Sequential Bioequivalence Approaches for Parallel Designs
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Regulators in EU, USA and Canada allow the use of two-stage approaches for evaluation of bioequivalence. The purpose of this paper is to evaluate such designs for parallel groups using trial simulations. The methods developed by Diane Potvin and co-workers were adapted to parallel designs. Trials were simulated and evaluated on basis of either equal or unequal variances between treatment groups. Methods B and C of Potvin et al., when adapted for parallel designs, protected well against type I error rate inflation under all of the simulated scenarios. Performance characteristics of the new parallel design methods showed little dependence on the assumption of equality of the test and reference variances. This is the first paper to describe the performance of two-stage approaches for parallel designs used to evaluate bioequivalence. The results may prove useful to sponsors developing formulations where crossover designs for bioequivalence evaluation are undesirable.
KEY WORDSbioequivalence parallel power sequential designs type I errors
Thanks to Helmut Schütz and Detlew Labes who provided valuable input.
- 1.Committee for Human Medicinal Products. Investigation of bioequivalence. CHMP. CPMP/EWP/QWP/1401/98 Rev. 1. 2010. http://www.ema.europa.eu/ema/pages/includes/document/open_document.jsp?webContentId=WC500070039. Accessed 1 Mar 2013.
- 2.United States Food and Drug Administration, Center for Drug Evaluation and Research. Statistical approaches to establishing bioequivalence. Guidance for industry: statistical approaches to establishing bioequivalence. 2001. http://www.fda.gov/downloads/Drugs/Guidances/ucm070244.pdf. Accessed 1 Mar 2013.
- 3.Therapeutic Products Directorate, Health Canada. Conduct and analysis of comparative bioavailability studies. 2012. http://www.hc-sc.gc.ca/dhp-mps/alt_formats/pdf/prodpharma/applic-demande/guide-ld/bio/gd_cbs_ebc_ld-eng.pdf. Accessed 1 Mar 2013.
- 7.Labes D. Power and sample size based on two one-sided t-tests (TOST) for (bio)equivalence studies. 2013. http://cran.r-project.org/web/packages/PowerTOST/PowerTOST.pdf. Accessed 1 Mar 2013.