An Exact Procedure for the Evaluation of Reference-Scaled Average Bioequivalence

The AAPS Journal
Laszlo Tothfalusi, Laszlo Endrenyi

Abstract

Reference-scaled average bioequivalence (RSABE) has been recommended by Food and Drug Administration (FDA), and in its closely related form by European Medicines Agency (EMA), for the determination of bioequivalence (BE) of highly variable (HV) and narrow therapeutic index (NTI) drug products. FDA suggested that RSABE be evaluated by an approximating procedure. Development of an alternative, numerically exact approach was sought. A new algorithm, called Exact, was derived for the assessment of RSABE. It is based upon the observation that the statistical model of RSABE follows a noncentral t distribution. The parameters of the distribution were derived for crossover and parallel-group study designs. Simulated BE studies of HV and NTI drugs compared the power and consumer risk of the proposed Exact method with those recommended by FDA and EMA. The Exact method had generally slightly higher power than the FDA approach. The consumer risks of the Exact and FDA procedures were generally below the nominal error risk with both methods except for the partial replicate design under certain heteroscedastic conditions. The estimator of RSABE was biased; simulations demonstrated the appropriateness of Hedges' correction. The FDA approach ha...Continue Reading

References

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May 28, 2009·Journal of Pharmacy & Pharmaceutical Sciences : a Publication of the Canadian Society for Pharmaceutical Sciences, Société Canadienne Des Sciences Pharmaceutiques·Laszlo Endrenyi, Laszlo Tothfalusi
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Citations

Mar 5, 2019·Journal of Biopharmaceutical Statistics·Yu-Ting WengChao Wang
Aug 30, 2017·Statistics in Medicine·Laszlo Tothfalusi, Laszlo Endrenyi
Feb 25, 2019·Journal of Pharmacokinetics and Pharmacodynamics·Laszlo Endrenyi, Laszlo Tothfalusi

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