Original Title: Évaluation du statut de phosphorylation de STAT3 par cytométrie en flux

Authors' objectives: The Ministère de la Santé et des Services sociaux (MSSS) has mandated the Institut national d'excellence en santé et en services sociaux (INESSS) to evaluate the relevance of introducing a new flow cytometry (FC) analysis into the Répertoire québécois et système de mesure des procédures de biologie médicale (hereinafter referred to as the Répertoire). This analysis is used to determine the phosphorylation status of the STAT3 (signal transducer and activator of transcription 3) protein in patients suspected of suffering from certain inborn errors of immunity (IEI).

Authors' results and conclusions: RESULTS (#1 POPULATION DIMENSION): IEIs are a group of rare genetic diseases that are generally caused by pathogenic genetic variants that compromise innate or adaptive immunity. STAT3-associated IEIs include hyper-IgE syndrome (Job syndrome) and childhood multisystem autoimmune disease type 1. Their manifestations include increased susceptibility to infections, stunted growth or various autoimmune diseases depending on the pSTAT3 defect. The presence of -anti-IL6 autoantibodies4 is a STAT3-associated phenocopy of IEI, which presents with decreased pSTAT3, recurrent skin and lung infections and systemic inflammation. Both children and adults are affected. Confirmation of the diagnosis enables a more precise prognosis to be made, and suitable therapeutic approaches to be adopted. (#2 CLINICAL DIMENSION): As these diseases are rare, data on the validity and clinical utility of STAT3 phosphorylation analysis are mainly derived from descriptive studies of cases or a few individuals. The test is reported to be sensitive and specific, helping to clarify or confirm the diagnosis of patients suspected of having STAT3-associated IEI. It is also used to assess the pathogenicity of variants identified by genetic analysis in the STAT3 gene and other genes involved in the STAT3 signaling pathway. (#3 ORGANIZATIONAL DIMENSION ): The applicant laboratory states that it has the capacity to conduct all analyses to cover the needs of the entire province, and to handle an increase in volume. (#4 SOCIO-CULTURAL DIMENSION): Many of the learned societies and clinicians consulted recommend the pSTAT3 test for the diagnosis of certain IEIs. The eventual addition of a functional test like pSTAT3 is in line with the Politique québécoise pour les maladies rares published in 2022 by the MSSS and completes the offer of molecular diagnosis of IEIs proposed by the Réseau québécois de diagnostic moléculaire (RQDM). (#5 ECONOMIC DIMENSION - EFFICIENCY): No economic studies assessing the cost-effectiveness of a test to determine pSTAT3 status have been identified. Given the absence of data linking the costs and anticipated clinical benefits of such a test, the INESSS cannot accurately conduct its own efficiency analysis. However, according to clinicians, several clinical benefits are expected in terms of optimizing patient management, at low cost. (#5.1 ECONOMIC DIMENSION - BUDGET IMPACT ANALYSIS): A budget impact analysis was also conducted, considering the costs associated with adding this test to the Répertoire. These costs were projected over a three-year timeframe from the perspective of the Quebec healthcare system. The addition of the proposed test could generate additional costs of around $5,500 over the first three years.

Authors' recommendations: The INESSS recommends that the analysis of pSTAT3 status determination by FC be included in the Répertoire, given that: • The clinical value of pSTAT3 status assessment by FC is recognized in the scientific literature and by the clinicians consulted. The test enables the detection of STAT3 (de)phosphorylation defects, confirmation of the presence of anti-IL-6 autoantibodies, and analysis of the pathogenicity of variants identified by genetic analysis. It assists in the appropriate management of patients, to reduce the diagnostic wandering often observed with rare diseases, and to offer appropriate treatment rapidly; • analysis has been available in the Quebec health and social services network for around ten years; • the use of analysis in the context of IEIs would be a responsible use of resources; • this analysis is recommended by learned societies and clinicians specializing in the diagnosis of certain IEIs. It is also in line with the Politique québécoise pour les maladies rares, and complements RQDM's IRE molecular diagnostic services; • the economic risk of listing the analysis in the Répertoire is considered to be very low. The designated laboratory(ies) must meet ISO 15189 requirements.

Authors' methods: The evaluation approach included a rapid review of the scientific literature, a grey literature search and an ad hoc consultation with clinicians specializing in hematologyoncology and immunology-allergology. A review of the economic literature was conducted on the cost-effectiveness of STAT3 phosphorylation assay (pSTAT3). A budgetary impact analysis considering the costs associated with adding this test to the Répertoire was also conducted. Costs were projected over a three-year timeframe from the perspective of the Quebec healthcare system. The findings of this evaluation procedure were used to guide the discussions and analysis process of the Direction de l'évaluation des médicaments et des technologies à fins de remboursement (DER).

Project Status: Completed

URL for project: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/evaluation-du-statut-de-phosphorylation-de-stat3-par-cytometrie-en-flux.html

Year Published: 2024

URL for published report: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/evaluation-du-statut-de-phosphorylation-de-stat3-par-cytometrie-en-flux.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)