Systematic review

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Clinical trials should begin and end with systematic reviews of relevant evidence

— Mike Clarke, Sally Hopewell, Iain Chalmers, 2016, PMID 20609983

All health researchers should begin their training by preparing at least one systematic review

— Kamal R Mahtani, 2016, PMID 27118697


A systematic review is a literature review focused on a single question which tries to identify, appraise, select and synthesize all high quality research evidence relevant to that question. Systematic reviews are generally regarded as the highest level of medical evidence by evidence-based medicine professionals. An understanding of systematic reviews and how to implement them in practice is becoming mandatory for all professionals involved in the delivery of health care.

Reporting standards


In 1987, Mulrow assessed review articles for the following criteria[1]:

  1. Was the specific purpose of the review stated?
  2. Were sources and methods of the citation search identified?
  3. Inclusion criteria: "Were explicit guidelines provided that determined the material included in and excluded from the review"?
  4. Validity assessment of included articles: "Was a methodologic validity assessment of material in the review performed"?
  5. Was the information systematically integrated with explication of data limitations and inconsistencies?
  6. Was the information integrated and weighted or pooled metrically?
  7. Was a summary of pertinent findings provided?
  8. Were specific directives for new research initiatives proposed?


The history of the QUORUM and PRISMA reporting standards are summarized[2].

  • QUORUM (QUality Of Reporting Of Meta-analyses) was started in 1999 to recommend reporting standards for meta-analyses of randomized controlled trials.
  • PRISMA (Preferred Reporting Items of Systematic reviews and Meta-Analyses) was started in 2009

Risk of bias assessment

Regarding randomized controlled trials, the Cochrane states, "The overall risk of bias for the result is the least favourable assessment across the domains of bias. Both the proposed domain-level and overall risk-of-bias judgements can be overridden by the review authors, with justification." and provides a table for "reaching an overall risk-of-bias judgement for a specific outcome"[3] Regarding non-randomized studies, the Cochrane states, "Judging a result to be at a particular level of risk of bias for an individual domain implies that the result has an overall risk of bias at least this severe."[4]

GRADE helps assess risk of bias[5][6].


A systematic review is a summary of healthcare research that uses explicit methods to perform a thorough literature search and critical appraisal of individual studies to identify the valid and applicable evidence.


Systematic reviews often, but not always, use appropriate techniques (meta-analysis) to combine these valid studies, or at least use grading of the levels of evidence depending on the methodology used.

Meta-narrative reviews

While many systematic reviews are based on an explicit quantitative meta-analysis of available data, there are also qualitative reviews which nonetheless adhere to the standards for gathering, analyzing and reporting evidence. The RAMESES reporting standards guide the creation of these reviews[7].

Modified in-vivo coding (MIC) can create heirarchial, thematic content analysis[8].

Living systematic reviews

Living systematic reviews have been described:

Umbrella reviews

An umbrella reviews "are systematic collections and assessments of multiple SRMAs done on a specific research topic" [9][10].

An example of an umbrella review is "Risk factors for type 2 diabetes mellitus"[11] and others[12][13].

Reporting standards have been developed in the PRIOR statement[14][15]

Cochrane collaboration

Many healthcare journals now publish systematic reviews, but the best-known source is the Cochrane Collaboration, a group of over 6,000 specialists in health care who systematically review randomised trials of the effects of treatments and, when appropriate, the results of other research. Cochrane reviews are published in the Cochrane Database of Systematic Reviews section of the Cochrane Library, which to date (February 2007) contains 2,893 complete reviews and 1,646 protocols.

The Cochrane Group provides a handbook for systematic reviewers of interventions, where they suggest that each systematic review should contain the following main sections:

  • Background
  • Objectives
  • Methods of the review
  • Results
  • Conclusion and discussion

There are seven steps for preparing and maintaining a systematic review, as outlined in the Cochrane Handbook:

  1. Formulating a problem
  2. Locating and selecting studies
  3. Critical appraisal of studies
  4. Collecting data
  5. Analyzing and presenting results
  6. Interpreting results
  7. Improving and updating reviews

Strengths and weaknesses

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 could be improved by a universally agreed upon set of standards and guidelines.[16]

A further study by the same group found that of 100 guidelines reviewed, 4% required updating within a year, and 11% after 2 years; this figure was higher in rapidly-changing fields of medicine, especially cardiovascular medicine.[17] 7% of systematic reviews needed updating at the time of publication. [17]

Teaching how to conduct systematic reviews may help teach research skills[18].

See also


  1. Mulrow CD (1987). "The medical review article: state of the science". Ann Intern Med. 106 (3): 485–8. doi:10.7326/0003-4819-106-3-485. PMID 3813259.
  2. Anonymous. History & Development of PRISMA. Available at
  3. Sterne JAC, Hernán MA, McAleenan A, Reeves BC, Higgins JPT. Chapter 25: Assessing risk of bias in a non-randomized study. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (editors). Cochrane Handbook for Systematic Reviews of Interventions version 6.4 (updated August 2023). Cochrane, 2023. Available at
  4. Sterne JAC, Hernán MA, McAleenan A, Reeves BC, Higgins JPT. Chapter 25: Assessing risk of bias in a non-randomized study. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (editors). Cochrane Handbook for Systematic Reviews of Interventions version 6.4 (updated August 2023). Cochrane, 2023. Available from
  5. Guyatt GH, Oxman AD, Vist G, Kunz R, Brozek J, Alonso-Coello P; et al. (2011). "GRADE guidelines: 4. Rating the quality of evidence--study limitations (risk of bias)". J Clin Epidemiol. 64 (4): 407–15. doi:10.1016/j.jclinepi.2010.07.017. PMID 21247734.
  6. What is GRADE? BMJ Best Practice: Evidence-based medicine (EBM) toolkit.
  7. Wong G, Greenhalgh T, Westhorp G, Buckingham J, Pawson R (2013). "RAMESES publication standards: meta-narrative reviews". BMC Med. 11: 20. doi:10.1186/1741-7015-11-20. PMC 3558334. PMID 23360661.
  8. Arije, Olujide Olusesan; Oyedun, Olaitan Oyekunle; Omisile, Idowu Olusola (2021-08-03). "Synthesizing qualitative research evidence from complex interventions by inductive thematic content analysis using modified in-vivo coding" Check |url= value (help). Academia Letters. doi:10.20935/AL2527. ISSN 2771-9359. Retrieved 2024-04-14.
  9. Belbasis L, Bellou V, Ioannidis JPA (2022). "Conducting umbrella reviews". BMJ Med. 1 (1): e000071. doi:10.1136/bmjmed-2021-000071. PMC 9951359 Check |pmc= value (help). PMID 36936579 Check |pmid= value (help).
  10. Ioannidis JP (2009). "Integration of evidence from multiple meta-analyses: a primer on umbrella reviews, treatment networks and multiple treatments meta-analyses". CMAJ. 181 (8): 488–93. doi:10.1503/cmaj.081086. PMC 2761440. PMID 19654195.
  11. Bellou V, Belbasis L, Tzoulaki I, Evangelou E (2018). "Risk factors for type 2 diabetes mellitus: An exposure-wide umbrella review of meta-analyses". PLoS One. 13 (3): e0194127. doi:10.1371/journal.pone.0194127. PMC 5860745. PMID 29558518.
  12. Laborda R, Díaz-Mayans J, Núñez A (1987). "[Hepatic and renal changes in albino rats caused by the administration of chromium (VI) in drinking water]". Rev Esp Fisiol. 43 (3): 275–9. PMID 3423388.
  13. Griebeler ML, Morey-Vargas OL, Brito JP, Tsapas A, Wang Z, Carranza Leon BG; et al. (2014). "Pharmacologic interventions for painful diabetic neuropathy: An umbrella systematic review and comparative effectiveness network meta-analysis". Ann Intern Med. 161 (9): 639–49. doi:10.7326/M14-0511. PMID 25364885.
  14. Gates M, Gates A, Pieper D, Fernandes RM, Tricco AC, Moher D, Brennan SE, Li T, Pollock M, Lunny C, Sepúlveda D, McKenzie JE, Scott SD, Robinson KA, Matthias K, Bougioukas KI, Fusar-Poli P, Whiting P, Moss SJ, Hartling L. Reporting guideline for overviews of reviews of healthcare interventions: development of the PRIOR statement
  15. Gates M, Gates A, Pieper D, Fernandes RM, Tricco AC, Moher D; et al. (2022). "Reporting guideline for overviews of reviews of healthcare interventions: development of the PRIOR statement". BMJ. 378: e070849. doi:10.1136/bmj-2022-070849. PMC 9361065 Check |pmc= value (help). PMID 35944924 Check |pmid= value (help).
  16. Moher D, Tetzlaff J, Tricco AC, Sampson M, Altman DG (2007). "Epidemiology and reporting characteristics of systematic reviews". PLoS Med. 4 (3): e78. doi:10.1371/journal.pmed.0040078. PMID 17388659.
  17. 17.0 17.1 Shojania KG, Sampson M, Ansari MT, Ji J, Doucette S, Moher D (2007). "How quickly do systematic reviews go out of date? A survival analysis". Ann. Intern. Med. 147 (4): 224–33. PMID 17638714.
  18. Himelhoch S, Edwards S, Ehrenreich M, Luber MP (September 2015). "Teaching Lifelong Research Skills in Residency: Implementation and Outcome of a Systematic Review and Meta-Analysis Course". J Grad Med Educ. 7 (3): 445–50. doi:10.4300/JGME-D-14-00505.1. PMC 4597958. PMID 26457153.

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