American Statistical Association New York City Metropolitan Area Chapter Memorial Sloan-Kettering Cancer Center Biostatistics Seminar

Toxicity grades underlie the definition of a dose limiting toxicity (DLT) but in the majority of phase I designs, the information contained in the individual grades is not used. Some authors have argued that it may be more appropriate to consider a polytomous rather than dichotomous response. We investigate whether the added information on individual grades can improve the operating characteristics of the Continual Reassessment Method (CRM). Four CRM-based designs were compared via simulations in terms of accuracy, patient allocation and precision. The results show that only modest improvements are observed when the information on grades is explored via the use of explicit models, where the parameters are known precisely. CRM with some use of grade information, increases the number of patients treated at the MTD by approximately 5%. The additional information from lower grades can lead to a small increase in the precision of our estimate of the MTD.