An independent programme that validates surrogate endpoints, setting by setting
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.
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.
- Trial design, endpoints and cost · A phase 3 trial takes years and hundreds of millions of dollars, and often answers a question that has already moved on.
- Biomarkers are not validated or standardised · Tests that decide who gets a drug are often not validated prospectively and are measured differently in every lab.
Many exciting laboratory findings that motivate drug programmes are weaker or less reliable than published, which helps explain the high failure rate of drugs entering clinical trials. It argues for pre-registration, detailed methods, data sharing and independent replication before major translational investment.
A drug that shrinks tumours or delays progression on scans has not necessarily been shown to help patients live longer or better. Patients and clinicians should ask what the endpoint was; regulators should insist on timely confirmatory trials; and trialists should validate surrogates before relying on them.
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not linked directly; found by shared links- IdeaPower trials to detect a benefit patients would value, not the smallest detectable one
Shares Prasad: most surrogate endpoints in cancer trials correlate poorly with survival, European Society for Medical Oncology (ESMO), American Society of Clinical Oncology (ASCO), Overall survival (OS).
- IdeaWin-ratio endpoints that weigh survival, toxicity and quality of life together
Shares Prasad: most surrogate endpoints in cancer trials correlate poorly with survival, European Society for Medical Oncology (ESMO), Overall survival (OS), Progression-free survival (PFS).
- TermSurrogate endpoint
Shares Pathologic complete response (pCR), Objective response rate (ORR), Accelerated approval, Overall survival (OS).
- IdeaLaunch prices indexed to the ESMO benefit scale, revisited when survival matures
Shares European Society for Medical Oncology (ESMO), American Society of Clinical Oncology (ASCO), Overall survival (OS), Progression-free survival (PFS).
- TermSurrogate endpoint
Shares Pathologic complete response (pCR), Accelerated approval, Progression-free survival (PFS), Minimal / molecular residual disease (MRD).
- IdeaSeamless phase 2/3 with pre-registered go rules as the default for new agents
Shares Overall survival (OS), Progression-free survival (PFS), Trial design, endpoints and cost.
- IdeaRequire a randomised phase 2 before any phase 3
Shares Objective response rate (ORR), Progression-free survival (PFS), Trial design, endpoints and cost.
- IdeaPre-specified crossover-adjusted survival in every trial that allows crossover
Shares European Society for Medical Oncology (ESMO), Overall survival (OS), Trial design, endpoints and cost.