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

Source: https://onco.cc/ideas/idea-reg-evidence-gate-before-repurposing-phase3/  
OnCo record `idea-reg-evidence-gate-before-repurposing-phase3` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- 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.
- Proposed 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

## Sources

- Bottleneck evidence (No incentive to repurpose cheap drugs): Pantziarka et al., The Repurposing Drugs in Oncology (ReDO) Project (ecancer 2014): https://doi.org/10.3332/ecancer.2014.442

## Connected records

- terms: [Real-world evidence](https://onco.cc/terms/real-world-evidence/)
- bottlenecks: [No incentive to repurpose cheap drugs](https://onco.cc/bottlenecks/b-generic-repurposing/), [Weak real-world evidence and registries](https://onco.cc/bottlenecks/b-real-world-evidence/)
- key papers: [The Repurposing Drugs in Oncology (ReDO) Project](https://onco.cc/key-papers/paper-pantziarka-ecancermedicalscience/)

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