AI Article Synopsis
- Optimal dose selection in clinical trials faces challenges when effective and toxic concentrations are similar, prompting the development of a novel quantitative approach for dose titration.
- A simulation system incorporating pharmacokinetics, pharmacodynamics, and varying types of variability was used to test different scenarios in optimizing drug titration while balancing efficacy and safety.
- The approach significantly reduced toxicity rates by 87.4% to 93.5% and increased efficacy by 52.7% to 243%, suggesting that interindividual variability may be less critical than other forms of variability in determining optimal dosing strategies.
Article 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 reduced by 87.4% to 93.5%, and those having efficacy was increased by 52.7% to 243%. Interindividual PK variability may have less impact on optimal cutoff values than other sources of variability. ROC/CTS methods for optimizing dose titration offer an individualized approach that leverages exposure-response relationships.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6263661 | PMC |
| http://dx.doi.org/10.1002/psp4.12354 | DOI Listing |
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