“Association Between Analytic Strategy and Estimates of Treatment Outcomes in Meta-Analyses”, Agnes Dechartres, Douglas G. Altman, Ludovic Trinquart, Isabelle Boutron, Philippe Ravaud2014-08-13 (scientific bias, meta-analysis; similar)⁠:

Importance: A persistent dilemma when performing meta-analyses is whether all available trials should be included in the meta-analysis.

Objectives: To compare treatment outcomes estimated by meta-analysis of all trials and several alternative analytic strategies: single most precise trial (ie. trial with the narrowest confidence interval), meta-analysis restricted to the 25% largest trials, limit meta-analysis (a meta-analysis model adjusted for small-study effect), and meta-analysis restricted to trials at low overall risk of bias.

Data Sources: 163 meta-analyses published 2008^–₂2010_14ya in high-impact-factor journals and 2011^–₂2013_11ya in the Cochrane Database of Systematic Reviews: 92 (705 randomized clinical trials [RCTs]) with subjective outcomes and 71 (535 RCTs) with objective outcomes.

Data Synthesis: For each meta-analysis, the difference in treatment outcomes between meta-analysis of all trials and each alternative strategy, expressed as a ratio of odds ratios (ROR), was assessed considering the dependency between strategies. A difference greater than 30% was considered substantial. RORs were combined by random-effects meta-analysis models to obtain an average difference across the sample. An ROR greater than 1 indicates larger treatment outcomes with meta-analysis of all trials. Subjective and objective outcomes were analyzed separately.

Results: Treatment outcomes were larger in the meta-analysis of all trials than in the single most precise trial (combined ROR, 1.13 [95% CI, 1.07–1.19]) for subjective outcomes and 1.03 (95% CI, 1.01–1.05) for objective outcomes. The difference in treatment outcomes between these strategies was substantial in 47⁄92 (51%) meta-analyses of subjective outcomes (meta-analysis of all trials showing larger outcomes in 40⁄47) and in 28⁄71 (39%) meta-analyses of objective outcomes (meta-analysis of all trials showing larger outcomes in 21⁄28). The combined ROR for subjective and objective outcomes was, respectively, 1.08 (95% CI, 1.04–1.13) and 1.03 (95% CI, 1.00–1.06) when comparing meta-analysis of all trials and meta-analysis of the 25% largest trials, 1.17 (95% CI, 1.11–1.22) and 1.13 (95% CI, 0.82–1.55) when comparing meta-analysis of all trials and limit meta-analysis, and 0.94 (95% CI, 0.86–1.04) and 1.03 (95% CI, 1.00–1.06) when comparing meta-analysis of all trials and meta-analysis restricted to trials at low risk of bias.

Conclusions & Relevance: Estimation of treatment outcomes in meta-analyses differs depending on the strategy used. This instability in findings can result in major alterations in the conclusions derived from the analysis and underlines the need for systematic sensitivity analyses. [discussion]

See Also:

• “The unpredictability paradox: review of empirical comparisons of randomized and non-randomized clinical trials”

• “Comparison of Evidence of Treatment Effects in Randomized and Nonrandomized Studies”

• “Contradicted and Initially Stronger Effects in Highly Cited Clinical Research”

• “Assessing treatment effects and publication bias across different specialties in medicine: a large empirical study of the Cochrane Database of Systematic Reviews”

• “Agreement of treatment effects for mortality from routinely collected data and subsequent randomized trials: meta-epidemiological survey”

• “Comparison of evidence on harms of medical interventions in randomized and nonrandomized studies”

• “Interpreting the evidence: choosing between randomized and non-randomized studies”

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