title: Improving the decision to pursue a phase 3 clinical trial by adjusting for patient-specific factors in evaluating phase 2 treatment efficacy data.
abstract: Phase 2 clinical trials are undertaken to provide evidence of treatment efficacy and safety. A test statistic that accounts for individual patient risk in the patient population is proposed and applied to a phase 2 clinical trial for castrate metastatic prostate cancer. The test statistic is computed to compare, for each patient, the observed 2-year survival outcome to the predicted 2-year survival probability. A logistic regression model, developed using historical data in the same patient population, is used to adjust for patient risk in predicting the 2-year survival probability. Goodness-of-fit procedures are performed to ensure that a proper model is fit to the data. The test result is compared to the score test, the binomial exact test, and Fisher's exact test, all of which use the average 2-year survival probability in the population as the parameter of interest. The results demonstrate the benefit of risk adjustment in determining treatment efficacy in a single-arm phase 2 trial. By adjusting for patient risk, this method can provide a more precise assessment of phase 2 treatment efficacy, thereby improving the decision whether to proceed to a phase 3 clinical trial.
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. hellerg@mskcc.org
authors.forename: Glenn
authors.initials: G
authors.lastname: Heller
authors.forename: Michael W
authors.initials: MW
authors.lastname: Kattan
authors.forename: Howard I
authors.initials: HI
authors.lastname: Scher
mesh_terms: D017322:Clinical Trials, Phase II as Topic / Q000379:methods* / Q000706:statistics & numerical data*; D017326:Clinical Trials, Phase III as Topic / Q000379:methods*; D003657:Decision Making; D034261:Epothilones / Q000627:therapeutic use; D006801:Humans; D016015:Logistic Models; D008297:Male; D015233:Models, Statistical; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000401:mortality; D020379:Risk Adjustment / Q000379:methods*; D016019:Survival Analysis; D016896:Treatment Outcome; D050257:Tubulin Modulators / Q000627:therapeutic use
chemical_list: D034261:Epothilones; D050257:Tubulin Modulators