Zetyra: A Validated, Regulatory-Aligned Calculator Suite for Adaptive and Bayesian Clinical Trial Design

Thomas M. Menino Convention & Exhibition Center 

AI-assisted tools are accelerating clinical trial design, but validation has not kept pace. Many tools lack formal validation against reference standards, produce non-reproducible outputs, and fail to capture methodological interactions in composed adaptive designs. These limitations become critical at regulatory submission, where operating characteristics must be defensible under both frequentist and Bayesian frameworks.
Zetyra is a browser-based statistical calculator suite designed to address this validation gap through transparent, reproducible, and regulator-aligned implementations across frequentist, Bayesian, adaptive, and master-protocol design modules. Methods are validated against established reference engines, including gsDesign, RBesT, pwr, and scipy, and validation is enforced through automated tests open to independent verification.
A central contribution is pipeline-level evaluation of composed adaptive designs, where Bayesian monitoring, sample size re-estimation (SSR), and response-adaptive randomization (RAR) update using overlapping interim information. Through simulation, we show that component-level validation is insufficient: under a mild prior-data conflict, Type I error reaches 0.0771 (+208% above nominal α = 0.025) even when individual components pass validation. A negative-control analysis moving SSR to an earlier interim shows negligible attenuation, identifying prior-data conflict rather than SSR timing as the dominant driver. In mechanism-isolation analysis, prior-data conflict and time trends interact super-additively, with the interaction estimate's 95% simulation interval excluding zero.
This talk presents Zetyra's validation framework and demonstrates how composed-design evaluation surfaces operating-characteristic failures that conventional component-wise validation can miss, aligning with the FDA's January 2026 draft guidance on Bayesian methodology in clinical trials.

Adaptive clinical trial design

Bayesian methods

Group sequential design

Sample size re-estimation

Response-adaptive randomization

Validation and reproducibility 

Biopharmaceutical Section