Original Title: Avis - Dosage du sC5b-9 plasmatique

Authors' objectives: The Institut national d’excellence en santé et en services sociaux (INESSS) has received a request to add a new assay to the Répertoire québécois et système de mesure des procédures de biologie médicale (hereinafter referred to as the Répertoire), through the evaluation mechanism for new medical biology assays. The mandate is to evaluate the relevance of introducing the plasma sC5b-9 assay to the Répertoire. This is the third evaluation for this mandate. As this request includes new elements, INESSS has re-evaluated the relevance of this assay from a provincial perspective.

Authors' results and conclusions: RESULTS (#1 SOCIOCULTURAL DIMENSION): This is the third evaluation of the relevance of introducing the sC5b-9 assay to the Répertoire. Since the publications in 2017 and 2018 by INESSS, new information has made it possible to address the concerns raised by members of the Comité délibératif permanent during previous evaluations, notably concerning the absence of consensus for a threshold concentration and the lack of diagnostic sensitivity and specificity. (#2 POPULATION DIMENSIONPOPULATION DIMENSION): Complement-mediated TMA represents a medical emergency due to the risk of rapid deterioration. If left untreated, patients face a potentially fatal prognosis. In clinical practice, eculizumab, a C5 inhibitor, is used to treat complement-mediated TMA. However, INESSS has never evaluated eculizumab for this condition since no application has been submitted by the drug's manufacturer. Other complement inhibitors are also available, with ongoing development of new ones. According to the clinicians consulted, there is a healthcare need for patients with TMA, as there is a lack of diagnostic tools to promptly identify complement-mediated TMA. Earlier diagnosis of this pathology would enable rapid initiation of complement inhibitor therapy. The sC5b-9 assay is one of the tools available to meet this healthcare need. However, a normal value does not exclude the diagnosis of complement-mediated TMA, nor does it rule out the possibility of introducing complement inhibitor therapy (#3 CLINICAL DIMENSION): The literature review identified 14 articles: 2 systematic reviews, 6 cohort studies, 4 case-control studies, 1 exploratory analysis of a phase III clinical study and 1 expert consensus. According to the literature and the clinicians consulted, the sC5b-9 assay is a useful test for investigating TMA etiology, but it cannot confirm a diagnosis on its own. A TMA must first be established according to well-defined criteria, including the presence of hemolytic anemia, thrombocytopenia, and schizocytes on blood smears. Moreover, a normal value does not necessarily rule out this diagnosis. After a transplant, the sC5b-9 assay is used as a diagnostic tool in the presence of appropriate clinical manifestations, when there is a suspicion that the patient could have TA-TMA. The sC5b-9 assay is also used to target patients who may be eligible for complement inhibitor therapy, without necessarily ruling out this treatment option if the observed value is normal. (#4 ORGANIZATIONAL DIMENSION): The sCb-9 assay is currently offered outside the Répertoire at CHU Sainte-Justine's hemostasis laboratory. No OPTILAB cluster other than Montreal-CHU Sainte-Justine performs this analysis locally, and none sees the value of adding it to its service offering at this time due to the low demand. Furthermore, current delays in obtaining results are in line with anticipated use. Should the sC5b-9 assay be added to the Répertoire, it would be considered appropriate if only one centre were designated. However, it would be advisable for analyses related to the search for TMA etiology to be accessible at the same centre, to be consistent with a patient's care trajectory. (#5 ECONOMIC DIMENSION- EFFICIENCY): No studies evaluating the efficiency of the sC5b-9 assay for the diagnosis of complement-mediated thrombotic microangiopathy (TMA) or for optimizing treatment with a complement inhibitor have been identified in the scientific literature. The costeffectiveness of the sC5b-9 assay could not be evaluated, given the absence of data quantifying the health benefits derived from its use. (#5.1 ECONOMIC DIMENSION- BUDGET IMPACT ANALYSIS): Based on the assumptions made, the introduction of the sC5b-9 assay to the Répertoire could cost approximately $92,000 over the first three years. It is estimated that 1,100 assays would be performed over this period. Sensitivity analyses show that the net impact of introducing the sC5b-9 assay to the Répertoire could vary from around $74,000 to $132,000 over three years.

Authors' recommendations: Considering the findings based on the five dimensions, INESSS recommends to the Ministère to introduce the plasma sC5b-9 assay to the Répertoire. Regarding the implementation of this assay, INESSS provides specific recommendations: • Maintain a response time consistent with anticipated use; • Should more than one centre be designated, ensure that assays related to the search for TMA etiology are offered at the same location, in order to facilitate the patient's care trajectory.

Authors' methods: The evaluation process included a review of the scientific literature, a search of the grey literature, and consultations with clinicians and other stakeholders. The methodology was organized based on the five dimensions outlined in the statement of principles of INESSS framework for the appraisal of the value of interventions in health and social services: sociocultural, populational, clinical, organizational, and economic. A review of the economic literature was conducted on the cost-effectiveness of the sC5b-9 assay. A budget impact analysis was performed considering the costs associated with the introduction of the sC5b-9 assay to the Répertoire. Costs were projected over a three-year timeframe from a healthcare system perspective. All scientific, contextual, and experiential data were interpreted and synthesized to guide the deliberative process of the Comité scientifique permanent (CDP) – Approches Diagnostiques et dépistage for the development of recommendations.

Project Status: Completed

URL for project: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/dosage-sc5b-9-plasmatique.html

Year Published: 2024

URL for published report: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/dosage-sc5b-9-plasmatique.html

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Canada

Province: Quebec

Organisation Name: Institut national d'excellence en sante et en services sociaux

Contact Address: L'Institut national d'excellence en sante et en services sociaux (INESSS) , 2021, avenue Union, bureau 10.083, Montreal, Quebec, Canada, H3A 2S9;Tel: 1+514-873-2563, Fax: 1+514-873-1369

Contact Name: demande@inesss.qc.ca

Contact Email: demande@inesss.qc.ca

Copyright: L'Institut national d'excellence en sante et en services sociaux (INESSS)