title: Problems of variable biomarker evaluation in stratified medicine research--A case study of ERCC1 in non-small-cell lung cancer.
abstract: OBJECTIVE
  Consistency of procedures for the evaluation of a predictive biomarker (including sample collection, processing, assay and scoring system) based on adequate evidence is necessary to implement research findings in clinical practice. As a case study we evaluated how a particular predictive biomarker, ERCC1, was assessed in research on platinum-based chemotherapy in non-small-cell lung cancer and what motivated the choice of procedure.
  
  
  METHODS
  A systematic review of studies completed since 2007 and ongoing was undertaken. Questionnaires on details of ERCC1 evaluation procedures and the rationale for their choice were sent to contacts of identified studies.
  
  
  RESULTS
  Thirty-three studies of platinum-based chemotherapy in non-small-cell lung cancer using ERCC1 were identified. A reply to the questionnaire was received for 16 studies. Procedures for ERCC1 evaluation varied substantially and included reverse transcriptase quantitative polymerase chain reaction (nine studies), immunohistochemistry (five studies) and other methods (multiple methods-two studies, NER polymorphism-one study). In five studies ERCC1 use was planned, but not undertaken. In nine data was insufficient to identify the procedure. For each assay there was variation across studies in the details of the laboratory techniques, scoring systems and methods for obtaining samples.
  
  
  CONCLUSIONS
  We found large variation across studies in ERCC1 evaluation procedures. This will limit the future comparability of results between these different studies. To enable evidence-based clinical practice, consensus is needed on a validated procedure to assess a predictive biomarker in the early phase of research. We believe that ERCC1 is not untypical of biomarkers being investigated for stratified medicine.
authors.affiliation: Cancer Research UK Clinical Trials Unit (CRCTU), MRC Midland Hub for Trials Methodology Research, Institute of Cancer and Genomic Sciences, University of Birmingham, United Kingdom. Electronic address: k.malottki@bham.ac.uk.
authors.forename: Kinga
authors.initials: K
authors.lastname: Malottki
authors.affiliation: Department of Medicine, Royal Marsden Hospital, London SW3 6JJ, United Kingdom.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Popat
authors.affiliation: Institute of Applied Health Research, University of Birmingham, United Kingdom.
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Deeks
authors.affiliation: Research Institute for Primary Care and Health Sciences, Keele University, United Kingdom.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Riley
authors.affiliation: Department of Histopathology, Royal Brompton and Harefield NHS Foundation Trust and National heart and Lung Institute, Imperial College, London, United Kingdom.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Nicholson
authors.affiliation: Cancer Research UK Clinical Trials Unit (CRCTU), MRC Midland Hub for Trials Methodology Research, Institute of Cancer and Genomic Sciences, University of Birmingham, United Kingdom.
authors.forename: Lucinda
authors.initials: L
authors.lastname: Billingham
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry* / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D004720:Endonucleases / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D019317:Evidence-Based Medicine; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry* / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D009944:Organoplatinum Compounds; C071447:ERCC1 protein, human; D004720:Endonucleases
keywords: Antineoplastic therapy; Biological markers; Carcinoma; Clinical trials as topic; Drug therapy; ERCC1 protein; Human; Non-small-cell lung