title: A small sample confidence interval approach to assess individual bioequivalence.
abstract: 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has recommended the introduction of individual bioequivalence (IBE) and population bioequivalence (PBE) methods in a draft guidance document. The proposal in the draft guidance includes criteria for IBE and PBE and recommends the use of non-parametric bootstrap 95 per cent upper confidence intervals for the conclusion of either IBE or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.
authors.affiliation: Biostatistics Section, Division of Clinical Pharmacology, Department of Medicine, Thomas Jefferson University, 132 S. 10th Street, 1170 Main Building, Philadelphia, PA 19107-5244, USA. terry.hyslop@mail.tju.edu
authors.forename: T
authors.initials: T
authors.lastname: Hyslop
authors.forename: F
authors.initials: F
authors.lastname: Hsuan
authors.forename: D J
authors.initials: DJ
authors.lastname: Holder
mesh_terms: D016001:Confidence Intervals; D018592:Cross-Over Studies; D017408:Guidelines as Topic; D006801:Humans; D015233:Models, Statistical; D013810:Therapeutic Equivalency; D014481:United States; D014486:United States Food and Drug Administration