{"entity":{"id":"idea-tr1-surrogate-validation-programme","kind":"idea","name":"An independent programme that validates surrogate endpoints, setting by setting","aka":[],"tldr":"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.","asOf":"2026-09-08","links":[{"label":"FDA Oncology Center of Excellence: Project Endpoint","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-endpoint"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["esmo","asco"],"pathways":[],"terms":["pfs","os","pcr","mrd","orr","accelerated-approval"],"trials":[],"people":[],"bottlenecks":["b-trial-design","b-biomarker-validation"],"keyPapers":["paper-reproducibility-project-cancer-biology-elife-2021"],"journals":[],"dependsOn":[],"notes":[],"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.","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","cost":"medium","horizonYears":4},"route":"/ideas/idea-tr1-surrogate-validation-programme/","neighbours":{"institution":[{"id":"asco","kind":"institution","name":"American Society of Clinical Oncology (ASCO)","route":"/institutions/asco/"},{"id":"esmo","kind":"institution","name":"European Society for Medical Oncology (ESMO)","route":"/institutions/esmo/"}],"term":[{"id":"accelerated-approval","kind":"term","name":"Accelerated approval","route":"/terms/accelerated-approval/"},{"id":"mrd","kind":"term","name":"Minimal / molecular residual disease (MRD)","route":"/terms/mrd/"},{"id":"orr","kind":"term","name":"Objective response rate (ORR)","route":"/terms/orr/"},{"id":"os","kind":"term","name":"Overall survival (OS)","route":"/terms/os/"},{"id":"pcr","kind":"term","name":"Pathologic complete response (pCR)","route":"/terms/pcr/"},{"id":"pfs","kind":"term","name":"Progression-free survival (PFS)","route":"/terms/pfs/"}],"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"},{"id":"b-trial-design","kind":"bottleneck","name":"Trial design, endpoints and cost","route":"/bottlenecks/b-trial-design/"}],"paper":[{"id":"paper-prasad-surrogate-endpoints-jama-im-2015","kind":"paper","name":"Prasad: most surrogate endpoints in cancer trials correlate poorly with survival","route":"/key-papers/paper-prasad-surrogate-endpoints-jama-im-2015/"},{"id":"paper-reproducibility-project-cancer-biology-elife-2021","kind":"paper","name":"Reproducibility Project: Cancer Biology found that landmark preclinical results mostly shrank or vanished on replication","route":"/key-papers/paper-reproducibility-project-cancer-biology-elife-2021/"}],"roadmap":[{"id":"trial-modernisation-roadmap","kind":"roadmap","name":"Trial modernisation roadmap: the randomised trial → platforms and adaptive designs → decentralised, pragmatic and always-on","route":"/roadmaps/trial-modernisation-roadmap/"}]}}