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Seamless, adaptive and Bayesian trial designs

aka seamless, seamless phase 2/3, seamless phase 1/2, phase 1/2, phase 2/3, adaptive design, adaptive trial, adaptive randomisation, response-adaptive randomisation, Bayesian, Bayesian adaptive, Bayesian design, I-SPY 2, I-SPY, master protocol, sample size re-estimation, adaptive enrichment, biomarker-selected, biomarker-enriched, all-comers, unselected, unselected population

Trial designs that change as data come in: merging phases so successful drugs move forward without pause, dropping arms or doses that are not working, adding new ones, and shifting randomisation toward what seems to help. Faster and more efficient, but they need careful statistics to stay honest.

Seamless phase 2/3 trials expand a successful cohort into a registrational one under a single protocol; phase 1/2 trials do the same from dose-finding to expansion. Adaptive platform trials such as I-SPY 2 (neoadjuvant breast cancer, Bayesian response-adaptive randomisation with 'graduation' of drugs likely to succeed in phase 3), STAMPEDE (multi-arm multi-stage in prostate cancer) and GBM AGILE test many drugs against a shared control. Enrichment designs restrict or shift enrolment to biomarker-positive patients when they respond better ('biomarker-selected' versus 'all-comers'). Pre-specified adaptation rules, alpha control and a firewall between the data monitoring committee and the sponsor are required for regulatory acceptance.

Category
Trials & regulation

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