title: Omics-based clinical trial designs.
abstract: OBJECTIVE
  The derivation of signatures using -omics technologies is increasingly integrated in the design of clinical trials in oncology. In this review, we investigate the clinical trial designs for the validation of prognostic and predictive signatures.
  
  
  RESULTS
  Using real-life breast cancer trial examples, we highlight the pros and cons of clinical utility designs for prognostic signatures. For predictive signatures, we first review alternative procedures to test the effect of treatment in the overall population as well as in the signature-positive or signature-negative subgroup. We proceed to show why the recent literature on signature-based strategy designs discourages the use of this design. We conclude by discussing adaptive signature designs to identify and validate a signature in a single trial using cross-validation techniques.
  
  
  CONCLUSIONS
  Use of -omics technologies should not be an add-on to clinical trials, it must become an integral part of their design.
authors.affiliation: International Drug Development Institute, Louvain-la-Neuve, Belgium. marc.buyse@iddi.com
authors.forename: Marc
authors.initials: M
authors.lastname: Buyse
authors.forename: Stefan
authors.initials: S
authors.lastname: Michiels
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D002986:Clinical Trials as Topic / Q000379:methods* / Q000592:standards*; D005260:Female; D023281:Genomics / Q000379:methods*; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D040901:Proteomics / Q000379:methods*