Interpretation of simulation studies for efficient estimation of population pharmacokinetic parameters
| Autor: | Brian Whiting, Catherine A. Howie, Ene I. Ette, Andrew W. Kelman |
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| Rok vydání: | 1993 |
| Předmět: |
Accuracy and precision
Population 030204 cardiovascular system & hematology 030226 pharmacology & pharmacy Sampling Studies 03 medical and health sciences 0302 clinical medicine Bias Statistics Confidence Intervals Medicine Humans Pharmacology (medical) Pharmacokinetics education Statistic education.field_of_study business.industry Estimation theory Sampling (statistics) Confidence interval NONMEM Standard error Evaluation Studies as Topic Research Design business Epidemiologic Methods |
| Zdroj: | The Annals of pharmacotherapy. 27(9) |
| ISSN: | 1060-0280 |
| Popis: | OBJECTIVE: To develop new approaches for evaluating results obtained from simulation studies used to determine sampling strategies for efficient estimation of population pharmacokinetic parameters. METHODS: One-compartment kinetics with intravenous bolus injection was assumed and the simulated data (one observation made on each experimental unit [human subject or animal]), were analyzed using NONMEM. Several approaches were used to judge the efficiency of parameter estimation. These included: (1) individual and joint confidence intervals (CIs) coverage for parameter estimates that were computed in a manner that would reveal the influence of bias and standard error (SE) on interval estimates; (2) percent prediction error (%PE) approach; (3) the incidence of high pair-wise correlations; and (4) a design number approach. The design number (Φ) is a new statistic that provides a composite measure of accuracy and precision (using SE). RESULTS: The %PE approach is useful only in examining the efficiency of estimation of a parameter considered independently. The joint CI coverage approach permitted assessment of the accuracy and reliability of all model parameter estimates. The Φ approach is an efficient method of achieving an accurate estimate of parameter(s) with good precision. Both the Φ for individual parameter estimation and the overall Φ for the estimation of model parameters led to optimal experimental design. CONCLUSIONS: Application of these approaches to the analyses of the results of the study was found useful in determining the best sampling design (from a series of two sampling times designs within a study) for efficient estimation of population pharmacokinetic parameters. |
| Databáze: | OpenAIRE |
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