# After approval, a pragmatic trial in the patients the pivotal trial excluded

Source: https://onco.cc/ideas/idea-tr1-post-approval-pragmatic-trial-in-excluded/  
OnCo record `idea-tr1-post-approval-pragmatic-trial-in-excluded` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Drugs are approved on trials of fit, younger patients and then given to everyone. A required follow-on trial in older, sicker and more diverse patients would show whether the benefit holds in real life.

## Summary

As a condition of approval, sponsors fund a pragmatic randomised trial with broad eligibility run in community settings, using routinely collected endpoints (OS, hospitalisation, treatment discontinuation) and minimal extra visits, modelled on the FDA's Project Pragmatica and the Pragmatica-Lung trial. Results feed label updates on dosing and benefit in the broader population.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: Pragmatic confirmatory trials will show a smaller but still positive effect in most cases and will identify at least some approved regimens whose benefit does not extend to the real-world population, leading to label changes.
- Rationale: Real-world outcomes are often worse than trial outcomes, and it is unknown how much is due to population differences versus care. Only randomisation in the broad population resolves this.
- Proposed test: Track Pragmatica-Lung and the next five such trials for enrolment speed, cost per patient and concordance with the pivotal effect size.
- Maturity: early-clinical
- Actor: regulator

## Sources

- FDA Oncology Center of Excellence: Project Pragmatica: https://www.fda.gov/about-fda/oncology-center-excellence/project-pragmatica
- Pragmatica-Lung (S2302) on ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT05633602

## Connected records

- institutions: [National Cancer Institute (NIH)](https://onco.cc/institutions/nci/)
- terms: [Real-world evidence](https://onco.cc/terms/real-world-evidence/)
- bottlenecks: [Older and multimorbid patients are excluded and undertreated](https://onco.cc/bottlenecks/b-aging-comorbidity/), [Trial design, endpoints and cost](https://onco.cc/bottlenecks/b-trial-design/), [Weak real-world evidence and registries](https://onco.cc/bottlenecks/b-real-world-evidence/)
- roadmaps: [Trial modernisation roadmap: the randomised trial → platforms and adaptive designs → decentralised, pragmatic and always-on](https://onco.cc/roadmaps/trial-modernisation-roadmap/)

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