Simon RM, Paik S, Hayes DFUse of archived specimens in evaluation of prognostic and predictive biomarkers. J Natl Cancer Inst 101: 1446-1452

Biometric Research Branch, National Cancer Institute, 9000 Rockville Pike, Bethesda, MD 20892-7434, USA.
Journal of the National Cancer Institute (Impact Factor: 12.58). 10/2009; 101(21):1446-52. DOI: 10.1093/jnci/djp335
Source: PubMed


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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Available from: Richard Simon, Sep 17, 2014
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    • "Assessment of study risk of bias. An assessment of the methodological quality of the studies included in meta-analyses was based on guidance for the evaluation of the conduct of biomarker studies that use archived tumour specimens (Simon et al, 2009; Patterson et al, 2011). For each included pharmacogenomic substudy of a RCT, four domains were used to assess the risk of bias (high, moderate, or low): (1) biomarker sample ascertainment, (2) assay analytical performance, (3) prespecified analysis plan, and (4) parent RCT. "
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    • "Validated molecular biomarkers that provide objective measures of tumor biology and improve risk stratification are needed [4] [5]. Clinical adoption of biomarkers requires that they (1) be analytically validated to provide robust, reproducible results; (2) be validated to predict clinically relevant end points; and (3) offer equivalent performance across a spectrum of disease including race and age [6] [7] [8]. "
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    • "Clinical data for biomarker development can come from retrospective or prospective clinical trials.23 Retrospective trial analysis requires that adequate biomarker specimens were collected in most of the study patients and analyzed according to a prespecified plan.24 The advantages of retrospective analysis include availability of adequate follow-up, the inclusion of patients with biomarker-positive and biomarker-negative cancers in the data set, and a cost savings over conducting an additional prospective trial. "
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