[Report: assessment of STAT5 phosphorylation status by flow cytometry]

Provost C, Muradqadam K
Record ID 32018013791
French
Original Title: Évaluation du statut de phosphorylation de STAT5 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 STAT5 (signal transducer and activator of transcription 5) protein in patients suspected of suffering from certain inborn errors of immunity (IEIs).
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. STAT5-associated IEIs include growth hormone insensitivity with immune dysregulation syndromes 1 (GHISID1) and 2 (GHISID2). Their symptoms include growth retardation, increased susceptibility to infections, immune deficiencies and various autoimmune diseases. The presence of antiGM-CSF autoantibodies4 is a phenocopy of STAT5-associated IEI, which presents with decreased pSTAT5, surfactant accumulation in alveoli and pulmonary insufficiency. 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): The results of the analysis could help improve patient management, particularly regarding the use of targeted therapies. The addition of the pSTAT5 test to the Répertoire would contribute to the rapid management of patients by limiting diagnostic errancy. It would also promote the availability of the test and standardize the diagnostic services offered for these rare diseases. (#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 cope with any increase in volume. (#4 SOCIO-CULTURAL DIMENSION): Many of the learned societies and clinicians consulted recommend the pSTAT5 test for the diagnosis of certain IEIs. The eventual addition of a functional test like pSTAT5 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): No economic studies evaluating the cost-effectiveness of a test to determine pSTAT5 status have been identified. Given the absence of data relating the anticipated clinical benefits to the costs of the method, 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. The addition of the proposed test could generate additional costs of approximately $21,800 over the first three years.
Authors' recommendations: The INESSS recommends that the analysis of pSTAT5 status determination by FC be included in the Répertoire, given that: • The test enables detection of pSTAT5 defects, confirmation of the presence of anti-GM-CSF autoantibodies, and analysis of the pathogenicity of variants identified by genetic analysis. It aids patient management by reducing the diagnostic wandering often observed with rare diseases, and enables appropriate treatment to be offered rapidly; • analysis has been available for several years in the Quebec healthcare system; • 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 IREs molecular diagnostic services; • the economic risk of listing the analysis in the Répertoire is considered very low. The designated laboratory(ies) must meet ISO 15189 requirements.
Authors' methods: The evaluation process involved a rapid review of the scientific literature, a grey literature search and an ad hoc consultation with clinicians specializing in hematology-oncology and immunology-allergology. A review of the economic literature was conducted on the cost-effectiveness of STAT5 phosphorylation analysis (pSTAT5). A budget impact analysis was also conducted, considering the costs associated with adding this test to the Repertoire. Costs were projected over a three-year time frame 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 aux fins de remboursement (DER).
Details
Project Status: Completed
Year Published: 2024
English language abstract: An English language summary is available
Publication Type: Full HTA
Country: Canada
Province: Quebec
MeSH Terms
  • Genetic Diseases, Inborn
  • Phosphorylation
  • Flow Cytometry
  • Genetic Testing
  • Immune System Diseases
  • Autoimmune Diseases
  • Immunologic Deficiency Syndromes
  • Primary Immunodeficiency Diseases
  • STAT5 Transcription Factor
  • Immunophenotyping
Contact
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)
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