Two-way sensitivity analysis strategy graph comparing risk reduction and adherence for isoniazid/rifapentine daily for one month (1HP).

<p>The clear area shows combinations of adherence and risk reduction for 1HP that are high enough that 1HP is a cost-saving regimen. In the cross-hatched area, all combinations of adherence and risk reduction for 1HP are too low, so isoniazid/rifapentine monthly for 12 weeks self-administered (3HP-SAT) is preferred regimen.</p

Model parameters and utility adjustments, point estimates and ranges for sensitivity analyses.

<p>Model parameters and utility adjustments, point estimates and ranges for sensitivity analyses.</p

Cost-effectiveness plot for six regimens plus the “no treatment” strategy.

<p>Superior regimens are lower in cost (toward the left) and greater in efficacy (toward the top). Incremental cost-effectiveness ratios (ICERs) are shown for the two most effective regimens referenced to the strategy of “no treatment.” <i>Abbreviations: MZ = moxifloxacin/pyrazinamide, ZEmb = pyrazinamide/ethambutol, MEth = moxifloxacin/ethionamide, MP = moxifloxacin/PA-824, M = moxifloxacin monotherapy. ICER = incremental cost-effectiveness ratio in dollars per quality-adjusted life-year</i>.</p

Two-way sensitivity analysis strategy graph comparing adherence for isoniazid/rifapentine daily for one month (1HP) vs. isoniazid/rifapentine weekly for three months self-administered (3HP-SAT).

<p>In the diagonal cross-hatched area, 1HP is cost-saving and therefore the preferred regimen. In the horizontal cross-hatched area, 3HP-SAT is cost-saving. In the shaded area, neither regimen is cost-saving when compared to isoniazid monotherapy daily for nine months (9H), which is the preferred regimen.</p

Costs in US$ associated with treating latent TB infection.

*<p> <i>Average cost of routine monitoring and evaluation for mild toxicity under the assumption that 40% of individuals will require monthly monitoring of transaminases and 1.4% will have toxicity that will require a physician visit but not result in treatment discontinuation.</i></p

Lifetime costs and quality-adjusted life-years (QALY) for all regimens, efficacy predicted by murine model: MP>MZ>>MEmb>MEth = Isoniazid>M = ZEmb.

<p>Regimens referenced to the lowest-cost strategy.</p><p>*Incremental cost-effectiveness ratios (ICERs) are calculated relative to next-lowest-effectiveness option.</p><p><i>Abbreviations: MZ = moxifloxacin+pyrazinamide, ZEmb = pyrazinamide+ethambutol, MEth = Moxifloxacin+ethionamide, MP = moxifloxacin+PA-824, M = moxifloxacin monotherapy</i>.</p

Schematic of decision tree.

<p>A. Primary tree showing decision point between regimens and probability of a positive or negative test given presence or absence of infection. B. Positive test subtree. Individuals begin “on treatment” then move to “off treatment” due to toxicity, non-adherence, or treatment completion. Patients in “off treatment” can develop active disease and move to “TB treatment;” after treatment for active disease, they move to “prior TB.” Age-related mortality and death from TB or toxicity is also included. The negative test subtree is similar to the positive test subtree without the “on treatment” branch. Abbreviations: MZ = moxifloxacin+pyrazinamide, ZEmb = pyrazinamide+ethambutol, MEth = Moxifloxacin+ethionamide, MP = moxifloxacin+PA-824, M = moxifloxacin monotherapy.</p

Strategy graph of efficacy vs. toxicity.

<p>Solid lines indicate thresholds (“isoclines”) for indifference given monthly drug costs of $129 (pyrazinamide/ethambutol),$181 (moxifloxacin/ethambutol), and $404 (moxifloxacin/ethionamide) per month. Shaded area indicates combinations of toxicity and efficacy for which drug treatment is cost-effective compared to the “no treatment” strategy beneath each of these isoclines. Dotted lines indicate the base-case estimates for efficacy and toxicity of moxifloxacin/ethambutol.</p

Utility adjustments for events occurring in the model, expressed as fractions of a life-year.

<p>Utility adjustments for events occurring in the model, expressed as fractions of a life-year.</p

Cost-effectiveness plot of the four regimens and the “no treatment” strategy.

<p>Incremental cost-effectiveness ratios (ICER) are represented by the inverse slope of the dotted and dashed lines between strategies. <i>Abbreviations: 9H = isoniazid daily for 9 months, 3HP = isoniazid plus rifapentine weekly for 3 months, 1HP = isoniazid plus rifapentine daily for 1 month. SAT = self-administered therapy, DOT = directly-observed therapy</i>.</p