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Bioequivalence revisited: non-parametric analysis of two-period cross-over studies
Computer Methods and Programs in Biomedicine
|August 1, 1993
Summary
This study explores non-parametric bioequivalence procedures for treatment, period, and sequence effects in crossover studies. A FORTRAN program (BIOEQNEW) is presented for calculating non-parametric confidence intervals and estimates.
Area of Science:
- Biostatistics
- Pharmacometrics
- Clinical Trial Design
Background:
- Existing non-parametric bioequivalence methods focus primarily on treatment effects.
- Computer implementation of these methods, including specific algorithms, requires detailed exploration.
- Extending non-parametric approaches to period and sequence effects offers a more comprehensive analysis.
Purpose of the Study:
- To explore Hauschke et al.'s non-parametric bioequivalence procedure for treatment effects.
- To investigate computer implementation aspects, including Meineke and De Hey's algorithm and a recursive algorithm.
- To extend non-parametric analysis to period and sequence effects, analogous to analysis of variance in two-period crossover studies.
Main Methods:
- Development and presentation of a FORTRAN program (BIOEQNEW) implementing Meineke and De Mey's algorithm.
- Generation of a table of indices for ranked intersubject-intergroup mean ratios or differences for up to sixty subjects.
- Application of non-parametric methods to treatment, period, and sequence effects in two-period crossover studies.
Main Results:
- A table is provided to establish non-parametric 90% confidence intervals for studies with up to sixty subjects.
- The non-parametric procedure is demonstrated to be applicable to period and sequence effects, not just treatment effects.
- The BIOEQNEW program offers non-parametric point estimates and confidence intervals for various effects, including a non-parametric version of Schuirmann's two one-sided tests procedure.
Conclusions:
- Non-parametric analysis in bioequivalence studies can be extended beyond treatment effects to include period and sequence effects.
- The FORTRAN program BIOEQNEW provides a versatile tool for non-parametric analysis in bioequivalence and other studies.
- This extended non-parametric procedure serves as a valuable analogue to analysis of variance for two-period crossover designs.
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