A Quantitative Benefit-Risk Analysis of Isoniazid for Treatment of Latent Tuberculosis Infection Using Incremental Benefit Framework

• Published in: Value in health 2013-01, Vol.16 (1), p.66-75
• Main Authors: Sadatsafavi, Mohsen, MD, PhD, Marra, Carlo, PharmD, PhD, Marra, Fawziah, PharmD, Moran, Onofre, MD, PhD, FitzGerald, J. Mark, MD, Lynd, Larry, PhD
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Age Factors; Algorithms; Antitubercular Agents - adverse effects; Antitubercular Agents - therapeutic use; Bacterial diseases; BCG Vaccine - administration & dosage; benefit-risk analysis; Biological and medical sciences; Canada; Comorbidity; Contact Tracing; Decision Support Techniques; decision uncertainty; Emigrants and Immigrants - statistics & numerical data; Health Policy; Human bacterial diseases; Humans; Immunization; Infection; Infectious diseases; Internal Medicine; Isoniazid - adverse effects; Isoniazid - therapeutic use; Latent Tuberculosis - drug therapy; Medical sciences; Miscellaneous; Models, Theoretical; Mycobacterium; Practice Guidelines as Topic; Public Health; Public health. Hygiene; Public health. Hygiene-occupational medicine; Quality-Adjusted Life Years; Registries; Risk assessment; Risk Assessment - methods; Screening; Time Factors; Tuberculin Test; Tuberculosis; Tuberculosis and atypical mycobacterial infections; Young Adult
• ISSN: 1098-3015; 1524-4733
• DOI: 10.1016/j.jval.2012.09.006

AbstractBackgroundWe undertook a quantitative benefit-risk analysis of a targeted isoniazid (INH) therapy for latent tuberculosis (TB) infection for different groups of contacts of active TB cases. MethodsWe developed a decision-analytic model to compare the treatment of latent TB infection in subgroups of contacts to no treatment over a 6-year time horizon in a Canadian setting. Contacts were stratified into 32 groups on the basis of five binary variables: type of contact (close or casual), tuberculin skin test (TST) results (positive or negative at 5 mm cutoff), Bacillus Calmette-Guérin vaccination status, place of birth (foreign- or Canadian-born), and age group (cutoff 35 years). Risk of TB reactivation was calculated for each subgroup from a longitudinal registry of contacts, adjusted for several potential confounders and comorbid conditions. We calculated the quality-adjusted life-years gained because of delayed or prevention of active TB via treatment of latent TB infection versus quality-adjusted life-years lost because of the adverse events to INH. ResultsA targeted policy based on adopting INH therapy only in subgroups with positive expected incremental net health benefit resulted in a different treatment decision than the current guidelines in five subgroups comprising 3.9% of the contacts. Namely, the targeted policy comprised no INH therapy in casual contacts with a positive vaccination history even with a positive TST result and INH therapy in foreign-born close contacts younger than 35 years even with a negative TST result. ConclusionsFrom a benefit-risk viewpoint, INH treatment of contacts should be tailored on the basis of risk assessment algorithms that consider a range of factors at the time of screening.