Use of archived specimens in evaluation of prognostic and predictive biomarkers

J Natl Cancer Inst. 2009 Nov 4;101(21):1446-52. doi: 10.1093/jnci/djp335. Epub 2009 Oct 8.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacology
  • Biomarkers, Tumor / analysis*
  • Evidence-Based Medicine
  • Humans
  • Practice Guidelines as Topic
  • Predictive Value of Tests
  • Prognosis*
  • Prospective Studies*
  • Randomized Controlled Trials as Topic*
  • Research Design*
  • Retrospective Studies*
  • Selection Bias
  • Tissue Banks*


  • Antineoplastic Agents
  • Biomarkers, Tumor