Adaptive design improvements in the continual reassessment method for phase I studies

✍ Scribed by Julie M. Heyd; Bradley P. Carlin

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 126 KB
• Volume: 18
• Category: Article
• ISSN: 0277-6715
• DOI: 10.1002/(sici)1097-0258(19990615)18:11<1307::aid-sim128>3.0.co;2-x

✦ Synopsis

The continual reassessment method (CRM) enables full and e$cient use of all data and prior information available in a phase I study. However, despite a number of recent enhancements to the method, its acceptance in actual clinical practice has been hampered by several practical di$culties. In this paper, we consider several further re"nements in the context of phase I oncology trials. In particular, we allow the trial to stop when the width of the posterior 95 per cent probability interval for the maximum tolerated dose (MTD) becomes su$ciently narrow (that is, when the information accumulating from the trial data reaches a prespeci"ed level). We employ a simulation study to evaluate "ve such stopping rules under three alternative states of prior knowledge regarding the MTD (accurate, too low and too high). Our results suggest our adaptive designs preserve the CRM's estimation ability while o!ering the possibility of earlier stopping of the trial.