title: The FOCUS4 design for biomarker stratified trials.
abstract: Randomised clinical trials (RCTs) remain the gold standard of evidence for the benefit of new therapeutics but standard designs fit awkwardly with key developments in biomarker-stratified drug development. Firstly, the unprecedented number of new agents being developed in oncology (usually with specific targets for which there may be predictive biomarkers) mandates a need for new trial designs that are more efficient in screening out new agents with modest likelihood of benefit, concentrating resources on the most promising ones. The multi-arm multi-stage (MAMS) design developed some years ago addresses this need. Secondly, biomarker-stratified trials, when tackled one biomarker/drug pairing at a time, are inherently highly inefficient. The FOCUS4 trial design was developed to overcome this problem, using a platform that incorporates multiple parallel biomarker-stratified RCTs in individual cohorts, and capable of adapting its design in response to developing evidence.
authors.affiliation: Medical Research Council Clinical Trials Unit, University College London, 125 Kingsway, London WC2B 6NH, UK. r.kaplan@ucl.ac.uk.
authors.forename: Richard
authors.initials: R
authors.lastname: Kaplan
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000473:pathology / Q000628:therapy*; D018572:Disease-Free Survival; D006801:Humans; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012107:Research Design
chemical_list: D014408:Biomarkers, Tumor
keywords: Stratified medicine; biomarkers; colorectal cancer; trials design