title: Biomarker-Guided Adaptive Trial Designs in Phase II and Phase III: A Methodological Review.
abstract: BACKGROUND
  Personalized medicine is a growing area of research which aims to tailor the treatment given to a patient according to one or more personal characteristics. These characteristics can be demographic such as age or gender, or biological such as a genetic or other biomarker. Prior to utilizing a patient's biomarker information in clinical practice, robust testing in terms of analytical validity, clinical validity and clinical utility is necessary. A number of clinical trial designs have been proposed for testing a biomarker's clinical utility, including Phase II and Phase III clinical trials which aim to test the effectiveness of a biomarker-guided approach to treatment; these designs can be broadly classified into adaptive and non-adaptive. While adaptive designs allow planned modifications based on accumulating information during a trial, non-adaptive designs are typically simpler but less flexible.
  
  
  RESULTS
  We have undertaken a comprehensive review of biomarker-guided adaptive trial designs proposed in the past decade. We have identified eight distinct biomarker-guided adaptive designs and nine variations from 107 studies. Substantial variability has been observed in terms of how trial designs are described and particularly in the terminology used by different authors. We have graphically displayed the current biomarker-guided adaptive trial designs and summarised the characteristics of each design.
  
  
  CONCLUSIONS
  Our in-depth overview provides future researchers with clarity in definition, methodology and terminology for biomarker-guided adaptive trial designs.
authors.affiliation: MRC North West Hub For Trials Methodology Research, Liverpool, United Kingdom.|Department of Biostatistics, Institute of Translational Medicine, University of Liverpool, L69 3GL, Liverpool, United Kingdom.
authors.forename: Miranta
authors.initials: M
authors.lastname: Antoniou
authors.affiliation: MRC North West Hub For Trials Methodology Research, Liverpool, United Kingdom.|Department of Biostatistics, Institute of Translational Medicine, University of Liverpool, L69 3GL, Liverpool, United Kingdom.
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Jorgensen
authors.affiliation: MRC North West Hub For Trials Methodology Research, Liverpool, United Kingdom.|Department of Biostatistics, Institute of Translational Medicine, University of Liverpool, L69 3GL, Liverpool, United Kingdom.
authors.forename: Ruwanthi
authors.initials: R
authors.lastname: Kolamunnage-Dona
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D017322:Clinical Trials, Phase II as Topic / Q000379:methods*; D017326:Clinical Trials, Phase III as Topic / Q000379:methods*; D006801:Humans; D057285:Precision Medicine / Q000379:methods*
chemical_list: D015415:Biomarkers