Comparing disease specific catastrophic cost estimates using longitudinal and cross-sectional designs: The example of tuberculosis.

BACKGROUND: There has been an increasing interest in assessing disease-specific catastrophic costs incurred by affected households as part of economic evaluations and to inform joint social/health policies for vulnerable groups. Although the longitudinal study design is the gold standard for estimating disease-specific household costs, many assessments are implemented with a cross-sectional design for pragmatic reasons. We aimed at identifying the potential biases of a cross-sectional design for estimating household cost, using the example of tuberculosis (TB), and exploring optimal approaches for sampling and interpolating cross-sectional cost data to estimate household costs. METHODS: Data on patient incurred costs, household income and coping strategies were collected from TB patients in Negros Occidental and Cebu in the Philippines between November 2018 and October 2020. The data collection tools were developed by adapting WHO Tuberculosis Patient Cost Surveys: A Handbook into a longitudinal study design. TB-specific catastrophic cost estimates were compared between longitudinal and simulated cross-sectional designs using different random samples from different times points in treatment (intensive and continuation phases). RESULTS: A total of 530 adult TB patients were enrolled upon TB diagnosis in this study. Using the longitudinal design, the catastrophic cost estimate for TB-affected households was 69 % using the output approach. The catastrophic cost estimates with the simulated cross-sectional design were affected by the reduction and recovery in household income during the episode of TB care and ranged from 40 to 55 %. CONCLUSION: Using longitudinally collected costs incurred by TB-affected households, we illustrated the potential limitations and implications of estimating household costs using a cross-sectional design. Not capturing changes in household income at multiple time points during the episode of the disease and estimating from inappropriate samples may result in biases that underestimates catastrophic cost.

Costs incurred by people with co-morbid tuberculosis and diabetes and their households in the Philippines.

OBJECTIVE: Diabetes is a risk factor for TB mortality and relapse. The Philippines has a high TB incidence with co-morbid diabetes. This study assessed the pre- and post-TB diagnosis costs incurred by people with TB and diabetes (TB-DM) and their households in the Philippines. METHODS: Longitudinal data was collected for costs, income, and coping mechanisms of TB-affected households in Negros Occidental and Cebu, the Philippines. Data collection was conducted four times during TB treatment. The data collection tools were developed by adapting WHO's cross-sectional questionnaire in the Tuberculosis Patient Cost Surveys: A Handbook into a longitudinal study design. Demographic and clinical characteristics, self-reported household income, number of facility visits, patient costs, the proportion of TB-affected households facing catastrophic costs due to TB (>20% of annual household income before TB), coping mechanisms, and social support received were compared by diabetes status at the time of TB diagnosis. RESULTS: 530 people with TB were enrolled in this study, and 144 (27.2%) had TB-DM based on diabetes testing at the time of TB diagnosis. 75.4% of people with TB-DM were more than 45 years old compared to 50.3% of people with TB-only (p<0.001). People with TB-DM had more frequent visits for TB treatment (120 vs 87 visits, p = 0.054) as well as for total visits for TB-DM treatment (129 vs 88 visits, p = 0.010) compared to those with TB-only. There was no significant difference in the proportion of TB-affected households facing catastrophic costs between those with TB-DM (76.3%) and those with TB-only (68.7%, p = 0.691). CONCLUSION: People with TB-DM in the Philippines face extensive health service use. However, this does not translate into substantial differences in the incidence of catastrophic cost. Further study is required to understand the incidence of catastrophic costs due to diabetes-only in the Philippines.

Effectiveness and cost-effectiveness of integrating the management of depression into routine HIV Care in Uganda (the HIV + D trial): A protocol for a cluster-randomised trial.

BACKGROUND: An estimated 8-30 % of people living with HIV (PLWH) have depressive disorders (DD) in sub-Saharan Africa. Of these, the majority are untreated in most of HIV care services. There is evidence from low- and middle- income countries of the effectiveness of both psychological treatments and antidepressant medication for the treatment of DD among PLWH, but no evidence on how these can be integrated into routine HIV care. This protocol describes a cluster-randomised trial to evaluate the effectiveness and cost-effectiveness of the HIV + D model for the integration of a collaborative stepped care intervention for DD into routine HIV care, which we have developed and piloted in Uganda. METHODS: Forty public health care facilities that provide HIV care in Kalungu, Masaka and Wakiso Districts will be randomly selected to participate in the trial. Each facility will recruit 10-30 eligible PLWH with DD and the total sample size will be 1200. The clusters will be randomised 1:1 to receive Enhanced Usual Care alone (EUC, i.e. HIV clinicians trained in Mental Health Gap Action Programme including guidelines on when and where to refer patients for psychiatric care) or EUC plus HIV + D (psychoeducation, Behavioural Activation, antidepressant medication and referral to a supervising mental health worker, delivered in a collaborative care stepwise approach). Eligibility criteria are PLWH attending the clinic, aged ≥ 18 years who screen positive on a depression screening questionnaire (Patient Health Questionnaire, PHQ-9 ≥ 10). The primary outcome is the mean depressive disorder symptom severity scores (assessed using the PHQ-9) at 3 months' post-randomisation, with secondary mental health, disability, HIV and economic outcomes measured at 3 and 12 months. The cost-effectiveness of EUC with HIV + D will be assessed from both the health system and the societal perspectives by collecting health system, patient and productivity costs and mean DD severity scores at 3 months, additional to health and non-health related quality of life measures (EQ-5D-5 L and OxCAP-MH). DISCUSSION: The study findings will inform policy makers and practitioners on the cost-effectiveness of a stepped care approach to integrate depression management in routine care for PLWH in low-resource settings. TRIAL REGISTRATION: ISRCTN, ISRCTN86760765. Registered 07 September 2017, https://doi.org/10.1186/ISRCTN86760765 .

Cultural and linguistic adaptation of the multi-dimensional OXCAP-MH for outcome measurement of mental health among people living with HIV/AIDS in Uganda: the Luganda version.

BACKGROUND: It is rare to find HIV/AIDS care providers in sub-Saharan Africa routinely providing mental health services, yet 8-30% of the people living with HIV have depression. In an ongoing trial to assess integration of collaborative care of depression into routine HIV services in Uganda, we will assess quality of life using the standard EQ-5D-5L, and the capability-based OxCAP-MH which has never been adapted nor used in a low-income setting. We present the results of the translation and validation process for cultural and linguistic appropriateness of the OxCAP-MH tool for people living with HIV/AIDS and depression in Uganda. METHODS: The translation process used the Concept Elaboration document, the source English version of OxCAP-MH, and the Back-Translation Review template as provided during the user registration process of the OxCAP-MH, and adhered to the Translation and Linguistic Validation process of the OxCAP-MH, which was developed following the international principles of good practice for translation as per the International Society for Pharmacoeconomics and Outcomes Research's standards. RESULTS: The final official Luganda version of the OxCAP-MH was obtained following a systematic iterative process, and is equivalent to the English version in content, but key concepts were translated to ensure cultural acceptability, feasibility and comprehension by Luganda-speaking people. CONCLUSION: The newly developed Luganda version of the OxCAP-MH can be used both as an alternative or as an addition to health-related quality of life patient-reported outcome measures in research about people living with HIV with comorbid depression, as well as more broadly for mental health research.

Disease characteristics and treatment of patients with diabetes mellitus attending government health services in Indonesia, Peru, Romania and South Africa.

OBJECTIVE: To describe the characteristics and management of Diabetes mellitus (DM) patients from low- and middle-income countries (LMIC). METHODS: We systematically characterised consecutive DM patients attending public health services in urban settings in Indonesia, Peru, Romania and South Africa, collecting data on DM treatment history, complications, drug treatment, obesity, HbA1c and cardiovascular risk profile; and assessing treatment gaps against relevant national guidelines. RESULTS: Patients (median 59 years, 62.9% female) mostly had type 2 diabetes (96%), half for >5 years (48.6%). Obesity (45.5%) and central obesity (females 84.8%; males 62.7%) were common. The median HbA1c was 8.7% (72 mmol/mol), ranging from 7.7% (61 mmol/mol; Peru) to 10.4% (90 mmol/mol; South Africa). Antidiabetes treatment included metformin (62.6%), insulin (37.8%), and other oral glucose-lowering drugs (34.8%). Disease complications included eyesight problems (50.4%), EGFR <60 ml/min (18.9%), heart disease (16.5%) and proteinuria (14.7%). Many had an elevated cardiovascular risk with elevated blood pressure (36%), LDL (71.0%) and smoking (13%), but few were taking antihypertensive drugs (47.1%), statins (28.5%) and aspirin (30.0%) when indicated. Few patients on insulin (8.0%), statins (8.4%) and antihypertensives (39.5%) reached treatment targets according to national guidelines. There were large differences between countries in terms of disease profile and medication use. CONCLUSION: DM patients in government clinics in four LMIC with considerable growth of DM have insufficient glycaemic control, frequent macrovascular and other complications, and insufficient preventive measures for cardiovascular disease. These findings underline the need to identify treatment barriers and secure optimal DM care in such settings.

Cost-effectiveness and resource implications of aggressive action on tuberculosis in China, India, and South Africa: a combined analysis of nine models.

BACKGROUND: The post-2015 End TB Strategy sets global targets of reducing tuberculosis incidence by 50% and mortality by 75% by 2025. We aimed to assess resource requirements and cost-effectiveness of strategies to achieve these targets in China, India, and South Africa. METHODS: We examined intervention scenarios developed in consultation with country stakeholders, which scaled up existing interventions to high but feasible coverage by 2025. Nine independent modelling groups collaborated to estimate policy outcomes, and we estimated the cost of each scenario by synthesising service use estimates, empirical cost data, and expert opinion on implementation strategies. We estimated health effects (ie, disability-adjusted life-years averted) and resource implications for 2016-35, including patient-incurred costs. To assess resource requirements and cost-effectiveness, we compared scenarios with a base case representing continued current practice. FINDINGS: Incremental tuberculosis service costs differed by scenario and country, and in some cases they more than doubled existing funding needs. In general, expansion of tuberculosis services substantially reduced patient-incurred costs and, in India and China, produced net cost savings for most interventions under a societal perspective. In all three countries, expansion of access to care produced substantial health gains. Compared with current practice and conventional cost-effectiveness thresholds, most intervention approaches seemed highly cost-effective. INTERPRETATION: Expansion of tuberculosis services seems cost-effective for high-burden countries and could generate substantial health and economic benefits for patients, although substantial new funding would be required. Further work to determine the optimal intervention mix for each country is necessary. FUNDING: Bill & Melinda Gates Foundation.

Costs to Health Services and the Patient of Treating Tuberculosis: A Systematic Literature Review.

BACKGROUND: Novel tuberculosis (TB) drugs and the need to treat drug-resistant tuberculosis (DR-TB) are likely to bring about substantial transformations in TB treatment in coming years. An evidence base for cost and cost-effectiveness analyses of these developments is needed. OBJECTIVE: Our objective was to perform a review of papers assessing provider-incurred as well as patient-incurred costs of treating both drug-susceptible (DS) and multidrug-resistant (MDR)-TB. METHODS: Five databases (EMBASE, Medline, the National Health Service Economic Evaluation Database, the Cost-Effectiveness Analysis Registry, and Latin American and Caribbean Health Services Literature) were searched for cost and economic evaluation full-text papers containing primary DS-TB and MDR-TB treatment cost data published in peer-reviewed journals between January 1990 and February 2015. No language restrictions were set. The search terms were a combination of 'tuberculosis', 'multidrug-resistant tuberculosis', 'cost', and 'treatment'. In the selected papers, study methods and characteristics, quality indicators and costs were extracted into summary tables according to pre-defined criteria. Results were analysed according to country income groups and for provider costs, patient costs and productivity losses. All values were converted to $US, year 2014 values, so that studies could be compared. RESULTS: We selected 71 treatment cost papers on DS-TB only, ten papers on MDR-TB only and nine papers that included both DS-TB and MDR-TB. These papers provided evidence on the costs of treating DS-TB and MDR-TB in 50 and 16 countries, respectively. In 31 % of the papers, only provider costs were included; 26 % included only patient-incurred costs, and the remaining 43 % estimated costs incurred by both. From the provider perspective, mean DS-TB treatment costs per patient were US$14,659 in high-income countries (HICs), US$840 in upper middle-income countries (UMICs), US$273 in lower middle-income (LMICs), and US$258 in low-income countries (LICs), showing a strong positive correlation. The respective costs for treating MDR-TB were US$83,365, US$5284, US$6313 and US$1218. Costs incurred by patients when seeking treatment for DS-TB accounted for an additional 3 % of the provider costs in HICs. A greater burden was seen in the other income groups, increasing the costs of DS-TB treatment by 72 % in UMICs, 60 % in LICs and 31 % in LMICs. When provider costs, patient costs and productivity losses were combined, productivity losses accounted for 16 % in HICs, 29 % in UMICs, 40 % in LMICs and 38 % in LICs. CONCLUSION: Cost data for MDR-TB treatment are limited, and the variation in delivery mechanisms, as well as the rapidly evolving diagnosis and treatment regimens, means that it is essential to increase the number of studies assessing the cost from both provider and patient perspectives. There is substantial evidence available on the costs of DS-TB treatment from all regions of the world. The patient-incurred costs illustrate that the financial burden of illness is relatively greater for patients in poorer countries without universal healthcare coverage.

Impact and cost-effectiveness of new tuberculosis vaccines in low- and middle-income countries.

To help reach the target of tuberculosis (TB) disease elimination by 2050, vaccine development needs to occur now. We estimated the impact and cost-effectiveness of potential TB vaccines in low- and middle-income countries using an age-structured transmission model. New vaccines were assumed to be available in 2024, to prevent active TB in all individuals, to have a 5-y to lifetime duration of protection, to have 40-80% efficacy, and to be targeted at "infants" or "adolescents/adults." Vaccine prices were tiered by income group (US $1.50-$10 per dose), and cost-effectiveness was assessed using incremental cost per disability adjusted life year (DALY) averted compared against gross national income per capita. Our results suggest that over 2024-2050, a vaccine targeted to adolescents/adults could have a greater impact than one targeted at infants. In low-income countries, a vaccine with a 10-y duration and 60% efficacy targeted at adolescents/adults could prevent 17 (95% range: 11-24) million TB cases by 2050 and could be considered cost-effective at $149 (cost saving to $387) per DALY averted. If targeted at infants, 0.89 (0.42-1.58) million TB cases could be prevented at $1,692 ($634-$4,603) per DALY averted. This profile targeted at adolescents/adults could be cost-effective at $4, $9, and $20 per dose in low-, lower-middle-, and upper-middle-income countries, respectively. Increased investments in adult-targeted TB vaccines may be warranted, even if only short duration and low efficacy vaccines are likely to be feasible, and trials among adults should be powered to detect low efficacies.