title: Potential cost-effectiveness of rifampin vs. isoniazid for latent tuberculosis: implications for future clinical trials.
abstract: METHODS
  Standard treatment for latent tuberculosis infection (LTBI) is 9 months daily isoniazid (9INH). An alternative is 4 months daily rifampin (4RMP), associated with better completion and less toxicity; however, its efficacy remains uncertain.
  
  
  OBJECTIVE
  To assess the cost-effectiveness of these regimens for treating LTBI in human immunodeficiency virus negative persons, using results from a recent clinical trial, plus different scenarios for 4RMP efficacy, and to estimate the costs of an adequately powered noninferiority trial and resulting savings from substitution with 4RMP.
  
  
  METHODS
  A decision-analysis model tracked TB contacts and lower-risk tuberculin reactors receiving 9INH, 4RMP or no treatment. For different 4RMP efficacy scenarios, we estimated the cost-effectiveness, sample size and cost of non-inferiority trials, and potential cost savings substituting 4RMP for 9INH for 10 years in Canada.
  
  
  RESULTS
  With an assumed 4RMP efficacy of 60%, 9INH was more effective but slightly more expensive. Above a threshold efficacy of 69%, 4RMP was cheaper and more effective than 9INH. If the true efficacy of 4RMP is ≥75%, a trial powered to detect non-inferiority with a lower limit of 60% estimated efficacy (~20 000 subjects) may lead to cost savings within 10 years, even with the extreme assumption that Canada bears the entire cost.
  
  
  CONCLUSIONS
  4RMP may be a reasonable alternative to 9INH. Costs of a large-scale non-inferiority trial may be offset by subsequent savings.
authors.affiliation: Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, Montreal, Quebec, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Esfahani
authors.forename: A
authors.initials: A
authors.lastname: Aspler
authors.forename: D
authors.initials: D
authors.lastname: Menzies
authors.forename: K
authors.initials: K
authors.lastname: Schwartzman
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics*; D001938:Brazil; D002170:Canada; D003362:Cost-Benefit Analysis; D003661:Decision Support Techniques; D004334:Drug Administration Schedule; D016527:Drug Costs; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics*; D055985:Latent Tuberculosis / Q000175:diagnosis / Q000188:drug therapy* / Q000191:economics* / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D018803:Models, Economic; D012107:Research Design; D012293:Rifampin / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics*; D012529:Saudi Arabia; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D007538:Isoniazid; D012293:Rifampin