SAGE IVD recommended fully listing lead, anodic stripping voltammetry (ASV) point-of-care test in the EDL 5
• as a disease-specific IVD for use in community settings and health facilities without laboratories (Section I.b. Lead exposure and poisoning);
• using anodic stripping voltammetry (ASV) point-of-care test as assay format;
• using capillary and venous whole blood as specimen type;
• to screen for, diagnose, and monitor lead exposure and poisoning in children, women of reproductive age, pregnant women, and people with occupational exposure.

The application proposed a test for detection and monitoring of lead poisoning. SAGE IVD members noted that lead exposure and poisoning is a significant public health problem causing neurodevelopmental, cognitive, and physiological damage. WHO guidelines emphasize its impact and highlight the need for robust diagnostic tools. Laboratory-based methods such as electrothermal atomic absorption spectroscopy (ETAAS), flame atomic absorption spectroscopy (FAAS), and inductively coupled plasma mass spectrometry (ICPMS) are reference standards but require sophisticated equipment and facilities. Anodic stripping voltammetry (ASV) is a simpler, more accessible option for point-of-care testing. SAGE IVD member noted the benefits of this method, namely rapid results, small sample needed, cost–effectiveness and usability in both non-laboratory settings and lab settings. Limitations included narrow analytical range and a need for confirmation for high lead levels (levels above 5 µg/dL should be confirmed by a high-complexity laboratory method). Some challenges noted by the SAGE IVD were: the need for clarity on regulatory warnings on the accuracy of commercial ASV devices; and the limited number of manufacturers producing ASV devices, raising concerns about cost and market accessibility. One member pointed out that the application mentioned equipment from only one manufacturer and it may not be easily available in LMICs; also the cost of the test was not mentioned. Another member pointed out the public health importance of the test with an example from Latin America which showed ASV’s potential in screening vulnerable populations in mining areas. The importance of a confirmatory test for high lead levels was stressed, although these are not are not currently included in the EDL. It was suggested that these could be included in the EDL based on WHO guideline and guidance documents (1,2). The general consensus favoured including ASV in the EDL5, with recommendations highlighting point-of-care capabilities and suggesting future submissions for confirmatory laboratory methods. Literature cited in the discussion 1. WHO guideline for clinical management of exposure to lead. Geneva: World Health Organization; 2021. Available at https://iris.who.int/handle/10665/347360 (accessed 15 January 2025). 2. Brief guide to analytical methods for measuring lead in blood, 2nd ed. Geneva: World Health Organization; 2020. Available at https://iris.who.int/handle/10665/333914 (accessed 15 January 2025).

It is difficult to appraise the evidence in an overall manner due to heterogeneity between studies. Here, the studies seem to provide answers to different questions about test agreement or diagnostic test accuracy performance, false positives during follow-up, follow-up testing rates, and reproducibility of lab measurements. Studies reporting diagnostic test accuracy used different assays and various (although also overlapping) thresholds for elevated lead blood concentrations, and compared capillary blood samples (including different methods to obtain capillary samples as index tests) with venous blood samples (as a reference test) using modified FAAS, ETAAS /GFAAS, or ASV. Only one study compared blood samples on different assays (ASV vs. ICP-MS) and reported the agreement of both assays using Bland-Altman plots. The sheer amount of (systematic) reviews and primary studies seem to underpin the importance of testing/screening/monitoring blood lead levels and lead exposure due to their associations with a wide variety of conditions and impairments. However, none of these references seem to report data about the impact of using (different) blood lead concentration tests on patient-related or health-related outcomes. Therefore, it is unclear which methods and assays should (not) be used when regarding their impact on patient-relevant or health-related outcomes. Furthermore, new cost-effectiveness studies may need to be performed that reflect costs and assumptions for current practice (e.g. assumptions about treatment success and including indirect costs) for screening strategies. Cost-effectiveness studies for diagnosic and monitoring roles of the test seem to be lacking.

The selection and use of essential in vitro diagnostics: report of the fifth meeting of the WHO Strategic Advisory Group of Experts on In Vitro Diagnostics, 2024. World Health Organization. (To be published)