David Moher and colleagues introduce PRISMA, an update of the QUOROM guidelines for reporting systematic reviews and meta-analyses

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Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement

Systematic reviews and meta-analyses have become increasingly important in health care. Clinicians read them to keep up to date with their field,1,2 and they are often used as a starting point for developing clinical practice guidelines. Granting agencies may require a systematic review to ensure there is justification for further research,3 and some health care journals are moving in this direction.4 As with all research, the value of a systematic review depends on what was done, what was found, and the clarity of reporting. As with other publications, the reporting quality of systematic reviews varies, limiting readers' ability to assess the strengths and weaknesses of those reviews.

Several early studies evaluated the quality of review reports. In 1987, Mulrow examined 50 review articles published in 4 leading medical journals in 1985 and 1986 and found that none met all 8 explicit scientific criteria, such as a quality assessment of included studies.5 In 1987, Sacks and colleagues6 evaluated the adequacy of reporting of 83 meta-analyses on 23 characteristics in 6 domains. Reporting was generally poor; between 1 and 14 characteristics were adequately reported (mean = 7.7; standard deviation = 2.7). A 1996 update of this study found little improvement.7

In 1996, to address the suboptimal reporting of meta-analyses, an international group developed a guidance called the QUOROM Statement (QUality Of Reporting Of Meta-analyses), which focused on the reporting of meta-analyses of randomized controlled trials.8 In this article, we summarize a revision of these guidelines, renamed PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses), which have been updated to address several conceptual and practical advances in the science of systematic reviews (Box 1).



Box 1

Conceptual issues in the evolution from QUOROM to PRISMA

Preferred reporting items for systematic reviews and meta-analyses: the PRISMA Statement.

Cochrane Reviews have recently started including the quantity I 2 to help readers assess the consistency of the results of studies in meta-analyses. What does this new quantity mean, and why is assessment of heterogeneity so important to clinical practice? 

Systematic reviews and meta-analyses can provide convincing and reliable evidence relevant to many aspects of medicine and health care.1 Their value is especially clear when the results of the studies they include show clinically important effects of similar magnitude. However, the conclusions are less clear when the included studies have differing results. In an attempt to establish whether studies are consistent, reports of meta-analyses commonly present a statistical test of heterogeneity. The test seeks to determine whether there are genuine differences underlying the results of the studies (heterogeneity), or whether the variation in findings is compatible with chance alone (homogeneity). However, the test is susceptible to the number of trials included in the meta-analysis. We have developed a new quantity, I 2, which we believe gives a better measure of the consistency between trials in a meta-analysis.

Assessment of the consistency of effects across studies is an essential part of meta-analysis. Unless we know how consistent the results of studies are, we cannot determine the generalisability of the findings of the meta-analysis. Indeed, several hierarchical systems for grading evidence state that the results of studies must be consistent or homogeneous to obtain the highest grading.2–4

Tests for heterogeneity are commonly used to decide on methods for combining studies and for concluding consistency or inconsistency of findings.5 6 But what does the test achieve in practice, and how should the resulting P values be interpreted?

A test for heterogeneity examines the null hypothesis that all studies are evaluating the same effect. The usual test statistic …

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Measuring inconsistency in meta-analyses

Objective: Funnel plots (plots of effect estimates against sample size) may be useful to detect bias in meta-analyses that were later contradicted by large trials. We examined whether a simple test of asymmetry of funnel plots predicts discordance of results when meta-analyses are compared to large trials, and we assessed the prevalence of bias in published meta-analyses. Design: Medline search to identify pairs consisting of a meta-analysis and a single large trial (concordance of results was assumed if effects were in the same direction and the meta-analytic estimate was within 30% of the trial); analysis of funnel plots from 37 meta-analyses identified from a hand search of four leading general medicine journals 1993-6 and 38 meta-analyses from the second 1996 issue of the Cochrane Database of Systematic Reviews . Main outcome measure: Degree of funnel plot asymmetry as measured by the intercept from regression of standard normal deviates against precision. Results: In the eight pairs of meta-analysis and large trial that were identified (five from cardiovascular medicine, one from diabetic medicine, one from geriatric medicine, one from perinatal medicine) there were four concordant and four discordant pairs. In all cases discordance was due to meta-analyses showing larger effects. Funnel plot asymmetry was present in three out of four discordant pairs but in none of concordant pairs. In 14 (38%) journal meta-analyses and 5 (13%) Cochrane reviews, funnel plot asymmetry indicated that there was bias. Conclusions: A simple analysis of funnel plots provides a useful test for the likely presence of bias in meta-analyses, but as the capacity to detect bias will be limited when meta-analyses are based on a limited number of small trials the results from such analyses should be treated with considerable caution. Key messages Systematic reviews of randomised trials are the best strategy for appraising evidence; however, the findings of some meta-analyses were later contradicted by large trials Funnel plots, plots of the trials9 effect estimates against sample size, are skewed and asymmetrical in the presence of publication bias and other biases Funnel plot asymmetry, measured by regression analysis, predicts discordance of results when meta-analyses are compared with single large trials Funnel plot asymmetry was found in 38% of meta-analyses published in leading general medicine journals and in 13% of reviews from the Cochrane Database of Systematic Reviews Critical examination of systematic reviews for publication and related biases should be considered a routine procedure

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Bias in meta-analysis detected by a simple, graphical test

Meta-Analysis in Clinical Trials*

Effects of Growth Hormone on Athletic Performance Systematic Review: The Effects of Growth Hormone on Athletic Performance

Studies of its test performance show that at commonly used cutoff thresholds, calcaneal quantitative ultrasound does not definitively exclude or confirm osteoporosis as diagnosed by a gold standard...

Meta-Analysis: Accuracy of Quantitative Ultrasound for Identifying Patients with Osteoporosis

Meta-analysis is a method of synthesizing the results of independent studies. We consider the case in which there are multiple treatments and a control, with the goal of estimating the relative effect of each treatment based on continuous outcomes. Even when all data are available, rather than only summary data, it has become common to use meta-analytic estimators of treatment contrasts. Alternatively, we could use a two-way analysis of variance model with no interaction in which one factor is study and one factor is treatment. For the unbalanced case, we obtain the surprising result that the standard meta-analysis estimates of treatment contrasts are identical to the least squares estimators of treatment contrasts in the linear model. Because a meta-analysis of individual patient data can be considerably more costly in terms of data retrieval than a meta-analysis of summary data, this equivalence provides for cost-efficient analysis.

Comparison of meta-analysis versus analysis of variance of individual patient data

Evidence-based health care is becoming increasingly popular and, at least in some settings, is being used to assist in the creation of health care policy.1Meta-analyses are a key component of evidence-based health care. Such analyses pool individual randomized controlled trials (RCTs) together to arrive at an overall estimate of the effect of the intervention under consideration. Meta-analyses offer several potential advantages. They provide a systematic and explicit method for synthesizing evidence, a quantitative overall estimate (and confidence intervals) derived from the individual studies, and early evidence as to the effectiveness of treatments, thus reducing the need for continued study. They also can address questions in specific subgroups that individual studies may not have examined. There has been a striking increase in the number of published meta-analyses of RCTs. One of the first medical metaanalyses was published inJAMAin 1955.2By June 1992, the number of meta-analyses

Meta-analysis of randomized controlled trials. A concern for standards;.

Estimates from individual studies included in a meta-analysis often are not in agreement, giving rise to statistical heterogeneity. In such cases, exploration of the causes of heterogeneity can advance knowledge by formulating novel hypotheses. We present a new method for visualizing between-study heterogeneity using combinatorial meta-analysis. The method is based on performing separate meta-analyses on all possible subsets of studies in a meta-analysis. We use the summary effect sizes and other statistics produced by the all-subsets meta-analyses to generate graphs that can be used to investigate heterogeneity, identify influential studies, and explore subgroup effects. This graphical approach complements alternative graphical explorations of data. We apply the method to numerous biomedical examples, to allow readers to develop intuition on the interpretation of the all-subsets graphical display. The proposed graphical approach may be useful for exploratory data analysis in systematic reviews. Copyright © 2012 John Wiley & Sons, Ltd.

Ingram Olkin

Papers

Effects of Growth Hormone on Athletic Performance Systematic Review: The Effects of Growth Hormone on Athletic Performance

Meta-Analysis: Accuracy of Quantitative Ultrasound for Identifying Patients with Osteoporosis

Comparison of meta-analysis versus analysis of variance of individual patient data

Meta-analysis of randomized controlled trials. A concern for standards;.

GOSH – a graphical display of study heterogeneity