Burden of non-adherence to latent tuberculosis infection drug therapy and the potential cost-effectiveness of adherence interventions in Canada: a simulation study


Abstract

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.

Keywords: adherence interventions; burden of disease; cost-effectiveness; health economics; public health; tuberculosis.

Conflict of interest statement

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.

Figures

Figure 1
Figure 1
Two-stage latent tuberculosis infection?(LTBI) treatment outcome decision analytic model.?The decision tree represents LTBI therapy outcomes based on isonicotinylhydrazide?(INH) as first choice therapy followed by rifampin?in cases of intolerance. The second stage was a Markov model that simulated the remaining time horizon where patients experienced a differential risk of tuberculosis?(TB) reactivation based on their adherence to drug therapy.
Figure 2
Figure 2
The relationship between an interventions’ effectiveness at improving adherence and maximum allowable cost at a WTP threshold of $C50?000/QALY.?Our primary analysis focused on the maximum allowable spending based on the efficacy of an intervention(s) that could improve adherence.?QALY, quality-adjusted life year; WTP, willingness to pay.
Figure 3
Figure 3
The likelihood that each intervention would be cost-effective (when interventions were individually compared with standard care) plotted as a function of intervention cost. Weekly SMS was the least sensitive to cost and would offer the highest probability of being cost-effective at most costs.
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