The SAGE IVD recommended conditional inclusion on the EDL of the IVD for measuring plasma levels of IgG, IgA and IgM for diagnosis of immunodeficiency, pending submission of evidence of its clinical usefulness, with testing in various regions in field surveys. The Group noted that use of the test is expensive and requires highly skilled laboratory technicians. No evidence was provided of its use in LMICs, except in a few countries in Central America. Furthermore, the submission did not include an evaluation of evidence that patients were treated with the associated EML drugs as a result of use of the test, and no evidence was given for its diagnostic accuracy or safety. No guidelines for its use appear to be available. Recommended test purpose: to identify patients with low immunoglobulin levels and monitor replacement. SAGE IVD reviewed additional evidence in 2020 (available at: https://iris.who.int/handle/10665/339064) and recommended reversing the conditional listing on the immunoglobulin levels (IgG, IgM, IgA) tests and fully list them in EDL 3.

Counterpart immunoglobulin replacement therapies are listed in the WHO EML for both adults and children. Use of the tests for diagnosis of immunodeficiencies is well established in international practice and incorporated into the best practice recommendations and diagnostic criteria of the American Academy of Allergy, Asthma and Immunology, the Jeffrey Model Foundation and the European Society for Immunodeficiencies. The test is recommended by a number of professional associations. The test methods have been standardized against the certified reference material in human serum of the Institute for Reference Materials and Measurements. In 2020 the applicant indicated that no systematic review of analytical accuracy exists for these tests; but the organization has tried to provide an alternative through international external quality assessment data. IPOPI also justified the addition of these assays by citing international studies of immunodeficiencies and international guidelines developed for immunodeficiency identification and treatment, including in resource-limited environments. Treatment for immunoglobulin deficiencies is already listed in the EML and these tests are basic tests required for diagnosis.

No detailed evidence or summary of evidence was provided to support this submission in 2019; however, the method has been the reference standard for estimation of immunoglobulins. Supporting evidence for inclusion of these tests is provided by the trials considered by the WHO essential medicines list (EML) for listing immunoglobulin therapies based on reported low values of IgG, IgM and IgA. SAGE IVD reviewed additional evidence in 2020 (available at: https://iris.who.int/handle/10665/339064) and recommended reversing the conditional listing on the immunoglobulin levels (IgG, IgM, IgA) tests in EDL 3.

World Health Organization. (‎2019)‎. The selection and use of essential in vitro diagnostics: report of the second meeting of the WHO Strategic Advisory Group of Experts on In Vitro Diagnostics (‎including the second WHO model list of essential in vitro diagnostics)‎. World Health Organization. https://iris.who.int/handle/10665/329527 ; World Health Organization. (‎2021)‎. The selection and use of essential in vitro diagnostics: report of the third meeting of the WHO Strategic Advisory Group of Experts on In Vitro Diagnostics, 2020 (‎including the third WHO model list of essential in vitro diagnostics)‎. World Health Organization. https://iris.who.int/handle/10665/339064