biostudies-literatureKaplan RCancer Research UKMedical Research CouncilNational Institute for Health Research (NIHR)4562-8https://www.ebi.ac.uk/biostudies/studies/S-EPMC4394353biostudies-literatureUnknown31(36)There is a pressing need for more-efficient trial designs for biomarker-stratified clinical trials. We suggest a new approach to trial design that links novel treatment evaluation with the concurrent evaluation of a biomarker within a confirmatory phase II/III trial setting. We describe a new protocol using this approach in advanced colorectal cancer called FOCUS4. The protocol will ultimately answer three research questions for a number of treatments and biomarkers: (1) After a period of first-line chemotherapy, do targeted novel therapies provide signals of activity in different biomarker-defined populations? (2) If so, do these definitively improve outcomes? (3) Is evidence of activity restricted to the biomarker-defined groups? The protocol randomizes novel agents against placebo concuJournal of clinical oncology : official journal of the American Society of Clinical OncologyEvaluating many treatments and biomarkers in oncology: a new design.PMC4394353MC_EX_G080081413363G070177011/100/50EME/11/100/50MC_U122861325UD99999939MC_UU_12023/25MC_UU_12023/3Kaplan RWilson RBrown LCrook AMaughan TParmar MFisher DfalseEvaluating many treatments and biomarkers in oncology: a new design.There is a pressing need for more-efficient trial designs for biomarker-stratified clinical trials. We suggest a new approach to trial design that links novel treatment evaluation with the concurrent evaluation of a biomarker within a confirmatory phase II/III trial setting. We describe a new protocol using this approach in advanced colorectal cancer called FOCUS4. The protocol will ultimately answer three research questions for a number of treatments and biomarkers: (1) After a period of first-line chemotherapy, do targeted novel therapies provide signals of activity in different biomarker-defined populations? (2) If so, do these definitively improve outcomes? (3) Is evidence of activity restricted to the biomarker-defined groups? The protocol randomizes novel agents against placebo concu2013-01-01T00:00:00Z2013 Dec2025-04-04T00:28:59.659Z2019-03-27T01:49:49ZS-EPMC43943532424869210.1200/JCO.2013.50.790510.1200/jco.2013.50.7905