Original Title: Statut de phosphorylation de STAT1 par cytométrie en flux

Authors' objectives: The Institut national d'excellence en santé et en services sociaux (INESSS) has received a request to introduce 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 phosphorylation status of the STAT1 protein by flow cytometry into the Répertoire.

Authors' results and conclusions: RESULTS (#1 SOCIO-CULTURAL DIMENSION): Several of the learned societies consulted on this subject recommend testing for pSTAT1 status in the diagnosis of certain IEIs. The clinicians consulted also share this opinion. The possible addition of a functional test such as pSTAT1 is in line with the Politique québécoise pour les maladies rares, Pour une meilleure reconnaissance et prise en charge des personnes atteintes de maladies rares, published in 2023. This policy aims to "optimize access to quality health care and services that are safe, equitable, inclusive, and adapted to the specific needs of culturally sensitive patients with rare diseases." (#2 POPULATION DIMENSION): The three types of dysfunctions associated with phosphorylation of the STAT1 protein (gain or loss of function and the presence of neutralizing anti-IFN-γ autoantibodies) can be detected by flow cytometry testing. Treatment of STAT1 dysfunction mainly includes often long-term combinations of antifungals or antibiotics, hematopoietic stem cell transplantation (HSCT), and inhibitors of the JAK/STAT pathway. The addition of the pSTAT1 test to the Répertoire would contribute to the rapid management of patients and help in the choice of treatment, thus limiting medical wandering for these patients. It would also promote the availability of the test and standardize the results obtained. (#3 CLINICAL DIMENSION): In order to document the validity and clinical utility of the test, eight papers were selected: six papers on loss and gain of function of STAT1 and two papers on the presence of antiIFN-γ autoantibodies. The data show that evaluation of pSTAT1 status helps to detect defects in the IL-12/IFN-γ amplification loop, validate STAT1 functional abnormalities and identify the presence of neutralizing anti-IFN-γ autoantibodies in patients clinically suspected of certain IEIs. It is also used to assess the functionality of variants of uncertain significance (VUSs) obtained after genetic analysis and helps target genetic investigations. Finally, there is some evidence that pSTAT1 improves patient management, particularly regarding the use of antibiotic prophylaxis, immunomodulation, or HSCT. (#4: ORGANIZATIONAL AND ECONOMIC DIMENSIONS): The pSTAT1 test has been offered by the Montreal-CHU Sainte-Justine laboratories since 2014. It was performed between 2014 and 2023 under a generic code that groups together all flow cytometry tests associated with a weighted value lower than that estimated for the pSTAT1 test. The applicant laboratory states that it has the capacity to perform all the tests to cover the needs of the entire province, and to cope with any increase in volume. According to the clinicians consulted, performing the test locally would save time and provide support in interpreting results. Access to other tests, such as the IL-12 assay, should remain available via shipments outside Quebec to cover exceptional needs. A response will be obtained within 24 to 36 hours; this timeframe is deemed adequate by the clinicians consulted. CONCLUSION: Considering the above findings, the INESSS recommends the introduction of the analysis of STAT1 phosphorylation status by flow cytometry to the Répertoire, given that: • This analysis is recommended by learned societies and clinicians specializing in the diagnosis of certain innate immune errors; • the scientific literature shows that the test enables detection of STAT1 dysfunction and verification of VUS functionality. It helps to ensure that patients are properly managed, so as to reduce the diagnostic wandering often observed with rare diseases, and to offer appropriate treatment rapidly; • analysis has been available for over ten years in the Quebec health and social services network; • the use of analysis in the context of IEIs would be a responsible use of resources; • 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 was conducted according to the overall value assessment approach advocated by the Institute in its Statement of Ethical Principles and Foundations, which stipulates that an intervention brings value insofar as its use or implementation contributes to the triple aim of the health and social services system in Quebec. The evaluation process included a review of the scientific literature, a grey literature search and an ad hoc consultation with clinicians specializing in pediatric and adult immunologyallergology. A review of the economic literature was conducted on the efficiency of STAT1 phosphorylation status (pSTAT1). A budget impact analysis was also conducted, considering the costs associated with adding this test to the Répertoire. Costs were projected over a three-year horizon from the perspective of the Quebec healthcare system. All scientific, contextual, and experiential data were interpreted and assessed using an approach based on an overall value assessment defined according to five dimensions: sociocultural, population-based, clinical, organizational, and economic. The findings of this evaluative approach were used to guide the discussions and analysis process of the Direction de l'évaluation des médicaments et des technologies à fins de remboursement.

Project Status: Completed

URL for project: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/evaluation-du-statut-de-phosphorylation-de-stat1-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-stat1-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)