Commentary For reprint orders, please contact: reprints@futuremedicine.com Commentary: measurement of biomarkers in medicine Jens P Goetze* ,1 , Lasse H Hansen 1 , Dijana Terzic 1 , Peter D Mark 1 , Nicolai J Wewer Albrechtsen 1 , Plomgaard Peter 1 & Jens F Rehfeld 1 1 Department of Clinical Biochemistry, Faculty of Health & Medical Sciences, University of Copenhagen, Copenhagen, Denmark *Author for correspondence: Tel.: +45 3545 2202; Fax: +45 3545 2880; JPG@dadlnet.dk “ After all, quantitation is the language in science; the experiment our scientific argument ” First draft submitted: 18 June 2018; Accepted for publication: 21 June 2018; Published online: 25 July 2018 Keywords: chromogranin A • gastrin • immunoassay • measurement • natriuretic peptide Immunoassays are decisive methods for measuring a multitude of blood-borne biomarkers. Today, biomarkers are considered a necessity in the move toward personalized medicine, as we need to know about individual measures prior to practicing individualized treatment. Some biomarkers are easy to quantitate; age and gender are still the two most prominent phenotypes with important clinical information. But other measures may also need to be pursued before we turn to blood-borne biomarkers. In the case of essential hypertension, for instance, it is a well-established fact that African–American people have a considerably higher risk of developing hypertension, which is largely based on genetics. But here, a simple phenotype can increase the medical attention to the problem. Nevertheless, laboratory biomarkers are closely connected to a future with personalized medicine: not only for diagnosis, but also to monitor the treatment effect. In this regard, it is no wonder that the pharmaceutical industry often associates biomarker measurement to drug therapy. However, before a biomarker is released for clinical use, a thorough phase of translational research is needed. During such phase, the methods for measuring biomarkers in plasma heavily rely on commercial assay kits, often in the form of an ELISA or RIA. In our experience, these methods often come with little or no validation information besides a simple imprecision profile. Therefore, we here provide some handpicked and practical guidelines to users of commercial assay kits, where there is a dire need for scientific scrutiny and skepticism. This will help to avoid time-consuming mismeasurement and, at worst, wrong conclusions. We will use peptide measurement as the general example, but the different issues are also relevant for other biochemical substances. The first point concerns the frequently used term ‘for research use only’. While this claim has the comfortable consequence that manufacturers cannot be held legally liable, it is not meaningful that the methods can be used for research only. Research is the base for future clinical behavior and the methods should be evaluated equally. As an example, we earlier tested different immunoassays for measuring the gut hormone gastrin [1,2], many of which came with the claim ‘for research use only’. After validation, however, we could show that several methods did not measure gastrin accurately. Given that gastrin measurement today is used as a biomarker of malignant tumor disease, applying such methodology in oncological research would entail wrong and misleading results. Thus, we suggest that users of commercial immunoassay kits seriously challenge the manufacturer. Why is the method only for research, which often equals clinical research? What would it take for the company not to use the clause – or is the user expected to provide this key set of experiments? And what if an assay is unreliable: will the company then step in or just keep selling the reagents? A second major pitfall is specificity. Some manufacturers provide some information of potential cross-reactivity, where they may have tested measurement of other peptides. However, they often test for cross-reactivity against components, where cross-reactivity is not likely, typically against other peptides having entirely different sequences and structures. To ensure specificity, the manufacturer should rather provide different types of experiments, for instance classical spiking experiments with the purified or synthetic component in question (Figure 1). Even better, chromatographic examination of plasma is a simple and informative method to visualize whether the assay measures Biomark. Med. (Epub ahead of print) ISSN 1752-0363 10.2217/bmm-2018-0210 C  2018 Future Medicine Ltd