{"entity":{"id":"idea-tr1-win-ratio-net-benefit-endpoint","kind":"idea","name":"Win-ratio endpoints that weigh survival, toxicity and quality of life together","aka":[],"tldr":"Every patient on the new drug is compared with every patient on the old one: who lived longer, and if equal, who had fewer serious side effects, and if still equal, who felt better. The share of 'wins' becomes the result.","summary":"Net benefit endpoints (win ratio, generalised pairwise comparisons, desirability of outcome ranking) rank prioritised outcomes hierarchically across all patient pairs. Cardiology adopted the win ratio for composite endpoints; oncology has used it only in exploratory analyses. The proposal is a pre-specified net-benefit endpoint with a published hierarchy (OS, then grade 3+ toxicity, then QoL deterioration) as a co-primary or key secondary in phase 3.","asOf":"2026-09-08","links":[{"label":"ESMO Magnitude of Clinical Benefit Scale","url":"https://www.esmo.org/guidelines/esmo-mcbs"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["esmo"],"pathways":[],"terms":["os","pfs","irae"],"trials":[],"people":["nathan-cherny"],"bottlenecks":["b-trial-design","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Net-benefit endpoints will separate regimens that PFS ranks as equivalent, will correlate better with patient preference studies than PFS, and will be accepted by regulators as supportive evidence within five years.","rationale":"Composite endpoints that ignore severity ordering are crude; hierarchical pairwise comparison uses the same data more efficiently and encodes what patients say they value.","test":"Apply the endpoint retrospectively to completed trials with individual patient data (e.g., through data-sharing platforms) and compare rankings to PFS and to ESMO-MCBS grades; then pre-specify it in a cooperative-group trial.","maturity":"speculative","actor":"research","cost":"small","horizonYears":3},"route":"/ideas/idea-tr1-win-ratio-net-benefit-endpoint/","neighbours":{"institution":[{"id":"esmo","kind":"institution","name":"European Society for Medical Oncology (ESMO)","route":"/institutions/esmo/"}],"term":[{"id":"irae","kind":"term","name":"Immune-related adverse events (irAEs)","route":"/terms/irae/"},{"id":"os","kind":"term","name":"Overall survival (OS)","route":"/terms/os/"},{"id":"pfs","kind":"term","name":"Progression-free survival (PFS)","route":"/terms/pfs/"}],"person":[{"id":"nathan-cherny","kind":"person","name":"Nathan Cherny","route":"/people/nathan-cherny/"}],"bottleneck":[{"id":"b-toxicity-qol","kind":"bottleneck","name":"Toxicity and quality of life are undervalued","route":"/bottlenecks/b-toxicity-qol/"},{"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/"}],"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/"}]}}