Extending the TITE CRM to Multiple Outcomes with Application to a Phase 1 Clinical Trial in Canine Hemangiosarcoma

Tables 1 6 present additional simulation results to evaluate the impact of varying π1, the cohort size and the average wating time between subject enrollment. Increasing π1 to 0.10 results in an increased probability of early termination for futility in Scenario 5 and 6 but drastically reduces the probability of correctly identify the optimal dose (Tables 1 and 2). Using cohorts of two resulted in a decrease in the probability of correctly identifying the optimal dose but an increase in the average number of subjects treated at the optimal dose and the probability of terminating for futility in Scenario 6 (Tables 3 and 4). In general, though, using cohorts of size two instead of cohorts of size three resulted in only modest differences in the operating characteristics of our study. Finally, we see that the average waiting time between subject enrollment has little impact on the probability of correctly identifying the optimal dose but the average number of subjects treated at the optimal dose increases as the waiting time between subjects increases and approaches the average number of subjects treated at the optimal dose for the binary case, which requires that full information be available for the previous cohort before enrolling a new cohort (Tables 5 and 6). This is encouraging because it suggests that our study would still have acceptable operating characteristics if enrollment were twice as fast