Use Of Rolling-Enrollment Designs To Accelerate Clinical Trials

By Pantelis Vlachos, Principal/Strategic Consultant, Cytel, Inc.

Popular statistical designs, such as CRM (O’Quigley et al., 1990), mTPI-2 (Guo et al., 2017), and i3+3 (Liu et al., 2020) typically enroll patients in cohorts and follow the enrolled cohort for a certain period (e.g., 28 days), and then apply sequential decisions that determine the dose level for each cohort based on the observed toxicity data. Accrual is suspended after enrollment of each cohort of patients until all the patients in the current cohort have been fully followed with definitive dose-limiting toxicity (DLT) or non-DLT outcomes. Cohort-based enrollment can thus slow down dose-finding trials since the outcomes of the previous cohort must be fully evaluated before the next cohort can be enrolled. This type of cohort-based designs can also be inefficient, especially if the trial needs to be frequently suspended. Read how to shorten the study duration of phase I trials and reduce the number of accrual suspensions with the use of rolling-enrollment designs is recommended which allows concurrent patient enrollment that is faster than cohort-base enrollment.