Impact and cost-effectiveness of the 6-month BPaLM regimen for rifampicin-resistant tuberculosis in Moldova: A mathematical modeling analysis.

BACKGROUND: Emerging evidence suggests that shortened, simplified treatment regimens for rifampicin-resistant tuberculosis (RR-TB) can achieve comparable end-of-treatment (EOT) outcomes to longer regimens. We compared a 6-month regimen containing bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) to a standard of care strategy using a 9- or 18-month regimen depending on whether fluoroquinolone resistance (FQ-R) was detected on drug susceptibility testing (DST). METHODS AND FINDINGS: The primary objective was to determine whether 6 months of BPaLM is a cost-effective treatment strategy for RR-TB. We used genomic and demographic data to parameterize a mathematical model estimating long-term health outcomes measured in quality-adjusted life years (QALYs) and lifetime costs in 2022 USD ($) for each treatment strategy for patients 15 years and older diagnosed with pulmonary RR-TB in Moldova, a country with a high burden of TB drug resistance. For each individual, we simulated the natural history of TB and associated treatment outcomes, as well as the process of acquiring resistance to each of 12 anti-TB drugs. Compared to the standard of care, 6 months of BPaLM was cost-effective. This strategy was estimated to reduce lifetime costs by $3,366 (95% UI: [1,465, 5,742] p < 0.001) per individual, with a nonsignificant change in QALYs (-0.06; 95% UI: [-0.49, 0.032] p = 0.790). For those stopping moxifloxacin under the BPaLM regimen, continuing with BPaL plus clofazimine (BPaLC) provided more QALYs at lower cost than continuing with BPaL alone. Strategies based on 6 months of BPaLM had at least a 93% chance of being cost-effective, so long as BPaLC was continued in the event of stopping moxifloxacin. BPaLM for 6 months also reduced the average time spent with TB resistant to amikacin, bedaquiline, clofazimine, cycloserine, moxifloxacin, and pyrazinamide, while it increased the average time spent with TB resistant to delamanid and pretomanid. Sensitivity analyses showed 6 months of BPaLM to be cost-effective across a broad range of values for the relative effectiveness of BPaLM, and the proportion of the cohort with FQ-R. Compared to the standard of care, 6 months of BPaLM would be expected to save Moldova's national TB program budget $7.1 million (95% UI: [1.3 million, 15.4 million] p = 0.002) over the 5-year period from implementation. Our analysis did not account for all possible interactions between specific drugs with regard to treatment outcomes, resistance acquisition, or the consequences of specific types of severe adverse events, nor did we model how the intervention may affect TB transmission dynamics. CONCLUSIONS: Compared to standard of care, longer regimens, the implementation of the 6-month BPaLM regimen could improve the cost-effectiveness of care for individuals diagnosed with RR-TB, particularly in settings with a high burden of drug-resistant TB. Further research may be warranted to explore the impact and cost-effectiveness of shorter RR-TB regimens across settings with varied drug-resistant TB burdens and national income levels.

Factors associated with tuberculosis treatment initiation among bacteriologically negative individuals evaluated for tuberculosis: an individual patient data meta-analysis.

Background: Globally, over one-third of pulmonary tuberculosis (TB) disease diagnoses are made based on clinical criteria after a negative diagnostic test result. Understanding factors associated with clinicians' decisions to initiate treatment for individuals with negative test results is critical for predicting the potential impact of new diagnostics. Methods: We performed a systematic review and individual patient data meta-analysis using studies conducted between January/2010 and December/2022 (PROSPERO: CRD42022287613). We included trials or cohort studies that enrolled individuals evaluated for TB in routine settings. In these studies participants were evaluated based on clinical examination and routinely-used diagnostics, and were followed for ≥1 week after the initial test result. We used hierarchical Bayesian logistic regression to identify factors associated with treatment initiation following a negative result on an initial bacteriological test (e.g., sputum smear microscopy, Xpert MTB/RIF). Findings: Multiple factors were positively associated with treatment initiation: male sex [adjusted Odds Ratio (aOR) 1.61 (1.31-1.95)], history of prior TB [aOR 1.36 (1.06-1.73)], reported cough [aOR 4.62 (3.42-6.27)], reported night sweats [aOR 1.50 (1.21-1.90)], and having HIV infection but not on ART [aOR 1.68 (1.23-2.32)]. Treatment initiation was substantially less likely for individuals testing negative with Xpert [aOR 0.77 (0.62-0.96)] compared to smear microscopy and declined in more recent years. Interpretation: Multiple factors influenced decisions to initiate TB treatment despite negative test results. Clinicians were substantially less likely to treat in the absence of a positive test result when using more sensitive, PCR-based diagnostics.

Safe inhalation pipe provision (SIPP): protocol for a mixed-method evaluation of an intervention to improve health outcomes and service engagement among people who use crack cocaine in England.

BACKGROUND: Over 180,000 people use crack cocaine in England, yet provision of smoking equipment to support safer crack use is prohibited under UK law. Pipes used for crack cocaine smoking are often homemade and/or in short supply, leading to pipe sharing and injuries from use of unsafe materials. This increases risk of viral infection and respiratory harm among a marginalised underserved population. International evaluations suggest crack pipe supply leads to sustained reductions in pipe sharing and use of homemade equipment; increased health risk awareness; improved service access; reduction in injecting and crack-related health problems. In this paper, we introduce the protocol for the NIHR-funded SIPP (Safe inhalation pipe provision) project and discuss implications for impact. METHODS: The SIPP study will develop, implement and evaluate a crack smoking equipment and training intervention to be distributed through peer networks and specialist drug services in England. Study components comprise: (1) peer-network capacity building and co-production; (2) a pre- and post-intervention survey at intervention and non-equivalent control sites; (3) a mixed-method process evaluation; and (4) an economic evaluation. Participant eligibility criteria are use of crack within the past 28 days, with a survey sample of ~ 740 for each impact evaluation survey point and ~ 40 for qualitative process evaluation interviews. Our primary outcome measure is pipe sharing within the past 28 days, with secondary outcomes pertaining to use of homemade pipes, service engagement, injecting practice and acute health harms. ANTICIPATED IMPACT: SIPP aims to reduce crack use risk practices and associated health harms; including through increasing crack harm reduction awareness among service providers and peers. Implementation has only been possible with local police approvals. Our goal is to generate an evidence base to inform review of the legislation prohibiting crack pipe supply in the UK. This holds potential to transform harm reduction service provision and engagement nationally. CONCLUSION: People who smoke crack cocaine in England currently have little reason to engage with harm reduction and drug services. Little is known about this growing population. This study will provide insight into population characteristics, unmet need and the case for legislative reform. TRIAL REGISTRATION: ISRCTN12541454  https://doi.org/10.1186/ISRCTN12541454.

A Scoping Review and Taxonomy of Epidemiological-Macroeconomic Models of COVID-19.

OBJECTIVES: The COVID-19 pandemic placed significant strain on many health systems and economies. Mitigation policies decreased health impacts but had major macroeconomic impact. This article reviews models combining epidemiological and macroeconomic projections to enable policy makers to consider both macroeconomic and health objectives. METHODS: A scoping review of epidemiological-macroeconomic models of COVID-19 was conducted, covering preprints, working articles, and journal publications. We assessed model methodologies, scope, and application to empirical data. RESULTS: We found 80 articles modeling both the epidemiological and macroeconomic outcomes of COVID-19. Model scope is often limited to the impact of lockdown on health and total gross domestic product or aggregate consumption and to high-income countries. Just 14% of models assess disparities or poverty. Most models fall under 4 categories: compartmental-utility-maximization models, epidemiological models with stylized macroeconomic projections, epidemiological models linked to computable general equilibrium or input-output models, and epidemiological-economic agent-based models. We propose a taxonomy comparing these approaches to guide future model development. CONCLUSIONS: The epidemiological-macroeconomic models of COVID-19 identified have varying complexity and meet different modeling needs. Priorities for future modeling include increasing developing country applications, assessing disparities and poverty, and estimating of long-run impacts. This may require better integration between epidemiologists and economists.

Adaptive Health Technology Assessment: A Scoping Review of Methods.

OBJECTIVES: Health technology assessment (HTA) is an established mechanism for explicit priority setting to support universal health coverage. However, full HTA requires significant time, data, and capacity for each intervention, which limits the number of decisions it can inform. Another approach systematically adapts full HTA methods by leveraging HTA evidence from other settings. We call this "adaptive" HTA (aHTA), although in settings where time is the main constraint, it is also called "rapid HTA." METHODS: The objectives of this scoping review were to identify and map existing aHTA methods, and to assess their triggers, strengths, and weaknesses. This was done by searching HTA agencies' and networks' websites, and the published literature. Findings have been narratively synthesized. RESULTS: This review identified 20 countries and 1 HTA network with aHTA methods in the Americas, Europe, Africa, and South-East Asia. These methods have been characterized into 5 types: rapid reviews, rapid cost-effectiveness analyses, rapid manufacturer submissions, transfers, and de facto HTA. Three characteristics "trigger" the use of aHTA instead of full HTA: urgency, certainty, and low budget impact. Sometimes, an iterative approach to selecting methods guides whether to do aHTA or full HTA. aHTA was found to be faster and more efficient, useful for decision makers, and to reduce duplication. Nevertheless, there is limited standardization, transparency, and measurement of uncertainty. CONCLUSIONS: aHTA is used in many settings. It has potential to improve the efficiency of any priority-setting system, but needs to be better formalized to improve uptake, particularly for nascent HTA systems.

Digital adherence technologies to improve tuberculosis treatment outcomes in China: a cluster-randomised superiority trial.

BACKGROUND: Drug-sensitive tuberculosis treatment requires 6 months of therapy, so adherence problems are common. Digital adherence technologies might improve tuberculosis treatment outcomes. We aimed to evaluate the effect of a daily reminder medication monitor, monthly review of adherence data by the health-care provider, and differentiated care for patients with adherence issues, on tuberculosis treatment adherence and outcomes. METHODS: We did a cluster-randomised superiority trial across four prefectures in China. 24 counties or districts (clusters) were randomly assigned (1:1) to intervention or control groups. We enrolled patients aged 18 years or older with GeneXpert-positive, rifampicin-sensitive pulmonary tuberculosis, who were receiving daily fixed-dose combination treatment. Patients in the intervention group received a medication monitor for daily drug-dosing reminders, monthly review of adherence data by health-care provider, and management of poor adherence; and patients in the control group received routine care (silent-mode monitor-measured adherence). Only the independent endpoints review committee who assessed endpoint data for some participants were masked to study group assignment. Patients were followed up (with sputum solid culture) at 12 and 18 months. The primary outcome was a composite of death, loss to follow-up, treatment failure, switch to multidrug-resistant tuberculosis treatment, or tuberculosis recurrence by 18 months from treatment start, analysed in the intention-to-treat population. Analysis accounted for study design with multiple imputation for the primary outcome. This trial is now complete and is registered with ISRCTN, 35812455. FINDINGS: Between Jan 26, 2017, and April 3, 2019, 15 257 patients were assessed for eligibility and 3074 were enrolled, 2686 (87%) of whom were included in the intention-to-treat population. 1909 (71%) of 2686 patients were male, 777 (29%) were female, and the median age was 44 years (IQR 29-58). By 18 months from treatment start, using multiple imputation for missing outcomes, 239 (16% [geometric mean of cluster-level proportion]) of 1388 patients in the control group and 224 (16%) of 1298 in the intervention group had a primary composite outcome event (289 [62%] of 463 events were loss to follow-up during treatment and 42 [9%] were tuberculosis recurrence). The intervention had no effect on risk of the primary composite outcome (adjusted risk ratio 1·01, 95% CI 0·73-1·40). INTERPRETATION: Our digital medication monitor intervention had no effect on unfavourable outcomes, which included loss to follow-up during treatment, tuberculosis recurrence, death, and treatment failure. There was a failure to change patient management following identification of treatment non-adherence at monthly reviews. A better understanding of adherence patterns and how they relate to poor outcomes, coupled with a more timely review of adherence data and improved implementation of differentiated care, may be required. FUNDING: Bill & Melinda Gates Foundation.

Correction: COVID-19 vaccination in Sindh Province, Pakistan: A modelling study of health impact and cost-effectiveness.

[This corrects the article DOI: 10.1371/journal.pmed.1003815.].

Cost-effectiveness of short, oral treatment regimens for rifampicin resistant tuberculosis.

Current options for treating tuberculosis (TB) that is resistant to rifampicin (RR-TB) are few, and regimens are often long and poorly tolerated. Following recent evidence from the TB-PRACTECAL trial countries are considering programmatic uptake of 6-month, all-oral treatment regimens. We used a Markov model to estimate the incremental cost-effectiveness of three regimens containing bedaquiline, pretomanid and linezolid (BPaL) with and without moxifloxacin (BPaLM) or clofazimine (BPaLC) compared with the current mix of long and short standard of care (SOC) regimens to treat RR-TB from the provider perspective in India, Georgia, Philippines, and South Africa. We estimated total costs (2019 USD) and disability-adjusted life years (DALYs) over a 20-year time horizon. Costs and DALYs were discounted at 3% in the base case. Parameter uncertainty was tested with univariate and probabilistic sensitivity analysis. We found that all three regimens would improve health outcomes and reduce costs compared with the current programmatic mix of long and short SOC regimens in all four countries. BPaL was the most cost-saving regimen in all countries, saving $112-$1,173 per person. BPaLM was the preferred regimen at a willingness to pay per DALY of 0.5 GDP per capita in all settings. Our findings indicate BPaL-based regimens are likely to be cost-saving and more effective than the current standard of care in a range of settings. Countries should consider programmatic uptake of BPaL-based regimens.

Stark choices: exploring health sector costs of policy responses to COVID-19 in low-income and middle-income countries.

OBJECTIVES: COVID-19 has altered health sector capacity in low-income and middle-income countries (LMICs). Cost data to inform evidence-based priority setting are urgently needed. Consequently, in this paper, we calculate the full economic health sector costs of COVID-19 clinical management in 79 LMICs under different epidemiological scenarios. METHODS: We used country-specific epidemiological projections from a dynamic transmission model to determine number of cases, hospitalisations and deaths over 1 year under four mitigation scenarios. We defined the health sector response for three base LMICs through guidelines and expert opinion. We calculated costs through local resource use and price data and extrapolated costs across 79 LMICs. Lastly, we compared cost estimates against gross domestic product (GDP) and total annual health expenditure in 76 LMICs. RESULTS: COVID-19 clinical management costs vary greatly by country, ranging between <0.1%-12% of GDP and 0.4%-223% of total annual health expenditure (excluding out-of-pocket payments). Without mitigation policies, COVID-19 clinical management costs per capita range from US$43.39 to US$75.57; in 22 of 76 LMICs, these costs would surpass total annual health expenditure. In a scenario of stringent social distancing, costs per capita fall to US$1.10-US$1.32. CONCLUSIONS: We present the first dataset of COVID-19 clinical management costs across LMICs. These costs can be used to inform decision-making on priority setting. Our results show that COVID-19 clinical management costs in LMICs are substantial, even in scenarios of moderate social distancing. Low-income countries are particularly vulnerable and some will struggle to cope with almost any epidemiological scenario. The choices facing LMICs are likely to remain stark and emergency financial support will be needed.

Lifetime burden of disease due to incident tuberculosis: a global reappraisal including post-tuberculosis sequelae.

BACKGROUND: Many individuals who survive tuberculosis disease face ongoing disability and elevated mortality risks. However, the impact of post-tuberculosis sequelae is generally omitted from policy analyses and disease burden estimates. We therefore estimated the global burden of tuberculosis, inclusive of post-tuberculosis morbidity and mortality. METHODS: We constructed a hypothetical cohort of individuals developing tuberculosis in 2019, including pulmonary and extrapulmonary disease. We simulated lifetime health outcomes for this cohort, stratified by country, age, sex, HIV status, and treatment status. We used disability-adjusted life-years (DALYs) to summarise fatal and non-fatal health losses attributable to tuberculosis, during the disease episode and afterwards. We estimated post-tuberculosis mortality and morbidity based on the decreased lung function caused by pulmonary tuberculosis disease. FINDINGS: Globally, we estimated 122 (95% uncertainty interval [UI] 98-151) million DALYs due to incident tuberculosis disease in 2019, with 58 (38-83) million DALYs attributed to post-tuberculosis sequelae, representing 47% (95% UI 37-57) of the total burden estimate. The increase in burden from post-tuberculosis varied substantially across countries and regions, driven largely by differences in estimated case fatality for the disease episode. We estimated 12·1 DALYs (95% UI 10·0-14·9) per incident tuberculosis case, of which 6·3 DALYs (5·6-7·0) were from the disease episode and 5·8 DALYs (3·8-8·3) were from post-tuberculosis. Per-case post-tuberculosis burden estimates were greater for younger individuals, and in countries with high incidence rates. The burden of post-tuberculosis was spread over the remaining lifetime of tuberculosis survivors, with almost a third of total DALYs (28%, 95% UI 23-34) accruing 15 or more years after incident tuberculosis. INTERPRETATION: Post-tuberculosis sequelae add substantially to the overall disease burden caused by tuberculosis. This hitherto unquantified burden has been omitted from most previous policy analyses. Future policy analyses and burden estimates should take better account of post-tuberculosis, to avoid the potential misallocation of funding, political attention, and research effort resulting from continued neglect of this issue. FUNDING: National Institutes of Health.

COVID-19 vaccination in Sindh Province, Pakistan: A modelling study of health impact and cost-effectiveness.

BACKGROUND: Multiple Coronavirus Disease 2019 (COVID-19) vaccines appear to be safe and efficacious, but only high-income countries have the resources to procure sufficient vaccine doses for most of their eligible populations. The World Health Organization has published guidelines for vaccine prioritisation, but most vaccine impact projections have focused on high-income countries, and few incorporate economic considerations. To address this evidence gap, we projected the health and economic impact of different vaccination scenarios in Sindh Province, Pakistan (population: 48 million). METHODS AND FINDINGS: We fitted a compartmental transmission model to COVID-19 cases and deaths in Sindh from 30 April to 15 September 2020. We then projected cases, deaths, and hospitalisation outcomes over 10 years under different vaccine scenarios. Finally, we combined these projections with a detailed economic model to estimate incremental costs (from healthcare and partial societal perspectives), disability-adjusted life years (DALYs), and incremental cost-effectiveness ratio (ICER) for each scenario. We project that 1 year of vaccine distribution, at delivery rates consistent with COVAX projections, using an infection-blocking vaccine at $3/dose with 70% efficacy and 2.5-year duration of protection is likely to avert around 0.9 (95% credible interval (CrI): 0.9, 1.0) million cases, 10.1 (95% CrI: 10.1, 10.3) thousand deaths, and 70.1 (95% CrI: 69.9, 70.6) thousand DALYs, with an ICER of $27.9 per DALY averted from the health system perspective. Under a broad range of alternative scenarios, we find that initially prioritising the older (65+) population generally prevents more deaths. However, unprioritised distribution has almost the same cost-effectiveness when considering all outcomes, and both prioritised and unprioritised programmes can be cost-effective for low per-dose costs. High vaccine prices ($10/dose), however, may not be cost-effective, depending on the specifics of vaccine performance, distribution programme, and future pandemic trends. The principal drivers of the health outcomes are the fitted values for the overall transmission scaling parameter and disease natural history parameters from other studies, particularly age-specific probabilities of infection and symptomatic disease, as well as social contact rates. Other parameters are investigated in sensitivity analyses. This study is limited by model approximations, available data, and future uncertainty. Because the model is a single-population compartmental model, detailed impacts of nonpharmaceutical interventions (NPIs) such as household isolation cannot be practically represented or evaluated in combination with vaccine programmes. Similarly, the model cannot consider prioritising groups like healthcare or other essential workers. The model is only fitted to the reported case and death data, which are incomplete and not disaggregated by, e.g., age. Finally, because the future impact and implementation cost of NPIs are uncertain, how these would interact with vaccination remains an open question. CONCLUSIONS: COVID-19 vaccination can have a considerable health impact and is likely to be cost-effective if more optimistic vaccine scenarios apply. Preventing severe disease is an important contributor to this impact. However, the advantage of prioritising older, high-risk populations is smaller in generally younger populations. This reduction is especially true in populations with more past transmission, and if the vaccine is likely to further impede transmission rather than just disease. Those conditions are typical of many low- and middle-income countries.

Exploring equity in health and poverty impacts of control measures for SARS-CoV-2 in six countries.

BACKGROUND: Policy makers need to be rapidly informed about the potential equity consequences of different COVID-19 strategies, alongside their broader health and economic impacts. While there are complex models to inform both potential health and macro-economic impact, there are few tools available to rapidly assess potential equity impacts of interventions. METHODS: We created an economic model to simulate the impact of lockdown measures in Pakistan, Georgia, Chile, UK, the Philippines and South Africa. We consider impact of lockdown in terms of ability to socially distance, and income loss during lockdown, and tested the impact of assumptions on social protection coverage in a scenario analysis. RESULTS: In all examined countries, socioeconomic status (SES) quintiles 1-3 were disproportionately more likely to experience income loss (70% of people) and inability to socially distance (68% of people) than higher SES quintiles. Improving social protection increased the percentage of the workforce able to socially distance from 48% (33%-60%) to 66% (44%-71%). We estimate the cost of this social protection would be equivalent to an average of 0.6% gross domestic product (0.1% Pakistan-1.1% Chile). CONCLUSIONS: We illustrate the potential for using publicly available data to rapidly assess the equity implications of social protection and non-pharmaceutical intervention policy. Social protection is likely to mitigate inequitable health and economic impacts of lockdown. Although social protection is usually targeted to the poorest, middle quintiles will likely also need support as they are most likely to suffer income losses and are disproportionately more exposed.

Cost-effectiveness of new MDR-TB regimens: study protocol for the TB-PRACTECAL economic evaluation substudy.

INTRODUCTION: Current treatment regimens for multidrug-resistant tuberculosis (MDR-TB) are long, poorly tolerated and have poor outcomes. Furthermore, the costs of treating MDR-TB are much greater than those for treating drug-susceptible TB, both for health service and patient-incurred costs. Urgent action is needed to identify short, effective, tolerable and cheaper treatments for people with both quinolone-susceptible and quinolone-resistant MDR-TB. We present the protocol for an economic evaluation (PRACTECAL-EE substudy) alongside an ongoing clinical trial (TB-PRACTECAL) aiming to assess the costs to patients and providers of new regimens, as well as their cost-effectiveness and impact on participant poverty levels. This substudy is based on data from the three countries participating in the main trial. METHODS AND ANALYSIS: Primary cost data will be collected from the provider and patient perspectives, following economic best practice. We will estimate the probability that new MDR-TB regimens containing bedaquiline, pretomanid and linezolid are cost-effective from a societal perspective as compared with the standard of care for MDR-TB patients in Uzbekistan, South Africa and Belarus. Analysis uses a Markov model populated with primary cost and outcome data collected at each study site. We will also estimate the impact of new regimens on prevalence of catastrophic patient costs due to TB. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the London School of Hygiene & Tropical Medicine and Médecins Sans Frontières. Local ethical approval will be sought in each study site. The results of the economic evaluation will be shared with the country health authorities and published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT04207112); Pre-results.

Correction to: A Systematic Review of Methodological Variation in Healthcare Provider Perspective Tuberculosis Costing Papers Conducted in Low- and Middle-Income Settings, Using An Intervention-Standardised Unit Cost Typology.

In the original version of this article, Fig. 3 was published in an incorrect format. The correct figure is published with this correction.

A Systematic Review of Methodological Variation in Healthcare Provider Perspective Tuberculosis Costing Papers Conducted in Low- and Middle-Income Settings, Using An Intervention-Standardised Unit Cost Typology.

BACKGROUND: There is a need for easily accessible tuberculosis unit cost data, as well as an understanding of the variability of methods used and reporting standards of that data. OBJECTIVE: The aim of this systematic review was to descriptively review papers reporting tuberculosis unit costs from a healthcare provider perspective looking at methodological variation; to assess quality using a study quality rating system and machine learning to investigate the indicators of reporting quality; and to identify the data gaps to inform standardised tuberculosis unit cost collection and consistent principles for reporting going forward. METHODS: We searched grey and published literature in five sources and eight databases, respectively, using search terms linked to cost, tuberculosis and tuberculosis health services including tuberculosis treatment and prevention. For inclusion, the papers needed to contain empirical unit cost estimates for tuberculosis interventions from low- and middle-income countries, with reference years between 1990 and 2018. A total of 21,691 papers were found and screened in a phased manner. Data were extracted from the eligible papers into a detailed Microsoft Excel tool, extensively cleaned and analysed with R software (R Project, Vienna, Austria) using the user interface of RStudio. A study quality rating was applied to the reviewed papers based on the inclusion or omission of a selection of variables and their relative importance. Following this, machine learning using a recursive partitioning method was utilised to construct a classification tree to assess the reporting quality. RESULTS: This systematic review included 103 provider perspective papers with 627 unit costs (costs not presented here) for tuberculosis interventions among a total of 140 variables. The interventions covered were active, passive and intensified case finding; tuberculosis treatment; above-service costs; and tuberculosis prevention. Passive case finding is the detection of tuberculosis cases where individuals self-identify at health facilities; active case finding is detection of cases of those not in health facilities, such as through outreach; and intensified case finding is detection of cases in high-risk populations. There was heterogeneity in some of the reported methods used such cost allocation, amortisation and the use of top-down, bottom-up or mixed approaches to the costing. Uncertainty checking through sensitivity analysis was only reported on by half of the papers (54%), while purposive and convenience sampling was reported by 72% of papers. Machine learning indicated that reporting on 'Intervention' (in particular), 'Urbanicity' and 'Site Sampling', were the most likely indicators of quality of reporting. The largest data gap identified was for tuberculosis vaccination cost data, the Bacillus Calmette-Guérin (BCG) vaccine in particular. There is a gap in available unit costs for 12 of 30 high tuberculosis burden countries, as well as for the interventions of above-service costs, tuberculosis prevention, and active and intensified case finding. CONCLUSION: Variability in the methods and reporting used makes comparison difficult and makes it hard for decision makers to know which unit costs they can trust. The study quality rating system used in this review as well as the classification tree enable focus on specific reporting aspects that should improve variability and increase confidence in unit costs. Researchers should endeavour to be explicit and transparent in how they cost interventions following the principles as laid out in the Global Health Cost Consortium's Reference Case for Estimating the Costs of Global Health Services and Interventions, which in turn will lead to repeatability, comparability and enhanced learning from others.

Examining Approaches to Estimate the Prevalence of Catastrophic Costs Due to Tuberculosis from Small-Scale Studies in South Africa.

BACKGROUND AND OBJECTIVE: In context of the End TB goal of zero tuberculosis (TB)-affected households encountering catastrophic costs due to TB by 2020, the estimation of national prevalence of catastrophic costs due to TB is a priority to inform programme design. We explore approaches to estimate the national prevalence of catastrophic costs due to TB from existing datasets as an alternative to nationally representative surveys. METHODS: We obtained, standardized and merged three patient-level datasets from existing studies on patient-incurred costs due to TB in South Africa. A deterministic cohort model was developed with the aim of estimating the national prevalence of catastrophic costs, using national data on the prevalence of TB and likelihood of loss to follow-up by income quintile and HIV status. Two approaches were tested to parameterize the model with existing cost data. First, a meta-analysis summarized study-level data by HIV status and income quintile. Second, a regression analysis of patient-level data also included employment status, education level and urbanicity. We summarized findings by type of cost and examined uncertainty around resulting estimates. RESULTS: Overall, the median prevalence of catastrophic costs for the meta-analysis and regression approaches were 11% (interquartile range [IQR] 9-13%) and 6% (IQR 5-8%), respectively. Both approaches indicated that the main burden of catastrophic costs falls on the poorest households. An individual-level regression analysis produced lower uncertainty around estimates than a study-level meta-analysis. CONCLUSIONS: This paper presents a novel application of existing data to estimate the national prevalence of catastrophic costs due to TB. This type of model could be useful for researchers and policy makers looking to inform certain policy decisions; however, some uncertainties remain due to limitations in data availability. There is an urgent need for standardized reporting of cost data and improved guidance on methods to collect income data to improve these estimates going forward.

Integrating economic and health evidence to inform Covid-19 policy in low- and middle- income countries.

Covid-19 requires policy makers to consider evidence on both population health and economic welfare. Over the last two decades, the field of health economics has developed a range of analytical approaches and contributed to the institutionalisation of processes to employ economic evidence in health policy. We present a discussion outlining how these approaches and processes need to be applied more widely to inform Covid-19 policy; highlighting where they may need to be adapted conceptually and methodologically, and providing examples of work to date. We focus on the evidential and policy needs of low- and middle-income countries; where there is an urgent need for evidence to navigate the policy trade-offs between health and economic well-being posed by the Covid-19 pandemic.