Anna Dossing1, Simon Tarp1, Daniel E Furst2, Christian Gluud3, George A Wells4, Joseph Beyene5, Bjarke B Hansen6, Henning Bliddal6, Robin Christensen7. 1. Department of Rheumatology, Musculoskeletal Statistics Unit, The Parker Institute, Frederiksberg Hospital, Nordre Fasanvej 57, 2000 Copenhagen, Denmark. 2. Department of Medicine, David Geffen School of Medicine, University of California, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA. 3. Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100 Copenhagen, Denmark. 4. Clinical Epidemiology Program, Department of Epidemiology and Community Medicine, Ottawa Hospital Research Institute, University of Ottawa, Room 3105, 451 Smyth Road, Ottawa, Ontario K1H 8M5, Canada. 5. Department of Clinical Epidemiology & Biostatistics, Faculty of Health Sciences, McMaster University, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada. 6. Department of Rheumatology, The Parker Institute, Frederiksberg Hospital, Nordre Fasanvej 57, 2000 Copenhagen, Denmark. 7. Department of Rheumatology, Musculoskeletal Statistics Unit, The Parker Institute, Frederiksberg Hospital, Nordre Fasanvej 57, 2000 Copenhagen, Denmark. Electronic address: Robin.Christensen@regionh.dk.
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.
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.
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