{"entity":{"id":"idea-bio1-pre-randomised-sequencing-trials","kind":"idea","name":"Randomise the next line of treatment before the first one fails","aka":[],"tldr":"Trials usually study one treatment at a time, so nobody knows the best order. Deciding the next step in advance, by lottery, answers the sequencing question at little extra cost.","summary":"Sequencing questions are almost never answered because patients leave the trial at progression. A pre-randomised design assigns the second-line option at the time of first-line enrolment, keeps patients within the protocol at progression, and collects the progression biopsy. Total sample size increases modestly, but the design yields a real strategy comparison rather than isolated line-by-line results.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Acquired resistance to every therapy): Soria et al., Osimertinib in untreated EGFR-mutated NSCLC (FLAURA, NEJM 2018)","url":"https://doi.org/10.1056/NEJMoa1713137"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["adc-sequencing","os"],"trials":[],"people":[],"bottlenecks":["b-resistance","b-trial-design"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Strategy-randomised sequencing trials detect clinically meaningful differences in overall survival between drug orders that line-by-line trials cannot detect, in at least one common setting.","rationale":"Overall survival depends on the whole sequence, not the first agent; oncology has repeatedly discovered that ordering matters (for example in metastatic colorectal and prostate cancer) only through retrospective analysis.","test":"Add pre-randomised second-line assignment to two ongoing first-line trials and compare information gained per patient with a matched conventional design.","maturity":"speculative","actor":"research","cost":"medium","horizonYears":6},"route":"/ideas/idea-bio1-pre-randomised-sequencing-trials/","neighbours":{"term":[{"id":"adc-sequencing","kind":"term","name":"ADC sequencing","route":"/terms/adc-sequencing/"},{"id":"os","kind":"term","name":"Overall survival (OS)","route":"/terms/os/"}],"bottleneck":[{"id":"b-resistance","kind":"bottleneck","name":"Acquired resistance to every therapy","route":"/bottlenecks/b-resistance/"},{"id":"b-trial-design","kind":"bottleneck","name":"Trial design, endpoints and cost","route":"/bottlenecks/b-trial-design/"}]}}