title: Adaptive designs for clinical trials assessing biomarker-guided treatment strategies.
abstract: BACKGROUND
  The Biomarker Strategy Design has been proposed for trials assessing the value of a biomarker in guiding treatment in oncology. In such trials, patients are randomised to either receive the standard chemotherapy treatment or a biomarker-directed treatment arm, in which biomarker status is used to guide treatment.
  
  
  METHODS
  Motivated by a current trial, we consider an adaptive design in which two biomarkers are assessed. The trial is conducted in two stages. In the first stage, patients in the biomarker-guided arm are assessed using a standard and an alternative cheaper biomarker, with the standard biomarker guiding treatment. An analysis comparing biomarker results is then used to choose the biomarker to use for the remainder of the trial. The new biomarker is used if the results for the two biomarkers are sufficiently similar.
  
  
  RESULTS
  We show that in practical situations the first-stage results can be used to adapt the trial without type I error rate inflation. We also show that there can be considerable cost gains with only a small loss in power in the case where the alternative biomarker is highly concordant with the standard one.
  
  
  CONCLUSIONS
  Adaptive designs have an important role in reducing the cost and increasing the clinical utility of trials evaluating biomarker-guided treatment strategies.
authors.affiliation: MRC Biostatistics Unit, Cambridge, UK.
authors.forename: J
authors.initials: J
authors.lastname: Wason
authors.affiliation: Warwick Clinical Trials Unit, Warwick Medical School, University of Warwick, Coventry, UK.
authors.forename: A
authors.initials: A
authors.lastname: Marshall
authors.affiliation: Warwick Clinical Trials Unit, Warwick Medical School, University of Warwick, Coventry, UK.
authors.forename: J
authors.initials: J
authors.lastname: Dunn
authors.affiliation: UCLH/UCL NIHR Biomedical Research Centre, London, UK.
authors.forename: R C
authors.initials: RC
authors.lastname: Stein
authors.affiliation: Warwick Medical School, University of Warwick, Coventry, UK.
authors.forename: N
authors.initials: N
authors.lastname: Stallard
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D003198:Computer Simulation; D005260:Female; D006801:Humans; D057285:Precision Medicine; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor