Zetyra: A Validated Suite of Statistical Calculators for Ecient Clinical Trial Design

Covariate adjustment, group sequential monitoring, and Bayesian predictive probability can substantially improve clinical trial efficiency, yet practical implementation barriers continue to limit adoption. We developed an integrated suite of statistical calculators accompanied by a fully reproducible validation framework addressing three methodologies: (1) CUPED variance reduction for baseline-adjusted power calculations; (2) group sequential boundaries via O'Brien-Fleming, Pocock, and alpha-spending functions; and (3) Bayesian predictive probability for interim decisions. Validation against reference implementations (gsDesign, closed-form solutions) across 51 automated tests yielded maximum deviation of 0.0046 z-score. The full validation suite is publicly available under MIT license, enabling independent verification and extension. Case studies illustrate impact: 30% sample size reduction through covariate adjustment (ρ=0.55) and 25% expected duration reduction via interim monitoring. We discuss implementation considerations in the context of regulatory guidance on covariate adjustment and Bayesian methods. This presentation demonstrates the integrated approach, shares lessons from building a reproducible validation framework, and invites community feedback on generalizing these methods.