Original Title: Dosage sanguin de la fludarabine par chromatographie liquide de haute performance couplée à la spectrométrie de masse en tandem (HPLC-MS/MS)

Authors' objectives: A request to introduce a new test to the Répertoire québécois et système de mesure des procédures de biologie médicale (hereinafter referred to as the Répertoire) has been submitted to the Institut national d'excellence en santé et en services sociaux (INESSS) in accordance with the evaluation mechanism for new biomedical tests. The mandate given was to evaluate the relevance of introducing the fludarabine blood test by highperformance liquid chromatography coupled with tandem mass spectrometry (HPLCMS/MS) to the Répertoire.

Authors' results and conclusions: RESULTS: (#1 POPULATION DIMENSION): In Quebec, by 2023, around 200 patients had been treated with allo-GCSH and around 100 with CAR-T therapy. According to clinicians, a majority of patients treated with alloGCSH and all patients treated with CAR-T therapy would have been exposed to fludarabine. These patients would represent the populations targeted by the test. Over the next few years, the number of patients for whom the test could be requested could increase considerably, particularly with the listing of new CAR-T therapies on the Liste des médicaments fournis en établissement. (#2 CLINICAL DIMENSION): Patients treated with allo-GCSH or CAR-T therapy who are under- or over-exposed to fludarabine have a higher instantaneous risk of mortality and adverse effects such as neurotoxicity than patients with an optimal level of exposure. Their probability of successful treatment and survival is also lower than that of patients with an optimal level of exposure. In a real-life setting, fludarabine blood level results by HPLC-MS/MS could be compared with the therapeutic range defining the optimal level of fludarabine exposure, to guide adjustment of the remaining dose(s) and thus help optimize the outcome of allo-GCSH or CAR-T therapy. (#3 ORGANIZATIONAL DIMENSION): The applying laboratory has both the material resources and the expertise to perform HPLC-MS/MS fludarabine blood testing for all of Québec. Testing implementation would add additional tasks for nursing staff, procedures for laboratory staff, as well as results to interpret and one or more tests to adjust for physicians and pharmacists in healthcare establishments. Offering the test in more than one centre could help ensure a turnaround time of less than 24 hours. (#4 SOCIO-CULTURAL DIMENSION): No recommendations in support of fludarabine blood testing by HPLC-MS/MS in the context of allo-GCSH or CAR-T therapy have been identified. Allo-GCSH and CAR-T therapies are costly interventions. Despite their survival benefits, the risk of rejection, relapse or mortality remains high, requiring the identification and control of variables that have the potential to optimize clinical outcomes. The HPLCMS/MS for blood testing of fludarabine is seen as one of the factors that clinicians could act on. (#5 ECONOMIC DIMENSION): Approximately 5,600 HPLC-MS/MS tests would be conducted over a three-year period, should fludarabine be added to the Répertoire. Therefore, the introduction of fludarabine blood testing by HPLC-MS/MS to the Repertoire could result in costs of approximately $424,000 ($352,000 to $488,000) for the first three years. Considering other CAR-T conditioning regimens and therapies, the budgetary impact would amount to $467,000 ($414,000 to $529,000) for 6,200 HPLC-MS/MS tests. However, it should be noted that the budget impact may be underestimated, as a second test was not considered for a limited number of patients. Finally, several other CAR-T therapies have been or are being evaluated by the INESSS, which could significantly increase the budgetary impact of the test.

Authors' recommendations: Members of the INESSS Standing Deliberative Committee - Diagnostic Approaches and Screening (CDP-ADD) recognize the innovative potential of the HPLC-MS/MS blood test for fludarabine, and unanimously support its inclusion in the Répertoire. Based on the above findings, the INESSS recommends that the Minister introduce the HPLCMS/MS blood test for fludarabine into the Répertoire. DETAILS ACCOMPANYING THE RECOMMENDATION: The response time of less than 24 hours must be observed. • The collaboration of the requesting centre's clinicians (hemato-oncologists and institutional pharmacists) is essential when using the test. They must be available to interpret results and guide testing adjustment, if necessary. • The test must meet ISO 15189 requirements.

Authors' methods: The evaluation process included a review of the scientific literature, a search of the grey literature, and consultations with hemato-oncologists, pharmacists in healthcare institutions and clinical biochemists. The methodology was based on seven evaluation questions covering the five dimensions of intervention value: population, clinical, organizational, sociocultural and economic. A budgetary impact analysis was conducted, including the costs associated with adding the test to the Répertoire. Costs were projected over a three-year period from the perspective of the Quebec healthcare system. All the scientific, contextual and experiential data were interpreted and evaluated using a comprehensive value-based approach, defined according to the five dimensions, to guide the deliberative process of members of the Standing Deliberative Committee - Diagnostic Approaches and Screening (CDP-ADD) in developing the recommendation.

Authors' identified further research: Given the importance of the uncertainties raised during the deliberations, the CDP-ADD members recommended that the INESSS re-evaluate the relevance of maintaining the test in the Répertoire within three years.

Project Status: Completed

URL for project: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/dosage-sanguin-de-la-fludarabine-par-chromatographie-liquide-de-haute-performance-couplee-a-la-spectrometrie-de-masse-en-tandem-hplc-ms-ms.html

Year Published: 2024

URL for published report: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/dosage-sanguin-de-la-fludarabine-par-chromatographie-liquide-de-haute-performance-couplee-a-la-spectrometrie-de-masse-en-tandem-hplc-ms-ms.html

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Canada

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)