Sample size re-estimation and other midcourse adjustments with sequential parallel comparison design.
Sequential parallel comparison design (SPCD) was proposed to reduce placebo response in a randomized trial with placebo comparator. Subjects are randomized between placebo and drug in stage 1 of the trial, and then, placebo non-responders are re-randomized in stage 2. Efficacy analysis includes all data from stage 1 and all placebo non-responding subjects from stage 2. This article investigates the possibility to re-estimate the sample size and adjust the design parameters, allocation proportion to placebo in stage 1 of SPCD, and weight of stage 1 data in the overall efficacy test statistic during an interim analysis.
a Department of Biostatistics , The University of North Carolina at Chapel Hill , Chapel Hill , North Carolina , USA.
Rachel K
RK
Silverman
a Department of Biostatistics , The University of North Carolina at Chapel Hill , Chapel Hill , North Carolina , USA.
Anastasia
A
Ivanova
D006801:Humans; D015990:Placebo Effect; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D018401:Sample Size
Adaptive design; SPCD; placebo response; sample size re-estimation; sequential parallel comparison design