Inferring systemic exposure from a pharmacokinetic screen: model-free and model-based approaches

Stat Med. 1995 May;14(9-10):955-68; discussion 969-70. doi: 10.1002/sim.4780140915.

Abstract

To infer patterns of average systemic exposure and to estimate individual exposures in phase III clinical trials of a new anxiolytic, two statistical methodologies were applied and compared: non-linear mixed-effect modelling, and a model-free approach based on quartiles of dose-normalized plasma concentrations of the drug. Although the model-based approach provides more quantitative insight about relationships between average exposure and demographic covariates, the model-free approach provides qualitatively similar results about average clearance and quantitatively similar results about individual exposures, and the model-free approach is easy and inexpensive to implement.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Age Factors
  • Analysis of Variance
  • Anti-Anxiety Agents / blood*
  • Anti-Anxiety Agents / pharmacokinetics*
  • Carbolines / blood
  • Carbolines / pharmacokinetics*
  • Clinical Trials, Phase I as Topic / statistics & numerical data
  • Clinical Trials, Phase III as Topic / statistics & numerical data
  • Data Interpretation, Statistical*
  • Dose-Response Relationship, Drug
  • Drug Evaluation / statistics & numerical data*
  • Female
  • Humans
  • Male
  • Metabolic Clearance Rate
  • Models, Statistical*
  • Normal Distribution
  • Sex Factors
  • Smoking / adverse effects
  • Statistics, Nonparametric

Substances

  • Anti-Anxiety Agents
  • Carbolines
  • abecarnil