title: A quantitative benefit-risk analysis of isoniazid for treatment of latent tuberculosis infection using incremental benefit framework.
abstract: BACKGROUND
  We 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.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  A 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.
  
  
  CONCLUSIONS
  From 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.
authors: Collaboration for Outcome Research and Evaluation, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada.
authors: Mohsen
authors: M
authors: Sadatsafavi
authors: Carlo
authors: C
authors: Marra
authors: Fawziah
authors: F
authors: Marra
authors: Onofre
authors: O
authors: Moran
authors: J Mark
authors: JM
authors: FitzGerald
authors: Larry
authors: L
authors: Lynd
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000465:Algorithms; D000995:Antitubercular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001500:BCG Vaccine / Q000008:administration & dosage; D002170:Canada; D016358:Contact Tracing; D003661:Decision Support Techniques; D054242:Emigrants and Immigrants / Q000706:statistics & numerical data; D006291:Health Policy; D006801:Humans; D007538:Isoniazid / Q000009:adverse effects / Q000627:therapeutic use*; D055985:Latent Tuberculosis / Q000188:drug therapy*; D008962:Models, Theoretical; D017410:Practice Guidelines as Topic; D019057:Quality-Adjusted Life Years; D012042:Registries; D018570:Risk Assessment / Q000379:methods; D013997:Time Factors; D014374:Tuberculin Test; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D001500:BCG Vaccine; D007538:Isoniazid