Enhancing Dose Selection in Phase I Cancer Trials: Extending the Bayesian Logistic Regression Model with Non-DLT Adverse Events Integration

This paper presents the Burdened Bayesian Logistic Regression Model (BBLRM), an enhancement to the Bayesian Logistic Regression Model (BLRM) for dose-finding in phase I oncology trials. Traditionally, the BLRM determines the maximum tolerated dose (MTD) based on dose-limiting toxicities (DLTs). However, clinicians often perceive model-based designs like BLRM as complex and less conservative than rule-based designs, such as the widely used 3+3 method. To address these concerns, the BBLRM incorporates non-DLT adverse events (nDLTAEs) into the model. These events, although not severe enough to qualify as DLTs, provide additional information suggesting that higher doses might result in DLTs. In the BBLRM, an additional parameter $\delta$ is introduced to account for nDLTAEs. This parameter adjusts the toxicity probability estimates, making the model more conservative in dose escalation. The $\delta$ parameter is derived from the proportion of patients experiencing nDLTAEs within each cohort and is tuned to balance the model's conservatism. This approach aims to reduce the likelihood of assigning toxic doses as MTD while involving clinicians more directly in the decision-making process. The paper includes a simulation study comparing BBLRM with the traditional BLRM across various scenarios. The simulations demonstrate that BBLRM significantly reduces the selection of toxic doses as MTD without compromising, and sometimes even increasing, the accuracy of MTD identification. These results suggest that integrating nDLTAEs into the dose-finding process can enhance the safety and acceptance of model-based designs in phase I oncology trials.