Clinical chemistry and laboratory medicine最新文献

{"title":"When patient change and interpretive applicability diverge: a two-axis framework for laboratory medicine.","authors":"Ziad Dabour, Kamel Dabour","doi":"10.1515/cclm-2026-1353","DOIUrl":"https://doi.org/10.1515/cclm-2026-1353","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Towards a suitable biomarker for childhood screening for familial hypercholesterolemia: a systematic literature review.","authors":"Vera H de Kleijne, Barbara A Hutten, Anita Boelen, Annet M Bosch, Willemijn E Corpeleijn, Wendy P J den Elzen, René Spijker, Annemieke C Heijboer, Monique Albersen","doi":"10.1515/cclm-2026-0689","DOIUrl":"https://doi.org/10.1515/cclm-2026-0689","url":null,"abstract":"<p><p>Familial hypercholesterolemia (FH) is a common genetic disorder causing elevated low-density lipoprotein cholesterol (LDL-c) concentrations from birth, resulting in a high risk of premature cardiovascular disease. Despite effective early treatment, FH remains underdiagnosed in children, highlighting the need for universal screening. This systematic review aims to evaluate the available evidence regarding suitable biomarkers for the purpose of universal screening for FH in childhood. The electronic databases Medline and Embase were systematically searched for studies comparing blood biomarkers in children with heterozygous FH and non-FH children. Of the 2,488 studies found, 35 were included. Although the data were constrained by considerable heterogeneity, LDL-c, total cholesterol (TC), and apolipoprotein B (ApoB) concentrations were consistently higher in children with FH across the included studies. Furthermore, increased non-high-density lipoprotein cholesterol (non-HDL-c), lathosterol, sitosterol and TC/HDL-c ratio, and a decreased squalene/TC ratio were found in children with FH. Only three screening studies combined biomarker (LDL-c, non-HDL-c and TC) and genetic testing simultaneously, revealing however limited sensitivity and specificity of these markers for FH screening in children. In this review, several biomarkers for FH screening in children were evaluated. As sensitivity and specificity data were generally not available or suboptimal, additional studies are needed to evaluate the screening performance of selected biomarkers in well-defined pediatric populations of suitable age and sex distribution, using valid analytical methods, and taking into account possible confounding factors. It is only through such studies that a well-considered selection of biomarkers can be made for the purpose of childhood screening for FH.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analytical performance and clinical classification value of a novel sandwich immunoassay for total testosterone measurement in low-concentration and hemodialysis populations.","authors":"He Shi, Huimei Wei, Shuaiwei Han, Minjie Liu, Bingjie Shui, Jijuan Gao, Yu Luo, Huaying Zhang, Huiai Lu, Pengcheng Tong, Huan He, Jianguo Wu","doi":"10.1515/cclm-2026-0886","DOIUrl":"10.1515/cclm-2026-0886","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the analytical performance and clinical classification value of a novel sandwich testosterone immunoassay, particularly for biochemical testosterone elevation in women and deficiency in male hemodialysis patients, using LC-MS/MS as the reference method.</p><p><strong>Methods: </strong>A total of 387 residual clinical serum samples were compared using Mindray TESTO, Siemens TSTII, and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Among these, 226 had testosterone concentrations <1.0 ng/mL, and 133 reproductive-age women were evaluated for biochemical hyperandrogenism classification. An additional 119 hemodialysis samples (94 men, 25 women) were assessed, with the 94 men evaluated for biochemical testosterone deficiency classification. Analyses included Passing-Bablok regression, Bland-Altman analysis, and independent imprecision, linearity, and interference studies.</p><p><strong>Results: </strong>The Mindray TESTO assay showed total CVs of 1.68-2.71 % and good linearity (r=0.9997). Cross-reactivity was generally low, although phenylbutazone produced biases exceeding ±10 %. Both immunoassays correlated strongly with LC-MS/MS, with Mindray TESTO showing higher correlation and narrower limits of agreement in low-concentration samples (r=0.9603 vs. 0.8920). In women of reproductive age, Mindray TESTO demonstrated higher sensitivity (88.89 vs. 11.11 %) and κ agreement (0.784 vs. 0.189) for biochemical hyperandrogenism classification. In male hemodialysis patients, it achieved higher accuracy (94.68 vs. 88.30 %) and κ agreement (0.838 vs. 0.680) for biochemical testosterone deficiency classification. The ROC AUCs did not differ significantly (0.966 vs. 0.956; p=0.2776).</p><p><strong>Conclusions: </strong>The novel sandwich immunoassay showed improved agreement with LC-MS/MS at low testosterone concentrations and favorable performance in classifying biochemical testosterone elevation and deficiency.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The second assessment of the commutability of candidate reference materials for the harmonization of blood neurofilament light chain measurements.","authors":"Ulf Andreasson, Vincent Delatour, Aleksandra Maceski, Johan Gobom, Burak Arslan, Elena Camporesi, Chiara Giangrande, Guy Auclair, Sofia Sandgren, Yoav Noam, David Wilson, Matt Polak, Niklas Norgren, Guy Mersch, Martine Dauwe, Sabine Sellner, Anna Liess, George B Sigal, Catherine Demos, Kaj Blennow, Henrik Zetterberg, Jens Kuhle","doi":"10.1515/cclm-2026-1384","DOIUrl":"10.1515/cclm-2026-1384","url":null,"abstract":"<p><strong>Objectives: </strong>Blood neurofilament light (NfL) is a sensitive biomarker of neuroaxonal injury, but substantial differences in absolute concentrations across analytical platforms underscore the need for assay standardization. This study aimed to evaluate the commutability of candidate reference materials (RMs) generated by spiking serum pools with cerebrospinal fluid (CSF) to support global assay harmonization.</p><p><strong>Methods: </strong>The study included 45 individual clinical serum samples and 30 candidate RMs. The RMs comprised three serum pools, each combined with each of three CSF pools at three concentration levels, in addition to the three unspiked serum pools. Commercial NfL measurement procedures (MPs) from six manufacturers (Roche, Fujirebio, Meso Scale Discovery, Bio-Techne, UmanDiagnostics, and Quanterix) were evaluated. Commutability was assessed using a difference in bias approach.</p><p><strong>Results: </strong>Spearman correlations between MPs were excellent (ρ=0.96-0.99), although regression slopes differed substantially, with differences up to a 46-fold. Across the 450 RM assessments, 62 % were classified as commutable, 37 % as indeterminate, and 0.66 % as non-commutable. Approximately two-thirds of the uncertainty in the difference in bias was attributable to MP imprecision rather than sample specific effects, suggesting that standardization of NfL measurements is feasible.</p><p><strong>Conclusions: </strong>Spiking serum pools with CSF appears to be an effective strategy for consistently producing commutable RMs for NfL measurement. Although the relatively high proportion of indeterminate results indicates a need for improved MP precision or additional replicate measurements, the study supports continued development of SI-traceable reference materials to facilitate standardization of NfL measurements in clinical practice.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Urine-derived light chain sequencing enables serum-based MRD monitoring in multiple myeloma.","authors":"Luciano H Di Stefano, Charissa Wijmands, Joannes F M Jacobs, Vincent Bonifay, Caroline Rougé Dubroc","doi":"10.1515/cclm-2026-1061","DOIUrl":"https://doi.org/10.1515/cclm-2026-1061","url":null,"abstract":"","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An LR-based risk stratification framework for assessing interlaboratory variability in HEp-2 IFA pattern interpretation.","authors":"Chaochao Zhang, Yingxin Dai, Dan Cao, Rong Chen, Zhiyuan Gao, Yifan Gong, Anni Guo, Xiaowei Huang, Aiping Liu, Tiantian Liu, Ce Shi, Yi Sun, Wenjuan Wang, Hongkun Wu, Jing Yang, Yiwen Yao, Lei Yu, Ying Zhang, Haiyin Zheng, Kaimin Mao, Min Li, Bing Zheng","doi":"10.1515/cclm-2026-1012","DOIUrl":"https://doi.org/10.1515/cclm-2026-1012","url":null,"abstract":"<p><strong>Objectives: </strong>Interlaboratory variability in HEp-2 indirect immunofluorescence assay (IFA) interpretation remains a major challenge. Conventional agreement metrics quantify disagreement but do not distinguish discrepancies by diagnostic relevance. We aimed to develop a likelihood ratio (LR)-based framework for clinically informed assessment of interpretation variability.</p><p><strong>Methods: </strong>Pattern-specific positive LRs were derived from 33,690 routine HEp-2 IFA records and used to classify patterns into four risk tiers. A pattern discrepancy score (PDS) was developed to quantify discrepancies according to risk-tier displacement. Interlaboratory variability was assessed using a standardized 200-specimen panel tested by 18 laboratories, and diagnostic performance was explored in six laboratories.</p><p><strong>Results: </strong>Pattern disagreement rates ranged from 17.5 to 50.0 %. PDS strongly correlated with disagreement rate (Spearman's ρ=0.936, p<0.001), but laboratories with similar disagreement rates differed in cross-tier discrepancy distribution. Most discrepancies remained within the same risk tier; among discordant interpretations involving high-risk reference patterns, 20.4 % crossed into another tier. Pattern concordance varied markedly, while titer agreement was moderate to almost perfect (weighted κ, 0.569-0.821). Across six laboratories, diagnostic performance varied (Youden Index, 0.391-0.617), but was not significantly associated with interpretation consistency.</p><p><strong>Conclusions: </strong>HEp-2 IFA interpretation variability differs in both frequency and potential diagnostic relevance. The LR-based framework and PDS complement conventional agreement measures by identifying discrepancies that alter diagnostic risk classification, potentially supporting risk-oriented proficiency assessment and targeted quality improvement.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Semen analysis external quality assessment: a paradigm shift from statistical consensus to biological variation-based analytical quality specifications.","authors":"Xiyan Wu, Weina Li","doi":"10.1515/cclm-2026-0896","DOIUrl":"https://doi.org/10.1515/cclm-2026-0896","url":null,"abstract":"<p><p>Semen analysis is the primary diagnostic tool for male fertility evaluation, yet its subjective nature introduces substantial interlaboratory variation that compromises result reliability; despite over three decades of external quality assessment (EQA) practice, coefficients of variation (CV) for core semen parameters remain unacceptably high worldwide. Synthesising evidence from 34 years of global EQA programmes, this review documents interlaboratory CVs of 12.7-138.0 %, 17.0-127.0 %, and 7-375 % for concentration, motility, and morphology, and identifies three structural dilemmas: (1) peer self-referencing bias in assigned value determination, (2) disconnection of allowable total error (TEa) from clinical need, (3) a cognitive threshold effect in morphological interpretation. The principal international schemes - CAP (USA), UK NEQAS, NCCL (China), and QUIP (Germany) - diverge markedly in specimen type, assigned value strategy, and acceptance criteria. We critically evaluate the transition from state-of-the-art to biological variation (BV)-based analytical quality specifications (APS), examine performance differentials between assisted reproductive technology (ART) centres and general clinical laboratories, and assess emerging technologies including AI-assisted morphology assessment and digital EQA platforms. The field is undergoing a paradigm shift from statistical peer consensus toward clinically driven BV-based APS, derived from intra-individual (CV1) and inter-individual (CVG) variation of semen parameters; However, AI systems exhibit systematic analytical bias compared with manual microscopy, which stems from training-set composition, annotator subjectivity, and visual fatigue caused by high-throughput workloads. Independent calibration and version-control validation should be completed prior to clinical application. Priority efforts encompass EQA framework harmonisation aligned with WHO Sixth Edition (2021) and ISO 23162:2021, measurement uncertainty incorporation into TEa derivation, prospective AI algorithm validation, split-sample parallel testing, and disaggregation of morphological APS by defect category (head, midpiece, and tail).</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population-specific pediatric reference intervals for complete blood count in Vietnamese children and their impact on clinical classification.","authors":"Dien Minh Tran, Anh Quynh Mai, Phuc Huu Phan, Tung Viet Cao, Mai Thi Chi Tran, Ronda F Greaves, Tze Ping Loh, Duyen Thi Nguyen","doi":"10.1515/cclm-2026-0766","DOIUrl":"https://doi.org/10.1515/cclm-2026-0766","url":null,"abstract":"<p><strong>Objectives: </strong>To establish age- and sex-specific reference intervals (RI) for complete blood count (CBC) parameters in healthy Vietnamese children aged 0 to <19 years and assess the impact of applying locally derived vs. non-local pediatric RI on abnormal flagging and clinical classification.</p><p><strong>Methods: </strong>A community-based cross-sectional study included 3,885 healthy Vietnamese children aged 0 to <19 years recruited through school-based health screening programs between April 2024 and November 2025. Peripheral venous blood samples were analyzed using the Sysmex XN-9000 hematology analyzer under standardized pre-analytical and analytical conditions with internal and external quality control. Outliers were excluded using the Tukey interquartile range method. Age and sex partitions were established through an integrated assessment of visual inspection, the Mann-Whitney U test, Cliff's delta, the Harris-Boyd method, and biological and clinical considerations. Reference intervals were established according to CLSI EP28-A3c using a nonparametric approach (2.5-97.5th percentiles), with 90 % confidence intervals estimated by bootstrap.</p><p><strong>Results: </strong>All CBC parameters showed age-related variation, supporting age-specific RI. Sex differences were limited to erythrocyte parameters, including red blood cell count, hemoglobin, and hematocrit, emerging after puberty; sex partitioning was unnecessary for most analytes. Application of the Vietnamese vs. CALIPER reference intervals in an outpatient cohort resulted in bidirectional reclassification, with 0.0-32.6 % of CALIPER-abnormal results reclassified as normal and 0.0-24.4 % of CALIPER-normal results reclassified as abnormal, depending on the analyte.</p><p><strong>Conclusions: </strong>This study establishes population-based pediatric CBC RI for Vietnamese children. Non-local pediatric RI may alter abnormal flagging and result interpretation in routine practice.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149080010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Target product profiles in laboratory medicine: a framework for defining test requirements and supporting outcome-based performance specifications.","authors":"Alison F Smith, Paola Cocco, Kile Green, Aisling Ponzo, Kerrie A Davies, Katy Bell, Bethany Shinkins, Mariska Leeflang, Gail Hayward, Mike Messenger","doi":"10.1515/cclm-2026-0956","DOIUrl":"https://doi.org/10.1515/cclm-2026-0956","url":null,"abstract":"<p><p>Despite rapid advances in diagnostics, many tests fail to deliver meaningful clinical or system value because their intended use, performance requirements, and implementation context were not clearly articulated early in development. Target product profiles (TPPs) offer a structured, consensus-based framework to define intended use, outline minimal and desirable performance specifications, and set operational expectations for testing technologies. This paper introduces the topic of TPPs, summarising their purpose, structure, and typical development pathways. We describe a three-phase development process of scoping, drafting, and consensus-building, and use real-world examples to illustrate how evidence, stakeholder input, and contextual constraints shape the specification of performance requirements. We highlight how TPPs can support the shift toward outcome-based performance specifications by providing a transparent mechanism to link test analytical and clinical performance with downstream clinical decision-making, patient outcomes, and system-level impact. We also propose strategies to strengthen the methodological robustness and transparency of TPPs and emphasise the essential role laboratory professionals play in ensuring feasibility and clinical relevance of TPP content. When developed collaboratively, including essential laboratory input, TPPs serve as practical tools that guide upstream test research and design and support ongoing verification, validation and life-cycle management, helping to ensure that tests are clinically meaningful, operationally implementable, and responsive to real-world healthcare needs. Ultimately, the integration of well-designed TPPs into test development pipelines has the potential to accelerate innovation that delivers real clinical value and strengthens the role of laboratory medicine in improving patient outcomes.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Garbage in, (mis)diagnosis out: making laboratory measurement bias visible and actionable across clinical algorithm outputs.","authors":"Niels van Noort, Marith van Schrojenstein Lantman, Mathie P G Leers, Remy J H Martens, Volkher Scharnhorst, Marc H M Thelen, Arjen-Kars Boer","doi":"10.1515/cclm-2026-1156","DOIUrl":"10.1515/cclm-2026-1156","url":null,"abstract":"<p><strong>Objectives: </strong>Clinical algorithms increasingly combine multiple laboratory measurands to support diagnosis, prognosis, and treatment decisions. Yet, measurement bias arising from differences in calibration, reagent lots, or analytical platforms can propagate through such algorithms in non-linear ways, shifting outputs and altering clinical classifications. Existing external quality assessment (EQA) programmes evaluate measurands individually and do not capture the cumulative effect of bias on algorithm behaviour. We present a framework that extends EQA to quantify and communicate the impact of laboratory-specific measurement bias on clinical algorithm outputs.</p><p><strong>Methods: </strong>Bias estimates derived from EQA results are injected into a representative patient cohort and propagated through the algorithm; when clinical outcomes are available, output shifts are translated into changes in clinically interpretable performance characteristics. Measurand-specific what-if analyses estimate the expected benefit of correcting individual bias. The framework is illustrated using the Fibrosis-4 (FIB-4) index and scalability is demonstrated on the ten-input CoLab COVID-19 severity score.</p><p><strong>Results: </strong>Participant-facing reports were developed that summarise deviation from a zero-bias reference, position each laboratory within the peer distribution, and identify which input measurands offer the greatest potential for performance recovery. Applied to FIB-4, the reports demonstrate how laboratories can locate themselves relative to clinically desired performance thresholds and receive actionable, measurand-specific guidance to prioritise corrective efforts.</p><p><strong>Conclusions: </strong>By translating bias-propagation analysis into interpretable laboratory reports, this framework bridges the gap between measurand-level analytical performance and clinical algorithm performance. It supports post-deployment monitoring, cross-laboratory comparability and verification, targeted quality improvement, and is applicable to any transparent formula-based clinical algorithm.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}