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A trial where everyone gets the new drug and there is no comparison group; success is judged by the share of tumours that shrink and for how long. Fast and small, it underpinned accelerated approvals for larotrectinib, sotorasib, tarlatamab and most CAR-T products, but it cannot show that patients live longer.
Single-arm phase 2 trials with objective response rate and duration of response as endpoints supported accelerated approvals for a series of targeted drugs in rare or heavily pretreated populations (larotrectinib, sotorasib, tarlatamab, most CAR-T products) where randomisation was impractical or considered unethical. Their weaknesses are patient selection, lack of a comparator for time-to-event endpoints, and susceptibility to response-evaluable population definitions; the FDA increasingly asks for a randomised confirmatory trial to be under way at approval and has issued guidance on when single-arm data suffice. External or synthetic control arms are attempts to add a comparator after the fact.
Shares AMNOG (Germany, 2011), Surrogate endpoint validation: which stand-ins have earned trust, Why trials fail: underpowered, wrong endpoint, control arm drift, subgroup fishing, crossover, Phase 1, 2 and 3 trials.
Shares NMTRC003/003B (DFMO maintenance), External and synthetic control arms, Basket trial, Phase 1, 2 and 3 trials.
Shares Blinding (double-blind, open-label, placebo-controlled), External and synthetic control arms, Clinical equipoise, Why trials fail: underpowered, wrong endpoint, control arm drift, subgroup fishing, crossover.
Shares Surrogate endpoint validation: which stand-ins have earned trust, Why trials fail: underpowered, wrong endpoint, control arm drift, subgroup fishing, crossover, Phase 1, 2 and 3 trials, Accelerated approval.
Shares Blinding (double-blind, open-label, placebo-controlled), External and synthetic control arms, Why trials fail: underpowered, wrong endpoint, control arm drift, subgroup fishing, crossover.
Shares Umbrella trial, Basket trial, Why trials fail: underpowered, wrong endpoint, control arm drift, subgroup fishing, crossover, Phase 1, 2 and 3 trials.
Shares Umbrella trial, Why trials fail: underpowered, wrong endpoint, control arm drift, subgroup fishing, crossover, Phase 1, 2 and 3 trials, Basket, umbrella, and platform trials.
Shares A phase 2a clinical study on the safety and efficacy of individualized dosed mebendazole in patients with advanced gastrointestinal cancer, Ivermectin with balstilimab or pembrolizumab in metastatic triple-negative breast cancer (Cedars-Sinai phase 1/2), Ivermectin.