Continual Reassessment Method for Late-Onset Toxicities Using Bayesian Data Augmentation
*Suyu Liu, MD Anderson Cancer Center  Guosheng Yin, University of Hong Kong  Ying Yuan, MD Anderson Cancer Center 

Keywords: Dose-finding, Late-onset, Bayesian

A major practical impediment when implementing adaptive dose-finding designs is that the toxicity outcome used by the decision rules may not be observed shortly after the initiation of the treatment. To address this issue, we propose the data augmentation continual reassessment method (DA-CRM) for dose finding. By naturally treating the unobserved toxicities as missing data, we show that such missing data are nonignorable in the sense that the missingness depends on the unobserved outcomes. The Bayesian data augmentation approach is used to sample both the missing data and model parameters from their posterior full conditional distributions. We evaluate the performance of the DA-CRM through extensive simulation studies, and also compare it with other existing methods. The results show that the proposed design satisfactorily resolves the issues related to late-onset toxicities and possesses desirable operating characteristics: treating patients more safely, and also selecting the maximum tolerated dose with a higher probability.