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An Assessment of FDA’s Dose-Scaling Approach to Evaluate Pharmacodynamic Bioequivalence

Kim SH.

RDD Europe 2013. Volume 1, 2013: 69-76.

Abstract:

For pharmacodynamic (PD) endpoints which exhibit nonlinearity in dose-response, the FDA recommends the “dose-scale” method to statistically analyze data from PD bioequivalence (BE) studies, including those for orally inhaled drug products. A simulation method was developed to estimate the study power of PD studies analyzed by the dose-scale approach, and to evaluate the applicability of the dose-scale approach to PD bioequivalence studies of orally inhaled drug products. The simulation method provided a good estimate of study power based on pilot data and may well be useful to predict statistical power when such data are available. The effects of between-subject and within-subject variability on study power were examined through simulations and were found to produce very similar effects on power. The simulations also indicated that the dose-scale approach was sensitive to the degree of dose-response (characterized by the DT /ED50 ratio), as well as differences in the value of F, the relative bioavailability of the test product.