title: Parameter estimation following an adaptive treatment selection trial design.
abstract: Two-stage, drop-the-losers designs for adaptive treatment selection have been considered by many authors. The distributions of conditional sufficient statistics and the Rao-Blackwell technique were used to obtain an unbiased estimate and to construct an exact confidence interval for the parameter of interest. In this paper, we characterize the selection process from a binomial drop-the-losers design using a truncated binomial distribution. We propose a new estimator and show that it is asymptotically consistent with a large sample size in either the first stage or the second stage. Supported by simulation analyses, we recommend the new estimator over the naive estimator and the Rao-Blackwell-type estimator based on its robustness in the finite-sample setting. We frame the concept as a simple and easily implemented procedure for phase 2 oncology trial design that can be confirmatory in nature, and we use an example to illustrate its application.
authors.affiliation: Celgene Corporation, Summit, NJ 07901, USA. xluo@celgene.com
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Luo
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Wu
authors.forename: Jie
authors.initials: J
authors.lastname: Xiong
mesh_terms: D017322:Clinical Trials, Phase II as Topic / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D015233:Models, Statistical; D009369:Neoplasms / Q000188:drug therapy; D012107:Research Design