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Abstract Background Costing and financing systematic implementation are recognized barriers to human immunodeficiency virus (HIV) prevention. In the absence of empiric implementation and economic data, perspectives from international stakeholders involved in developing and supporting daily oral pre-exposure prophylaxis (PrEP) policy, and programs can provide critical insights for developing costed plans to support and accelerate the rollout of novel long-acting PrEP (LA-PrEP) methods, such as the monthly dapivirine vaginal ring (PrEP ring). Methods We interviewed stakeholders from purposively selected international organizations about anticipated PrEP-ring implementation costs, evidence gaps and key process steps for developing a costed rollout plan template (CRPT). We deductively analysed interviews. Results The 27 stakeholders (11 donors, 10 nongovernmental, 4 academic/research, 2 multilateral) identified 10 cost-related themes: 7 for planning and implementation and 3 for financing, costing and budgeting. Planning and implementation cost considerations included: (1) actionable target setting; (2) multilevel communication strategies for awareness-raising, demand creation, client-level adherence and choice counselling; (3) human resources, encompassing task shifting and integration into non-HIV services; (4) supply chain costs, including commodities, manufacturing diversification, packaging and forecasting; (5) laboratory infrastructure and monitoring; (6) updated health information systems and metrics to monitor and evaluate multiple methods integrated into HIV, non-HIV and de-medicalized delivery settings; and (7) technical assistance and knowledge management. Themes for financing, costing and budgeting comprised: (8) cost and budget analyses, such as cost–effectiveness; (9) economic evidence gaps on service integration; and (10) innovative or co-financing for sustainable and equitable allocation of limited financial resources to support accelerated PrEP-ring delivery. We organized these themes within the CRPT. Conclusions The CRPT could expedite planning and enhance the pace and scale of optimized, systematic and sustainable delivery of PrEP methods. Further research is needed to evaluate use cases of the CRPT.

Abstract Background The arc of Bühler (AOB) is a residual embryonal anastomosis between the celiac artery (CA) and the superior mesenteric artery (SMA). Although usually asymptomatic, it has clinical relevance when compensatory reverse flow between the SMA and the CA in response to celiac artery obstruction leads to aneurysm formation and bleeding. Endovascular coiling is the mainstay therapy because of the deep AOB retropancreatic location, which hinders open surgery. Case presentation We herein report a case of a 2.8-cm AOB saccular aneurysm and LAM compression of celiac trunk in a 47-year-old man during rehabilitation following motorcycle trauma and vertebral surgery. The patient was considered unsuitable for surgery. Neither conventional coiling nor bare-metal stent and balloon-assisted techniques for coiling were suitable because of the wide necked saccular shape of AOB aneurysm interposed between the SMA and the floor of celiac trunk. To exclude the aneurysm from direct SMA inflow and permit safe and efficient coiling to rule out retrograde sac perfusion, a 9-mm polytetrafluoroethylene stent graft (Viabahn; Gore, Phoenix, AZ, USA) was positioned in the mesenteric artery, followed by antegrade periprosthetic high-density packed coiling of the aneurysm. The AOB remained excluded from mesenteric perfusion. The patient’s clinical condition and abdominal contrast-enhanced multislice computed tomographic findings were unremarkable at the 9-year follow-up. Conclusion The 9 year long-term efficacy in our case raises the possibility that perigraft coiling following stent-graft deployment in the SMA may represent a valuable technical option for large Bühler aneurysms that are not amenable to stand-alone coiling.

Abstract Background One third to two thirds of people with schizophrenia have persistent psychotic symptoms despite clozapine treatment. Under real-world circumstances, the need to provide effective therapeutic interventions to patients who do not have an optimal response to clozapine has been cited as the most common reason for simultaneously prescribing a second antipsychotic drug in combination treatment strategies. In a clinical area where the pressing need of providing therapeutic answers has progressively increased the occurrence of antipsychotic polypharmacy, despite the lack of robust evidence of its efficacy, we sought to implement a pre-planned protocol where two alternative therapeutic answers are systematically provided and evaluated within the context of a pragmatic, multicentre, independent randomised study. Methods/Design The principal clinical question to be answered by the present project is the relative efficacy and tolerability of combination treatment with clozapine plus aripiprazole compared with combination treatment with clozapine plus haloperidol in patients with an incomplete response to treatment with clozapine over an appropriate period of time. This project is a prospective, multicentre, randomized, parallel-group, superiority trial that follow patients over a period of 12 months. Withdrawal from allocated treatment within 3 months is the primary outcome. Discussion The implementation of the protocol presented here shows that it is possible to create a network of community psychiatric services that accept the idea of using their everyday clinical practice to produce randomised knowledge. The employed pragmatic attitude allowed to randomly allocate more than 100 individuals, which means that this study is the largest antipsychotic combination trial conducted so far in Western countries. We expect that the current project, by generating evidence on whether it is clinically useful to combine clozapine with aripiprazole rather than with haloperidol, provides physicians with a solid evidence base to be directly applied in the routine care of patients with schizophrenia. Trial Registration Clincaltrials.gov Identifier: NCT00395915

Abstract Introduction Several low‐ and middle‐income countries (LMICs) are preparing to introduce long‐acting pre‐exposure prophylaxis (LAP). Amid multiple pre‐exposure prophylaxis (PrEP) options and constrained funding, decision‐makers could benefit from systematic implementation planning and aligned costs. We reviewed national costed implementation plans (CIPs) to describe relevant implementation inputs and activities (domains) for informing the costed rollout of LAP. We assessed how primary costing evidence aligned with those domains. Methods We conducted a rapid review of CIPs for oral PrEP and family planning (FP) to develop a consensus of implementation domains, and a scoping review across nine electronic databases for publications on PrEP costing in LMICs between January 2010 and June 2022. We extracted cost data and assessed alignment with the implementation domains and the Global Health Costing Consortium principles. Results We identified 15 implementation domains from four national PrEP plans and FP‐CIP template; only six were in all sources. We included 66 full‐text manuscripts, 10 reported LAP, 13 (20%) were primary cost studies‐representing seven countries, and none of the 13 included LAP. The 13 primary cost studies included PrEP commodities (n = 12), human resources (n = 11), indirect costs (n = 11), other commodities (n = 10), demand creation (n = 9) and counselling (n = 9). Few studies costed integration into non‐HIV services (n = 5), above site costs (n = 3), supply chains and logistics (n = 3) or policy and planning (n = 2), and none included the costs of target setting, health information system adaptations or implementation research. Cost units and outcomes were variable (e.g. average per person‐year). Discussion LAP planning will require updating HIV prevention policies, technical assistance for logistical and clinical support, expanding beyond HIV platforms, setting PrEP achievement targets overall and disaggregated by method, extensive supply chain and logistics planning and support, as well as updating health information systems to monitor multiple PrEP methods with different visit schedules. The 15 implementation domains were variable in reviewed studies. PrEP primary cost and budget data are necessary for new product introduction and should match implementation plans with financing. Conclusions As PrEP services expand to include LAP, decision‐makers need a framework, tools and a process to support countries in planning the systematic rollout and costing for LAP.

The M72/AS01E tuberculosis vaccine has shown 50% efficacy in preventing pulmonary TB disease in infected 18–50 year olds. Here, the authors demonstrate that, in most scenarios modelled, vaccination of adolescents would also be cost effective in two high incidence settings, South Africa and India.

Introduction Nosocomial Mycobacterium tuberculosis (Mtb) transmission substantially impacts health workers, patients and communities. Guidelines for tuberculosis infection prevention and control (TB IPC) exist but implementation in many settings remains suboptimal. Evidence is needed on cost-effective investments to prevent Mtb transmission that are feasible in routine clinic environments.Methods A set of TB IPC interventions was codesigned with local stakeholders using system dynamics modelling techniques that addressed both core activities and enabling actions to support implementation. An economic evaluation of these interventions was conducted at two clinics in KwaZulu-Natal, employing agent-based models of Mtb transmission within the clinics and in their catchment populations. Intervention costs included the costs of the enablers (eg, strengthened supervision, community sensitisation) identified by stakeholders to ensure uptake and adherence.Results All intervention scenarios modelled, inclusive of the relevant enablers, cost less than US$200 per disability-adjusted life-year (DALY) averted and were very cost-effective in comparison to South Africa’s opportunity cost-based threshold (US$3200 per DALY averted). Two interventions, building modifications to improve ventilation and maximising use of the existing Central Chronic Medicines Dispensing and Distribution system to reduce the number of clinic attendees, were found to be cost saving over the 10-year model time horizon. Incremental cost-effectiveness ratios were sensitive to assumptions on baseline clinic ventilation rates, the prevalence of infectious TB in clinic attendees and future HIV incidence but remained highly cost-effective under all uncertainty analysis scenarios.Conclusion TB IPC interventions in clinics, including the enabling actions to ensure their feasibility, afford very good value for money and should be prioritised for implementation within the South African health system.

In clinical settings where airborne pathogens, such as Mycobacterium tuberculosis, are prevalent, they constitute an important threat to health workers and people accessing healthcare. We report key insights from a 3-year project conducted in primary healthcare clinics in South Africa, alongside other recent tuberculosis infection prevention and control (TB-IPC) research. We discuss the fragmentation of TB-IPC policies and budgets; the characteristics of individuals attending clinics with prevalent pulmonary tuberculosis; clinic congestion and patient flow; clinic design and natural ventilation; and the facility-level determinants of the implementation (or not) of TB-IPC interventions. We present modeling studies that describe the contribution of M. tuberculosis transmission in clinics to the community tuberculosis burden and economic evaluations showing that TB-IPC interventions are highly cost-effective. We argue for a set of changes to TB-IPC, including better coordination of policymaking, clinic decongestion, changes to clinic design and building regulations, and budgeting for enablers to sustain implementation of TB-IPC interventions. Additional research is needed to find the most effective means of improving the implementation of TB-IPC interventions; to develop approaches to screening for prevalent pulmonary tuberculosis that do not rely on symptoms; and to identify groups of patients that can be seen in clinic less frequently.

Objectives: Disease transmission models are used in impact assessment and economic evaluations of infectious disease prevention and treatment strategies, prominently so in the COVID-19 response. These models rarely consider dimensions of equity relating to the differential health burden between individuals and groups. We describe concepts and approaches which are useful when considering equity in the priority setting process, and outline the technical choices concerning model structure, outputs, and data requirements needed to use transmission models in analyses of health equity. Methods: We reviewed the literature on equity concepts and approaches to their application in economic evaluation and undertook a technical consultation on how equity can be incorporated in priority setting for infectious disease control. The technical consultation brought together health economists with an interest in equity-informative economic evaluation, ethicists specialising in public health, mathematical modellers from various disease backgrounds, and representatives of global health funding and technical assistance organisations, to formulate key areas of consensus and recommendations. Results: We provide a series of recommendations for applying the Reference Case for Economic Evaluation in Global Health to infectious disease interventions, comprising guidance on 1) the specification of equity concepts; 2) choice of evaluation framework; 3) model structure; and 4) data needs. We present available conceptual and analytical choices, for example how correlation between different equity- and disease-relevant strata should be considered dependent on available data, and outline how assumptions and data limitations can be reported transparently by noting key factors for consideration. Conclusions: Current developments in economic evaluations in global health provide a wide range of methodologies to incorporate equity into economic evaluations. Those employing infectious disease models need to use these frameworks more in priority setting to accurately represent health inequities. We provide guidance on the technical approaches to support this goal and ultimately, to achieve more equitable health policies.

Abstract Background Despite recent advances through the development pipeline, how novel tuberculosis (TB) vaccines might affect rifampicin-resistant and multidrug-resistant tuberculosis (RR/MDR-TB) is unknown. We investigated the epidemiologic impact, cost-effectiveness, and budget impact of hypothetical novel prophylactic prevention of disease TB vaccines on RR/MDR-TB in China and India. Methods We constructed a deterministic, compartmental, age-, drug-resistance- and treatment history-stratified dynamic transmission model of tuberculosis. We introduced novel vaccines from 2027, with post- (PSI) or both pre- and post-infection (P&PI) efficacy, conferring 10 years of protection, with 50% efficacy. We measured vaccine cost-effectiveness over 2027–2050 as USD/DALY averted-against 1-times GDP/capita, and two healthcare opportunity cost-based (HCOC), thresholds. We carried out scenario analyses. Results By 2050, the P&PI vaccine reduced RR/MDR-TB incidence rate by 71% (UI: 69–72) and 72% (UI: 70–74), and the PSI vaccine by 31% (UI: 30–32) and 44% (UI: 42–47) in China and India, respectively. In India, we found both USD 10 P&PI and PSI vaccines cost-effective at the 1-times GDP and upper HCOC thresholds and P&PI vaccines cost-effective at the lower HCOC threshold. In China, both vaccines were cost-effective at the 1-times GDP threshold. P&PI vaccine remained cost-effective at the lower HCOC threshold with 49% probability and PSI vaccines at the upper HCOC threshold with 21% probability. The P&PI vaccine was predicted to avert 0.9 million (UI: 0.8–1.1) and 1.1 million (UI: 0.9–1.4) second-line therapy regimens in China and India between 2027 and 2050, respectively. Conclusions Novel TB vaccination is likely to substantially reduce the future burden of RR/MDR-TB, while averting the need for second-line therapy. Vaccination may be cost-effective depending on vaccine characteristics and setting.

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

Background Elevated rates of tuberculosis in healthcare workers demonstrate the high rate of Mycobacterium tuberculosis (Mtb) transmission in health facilities in high-burden settings. In the context of a project taking a whole systems approach to tuberculosis infection prevention and control (IPC), we aimed to evaluate the potential impact of conventional and novel IPC measures on Mtb transmission to patients and other clinic attendees.Methods An individual-based model of patient movements through clinics, ventilation in waiting areas, and Mtb transmission was developed, and parameterised using empirical data from eight clinics in two provinces in South Africa. Seven interventions—codeveloped with health professionals and policy-makers—were simulated: (1) queue management systems with outdoor waiting areas, (2) ultraviolet germicidal irradiation (UVGI) systems, (3) appointment systems, (4) opening windows and doors, (5) surgical mask wearing by clinic attendees, (6) simple clinic retrofits and (7) increased coverage of long antiretroviral therapy prescriptions and community medicine collection points through the Central Chronic Medicine Dispensing and Distribution (CCMDD) service.Results In the model, (1) outdoor waiting areas reduced the transmission to clinic attendees by 83% (IQR 76%–88%), (2) UVGI by 77% (IQR 64%–85%), (3) appointment systems by 62% (IQR 45%–75%), (4) opening windows and doors by 55% (IQR 25%–72%), (5) masks by 47% (IQR 42%–50%), (6) clinic retrofits by 45% (IQR 16%–64%) and (7) increasing the coverage of CCMDD by 22% (IQR 12%–32%).Conclusions The majority of the interventions achieved median reductions in the rate of transmission to clinic attendees of at least 45%, meaning that a range of highly effective intervention options are available, that can be tailored to the local context. Measures that are not traditionally considered to be IPC interventions, such as appointment systems, may be as effective as more traditional IPC measures, such as mask wearing.

Objective To determine the prevalence of tuberculosis (TB) and HIV in 13 Zambian correctional facilities.Methods Cross-sectional study.Setting 13 correctional facilities in seven of the 10 provinces in Zambia.Participants All incarcerated individuals were eligible for TB and HIV screening and testing. Of the total study population of 9695 individuals, which represent 46.2% of total correctional population at the beginning of the study, 8267 and 8160 were screened for TB and HIV, respectively.Interventions TB and HIV screening and testing was done between July 2018 and February 2019.Primary outcome measures All forms of TB, bacteriologically confirmed TB, drug-resistant TB, HIV.Results Prevalence of all forms of TB and bacteriologically confirmed TB was 1599 (1340–1894) per 100 000 population and 1056 (847–1301) per 100 000 population, respectively. Among those with bacteriologically confirmed TB, 4.6% (1.3%–11.4%) had drug-resistant TB.There was no statistically significant difference in the prevalence of all forms of TB, bacteriologically confirmed TB and drug resistant TB between adults and juveniles: (p=0.82), (p=0.23), (p=0.68) respectively. Of the bacteriologically confirmed TB cases, 28.7% were asymptomatic. The prevalence of HIV was 14.3% (13.6%–15.1%). The prevalence of HIV among females was 1.8 times the prevalence of HIV among males (p=0.01).Conclusion Compared with the study in 2011 which screened inmates representing 30% of the country’s inmate population, then the prevalence of all forms of TB and HIV in correctional facilities has reduced by about 75% and 37.6%, respectively. However, compared with the general population, the prevalence of all forms of TB and HIV was 3.5 and 1.3 times higher, respectively. TB/HIV programmes in correctional facilities need further strengthening to include aspects of juvenile-specific TB programming and gender responsive HIV programming.

Priority setting for infectious disease control is increasingly concerned with physical input constraints and other real-world restrictions on implementation and on the decision process. These health system constraints determine the ‘feasibility’ of interventions and hence impact. However, considering them within mathematical models places additional demands on model structure and relies on data availability. This review aims to provide an overview of published methods for considering constraints in mathematical models of infectious disease.We systematically searched the literature to identify studies employing dynamic transmission models to assess interventions in any infectious disease and geographical area that included non-financial constraints to implementation. Information was extracted on the types of constraints considered and how these were identified and characterised, as well as on the model structures and techniques for incorporating the constraints.A total of 36 studies were retained for analysis. While most dynamic transmission models identified were deterministic compartmental models, stochastic models and agent-based simulations were also successfully used for assessing the effects of non-financial constraints on priority setting. Studies aimed to assess reductions in intervention coverage (and programme costs) as a result of constraints preventing successful roll-out and scale-up, and/or to calculate costs and resources needed to relax these constraints and achieve desired coverage levels. We identified three approaches for incorporating constraints within the analyses: (i) estimation within the disease transmission model; (ii) linking disease transmission and health system models; (iii) optimising under constraints (other than the budget).The review highlighted the viability of expanding model-based priority setting to consider health system constraints. We show strengths and limitations in current approaches to identify and quantify locally-relevant constraints, ranging from simple assumptions to structured elicitation and operational models. Overall, there is a clear need for transparency in the way feasibility is defined as a decision criteria for its systematic operationalisation within models.

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.

South Africa has the highest tuberculosis (TB) disease incidence rate in the world, and TB is the leading infectious cause of death. Decisions on, and funding for, TB prevention and care policies are decentralised to the provincial governments and therefore, tools to inform policy need to operate at this level. We describe the use of a mathematical model planning tool at provincial level in a high HIV and TB burden country, to estimate the impact on TB burden of achieving the 90-(90)-90 targets of the Stop TB Partnership Global Plan to End TB. "TIME Impact" is a freely available, user-friendly TB modelling tool. In collaboration with provincial TB programme staff, and the South African National TB Programme, models for three (of nine) provinces were calibrated to TB notifications, incidence, and screening data. Reported levels of TB programme activities were used as baseline inputs into the models, which were used to estimate the impact of scale-up of interventions focusing on screening, linkage to care and treatment success. All baseline models predicted a trend of decreasing TB incidence and mortality, consistent with recent data from South Africa. The projected impacts of the interventions differed by province and were greatly influenced by assumed current coverage levels. The absence of provincial TB burden estimates and uncertainty in current activity coverage levels were key data gaps. A user-friendly modelling tool allows TB burden and intervention impact projection at the sub-national level. Key sub-national data gaps should be addressed to improve the quality of sub-national model predictions.

Abstract Background Provision of HIV prevention and sexual and reproductive health services in Zambia is largely characterized by discrete service provision with weak client referral and linkage. The literature reveals gaps in the continuity of care for HIV and sexual and reproductive health. This study assessed whether improved service delivery models increased the uptake and cost-effectiveness of HIV and sexual and reproductive health services. Methods Adult clients 18+ years of age accessing family planning (females), HIV testing and counseling (females and males), and male circumcision services (males) were recruited, enrolled and individually randomized to one of three study arms: 1) the standard model of service provision at the entry point (N = 1319); 2) an enhanced counseling and referral to add-on service with follow-up (N = 1323); and 3) the components of study arm two, with the additional offer of an escort (N = 1321). Interviews were conducted with the same clients at baseline, six weeks and six months. Uptake of services for HIV, family planning, male circumcision, and cervical cancer screening at six weeks and six months were the primary endpoints. Pairwise chi-square and multivariable logistic regression statistical tests assessed differences across study arms, which were also assessed for incremental cost-efficiency and cost-effectiveness. Results A total of 3963 clients, 1920 males and 2043 females, were enrolled; 82 % of participants at six weeks were tracked and 81 % at six months; follow-up rates did not vary significantly by study arm. The odds of clients accessing HIV testing and counseling, cervical cancer screening services among females, and circumcision services among males varied significantly by study arm at six weeks and six months; less consistent findings were observed for HIV care and treatment. Client uptake of family planning services did not vary significantly by study arm. Integrated services were found to be more efficiently provided than vertical service provision; the cost-effectiveness for HIV/AIDS and cervical cancer was high in the enhanced service models. Conclusions Study results provide evidence for increasing the linkages and integration of a selection of HIV and sexual and reproductive health services. The study provided cost-effective service delivery models that enhanced the likelihood of clients accessing some additional needed health services. Trial registration ISRCTN84228514 Retrospectively registered. The study was retrospectively registered in the ISRCTN clinical trials registry on 06 October 2015. The first recruitment of participants occurred on 17 December 2013.

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

BackgroundMultiple 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 findingsWe 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.ConclusionsCOVID-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.

Abstract Background Evidence on the relative costs and effects of interventions that do not consider ‘real-world’ constraints on implementation may be misleading. However, in many low- and middle-income countries, time and data scarcity mean that incorporating health system constraints in priority setting can be challenging. Methods We developed a ‘proof of concept’ method to empirically estimate health system constraints for inclusion in model-based economic evaluations, using intensified case-finding strategies (ICF) for tuberculosis (TB) in South Africa as an example. As part of a strategic planning process, we quantified the resources (fiscal and human) needed to scale up different ICF strategies (cough triage and WHO symptom screening). We identified and characterised three constraints through discussions with local stakeholders: (1) financial constraint: potential maximum increase in public TB financing available for new TB interventions; (2) human resource constraint: maximum current and future capacity among public sector nurses that could be dedicated to TB services; and (3) diagnostic supplies constraint: maximum ratio of Xpert MTB/RIF tests to TB notifications. We assessed the impact of these constraints on the costs of different ICF strategies. Results It would not be possible to reach the target coverage of ICF (as defined by policy makers) without addressing financial, human resource and diagnostic supplies constraints. The costs of addressing human resource constraints is substantial, increasing total TB programme costs during the period 2016–2035 by between 7% and 37% compared to assuming the expansion of ICF is unconstrained, depending on the ICF strategy chosen. Conclusions Failure to include the costs of relaxing constraints may provide misleading estimates of costs, and therefore cost-effectiveness. In turn, these could impact the local relevance and credibility of analyses, thereby increasing the risk of sub-optimal investments.

Abstract Background Adolescents in less developed countries such as Zambia often face multi-faceted challenges for achieving successful transitions through adolescence to early adulthood. The literature has noted the need to introduce interventions during this period, particularly for adolescent girls, with the perspective that such investments have significant economic, social and health returns to society. The Adolescent Girls Empowerment Programme (AGEP) was an intervention designed as a catalyst for change for adolescent girls through themselves, to their family and community. Methods/design AGEP was a multi-sectoral intervention targeting over 10,000 vulnerable adolescent girls ages 10–19 in rural and urban areas, in four of the ten provinces of Zambia. At the core of AGEP were mentor-led, weekly girls’ group meetings of 20 to 30 adolescent girls participating over two years. Three curricula ― sexual and reproductive health and lifeskills, financial literacy, and nutrition ― guided the meetings. An engaging and participatory pedagogical approach was used. Two additional program components, a health voucher and a bank account, were offered to some girls to provide direct mechanisms to improve access to health and financial services. Embedded within AGEP was a rigorous multi-arm randomised cluster trial with randomization to different combinations of programme arms. The study was powered to assess the impact across a set of key longer-term outcomes, including early marriage and first birth, contraceptive use, educational attainment and acquisition of HIV and HSV-2. Baseline behavioural surveys and biological specimen collection were initiated in 2013. Impact was evaluated immediately after the program ended in 2015 and will be evaluated again after two additional years of follow-up in 2017. The primary analysis is intent-to-treat. Qualitative data are being collected in 2013, 2015 and 2017 to inform the programme implementation and the quantitative findings. An economic evaluation will evaluate the incremental cost-effectiveness of each component of the intervention. Discussion The AGEP program and embedded evaluation will provide detailed information regarding interventions for adolescent girls in developing country settings. It will provide a rich information and data source on adolescent girls and its related findings will inform policy-makers, health professionals, donors and other stakeholders. Trial registration ISRCTN29322231 . March 04 2016; retrospectively registered.

Background: Low- and middle-income countries need to sustain efficiency and equity in health financing on their way to universal health care coverage. However, systems meant to generate quality economic information are often deficient in such settings. We assessed the feasibility of streamlining cost accounting systems within the Kenyan health sector to illustrate the pragmatic challenges and opportunities. Design: We reviewed policy documents, and conducted field observations and semi-structured interviews with key informants in the health sector. We used an adapted Human, Organization and Technology fit (HOT-fit) framework to analyze the components and standards of a cost accounting system. Results: Among the opportunities for a viable cost accounting system, we identified a supportive broad policy environment, political will, presence of a national data reporting architecture, good implementation experience with electronic medical records systems, and the availability of patient clinical and resource use data. However, several practical issues need to be considered in the design of the system, including the lack of a framework to guide the costing process, the lack of long-term investment, the lack of appropriate incentives for ground-level staff, and a risk of overburdening the current health management information system. Conclusion: To facilitate the implementation of cost accounting into the health sector, the design of any proposed system needs to remain simple and attuned to the local context.

Background: Current guidelines for the conduct of cost-effectiveness analysis (CEA) are mainly applicable to facility-based interventions in high-income settings. Differences in the unit of analysis and the high cost of data collection can make these guidelines challenging to follow within public health trials in low- and middle- income settings. Objective: This paper reflects on the challenges experienced within our own work and proposes solutions that may be useful to others attempting to collect, analyse, and compare cost data between public health research sites in low- and middle-income countries. Design: We describe the generally accepted methods (norms) for collecting and analysing cost data in a single-site trial from the provider perspective. We then describe our own experience applying these methods within eight comparable cluster randomised, controlled, trials. We describe the strategies used to maximise adherence to the norm, highlight ways in which we deviated from the norm, and reflect on the learning and limitations that resulted. Results: When the expenses incurred by a number of small research sites are used to estimate the cost-effectiveness of delivering an intervention on a national scale, then deciding which expenses constitute ‘start-up’ costs will be a nontrivial decision that may differ among sites. Similarly, the decision to include or exclude research or monitoring and evaluation costs can have a significant impact on the findings. We separated out research costs and argued that monitoring and evaluation costs should be reported as part of the total trial cost. The human resource constraints that we experienced are also likely to be common to other trials. As we did not have an economist in each site, we collaborated with key personnel at each site who were trained to use a standardised cost collection tool. This approach both accommodated our resource constraints and served as a knowledge sharing and capacity building process within the research teams. Conclusions: Given the practical reality of conducting randomised, controlled trials of public health interventions in low- and middle- income countries, it is not always possible to adhere to prescribed guidelines for the analysis of cost effectiveness. Compromises are frequently required as researchers seek a pragmatic balance between rigor and feasibility. There is no single solution to this tension but researchers are encouraged to be mindful of the limitations that accompany compromise, whilst being reassured that meaningful analyses can still be conducted with the resulting data.

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.

The available data on routine immunization in Nigeria show a disparity in coverage between Northern and Southern Nigeria, with the former performing worse. The effect of socio-cultural differences on health-seeking behaviour has been identified in the literature as the main cause of the disparity. Our study analyses the role of supply-side determinants, particularly access to services, in causing these disparities.Using routine government data, we compared supply-side determinants of access in two Northern states with two Southern states. The states were identified using criteria-based purposive selection such that the comparisons were made between a low-coverage state in the South and a low-coverage state in the North as well as between a high-coverage state in the South and a high-coverage state in the North.Human resources and commodities at routine immunization service delivery points were generally insufficient for service delivery in both geographical regions. While disparities were evident between individual states irrespective of regional location, compared to the South, residents in Northern Nigeria were more likely to have vaccination service delivery points located within a 5 km radius of their settlements.Our findings suggest that regional supply-side disparities are not apparent, reinforcing the earlier reported socio-cultural explanations for disparities in routine immunization service uptake between Northern and Southern Nigeria. Nonetheless, improving routine immunisation coverage services require that there are available human resources and that health facilities are equitably distributed.

INTRODUCTION: A rapid assessment of avoidable blindness (RAAB) was conducted in Southern Zambia to establish the prevalence and causes of blindness in order to plan effective services and advocate for support for eye care to achieve the goals of VISION 2020: the right to sight. METHODS: Cluster randomisation was used to select villages in the survey area. These were further subdivided into segments. One segment was selected randomly and a survey team moved from house to house examining everyone over the age of 50 years. Each individual received a visual acuity assessment and simple ocular examination. Data was recorded on a standard proforma and entered into an established software programme for analysis. RESULTS: 2.29% of people over the age of 50 were found to be blind (VA

Abstract Background Economic viability of treatments for primary open-angle glaucoma (POAG) should be assessed objectively to prioritise health care interventions. This study aims to identify the methods for eliciting utility values (UVs) most sensitive to differences in visual field and visual functioning in patients with POAG. As a secondary objective, the dimensions of generic health-related and vision-related quality of life most affected by progressive vision loss will be identified. Methods A total of 132 POAG patients were recruited. Three sets of utility values (EuroQoL EQ-5D, Short Form SF-6D, Time Trade Off) and a measure of perceived visual functioning from the National Eye Institute Visual Function Questionnaire (VFQ-25) were elicited during face-to-face interviews. The sensitivity of UVs to differences in the binocular visual field, visual acuity and visual functioning measures was analysed using non-parametric statistical methods. Results Median utilities were similar across Integrated Visual Field score quartiles for EQ-5D (P = 0.08) whereas SF-6D and Time-Trade-Off UVs significantly decreased (p = 0.01 and p = 0.001, respectively). The VFQ-25 score varied across Integrated Visual Field and binocular visual acuity groups and was associated with all three UVs (P ≤ 0.001); most of its vision-specific sub-scales were associated with the vision markers. The most affected dimension was driving. A relationship with vision markers was found for the physical component of SF-36 and not for any dimension of EQ-5D. Conclusions The Time-Trade-Off was more sensitive than EQ-5D and SF-6D to changes in vision and visual functioning associated with glaucoma progression but could not measure quality of life changes in the mildest disease stages.