An Adaptive Three-Arm Comparative Clinical Endpoint Bioequivalence Study Design With Unblinded Sample Size...

Area of Science:

• Pharmacokinetics and Drug Development
• Clinical Trial Design
• Biostatistics

Background:

• Traditional three-arm bioequivalence (BE) studies comparing generic (T) to reference (R) drugs over placebo (P) can be under- or over-powered due to uncertain parameters.
• Fixed study designs may lead to failure or increased costs, impacting generic drug accessibility.

Purpose of the Study:

• To propose a novel two-stage adaptive clinical endpoint BE study design.
• To enhance efficiency, reduce costs, and improve the success rate of bioequivalence studies for generic drugs.

Main Methods:

• The proposed design incorporates unblinded sample size re-estimation and optimized allocation ratios.
• It includes optional re-estimation of effect size and treatment means (R and P) at interim analysis.
• The method analytically guarantees control of the Type 1 error rate.

Main Results:

• The adaptive design reduces average sample size for overpowered studies and increases it for underpowered ones.
• It improves statistical power compared to fixed or group sequential designs.
• The approach offers flexibility through optional re-estimation of key parameters.

Conclusions:

• The proposed adaptive BE study design offers a more efficient and cost-effective alternative to fixed designs.
• This methodology can increase the success rate of bioequivalence studies, facilitating faster generic drug approval.
• Ultimately, this contributes to making generic medications more affordable and accessible to the public.