NEW STATISTICAL STRATEGY FOR MONITORING SAFETY AND EFFICACY IN SINGLE-ARM CLINICAL-TRIALS

Purpose: Efficacy and toxicity are both important outcomes in cancer c linical trials. Nonetheless, most statistical designs for phase II tri als only provide rules for evaluating treatment efficacy, and moreover only allow early stopping after fixed cohorts of patients have been t reated. We illustrate a new statistical design strategy for monitoring both adverse and efficacy outcomes on a patient-by-patient basis in p hase II and other single-arm clinical trials. Design: The new strategy is used to design a phase II trial of the experimental regimen idarub icin plus cytarabine (ara-C) plus cyclosporine for treatment of patien ts with intermediate-prognosis acute myelogenous leukemia (AML). The d esign requires a maximum of 56 patients and provides continuous monito ring boundaries to terminate the trial if the toxicity rate is unaccep tably high or the complete remission (CR) rate is unacceptably low com pared with the rates of these events with the standard regimen of anth racycline plus ara-C. Results: The design has an 88% to 91% probabilit y of stoping the trial early with ct median of 15 to 18 patients if th e toxicity rate of the experimental regimen is .05 to .10 above that o f the standard and there is no improvement in the CR rate, If there is a .15 improvement in the CR rate and the toxicity rate is no more tha n .05 above that of the standard, then there is at least an 83% probab ility that the trial will run to completion. Conclusion: The proposed monitoring strategy provides a flexible, practical means to continuous ly monitor both safety and efficacy in single-arm cancer clinical tria ls. The design strategy can be implemented easily using a freely avail able menu-driven computer program, and provides a scientifically sound alternative to the use of ad hoc safety monitoring rules. (C) 1996 by American Society of Clinical Oncology.