Compared with no screening, screening with TST resulted in undiscounted life-expectancy gains between 0.00 and 0.24 life months (0.00–0.13 discounted quality-adjusted life months) at an incremental cost from $50–$140 depending on the risk-group. Compared with TST screening, IGRA screening resulted in undiscounted life expectancy gains of 0.00–0.01 life months (0.00–0.008 discounted quality-adjusted life months) at incremental costs ranging from a savings of $10 to a cost of $20. The cost-effectiveness of screening for LTBI with TST or IGRA varied by risk-group, with four patterns of cost-effectiveness emerging related to four categories of risk: (1) patients at the highest risk of reactivation (close contacts and those living with HIV infection; (2) the foreign-born (both recent immigrants to the United States and those living in the United States for >5 yr); (3) vulnerable persons (the homeless, injection drug users, and former prisoners); and (4) individuals with chronic medical conditions ().
BASE CASE RESULTS OF AN ANALYSIS OF SCREENING FOR LTBI IN THE UNITED STATES
Patients at the Highest Risk of Reactivation
In close-contact children and adults and in individuals infected with HIV, the ICER of screening with TST compared with no screening was less than $50,000 per QALY, as was the ICER of screening with IGRA compared with TST. Although the sensitivity of IGRA was slightly lower than that of TST, because IGRA screening requires only one visit to obtain and interpret results, IGRA minimized loss to follow-up and increased receipt of test results. Thus, IGRA identified a greater number of patients with LTBI than TST screening identified, and IGRA screening was associated with longer life expectancy.
Recent Immigrants and Foreign-born Residents Living in the United States for More Than 5 Years
In recent immigrants to the United States and foreign-born residents who have lived in the United States for more than 5 years (foreign-born residents), IGRA screening resulted in either cost savings compared with TST, or in extended life expectancy with a lower cost per QALY gained compared with TST. Thus, IGRA dominated TST, meaning that any resources dedicated to using TST to screen would be better used providing IGRA screening.
In these risk-groups, IGRA dominated TST for two reasons. First, because IGRA reduced loss to follow-up, it functioned as a more sensitive screening test than TST, and led to longer mean life expectancy. Second, IGRA was substantially more specific than TST (99% vs. 92% specific), and therefore provided cost savings by minimizing the number of patients unnecessarily treated for LTBI.
The ICER of IGRA screening compared with no screening was less than $50,000 per QALY gained for recent immigrant adults and was less than $100,000 per QALY gained for recent immigrant children and foreign-born residents up to age 45 years. The ICER of IGRA screening compared with no screening for foreign-born residents age 45–64 years was $103,000 per QALY gained. In addition, as a result of a large population of foreign-born United States residents, and a relatively small number needed to screen to prevent one case of active TB, screening the foreign-born living in the United States for more than 5 years could potentially prevent more than 65,000 cases of active TB over the lifetime of those individuals, one of the largest potential absolute impacts of any risk-group ().
Figure 1. Number of cases of active tuberculosis (TB) preventable through latent tuberculosis infection (LTBI) screening in each risk-group considered by current United States LTBI screening guidelines. The bar graph depicts the absolute number of cases of active (more ...)
The ICER of screening with TST compared with no screening was $95,000 per QALY gained in the homeless, $104,600 per QALY gained in injection drug users, and $147,600 per QALY gained in former prisoners. The ICER of IGRA was $194,300 for the homeless and more than $200,000 per QALY gained in injection drug users and former prisoners. In these risk-groups, IGRA continued to have a better case detection rate than TST, but improved case detection resulted in little life-expectancy gain because the risk of reactivation TB was small, and the rate of INH completion low.
Individuals with Chronic Medical Conditions
In patients taking immunosuppressive medications, the ICER of screening with TST compared with no screening was $129,000 per QALY gained. In all other risk-groups, including underweight patients, gastrectomy patients, and patients with silicosis, diabetes, and end-stage renal disease, the ICER of using TST to screen for LTBI compared with no screening was greater than $200,000 per QALY gained and the ICER of using IGRA to screen for LTBI compared with using TST was greater than $300,000 per QALY gained. In these risk-groups, the prevalence of LTBI was low, and the risk of reactivation TB was reduced by competing risks of mortality, such that no screening test was cost-effective.
Sensitivity Analyses on Rate of Reactivation TB
When we assumed the lower rate of reactivation TB observed in the Glades Health Survey (low estimate), the ICER of IGRA screening remained less than $100,000 per QALY gained in close-contact adults and children, recent immigrant adults, and individuals infected with HIV. The ICER of both TST and IGRA screening was greater than $100,000 per QALY gained in all other risk-groups (). However, assuming the higher rate of reactivation that informs current United States screening guidelines (prior estimate), the ICER of TST screening was less than $100,000 per QALY gained in the homeless, injection drug users, and patients taking immunosuppressive medications. The ICER of IGRA screening was less than $100,000 per QALY gained in close-contact children and adults, individuals infected with HIV, recent immigrants to the United States, and foreign-born United States residents up to age 65 years ().
COST-EFFECTIVENESS OF SCREENING FOR LATENT TUBERCULOSIS INFECTION USING TST OR IGRA UNDER VARYING ESTIMATES OF THE RATE OF REACTIVATION TB
Sensitivity Analyses on TST and IGRA Test Characteristics
In recent immigrants and foreign-born United States residents, screening with either TST or IGRA was cost-effective across all plausible estimates of sensitivity. The ICER of IGRA compared with TST was sensitive to TST specificity, but remained less than $100,000 per QALY gained across a wide range of assumptions about test characteristics ().
Figure 2. Two-way sensitivity analysis of the incremental cost-effectiveness ratio of screening for latent tuberculosis infection (LTBI) using tuberculin skin test (TST) or interferon-γ release assays (IGRA) in foreign-born residents living in the United (more ...)
In close-contact adults, the impact of false-negative results was larger than that of false-positive results and test sensitivity determined cost-effectiveness. TST sensitivity, however, was mitigated by imperfect follow-up for TST results. Thus, IGRA remained cost-effective as long as the sensitivity of IGRA was greater than 79% (base case 83%) (see Figure E3 in the online supplement). If we assumed that 100% of patients returned for TST reading, however, TST was more sensitive than IGRA and provided greater life expectancy at lower cost (Table E1).
Sensitivity Analyses on Cost of IGRA
In foreign-born residents living in the United States for more than 5 years, age 25–44 years, the ICER of IGRA compared with TST screening was less than $100,000 per QALY gained across a range of estimates of IGRA test cost and TST test specificity. In the base case (TST specificity in the foreign-born = 92%), IGRA screening remained cost-effective up to an IGRA test cost of $64 (base case assumption $52). If the specificity of TST screening is only 85%, IGRA screening remained cost-effective up to an IGRA test cost of $83 (see Figure E4).
Additional Sensitivity Analyses
Patient age affected cost-effectiveness results through its impact on the lifetime risk of reactivation. When we increased the mean age to 65 years, screening remained cost-effective only for close-contact adults of a case of active TB and persons infected with HIV (Table E2).
INH toxicity had little impact on the cost-effectiveness of screening. When we both halved or doubled the rate of INH toxicity, the ICER of screening did not shift across the $100,000 per QALY threshold for any risk-group (Table E3).
Rates of INH treatment initiation and adherence to INH therapy had the greatest impact on cost-effectiveness in the homeless, injection drug users, and former prisoners, where very low rates of INH adherence reduced cost-effectiveness compared with the base case scenario (Tables E4 and E5).
The cost-effectiveness of screening was also sensitive to changes in estimates of the quality of life in patients who recovered from active TB. In the base case, we assumed that patients cured of active TB returned to full health. If a history of cured active TB was associated with a life-long 10% decrement in quality of life, the cost-effectiveness of screening with either IGRA or TST was less than $100,000 per QALY gained for all cohorts except foreign-born United States residents aged 65 years or older, and patients with silicosis, diabetes, and end-stage renal disease (Table E6).