Dual‐agent dose‐finding in Phase I clinical trial—An extension of rapid enrollment design

Abstract

Dual‐agent treatment has become more and more popular in clinical trials. We have developed an approach called rapid enrollment dual‐agent design (REDD) for dose‐finding in Phase I clinical trials. This approach aims to administer treatment to patients using a dose combination that is highly probable to be the target dose combination. Unlike other non‐model‐based designs, rapid enrollment designs (RED and REDD) do not require waiting for all patients to complete an assessment before the assignment of the next participant. Simulations showed that across several scenarios, the average performance of REDD is comparable to that of the Bayesian optimal interval (BOIN) design and the partial order continual reassessment method (POCRM). The simulation results of REDD for late‐onset toxicity assessments demonstrated that assigning patients to a dose combination as they are being enrolled, without waiting for the most recent cohort of patients to complete their follow‐up, does not significantly compromise the quality of the maximum tolerated dose (MTD) estimation. Instead, it saves a considerable amount of time in clinical trial enrollment. User‐friendly online applications have also been created to further facilitate the adoption of rapid enrollment designs in Phase I trials. In summary, being similar to BOIN and POCRM in performance, REDD is an approach that is easily comprehensible, straightforward to implement and offers an advantage of enrolling patients without having to wait for all current patients to complete their follow‐ups for toxicity.