{"entity":{"id":"idea-tr1-power-for-meaningful-benefit","kind":"idea","name":"Power trials to detect a benefit patients would value, not the smallest detectable one","aka":[],"tldr":"A trial can be designed to detect a tiny improvement that is statistically real but too small to matter. Protocols should state up front what size of benefit would be worth having, and be built to detect that.","summary":"Protocols pre-declare the smallest benefit patients would value, using the ESMO-MCBS or ASCO Value Framework thresholds (e.g., a hazard ratio and absolute gain in median OS or PFS), justify the sample size against it, and report whether the observed effect met it. Regulators and HTA bodies use the pre-declared threshold in review, discouraging trials sized to detect trivial differences.","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","asco"],"pathways":[],"terms":["hazard-ratio","os","pfs"],"trials":[],"people":["nathan-cherny"],"bottlenecks":["b-trial-design","b-drug-pricing"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Requiring a pre-declared meaningful benefit will reduce the number of approvals with marginal absolute gains and will shift sample sizes and endpoints toward those that capture patient-relevant differences.","rationale":"Analyses of approved cancer drugs show many with small absolute survival gains; sample-size inflation makes trivial effects significant. Pre-declaration is the standard in non-inferiority trials and could be symmetric.","test":"Audit recent approvals against ESMO-MCBS grades; pilot pre-declaration in cooperative-group protocols and track whether the observed effects meet it.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":2},"route":"/ideas/idea-tr1-power-for-meaningful-benefit/","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":"hazard-ratio","kind":"term","name":"Hazard ratio (HR)","route":"/terms/hazard-ratio/"},{"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-drug-pricing","kind":"bottleneck","name":"Prices and value","route":"/bottlenecks/b-drug-pricing/"},{"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/"}]}}