Multi-arm, multi-stage trials to answer which order to give approved drugs
Several drugs are approved for the same cancer, but nobody tests which order works best because no company benefits from the answer. Public multi-arm trials could settle these questions efficiently.
Cooperative groups run multi-arm multi-stage (MAMS) trials comparing sequences of already-approved agents (e.g., ADC then checkpoint inhibitor versus the reverse; endocrine-CDK4/6 sequencing; TKI order in RCC), with interim futility dropping of arms and OS or TTF across the sequence as the primary endpoint. Drug supply comes from companies under a neutral-access agreement; funding from payers and public agencies who bear the cost of wrong sequences.
- Trial design, endpoints and cost · A phase 3 trial takes years and hundreds of millions of dollars, and often answers a question that has already moved on.
- Incentives reward me-too drugs and marginal gains · The system pays the same for a drug that adds two months as for a cure, so companies race to copy rather than to cure.
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