Biomarkers in clinical practice: opportunities and challenges

Paul E. Rapp, Ph.D.; Adele M. K. Gilpin, Ph.D., J.D.

Published 31 January 2025

Citation Rapp, P. E. and Gilpin, A. M. K., 2025. Biomarkers in clinical practice: opportunities and challenges. Medical Research Archives, 10(1).

Abstract

Many proposed biomarkers fail to produce clinically actionable results. Simply put, the research problem addressed here is: why do most biomarker projects fail? In this contribution we describe four commonly encountered problems and offer solutions that address these challenges.

Keywords

• Biomarkers
• Clinical practice
• Research challenges
• Opportunities

I. Introduction

The use of biomarkers in clinical practice presents extraordinarily complex challenges. In this contribution we describe several issues that must be addressed in the biomarker discovery process. What follows is not a comprehensive review of the literature but rather is based on clinical observation with supporting evidence from the referred literature. In the current literature the term “biomarker” is often used casually. This is changing. In the United States the FDA-NIH (Food and Drug Administration – National Institutes of Health) Biomarker Working Group provided a definition of a biomarker: “A biomarker is characterized as an objective measure of disease or treatment response.” This definition is important because it provides a framework for understanding the complexities of biomarkers.

II. Model selection and validation

Model selection and validation can often be improved by incorporating more variables into a model. For example, at the initial stage of EEG analysis, the selection of features can be critical. The model must be validated using independent datasets to ensure that it generalizes well.

III. Challenges in biomarker identification

There are several reasons that can explain the failure of a candidate monitoring biomarker to track clinical status. The first, and possibly most common, is that the original identification as a biomarker was flawed. Sample sizes in clinical studies can result in false positive identifications of biomarkers. Hajcak, et al. (2012) directed attention to another possibility. It is possible that the biomarker fails to capture the underlying pathology, leading to misleading conclusions.

IV. Paths forward

Systematic implementation of data sharing, software sharing and preregistration will not come easily or quickly to the biomedical research community. We nonetheless suggest that the path forward in biomarker discovery will not only require scientific advances but also cultural change.

V. Conclusion

In conclusion, the challenges ahead for biomarker studies have been published. The magnitude of the challenges ahead should not be underestimated; thus, conversely, the magnitude of the opportunity should not be underestimated.

References

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