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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