Version Compatibility

Reference examples tested with: R rpact 4.2+ (Wassmer/Brannath), gsDesign 3.6+ and gsDesign2 1.1+ (Anderson/Merck), adaptr, simtrial. Commercial: East/EastHorizon (Cytel), ADDPLAN (ICON), FACTS (Berry Consultants).

Before using code patterns, verify installed versions match. If versions differ:

• R: packageVersion('<pkg>') then ?function_name
• Python adaptive packages are limited; R is the regulatory de facto standard

If code throws an error, introspect the installed package and adapt the example to match the actual API rather than retrying.

Adaptive Clinical Trial Designs

"Design an adaptive trial" -> Pre-specify a design with one or more interim adaptations (early stopping, sample-size re-estimation, treatment selection, population enrichment, randomisation ratio changes) that strongly controls Type-I error at the trial-wide level via combination tests or the Conditional Rejection Probability principle.

Regulatory Status -- The 2024-2026 Landscape

FDA 2019 Final Adaptive Designs Guidance (Federal Register 2019-25986, Dec 2 2019) finalised the 2010 and 2018 drafts. Recognises 5 design types: group-sequential, blinded SSR, unblinded SSR, adaptive enrichment, adaptive randomisation.

FDA 2022 Final Master Protocols Guidance (March 2022, NOT 2018 — common citation error): basket (one drug, many diseases), umbrella (multiple drugs, one disease), platform (perpetual, drugs enter/exit).