Average bioequivalence evaluation: general methods for pilot trials.

Area of Science:

• Pharmaceutical Sciences
• Clinical Trials
• Biostatistics

Background:

• Bioequivalent (BE) drug development commonly uses a two-step strategy involving pilot and pivotal trials.
• Pilot BE trials are often inappropriately designed and analyzed using pivotal trial criteria due to a lack of specific methods.
• This leads to inefficiencies and potential issues in drug product evaluation.

Purpose of the Study:

• To propose a novel Pilot Acceptance Range method for analyzing pilot BE trials within a two-step strategy.
• To provide a framework for appropriate pilot BE trial design and analysis.
• To address the gap in established methods for pilot BE trial evaluation.

Main Methods:

• Development of the Pilot Acceptance Range method for pilot BE trial analysis.
• Derivation of the power function for crossover pilot BE trial design.
• Introduction of a sample size determination method for pilot BE trials.

Main Results:

• The proposed Pilot Acceptance Range method offers a specific criterion for pilot BE trial analysis.
• The derived power function and sample size method facilitate appropriate pilot BE trial design.
• This approach aims to improve the reliability of the first step in the two-step BE strategy.

Conclusions:

• The Pilot Acceptance Range method provides a statistically sound approach for pilot BE trials.
• Implementing this method can enhance the efficiency and accuracy of bioequivalence studies.
• This contributes to more robust clinical development of bioequivalent drug products.