Criteria for Scientific Evaluation of Novel Markers: A Perspective

Reports of novel (bio)markers are abundant in the medical literature. These markers range from simple blood or urine markers to those obtained from, e.g., genomics, proteomics, and imaging techniques; and they vary in accuracy, invasiveness of measurement, and cost. The challenge for clinicians and medical researchers is to optimally exploit existing and new markers or tests. The American Heart Association recently issued a guideline with recommendations for research on prognostic markers for cardiovascular outcomes. I elaborate on various aspects of this guideline, extend it to other types of markers and other clinical domains, and add various recommendations to further guide researchers, practicing physicians and laboratory workers involved in the study, application, or measurement of markers. One can hardly open a medical journal without encountering an article describing a novel (bio)marker or a potential causal or predictive role of an existing marker for a given outcome. A quick Medline search on “biomarker” yielded 466 400 hits, and if the search was restricted to the year 2009, 30 146 hits (through December 31). These markers range from simple blood or urine markers to those obtained from, e.g., genomics, proteomics, and electrophysiology and imaging techniques. They can vary markedly in accuracy, invasiveness of measurement, and cost. Because of liberal guidelines for their introduction, new markers or tests are often presented too early to the medical profession, potentially leading to overuse and, thus, extra burden and costs to patients, the healthcare industry, and the economy. The challenge for clinicians and medical researchers is how to optimally apply existing and new markers/tests; meeting this challenge, however, requires rigorous evaluation of markers and tests. Whereas methods for drug research are well established, a proper framework to quantify the clinical value of (novel) markers or tests is both currently underdeveloped and urgently needed. Recently, Hlatky and colleagues …