Impact of Delayed Outcomes, Accrual Rates, and Prognostic Variables on a Simulated Randomized Trial with Adaptive Enrichment

• Activity Number: 231
• Type: Topic Contributed
• Date/Time: Monday, August 10, 2015 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Tianchen Qian*
• Keywords: adaptive enrichment design ; group sequential design ; short-term outcome ; improved precision ; semiparametric estimator

Abstract

Adaptive enrichment designs involve rules for restricting enrollment to a subset of the population during the course of an ongoing trial. This can be used to target those who benefit from the experimental treatment. To leverage prognostic information in baseline variables and short-term outcomes, we use a semiparametric, locally efficient estimator. We assess, through simulation studies, how different design parameters affect performance in terms of precision, power, sample size, and trial duration. Our simulation distributions mimic features of data from the Alzheimer's Disease Neuroimaging Initiative study, where there are two subpopulations of interest. We investigate the impact of changes to the following: the enrollment rate, the delay time between enrollment and observation of the primary outcome, and the prognostic value of baseline variables and short-term outcomes.