Technical Report XXIX
Uncertainty Estimation of Diagnostic Accuracy Measures under Parametric Distributions
RA Chatzimichail, T Chatzimichail, AT Hatjimihail
Abstract
Background: Diagnostic accuracy measures (DAMs) are widely used in evaluating diagnostic tests, yet their uncertainty is often underreported or inconsistently quantified, which can bias threshold-based decisions in clinical practice.
Methods: We developed a computational framework to estimate the measurement, sampling, and combined uncertainty of sixteen DAMs for threshold-based screening or diagnostic tests under three measurand distributional models: normal, lognormal, and gamma. Measurement uncertainty is modelled with linear and nonlinear heteroscedastic functions. Uncertainty is propagated using a first-order Taylor-series expansion. Optimality conditions are derived numerically where applicable. The framework has been implemented in the freely available program DiagAccU, in Wolfram Language, allowing parameter specification and estimation and plotting of the DAMs and their uncertainties and confidence intervals (CIs).
Results: We used fasting plasma glucose for diabetes diagnosis as an illustrative case study. At extreme thresholds, ratio-type measures showed widened CIs. Agreement, association, and concordance based indices exhibited comparatively stable behaviour and typically attained interior optima. Confirmatory objectives favoured higher thresholds emphasising specificity, whereas exclusionary objectives favoured lower thresholds emphasising sensitivity. These findings support reporting threshold-wise confidence intervals and aligning cut-off point selection with the intended clinical objective.
Conclusions: This framework offers a novel integrated, diagnostic threshold based approach for estimating uncertainty across a broad spectrum of DAMs, promoting reproducibility and uptake in laboratory medicine and diagnostic research, and directly supporting clinical decision-making for confirmatory diagnosis, diagnosis for exclusion, and triage.
First Published
21/09/2025
Revised
28/09/2025
Citation
Chatzimichail RA, Chatzimichail T, Hatjimihail AT. Uncertainty Estimation of Diagnostic Accuracy Measures under Parametric Distributions. Technical Report XXIX. Hellenic Complex Systems Laboratory; 2025. Available at: https://www.hcsl.com/TR/hcsltr29/hcsltr29.pdf
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