ideasIdea
Mandatory real-world reporting for patients excluded from pivotal trials
Older, frailer and sicker patients are usually kept out of trials but make up most of those treated. Require companies to report how these patients do in practice.
Pivotal trials exclude patients over 75, with poor performance status, organ dysfunction, brain metastases or HIV, yet these groups receive the drug after approval. The proposal is a post-marketing requirement: within two years of approval, sponsors report real-world effectiveness and toxicity in pre-specified excluded subgroups using structured registry data, with results added to the label.
Hypothesis
Mandated reporting will reveal clinically meaningful differences in toxicity or benefit in excluded populations for a substantial share of new approvals, changing prescribing in those groups.
Rationale
Real-world studies of checkpoint inhibitors in performance status 2 patients found survival far below trial results; such findings currently depend on academic interest rather than requirement.
What would test it
Retrospectively produce excluded-population reports for ten recent approvals using existing federated data; measure how often the findings would have changed guideline recommendations.
Maturity
speculative
Who has to act
regulator
Cost to try
Medium ($1M to $50M)
Years to first evidence
3
Bottlenecks it attacks
- Weak real-world evidence and registries · We do not reliably know what happens to patients after approval, so we cannot tell which drugs deliver in practice.
- Older and multimorbid patients are excluded and undertreated · Most people with cancer are over 65 but most trial patients are younger and fitter. We guess how to treat the majority.
- Trials do not represent the people who get cancer · Older, Black, Hispanic, Asian, rural, poor and multimorbid patients are under-represented, so results may not apply to them.