Comparison of average and population bioequivalence approach

Area of Science:

• Pharmacokinetics and Drug Development
• Biostatistics in Pharmaceutical Research

Background:

• Bioequivalence studies are crucial for generic drug approval.
• Two common approaches for assessing bioequivalence are the average bioequivalence (ABE) and population bioequivalence (PBE) methods.
• Understanding the differences and sensitivities of these methods is vital for accurate drug evaluation.

Purpose of the Study:

• To compare the outcomes of average bioequivalence and population bioequivalence approaches.
• To analyze bioequivalence study data from published literature.

Main Methods:

• A literature search was conducted on MEDLINE for bioequivalence studies published between 1980 and 1989.
• Seventeen datasets for AUC and 12 for Cmax were analyzed.
• Logarithmic conversion was applied, followed by assessments of average bioequivalence, population bioequivalence, and variance inequality (F-test).

Main Results:

• Population bioequivalence criteria were met by more datasets (13/17 AUC, 8/12 Cmax) than average bioequivalence criteria (11/17 AUC, 3/12 Cmax).
• Discrepancies were observed, with some datasets passing one criterion but not the other.
• Population bioequivalence showed a stronger correlation with bioavailability variance (r=0.708) than with average bioavailability (r=0.412).

Conclusions:

• The population bioequivalence approach identified bioequivalence more frequently than the average bioequivalence approach in the analyzed studies.
• Population bioequivalence appears to be more sensitive to variations in bioavailability variance than to average bioavailability differences.
• These findings highlight the distinct characteristics and potential impacts of different bioequivalence assessment methods.