Original Title: Avis - Détection de la mutation D816V du gène KIT par TAAN

Authors' objectives: A request to include a new test in the Répertoire québécois et système de mesure des procédures de biologie médicale (hereinafter the “Répertoire”) was filed by the Hôpital Maisonneuve-Rosemont (HMR)’s molecular diagnosis laboratory and sent to INESSS as per the procedure for the evaluation of new medical laboratory tests.

Authors' results and conclusions: RESULTS (#1 SOCIOCULTURAL DIMENSION): The World Health Organization (WHO) recommends using the detection of the KIT D816V mutation as one of the minor diagnostic criteria for systemic mastocytosis. For this, the preferred method is NAAT, as also emphasized by the National Comprehensive Cancer Network (NCCN) and the European Competence Network on Mastocytosis (ECNM). Since systemic mastocytosis is difficult to diagnose, a number of national and international organizations have been created to support people with this disorder and to provide information to health professionals in order to improve their knowledge of it. (#2 POPULATIONAL DIMENSION): Systemic mastocytosis is a rare disorder that can cause major complications, such as anaphylaxis and osteoporosis, if it is not treated. It is difficult to cure, but the symptoms can be reduced. KIT D816V mutation detection by NAAT is used to diagnose systemic mastocytosis. If the KIT D816V mutation is not detected, despite the persistence of systemic mastocytosis symptoms, it may be important to perform whole KIT gene sequencing to detect other mutations that might be associated with the disorder. Although this test has been available in Québec for nearly 10 years and is used to diagnose systemic mastocytosis, it is not in the Répertoire. (#3 CLINICAL DIMENSION): Seven studies supporting the clinical validity of this test, five of which also present clinical utility data, were found. According to the studies consulted, the clinical value of KIT D816V mutation detection by NAAT for diagnosing systemic mastocytosis is recognized. Furthermore, the sensitivity of NAAT for detecting this mutation also depends on the type of systemic mastocytosis, i.e, indolent, smouldering or advanced. In terms of clinical utility, KIT D816V mutation detection is used to assess the risk level for systemic mastocytosis and to determine if the affected individual’s prognosis is favourable or unfavourable. Moreover, the detection of this mutation by NAAT appears to be of help in the therapeutic monitoring of systemic mastocytosis. According to the clinicians consulted, early diagnosis of systemic mastocytosis helps limit the occurrence of its complications, such as organopathy and osteoporosis. (#4 ORGANIZATIONAL DIMENSION): KIT D816V mutation detection is available and is being used in Québec’s health and social services system. However, including it in the Répertoire would make it official and would lead to better dissemination of the test. This could result in a slight increase in the test volume, despite the rarity of systemic mastocytosis. Clinicians find a turnaround time of 4 to 6 weeks acceptable. The test would be ordered mainly by specialists, such as hematologists/oncologists, internists, certain dermatologists who specialize in oncology, allergists and rheumatologists. The laboratory should offer health professionals an information session on the test, its role and its interpretation. (#5 ECONOMIC DIMENSION): The cost-effectiveness of the proposed test cannot be accurately determined, given that the clinical outcomes and the costs cannot be reliably measured or approximated. The weighted value of this test is $69,66. Additionally, there is the cost of $2,70 attributable to specimen transport. Including the test in Répertoire could generate costs of $3,907 over the first 3 years. The sensitivity analyses performed show that the net impact of the proposed test could vary from $0 to $7,815. CONCLUSION: In light of the above, INESSS recommends that the NAAT test for detecting the KIT D816V mutation be included in the Répertoire, given that: • This test is one of the five WHO criteria for confirming a diagnosis of SM; • The clinical value of detecting the KIT D816V mutation by NAAT is recognized in the scientific literature and by clinicians. It is used to assess the risk of SM and to determine if the affected individual has a favourable or unfavourable prognosis. In addition, it can be of help in the therapeutic monitoring of SM. • The test has been available in Québec’ health and social services system for more than 10 years. • Using the test in the context of SM would not constitute an irresponsible use of resources; • The anticipated economic risk associated with including the test in the Répertoire is considered low. The designated laboratory or laboratories will have to meet the requirements of ISO 15189.

Authors' methods: The assessment process includes a review of the scientific, clinical and economic literature, a search of the gray literature, and consultations with clinicians and other stakeholders. The methodology was used for six assessment questions concerning the five dimensions outlined in INESSS’s statement of principles for the framework for appraising the value of interventions. A budget impact analysis examining the costs associated with including a test for detecting the KIT D816V mutation was performed. The costs were projected over a 3-year time horizon from the perspective of Québec’s health-care system. All of the scientific, contextual and experiential data were interpreted for the purpose of determining the relevance of recommending to the Minister of Health and Social Services the inscription of the test in the Répertoire.

Project Status: Completed

URL for project: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/detection-de-la-mutation-d816v-du-gene-kit-par-taan.html

Year Published: 2024

URL for published report: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/detection-de-la-mutation-d816v-du-gene-kit-par-taan.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)