title: Bayesian decision theoretic two-stage design in phase II clinical trials with survival endpoint.
abstract: In this paper, we consider two-stage designs with failure-time endpoints in single-arm phase II trials. We propose designs in which stopping rules are constructed by comparing the Bayes risk of stopping at stage I with the expected Bayes risk of continuing to stage II using both the observed data in stage I and the predicted survival data in stage II. Terminal decision rules are constructed by comparing the posterior expected loss of a rejection decision versus an acceptance decision. Simple threshold loss functions are applied to time-to-event data modeled either parametrically or nonparametrically, and the cost parameters in the loss structure are calibrated to obtain desired type I error and power. We ran simulation studies to evaluate design properties including types I and II errors, probability of early stopping, expected sample size, and expected trial duration and compared them with the Simon two-stage designs and a design, which is an extension of the Simon's designs with time-to-event endpoints. An example based on a recently conducted phase II sarcoma trial illustrates the method.
authors.affiliation: Biostatistics Unit, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI 48109, USA. zhaolili@umich.edu
authors.forename: Lili
authors.initials: L
authors.lastname: Zhao
authors.forename: Jeremy M G
authors.initials: JM
authors.lastname: Taylor
authors.forename: Scott M
authors.initials: SM
authors.lastname: Schuetze
mesh_terms: D001499:Bayes Theorem; D017322:Clinical Trials, Phase II as Topic / Q000379:methods*; D003198:Computer Simulation; D003520:Cyclophosphamide / Q000627:therapeutic use; D018572:Disease-Free Survival; D006801:Humans; D012107:Research Design; D012509:Sarcoma / Q000188:drug therapy; D020123:Sirolimus / Q000627:therapeutic use
chemical_list: D003520:Cyclophosphamide; D020123:Sirolimus