A curve similarity approach to parallelism testing in bioassay

J Biopharm Stat. 2020 Jul 3;30(4):721-733. doi: 10.1080/10543406.2020.1730875. Epub 2020 Mar 12.

Abstract

Potency determination via bioassay is a relative measure that requires an evaluation of parallelism between the dose-response relationships of a reference standard and a sample material. Typical approaches for assessing parallelism include difference ([Formula: see text]-value) and equivalence tests. These traditional methods rely on a statistical assessment of model parameters as opposed to direct evaluation of the similarity of the dose-response curves. We propose a simple curve similarity approach that tests the hypothesis that the sample material is a dilution or concentration of the reference standard. The test is achieved by quantifying and normalizing the total area between the two curves and provides a single composite measure of parallelism. Both a frequentist and a Bayesian approach to the test are provided. We show through a simulation study that the curve similarity approach overcomes the drawbacks of the traditional methods and is effective at detecting parallelism and non-parallelism for bioassays.

Keywords: 4PL; Equivalence; dose-response; pharmaceutical; potency; reference standard.

MeSH terms

  • Animals
  • Bayes Theorem
  • Biological Assay / statistics & numerical data*
  • Computer Simulation
  • Data Interpretation, Statistical
  • Dose-Response Relationship, Drug
  • Humans
  • Models, Statistical
  • Monte Carlo Method
  • Research Design / statistics & numerical data*
  • Therapeutic Equivalency