Scientific Publications by FDA Staff

Clin Trials 2013 Oct;10(5):666-76

Analytical and clinical evaluation of biomarkers assays: When are biomarkers ready for prime time?

Pennello GA

BACKGROUND: Biomarker assays can be evaluated for analytical performance (ability of assay to measure the biomarker quantity) and clinical performance (ability of assay result to inform of the clinical condition of interest). Additionally, a biomarker assay is said to have clinical utility if it ultimately improves patient outcomes when used as intended. PURPOSE: This article reviews analytical and clinical performance studies of biomarker assay tests and also some designs of clinical utility studies. RESULTS: Appropriate design and statistical analysis of analytical and clinical evaluation studies depend on the intended clinical use of the test. Some key aspects to valid performance studies include using subjects who are independent of those used to develop the test, masking users of the test to any other available test or reference results, and including in the primary statistical analysis subjects with unavailable results in an intention-to-diagnose analysis. Ingenuity in study design and analysis may be required for efficient and unbiased estimation of performance. LIMITATIONS: Performance studies need to be carefully planned as they can be prone to many sources of bias. Analytical inaccuracy can hamper the clinical performance of biomarkers. CONCLUSIONS: As biomedical research and technology advance, challenges in study design and statistical analysis will continue to emerge for analytical and clinical performance studies of biomarker assays. Although not emphasized in some circles, the analytical performance of a biomarker assay is important to characterize. Analytical performance studies have many study design and statistical analysis challenges that deserve further attention.