people are involved in systematic review, and may be used as a way to support the decision-making of systematic review authors in planning how to involve people in future reviews[50].

While there has been some criticism of how Cochrane prioritises systematic reviews[51], a recent project involved people in helping identify research priorities to inform future Cochrane Reviews.[52][53]

In 2014, the Cochrane-Wikipedia partnership was formalised. This supports the inclusion of relevant evidence within all Wikipedia medical articles, as well as other processes to help ensure that medical information included in Wikipedia is of the highest quality and accuracy.[54]

Learning resources[edit]

Cochrane has produced many learning resources to help people understand what systematic reviews are, and how to do them. A majority of the learning resources can be found at the 'Cochrane Training' webpage[55], which also includes a link to the book 'Testing Treatments', which has been translated into many languages[56]. In addition Cochrane has created a short video 'What are Systematic Reviews' which explains in plain English how they work and what they are used for [57]. The video has been translated into multiple languages and viewed over 126,000 times (as of June 2019). In addition, an animated storyboard version was produced and all the video resources were released in multiple versions under Creative Commons for others to use and adapt [58][59][60].

Social sciences[edit]

Groups like the Campbell Collaboration promote the use of systematic reviews in social, behavioral, and educational areas of evidence-based policy. The quasi-standard for systematic review in the social sciences is based on the procedures proposed by the Campbell Collaboration, which is one of a number of groups promoting evidence-based policy in the social sciences. The Campbell Collaboration "helps people make well-informed decisions by preparing, maintaining and disseminating systematic reviews in education, crime and justice, social welfare and international development.[61] The Campbell Collaboration is a sibling initiative of Cochrane, and was created in 2000 at the inaugural meeting in Philadelphia, USA, attracting 85 participants from 13 countries.[62]

Business and economics[edit]

Due to the different nature of research fields outside of the natural sciences, the aforementioned methodological steps cannot easily be applied in business research. Some attempts to transfer the procedures from medicine to business research have been made, [63] including a step-by-step approach.[64] and developing a standard procedure for conducting systematic literature reviews in business and economics.

International development research[edit]

Systematic reviews are increasingly prevalent in other fields, such as international development research.[65] Subsequently, a number of donors (including the UK Department for International Development (DFID) and AusAid) are focusing more attention and resources on testing the appropriateness of systematic reviews in assessing the impacts of development and humanitarian interventions.[65]

Limitations[edit]

Currency and risk of bias[edit]

While systematic reviews are regarded as the strongest form of medical evidence, a review of 300 studies found that not all systematic reviews were equally reliable, and that their reporting can be improved by a universally agreed upon set of standards and guidelines.[66] A further study by the same group found that of 100 systematic reviews monitored, 7% needed updating at the time of publication, another 4% within a year, and another 11% within 2 years; this figure was higher in rapidly changing fields of medicine, especially cardiovascular medicine.[67] A 2003 study suggested that extending searches beyond major databases, perhaps into grey literature, would increase the effectiveness of reviews.[68]

Some authors have highlighted problems with systematic reviews, particularly those conducted by the Cochrane, noting that published reviews are often biased, out of date and excessively long.[69] Cochrane reviews have been criticized as not being sufficiently critical in the selection of trials and including too many of low quality. They proposed several solutions, including limiting studies in meta-analyses and reviews to registered clinical trials, requiring that original data be made available for statistical checking, paying greater attention to sample size estimates, and eliminating dependence on only published data.

Some of these difficulties were noted as early as 1994:

"much poor research arises because researchers feel compelled for career reasons to carry out research that they are ill equipped to perform, and nobody stops them."[70]

Methodological limitations of meta-analysis have also been noted.[71] Another concern is that the methods used to conduct a systematic review are sometimes changed once researchers see the available trials they are going to include.[72] Some website have described retractions of systematic reviews and published reports of studies included in published systematic reviews.[73][74][75]

Poor compliance with review guidelines[edit]

The explosion in growth of systematic reviews in recent years has been accompanied by the attendant issue of poor compliance with PRISMA guidelines, particularly in areas such as declaration of registered study protocols, funding source declaration, risk of bias data, and description of clear study objectives[76][77][78][79].

A host of studies have identified weaknesses in the rigor and reproducibility of search strategies in systematic reviews[80][81][82][83][84][85]. In order to remedy this issue, a new PRISMA guideline extension called PRISMA-S is being developed to improve the quality, reporting, and reproducibility of systematic review search strategies[86][87]. Furthermore, tools and checklists for peer-reviewing search strategies have been created, such as the Peer Review of Electronic Search Strategies (PRESS) guidelines[88].

A key challenge for using systematic reviews in clinical practice and healthcare policy is assessing the quality of a given review. Consequently, a range of appraisal tools to evaluate systematic reviews have been designed. The two most popular measurement instruments and scoring tools for systematic review quality assessment are AMSTAR[89][90][91] and ROBIS[92].

Limited reporting of clinical trials and data from human studies[edit]

The 'AllTrials' campaign highlights that around half of clinical trials have never reported results and works to improve reporting.[93] This lack of reporting has extremely serious implications for research, including systematic reviews, as it is only possible to synthesize data of published studies. In addition, 'positive' trials were twice as likely to be published as those with 'negative' results.[94] At present, it is legal for for-profit companies to conduct clinical trials and not publish the results.[95] For example, in the past 10 years 8.7 million patients have taken part in trials that haven’t published results.[95] These factors mean that it is likely there is a significant publication bias, with only 'positive' or perceived favorable results being published. A recent systematic review of industry sponsorship and research outcomes concluded that 'sponsorship of drug and device studies by the manufacturing company leads to more favorable efficacy results and conclusions than sponsorship by other sources' and that the existence of an industry bias that cannot be explained by standard 'Risk of bias' assessments.[96]

Systematic reviews of such a bias may amplify the effect, although it is important to note that the flaw is in the reporting of research in general, not in the systematic review process.

Additional information[edit]

Acknowledgements[edit]

Any people, organisations, or funding sources that you would like to thank.

Competing interests[edit]

Any conflicts of interest that you would like to declare. Otherwise, a statement that the authors have no competing interest.

Ethics statement[edit]

An ethics statement, if appropriate, on any animal or human research performed should be included here or in the methods section.

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