SAGE IVD recommended listing the immunofixation 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 an immunofixation electrophoresis test using gel electrophoresis as assay format in the EDL 5. Immunofixation was the third assay discussed for diagnosis of multiple myeloma and gammopathies. Immunofixation is a next step after identifying M protein, which is crucial for diagnosing and managing plasma cell disorders. This technique has been widely used since the 1970s despite the limited publication of modern clinical evidence. Although diagnostic performance evidence is limited, it is sufficient to establish validity. A SAGE IVD member noted that this technique is a minimum requirement for any LMIC wanting to set up a multiple myeloma service for diagnosis and monitoring of this cancer. Inclusion of cerebrospinal fluid as a specimen was discussed, but it was considered this was not commonly used for multiple myeloma and gammopathies and more relevant to neurological disorders. The potential for future exploration of immunofixation applications beyond serum and urine was noted. The consensus of the SAGE IVD was to include the test in the EDL 5, with no changes proposed to the current scope and recommendations.

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)