Article

Use of Archived Specimens in Evaluation of Prognostic and Predictive Biomarkers

Biometric Research Branch, National Cancer Institute, 9000 Rockville Pike, Bethesda, MD 20892-7434, USA.
CancerSpectrum Knowledge Environment (Impact Factor: 15.16). 10/2009; 101(21):1446-52. DOI: 10.1093/jnci/djp335
Source: PubMed

ABSTRACT The development of tumor biomarkers ready for clinical use is complex. We propose a refined system for biomarker study design,
conduct, analysis, and evaluation that incorporates a hierarchal level of evidence scale for tumor marker studies, including
those using archived specimens. Although fully prospective randomized clinical trials to evaluate the medical utility of a
prognostic or predictive biomarker are the gold standard, such trials are costly, so we discuss more efficient indirect “prospective–retrospective”
designs using archived specimens. In particular, we propose new guidelines that stipulate that 1) adequate amounts of archived
tissue must be available from enough patients from a prospective trial (which for predictive factors should generally be a
randomized design) for analyses to have adequate statistical power and for the patients included in the evaluation to be clearly
representative of the patients in the trial; 2) the test should be analytically and preanalytically validated for use with
archived tissue; 3) the plan for biomarker evaluation should be completely specified in writing before the performance of
biomarker assays on archived tissue and should be focused on evaluation of a single completely defined classifier; and 4)
the results from archived specimens should be validated using specimens from one or more similar, but separate, studies.

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