When patient change and interpretive applicability diverge: a two-axis framework for laboratory medicine

Abstract Personalised laboratory medicine has advanced through reference change values, personalised reference intervals and decision limits, multivariate reference models, and indication-aware interpretation. Yet these developments do not resolve a distinct problem: evidence of within-person change and evidence supporting the applicability of an interpretive system answer different clinical questions and may diverge. We propose a two-axis reporting framework that keeps these evidentiary objects separate. After confirming adequate measurement integrity and comparability, Axis D (deviation) represents evidence of meaningful deviation from the patient’s own expected state, while Axis A (applicability) represents the evidentiary warrant for applying a reference system, decision limit, prediction rule, equation, or algorithm to that patient and setting. The distinctive proposition is the coupling rule: applicability determines whether an interpreter can support diagnostic closure of the question a change signal opens, so that in the High D/Low A state – change–applicability discordance – a meaningful patient-specific change should not be neutralised by reassurance from an interpreter whose applicability is weakly supported; instead, independent or better-applicable evidence should be considered in proportion to clinical risk. The motivation parallels precision dosing, where appropriateness depends on patient characteristics. This is not a new diagnostic score; it is a reporting and decision scaffold whose value should be tested and rejected if it fails to improve decision quality or net clinical benefit. Existing frameworks help clinicians choose, personalise, validate, and contextualise the interpreter; the two-axis framework addresses what to do when evidence about the patient and evidence about the interpreter disagree.