Reported methodologic quality and discrepancies between large and small randomized trials in meta-analyses

Purpose: To explore whether reported methodologic quality affects estimated Intervention effects in randomized trials and contributes to discrepancies between the results of large randomized trials and small randomized trials in meta-analyses. Data Sources: meta-analyses of randomized trials that included at least one large trial (greater than or equal to 1000 participants) were Included, re gardless of the therapeutic area. Eligible meta-analyses were identified th rough electronic searches and bibliographies of relevant articles. Study Selection: Full-length randomized trials. Data Extraction: Methodologic quality was assessed according to reported ra ndomization, double blinding, and follow-up as separate components and by u sing the Jadad composite scale. Data Synthesis: Fourteen meta-analyses involving 190 randomized trials from eight therapeutic areas were included. Compared with large trials, interve ntion effects were exaggerated in small trials with inadequate allocation s equence generation (ratio of odds ratios, 0.46 [95% Cl, 0.25 to 0.83]; P = 0.011), inadequate allocation concealment (ratio of odds ratios, 0.49 [Cl, 0.27 to 0.86]; P = 0.014), and no double blinding (ratio of odds ratios, 0. 52 [Cl, 0.28 to 0.96]; P = 0.01). Large trials did not differ significantly from small trials with adequate generation of the allocation sequence, ade quate allocation concealment, or adequate double blinding. No association w as seen between reported follow-up and intervention effects. The Jadad scal e provided no additional information because the scale and the quality comp onents overlapped substantially. Conclusions: inadequate generation of the allocation sequence, allocation c oncealment, and double blinding lead to exaggerated estimates of interventi on benefit and may contribute to discrepancies between the results of large randomized trials and small randomized trials in meta-analyses.