BAR12: Bayesian Autoregressive Phase 1-2 Design for Cell Therapy Trials With Manufacturing Changes

Area of Science:

• Biostatistics
• Clinical Trial Design
• Cell Therapy Manufacturing

Background:

• Early-phase cell therapy trials often require manufacturing "tweaks" to optimize product quality.
• These modifications can alter dose-response distributions, complicating trial design.
• Existing statistical methods may not adequately account for such in-trial changes.

Purpose of the Study:

• To propose a novel statistical design for phase 1-2 cell therapy trials that accommodates manufacturing tweaks.
• To ensure that dose-finding and safety monitoring remain robust despite product modifications.
• To improve the efficiency and accuracy of dose selection in adaptive trial settings.

Main Methods:

• Development of the Bayesian AutoRegressive Phase 1-2 (BAR12) design.
• Utilizes a first-order autoregressive model with spike-and-slab priors.
• Incorporates pre- and post-tweak toxicity and efficacy parameter distributions.

Main Results:

• Simulations demonstrate BAR12's superior operating characteristics compared to conventional designs.
• BAR12 shows higher probabilities of correct dose selection.
• Efficiently allocates more patients to optimal doses and monitors for safety.

Conclusions:

• The BAR12 design offers a robust statistical framework for cell therapy trials with manufacturing modifications.
• It enhances the ability to identify optimal and safe doses.
• Facilitates adaptive trial management without compromising statistical integrity.