# An independent programme that validates surrogate endpoints, setting by setting

Source: https://onco.cc/ideas/idea-tr1-surrogate-validation-programme/  
OnCo record `idea-tr1-surrogate-validation-programme` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Trials often measure a stand-in for survival, such as time until the cancer grows on scans. An independent body would test, for each cancer and treatment type, whether the stand-in actually predicts survival, and publish the answer.

## Summary

A standing, publicly funded consortium performs individual-patient-data meta-analyses of completed randomised trials to quantify trial-level surrogacy (correlation of treatment effects on PFS, pCR, MRD, ORR with effects on OS or QoL) by disease setting and drug class, publishes surrogate threshold effects, and maintains a public register of validated, unvalidated and refuted surrogates. Regulators reference the register when accepting surrogate-based endpoints.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: Where the register rates a surrogate as weak, requiring OS or QoL co-primary endpoints will not slow approval by more than a year on average, and post-marketing withdrawals for lack of benefit will fall.
- Rationale: Systematic reviews have found trial-level surrogacy of PFS for OS is strong in some settings and poor in others, yet the same endpoint is accepted across settings. Data sharing platforms now make IPD meta-analysis feasible at scale.
- Proposed test: Fund the programme for three cancers with the most surrogate-based approvals and compare regulators' endpoint decisions before and after the register exists.
- Maturity: early-clinical
- Actor: research

## Sources

- FDA Oncology Center of Excellence: Project Endpoint: https://www.fda.gov/about-fda/oncology-center-excellence/project-endpoint

## Connected records

- institutions: [American Society of Clinical Oncology (ASCO)](https://onco.cc/institutions/asco/), [European Society for Medical Oncology (ESMO)](https://onco.cc/institutions/esmo/)
- terms: [Accelerated approval](https://onco.cc/terms/accelerated-approval/), [Minimal / molecular residual disease (MRD)](https://onco.cc/terms/mrd/), [Objective response rate (ORR)](https://onco.cc/terms/orr/), [Overall survival (OS)](https://onco.cc/terms/os/), [Pathologic complete response (pCR)](https://onco.cc/terms/pcr/), [Progression-free survival (PFS)](https://onco.cc/terms/pfs/)
- bottlenecks: [Biomarkers are not validated or standardised](https://onco.cc/bottlenecks/b-biomarker-validation/), [Trial design, endpoints and cost](https://onco.cc/bottlenecks/b-trial-design/)
- key papers: [Prasad: most surrogate endpoints in cancer trials correlate poorly with survival](https://onco.cc/key-papers/paper-prasad-surrogate-endpoints-jama-im-2015/), [Reproducibility Project: Cancer Biology found that landmark preclinical results mostly shrank or vanished on replication](https://onco.cc/key-papers/paper-reproducibility-project-cancer-biology-elife-2021/)
- 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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