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Review
. 2022 Mar 6:5:100151.
doi: 10.1016/j.jtauto.2022.100151. eCollection 2022.

Rational development and application of biomarkers in the field of autoimmunity: A conceptual framework guiding clinicians and researchers

Mirjam Kolev  1 , Michael P Horn  2 , Nasser Semmo  1 , Michael Nagler  2
Affiliations
Review

Rational development and application of biomarkers in the field of autoimmunity: A conceptual framework guiding clinicians and researchers

Mirjam Kolev et al. J Transl Autoimmun. .

Abstract

Clear guidance is needed in the development and implementation of laboratory biomarkers in medicine. So far, no standardized phased approach is established that would pilot researchers and clinicians in this process. This leads to often incompletely validated biomarkers, which can bear the consequence of wrong applications, misinterpretation and inadequate management in the clinical context. In this conceptual article, we describe a stepwise approach to develop and comprehensively validate laboratory biomarkers. We will delineate basic steps including technical performance, pre-analytical issues, and biological variation, as well as advanced aspects of biomarker utility comprising interpretability, diagnostic and prognostic accuracy, and health-care outcomes. These aspects will be illustrated by using well-known examples from the field of immunology. The application of this conceptual framework will guide researchers in conducting meaningful projects to develop and evaluate biomarkers for the use in clinical practice. Furthermore, clinicians will be able to adequately interpret pre-clinical and clinical diagnostic literature and rationally apply biomarkers in clinical practice. Improvement in the implementation and application of biomarkers might relevantly change the management and outcomes of our patients for the better.

Keywords: Biomarkers; Diagnostic techniques and procedures; Diagnostic test approval; Laboratories / standards; Predictive value of tests; Sensitivity and specificity.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Laboratory testing answers diagnostic questions by changing the pre-test probability of a disease (e.g., the prevalence in a particular setting) into a post-test probability that supports clinical decision-making. Ideally, a certain disease can be ruled-in or ruled-out without further testing. Likewise, laboratory testing can answer prognostic questions or facilitate monitoring. The utility of laboratory tests to answer clinical questions strongly depends on the diagnostic accuracy in real-life clinical settings.
Fig. 2
Fig. 2
A conceptual framework for the development and implementation of laboratory tests. Adapted from Nagler M, Hämostaseologie 2020.
See this image and copyright information in PMC

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References

    1. Moons K.G. Criteria for scientific evaluation of novel markers: a perspective. Clin. Chem. 2010;56(4):537–541. - PubMed
    1. Knottnerus J.A., van Weel C., Muris J.W. Evaluation of diagnostic procedures. BMJ. 2002;324(7335):477–480. - PMC - PubMed
    1. Nagler M. Translating laboratory tests into clinical practice: a conceptual framework. Hämostaseologie. 2020;40(4):420–429. - PubMed
    1. Lijmer J.G., Leeflang M., Bossuyt P.M. Proposals for a phased evaluation of medical tests. Med. Decis. Making. 2009;29(5):E13–E21. - PubMed
    1. Price C.P., Christenson R.H. second ed. AACC Press; Washington, DC: 2007. Evidence-based Laboratory Medicine: Principles, Practice, and Outcomes.