Cost-effectiveness and health impact of screening and treatment of Mycobacterium tuberculosis infection among formerly incarcerated individuals in Brazil: a Markov modelling study.

BACKGROUND: Individuals who were formerly incarcerated have high tuberculosis incidence, but are generally not considered among the risk groups eligible for tuberculosis prevention. We investigated the potential health impact and cost-effectiveness of Mycobacterium tuberculosis infection screening and tuberculosis preventive treatment (TPT) for individuals who were formerly incarcerated in Brazil. METHODS: Using published evidence for Brazil, we constructed a Markov state transition model estimating tuberculosis-related health outcomes and costs among individuals who were formerly incarcerated, by simulating transitions between health states over time. The analysis compared tuberculosis infection screening and TPT, to no screening, considering a combination of M tuberculosis infection tests and TPT regimens. We quantified health effects as reductions in tuberculosis cases, tuberculosis deaths, and disability-adjusted life-years (DALYs). We assessed costs from a tuberculosis programme perspective. We report intervention cost-effectiveness as the incremental costs per DALY averted, and tested how results changed across subgroups of the target population. FINDINGS: Compared with no intervention, an intervention incorporating tuberculin skin testing and treatment with 3 months of isoniazid and rifapentine would avert 31 (95% uncertainty interval 14-56) lifetime tuberculosis cases and 4·1 (1·4-5·8) lifetime tuberculosis deaths per 1000 individuals, and cost US$242 per DALY averted. All test and regimen combinations were cost-effective compared with no screening. Younger age, longer incarceration, and more recent prison release were each associated with significantly greater health benefits and more favourable cost-effectiveness ratios, although the intervention was cost-effective for all subgroups examined. INTERPRETATION: M tuberculosis infection screening and TPT for individuals who were formerly incarcerated appears cost-effective, and would provide valuable health gains. FUNDING: National Institutes of Health. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Evaluation of a social protection policy on tuberculosis treatment outcomes: A prospective cohort study.

BACKGROUND: Tuberculosis (TB) still represents a major public health problem in Latin America, with low success and high default rates. Poor adherence represents a major threat for TB control and promotes emergence of drug-resistant TB. Expanding social protection programs could have a substantial effect on the global burden of TB; however, there is little evidence to evaluate the outcomes of socioeconomic support interventions. This study evaluated the effect of a conditional cash transfer (CCT) policy on treatment success and default rates in a prospective cohort of socioeconomically disadvantaged patients. METHODS AND FINDINGS: Data were collected on adult patients with first diagnosis of pulmonary TB starting treatment in public healthcare facilities (HCFs) from 16 health departments with high TB burden in Buenos Aires who were followed until treatment completion or abandonment. The main exposure of interest was the registration to receive the CCT. Other covariates, such as sociodemographic and clinical variables and HCFs' characteristics usually associated with treatment adherence and outcomes, were also considered in the analysis. We used hierarchical models, propensity score (PS) matching, and inverse probability weighting (IPW) to estimate treatment effects, adjusting for individual and health system confounders. Of 941 patients with known CCT status, 377 registered for the program showed significantly higher success rates (82% versus 69%) and lower default rates (11% versus 20%). After controlling for individual and system characteristics and modality of treatment, odds ratio (OR) for success was 2.9 (95% CI 2, 4.3, P < 0.001) and default was 0.36 (95% CI 0.23, 0.57, P < 0.001). As this is an observational study evaluating an intervention not randomly assigned, there might be some unmeasured residual confounding. Although it is possible that a small number of patients was not registered into the program because they were deemed not eligible, the majority of patients fulfilled the requirements and were not registered because of different reasons. Since the information on the CCT was collected at the end of the study, we do not know the exact timing for when each patient was registered for the program. CONCLUSIONS: The CCT appears to be a valuable health policy intervention to improve TB treatment outcomes. Incorporating these interventions as established policies may have a considerable effect on the control of TB in similar high-burden areas.

Representations on adherence to the treatment of Multidrug-Resistant Tuberculosis.

OBJECTIVE: To identify representations regarding adherence to the treatment of multidrug-resistant tuberculosis from the perspective of patients who were discharged upon being cured. METHOD: A qualitative study with patients who completed the drug treatment for multidrug-resistant tuberculosis in São Paulo. Social Determination was used to interpret the health-disease process, and the testimonies were analyzed according to dialectical hermeneutics and the discourse analysis technique. RESULTS: Twenty-one patients were interviewed. The majority (80.9%) were men, in the productive age group (90.4%) and on sick leave or unemployed (57.2%) during the treatment. Based on the testimonies, three categories associated with adherence to treatment emerged: the desire to live, support for the development of treatment and care provided by the health services. CONCLUSION: For the study sample, adherence to the treatment of multidrug-resistant tuberculosis was related to having a life project and support from the family and health professionals. Free treatment is fundamental for adherence, given the fragilities arising from the social insertion of people affected by the disease. Therefore, special attention is required from the health services to understand patient needs.

A randomized controlled study of socioeconomic support to enhance tuberculosis prevention and treatment, Peru.

OBJECTIVE: To evaluate the impact of socioeconomic support on tuberculosis preventive therapy initiation in household contacts of tuberculosis patients and on treatment success in patients. METHODS: A non-blinded, household-randomized, controlled study was performed between February 2014 and June 2015 in 32 shanty towns in Peru. It included patients being treated for tuberculosis and their household contacts. Households were randomly assigned to either the standard of care provided by Peru's national tuberculosis programme (control arm) or the same standard of care plus socioeconomic support (intervention arm). Socioeconomic support comprised conditional cash transfers up to 230 United States dollars per household, community meetings and household visits. Rates of tuberculosis preventive therapy initiation and treatment success (i.e. cure or treatment completion) were compared in intervention and control arms. FINDINGS: Overall, 282 of 312 (90%) households agreed to participate: 135 in the intervention arm and 147 in the control arm. There were 410 contacts younger than 20 years: 43% in the intervention arm initiated tuberculosis preventive therapy versus 25% in the control arm (adjusted odds ratio, aOR: 2.2; 95% confidence interval, CI: 1.1-4.1). An intention-to-treat analysis showed that treatment was successful in 64% (87/135) of patients in the intervention arm versus 53% (78/147) in the control arm (unadjusted OR: 1.6; 95% CI: 1.0-2.6). These improvements were equitable, being independent of household poverty. CONCLUSION: A tuberculosis-specific, socioeconomic support intervention increased uptake of tuberculosis preventive therapy and tuberculosis treatment success and is being evaluated in the Community Randomized Evaluation of a Socioeconomic Intervention to Prevent TB (CRESIPT) project.

Health outcomes of bedaquiline in the treatment of multidrug-resistant tuberculosis in selected high burden countries.

BACKGROUND: Less than one-third of patients who are estimated to be infected with multidrug-resistant tuberculosis (MDR-TB) receive MDR-TB treatment regimens, and only 48% of those who received treatment have successful outcomes. Despite current regimens, newer, more effective and cost-effective approaches to treatment are needed. The aim of the study was to project health outcomes and impact on healthcare resources of adding bedaquiline to the treatment regimen of MDR-TB in selected high burden countries: Estonia, Russia, South Africa, Peru, China, the Philippines, and India. METHODS: This study adapted an existing Markov model to estimate the health outcomes and impact on total healthcare costs of adding bedaquiline to current MDR-TB treatment regimens. A price threshold analysis was conducted to determine the price range at which bedaquiline would be cost-effective. RESULTS: Adding bedaquiline to the background regimen (BR) resulted in increased disability-adjusted life years (DALYs) averted, and reduced total healthcare costs (excluding treatment acquisition costs) compared with BR alone in all countries analyzed. Addition of bedaquiline to BR resulted in savings to healthcare costs compared with BR alone in all countries analyzed, with the highest impact expected in Russia (US$194 million) and South Africa (US$43 million). The price per regimen at which bedaquiline would be cost-effective ranged between US$23,904-US$203,492 in Estonia, Russia, Peru, South Africa, and China (high and upper middle-income countries) and between US$6,996-US$20,323 in the Philippines and India (lower middle-income countries); however, these cost-effective prices do not necessarily address concerns about affordability. CONCLUSIONS: Adding bedaquiline to BR provides improvements in health outcomes and reductions in healthcare costs in high MDR-TB burden countries. The range of prices per regimen for which bedaquiline would be cost-effective varied between countries.

Cost and cost-effectiveness of tuberculosis treatment shortening: a model-based analysis.

BACKGROUND: Despite improvements in treatment success rates for tuberculosis (TB), current six-month regimen duration remains a challenge for many National TB Programmes, health systems, and patients. There is increasing investment in the development of shortened regimens with a number of candidates in phase 3 trials. METHODS: We developed an individual-based decision analytic model to assess the cost-effectiveness of a hypothetical four-month regimen for first-line treatment of TB, assuming non-inferiority to current regimens of six-month duration. The model was populated using extensive, empirically-collected data to estimate the economic impact on both health systems and patients of regimen shortening for first-line TB treatment in South Africa, Brazil, Bangladesh, and Tanzania. We explicitly considered 'real world' constraints such as sub-optimal guideline adherence. RESULTS: From a societal perspective, a shortened regimen, priced at USD1 per day, could be a cost-saving option in South Africa, Brazil, and Tanzania, but would not be cost-effective in Bangladesh when compared to one gross domestic product (GDP) per capita. Incorporating 'real world' constraints reduces cost-effectiveness. Patient-incurred costs could be reduced in all settings. From a health service perspective, increased drug costs need to be balanced against decreased delivery costs. The new regimen would remain a cost-effective option, when compared to each countries' GDP per capita, even if new drugs cost up to USD7.5 and USD53.8 per day in South Africa and Brazil; this threshold was above USD1 in Tanzania and under USD1 in Bangladesh. CONCLUSION: Reducing the duration of first-line TB treatment has the potential for substantial economic gains from a patient perspective. The potential economic gains for health services may also be important, but will be context-specific and dependent on the appropriate pricing of any new regimen.

The cost-effectiveness of treating triple coinfection with HIV, tuberculosis and hepatitis C virus.

OBJECTIVES: The objective of this study was to estimate the cost-effectiveness of treating patients infected with HIV and simultaneously coinfected with tuberculosis (TB) and hepatitis C virus (HCV). METHODS: A mathematical model for HIV coinfection with TB and HCV is introduced. The model was designed to incorporate parameters of control for the coverage of care, which makes it useful for performing cost-effectiveness analysis of public policies. A cost-effectiveness analysis of early medical care of patients with TB and HCV coinfection, with coverage of 0 (basal), 25, 50, 75 and 100%, was performed for the whole cohort of patients and a special analysis was performed in a selected population with triple infection. RESULTS: The cost per resolved infection and the cost per year of life gained were found to be very cost-effective for the population with triple infection, for all different coverages. CONCLUSIONS: It is known that treating patients with HIV who are coinfected with TB or HCV implies high cost and low efficacy, but it is possible that the population with triple infections could achieve important benefits in terms of years of life gained.

[Tuberculosis 110 years after the Nobel Prize awarded to Koch]. / La tuberculosis a 110 años del Premio Nobel de Koch.

The Nobel Prize in Physiology or Medicine was awarded in 1905 to Robert Koch "for his investigations and discoveries in relation to tuberculosis (TB)". He discovered the causal agent of TB, described the four principles that since then have guided research in communicable diseases and also prepared the old tuberculin, a bacillary extract that failed as a healing element but allowed the early diagnosis of TB infection and promoted the understanding of cellular immunity. After his death, the most conspicuous achievements against TB were the BCG vaccine, and the discovery of streptomycin, the antibiotic that launched the era of the effective treatment of TB. Drug-resistance soon appeared. In Argentina, studies on drug resistance began in the 60s. In the 70s, shortened anti-TB drug schemes were introduced consisting in two-month treatment with four drugs, followed by four months with two drugs. The incidence of TB decreased worldwide, but the immune depression associated with awarded together with the misuse of anti-TB drugs allowed the emergence of multidrug resistance and extensive resistance, with the emergence of nosocomial outbreaks worldwide, including Argentina. New rapid diagnostic methods based on molecular biology were developed and also new drugs, but the treatment of multidrug resistant and extensively resistant TB is still difficult and expensive. TB research has marked several milestones in medical sciences, including the monumental Koch postulates, the tuberculin skin test that laid the basis for understanding cell-mediated immunity, the first design of randomized clinical trials and the use of combined multi-drug treatments.

Cost-effectiveness of tuberculosis screening and isoniazid treatment in the TB/HIV in Rio (THRio) Study.

OBJECTIVE: To estimate the incremental cost-effectiveness of tuberculosis (TB) screening and isoniazid preventive therapy (IPT) among human immunodeficiency virus (HIV) infected adults in Rio de Janeiro, Brazil. DESIGN: We used decision analysis, populated by data from a cluster-randomized trial, to project the costs (in 2010 USD) and effectiveness (in disability-adjusted life years [DALYs] averted) of training health care workers to implement the tuberculin skin test (TST), followed by IPT for TST-positive patients with no evidence of active TB. This intervention was compared to a baseline of usual care. We used time horizons of 1 year for the intervention and 20 years for disease outcomes, with all future DALYs and medical costs discounted at 3% per year. RESULTS: Providing this intervention to 100 people would avert 1.14 discounted DALYs (1.57 undiscounted DALYs). The median estimated incremental cost-effectiveness ratio was $2273 (IQR $1779-$3135) per DALY averted, less than Brazil's 2010 per capita gross domestic product (GDP) of $11,700. Results were most sensitive to the cost of providing the training. CONCLUSION: Training health care workers to screen HIV-infected adults with TST and provide IPT to those with latent tuberculous infection can be considered cost-effective relative to the Brazilian GDP per capita.

[Extensively drug-resistant tuberculosis (XDR-TB): successful therapies used in the clinic to the disease]. / Tuberculosis extensamente resistente a antibióticos (TB-XDR): terapias utilizadas con éxito en la clínica para curar la enfermedad.

Mycobacterial species have practically evolved along humankind, sometimes provoking serious diseases. Among them, tuberculosis (TB), produced by M. tuberculosiscomplex bacteria, is historically the single most devastating infectious agent. Like many other microorganisms, M. tuberculosis resistant to antibiotics have risen as a consequence of selective pressure for mutants able to persist despite being attacked with drugs that would otherwise erradicate them from the infected person. Given the current long-term (6-9 months) therapy with multiple antibiotics, many people abandon their treatments, therefore promoting that bacteria that were not eliminated during therapy get exposed to suboptimal antibiotic concentrations, probably leading to mutations and drug resistance. In this scenario, extremely-drug resistant (XDR) TB was recognized not more than a decade ago, prompting concerns for a more complicated drug regimen with few available molecules. In recent years, either old antibiotics have been rediscovered as good measures to control XDR-TB, or new ones have emerged as alternatives to cure patients of this type of infection. In this work we aim to provide the medical community in Mexico with information of such drug regimens that have succesfully worked, in order to get their consideration for use in our country.

Social, economic, and psychological impacts of MDR-TB treatment in Tijuana, Mexico: a patient's perspective.

SETTING: The State of Baja California, Mexico, had the highest prevalence of multidrug-resistant tuberculosis (MDR-TB) in Mexico in 2009. OBJECTIVE: To understand the socio-economic burden of MDR-TB disease and its treatment on patients in Tijuana and Mexicali, Mexico. DESIGN: From July to November 2009, qualitative interviews were conducted with 12 patients enrolled in a US-Mexico binational MDR-TB treatment program, Puentes de Esperanza (Bridges of Hope), which was designed to support MDR-TB patients. In-depth interviews were coded to identify major themes in patient experiences of MDR-TB diagnosis and care. RESULTS: While some patients were able to maintain their pre-MDR-TB lives to a limited extent, most patients reported losing their sense of identity due to their inability to work, social isolation, and stigmatization from family and friends. The majority of participants expressed appreciation for Puentes' role in 'saving their lives'. CONCLUSION: Being diagnosed with MDR-TB and undergoing treatment imposes significant psychological, social and economic stress on patients. Strong social support elements within Puentes helped alleviate these burdens. Improvements to the program might include peer-support groups for patients undergoing treatment and transitioning back into the community after treatment.

Can Brazil play a more important role in global tuberculosis drug production? An assessment of current capacity and challenges.

BACKGROUND: Despite the existence of effective treatment, tuberculosis is still a global public health issue. The World Health Organization recommends a six-month four-drug regimen in fixed-dose combination formulation to treat drug sensitive tuberculosis, and long course regimens with several second-line drugs to treat multi-drug resistant tuberculosis. To achieve the projected tuberculosis elimination goal by 2050, it will be essential to ensure a non-interrupted supply of quality-assured tuberculosis drugs. However, quality and affordable tuberculosis drug supply is still a significant challenge for National Tuberculosis Programs. DISCUSSION: Quality drug production requires a combination of complex steps. The first challenge is to guarantee the quality of tuberculosis active pharmaceutical ingredients, then ensure an adequate manufacturing process, according to international standards, to guarantee final product's safety, efficacy and quality. Good practices for storage, transport, distribution and quality control procedures must follow. In contrast to other high-burden countries, Brazil produces tuberculosis drugs through a strong network of public sector drug manufacturers regulated by a World Health Organization-certified national sanitary authority. The installed capacity for production surpasses the 71,000 needed treatments in the country. However, in order to be prepared to act as a global supplier, important bottlenecks are to be overcome. This article presents an in-depth analysis of the current status of production of tuberculosis drugs in Brazil and the bottlenecks and opportunities for the country to sustain national demand and play a role as a potential global supplier. Raw material and drug production, quality control, international certification and pre-qualification, political commitment and regulatory aspects are discussed, as well recommendations for tackling these bottlenecks. This discussion becomes more important as new drugs and regimens to treat tuberculosis are expected in a close future. SUMMARY: International manufacturers of raw material for tuberculosis treatment should undergo certification and pre-qualify their active pharmaceutical ingredients as a first step to ensure quality of tuberculosis drugs. At the country level, Brazilian public manufacturers should apply for international certification and tuberculosis drugs should be pre-qualified by international organisms. Finally, only with political commitment and large-scale production will Brazilian public sector manufacturers be able to partially supply the global market.

Free tuberculosis diagnosis and treatment are not enough: patient cost evidence from three continents.

SETTING: The National Tuberculosis Programs of Ghana, Viet Nam and the Dominican Republic. OBJECTIVE: To assess the direct and indirect costs of tuberculosis (TB) diagnosis and treatment for patients and households. DESIGN: Each country translated and adapted a structured questionnaire, the Tool to Estimate Patients' Costs. A random sample of new adult patients treated for at least 1 month was interviewed in all three countries. RESULTS: Across the countries, 27-70% of patients stopped working and experienced reduced income, 5-37% sold property and 17-47% borrowed money due to TB. Hospitalisation costs (US$42-118) and additional food items formed the largest part of direct costs during treatment. Average total patient costs (US$538-1268) were equivalent to approximately 1 year of individual income. CONCLUSION: We observed similar patterns and challenges of TB-related costs for patients across the three countries. We advocate for global, united action for TB patients to be included under social protection schemes and for national TB programmes to improve equitable access to care.

[Cost-effectiveness of an alternative tuberculosis treatment: home-based guardian monitoring of patients]. / Costo-efectividad de un tratamiento antituberculoso alternativo: seguimiento a convivientes residenciales de los pacientes.

OBJECTIVE: Estimate the cost-effectiveness ratio of the directly observed treatment short course (DOTS) for treatment of tuberculosis (TB), comparing it to a variation of this treatment that includes increased home-based guardian monitoring of patients (DOTS-R). METHODS: Taking a social perspective that includes the costs for the health institutions, the patients, and their family members, and for other entities that contribute to making operation of the program effective, the costs incurred with each of the two strategies were evaluated and the cost-effectiveness ratios were estimated adopting the measures of effect used by the control programs. The estimate of the cost of each of the two strategies includes the cost to the health institutions that administer treatment, the patients and their family members, and the cost to the Ministry of Health that manages public health programs on the municipal level. Based on these costs and the number of cases cured and treatments completed as outcome measures of each of the strategies evaluated, the cost-effectiveness ratio and incremental cost were calculated. RESULTS: The DOTS-R was found to be more cost-effective for achievement of successful treatments than the DOTS. The DOTS-R recorded costs of US$ 1 122.40 to US$ 1 152.70 for each case cured compared to values of US$ 1 137.00 to US$ 1 494.30 for the DOTS. The percentage of cases treated successfully was higher with DOTS-R than with DOTS. CONCLUSIONS: The DOTS-R is a promising cost-effective alternative for improved control of TB in endemic areas. It is recommended that the health authorities include home-based guardian monitoring of patients in their institutional management of the TB program, with the participation of health workers and the physical and financial resources that currently support this program.

Costo-efectividad de un tratamiento antituberculoso alternativo: seguimiento a convivientes residenciales de los pacientes / Cost-effectiveness of an alternative tuberculosis treatment: home-based guardian monitoring of patients

Objetivo. Estimar la relación de costo-efectividad del tratamiento de corta duración bajoobservación directa (DOTS), comparándolo con una variación de dicho tratamiento, que incluyeun mayor seguimiento a los convivientes residenciales de los pacientes (DOTS-R) parael tratamiento de tuberculosis (TB).Métodos. Tomando una perspectiva social que incluye los costos para las institucionesde salud, para los pacientes y sus familiares, y para otras entidades que contribuyen a hacerefectiva la operación del programa, se evaluaron los costos incurridos con cada una de las dosestrategias y se estimaron razones costo-efectividad adoptando las medidas de efecto usadas porlos programas de control. La estimación de los costos de cada una de las dos estrategias incluyelos correspondientes a las instituciones de salud que administran el tratamiento, los pacientesy sus familiares, y los de la secretaría de salud que gestiona los programas de salud pública anivel municipal. Con base en estos costos y el número de casos curados y tratamientos terminadoscomo medidas de resultado de cada una de las estrategias evaluadas, se calcularon lasrazones costo-efectividad y costo incremental.Resultados. El DOTS-R se halló más costo-efectivo para lograr tratamientos exitosos queel DOTS. El DOTS-R registró costos de entre US$ 1 122,4 y US$ 1 152,7 por caso curado,comparados con valores de entre US$ 1 137,0 y US$ 1 494,3 correspondientes al DOTS. Laproporción de casos tratados con éxito fue mayor con DOTS-R que con DOTS.Conclusiones. El DOTS-R es una alternativa costo-efectiva promisoria para mejorar elcontrol de la TB en sitios endémicos. Se recomienda a las autoridades del sector salud incorporaren su gestión institucional del programa contra la TB, acciones de seguimiento de losconvivientes de pacientes, con la participación del personal de salud y los recursos físicos yfinancieros que apoyan actualmente dicho programa.

Objective. Estimate the cost-effectiveness ratio of the directly observed treatmentshort course (DOTS) for treatment of tuberculosis (TB), comparing it to a variation ofthis treatment that includes increased home-based guardian monitoring of patients(DOTS-R).Methods. Taking a social perspective that includes the costs for the healthinstitutions, the patients, and their family members, and for other entities thatcontribute to making operation of the program effective, the costs incurred with eachof the two strategies were evaluated and the cost-effectiveness ratios were estimatedadopting the measures of effect used by the control programs. The estimate of the costof each of the two strategies includes the cost to the health institutions that administertreatment, the patients and their family members, and the cost to the Ministry ofHealth that manages public health programs on the municipal level. Based on thesecosts and the number of cases cured and treatments completed as outcome measuresof each of the strategies evaluated, the cost-effectiveness ratio and incremental costwere calculated.Results. The DOTS-R was found to be more cost-effective for achievement ofsuccessful treatments than the DOTS. The DOTS-R recorded costs of US$ 1 122.40 toUS$ 1 152.70 for each case cured compared to values of US$ 1 137.00 to US$ 1 494.30for the DOTS. The percentage of cases treated successfully was higher with DOTS-Rthan with DOTS.Conclusions. The DOTS-R is a promising cost-effective alternative for improvedcontrol of TB in endemic areas. It is recommended that the health authorities includehome-based guardian monitoring of patients in their institutional management of theTB program, with the participation of health workers and the physical and financialresources that currently support this program.

Potential cost-effectiveness of rifampin vs. isoniazid for latent tuberculosis: implications for future clinical trials.

SETTING: Standard treatment for latent tuberculosis infection (LTBI) is 9 months daily isoniazid (9INH). An alternative is 4 months daily rifampin (4RMP), associated with better completion and less toxicity; however, its efficacy remains uncertain. OBJECTIVES: To assess the cost-effectiveness of these regimens for treating LTBI in human immunodeficiency virus negative persons, using results from a recent clinical trial, plus different scenarios for 4RMP efficacy, and to estimate the costs of an adequately powered noninferiority trial and resulting savings from substitution with 4RMP. DESIGN: A decision-analysis model tracked TB contacts and lower-risk tuberculin reactors receiving 9INH, 4RMP or no treatment. For different 4RMP efficacy scenarios, we estimated the cost-effectiveness, sample size and cost of non-inferiority trials, and potential cost savings substituting 4RMP for 9INH for 10 years in Canada. RESULTS: With an assumed 4RMP efficacy of 60%, 9INH was more effective but slightly more expensive. Above a threshold efficacy of 69%, 4RMP was cheaper and more effective than 9INH. If the true efficacy of 4RMP is ≥75%, a trial powered to detect non-inferiority with a lower limit of 60% estimated efficacy (~20 000 subjects) may lead to cost savings within 10 years, even with the extreme assumption that Canada bears the entire cost. CONCLUSION: 4RMP may be a reasonable alternative to 9INH. Costs of a large-scale non-inferiority trial may be offset by subsequent savings.

Patients' costs and cost-effectiveness of tuberculosis treatment in DOTS and non-DOTS facilities in Rio de Janeiro, Brazil.

BACKGROUND: Costs of tuberculosis diagnosis and treatment may represent a significant burden for the poor and for the health system in resource-poor countries. OBJECTIVES: The aim of this study was to analyze patients' costs of tuberculosis care and to estimate the incremental cost-effectiveness ratio (ICER) of the directly observed treatment (DOT) strategy per completed treatment in Rio de Janeiro, Brazil. METHODS: We interviewed 218 adult patients with bacteriologically confirmed pulmonary tuberculosis. Information on direct (out-of-pocket expenses) and indirect (hours lost) costs, loss in income and costs with extra help were gathered through a questionnaire. Healthcare system additional costs due to supervision of pill-intake were calculated considering staff salaries. Effectiveness was measured by treatment completion rate. The ICER of DOT compared to self-administered therapy (SAT) was calculated. PRINCIPAL FINDINGS: DOT increased costs during the treatment phase, while SAT increased costs in the pre-diagnostic phase, for both the patient and the health system. Treatment completion rates were 71% in SAT facilities and 79% in DOT facilities. Costs per completed treatment were US$ 194 for patients and U$ 189 for the health system in SAT facilities, compared to US$ 336 and US$ 726 in DOT facilities. The ICER was US$ 6,616 per completed DOT treatment compared to SAT. CONCLUSIONS: Costs incurred by TB patients are high in Rio de Janeiro, especially for those under DOT. The DOT strategy doubles patients' costs and increases by fourfold the health system costs per completed treatment. The additional costs for DOT may be one of the contributing factors to the completion rates below the targeted 85% recommended by WHO.