title: Critical review of published microarray studies for cancer outcome and guidelines on statistical analysis and reporting.
abstract: BACKGROUND
  Both the validity and the reproducibility of microarray-based clinical research have been challenged. There is a need for critical review of the statistical analysis and reporting in published microarray studies that focus on cancer-related clinical outcomes.
  
  
  METHODS
  Studies published through 2004 in which microarray-based gene expression profiles were analyzed for their relation to a clinical cancer outcome were identified through a Medline search followed by hand screening of abstracts and full text articles. Studies that were eligible for our analysis addressed one or more outcomes that were either an event occurring during follow-up, such as death or relapse, or a therapeutic response. We recorded descriptive characteristics for all the selected studies. A critical review of outcome-related statistical analyses was undertaken for the articles published in 2004.
  
  
  RESULTS
  Ninety studies were identified, and their descriptive characteristics are presented. Sixty-eight (76%) were published in journals of impact factor greater than 6. A detailed account of the 42 studies (47%) published in 2004 is reported. Twenty-one (50%) of them contained at least one of the following three basic flaws: 1) in outcome-related gene finding, an unstated, unclear, or inadequate control for multiple testing; 2) in class discovery, a spurious claim of correlation between clusters and clinical outcome, made after clustering samples using a selection of outcome-related differentially expressed genes; or 3) in supervised prediction, a biased estimation of the prediction accuracy through an incorrect cross-validation procedure.
  
  
  CONCLUSIONS
  The most common and serious mistakes and misunderstandings recorded in published studies are described and illustrated. Based on this analysis, a proposal of guidelines for statistical analysis and reporting for clinical microarray studies, presented as a checklist of "Do's and Don'ts," is provided.
authors.affiliation: Biometric Research Branch, Division of Cancer Treatment and Diagnosis, National Cancer Institute, 9000 Rockville Pike, Bethesda, MD 20892, USA.
authors.forename: Alain
authors.initials: A
authors.lastname: Dupuy
authors.forename: Richard M
authors.initials: RM
authors.lastname: Simon
mesh_terms: D015982:Bias; D016000:Cluster Analysis; D003627:Data Interpretation, Statistical; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008499:Medical Records / Q000592:standards*; D009369:Neoplasms / Q000235:genetics / Q000628:therapy; D020411:Oligonucleotide Array Sequence Analysis / Q000592:standards*; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D016896:Treatment Outcome