Taking a new biomarker into routine use – A perspective from the routine clinical biochemistry laboratory

Abstract

There is increasing pressure to provide cost-effective healthcare based on “best practice.” Consequently, new biomarkers are only likely to be introduced into routine clinical biochemistry departments if they are supported by a strong evidence base and if the results will improve patient management and outcome. This requires convincing evidence of the benefits of introducing the new test, ideally reflected in fewer hospital admissions, fewer additional investigations and/or fewer clinic visits. Carefully designed audit and cost-benefit studies in relevant patient groups must demonstrate that introducing the biomarker delivers an improved and more effective clinical pathway. From the laboratory perspective, pre-analytical requirements must be thoroughly investigated at an early stage. Good stability of the biomarker in relevant physiological matrices is essential to avoid the need for special processing. Absence of specific timing requirements for sampling and knowledge of the effect of medications that might be used to treat the patients in whom the biomarker will be measured is also highly desirable. Analytically, automation is essential in modern high-throughput clinical laboratories. Assays must therefore be robust, fulfilling standard requirements for linearity on dilution, precision and reproducibility, both within- and between-run. Provision of measurements by a limited number of specialized reference laboratories may be most appropriate, especially when a new biomarker is first introduced into routine practice.

Design of Tumor Biomarker–Monitoring Trials: A Proposal by the European Group on Tumor Markers

“…To reinforce points we have made earlier in this article and other authors have noted (20,30 ), however, we note that there is substantial potential for bias in phase II studies. This conclusion is illustrated by results from a prospective randomized clinical trial in which outcomes for clinically disease-free ovarian cancer patients monitored routinely with CA125 were compared with patients who were not so monitored (31 ).…”

“…An estimate of the inherent within-individual biological variation (19 ), along with a realistic estimate of the analytical imprecision (20 ), is an essential prerequisite for assessing the clinical importance of observed changes in biomarker concentration. Data on biological variation can be derived from populations of healthy individuals, patients who have undergone curative surgery and are apparently disease free, patients with advanced but stable disease, or patients with benign disease (19 ); data involving many biomarkers are tabulated separately (21 ).…”

“…For example, if the samples are obtained from a biobank, individual samples from the same patient should be analyzed in separate runs, as would occur in routine practice. Rigorous quality-assurance procedures for the biobankincluding its organization, management, and procedures for sample handling (e.g., time interval from sampling to analysis, storage conditions, number of freeze-thaw cycles), as well as comprehensive clinical data relating to the specimens themselves-must be in place, of course, and be documented appropriately (16,20 ).…”

“…This recommendation is based on a metaanalysis demonstrating that only monitoring studies that included carcinoembryonic antigen had a significant impact on survival. Introduction of a new biomarker should be considered only if its performance is superior to that of the diagnostic tests (imaging, biochemistry, and so forth) it is replacing or supplementing (e.g., because it is less invasive, more convenient, and/or less costly) (20 ).…”

Commercialized biomarkers: new horizons in prostate cancer diagnostics

“…Successfully translating a biomarker into routine clinical use requires a collaborative effort between the research laboratory and diagnostic industry (who develop and translate a concept onto a practical reliable tool), the clinicians (who identify the unanswered clinical questions) and the clinical laboratory (which evaluates the tool in real-life practice) [84]. Rigorous validation steps should be followed to confirm clinical utility of a new test in prospective studies on large multicentre cohorts.…”