Accounting for Carryover Toxicity in Phase I Clinical Trials with Intra-Patient Dose Escalation.

Intra-patient dose escalation (IPDE) provides a strategy for more efficient Phase I clinical trials. However, IPDE poses additional challenges due to the need to account for carryover toxicity from previous dosings a patient has received. To that end, we propose two CRM-based approaches to IPDE that incorporate potential carryover toxicity. We compare these methods to the CRM without IPDE and the AIDE-CRM, an existing Bayesian adaptive approach to IPDE. In simulations across a range of scenarios, we show that our approaches have similar operating characteristics to the CRM without IPDE, but with a 20% reduction in time and participants needed to complete the trial; these results hold even in the presence of strong carryover toxicity that hinders the performance of the AIDE-CRM.