{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T18:55:34Z","timestamp":1792522534535,"version":"4.5.0"},"reference-count":18,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Calculated tests propagate component analytical errors, yet laboratories monitor only the measured components, rarely the calculated quantity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using analytical performance specifications (APSs) from the European Federation of Clinical Chemistry and Laboratory Medicine Biological Variation Database, we propagated bias and imprecision through 5 calculated tests (low-density lipoprotein cholesterol [LDL-C], anion gap, albumin-corrected calcium, the Homeostatic Model Assessment of Insulin Resistance [HOMA-IR], and the De Ritis ratio), representing difference, linear correction, product, and ratio structures. Difference-based and linear-based tests were assessed across clinical scenarios; the ratio was validated by Monte Carlo simulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>At desirable component APSs, the combined total error was 2.1% to 2.8% for albumin-corrected calcium, 25.9% for the De Ritis ratio, and 34% for the HOMA-IR. At typical values, combined errors for LDL-C and the anion gap were 18.5% and 20.8%, respectively, exceeding their respective allowable total error targets (12.0% and 11.3%). Error was concentration dependent: the anion-gap error decreased to 7.4% at 28\u2009mmol\/L but increased to 43.0% at 6\u2009mmol\/L; the LDL-C error reached 28.6% at 60\u2009mg\/dL. The allowable total error\u2013based estimate closely matched the quadrature-bias estimate but underestimated worst-case error.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Acceptable component performance does not ensure acceptable performance of calculated tests. Derived quantities require specific APSs, and results near clinical decision limits should be interpreted within concentration-dependent analytical gray zones.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/labmed\/lmag068","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T11:20:42Z","timestamp":1788520842000},"source":"Crossref","is-referenced-by-count":1,"title":["Combined total error in calculated clinical chemistry tests: component analytical error is magnified and decision threshold gray zones widen"],"prefix":"10.1093","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4453-6339","authenticated-orcid":false,"given":"Alper","family":"G\u00fcm\u00fc\u015f","sequence":"first","affiliation":[{"name":"Medical Biochemistry Laboratory, University of Health Sciences T\u00fcrkiye, Istanbul Ba\u015fak\u015fehir \u00c7am and Sakura City Hospital Health Application and Research Center, Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"2026092311472109700_lmag068-B1","volume-title":"Evaluation of Measurement Data\u2014Guide to the Expression of Uncertainty in Measurement (GUM).","author":"JCGM 100:2008","year":"2008"},{"key":"2026092311472109700_lmag068-B2","volume-title":"Medical Laboratories\u2014Practical Guidance for the Estimation of Measurement Uncertainty","author":"ISO\/TS 20914:2019","year":"2019"},{"key":"2026092311472109700_lmag068-B3","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1093\/clinchem\/20.7.825","article-title":"Criteria for judging precision and accuracy in method development and evaluation","volume":"20","author":"Westgard","year":"1974","journal-title":"Clin Chem"},{"key":"2026092311472109700_lmag068-B4","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1515\/cclm-2015-0997","article-title":"Total error vs. measurement uncertainty: revolution or evolution?","volume":"54","author":"Oosterhuis","year":"2016","journal-title":"Clin Chem Lab Med"},{"key":"2026092311472109700_lmag068-B5","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1016\/j.clinbiochem.2006.12.014","article-title":"Error propagation in calculated ratios","volume":"40","author":"Holmes","year":"2007","journal-title":"Clin Biochem"},{"key":"2026092311472109700_lmag068-B6","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1093\/clinchem\/18.6.499","article-title":"Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge","volume":"18","author":"Friedewald","year":"1972","journal-title":"Clin Chem"},{"key":"2026092311472109700_lmag068-B7","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1007\/s00125-013-3121-8","article-title":"HOMA and Matsuda indices of insulin sensitivity: poor correlation with minimal model-based estimates of insulin sensitivity in longitudinal settings","volume":"57","author":"Xiang","year":"2014","journal-title":"Diabetologia"},{"key":"2026092311472109700_lmag068-B8","first-page":"131","article-title":"Calculated chemistry parameters\u2014do they need to be harmonised?","volume":"37","author":"Hughes","year":"2016","journal-title":"Clin Biochem Rev"},{"key":"2026092311472109700_lmag068-B9","author":"Aarsand","year":"2026"},{"key":"2026092311472109700_lmag068-B10","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1515\/cclm-2015-0067","article-title":"Defining analytical performance specifications: consensus statement from the 1st Strategic Conference of the European Federation of Clinical Chemistry and Laboratory Medicine","volume":"53","author":"Sandberg","year":"2015","journal-title":"Clin Chem Lab Med"},{"key":"2026092311472109700_lmag068-B11","volume-title":"Biological Variation: From Principles to Practice","author":"Fraser","year":"2001"},{"key":"2026092311472109700_lmag068-B12","volume-title":"Evaluation of Measurement Data\u2014Supplement 1 to the GUM\u2014Propagation of Distributions Using a Monte Carlo Method","author":"JCGM 101:2008","year":"2008"},{"key":"2026092311472109700_lmag068-B13","doi-asserted-by":"publisher","first-page":"1414","DOI":"10.1093\/clinchem\/41.10.1414","article-title":"National Cholesterol Education Program Working Group on Lipoprotein Measurement. 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