When Laboratory Tests Can Mislead Even When They Appear Plausible
Open accessAbstract
ABSTRACT A laboratory test has three phases, pre-analytical, analytical and post-analytical. The purpose of this review is to highlight an issue concerning the analytical phase of one of the most widely deployed groups of in vitro diagnostic tests using a common technology – namely immunoassay. Immunoassay entails an inherently high error rate and, therefore, has the potential for inaccurate and misleading results susceptible to misinterpretation and/or diagnostic misapplication by clinicians. An approach based on Bayesian inference (without mathematics or equations) – illustrated by examples – is presented; this may help clinicians in discerning potentially erroneous results even when they appear plausible and not unreasonable. Essentially, false positive results are most likely to occur when the disease prevalence/incidence is low. False negative results become more prominent when the prevalence/incidence of disease increases. When concern is raised, available follow-up laboratory tests should be initiated to establish with confidence the diagnostic reliability or unreliability of such results.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Both types of errors undermine the reliability of diagnostic tests for patients and clinicians, reducing overall trust in the diagnostic process.
“Both types of errors undermine the reliability of diagnostic tests for patients and clinicians, reducing overall trust in the diagnostic process [193].”
From Toward Safer Diagnoses: A SEIPS-Based Narrative Review of Diagnostic Errors (2026) · cites this paper as [193]
The Immunoassays section explains that false positives can prompt unnecessary intervention, while false negatives can deny patients needed treatment. The Abstract also describes immunoassay results as potentially inaccurate and misleading. The paper does not say that these errors reduce patients’ or clinicians’ overall trust in the diagnostic process, and its discussion concerns immunoassays rather than diagnostic tests generally. (LLM, conf=0.84)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 19 · Cited by 33
Research works printed but not linked: 19
- Ismail AAA. Identifying and reducing potentially wrong immuno- assay results even when plausible and "not-unreasonable" . Adv Clin Chem 2014 ; 66 : 241 -93 .
- Bjerner J , BØmer OP , Nustad K . The war on heterophilic antibody interference . Clin Chem 2005 ; 51 : 9 -11 .
- Rotmensch S , Cole LA . False diagnosis and needless therapy of presumed malignant disease in women with false-positive human chorionic gonadotropin concentrations . Lancet 2000 ; 355 : 712-5 .
- Mills F , Jeffery J , Mackenzie A , Cranfield A , Ayling RM . An immuno- globulin G complexed form of thyroid stimulating hormone (macro thyroid-stimulating hormone) is a cause of elevated serum thyroid- stimulating hormone concentration . Ann Clin Biochem 2013 ; 50 : 416 -20 .
- Saiegh L , Odeh M , Elias L et al . A possible analytical and clinical role of endogenous antibodies causing discrepant adrenocortico- tropic hormone measurement in a case of ectopic Cushing's syn- drome . Ann Clin Biochem 2014 ; 51 : 490 -4 .
- Plebani M , Mion M , Altinier et al . False positive troponin I attrib- uted to a macrocomplex . Clin Chem 2002 ; 48 : 677 -8 .
- Norden AGW , Jackson RA , Norden LE et al . Misleading results from immunoassays of serum free thyroxine in the presence of rheumatoid factor . Clin Chem 1997 ; 43 : 957 -62 .
- Bolland MJ , Chiu WW , Davidson JS , Croxson MS . Heterophilic antibodies may cause falsely lowered serum cortisol values . J Endocrinol Invest 2005 ; 28 : 643 -5 .
- Ross HA , Menheere PPCA , Thomas CMG et al . Interference from heterophilic antibodies in seven current TSH assays . Ann Clin Biochem 2008 ; 45 : 616 -8 .
- Surks MI , Ortiz E , Daniels GH et al . Subclinical thyroid disease: Scientific review and guidelines for diagnosis and management . JAMA 2004 ; 291 : 228 -38 .
- Weetman AP . Fortnightly review. Hypothyroidism: screening and subclinical disease . BMJ 1997 ; 314 : 1175 -7 .
- Monzani F , Dardano A , Caraccio N . Does treating subclinical hypothyroidism improve markers of cardiovascular risk? Treat Endocrinol 2006 ; 5 : 65 -81 .
- Carlton E , Greenslade J , Cullen L et al . Evaluation of high-sensitivity cardiac troponin I levels in patients with suspected acute coronary syndrome . JAMA Cardiol 2016 ; 1 : 405 -12 .
- Choy KW , Teng J , Wijeratne N , Tan CY , Doery JCG . Immunoassay interference complicating management of Cushing's disease: the onus is on the clinician and the laboratory . Ann Clin Biochem 2017 ; 54 : 183 -4 .
- Ismail AAA , Walker PL , Barth JH et al . Wrong biochemistry results: two case reports and observational study in 5310 patients on potentially misleading thyroid stimulating hormone and gonado- tropins immunoassay results . Clin Chem 2002 ; 48 : 2023 -29 .
- Legendre-Bazydlo LA , Haverstick DM , Kennedy JLW , Dent JM , Burns DE . Persistent increase in cardiac troponin I in plasma without evidence of cardiac injury . Clin Chem 2010 ; 56 : 702 -5 .
- Bohner J , von Pape KW , Hannes W , Stegmann T . False negative immunoassay results from cardiac troponin I probably due to cir- culating troponin I autoantibodies . Clin Chem 1996 ; 42 : 2046 -7 .
- Eriksson S , Halenius H , Pulkki K , Hellman J , Petterson K . Negative interference in cardiac troponin I immunoassays by circulating tro- ponin autoantibodies . Clin Chem 2005 ; 51 : 839 -17 .
- Wang H , Bi X , Xu L , Li Y . Negative interference by rheumatoid factor in alpha-fetoprotein chemiluminescent microparticle immunoassay . Ann Clin Biochem 2017 ; 54 : 55 -9 .
- Authors
- Ismail, A. A.
- Corresponding author
- Ismail, Adel AA
- ORCID
- Ismail, Adel AA
- Venue
- Clinical Medicine
- Publisher
- Elsevier BV
- Published
- 2017-08
- Volume
- 17
- Issue
- 4
- Pages
- 329-332
- ISSN
- 1470-2118 (ISSN-L)
- PMC
- PMC6297641
- OpenAlex
- W2741825985
- Cited by
- 33
- References
- 19
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 9 · 2023: 2 · 2022: 1 · 2021: 4 · 2020: 3 · 2019: 2
- FWCI
- 1.01
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Clinical Medicine (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
- Health Sciences › Medicine › Family Practice › Clinical Reasoning and Diagnostic Skills
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Epidemiology
- Keywords
- immunoassay, laboratory test errors, false positives, false-negative results, disease prevalence, Bayesian inference, diagnostic test interpretation, pre-analytical phase, post-analytical phase, follow-up testing, diagnostic reliability
- MeSH terms
- Bayes Theorem, Diagnostic Errors, Humans, Immunoassay, Reproducibility of Results, Clinical Laboratory Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
