Sample size calculation in three-arm equivalence trials including a placebo for binary clinical endpoints

Area of Science:

• Clinical Trials
• Pharmacoeconomics
• Biostatistics

Background:

• Three-arm equivalence trials comparing generic (T) to innovator (R) drugs with a placebo (P) are recommended by regulatory bodies.
• Equivalence is confirmed only if the T vs. R equivalence test and both T vs. P and R vs. P superiority tests are met.

Purpose of the Study:

• To propose novel sample size calculation methods for three-arm equivalence trials with binary endpoints.
• To address limitations in existing methods that overlook the R vs. P superiority test.

Main Methods:

• Developed two new sample size calculation methods for three-arm trials.
• Incorporated the equivalence test (ratio of two rates) and both superiority tests (T vs. P, R vs. P).
• Proposed a grid search approach for optimizing sample size allocation across the three arms.

Main Results:

• The proposed methods simultaneously account for all necessary statistical tests for equivalence.
• The grid search aids in determining the most efficient distribution of participants among treatment groups.
• Ensures adequate statistical power for all hypothesis tests.

Conclusions:

• The new sample size calculation methods provide a more comprehensive approach for designing three-arm equivalence trials.
• These methods improve the reliability of establishing drug equivalence by considering all regulatory criteria.
• Optimized sample allocation enhances trial efficiency and resource utilization.