Consequences of Performing Parallel Dose Finding Trials in Heterogeneous Groups of Patients.

ABSTRACT: Patient heterogeneity, in which patients can be grouped by risk of toxicity, is a design challenge in early phase dose finding trials. Carrying out independent trials for each group is a readily available approach for dose finding. However, this often leads to dose recommendations that violate the known order of toxicity risk by group, or reversals in dose recommendation. In this manuscript, trials for partially ordered groups are simulated using four approaches: independent parallel trials using the continual reassessment method (CRM), Bayesian optimal interval design, and 3 + 3 methods, as well as CRM for partially ordered groups. Multiple group order structures are considered, allowing for varying amounts of group frailty order information. These simulations find that parallel trials in

SUBMITTER: Horton BJ 

PROVIDER: S-EPMC6555302 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature