A comparison of methods of benchmark-dose estimation for continuous response data

Risk Anal. 1999 Jun;19(3):453-9. doi: 10.1023/a:1007052729375.

Abstract

Methods of quantitative risk assessment for toxic responses that are measured on a continuous scale are not well established. Although risk-assessment procedures that attempt to utilize the quantitative information in such data have been proposed, there is no general agreement that these procedures are appreciably more efficient than common quantal dose-response procedures that operate on dichotomized continuous data. This paper points out an equivalence between the dose-response models of the nonquantal approach of Kodell and West and a quantal probit procedure, and provides results from a Monte Carlo simulation study to compare coverage probabilities of statistical lower confidence limits on dose corresponding to specified additional risk based on applying the two procedures to continuous data from a dose-response experiment. The nonquantal approach is shown to be superior, in terms of both statistical validity and statistical efficiency.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antitubercular Agents / adverse effects
  • Benchmarking*
  • Bias
  • Computer Simulation
  • Confidence Intervals
  • Dose-Response Relationship, Drug
  • Drug-Related Side Effects and Adverse Reactions*
  • Isoniazid / adverse effects
  • Isoniazid / analogs & derivatives
  • Likelihood Functions
  • Linear Models
  • Models, Statistical*
  • Monte Carlo Method
  • Normal Distribution
  • Pharmaceutical Preparations / administration & dosage
  • Probability
  • Rats
  • Rats, Inbred F344
  • Reproducibility of Results
  • Risk Assessment*
  • Weight Gain / drug effects

Substances

  • Antitubercular Agents
  • Pharmaceutical Preparations
  • aconiazide
  • Isoniazid