NEW CLINICAL-TRIAL DESIGNS FOR PHASE-I STUDIES IN HEMATOLOGY AND ONCOLOGY - PRINCIPLES AND PRACTICE OF THE CONTINUAL REASSESSMENT MODEL

Clinical phase I studies in Hematology and Oncology are characterized by specific ethical and methodological considerations. Among these, th e determination of a safe starting dose, tile definition of dose escal ation schemes and tile strategies of cohort size expansion per dose le vel and toxicities observed are of crucial importance. This review wil l focus on the continual reassessment method, a novel Bayesian-based a pproach to the conceptual design of clinical phase I studies in Hemato logy and Oncology. The original method as described by O'Quigley et al . [Biometrics 1990;46:33-48] will be reviewed as well as modifications which are intended to increase patient safety Finally, clinical appli cations of the modified Continual Reassessment Method will be discusse d.