{"entity":{"id":"idea-cost-shorter-course-trials","kind":"idea","name":"Fund trials that test shorter courses of the most expensive adjuvant drugs","aka":[],"tldr":"The PERSEPHONE trial showed six months of trastuzumab after surgery is as good as twelve, halving the drug cost; no company will run such trials, so public funders and charities must.","summary":"PERSEPHONE (Earl et al., Lancet 2019) randomised 4,089 women with HER2-positive early breast cancer to six or twelve months of adjuvant trastuzumab and found four-year disease-free survival of 89.4% versus 89.8%, meeting non-inferiority, with less cardiotoxicity. Adjuvant durations for checkpoint inhibitors (one year), CDK4/6 inhibitors (two to three years) and PARP inhibitors (one year) were set without duration-finding studies. A dedicated de-escalation trial fund, on the model of the UK National Institute for Health and Care Research that paid for PERSEPHONE, would test the highest-spend adjuvant regimens.","asOf":"2026-09-10","links":[{"label":"Earl et al., Lancet 2019: PERSEPHONE","url":"https://doi.org/10.1016/S0140-6736(19)30650-6"}],"tags":[],"related":[],"cancers":["breast-her2-positive","breast-hr-positive"],"sections":[],"technologies":[],"targets":[],"drugs":["trastuzumab","pembrolizumab","abemaciclib","olaparib"],"companies":[],"institutions":["nci","cruk"],"pathways":[],"terms":[],"trials":["persephone"],"people":[],"bottlenecks":["b-dose-optimisation","b-drug-pricing","b-trial-design","b-incentive-misalignment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"At least two of five adjuvant de-escalation trials will demonstrate non-inferiority, each saving more than a third of the drug cost for that indication.","rationale":"Manufacturers have no incentive to shorten courses; the payer has every incentive and the evidence base for adjuvant durations is thin.","test":"A funded portfolio of five randomised non-inferiority duration trials run through cooperative groups, with pre-registered margins and cost-effectiveness analyses.","maturity":"early-clinical","actor":"philanthropy","cost":"large","horizonYears":6},"route":"/ideas/idea-cost-shorter-course-trials/","neighbours":{"cancer":[{"id":"breast-her2-positive","kind":"cancer","name":"HER2-positive breast cancer","route":"/cancers/breast-her2-positive/"},{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"}],"drug":[{"id":"abemaciclib","kind":"drug","name":"Abemaciclib","route":"/drugs/abemaciclib/"},{"id":"olaparib","kind":"drug","name":"Olaparib","route":"/drugs/olaparib/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}],"institution":[{"id":"cruk","kind":"institution","name":"Cancer Research UK","route":"/institutions/cruk/"},{"id":"nci","kind":"institution","name":"National Cancer Institute (NIH)","route":"/institutions/nci/"}],"trial":[{"id":"persephone","kind":"trial","name":"PERSEPHONE","route":"/trials/persephone/"}],"bottleneck":[{"id":"b-incentive-misalignment","kind":"bottleneck","name":"Incentives reward me-too drugs and marginal gains","route":"/bottlenecks/b-incentive-misalignment/"},{"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/"},{"id":"b-dose-optimisation","kind":"bottleneck","name":"Wrong doses","route":"/bottlenecks/b-dose-optimisation/"}],"roadmap":[{"id":"global-access-roadmap","kind":"roadmap","name":"Global access and affordability roadmap: essential medicines and generics → biosimilars and frugal trials → reliance, pooling and homegrown innovation","route":"/roadmaps/global-access-roadmap/"},{"id":"hormonal-therapy-roadmap","kind":"roadmap","name":"Hormonal therapy roadmap: removing the ovaries → tamoxifen → oral degraders switched by a blood test","route":"/roadmaps/hormonal-therapy-roadmap/"}]}}