title: Covariate-adjusted adaptive randomization in a sarcoma trial with multi-stage treatments.
abstract: We present a Bayesian design for a multi-centre, randomized clinical trial of two chemotherapy regimens for advanced or metastatic unresectable soft tissue sarcoma. After randomization, each patient receives up to four stages of chemotherapy, with the patient's disease evaluated after each stage and categorized on a trinary scale of severity. Therapy is continued to the next stage if the patient's disease is stable, and is discontinued if either tumour response or treatment failure is observed. We assume a probability model that accounts for baseline covariates and the multi-stage treatment and disease evaluation structure. The design uses covariate-adjusted adaptive randomization based on a score that combines the patient's probabilities of overall treatment success or failure. The adaptive randomization procedure generalizes the method proposed by Thompson (1933) for two binomial distributions with beta priors. A simulation study of the design in the context of the sarcoma trial is presented.
authors.affiliation: Department of Biostatistics, Box 447, The University of Texas, MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, U.S.A. rex@mdanderson.org
authors.forename: Peter F
authors.initials: PF
authors.lastname: Thall
authors.forename: J Kyle
authors.initials: JK
authors.lastname: Wathen
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001499:Bayes Theorem; D006801:Humans; D011336:Probability; D012509:Sarcoma / Q000188:drug therapy*; D012983:Soft Tissue Neoplasms / Q000188:drug therapy*; D014481:United States
chemical_list: D000970:Antineoplastic Agents