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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.
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.
Shares Prasad: most surrogate endpoints in cancer trials correlate poorly with survival, European Society for Medical Oncology (ESMO), Trial modernisation roadmap: the randomised trial → platforms and adaptive designs → decentralised, pragmatic and always-on, Progression-free survival (PFS).
Shares Prasad: most surrogate endpoints in cancer trials correlate poorly with survival, European Society for Medical Oncology (ESMO), American Society of Clinical Oncology (ASCO), Progression-free survival (PFS).
Shares European Society for Medical Oncology (ESMO), American Society of Clinical Oncology (ASCO), Progression-free survival (PFS), Overall survival (OS).
Shares Trial modernisation roadmap: the randomised trial → platforms and adaptive designs → decentralised, pragmatic and always-on, Progression-free survival (PFS), Biomarkers are not validated or standardised, Trial design, endpoints and cost.
Shares Objective response rate (ORR), Accelerated approval, Trial modernisation roadmap: the randomised trial → platforms and adaptive designs → decentralised, pragmatic and always-on, Pathologic complete response (pCR).
Shares Progression-free survival (PFS), Overall survival (OS), Trial design, endpoints and cost.
Shares Accelerated approval, Overall survival (OS), Trial design, endpoints and cost.
Shares Objective response rate (ORR), Progression-free survival (PFS), Trial design, endpoints and cost.