Use of dose modification schedules is effective for blinding trials of warfarin: evidence from the WASID study.
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.


OBJECTIVE
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.


CONCLUSIONS
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.
Hertzberg
Vicki
V
Department of Biostatistics, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA. vhertzb@sph.emory.edu
Chimowitz
Marc
M
Lynn
Michael
M
Chester
Cristen
C
Asbury
William
W
Cotsonis
George
G
D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D003627:Data Interpretation, Statistical; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D006801:Humans; D015337:Multicenter Studies as Topic; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012107:Research Design; D020521:Stroke / Q000517:prevention & control; D014859:Warfarin / Q000008:administration & dosage / Q000627:therapeutic use*
D000925:Anticoagulants; D014859:Warfarin; D001241:Aspirin