February 9, 2021
Keaven Anderson, PhD
Scientific AVP, Methodology Research, Biostatistics at Merck
Group Sequential Design Assuming Delayed Benefit
Abstract: We consider an asymptotic approach to design of group sequential trials with a potentially delayed effects. Logrank, weighted logrank tests and combination tests are of primary interest, but we also consider restricted mean survival. The asymptotic approach allows both quick derivation of study design properties that are also easily verified using simulation. We rely heavily on work done by Tsiatis, 1981 published while he was at the HSPH. The impact of a potential delay in treatment effect on timing of analyses, study boundaries and sample size are demonstrated. The value of a robust design that is well powered under a variety of assumptions is emphasized. Open source software is provided for implementation. Given the current regulatory climate, logrank testing may still be preferred for these trials, but we hope that efficiencies and Type I error control associated with alternatives may make other options more acceptable for future consideration.
YouTube Link: https://www.youtube.com/watch?v=DhwZOX5uMKU