Impact of trial attrition rates on treatment effect estimates in chronic inflammatory diseases: A meta‐epidemiological study

Abstract

The objective of this meta‐epidemiological study was to explore the impact of attrition rates on treatment effect estimates in randomised trials of chronic inflammatory diseases (CID) treated with biological and targeted synthetic disease‐modifying drugs. We sampled trials from Cochrane reviews. Attrition rates and primary endpoint results were retrieved from trial publications; Odds ratios (ORs) were calculated from the odds of withdrawing in the experimental intervention compared to the control comparison groups (i.e., differential attrition), as well as the odds of achieving a clinical response (i.e., the trial outcome). Trials were combined using random effects restricted maximum likelihood meta‐regression models and associations between estimates of treatment effects and attrition rates were analysed. From 37 meta‐analyses, 179 trials were included, and 163 were analysed (301 randomised comparisons; n = 62,220 patients). Overall, the odds of withdrawal were lower in the experimental compared to control groups (random effects summary OR = 0.45, 95% CI, 0.41–0.50). The corresponding overall treatment effects were large (random effects summary OR = 4.43, 95% CI 3.92–4.99) with considerable heterogeneity across interventions and clinical specialties (I2 = 85.7%). The ORs estimating treatment effect showed larger treatment benefits when the differential attrition was more prominent with more attrition in the control group (OR = 0.73, 95% CI 0.55–0.96). Higher attrition rates from the control arm are associated with larger estimated benefits of treatments with biological or targeted synthetic disease‐modifying drugs in CID trials; differential attrition may affect estimates of treatment benefit in randomised trials.