SAGE IVD recommended listing the protein electrophoresis test category in EDL 5:
• as a disease-specific IVD for use in health care facilities with clinical laboratories (Section II.b Cancer);
• using gel electrophoresis as assay format;
• using serum and urine as specimen types;
• to aid in the diagnosis, monitoring and prognosis of monoclonal gammopathies. SAGE IVD also recommended including a note to the EDL stating that this test is recommended for use in specialized health care settings/clinical laboratories.

The application proposed the inclusion of a protein electrophoresis test using gel electrophoresis as assay format to aid in the diagnosis, monitoring, and prognosis of monoclonal gammopathies. Multiple myeloma is a significant global health burden, representing over 1% of all cancers. Advances in the management of blood cancers have been made and new treatments are coming through all the time so early diagnosis is important. This test has been in use since the mid-20th century and is still a critical diagnostic tool, despite advances in technology (e.g. capillary electrophoresis), due to its accessibility and cost-effectiveness in certain settings. It was recognized that protein electrophoresis is a foundational diagnostic test and is included in clinical guidelines. Some concern was expressed about the lack of high-quality, systematic studies supporting its clinical utility but the technique was established long before the current standards of medical evidence and is widely accepted. SAGE IVD members discussed the use of automated versus manual gel electrophoresis methods and agreed not to specify. They acknowledged disparities in access to cancer diagnostics in LMICs, and emphasized the need for centralized but accessible testing frameworks. The group agreed that gel electrophoresis should be added to the EDL 5 under the cancer section. This classification emphasizes its role in a structured cancer diagnostic pathway rather than as a general diagnostic tool. There should be flexibility for countries to adapt inclusion based on resources and infrastructure.

No systematic reviews on diagnostic accuracy of protein tests (PEP, IFE, FLC) were provided by the applicant. Primary studies on (comparative) diagnostic accuracy in clinically relevant settings (in which suspected patients are included) are lacking. Only one reference (#28) provided relevant evidence, but the sample is small and the reference standard may be at high risk of introducing bias. There were no systematic reviews on clinical utility. Although the current evidence does not support clinical utility, the iStopMM study (reference #36) implies that trial results are underway, which would allow for an excellent comparison of the value of PEP (gel+ capillary) + FLC on clinical outcomes. Currently there are no cost-effectiveness studies available, and thus insufficient evidence for cost-effectiveness of protein tests. Current evidence on diagnostic accuracy is lacking for protein tests. More studies on comparative diagnostic accuracy of these tests compared to contemporary alternative tests are warranted to make an informed evidence based decision. Downstream consequences on clinical utility and cost-effectiveness are unknown, and depend greatly on clinical consequences, and availability and effectiveness of treatment.

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)