pathway from disease biomarker discovery to clinical test; the underdeveloped and inconsistent standards of evidence to assess biomarker validity; the heterogeneity of patients with a given diagnosis; and the lack of appropriate study designs and analytical methods for these analyses (IOM, 2007). Some also have questioned the excitement afforded omics-based discoveries, suggesting that advancements will have primarily modest effects in patient care (Burke and Psaty, 2007).

Nevertheless, patients themselves recognize the promise of molecularly driven medicine and are looking to the scientific community to provide validated, reliable clinical tests that accurately measure and predict response to treatment and provide more effective ways of screening for disease. Among scientists and clinicians, omics-based tests are seen as presenting opportunities for important new clinical trial design strategies and hopefully reducing the time and cost of developing new treatments (Macconaill and Garraway, 2010).

ORIGIN OF THE TASK

As is true in all areas of scientific research, rigorous standards must be applied to assess the validity of any study results, particularly if the study involves patients. Recently, the scientific community raised serious concerns about several omics-based tests developed to predict sensitivity to chemotherapeutic agents, developed by investigators at Duke University. The initial papers describing these omics-based tests garnered extensive attention because results suggested a potential major advance in the discovery and use of omics-based tests to direct choice of therapy for individual cancer patients. Almost from the time of initial publication, however, concerns were raised about the validity of these gene expression–based tests; Keith Baggerly and Kevin Coombes of MD Anderson Cancer Center first approached the Duke University principal investigators, Anil Potti and Joseph Nevins, with questions on November 8, 2006 (Baggerly, 2011), soon after the October 22 electronic publication of the article (PubMed, 2006). Clinical investigators at their institution were interested in using the methods, but the statisticians could not reproduce the results with the publicly available data and information. These concerns were heightened upon the publication of an article by Baggerly and Coombes (2009), detailing several errors in the development of the tests, inconsistencies between primary data and data used in the articles, and the inability to reproduce results reported by the investigators. In addition, in July 2010, a letter to the director of the National Cancer Institute (NCI) signed by a group of more than 30 respected statisticians and bioinformatics scientists brought additional scrutiny to these concerns, especially because these omics-based tests were being used in clinical trials to direct patient care (Baron et al., 2010).



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