Article, Early Access,
Impact of trial attrition rates on treatment effect estimates in chronic inflammatory diseases: A meta-epidemiological study
Affiliations
- [1] Univ Hosp Southern Denmark, Dept Clin Res, Aabenraa, Denmark [NORA names: Region of Southern Denmark; Hospital; Denmark; Europe, EU; Nordic; OECD];
- [2] Univ Hosp Southern Denmark, Dept Clin Res, Aabenraa, Denmark [NORA names: SDU University of Southern Denmark; University; Denmark; Europe, EU; Nordic; OECD];
- [3] Bispebjerg & Frederiksberg Hosp, Parker Inst, Clin Res Unit, Copenhagen, Denmark [NORA names: Capital Region of Denmark; Hospital; Denmark; Europe, EU; Nordic; OECD];
- [4] Bispebjerg & Frederiksberg Hosp, Parker Inst, Clin Res Unit, Copenhagen, Denmark [NORA names: KU University of Copenhagen; University; Denmark; Europe, EU; Nordic; OECD];
- [5] Stanford Univ, Dept Epidemiol & Populat Hlth, Sch Med, Stanford, CA USA [NORA names: United States; America, North; OECD];
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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.