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

TY - JOUR

T1 - Modified intention-to-treat analysis did not bias trial results

AU - Dossing, Anna

AU - Tarp, Simon

AU - Furst, Daniel E

AU - Gluud, Christian

AU - Wells, George A

AU - Beyene, Joseph

AU - Hansen, Bjarke Brandt

AU - Bliddal, Henning

AU - Christensen, Robin

N1 - Copyright © 2016 Elsevier Inc. All rights reserved.

PY - 2016/4/1

Y1 - 2016/4/1

N2 - 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.

AB - 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.

U2 - 10.1016/j.jclinepi.2015.11.003

DO - 10.1016/j.jclinepi.2015.11.003

M3 - Review

C2 - 26562052

SN - 0895-4356

VL - 72

SP - 66

EP - 74

JO - Journal of Clinical Epidemiology

JF - Journal of Clinical Epidemiology

ER -