{"entity":{"id":"idea-reg-evidence-gate-before-repurposing-phase3","kind":"idea","name":"Require genetic and target-trial evidence before funding any repurposing phase 3","aka":[],"tldr":"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.","summary":"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.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (No incentive to repurpose cheap drugs): Pantziarka et al., The Repurposing Drugs in Oncology (ReDO) Project (ecancer 2014)","url":"https://doi.org/10.3332/ecancer.2014.442"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence"],"trials":[],"people":[],"bottlenecks":["b-generic-repurposing","b-real-world-evidence"],"keyPapers":["paper-pantziarka-ecancermedicalscience"],"journals":[],"dependsOn":[],"notes":[],"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.","test":"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","actor":"research","cost":"small","horizonYears":2},"route":"/ideas/idea-reg-evidence-gate-before-repurposing-phase3/","neighbours":{"term":[{"id":"real-world-evidence","kind":"term","name":"Real-world evidence","route":"/terms/real-world-evidence/"}],"bottleneck":[{"id":"b-generic-repurposing","kind":"bottleneck","name":"No incentive to repurpose cheap drugs","route":"/bottlenecks/b-generic-repurposing/"},{"id":"b-real-world-evidence","kind":"bottleneck","name":"Weak real-world evidence and registries","route":"/bottlenecks/b-real-world-evidence/"}],"paper":[{"id":"paper-pantziarka-ecancermedicalscience","kind":"paper","name":"The Repurposing Drugs in Oncology (ReDO) Project","route":"/key-papers/paper-pantziarka-ecancermedicalscience/"}]}}