Ramachandran, S, Konig, C, Hackett, G, Livingston, M and Strange, RC (2018) Managing Clinical Heterogeneity: An Argument for Benefit-Based Action Limits. Journal of Engineering in Medical Diagnostics and Therapy, 1 (3). ISSN 2572-7966

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The use of reference ranges is well established in medical practice and research. Classically, a range would be derived from the local healthy population and matched in age, gender, and other characteristics to the patients under investigation. However, recruiting suitable controls is problematic and the derivation of the range by excluding 2.5% at each end of the distribution results in 5% of the values being arbitrarily discarded. Thus, the traditional reference range is derived using statistical and not clinical principles. While these considerations are recognized by clinicians, it is often not realized that the application of whole population derived reference ranges to complex pathologies that comprise patient subgroups may be problematic. Such subgroups may be identified by phenotypes including genetic etiology, variations in exposure to a causative agent, and tumor site. In this review, we provide examples of how subgroups can be identified in diverse pathologies and how better management can be achieved using evidence-based action limits rather than reference ranges. We give examples from our clinical experience of problems arising from using the wrong reference ranges for the clinical situation. Identifying subgroups will often enable clinicians to derive specific action limits for treatment that will lead to customized management and researchers a route into the study of complex pathologies.

Item Type: Article
Additional Information: The final published version is available online at http://medicaldiagnostics.asmedigitalcollection.asme.org/article.aspx?articleid=2675183
Uncontrolled Keywords: laboratory results, heterogeneity, reference ranges, action limits, evidencebased medicine, lipid lowering therapy, testosterone replacement therapy
Subjects: R Medicine > R Medicine (General)
Divisions: Faculty of Medicine and Health Sciences > Institute for Science and Technology in Medicine
Depositing User: Symplectic
Date Deposited: 13 Apr 2018 13:43
Last Modified: 12 Apr 2019 01:30
URI: https://eprints.keele.ac.uk/id/eprint/4749

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