A user-friendly, open-source tool to project impact and cost of diagnostic tests for tuberculosis
- Johns Hopkins Bloomberg School of Public Health, United States
- Johns Hopkins University, United States
- Massachusetts General Hospital, United States
- University of Sheffield, United Kingdom
Figures
Figure 1
Overview of user-friendly model.
Users are asked, via open-source computer script or Web interface, to select one of the nine diagnostic strategies and to provide unit costs and three basic epidemiological parameters (TB incidence, …
Figure 2
Transmission model of TB diagnosis.
Boxes represent sub-populations in the model, and arrows represent rates of movement between those sub-populations. Parallel structures exist for: (a) HIV-infected vs HIV-uninfected; (b) …
Figure 3
Incremental 5-year cost and impact of TB diagnostic strategies, high-incidence setting.
Shown are cumulative projected 5-year costs and impact (averted TB cases [panel A] or MDR-TB cases [panel B]) of each diagnostic strategy described in the Introduction, incremental to the baseline …
Figure 4
Relative impact of diagnostic strategies in emblematic settings.
Shown are projected changes in TB incidence, MDR-TB incidence, TB mortality, and costs (in Year 1 and Year 5 after immediate implementation), relative to baseline (Strategy 1) after implementing …
Tables
Table 1
Model input parameters*
| Parameter | Value | Reference(s)/Rationale |
|---|---|---|
| TB and HIV Transmission | ||
| Transmission rate, per smear-positive/highly infectious person-year | Calibrated to user-defined TB incidence† | |
| Proportional reduction in per-case transmission rate, MDR-TB | Calibrated to user-defined MDR-TB prevalence† | |
| Proportional reduction in fitness, isoniazid-monoresistant TB | 25% of MDR-TB reduction | Assumption |
| HIV incidence rate, per year | Calibrated to user-defined HIV prevalence† | |
| Relative transmission rate from smear-negative/less infectious TB | 0.22 | (Behr et al., 1999) |
| Proportion of pulmonary TB that is smear-positive/highly infectious | ||
| HIV-negative | 0.63 | (Steingart et al., 2006a; Steingart et al., 2006b) |
| HIV-infected | 0.50 | (Getahun et al., 2007) |
| TB Progression | ||
| Endogenous reactivation rate | ||
| HIV-negative | 0.0005/year | (Horsburgh et al., 2010) |
| HIV-infected | 0.05/year | (Antonucci et al., 1995) |
| Proportion of recent infections resulting in rapid progression | ||
| HIV-negative | 0.14 | (Vynnycky and Fine, 1997; Dye et al., 1998) |
| HIV-infected | 0.47 | 0.75 without ART, (Daley et al., 1992) |
| 75% reduction if on ART, (Williams et al., 2010) 50% ART coverage | ||
| Reduction in TB rapid progression probability due to latent TB infection (HIV-negative only) | 0.79 | (Andrews et al., 2012) |
| TB Mortality and Resolution | ||
| Life expectancy at age 15 | 55 years | (World Bank, 2012) |
| Annual mortality from HIV | 0.05/year | (UNAIDS, 2012) |
| Annual mortality from TB | ||
| HIV-negative, smear-positive/highly infectious | 0.23/year | (Tiemersma et al., 2011) |
| HIV-negative, smear-negative/less infectious | 0.07/year | (Tiemersma et al., 2011) |
| HIV-infected | 1.0/year | (Corbett et al., 2003; Corbett et al., 2007; Wood et al., 2007) |
| Rate of spontaneous TB resolution (HIV-negative only) | ||
| Smear-positive/highly infectious | 0.1/year | (Tiemersma et al., 2011) |
| Smear-negative/less infectious | 0.27/year | (Tiemersma et al., 2011) |
| TB Treatment Outcomes and Emergence of Drug Resistance | ||
| Probability of failure or relapse (within 1 year) | ||
| Drug-susceptible | 0.04 | (World Health Organization, 2012) |
| INH-monoresistant, first-line therapy | 0.21 | (Menzies et al., 2009b) |
| INH-monoresistant, retreatment or 2nd-line | 0.16 | (Menzies et al., 2009b) |
| MDR-TB, first-line or retreatment | 0.50 | (Espinal et al., 2000) |
| MDR-TB, second-line therapy | 0.30 | (World Health Organization, 2010) |
| Proportion of one-year recurrence due to failure | ||
| Drug-susceptible | 0.14 | (Lew et al., 2008) |
| INH-monoresistant | 0.33 | |
| MDR-TB | 0.56 | |
| Probability of acquired drug resistance (per treatment course) | ||
| Susceptible becoming INH-monoresistant | 0.001 | (Menzies et al., 2009a; Menzies et al., 2009b) |
| Susceptible becoming MDR-TB | 0.002 | |
| INH-monoresistant becoming MDR-TB | 0.045 | |
| If treated with 2 effective drugs for >6 mos | 0.017 | |
| Behavioral Parameters | ||
| Infectious months before starting to seek care | ||
| HIV-negative | 9 months | (Dowdy et al., 2013) |
| HIV-infected | 1 month | (Corbett et al., 2004) |
| Diagnostic frequency while seeking care | 5.0/year | (Storla et al., 2008; Sreeramareddy et al., 2009) |
| Probability of treatment in a TB patient whose microbiological test is negative | 0.25 | (Wilkinson et al., 2000; Dowdy et al., 2008) |
| Loss to follow-up between diagnostic presentation and treatment initiation | ||
| Sputum smear or GXP (not same-day) | 0.15 | (MacPherson et al., 2014) |
| Culture (microcolony or commercial liquid) | 0.25 | (Dowdy et al., 2008) |
| Same-day diagnosis | 0 | Assumption |
| Diagnostic Accuracy | ||
| Sensitivity for smear-negative/less-infectious TB | ||
| Sputum smear microscopy | 0 | |
| Xpert MTB/RIF | 0.72 | (Brownell et al., 2012) |
| Culture (microcolony or commercial liquid) | 0.85 | (Cruciani et al., 2004; Leung et al., 2012) |
| Specificity for TB | (Steingart et al., 2006; Boehme et al., 2011; Leung et al., 2012) | |
| Sputum smear microscopy | 0.98 | |
| Xpert MTB/RIF | 0.98 | |
| Microcolony culture | 0.98 | |
| Sensitivity for drug resistance (if TB detected) | ||
| Microcolony culture (rifampin and isoniazid) | 0.98 | (Minion et al., 2010) |
| Xpert MTB/RIF (rifampin only) | 0.94 | (Boehme et al., 2011) |
| Specificity for drug resistance (if TB detected) | ||
| Microcolony culture (isoniazid) | 0.96 | (Minion et al., 2010) |
| Microcolony culture (rifampin) | 0.99 | (Minion et al., 2010) |
| Xpert MTB/RIF (rifampin) | 0.98 | (Boehme et al., 2011) |
| Diagnostic Delay and non-TB Care-Seeking | ||
| Days from presentation to treatment initiation | ||
| Sputum smear or Xpert MTB/RIF | 7 days | Assume 1 week |
| Microcolony or commercial liquid culture | 30 days | (Boehme et al., 2011) |
| Months of therapy before a failing regimen will be changed, or before default and recurrence | 6 months | Assumption |
| Annual rate of diagnostic evaluation for TB, among people who do not have active TB | 0.01/year | 10% of suspects have TB, high-incidence setting |
| Cost Parameters (user-defined; values below for comparison purposes only) | ||
| Per-patient cost of TB therapy | ||
| First-line | US$500 | User-defined |
| Retreatment | US$1000 | (Vassall et al., 2011) |
| Second-line/MDR | US$5000 | (Vassall et al., 2011) |
| Outpatient visit (diagnosis or follow-up) | US$10 | (Vassall et al., 2011) |
| Per-test cost: | ||
| Sputum smear | US$2 | (Vassall et al., 2011) |
| Same-day sputum smear | US$10 | Assumption |
| Xpert MTB/RIF | US$15 | (Vassall et al., 2011) |
| Same-day Xpert MTB/RIF | US$30 | Assumption |
| Microcolony culture (with DST) | US$5 | (Solari et al., 2011) |
| Commercial liquid-media culture | US$20 | (Vassall et al., 2011) |
| Commercial liquid-media culture + DST | US$40 | (Vassall et al., 2011) |
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*
In the actual model program (Supplementary file 1), users can change any parameter based on local values.
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†
For reference, the transmission rate (in infections per person-year during diagnosis-seeking active TB) is 36.9 in the reference scenario, 14.0 in the low-incidence scenario, 25.4 in the high MDR scenario, and 12.9 in the high HIV scenario. Corresponding proportional reductions in MDR-TB transmission rate are 0.23, 0.23, 0.21, and 0.19; and HIV incidence estimates (per 1000 adult person-years) are 0.7, 0.6, 0.6, and 18.9.
Table 2
Model parameters and symbolic representations
| Parameter | Representation | Baseline value (see Table 1) |
|---|---|---|
| Transmission rate (transmission events per highly infectious person-year) | β | Calibrated to TB incidence |
| Proportional reduction in per-case transmission rate | ||
| Drug-susceptible TB | φ0 | 1.0 |
| Isoniazid-monoresistant TB | φ1 | 25%* of φ2 |
| MDR-TB | φ2 | Calibrated |
| HIV incidence rate, per year | θ | Calibrated to HIV prevalence |
| Relative transmission rate from smear-negative/less infectious TB | ζ | 0.22 |
| Proportion of pulmonary TB that is smear-positive/highly infectious | ||
| HIV-negative | ψ0 | 0.63 |
| HIV-infected | ψ1 | 0.50 |
| Endogenous reactivation rate, per year | ||
| HIV-negative | ε0 | 0.005 |
| HIV-infected | ε1 | 0.05 |
| Proportion of recent infections resulting in rapid progression | ||
| HIV-negative | π0 | 0.14 |
| HIV-infected | π1 | 0.47 |
| Reduction in TB rapid progression probability due to latent TB infection | ||
| HIV-negative | ι | 0.79 |
| HIV-infected | Not included | 0 |
| Baseline mortality rate, per year | μbl | 1/55 = 0.018 |
| Additional HIV-related mortality rate, per year | μh | 0.05 |
| Additional untreated TB-related mortality rate, per year | ||
| HIV-negative, smear-positive/highly infectious | μt1 | 0.23 |
| HIV-negative, smear-negative/less infectious | μt0 | 0.07 |
| HIV-infected | μth | 1.0 |
| Rate of spontaneous TB resolution, per year | ||
| Smear-positive/highly infectious | ν1 | 0.1 |
| Smear-negative/less infectious | ν0 | 0.27 |
| HIV-infected | Not included | 0 |
| Rate of starting diagnosis-seeking in active TB, per year | ||
| HIV-negative | δe0 | 1.33 (9 months) |
| HIV-infected | δe1 | 12 (1/month) |
| Rate of progression: ineffective therapy to repeat therapy (failure) or active TB (relapse), per year | δf | 6/12 = 0.5 |
| Rate of diagnostic evaluation for TB, per year | ||
| Late active TB | Input into decision tree | 5.0 |
| No active TB | τ0 | 0.01 |
| Decision tree outputs (in addition to unit costs): | Vary by intervention | |
| Successful diagnosis rate of late active TB, per year | σhdip | |
| Rate of movement from successful diagnosis to treatment (1/diagnostic delay), per year | ρhdip | |
| Ineffective diagnosis rate of late active TB, per year | κhdip | |
| Rate of diagnosis and treatment leading to new resistance, per year | ||
| susceptible to INH-monoresistant | αsihip | |
| susceptible to MDR | αsmhip | |
| INH-monoresistant to MDR | αimhip |
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*
Calculated such that (1−φ1) = 0.25*(1−φ2).
Additional files
-
Supplementary file 1
Model code
- https://doi.org/10.7554/eLife.02565.009
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Supplementary file 2
Model interface and user manual
- https://doi.org/10.7554/eLife.02565.010
