Evaluation of Continual Reassessment Method with Lagged Group: A Study Design for Early-Phase Dose-Finding Clinical Trials (306534)Christopher Coffey, University of Iowa
Eric Foster, Ferring Pharmaceuticals
*Anne E. Welhaven, University of Iowa
Keywords: Clinical Trials, Early Phase Trial Modifications
Evaluation of interventions in early phase stroke trials can be complex due to a need to treat study participants as rapidly as possible. The motivating study used Continual Reassessment Method (CRM) to guide dose assignment. Study design and rapid recruitment rates led to a high number of participants assigned placebo. A potential solution was to use the Time-to-Event (TITE) CRM, however this design may be influenced by late onset dose limiting toxicities (DLTs). The CRM design was modified by including a lagged group to reduce extra placebo patients. A simulation study was done to evaluate performance. The results support comparable performance to CRM for appropriate dose selection, treatment at unsafe doses, and early stopping due to toxicity. Moreover, this modification leads to reduced study duration and needed sample size compared to CRM. Additionally, this modification is robust to DLT onset times, but does have higher total sample size and longer study duration compared to TITE-CRM. Overall, lagged CRM is an efficient method of accommodating rapid recruitment rates and late onset DLT. This design could be used in future research to plan adaptive early phase clinical trials.