A small sample confidence interval approach to assess individual bioequivalence.


Journal Article

The concept of interchangeable pharmaceutical products has been examined in great detail in the literature. Anderson and Hauck proposed a statistical random coefficient model to study 'switchability', and coined the phrase 'individual bioequivalence' which they defined with a probability-based inequality. Since that paper there has been considerable work and discussion. The Food and Drug Administration has recommended the introduction of individual bioequivalence (IBE) and population bioequivalence (PBE) methods in a draft guidance document. The proposal in the draft guidance includes criteria for IBE and PBE and recommends the use of non-parametric bootstrap 95 per cent upper confidence intervals for the conclusion of either IBE or PBE. However, this method requires intensive computations. We have developed an alternative confidence interval procedure to assess IBE by the FDA recommended criteria. This method utilizes Howe's approximation I to a Cornish-Fisher expansion. Our proposed method is applicable to balanced or unbalanced data in a broad class of extended cross-over designs, and can be easily programmed using readily available software.

Full Text

Cited Authors

  • Hyslop, T; Hsuan, F; Holder, DJ

Published Date

  • October 30, 2000

Published In

Volume / Issue

  • 19 / 20

Start / End Page

  • 2885 - 2897

PubMed ID

  • 11033583

Pubmed Central ID

  • 11033583

International Standard Serial Number (ISSN)

  • 0277-6715

Digital Object Identifier (DOI)

  • 10.1002/1097-0258(20001030)19:20<2885::aid-sim553>3.0.co;2-h


  • eng

Conference Location

  • England