Statistical issues on the FDA conjugated estrogen tablets bioequivalence guidance

This paper considers some key statistical issues embedded in the Guidance on Conjugated Estrogen Tablets - In Vivo Bioequivalence and In Vitro Drug Release issued by the United States Form and Drug Administration in 1991. These statistical issues are addressed for the single dose fasting study stated in the guidance and include study design, sample size determination, the multiplicity of studies and ingredients, the use of baseline measurements, logarithmic transformation versus the presence of a significant carryover effect, and others. For each issue, objective evaluation and constructive comments and suggestions which are useful in bioequivalence assessment for conjugated estrogen tablets are provided. In addition, the United States Pharmacopeia (USP) and Food and Drug Administration (FDA) requirements for drug release (in vitro dissolution) testing are reviewed. A bioequivalence concept for assessing the similarity between the dissolution profiles of drug products is proposed.

Duke Scholars

Author Shein-Chung Chow Biostatistics & Bioinformatics, Division of Biostatistics