OnCo
ideasIdea

Require genetic and target-trial evidence before funding any repurposing phase 3

The big metformin cancer trial failed after years and millions, despite strong observational hints. Cheaper checks on causality should be passed before funding the next one.

MA.32 (metformin in breast cancer) was negative despite extensive observational support that was later attributed to immortal-time and confounding biases. Mendelian randomisation using drug-target genetic proxies, target trial emulation with active-comparator new-user designs in large health records, and pre-registered replication across independent databases can test causal plausibility for a fraction of a trial's cost. The proposal is a funding rule: repurposing phase 3 trials receive public funding only after a standardised evidence gate (genetic support where a proxy exists, at least two concordant target trial emulations, and a plausible dose-response) has been passed and published.

Hypothesis
Trials passing the gate have a positive-result rate at least twice that of historical repurposing phase 3 trials, and the gate rejects most candidates whose observational support is driven by bias.
Rationale
Drugs with genetic support for their target succeed in development at roughly double the rate; the same logic should apply to repurposing, and target trial emulation can now be run in weeks on national data.
What would test it
Retrospectively apply the gate to the ten completed oncology repurposing phase 3 trials and check whether it would have predicted their outcomes; then apply prospectively to the next funding round.
Maturity
early clinical
Who has to act
research
Cost to try
Small (under $1M)
Years to first evidence
2
Bottlenecks it attacks

Connected

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