Review and recommendations on the current practice of meta-analyses: a guide to appraise the evidence

Osnabrugge, Ruben L.J.; Capodanno, Davide; Cummins, Paul; Kappetein, Pieter; Serruys, Patrick W.

doi:10.4244/eijv9i9a172

Cited by 8 publications

(7 citation statements)

References 52 publications

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“…Finally, a consistent finding across all metaanalyses was the approximately 2-fold increase in definite or probable device thrombosis with BVSs, which was significant in three out of five studies (11,12,14). Overlapping metaanalyses can result in a certain degree of ambiguity when they come to discordant conclusions (17). Indeed, the conclusions of the abstract of these meta-analyses also sound different, ranging between the positive outlook of Stone et …”

Section: Editorialmentioning

confidence: 85%

“…At this early stage of data collection (i.e., with only ≤1-year data available in most BVSs studies), and because judgment inevitably involves assigning subjective weights to pros and cons of each meta-analytical approach, the answer may be arbitrary. The reader may personally refer to published methods and checklists to map the quality of the 5 metaanalyses described in this article, and come to a personal conclusion (17).…”

Section: Al ("Bvs Did Not Lead To Different Rates Of Composite Patiementioning

confidence: 99%

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Overlapping meta-analyses of bioresorbable vascular scaffolds versus everolimus-eluting stents: bringing clarity or confusion?

Capodanno¹

2016

J. Thorac. Dis.

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Section: Editorialmentioning

confidence: 85%

Section: Al ("Bvs Did Not Lead To Different Rates Of Composite Patiementioning

confidence: 99%

Overlapping meta-analyses of bioresorbable vascular scaffolds versus everolimus-eluting stents: bringing clarity or confusion?

Capodanno¹

2016

J. Thorac. Dis.

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“…12 This practice leads to increasing duplication of meta-analyses on the same topic. 53 A recent study showed that 67% of the reviewed meta-analyses had at least one overlapping and 5% of the topics were studied in at least eight overlapping meta-analyses.…”

Section: Evaluating Discordant Meta-analysesmentioning

confidence: 99%

“…Greater awareness and understanding of the subjectivity of meta-analyses and the impact of methodological choices on their results will enhance the appreciation of meta-analyses as high level of evidence. 12 In 2010, the US Food and Drug Administration recommended CYP2C19 genotyping for individualized antiplatelet management. 4,6 Based on a reevaluation of then-current and later meta-analyses, we conclude that this recommendation is currently not evidence based.…”

Section: Evaluating Discordant Meta-analysesmentioning

confidence: 99%

A systematic review and critical assessment of 11 discordant meta-analyses on reduced-function CYP2C19 genotype and risk of adverse clinical outcomes in clopidogrel users

Osnabrugge

Head

Zijlstra

et al. 2015

Genetics in Medicine

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Clopidogrel, in combination with aspirin, is a standard treatment for patients with acute coronary syndrome and is one of the top-selling drugs in the world.1,2 However, there is substantial interindividual variability in response. Polymorphisms of the cytochrome P450 (CYP) gene have been identified as a potential risk factor for nonresponse.3 This gene plays a central role in drug-metabolizing processes in the liver, and clopidogrel makes use of these processes to transform into an active metabolite capable of inhibiting platelet aggregation. Identification of CYP2C19 polymorphisms could lead to personalized treatment based on genotype in patients with acute coronary syndrome, and therefore, the US Food and Drug Administration recommends CYP2C19 genotyping for individualized antiplatelet management. 4 The association between CYP2C19 loss-of-function alleles and clinical efficacy of clopidogrel has been studied extensively, and several meta-analyses have summarized the results of those studies.5-8 Systematic reviews and meta-analyses are often considered the highest level of evidence, 9-11 and their popularity in the cardiovascular field increased almost 13 times as fast as the increase in number of published randomized clinical trials. 12However, the interpretation of meta-analyses is confusing when the conclusions of overlapping meta-analyses are discordant. Some meta-analyses on CYP2C19 loss-of-function and clinical efficacy of clopidogrel conclude that the association is proven, 7,8 whereas others conclude the opposite. 5,6 Our objective was to systematically evaluate the discordant evidence for the association between CYP2C19 loss-offunction alleles and clinical efficacy of clopidogrel through a critical methodological appraisal of published meta-analyses. MATERIALS AND METHODSOur review adheres to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement, 13 and we consulted the Cochrane Handbook for Systematic Reviews of Interventions for methodological aspects of meta-analyses. We systematically investigated how 11 overlapping meta-analyses on the association between CYP2C19 loss-of-function alleles and clinical efficacy of clopidogrel could yield contradictory outcomes. The results of the meta-analyses differed because more recent metaanalyses included more primary studies and some had not included conference abstracts. Conclusions differed because between-study heterogeneity and publication bias were handled differently across meta-analyses. All meta-analyses on the clinical end point observed significant heterogeneity and several reported evidence for publication bias, but only one out of eight statistically significant meta-analyses concluded that therefore the association was unproven and one other refrained from quantifying a pooled estimate because of heterogeneity. For the end point stent thrombosis, all meta-analyses reported statistically significant associations with CYP2C19 loss-of-function alleles with no statistically significant evidence for heterogeneity, b...

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“…In the cardiovascular literature, both the publication of meta-analyses and their relative contribution to the literature expanded dramatically during the first decade of this century, with the number of meta-analyses increasing >500% from 2000 to 2012 and the ratio of randomized trials to meta-analyses falling from >10:1 to <3:1. 8 Although the sheer number of meta-analyses does not necessarily speak to appropriateness or necessity, there also seems to be increasing redundancy. For example, Siontis et al 9 found that, for two thirds of medical meta-analyses published in 2010, there was at least 1, and often multiple, overlapping meta-analysis on the same topic.…”

mentioning

confidence: 99%

Recapitulation and Synthesis

McElhinney

2016

Circ: Cardiovascular Interventions

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T he highest ideal in medical practice is fully informed, evidence-driven practice. In pursuit of that ephemeral goal, clinical research in interventional cardiology is at an all-time high. One of the most rapidly growing domains of clinical research in interventional cardiology and other medical fields has been metaresearch-systematic reviews and the meta-analyses they feed. In this journal alone, for example, 13 meta-analyses were published between 2013 and 2015, and 7 of the 112 original articles that appeared in 2015 fell into this category.1-7 Given the proliferation of such studies, in this journal and in the field more broadly, it seems an opportune moment to reflect briefly on their place in the evolving literature on structural interventions.Although articles reporting the results of meta-analysis have become increasingly pervasive in recent years, the statistical methodology and discipline are not new, having been pioneered >40 years ago. Wielded judiciously and effectively, meta-analysis can be one of the most important tools available for integrating and demystifying clinical research. It is ideally suited for synthesizing data from multiple sources in the service of seeking clarity around important questions for which there is no clear answer-for example, when trials yield conflicting results, and there are multiple underpowered or unfocused studies. Targeted finely and executed expertly, meta-analysis can and should serve as some of the highest-level evidence for clinical decision making and for subsequent trial design. However, reality is not always in keeping with the ideal.There is increasing evidence that the meta-analysis machine is bloated. In the cardiovascular literature, both the publication of meta-analyses and their relative contribution to the literature expanded dramatically during the first decade of this century, with the number of meta-analyses increasing >500% from 2000 to 2012 and the ratio of randomized trials to meta-analyses falling from >10:1 to <3:1. 8 Although the sheer number of meta-analyses does not necessarily speak to appropriateness or necessity, there also seems to be increasing redundancy. For example, Siontis et al 9 found that, for two thirds of medical meta-analyses published in 2010, there was at least 1, and often multiple, overlapping meta-analysis on the same topic. To be sure, meta-analyses on the same topic can differ in important respects and provide unique and complementary value, but discordance between overlapping studies can muddy, rather than clarify, the question, belying the purpose of a meta-analysis. In an effort to streamline the pipeline of meta-analyses, creating transparency and reducing redundancy, investigators at the Center for Reviews and Dissemination at the University of York developed PROSPERO, a Web-based system for registration of systematic reviews that was activated 5 years ago. 10Overlapping and redundancy are not the only concerning observations. Just as important, there is the issue of quality. As Berlin and Golub 11 recently expl...

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Review and recommendations on the current practice of meta-analyses: a guide to appraise the evidence

Cited by 8 publications

References 52 publications

Overlapping meta-analyses of bioresorbable vascular scaffolds versus everolimus-eluting stents: bringing clarity or confusion?

Overlapping meta-analyses of bioresorbable vascular scaffolds versus everolimus-eluting stents: bringing clarity or confusion?

A systematic review and critical assessment of 11 discordant meta-analyses on reduced-function CYP2C19 genotype and risk of adverse clinical outcomes in clopidogrel users

Recapitulation and Synthesis

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