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Burden of non-adherence to latent tuberculosis infection drug therapy and the potential cost-effectiveness of adherence interventions in Canada: a simulation study
  1. Anik R Patel1,
  2. Jonathon R Campbell2,
  3. Mohsen Sadatsafavi2,
  4. Fawziah Marra2,
  5. James C Johnston1,
  6. Kirsten Smillie1,
  7. Richard T Lester1
  1. 1 Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
  2. 2 Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada
  1. Correspondence to Dr. Anik R Patel; anikpa{at}, anikpatel10{at}


Objective Pharmaceutical treatment of latent tuberculosis infection (LTBI) reduces the risk of progression to active tuberculosis (TB); however, poor adherence tempers the protective effect. We aimed to estimate the health burden of non-adherence, the maximum allowable cost of hypothetical new adherence interventions to be cost-effective and the potential value of existing adherence interventions for patients with low-risk LTBI in Canada.

Design A microsimulation model of LTBI progression over 25 years.

Setting General practice in Canada.

Participants Individuals with LTBI who are initiating drug therapy.

Interventions A hypothetical intervention with a range of effectiveness was evaluated. Existing drug adherence interventions including peer support, two-way text messaging support, enhanced adherence counselling and adherence incentives were also evaluated.

Primary and secondary outcome measures Simulation outcomes included healthcare costs, TB incidence, TB deaths and quality-adjusted life years (QALYs). Base case results were interpreted against a willingness-to-pay threshold of $C50 000/QALY.

Results Compared with current adherence levels, full adherence to LTBI drug therapy could reduce new TB cases from 90.3 cases per 100 000 person-years to 35.9 cases per 100 000 person-years and reduce TB-related deaths from 7.9 deaths per 100 000 person-years to 3.1 deaths per 100 000 person-years. An intervention that increases relative adherence by 40% would bring the population near full adherence to drug therapy and could have a maximum allowable annual cost of approximately $C450 per person to be cost-effective. Based on estimates of effect sizes and costs of existing adherence interventions, we found that they yielded between 900 and 2400 additional QALYs per million people, reduced TB deaths by 5%–25% and were likely to be cost-effective over 25 years.

Conclusion Full adherence could reduce the number of future TB cases by nearly 60%, offsetting TB-related costs and health burden. Several existing interventions are could be cost-effective to help achieve this goal.

  • burden of disease
  • health economics
  • tuberculosis
  • public health
  • cost-effectiveness
  • adherence interventions

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  • Contributors AP conceived the study, participated in design of the study, conducted data analysis and drafted the final manuscript. JRC participated in design of the study, conducted data analysis and helped draft the final manuscript. MS participated in design of the study and helped to draft the final manuscript. FM participated in design of the study and helped to draft the final manuscript. JJ participated in design of the study and helped to draft the final manuscript. KS participated in data analysis and helped to draft the final manuscript. RTL conceived the study, secured funding for the study, participated in design of the study and helped to draft the final manuscript. All authors have read and approved the final manuscript.

  • Funding This study was supported by the British Columbia Lung Association (reference no F10906110) and the Canadian Institutes of Health Research Partnerships for Health System Improvement (reference no 267385). AP was supported in part by the National Institute of Mental Health of the National Institutes of Health under grant no R01MH097558901 and by the Canadian HIV Trials Network. JJ and RTL were supported in part by a Michael Smith Foundation award for Health Research Scholars.

  • Competing interests RTL is executive and scientific director of the WelTel International Health Society and WelTel, which develop and implement mobile health solutions. The remaining authors declare that they have no competing interests.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement No additional data are available.

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