A fit-for-purpose approach to analytical sensitivity applied to a cardiac troponin assay: time to escape the ‘highly-sensitive’ trap
-
Jacobus P.J. Ungerer
und
Carel J. Pretorius
Abstract
Background: Highly-sensitive cardiac troponin (cTn) assays are being introduced into the market. In this study we argue that the classification of cTn assays into sensitive and highly-sensitive is flawed and recommend a more appropriate way to characterize analytical sensitivity of cTn assays.
Study: The raw data of 2252 cardiac troponin I (cTnI) tests done in duplicate with a ‘sensitive’ assay was extracted and used to calculate the cTnI levels in all, including those below the ‘limit of detection’ (LoD) that were censored. Duplicate results were used to determine analytical imprecision.
Results: We show that cTnI can be quantified in all samples including those with levels below the LoD and that the actual margins of error decrease as concentrations approach zero.
Conclusions: The dichotomous classification of cTn assays into sensitive and highly-sensitive is theoretically flawed and characterizing analytical sensitivity as a continuous variable based on imprecision at 0 and the 99th percentile cut-off would be more appropriate.
Acknowledgments
We would like to acknowledge the advice from Shirley Tyack.
Conflict of interest statement
Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article. Research funding played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
Research funding: Support received in the form of consumables from Roche, Beckman Coulter, Abbott and Siemens. None of these sponsors had a role in the preparation, review, or approval of this manuscript.
Employment or leadership: None declared.
Honorarium: None received.
References
1. De Lemos JA. Increasingly sensitive assays for cardiac troponins. A review. J Am Med Assoc 2013;309:2262–9.10.1001/jama.2013.5809Suche in Google Scholar PubMed
2. Korley FK, Jaffe AS. Preparing the United States for high-sensitivity cardiac troponin assays. J Am Coll Cardiol 2013;61:1753–8.10.1016/j.jacc.2012.09.069Suche in Google Scholar PubMed
3. Reichlin T, Hochholzer W, Bassetti S, Steuer S, Stelzig C, Hartwiger S, et al. Early diagnosis of myocardial infarction with sensitive cardiac troponin assays. New Engl J Med 2009;36:858–67.10.1056/NEJMoa0900428Suche in Google Scholar PubMed
4. Reiter M, Twerenbold R, Reichlin T, Benz B, Haaf P, Meissner J, et al. Early diagnosis of myocardial infarction in patients with pre-existing coronary artery disease using more sensitive cardiac troponin assays. Eur Heart J 2012;33:988–97.10.1093/eurheartj/ehr376Suche in Google Scholar PubMed
5. Borna C, Thelin J, Öhlin B, Erlinge D, Ekelund U. High-sensitivity troponin T as a diagnostic tool for acute coronary syndrome in the real world: an observational study. Eur J Emerg Med 2013 Jun 7. [Epub ahead of print].10.1097/MEJ.0b013e328362a71bSuche in Google Scholar PubMed
6. Christenson RH, Phillips D. Sensitive and high sensitive next generation cardiac troponin assays: more than just a name. Pathology 2011;43:213–9.Suche in Google Scholar
7. Apple FS, Collinson PO. Analytical characteristics of high-sensitivity cardiac troponin assays. Clin Chem 2012;58: 54–61.10.1373/clinchem.2011.165795Suche in Google Scholar PubMed
8. Apple FS, Ler R, Murakami MA. Determination of 19 cardiac troponin I and T assay 99th percentile values from a common presumably healthy population. Clin Chem 2012;58:1574–81.10.1373/clinchem.2012.192716Suche in Google Scholar PubMed
9. Apple FS, Saenger AK. The state of cardiac troponin assays: looking bright and moving in the right direction. Clin Chem 2013;59:1014–6.10.1373/clinchem.2013.203307Suche in Google Scholar PubMed
10. Apple F. A new season for cardiac troponin assays: it’s time to keep a scorecard. Clin Chem 2009;55:303–6.10.1373/clinchem.2009.128363Suche in Google Scholar PubMed
11. Keller T, Münzel T, Blankenberg S. Making it more sensitive. The new era of troponin use. Circulation 2011;123:1361–3.10.1161/CIRCULATIONAHA.111.023200Suche in Google Scholar PubMed
12. Currie LA. Detection and quantification limits: origins and historical overview. Analytica Chim Acta 1999;391:127–34.10.1016/S0003-2670(99)00105-1Suche in Google Scholar
13. Olivieri AC, Faber NM, Ferré J, Boqué R, Kalivas JH, Mark H. Uncertainty estimation and figures of merit for multivariate calibration (IUPAC technical report). Pure Appl Chem 2006;78:633–61.10.1351/pac200678030633Suche in Google Scholar
14. Cressie N. Limits of detection. Chemom Intell Lab Syst 1994;22:161–3.10.1016/0169-7439(93)E0061-8Suche in Google Scholar
15. Spiegelman CH. A discussion of issues raised by Lloyd Currie and a cross disciplinary view of detection limits and estimating parameters that are often at or near zero. Chemom Intell Lab Syst 1997;37:183–8.Suche in Google Scholar
16. Currie LA. Limits for qualitative detection and quantitative determination. Application to radiochemistry. Anal Chem 1968;40:586–93.10.1021/ac60259a007Suche in Google Scholar
17. Armbruster DA, Pry T. Limit of blank, limit of detection and limit of quantification. Clin Biochem Rev 2008;29(Suppl i):S49–52.Suche in Google Scholar
18. Clinical and Laboratory Standards Institute. Protocols for determination of limits of detection and limits of quantification; approved guidelines. CLSI document EP17. Wayne, PA: CLSI; 2004.Suche in Google Scholar
19. Thompson M. Do we really need detection limits? Analyst 1998;123:405–7.10.1039/a705702dSuche in Google Scholar
20. Thygesen K, Alpert JS, Jaffe As, Simoons ML, Chaitman BR, White HD, et al. Third universal definition of myocardial infarction. J Am Coll Cardiol 2012;60:1581–98.10.1016/j.jacc.2012.08.001Suche in Google Scholar PubMed
21. IFFC troponin table. Available from: http://www.ifcc.org/media/218183/IFCC%20Tables%20ug_L_Update_December%202012.pdf. Accessed October 2013.Suche in Google Scholar
22. Pretorius CJ, Dimeski G, O’Rourke PK, Marquart L, Tyack SA, Wilgen U, et al. Outliers as a cause of false cardiac troponin results: investigating the robustness of 4 contemporary assays. Clin Chem 2011;57:710–8.10.1373/clinchem.2010.159830Suche in Google Scholar PubMed
23. Pretorius CJ, Wilgen U, Ungerer JP. Serial cardiac troponin differences measured on four contemporary analyzers: relative differences, actual differences and reference change values compared. Clin Chim Acta 2012;413:1786–91.10.1016/j.cca.2012.07.001Suche in Google Scholar PubMed
©2014 by Walter de Gruyter Berlin/Boston
Artikel in diesem Heft
- Masthead
- Masthead
- Editorials
- Inflammatory bowel diseases: where we are and where we should go
- Thrombophilia testing. Useful or hype?
- Reviews
- Inflammatory bowel diseases: from pathogenesis to laboratory testing
- Crohn’s disease specific pancreatic antibodies: clinical and pathophysiological challenges
- Point/Counterpoint
- The utility of thrombophilia testing
- The futility of thrombophilia testing
- Genetics and Molecular Diagnostics
- Identification of an 18 bp deletion in the TWIST1 gene by CO-amplification at lower denaturation temperature-PCR (COLD-PCR) for non-invasive prenatal diagnosis of craniosynostosis: first case report
- General Clinical Chemistry and Laboratory Medicine
- Agreement of seven 25-hydroxy vitamin D3 immunoassays and three high performance liquid chromatography methods with liquid chromatography tandem mass spectrometry
- First trimester pregnancy-associated plasma protein A and human chorionic gonadotropin-beta in early and late pre-eclampsia
- S100B blood level measurement to exclude cerebral lesions after minor head injury: the multicenter STIC-S100 French study
- NGAL, L-FABP, and KIM-1 in comparison to established markers of renal dysfunction
- Value-added reporting of antinuclear antibody testing by automated indirect immunofluorescence analysis
- Cardiovascular Diseases
- A fit-for-purpose approach to analytical sensitivity applied to a cardiac troponin assay: time to escape the ‘highly-sensitive’ trap
- Diabetes
- A simple and precise method for direct measurement of fractional esterification rate of high density lipoprotein cholesterol by high performance liquid chromatography
- Infectious Diseases
- Detection of unamplified HCV RNA in serum using a novel two metallic nanoparticle platform
- Increased plasma arginase activity in human sepsis: association with increased circulating neutrophils
- Corrigendum
- The relationship between estimated average glucose and fasting plasma glucose
- Letter to the Editors
- The obsessive-compulsory clinical pathologist
- Prism effect of specimen receiving – generation of fundamentals for the smooth progress of analytical processing
- Preanalytical errors: the professionals’ perspective
- Corrected reports in laboratory medicine in a Chinese university hospital for 3 years
- Comparison of an enzymatic assay with liquid chromatography-pulsed amperometric detection for the determination of lactulose and mannitol in urine of healthy subjects and patients with active celiac disease
- Effect of freezing-thawing process on neuron specific enolase concentration in severe traumatic brain injury sera samples
- Undetected creatinine levels
- The effect of centrifugation on three urine protein assays: benzethonium chloride, benzalkonium chloride and pyrogallol red
Artikel in diesem Heft
- Masthead
- Masthead
- Editorials
- Inflammatory bowel diseases: where we are and where we should go
- Thrombophilia testing. Useful or hype?
- Reviews
- Inflammatory bowel diseases: from pathogenesis to laboratory testing
- Crohn’s disease specific pancreatic antibodies: clinical and pathophysiological challenges
- Point/Counterpoint
- The utility of thrombophilia testing
- The futility of thrombophilia testing
- Genetics and Molecular Diagnostics
- Identification of an 18 bp deletion in the TWIST1 gene by CO-amplification at lower denaturation temperature-PCR (COLD-PCR) for non-invasive prenatal diagnosis of craniosynostosis: first case report
- General Clinical Chemistry and Laboratory Medicine
- Agreement of seven 25-hydroxy vitamin D3 immunoassays and three high performance liquid chromatography methods with liquid chromatography tandem mass spectrometry
- First trimester pregnancy-associated plasma protein A and human chorionic gonadotropin-beta in early and late pre-eclampsia
- S100B blood level measurement to exclude cerebral lesions after minor head injury: the multicenter STIC-S100 French study
- NGAL, L-FABP, and KIM-1 in comparison to established markers of renal dysfunction
- Value-added reporting of antinuclear antibody testing by automated indirect immunofluorescence analysis
- Cardiovascular Diseases
- A fit-for-purpose approach to analytical sensitivity applied to a cardiac troponin assay: time to escape the ‘highly-sensitive’ trap
- Diabetes
- A simple and precise method for direct measurement of fractional esterification rate of high density lipoprotein cholesterol by high performance liquid chromatography
- Infectious Diseases
- Detection of unamplified HCV RNA in serum using a novel two metallic nanoparticle platform
- Increased plasma arginase activity in human sepsis: association with increased circulating neutrophils
- Corrigendum
- The relationship between estimated average glucose and fasting plasma glucose
- Letter to the Editors
- The obsessive-compulsory clinical pathologist
- Prism effect of specimen receiving – generation of fundamentals for the smooth progress of analytical processing
- Preanalytical errors: the professionals’ perspective
- Corrected reports in laboratory medicine in a Chinese university hospital for 3 years
- Comparison of an enzymatic assay with liquid chromatography-pulsed amperometric detection for the determination of lactulose and mannitol in urine of healthy subjects and patients with active celiac disease
- Effect of freezing-thawing process on neuron specific enolase concentration in severe traumatic brain injury sera samples
- Undetected creatinine levels
- The effect of centrifugation on three urine protein assays: benzethonium chloride, benzalkonium chloride and pyrogallol red
