SAGE IVD recommended including the high-sensitivity troponin I (hs-cTnl) test category in EDL 4
• in Section II.b Cardiovascular health;
• using the immunoassay format;
• using serum and plasma as specimen types;
• to aid in the diagnosis of acute myocardial infarction. The group also recommended adding hs-cTnT to EDL 4 for consistency with the existing entry for a troponin test in EDL 3 and because the markers are similarly used. The experts further recommended introducing a new section in the EDL to be called II.b: Cardiovascular health. SAGE IVD also recommended linking the EDL entry to the WHO HEARTS technical package for cardiovascular disease management in primary health care.

Both hs-cTnT and hs-cTnI assays are essential tools in the management of coronary artery disease and the differential diagnosis of acute myocardial infarction. SAGE IVD raised several concerns related to the confusing nature of this application. The application was ostensibly for a POC test, but the data supporting the POC were limited and referred only to diagnostic performance. Evidence on how to frame the diagnostic algorithm and on the clinical utility of the assay was all based on laboratory testing. The experts know of no studies of POC capillary finger-stick tests outside of the hospital setting. Moreover, in 2020 the European Society of Cardiology (ESC) recommended against POC tests for the management of acute coronary syndromes. The FDA has also not approved any POC troponin test. One SAGE IVD member pointed out that this POC is intended for use in primary health care in remote areas; but if angioplasty or fibrinolysis are not available within 90 minutes, the proposition makes little sense. The experts also raised a methodological question about the predictive value of the test in low-prevalence settings. SAGE IVD noted that Médecins Sans Frontières have made POC tests a priority in general in the interest of faster, more affordable results. Nonetheless, the SAGE IVD group maintained that more data are needed on the clinical validity of the tests and to ensure adequate performance, particularly with regard to false positives and negatives. For these reasons, SAGE IVD agreed to list the submission as a laboratory-based test only but emphasized that the group fully supports further research into the POC version of the test and eventual application to EDL 5 with better evidence. Literature cited in the discussion: -HEARTS: technical package for cardiovascular disease management in primary health care: risk-based CVD management. Geneva: World Health Organization; 2020 (https://apps.who.int/iris/handle/10665/333221, accessed 30 July 2023). -Hindricks G, Potpara T, Dagres N, Arbelo E, Bax JJ, Blomström-Lundqvist C et al. 2020 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment element. Eur Heart J. 2021:42(5):373–498 (https://academic.oup.com/eurheartj/article/42/5/373/5899003, accessed 14 December 2022).

Although the evidence provided in this application is incomplete and nonspecific, the existence of very well established guidelines in the European Union (EU), the United Kingdom and the United States with clear underpinnings and recommendations on high-sensitivity cardiac troponin I (hs-cTnI) makes it clear that there is high value in the hs-cTnI test. International guidelines endorse hs-cTnI. As such, no further evidence is warranted from the applicant. However, to make the application more complete,the following should have been considered: a) Specify condition(s) of interest. In this application CVD and myocardial infarction are used back and forth. The applicant used multiple interchangeable terms throughout the application (myocardial infarction, acute coronary syndrome, CVD). b) Provide more insight into the quality-of-life impact of the disease/condition of interest. c) Provide more insight into the costs and impact on costs of a potential intervention. d) The systematic review submitted does not mention POC test(s), so performance may differ significantly. e) Only one commercially available test has been reported in the scientific literature, and the domain of that publication is not the same (healthy vs symptomatic individuals).

World Health Organization. (‎2023)‎. The selection and use of essential in vitro diagnostics: report of the fourth meeting of the WHO Strategic Advisory Group of Experts on In Vitro Diagnostics, 2022 (‎including the fourth WHO model list of essential in vitro diagnostics)‎. World Health Organization. https://iris.who.int/handle/10665/373322