How to Use Phoenix RSABE templates

Traditional average bioequivalence (ABE) methodology requires prohibitively large sample sizes when used with highly variable drugs and drug products (HVDs/HVDPs), which are defined as products with intra-subject CV% of the reference greater than 30%. This increases the expense of BE studies, places more study subjects at risk, and ultimately limits the availability of generics. Reference-scaled average bioequivalence (RSABE) methodology is increasingly used to demonstrate bioequivalence for HVDs/HVDPs. Specifics of RSABE methodology vary between regulatory agencies, but both the European Medicines Agency (EMA) and the United States Food and Drug Administration (FDA) require that subjects receive the reference drug more than once, eg, replicated 3-period (RRT/RTR/TRR) or 4-period (RTRT/TRTR) crossover designs, so that the BE analysis accounts for within-subject variability.

The Phoenix WinNonlin software provides a BE module to perform average bioequivalence but this module is not currently designed for a complete RSABE analysis. However, RSABE can be performed in Phoenix WinNonlin 6.3 using reusable template projects and workflows for both EMA and FDA approaches. These template projects require minimal input from the user in order to be used with any input dataset from a replicated 3-period or 4-period crossover design. These Phoenix template projects are available for free download, and this webinar demonstrated how they work.

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