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termsTerm

Confirmatory trial

aka confirmatory, confirmatory study, confirmatory phase 3, confirmatory evidence, post-marketing requirement, postmarketing requirement, post-approval trial, verify clinical benefit, conversion to full approval, dangling approval, dangling accelerated approval

The randomised trial a company must run after an accelerated approval to prove the drug really helps patients live longer or better. If it fails or never finishes, the approval is supposed to be withdrawn.

Accelerated approvals rest on surrogate endpoints (response rate, pCR, MRD) from single-arm or early trials; the confirmatory trial tests overall survival, progression-free survival or another clinical benefit against a control. The 2022 FDORA law lets the FDA require the confirmatory trial to be under way at approval and streamlines withdrawal when it fails. Notable failures and withdrawals include PI3K inhibitors in lymphoma, several checkpoint-inhibitor indications ('dangling approvals' reviewed by ODAC in 2021), and melphalan flufenamide. Regulators increasingly scrutinise whether the confirmatory population matches the accelerated one (STARGLO complete response letter).

Category
Trials & regulation

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