Receiver Operating Characteristic Analysis and Clinical Trial Simulation to Inform Dose Titration Decisions.
CPT Pharmacometrics Syst Pharmacol
; 7(11): 771-779, 2018 11.
Article
em En
| MEDLINE
| ID: mdl-30246497
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Curva ROC
/
Ensaios Clínicos como Assunto
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
CPT Pharmacometrics Syst Pharmacol
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos