{"entity":{"id":"dose-escalation-design","kind":"term","name":"Dose-escalation designs (3+3, BOIN, dose-expansion)","aka":["3+3","3 + 3","3+3 design","rule-based design","BOIN","Bayesian optimal interval","CRM","continual reassessment method","mTPI","TITE-CRM","model-based dose finding","model-based design","dose-finding","dose finding","dose-finding study","dose escalation cohort","dose escalation","dose-escalation","dose escalation phase","dose-expansion","dose expansion","expansion phase","accelerated titration","backfill cohort","dose level","dose levels","cohort of 3","backfill cohorts","model-based designs"],"tldr":"How a phase 1 trial climbs from a tiny starting dose to a useful one: the old 3+3 design treats three patients at a time and moves up if none has serious toxicity; newer statistical designs (BOIN, CRM) use all the data to pick doses more accurately with fewer patients on ineffective levels.","summary":"The 3+3 design (still the most used) is simple but imprecise, treats a large share of patients at sub-therapeutic doses and identifies the MTD poorly; model-based designs such as the continual reassessment method and the Bayesian optimal interval design estimate the toxicity curve continuously and are recommended by the FDA and methodologists, with time-to-event versions handling late toxicities. After escalation, dose-expansion cohorts (often 20-40 patients per tumour type) gather efficacy signals and may be randomised between two doses under Project Optimus. Accelerated titration and single-patient cohorts speed the early low-dose levels, and backfill cohorts add patients at lower doses to inform dose optimisation.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Phase_I_clinical_trial#Dose_escalation","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Phase_I_clinical_trial#Dose_escalation"}],"tags":[],"related":["dose-limiting-toxicity","mtd","rp2d","first-in-human","project-optimus","bayesian-trial-design","seamless-adaptive","trial-phases"],"cancers":[],"sections":["drug-discovery"],"technologies":["project-optimus"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["rejoice-ovarian01","low-dose-nivolumab-tmh"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},"route":"/terms/dose-escalation-design/","neighbours":{"term":[{"id":"bayesian-trial-design","kind":"term","name":"Bayesian trial design","route":"/terms/bayesian-trial-design/"},{"id":"dose-limiting-toxicity","kind":"term","name":"Dose-limiting toxicity (DLT)","route":"/terms/dose-limiting-toxicity/"},{"id":"first-in-human","kind":"term","name":"First-in-human (FIH) trial","route":"/terms/first-in-human/"},{"id":"mtd","kind":"term","name":"Maximum tolerated dose (MTD)","route":"/terms/mtd/"},{"id":"trial-phases","kind":"term","name":"Phase 1, 2 and 3 trials","route":"/terms/trial-phases/"},{"id":"project-optimus","kind":"term","name":"Project Optimus","route":"/terms/project-optimus/"},{"id":"rp2d","kind":"term","name":"Recommended phase 2 dose (RP2D)","route":"/terms/rp2d/"},{"id":"seamless-adaptive","kind":"term","name":"Seamless, adaptive and Bayesian trial designs","route":"/terms/seamless-adaptive/"}],"section":[{"id":"drug-discovery","kind":"section","name":"Drug Discovery Platforms","route":"/fronts/drug-discovery/"}],"trial":[{"id":"low-dose-nivolumab-tmh","kind":"trial","name":"Low-dose nivolumab plus metronomic chemotherapy (Tata Memorial)","route":"/trials/low-dose-nivolumab-tmh/"},{"id":"rejoice-ovarian01","kind":"trial","name":"REJOICE-Ovarian01","route":"/trials/rejoice-ovarian01/"}],"paper":[{"id":"paper-patil-mebendazole-glioma-phase-1-cancer-med-2020","kind":"paper","name":"Reverse swing-M, phase 1 study of repurposing mebendazole in recurrent high-grade glioma","route":"/key-papers/paper-patil-mebendazole-glioma-phase-1-cancer-med-2020/"}]}}