[Blood determination of a panel of anti-tuberculosis drugs using a multiplex approach by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) in the context of clinical pharmacometrics]

Zaoui K, Jolicoeur A
Record ID 32018013796
French
Original Title: Dosage sanguin d’un panel d’antituberculeux selon une approche multiplexe par chromatographie liquide couplée à la spectrométrie de masse en tandem (LC-MS/MS) dans un contexte de pharmacométrie clinique
Authors' objectives: A request to include a new test in the Répertoire québécois et système de mesure des procédures de biologie médicale (hereinafter referred to as the Répertoire) has been submitted to the Ministère de la Santé et des Services sociaux (MSSS) by the Grappe Montréal-CUSM (hereinafter referred to as the applicant laboratory). The MSSS has mandated the Institut national d'excellence en santé et en services sociaux (INESSS) to evaluate the relevance of including the blood determination of a panel of anti-tuberculosis drugs in the Répertoire, using a multiplex LC-MS/MS approach in the context of clinical pharmacometrics.
Authors' results and conclusions: RESULTS (#1 POPULATION DIMENSION): In Québec, active tuberculosis is a mandatory reportable disease that requires mandatory treatment. • The treatment of tuberculosis is complex and relies mainly on a combination of antibiotics administered over a prolonged period. • Anti-tuberculosis drugs can cause a number of significant side effects. (#2 CLINICAL DIMENSION): Individual pharmacokinetic variability, depending in particular on age, HIV status, diabetes and other comorbidities, may modify blood concentrations of antituberculosis drugs. • Several studies have shown that monitoring the blood concentration of antituberculosis drugs in conjunction with dose adjustments enables concentrations to be achieved within the targeted therapeutic range. • Some data suggest that adjusting TB drug doses in the context of clinical pharmacometrics may reduce the time to sputum culture negativation and the overall duration of treatment. (#3 ORGANIZATIONAL DIMENSION): At present, the dosage of anti-tuberculosis drugs is only available outside Quebec. • Should the analysis be added to the Répertoire, it is reasonable to assume that the volume will be higher than that of tests currently performed outside Quebec. (#4 SOCIO-CULTURAL DIMENSION): According to these agencies, TB drug concentration monitoring should be considered in cases of relapse, failure, slow response or resistance to TB drugs, as well as in patients with co-morbidities such as diabetes, HIV, malnutrition and malabsorption. • These agencies do not mention any clinically relevant turnaround times associated with anti-tuberculosis drug dosing. • The clinicians consulted indicated that the pharmacometrics of anti-tuberculosis drugs would reduce the duration of isolation and its negative socio-economic impacts, particularly in remote areas. (#5 ECONOMIC DIMENSION): Many assays are currently sent outside Quebec for analysis. The average cost of an assay performed outside Quebec is $1,761, whereas it is $654 when performed by the requesting laboratory. Performing them in Quebec would therefore be a more efficient strategy. • On average, INESSS anticipates that TB drug testing will be required for 90 patients over a 3-year period. This equates to an approximate volume of 333 samples over 3 years.
Authors' recommendations: In light of the above findings, INESSS recommends that the Minister of Health include a multiplex LCMS/MS blood test for a panel of anti-tuberculosis drugs in the Répertoire, in the context of clinical pharmacometrics. In order to maximize its clinical relevance, TB drug pharmacometrics should be used in patients with active TB in the following medical conditions: - suboptimal clinical course during treatment; - drug interactions; - pharmacodynamic/kinetic issues (e.g. liver and kidney disease, diabetes, pregnancy, age); - tuberculosis at risk of unfavorable evolution during treatment; - suspected non-compliance.  Comply with a laboratory response time of 10 to 14 days for regular orders and 4 to 7 days for urgent orders, including severe clinical cases, hospitalized patients or cases of resistant tuberculosis, as well as samples from remote regions or territories.  Follow-up on test implementation over the next few years to document volume.  Promote research and the dissemination of scientific findings on the dosing of anti-tuberculosis drugs in the Quebec context.  Should it be included in the Répertoire, the analysis will have to meet ISO 15189 requirements.
Authors' methods: To answer the evaluation questions, a rapid review of the scientific literature was conducted, based on publications listed in bibliographic databases and other information sources. In addition, consultations were held with clinicians and other stakeholders. The methodology was deployed around eleven evaluation questions covering the five dimensions of the INESSS's framework for assessing the value of interventions. A budgetary impact analysis was conducted, taking into account the costs associated with the introduction of blood testing for a panel of anti-tuberculosis drugs in the Repertory. Costs were projected over a three-year timeframe from a healthcare system perspective. All the scientific, contextual and experiential data were interpreted and synthesized in findings to guide the deliberative process of the members of the Comité délibératif permanent - Approches diagnostiques et dépistage (CDP-ADD) in developing the recommendation.
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
  • Antitubercular Agents
  • Drug Monitoring
  • Tandem Mass Spectrometry
  • Liquid Chromatography-Mass Spectrometry
  • Tuberculosis
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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