Empirical Evidence of Study Design Biases in Randomized Trials: Systematic Review of Meta-Epidemiological Studies

To synthesise evidence on the average bias and heterogeneity associated with reported methodological features of randomized trials. Systematic review of meta-epidemiological studies. We retrieved eligible studies included in a recent AHRQ-EPC review on this topic (latest search September 2012), and...

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Vydáno v:PloS one Ročník 11; číslo 7; s. e0159267
Hlavní autoři: Page, Matthew J., Higgins, Julian P. T., Clayton, Gemma, Sterne, Jonathan A. C., Hróbjartsson, Asbjørn, Savović, Jelena
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States Public Library of Science 11.07.2016
Public Library of Science (PLoS)
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ISSN:1932-6203, 1932-6203
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Shrnutí:To synthesise evidence on the average bias and heterogeneity associated with reported methodological features of randomized trials. Systematic review of meta-epidemiological studies. We retrieved eligible studies included in a recent AHRQ-EPC review on this topic (latest search September 2012), and searched Ovid MEDLINE and Ovid EMBASE for studies indexed from Jan 2012-May 2015. Data were extracted by one author and verified by another. We combined estimates of average bias (e.g. ratio of odds ratios (ROR) or difference in standardised mean differences (dSMD)) in meta-analyses using the random-effects model. Analyses were stratified by type of outcome ("mortality" versus "other objective" versus "subjective"). Direction of effect was standardised so that ROR < 1 and dSMD < 0 denotes a larger intervention effect estimate in trials with an inadequate or unclear (versus adequate) characteristic. We included 24 studies. The available evidence suggests that intervention effect estimates may be exaggerated in trials with inadequate/unclear (versus adequate) sequence generation (ROR 0.93, 95% CI 0.86 to 0.99; 7 studies) and allocation concealment (ROR 0.90, 95% CI 0.84 to 0.97; 7 studies). For these characteristics, the average bias appeared to be larger in trials of subjective outcomes compared with other objective outcomes. Also, intervention effects for subjective outcomes appear to be exaggerated in trials with lack of/unclear blinding of participants (versus blinding) (dSMD -0.37, 95% CI -0.77 to 0.04; 2 studies), lack of/unclear blinding of outcome assessors (ROR 0.64, 95% CI 0.43 to 0.96; 1 study) and lack of/unclear double blinding (ROR 0.77, 95% CI 0.61 to 0.93; 1 study). The influence of other characteristics (e.g. unblinded trial personnel, attrition) is unclear. Certain characteristics of randomized trials may exaggerate intervention effect estimates. The average bias appears to be greatest in trials of subjective outcomes. More research on several characteristics, particularly attrition and selective reporting, is needed.
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Conceived and designed the experiments: MJP JPTH JS. Performed the experiments: MJP GC. Analyzed the data: MJP JPTH. Wrote the paper: MJP JPTH GC JACS AH JS.
Competing Interests: JACS, AB and JS are authors of a study included in this review, but were not involved in the eligibility assessment or data extraction of these studies. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials. All other authors declare no competing interests.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0159267