{"entity":{"id":"idea-tr1-randomised-phase-2-before-phase-3","kind":"idea","name":"Require a randomised phase 2 before any phase 3","aka":[],"tldr":"Phase 3 trials are often launched on a small single-arm response-rate study with no comparison group, and most then fail. Requiring a randomised phase 2 with a concurrent control first, with exceptions only for large effects in refractory settings, would filter out weak drugs earlier.","summary":"Sponsors and regulators adopt an expectation that phase 3 in a new indication is preceded by a randomised phase 2 (or the phase 2 portion of a seamless design) with a concurrent control, rather than a single-arm response-rate study. Exceptions for very large single-arm effects in refractory settings.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trial design, endpoints and cost): Davis et al., Availability of evidence of benefits on survival and quality of life of cancer drugs approved by EMA 2009-13 (BMJ 2017)","url":"https://doi.org/10.1136/bmj.j4530"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["orr","pfs"],"trials":[],"people":[],"bottlenecks":["b-trial-design","b-negative-results"],"keyPapers":["paper-davis-bmj"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Programmes with a randomised phase 2 will have a phase 3 success rate at least 15 percentage points higher than programmes proceeding from single-arm phase 2, and overall development cost per approval will fall despite the added step.","rationale":"Response rates in single-arm studies are poor predictors of survival benefit, and phase 3 oncology failure rates are among the highest of any therapeutic area. Randomised phase 2 also yields early estimates for planning the phase 3.","test":"Compare phase 3 success rates for programmes with and without randomised phase 2 across a decade of registry data, adjusting for indication and mechanism.","maturity":"early-clinical","actor":"industry","cost":"medium","horizonYears":3},"route":"/ideas/idea-tr1-randomised-phase-2-before-phase-3/","neighbours":{"term":[{"id":"orr","kind":"term","name":"Objective response rate (ORR)","route":"/terms/orr/"},{"id":"pfs","kind":"term","name":"Progression-free survival (PFS)","route":"/terms/pfs/"}],"bottleneck":[{"id":"b-negative-results","kind":"bottleneck","name":"Failures are hidden","route":"/bottlenecks/b-negative-results/"},{"id":"b-trial-design","kind":"bottleneck","name":"Trial design, endpoints and cost","route":"/bottlenecks/b-trial-design/"}],"paper":[{"id":"paper-davis-bmj","kind":"paper","name":"Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009-13","route":"/key-papers/paper-davis-bmj/"}]}}