OnCo
ideasIdea

Default-inclusive eligibility: sponsors must justify every exclusion criterion

Trials should let people in unless there is a scientific or safety reason to keep them out. Every exclusion rule would need a written reason, reviewed like the rest of the protocol.

Regulators and ethics committees would require a one-line scientific or safety justification for each exclusion criterion, with a default set of permitted criteria (the ASCO-Friends of Cancer Research broadened criteria on brain metastases, organ function, prior malignancies, HIV and hepatitis) needing no justification and anything stricter needing one. The FDA's 2020 eligibility guidances describe what is reasonable; this idea makes the reasonable set the default and puts the burden of proof on restriction.

Hypothesis
Protocols written under a justify-every-exclusion rule will have at least a third fewer exclusion criteria and a measurably higher fraction of real-world patients eligible (as simulated against a real-world oncology dataset), without an increase in grade 5 adverse events attributable to the broadened population.
Rationale
Analyses of protocol eligibility against real-world data show that many criteria are copied from earlier protocols and that relaxing them changes the eligible pool substantially with little effect on the estimated hazard ratio. Ethics review already asks for justification of risk; asking for justification of exclusion is symmetric and cheap.
What would test it
A cooperative group or single regulator pilots the rule for 12 months on all new phase 2/3 oncology protocols, comparing criterion counts, simulated eligible fraction and later serious-adverse-event rates against the prior year's protocols.
Maturity
early clinical
Who has to act
regulator
Cost to try
Small (under $1M)
Years to first evidence
2
Bottlenecks it attacks

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