Abstract
BACKGROUND: Randomized clinical trials are blinded to prevent knowledge of treatment assignment from influencing outcomes and their assessments, thus protecting the trial's scientific integrity. Trials involving a warfarin treatment arm are difficult to blind due to the need to continuously adjust dose. PURPOSE: We sought to examine the effectiveness of blinding secondary stroke prevention trials with a warfarin treatment arm in which the blinding system incorporates use of placebo warfarin dose modification schedules for patients in the placebo warfarin arm. METHODS: We examined treatment assignment guesses of 569 patients or their next of kin as well as study coordinators and principal neurologists at the clinical sites in a multicenter, randomized, double-dummy, double-blinded clinical trial of warfarin and aspirin using dose adjustment schedules for management of placebo warfarin. RESULTS: Overall, the crude rates of correct responses are 60% for patient/proxy, 66% for study coordinator, and 56% for principal neurologist. Several indices were used to assess the consistency of guesses with what would be expected if the guessing were done completely at random, and all measures indicate adequate blinding. LIMITATIONS: Comparison to other trials using warfarin is difficult due to limited data and differences in assessment of blinding. However, results compared favorably to one existing trial. CONCLUSIONS: Placebo warfarin dose adjustment schedules can protect blinding adequately in trials involving warfarin.