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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.
Showing the technology this term belongs to: Digital twins and virtual control arms.
Shares Stepped-wedge design, N-of-1 trial, SMART design (sequential multiple assignment randomised trial), Cluster-randomised trial.
Shares Umbrella trial, Data monitoring committee (DSMB, IDMC), Estimands and intercurrent events (ICH E9(R1)), Group sequential design, stopping rules and alpha spending.
Shares Response-adaptive randomisation, Statistical power, sample size and re-estimation, Data monitoring committee (DSMB, IDMC), Group sequential design, stopping rules and alpha spending.
Shares Bayesian trial design, Statistical power, sample size and re-estimation, Group sequential design, stopping rules and alpha spending, Interim analysis, readout and data cut-off.
Shares First-in-human (FIH) trial, Cluster-randomised trial, Registry-based randomised trial, Decentralised trial.
Shares Window-of-opportunity trial, First-in-human (FIH) trial, Data monitoring committee (DSMB, IDMC), Interim analysis, readout and data cut-off.
Shares First-in-human (FIH) trial, Cluster-randomised trial, Data monitoring committee (DSMB, IDMC), Phase 1, 2 and 3 trials.
Shares Stepped-wedge design, Estimands and intercurrent events (ICH E9(R1)), Non-inferiority margin and equivalence trials, Why trials fail: underpowered, wrong endpoint, control arm drift, subgroup fishing, crossover.