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Improving the Decision to Pursue a Phase 3 Clinical Trial by Adjusting for Patient-Specific Factors in Evaluating Phase 2 Treatment Efficacy Data

Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, hellerg{at}mskcc.org

Michael W. Kattan, PhD

Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio

Howard I. Scher, MD

Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY

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.

Key Words: Key words: analysis of phase 2 clinical trial data • heterogeneous patient population • model-based test statistic. (Med Decis Making 2007;27:380—386)

Medical Decision Making, Vol. 27, No. 4, 380-386 (2007)
DOI: 10.1177/0272989X07303826


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