Choosing optimal doses to be used in clinical trials for potential new therapies is difficult as data can be limited. The ability to identify relevant doses is further complicated when the difference between concentrations that are efficacious and those causing toxicity are narrow. Add to these issues the need to not overshoot or undershoot a target dose for approval and variability within subjects and the task is even more daunting. Quantitative methods that can improve selection of optimal doses especially for drugs with narrow therapeutic indexes provides a means to explore dose titration schemes that might not be otherwise be considered possible due to safety concerns. This paper explores the use of combining Receiver Operating Characteristic (ROC) Analysis and Clinical Trial Simulation (CTS) in optimizing dose titration algorithms. The authors simulate five PK-related scenarios using different degrees of variability added to a base scenario with low variability.
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