Modified intention-to-treat analysis did not bias trial results

Abstract Objective To investigate whether analysis of the modified intention-to-treat (mITT) population with postrandomization exclusion of patients from analysis is associated with biased estimates of treatment effect compared to the conservative intention-to-treat (ITT) population. Study Design and Setting Placebo-controlled, blinded randomized trials on biological or targeted interventions for rheumatoid arthritis were identified through a systematic search. Two authors independently extracted data. A random-effects meta-analysis was used to combine odds ratios as an expression of treatment effect and stratify according to the different analysis populations. Results Seventy-two randomized trials were included and analyzed (23,842 patients). Thirty trials analyzed the ITT population, 37 analyzed an mITT population, and 5 trials had an unclear analysis population. The treatment effect of active intervention compared to control, when based on mITT, was comparable to ITT (odds ratio 3.76 [95% confidence interval 3.09, 4.57], and 3.47 [2.77, 4.34]; comparison P  = 0.60). Conclusion We found no difference in the treatment effect between randomized trials using ITT and mITT analyses populations. This suggests that the mITT approach in rheumatoid arthritis trials investigating biological or targeted interventions does not introduce bias compared to ITT.