Sequential parallel comparison design with binary and time-to-event outcomes

Statistics in Medicine
Rachel K SilvermanJason Fine

Abstract

Sequential parallel comparison design (SPCD) has been proposed to increase the likelihood of success of clinical trials especially trials with possibly high placebo effect. Sequential parallel comparison design is conducted with 2 stages. Participants are randomized between active therapy and placebo in stage 1. Then, stage 1 placebo nonresponders are rerandomized between active therapy and placebo. Data from the 2 stages are pooled to yield a single P value. We consider SPCD with binary and with time-to-event outcomes. For time-to-event outcomes, response is defined as a favorable event prior to the end of follow-up for a given stage of SPCD. We show that for these cases, the usual test statistics from stages 1 and 2 are asymptotically normal and uncorrelated under the null hypothesis, leading to a straightforward combined testing procedure. In addition, we show that the estimators of the treatment effects from the 2 stages are asymptotically normal and uncorrelated under the null and alternative hypothesis, yielding confidence interval procedures with correct coverage. Simulations and real data analysis demonstrate the utility of the binary and time-to-event SPCD.

References

Aug 1, 1994·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·M H Trivedi, H Rush
Sep 13, 2007·Clinical Trials : Journal of the Society for Clinical Trials·Roy N Tamura, Xiaohong Huang
Nov 26, 2009·Biometrics·Martha Nason, Dean Follmann
Dec 21, 2010·Statistics in Medicine·Boikanyo Makubate, Stephen Senn
Jul 1, 2011·Statistical Methods in Medical Research·Jozefien Buyze, Els Goetghebeur
Aug 2, 2011·Statistics in Medicine·Anastasia IvanovaDavid A Schoenfeld

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Citations

Dec 13, 2019·Pharmaceutical Statistics·Gosuke Homma, Takashi Daimon
Sep 30, 2020·Journal of Biopharmaceutical Statistics·Anastasia Ivanova, Bahjat Qaqish
Aug 29, 2019·Biometrical Journal. Biometrische Zeitschrift·Gosuke Homma, Takashi Daimon
Jan 6, 2022·Journal of Biopharmaceutical Statistics·Feiran JiaoSara Jimenez

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