Receiver Operating Characteristic Analysis and Clinical Trial Simulation to Inform Dose Titration Decisions.

ABSTRACT: Optimal dose selection in clinical trials is problematic when efficacious and toxic concentrations are close. A novel quantitative approach follows for optimizing dose titration in clinical trials. A system of pharmacokinetics (PK), pharmacodynamics, efficacy, and toxicity was simulated for scenarios characterized by varying degrees of different types of variability. Receiver operating characteristic (ROC) and clinical trial simulation (CTS) were used to optimize drug titration by maximizing efficacy/safety. The scenarios included were a low-variability base scenario, and high residual (20%), interoccasion (20%), interindividual (40%), and residual plus interindividual variability scenarios, and finally a shallow toxicity slope scenario. The percentage of subjects having toxicity was reduc

SUBMITTER: Clements JD 

PROVIDER: S-EPMC6263661 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature