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Abstract Background The COVID-19 pandemic has highlighted the importance of evidence-informed priority setting and situational analysis in pandemic preparedness and response. Health Technology Assessment (HTA) has been identified as an essential tool for evidence-informed decision-making in healthcare. However, the potential role of HTA in pandemic preparedness and response in Africa has yet to be explored. The objective of this scoping review is to ascertain the current understanding of the possible role of HTA in Africa to support future pandemic preparedness and response. Methods We will conduct a scoping review of literature published between 2010 and 2024. Electronic databases like Embase, PubMed, Scopus, Web of Science, and Google Scholar will be utilized to perform the search. We will also search grey literature sources such as websites of relevant organizations and government agencies. The search will only include studies that were conducted in the English language. Two reviewers will evaluate the titles and abstracts of the publications independently to determine their eligibility using Covidence. Full-text articles will be reviewed for eligibility and data extraction. The data will be extracted using a standardized form. The extracted data will include information on the study design, objectives, methods, findings, and conclusions. The thematic analysis approach will guide the data analysis. Themes and sub-themes will be identified and reported. The review will be reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. Discussion This scoping review will identify the existing knowledge on the potential role of HTA in Africa to support future pandemic preparedness and response. The findings will aid in identifying deficiencies in knowledge and provide valuable insights for future study. Additionally, they will inform policy-makers and other stakeholders about the potential contribution of the Health Technology Assessment (HTA) in enhancing Africa’s readiness and response to pandemics.

Introduction Worldwide, countries have the challenge of meeting the ever-increasing demand for healthcare amidst limited resources. While priority setting is necessary in all settings, it is especially critical in low- and middle-income countries because of their often-low budgetary allocations for health. Despite the long history of disease programmes supported by the Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM) in Ghana, there is limited evidence on the approaches used in priority setting for the three disease programmes. This study aimed at exploring the priority-setting approaches adopted by the GFATM-supported programmes in Ghana.Methods In-depth interviews of ten key informants from the three disease programmes, the Ministry of Health and global health partners were conducted. Interviews were transcribed verbatim and analysed both inductively and deductively.Results We identified four main approaches for priority setting: (1) identification of health needs, (2) stakeholder participation, (3) transparency of the process and (4) contextual factors. Priorities were identified through national health strategies and mandates, development/health partners and global mandates and internally generated data and surveillance. The main actors participating in the decision-making or priority setting were ministries and agencies, development partners, research institutions, committees and working groups. These actors had varying influences and power. The involvement of the general public was limited in the priority-setting process. The approaches were often documented and disseminated through various mediums. Contextual factors reported were mainly barriers that affected priority setting, and these included inadequate funding, aligning priorities with funders and interruptions in the priority-setting process.Conclusion While explicit priority-setting approaches are being expanded globally to support resource allocation decisions in health more generally, evidence from our study suggests that their use in the three GFATM-supported programmes was limited.

BackgroundTuberculosis (TB) imposes a substantial health and economic burden on many populations and countries, but lack of funding has significantly contributed to several countries falling short of global TB reduction targets. Furthermore, existing assessments of the economic impact of TB do not capture the impacts on productivity and economic growth or the pathways by which epidemiology, demography, and the economy interact. Evidence is needed to answer how investment in treatment and control measures may help to mitigate the twin Indian health and macroeconomic burdens of TB over the coming decades.Methods and findingsWe develop a fully integrated dynamic macroeconomic-health-demographic simulation model for India, the country with the largest national TB burden, and use it to estimate the macroeconomic return to investment in TB treatment. Our estimated results indicate that, over 2021 to 2040, the health and macroeconomic burdens of TB in India will include over 62.4m incident cases, 8.1m TB-related deaths and a cumulative gross domestic product (GDP) loss of US$146.4bn. Low-income households will bear larger health and relative economic burdens while larger absolute economic burdens will fall on high-income households. Achieving the World Health Organisation's End TB target of 90% case detection could reduce clinical and demographic disease burdens by 75% to 89% and reduce the macroeconomic burden by US$120.2bn. Developing a 95% effective pan-TB treatment regimen would reduce the same burdens by 25% to 31% and US$35.3bn, respectively, while less effective but immediately achievable scaling-up of existing treatment regimens would reduce burdens by 20% to 25% and US$28.4bn, respectively. If an increase in case detection to 90% could be combined with 95% effective pan-TB treatment, it could reduce clinical and demographic disease burdens by 78% to 91% and reduce the macroeconomic burden by US$124.2bn. In order to develop this complex integrated model framework, some aspects of the epidemiological model were simplified such that the model does not capture, for example, separate modelling of drug susceptible and multidrug-resistant (MDR) cases or separate public/private healthcare provision. However, future iterations of the model could address these limitations.ConclusionsIn this study, we find that even our least effective, but most accessible, revised TB treatment regimen has the potential to generate US$28bn in GDP gains. Clearly, the economic gains of increasing case detection rates and implementing improved TB treatment regimens hinges on both the feasibility and timeframe over which they can be achieved in practice. Nevertheless, the revised TB treatment regimen is readily accessible, and our results therefore demonstrate that there is room for undertaking substantial additional investment in control and treatment of TB in India, in order to reduce the suffering of TB patients while maintaining acceptable provision of resourcing elsewhere in the Indian economy.

Abstract Background Nigeria commenced rollout of vaccination for coronavirus disease 2019 (COVID-19) in March 2021 as part of the national public health response to the pandemic. Findings from appropriately contextualized cost–effectiveness analyses (CEA) as part of a wider process involving health technology assessment (HTA) approaches have been important in informing decision-making in this area. In this paper we outline the processes that were followed to identify COVID-19 vaccine stakeholders involved in the selection, approval, funding, procurement and rollout of vaccines in Nigeria, and describe the process routes we identified to support uptake of HTA-related information for evidence-informed policy in Nigeria. Methods Our approach to engaging with policy-makers and other stakeholders as part of an HTA of COVID vaccination in Nigeria consisted of three steps, namely: (i) informal discussions with key stakeholders; (ii) stakeholder mapping, analysis and engagement; and (iii) communication and dissemination strategies for the HTA-relevant evidence produced. The analysis of the stakeholder mapping uses the power/interest grid framework. Results The informal discussion with key stakeholders generated six initial policy questions. Further discussions with policy-makers yielded three suitable policy questions for analysis: which COVID-19 vaccines should be bought; what is the optimal mode of delivery of these vaccines; and what are the cost and cost–effectiveness of vaccinating people highlighted in Nigeria’s phase 2 vaccine rollout prioritized by the government, especially the inclusion of those aged between 18 and 49 years. The stakeholder mapping exercise highlighted the range of organizations and groups within Nigeria that could use the information from this HTA to guide decision-making. These stakeholders included both public/government, private and international organizations The dissemination plan developed included disseminating the full HTA results to key stakeholders; production of policy briefs; and presentation at different national and international conferences and peer-reviewed publications. Conclusions HTA processes that involve stakeholder engagement will help ensure important policy questions are taken into account when designing any HTA including any underpinning evidence generation. Further guidance about stakeholder engagement throughout HTA is required, especially for those with low interest in vaccine procurement and use.

Background Rapid diagnostic tests (RDTs) for coronavirus disease (COVID) are used in low- and middle-income countries (LMICs) to inform treatment decisions. However, to date, it is unclear when this use is cost-effective. Existing analyses are limited to a narrow set of countries and uses. The aim of this study is to assess the cost-effectiveness of COVID RDTs to inform the treatment of patients with severe illness in LMICs, considering real world practice. Methods and findings We assessed the cost-effectiveness of COVID testing across LMICs using a decision tree model, differentiating results by country income level, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) prevalence, and testing scenario (none, RDTs, polymerase chain reaction tests-PCRs and combinations). LMIC experts defined realistic care pathways and treatment options. Using a healthcare provider perspective and net monetary benefit approach, we assessed both intended (COVID symptom alleviation) and unintended (treatment side effects) health and economic impacts for each testing scenario. We included the side effects of corticosteroids, which are often the only available treatment for COVID. Because side effects depend both on the treatment and the patient's underlying illness (COVID or COVID-like illnesses, such as influenza), we considered the prevalence of COVID-like illnesses in our analyses. We found that SARS-CoV-2 testing of patients with severe COVID-like illness can be cost-effective in all LMICs, though only in some circumstances. High influenza prevalence among suspected COVID cases improves cost-effectiveness, since incorrectly provided corticosteroids may worsen influenza outcomes. In low- and some lower-middle-income countries, only patients with a high index of suspicion for COVID should be tested with RDTs, while other patients should be presumed to not have COVID. In some lower-middle-income and upper-middle-income countries, suspected severe COVID cases should almost always be tested. Further, in these settings, negative test results in patients with a high initial index of suspicion should be confirmed through PCR and, during influenza outbreaks, positive results in patients with a low initial index of suspicion should also be confirmed with a PCR. The use of interleukin-6 receptor blockers, when supported by testing, may also be cost-effective in higher-income LMICs. The cost at which they would be cost-effective in low-income countries ($162 to $406 per treatment course) is below current prices. The primary limitation of our analysis is substantial uncertainty around some of the parameters in our model due to limited data, most notably on current COVID mortality with standard of care, and insufficient evidence on the impact of corticosteroids on patients with severe influenza. Conclusions COVID testing can be cost-effective to inform treatment of LMIC patients with severe COVID-like disease. The optimal algorithm is driven by country income level and health budgets, the level of suspicion that the patient may have COVID, and influenza prevalence. Further research to better characterize the unintended effects of corticosteroids, particularly on influenza cases, could improve decision making around the treatment of those with COVID-like symptoms in LMICs., Author(s): Gabrielle Bonnet 1,*, John Bimba 2,3, Chancy Chavula 4, Harunavamwe N. Chifamba 5, Titus H. Divala 6, Andres G. Lescano 7, Mohammed Majam 8, Danjuma Mbo 9, Auliya A. [...]

We read with great interest the recent paper by Lo et al., who argue that there is an urgent need to ensure the quality of modelling evidence used to support international and national guideline development. Here we outline efforts by the Tuberculosis Modelling and Analysis Consortium, together with the World Health Organization Global Task Force on Tuberculosis Impact Measurement, to develop material to improve the quality and transparency of country-level tuberculosis modelling to inform decision-making.

BackgroundRapid diagnostic tests (RDTs) for coronavirus disease (COVID) are used in low- and middle-income countries (LMICs) to inform treatment decisions. However, to date, it is unclear when this use is cost-effective. Existing analyses are limited to a narrow set of countries and uses. The aim of this study is to assess the cost-effectiveness of COVID RDTs to inform the treatment of patients with severe illness in LMICs, considering real world practice.Methods and findingsWe assessed the cost-effectiveness of COVID testing across LMICs using a decision tree model, differentiating results by country income level, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) prevalence, and testing scenario (none, RDTs, polymerase chain reaction tests-PCRs and combinations). LMIC experts defined realistic care pathways and treatment options. Using a healthcare provider perspective and net monetary benefit approach, we assessed both intended (COVID symptom alleviation) and unintended (treatment side effects) health and economic impacts for each testing scenario. We included the side effects of corticosteroids, which are often the only available treatment for COVID. Because side effects depend both on the treatment and the patient's underlying illness (COVID or COVID-like illnesses, such as influenza), we considered the prevalence of COVID-like illnesses in our analyses. We found that SARS-CoV-2 testing of patients with severe COVID-like illness can be cost-effective in all LMICs, though only in some circumstances. High influenza prevalence among suspected COVID cases improves cost-effectiveness, since incorrectly provided corticosteroids may worsen influenza outcomes. In low- and some lower-middle-income countries, only patients with a high index of suspicion for COVID should be tested with RDTs, while other patients should be presumed to not have COVID. In some lower-middle-income and upper-middle-income countries, suspected severe COVID cases should almost always be tested. Further, in these settings, negative test results in patients with a high initial index of suspicion should be confirmed through PCR and, during influenza outbreaks, positive results in patients with a low initial index of suspicion should also be confirmed with a PCR. The use of interleukin-6 receptor blockers, when supported by testing, may also be cost-effective in higher-income LMICs. The cost at which they would be cost-effective in low-income countries ($162 to $406 per treatment course) is below current prices. The primary limitation of our analysis is substantial uncertainty around some of the parameters in our model due to limited data, most notably on current COVID mortality with standard of care, and insufficient evidence on the impact of corticosteroids on patients with severe influenza.ConclusionsCOVID testing can be cost-effective to inform treatment of LMIC patients with severe COVID-like disease. The optimal algorithm is driven by country income level and health budgets, the level of suspicion that the patient may have COVID, and influenza prevalence. Further research to better characterize the unintended effects of corticosteroids, particularly on influenza cases, could improve decision making around the treatment of those with COVID-like symptoms in LMICs.

Abstract Background The war in South Sudan has displaced more than four million people, with Uganda hosting the largest number of South Sudanese refugees. Research in Uganda has shown elevated levels of alcohol misuse and psychological distress among these refugees. The World Health Organization (WHO) has developed a trans-diagnostic scalable psychological intervention called Problem Management Plus (PM +) to reduce psychological distress among populations exposed to adversities. Our study aims to evaluate the effectiveness and cost-effectiveness of the CHANGE intervention, which builds on PM + , to also address alcohol misuse through problem-solving therapy and selected behavioural strategies for dealing with alcohol use disorders. We hypothesise that the CHANGE intervention together with enhanced usual care (EUC) will be superior to EUC alone in increasing the percentage of days abstinent. Methods A parallel-arm individually randomised controlled trial will be conducted in the Rhino Camp and Imvepi settlements in Uganda. Five hundred adult male South Sudanese refugees with (i) elevated levels of alcohol use (between 8 and 20 on the Alcohol Use Disorder Identification Test [AUDIT]); and (ii) psychological distress (> 16 on the Kessler Psychological Distress Scale) will be randomly assigned 1:1 to EUC or CHANGE and EUC. CHANGE will be delivered by lay healthcare providers over 6 weeks. Outcomes will be assessed at 3 and 12 months post-randomisation. The primary outcome is the percentage of days abstinent, measured by the timeline follow-back measure at 3 months. Secondary outcomes include percentage of days abstinent at 12 months and alcohol misuse (measured by the AUDIT), psychological distress (i.e. depression, anxiety, posttraumatic stress disorder), functional disability, perpetration of intimate partner violence, and health economic indicators at 3 and 12 months. A mixed-methods process evaluation will investigate competency, dose, fidelity, feasibility, and acceptability. Primary analyses will be intention-to-treat. Discussion CHANGE aims to address alcohol misuse and psychological distress with male refugees in a humanitarian setting. If it is proven to be effective, it can help fill an important under-researched gap in humanitarian service delivery. Trial registration ISRCTN ISRCTN10360385. Registered on 30 January 2023.

Abstract Background Avahan, the India AIDS Initiative, delivers HIV prevention services to high-risk populations at scale. Although the broad costs of such HIV interventions are known, to-date there has been little data available on the comparative costs of reaching different target groups, including female sex workers (FSWs), replace with ‘high risk men who have sex with men (HR-MSM) and trans-genders. Methods Costs are estimated for the first three years of Avahan scale up differentiated by typology of female sex workers (brothel, street, home, lodge based, bar based), HR-MSM and transgenders in urban districts in India: Mumbai and Thane in Maharashtra and Bangalore in Karnataka. Financial and economic costs were collected prospectively from a provider perspective. Outputs were measured using data collected by the Avahan programme. Costs are presented in US$2008. Results Costs were found to vary substantially by target group. Non-governmental organisations (NGOs) working with transgender populations had a higher mean cost (US $116) per person reached compared to those dealing primarily with FSWs (US $75-96) and MSWs (US $90) by the end of year three of the programme in Mumbai. The mean cost of delivering the intervention to HR-MSMs (US $42) was higher than delivering it to FSWs (US $37) in Bangalore. The package of services delivered to each target group was similar, and our results suggest that cost variation is related to the target population size, the intensity of the programme (in terms of number of contacts made per year) and a number of specific issues related to each target group. Conclusions Based on our data policy makers and program managers need to consider the ease of accessing high risk population when planning and budgeting for HIV prevention services for these populations and avoid funding programmes on the basis of target population size alone.

Abstract Background Rapid diagnostic testing may support improved treatment of COVID patients. Understanding COVID testing and care pathways is important for assessing the impact and cost-effectiveness of testing in the real world, yet there is limited information on these pathways in low-and-middle income countries (LMICs). We therefore undertook an expert consultation to better understand testing policies and practices, clinical screening, the profile of patients seeking testing or care, linkage to care after testing, treatment, lessons learnt and expected changes in 2023. Methods We organized a qualitative consultation with ten experts from seven LMICs (India, Indonesia, Malawi, Nigeria, Peru, South Africa, and Zimbabwe) identified through purposive sampling. We conducted structured interviews during six regional consultations, and undertook a thematic analysis of responses. Results Participants reported that, after initial efforts to scale-up testing, the policy priority given to COVID testing has declined. Comorbidities putting patients at heightened risk (e.g., diabetes) mainly relied on self-identification. The decision to test following clinical screening was highly context-/location-specific, often dictated by local epidemiology and test availability. When rapid diagnostic tests were available, public sector healthcare providers tended to rely on them for diagnosis (alongside PCR for Asian/Latin American participants), while private sector providers predominantly used polymerase chain reaction (PCR) tests. Positive test results were generally taken at ‘face value’ by clinicians, although negative tests with a high index of suspicion may be confirmed with PCR. However, even with a positive result, patients were not always linked to care in a timely manner because of reluctance to receiving care or delays in returning to care centres upon clinical deterioration. Countries often lacked multiple components of the range of therapeutics advised in WHO guidelines: notably so for oral antivirals designed for high-risk mild patients. Severely ill patients mostly received corticosteroids and, in higher-resourced settings, tocilizumab. Conclusions Testing does not always prompt enhanced care, due to reluctance on the part of patients and limited therapeutic availability within clinical settings. Any analysis of the impact or cost-effectiveness of testing policies post pandemic needs to either consider investment in optimal treatment pathways or constrain estimates of benefits based on actual practice.

Abstract Background Countries around the world are increasingly rethinking the design of their health benefit package to achieve universal health coverage. Countries can periodically revise their packages on the basis of sectoral cost-effectiveness analyses, i.e. by evaluating a broad set of services against a ‘doing nothing’ scenario using a budget constraint. Alternatively, they can use incremental cost-effectiveness analyses, i.e. to evaluate specific services against current practice using a threshold. In addition, countries may employ hybrid approaches which combines elements of sectoral and incremental cost-effectiveness analysis - a country may e.g. not evaluate the comprehensive set of all services but rather relatively small sets of services targeting a certain condition. However, there is little practical guidance for countries as to which kind of approach they should follow. Methods The present study was based on expert consultation. We refined the typology of approaches of cost-effectiveness analysis for benefit package design, identified factors that should be considered in the choice of approach, and developed recommendations. We reached consensus among experts over the course of several review rounds. Results Sectoral cost-effectiveness analysis is especially suited in contexts with large allocative inefficiencies in current service provision and can, in theory, realize large efficiency gains. However, it may be challenging to implement a comprehensive redesign of the package in practice. Incremental cost-effectiveness analysis is especially relevant in contexts where specific new services may impact the sustainability of the health system. It may potentially support efficiency improvement, but its focus has typically been on new services while existing inefficiencies remain unchallenged. The use of hybrid approach may be a way forward to address the strengths and weaknesses of sectoral and incremental analysis areas. Such analysis may be especially useful to target disease areas with suspected high inefficiencies in service provision, and would then make good use of the available research capacity and be politically rewarding. However, disease-specific analyses bear the risk of not addressing resource allocation inefficiencies across disease areas. Conclusions Countries should carefully select their approach of cost-effectiveness analyses for benefit package design, based on their decision-making context.

BackgroundThe World Health Organization (WHO) plays a crucial role in producing global guidelines. In response to previous criticism, WHO has made efforts to enhance the process of guideline development, aiming for greater systematicity and transparency. However, it remains unclear whether these changes have effectively addressed these earlier critiques. This paper examines the policy process employed by WHO to inform guideline recommendations, using the update of the WHO Consolidated HIV Testing Services (HTS) Guidelines as a case study.MethodsWe observed guideline development meetings and conducted semi-structured interviews with key participants involved in the WHO guideline-making process. The interviews were recorded, transcribed, and analysed thematically. The data were deductively coded and analysed in line with the main themes from a published conceptual framework for context-based evidence-based decision making: introduction, interpretation, and application of evidence.ResultsThe HTS guideline update was characterized by an inclusive and transparent process, involving a wide range of stakeholders. However, it was noted that not all stakeholders could participate equally due to gaps in training and preparation, particularly regarding the complexity of the Grading Recommendations Assessment Development Evaluation (GRADE) framework. We also found that WHO does not set priorities for which or how many guidelines should be produced each year and does not systematically evaluate the implementation of their recommendations. Our interviews revealed disconnects in the evidence synthesis process, starting from the development of systematic review protocols. While GRADE prioritizes evidence from RCTs, the Guideline Development Group (GDG) heavily emphasized “other” GRADE domains for which little or no evidence was available from the systematic reviews. As a result, expert judgements and opinions played a role in making recommendations. Finally, the role of donors and their presence as observers during GDG meetings was not clearly defined.ConclusionWe found a need for a different approach to evidence synthesis due to the diverse range of global guidelines produced by WHO. Ideally, the evidence synthesis should be broad enough to capture evidence from different types of studies for all domains in the GRADE framework. Greater structure is required in formulating GDGs and clarifying the role of donors through the process.

ObjectiveDiabetes 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.MethodsLongitudinal 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.Results530 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 (pConclusionPeople 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.

Tuberculosis is a major infectious disease worldwide, but currently available diagnostics have suboptimal accuracy, particularly in patients unable to expectorate, and are often unavailable at the point-of-care in resource-limited settings. Test/treatment decision are, therefore, often made on clinical grounds. We hypothesized that contextual factors beyond disease probability may influence clinical decisions about when to test and when to treat for tuberculosis. This umbrella review aimed to identify such factors, and to develop a framework for uncertainty in tuberculosis clinical decision-making. Systematic reviews were searched in seven databases (MEDLINE, CINAHL Complete, Embase, Scopus, Cochrane, PROSPERO, Epistemonikos) using predetermined search criteria. Findings were classified as barriers and facilitators for testing or treatment decisions, and thematically analysed based on a multi-level model of uncertainty in health care. We included 27 reviews. Study designs and primary aims were heterogeneous, with seven meta-analyses and three qualitative evidence syntheses. Facilitators for decisions to test included providers' advanced professional qualification and confidence in tests results, availability of automated diagnostics with quick turnaround times. Common barriers for requesting a diagnostic test included: poor provider tuberculosis knowledge, fear of acquiring tuberculosis through respiratory sampling, scarcity of healthcare resources, and complexity of specimen collection. Facilitators for empiric treatment included patients' young age, severe sickness, and test inaccessibility. Main barriers to treatment included communication obstacles, providers' high confidence in negative test results (irrespective of negative predictive value). Multiple sources of uncertainty were identified at the patient, provider, diagnostic test, and healthcare system levels. Complex determinants of uncertainty influenced decision-making. This could result in delayed or missed diagnosis and treatment opportunities. It is important to understand the variability associated with patient-provider clinical encounters and healthcare settings, clinicians' attitudes, and experiences, as well as diagnostic test characteristics, to improve clinical practices, and allow an impactful introduction of novel diagnostics.

As financial risk protection is one of the goals towards universal health coverage, detailed information on costs, catastrophic costs and other economic consequences related to any disease are required for designing social protection measures. End Tuberculosis (TB) Strategy set a milestone of achieving zero catastrophic cost by 2020. However, a recent literature review noted that 7%-32% TB affected households in India faced catastrophic cost. Studies included in the review were small scale cross-sectional. We followed a cohort of 1482 notified drug-susceptible TB patients from four states in India: Assam, Maharashtra, Tamil Nadu, and West Bengal to provide a comprehensive picture of economic burden associated with TB treatment. Treatment cost was calculated using World Health Organization guidelines on TB patient cost survey and both human capital and output approaches of indirect cost (time, productivity, and income loss related to an episode) calculation were used to provide the range of households currently facing catastrophic cost. Depending on choice of indirect cost calculation method, 30%-61% study participants faced catastrophic cost. For over half of them, costs became catastrophic even before starting TB treatment as there was average 7-9 weeks delay from symptom onset to treatment initiation which was double the generally accepted delay of 4 weeks. During that period, they made average 8-11 visits to different providers and spent money on consultations, drugs, tests, and travel. Following the largest cohort of drug-susceptible TB patients till date, the study concluded that a significant proportion of study participants faced catastrophic cost and the proportion was much higher when income loss was considered as indirect cost calculation method. Therefore, ensuring uninterrupted livelihood during TB treatment is an absolute necessity. Another reason of high cost was the delay in diagnosis and costs incurred during pre-diagnosis period. This delay and consequently, economic burden, can be reduced by both supply side (intense private sector engagement, rapid diagnosis) and demand side (community engagement) initiatives. Reimbursement of expenses incurred before treatment initiation could be used as short-term measure for mitigating financial hardship.

Abstract Background In sub-Saharan Africa (SSA) there are strong arguments for the provision of integrated sexual and reproductive health (SRH) and HIV services. Most HIV transmissions are sexually transmitted or associated with pregnancy, childbirth, and breastfeeding. Many of the behaviours that prevent HIV transmission also prevent sexually transmitted infections and unintended pregnancies. There is potential for integration to increase the coverage of HIV services, as individuals who use SRH services can benefit from HIV services and vice-versa, as well as increase cost-savings. However, there is a dearth of empirical evidence on effective models for integrating HIV/SRH services. The need for robust evidence led a consortium of three organizations – International Planned Parenthood Federation, Population Council and the London School of Hygiene & Tropical Medicine – to design/implement the Integra Initiative. Integra seeks to generate rigorous evidence on the feasibility, effectiveness, cost and impact of different models for delivering integrated HIV/SRH services in high and medium HIV prevalence settings in SSA. Methods/design A quasi-experimental study will be conducted in government clinics in Kenya and Swaziland – assigned into intervention/comparison groups. Two models of service delivery are investigated: integrating HIV care/treatment into 1) family planning and 2) postnatal care. A full economic-costing will be used to assess the costs of different components of service provision, and the determinants of variations in unit costs across facilities/service models. Health facility assessments will be conducted at four time-periods to track changes in quality of care and utilization over time. A two-year cohort study of family planning/postnatal clients will assess the effect of integration on individual outcomes, including use of SRH services, HIV status (known/unknown) and pregnancy (planned/unintended). Household surveys within some of the study facilities’ catchment areas will be conducted to profile users/non-users of integrated services and demand/receipt of integrated services, before-and-after the intervention. Qualitative research will be conducted to complement the quantitative component at different time points. Integra takes an embedded ‘programme science’ approach to maximize the uptake of findings into policy/practice. Discussion Integra addresses existing evidence gaps in the integration evaluation literature, building on the limited evidence from SSA and the expertise of its research partners. Trial registration Current Controlled Trials NCT01694862

Abstract Background There is a global interest in institutionalizing health technology assessment (HTA) as an approach for explicit healthcare priority-setting. Institutionalization of HTA refers to the process of conducting and utilizing HTA as a normative practice for guiding resource allocation decisions within the health system. In this study, we aimed to examine the factors that were influencing institutionalization of HTA in Kenya. Methods We conducted a qualitative case study using document reviews and in-depth interviews with 30 participants involved in the HTA institutionalization process in Kenya. We used a thematic approach to analyze the data. Results We found that institutionalization of HTA in Kenya was being supported by factors such as establishment of organizational structures for HTA; availability of legal frameworks and policies on HTA; increasing availability of awareness creation and capacity-building initiatives for HTA; policymakers’ interests in universal health coverage and optimal allocation of resources; technocrats’ interests in evidence-based processes; presence of international collaboration for HTA; and lastly, involvement of bilateral agencies. On the other hand, institutionalization of HTA was being undermined by limited availability of skilled human resources, financial resources, and information resources for HTA; lack of HTA guidelines and decision-making frameworks; limited HTA awareness among subnational stakeholders; and industries’ interests in safeguarding their revenue. Conclusions Kenya’s Ministry of Health can facilitate institutionalization of HTA by adopting a systemic approach that involves: - (a) introducing long-term capacity-building initiatives to strengthen human and technical capacity for HTA; (b) earmarking national health budgets to ensure adequate financial resources for HTA; (c) introducing a cost database and promoting timely data collection to ensure availability of data for HTA; (d) developing context specific HTA guidelines and decision-making frameworks to facilitate HTA processes; (e) conducting deeper advocacy to strengthen HTA awareness among subnational stakeholders; and (f) managing stakeholders’ interests to minimize opposition to institutionalization of HTA.

With the legalization of marijuana smoking in several states of the United States and many other countries for medicinal and recreational use, the possibility of its release into the environment cannot be overruled. Currently, the environmental levels of marijuana metabolites are not monitored on a regular basis, and their stability in the environment is not well understood. Laboratory studies have linked delta 9-tetrahydrocannabinol (Δ9-THC) exposure with behavioral abnormalities in some fish species; however, their effects on endocrine organs are less understood. To understand the effects of THC on the brain and gonads, we exposed adult medaka (Oryzias latipes, Hd-rR strain, both male and female) to 50 ug/L THC for 21 days spanning their complete spermatogenic and oogenic cycles. We examined transcriptional responses of the brain and gonads (testis and ovary) to Δ9-THC, particularly molecular pathways associated with behavioral and reproductive functions. The Δ9-THC effects were more profound in males than females. The Δ9-THC-induced differential expression pattern of genes in the brain of the male fish suggested pathways to neurodegenerative diseases and pathways to reproductive impairment in the testis. The present results provide insights into endocrine disruption in aquatic organisms due to environmental cannabinoid compounds.

Abstract Background A recurrent feature of infectious diseases is the observation that different individuals show different levels of secondary transmission. This inter-individual variation in transmission potential is often quantified by the dispersion parameter k. Low values of k indicate a high degree of variability and a greater probability of superspreading events. Understanding k for COVID-19 across contexts can assist policy makers prepare for future pandemics. Methods A literature search following a systematic approach was carried out in PubMed, Embase, Web of Science, Cochrane Library, medRxiv, bioRxiv and arXiv to identify publications containing epidemiological findings on superspreading in COVID-19. Study characteristics, epidemiological data, including estimates for k and R0, and public health recommendations were extracted from relevant records. Results The literature search yielded 28 peer-reviewed studies. The mean k estimates ranged from 0.04 to 2.97. Among the 28 studies, 93% reported mean k estimates lower than one, which is considered as marked heterogeneity in inter-individual transmission potential. Recommended control measures were specifically aimed at preventing superspreading events. The combination of forward and backward contact tracing, timely confirmation of cases, rapid case isolation, vaccination and preventive measures were suggested as important components to suppress superspreading. Conclusions Superspreading events were a major feature in the pandemic of SARS-CoV-2. On the one hand, this made outbreaks potentially more explosive but on the other hand also more responsive to public health interventions. Going forward, understanding k is critical for tailoring public health measures to high-risk groups and settings where superspreading events occur.

Abstract Economic analyses of healthcare interventions are an important consideration in evidence-based policymaking. A key component of such analyses is the costs of interventions, for which most are familiar with using budgets and expenditures. However, economic theory states that the true value of a good/service is the value of the next best alternative forgone as a result of using the resource and therefore observed prices or charges do not necessarily reflect the true economic value of resources. To address this, economic costs are a fundamental concept within (health) economics. Crucially, they are intended to reflect the resources’ opportunity costs (the forgone opportunity to use those resources for another purpose) and they are based on the value of the resource's next-best alternative use that has been forgone. This is a broader conceptualization of a resource’s value than its financial cost and recognizes that resources can have a value that may not be fully captured by their market price and that by using a resource it makes it unavailable for productive use elsewhere. Importantly, economic costs are preferred over financial costs for any health economic analyses aimed at informing decisions regarding the optimum allocation of the limited/competing resources available for healthcare (such as health economic evaluations), and they are also important when considering the replicability and sustainability of healthcare interventions. However, despite this, economic costs and the reasons why they are used is an area that can be misunderstood by professionals without an economic background. In this paper, we outline to a broader audience the principles behind economic costs and when and why they should be used within health economic analyses. We highlight that the difference between financial and economic costs and what adjustments are needed within cost calculations will be influenced by the context of the study, the perspective, and the objective.

Abstract Background Vaccination is a key tool against COVID-19. However, in many settings it is not clear how acceptable COVID-19 vaccination is among the general population, or how hesitancy correlates with risk of disease acquisition. In this study we conducted a nationally representative survey in Pakistan to measure vaccination perceptions and social contacts in the context of COVID-19 control measures and vaccination programmes. Methods We conducted a vaccine perception and social contact survey with 3,658 respondents across five provinces in Pakistan, between 31 May and 29 June 2021. Respondents were asked a series of vaccine perceptions questions, to report all direct physical and non-physical contacts made the previous day, and a number of other questions regarding the social and economic impact of COVID-19 and control measures. We examined variation in perceptions and contact patterns by geographic and demographic factors. We describe knowledge, experiences and perceived risks of COVID-19. We explored variation in contact patterns by individual characteristics and vaccine hesitancy, and compared to patterns from non-pandemic periods. Results Self-reported adherence to self-isolation guidelines was poor, and 51% of respondents did not know where to access a COVID-19 test. Although 48.1% of participants agreed that they would get a vaccine if offered, vaccine hesitancy was higher than in previous surveys, and greatest in Sindh and Baluchistan provinces and among respondents of lower socioeconomic status. Participants reported a median of 5 contacts the previous day (IQR: 3–5, mean 14.0, 95%CI: 13.2, 14.9). There were no substantial differences in the number of contacts reported by individual characteristics, but contacts varied substantially among respondents reporting more or less vaccine hesitancy. Contacts were highly assortative, particularly outside the household where 97% of men's contacts were with other men. We estimate that social contacts were 9% lower than before the COVID-19 pandemic. Conclusions Although the perceived risk of COVID-19 in Pakistan is low in the general population, around half of participants in this survey indicated they would get vaccinated if offered. Vaccine impact studies which do not account for correlation between social contacts and vaccine hesitancy may incorrectly estimate the impact of vaccines, for example, if unvaccinated people have more contacts.

BACKGROUND: One critical element to optimize funding decisions involves the cost and efficiency implications of implementing alternative program components and configurations. Program planners, policy makers and funders alike are in need of relevant, strategic data and analyses to help them plan and implement effective and efficient programs. Contrary to widely accepted conceptions in both policy and academic arenas, average costs per service (so-called unit costs) vary considerably across implementation settings and facilities. The objective of this work is twofold: 1) to estimate the variation of VMMC unit costs across service delivery platforms (SDP) in Sub-Saharan countries, and 2) to develop and validate a strategy to extrapolate unit costs to settings for which no data exists. METHODS: We identified high-quality VMMC cost studies through a literature review. Authors were contacted to request the facility-level datasets (primary data) underlying their results. We standardized the disparate datasets into an aggregated database which included 228 facilities in eight countries. We estimated multivariate models to assess the correlation between VMMC unit costs and scale, while simultaneously accounting for the influence of the SDP (which we defined as all possible combinations of type of facility, ownership, urbanicity, and country), on the unit cost variation. We defined SDP as any combination of such four characteristics. Finally, we extrapolated VMMC unit costs for all SDPs in 13 countries, including those not contained in our dataset. RESULTS: The average unit cost was 73 USD (IQR: 28.3, 100.7). South Africa showed the highest within-country cost variation, as well as the highest mean unit cost (135 USD). Uganda and Namibia had minimal within-country cost variation, and Uganda had the lowest mean VMMC unit cost (22 USD). Our results showed evidence consistent with economies of scale. Private ownership and Hospitals were significant determinants of higher unit costs. By identifying key cost drivers, including country- and facility-level characteristics, as well as the effects of scale we developed econometric models to estimate unit cost curves for VMMC services in a variety of clinical and geographical settings. CONCLUSION: While our study did not produce new empirical data, our results did increase by a tenfold the availability of unit costs estimates for 128 SDPs in 14 priority countries for VMMC. It is to our knowledge, the most comprehensive analysis of VMMC unit costs to date. Furthermore, we provide a proof of concept of the ability to generate predictive cost estimates for settings where empirical data does not exist.

There is global interest in institutionalizing Health Technology Assessment (HTA) to inform resource allocation decisions. However, institutionalization of HTA remains limited particularly in low- and lower-middle-income countries. We conducted this scoping review to synthesize evidence on factors that influence the institutionalization of HTA at the macro (national)-level across countries globally. We searched for relevant literature in six databases namely PubMed, Embase, CINAHL, Scopus, EconLit, and Google Scholar. We conducted the last search on December 31, 2021. We identified 77 articles that described factors that influence institutionalization of HTA across 135 high-, middle-, and low-income countries. We analyzed these articles thematically. We identified five sets of factors that influence the institutionalization of HTA across countries of different income levels. These factors include: (1) organizational resources such as organizational structures, and skilled human, financial, and information resources; (2) legal frameworks, policies, and guidelines for HTA; (3) learning and advocacy for HTA; (4) stakeholder-related factors such as stakeholders’ interests, awareness, and understanding; and (5) collaborative support for HTA through international networks and non-governmental and multi-lateral organizations. Countries seeking to institutionalize HTA should map the availability of the factors identified in this review. Developing these factors wherever necessary can influence a country’s capacity to institutionalize the conduct and use of HTA.

All health systems must set priorities. Evidence-informed priority-setting (EIPS) is a specific form of systematic priority-setting which involves explicit consideration of evidence to determine the healthcare interventions to be provided. The international Decision Support Initiative (iDSI) was established in 2013 as a collaborative platform to catalyze faster progress on EIPS, particularly in low- and middle-income countries. This article summarizes the successes, challenges, and lessons learned from ten years of iDSI partnering with countries to develop EIPS institutions and processes. This is a thematic documentary analysis, structured by iDSI’s theory of change, extracting successes, challenges, and lessons from three external evaluations and 19 internal reports to funders. We identified three phases of iDSI’s work—inception (2013–15), scale-up (2016–2019), and focus on Africa (2019–2023). iDSI has established a global platform for coordinating EIPS, advanced the field, and supported regional networks in Asia and Africa. It has facilitated progress in securing high-level commitment to EIPS, strengthened EIPS institutions, and developed capacity for health technology assessments. This has resulted in improved decisions on service provision, procurement, and clinical care. Major lessons learned include the importance of sustained political will to develop EIPS; a clear EIPS mandate; inclusive governance structures appropriate to health financing context; politically sensitive and country-led support to EIPS, taking advantage of policy windows for EIPS reforms; regional networks for peer support and long-term sustainability; utilization of context appropriate methods such as adaptive HTA; and crucially, donor-funded global health initiatives supporting and integrating with national EIPS systems, not undermining them.

Abstract Background The COVID-19 vaccine supply shortage in 2021 constrained roll-out efforts in Africa while populations experienced waves of epidemics. As supply improves, a key question is whether vaccination remains an impactful and cost-effective strategy given changes in the timing of implementation. Methods We assessed the impact of vaccination programme timing using an epidemiological and economic model. We fitted an age-specific dynamic transmission model to reported COVID-19 deaths in 27 African countries to approximate existing immunity resulting from infection before substantial vaccine roll-out. We then projected health outcomes (from symptomatic cases to overall disability-adjusted life years (DALYs) averted) for different programme start dates (01 January to 01 December 2021, n = 12) and roll-out rates (slow, medium, fast; 275, 826, and 2066 doses/million population-day, respectively) for viral vector and mRNA vaccines by the end of 2022. Roll-out rates used were derived from observed uptake trajectories in this region. Vaccination programmes were assumed to prioritise those above 60 years before other adults. We collected data on vaccine delivery costs, calculated incremental cost-effectiveness ratios (ICERs) compared to no vaccine use, and compared these ICERs to GDP per capita. We additionally calculated a relative affordability measure of vaccination programmes to assess potential nonmarginal budget impacts. Results Vaccination programmes with early start dates yielded the most health benefits and lowest ICERs compared to those with late starts. While producing the most health benefits, fast vaccine roll-out did not always result in the lowest ICERs. The highest marginal effectiveness within vaccination programmes was found among older adults. High country income groups, high proportions of populations over 60 years or non-susceptible at the start of vaccination programmes are associated with low ICERs relative to GDP per capita. Most vaccination programmes with small ICERs relative to GDP per capita were also relatively affordable. Conclusion Although ICERs increased significantly as vaccination programmes were delayed, programmes starting late in 2021 may still generate low ICERs and manageable affordability measures. Looking forward, lower vaccine purchasing costs and vaccines with improved efficacies can help increase the economic value of COVID-19 vaccination programmes.

Abstract Background Globally, nearly half of all deaths among children under the age of 5 years can be attributed to malaria, diarrhoea, and pneumonia. A significant proportion of these deaths occur in sub-Saharan Africa. Despite several programmes implemented in sub-Saharan Africa, the burden of these illnesses remains persistently high. To mobilise resources for such programmes it is necessary to evaluate their costs, costs-effectiveness, and affordability. This study aimed to estimate the provider costs of treating malaria, diarrhoea, and pneumonia among children under the age of 5 years in routine settings at the health facility level in rural Uganda and Mozambique. Methods Service and cost data was collected from health facilities in midwestern Uganda and Inhambane province, Mozambique from private and public health facilities. Financial and economic costs of providing care for childhood illnesses were investigated from the provider perspective by combining a top-down and bottom-up approach to estimate unit costs and annual total costs for different types of visits for these illnesses. All costs were collected in Ugandan shillings and Mozambican meticais. Costs are presented in 2021 US dollars. Results In Uganda, the highest number of outpatient visits were for children with uncomplicated malaria and of inpatient admissions were for respiratory infections, including pneumonia. The highest unit cost for outpatient visits was for pneumonia (and other respiratory infections) and ranged from $0.5 to 2.3, while the highest unit cost for inpatient admissions was for malaria ($19.6). In Mozambique, the highest numbers of outpatient and inpatient admissions visits were for malaria. The highest unit costs were for malaria too, ranging from $2.5 to 4.2 for outpatient visits and $3.8 for inpatient admissions. The greatest contributors to costs in both countries were drugs and diagnostics, followed by staff. Conclusions The findings highlighted the intensive resource use in the treatment of malaria and pneumonia for outpatient and inpatient cases, particularly at higher level health facilities. Timely treatment to prevent severe complications associated with these illnesses can also avoid high costs to health providers, and households. Trial registration: ClinicalTrials.gov, identifier: NCT01972321.

BackgroundThe majority of post-neonatal deaths in children under 5 are due to malaria, diarrhoea and pneumonia (MDP). The WHO recommends integrated community case management (iCCM) of these conditions using community-based health workers (CHW). However iCCM programmes have suffered from poor implementation and mixed outcomes. We designed and evaluated a technology-based (mHealth) intervention package 'inSCALE' (Innovations At Scale For Community Access and Lasting Effects) to support iCCM programmes and increase appropriate treatment coverage for children with MDP.MethodsThis superiority cluster randomised controlled trial allocated all 12 districts in Inhambane Province in Mozambique to receive iCCM only (control) or iCCM plus the inSCALE technology intervention. Population cross-sectional surveys were conducted at baseline and after 18 months of intervention implementation in approximately 500 eligible households in randomly selected communities in all districts including at least one child less than 60 months of age where the main caregiver was available to assess the impact of the intervention on the primary outcome, the coverage of appropriate treatment for malaria, diarrhoea and pneumonia in children 2-59months of age. Secondary outcomes included the proportion of sick children who were taken to the CHW for treatment, validated tool-based CHW motivation and performance scores, prevalence of cases of illness, and a range of secondary household and health worker level outcomes. All statistical models accounted for the clustered study design and variables used to constrain the randomisation. A meta-analysis of the estimated pooled impact of the technology intervention was conducted including results from a sister trial (inSCALE-Uganda).FindingsThe study included 2740 eligible children in control arm districts and 2863 children in intervention districts. After 18 months of intervention implementation 68% (69/101) CHWs still had a working inSCALE smartphone and app and 45% (44/101) had uploaded at least one report to their supervising health facility in the last 4 weeks. Coverage of the appropriate treatment of cases of MDP increased by 26% in the intervention arm (adjusted RR 1.26 95% CI 1.12-1.42, pInterpretationThe inSCALE intervention led to an improvement in appropriate treatment of common childhood illnesses when delivered at scale in Mozambique. The programme will be rolled out by the ministry of health to the entire national CHW and primary care network in 2022-2023. This study highlights the potential value of a technology intervention aimed at strengthening iCCM systems to address the largest causes of childhood morbidity and mortality in sub-Saharan Africa.

The inSCALE cluster randomised controlled trial in Uganda evaluated two interventions, mHealth and Village Health Clubs (VHCs) which aimed to improve Community Health Worker (CHW) treatment for malaria, diarrhoea, and pneumonia within the national Integrated Community Case Management (iCCM) programme. The interventions were compared with standard care in a control arm. In a cluster randomised trial, 39 sub-counties in Midwest Uganda, covering 3167 CHWs, were randomly allocated to mHealth; VHC or usual care (control) arms. Household surveys captured parent-reported child illness, care seeking and treatment practices. Intention-to-treat analysis estimated the proportion of appropriately treated children with malaria, diarrhoea, and pneumonia according to WHO informed national guidelines. The trial was registered at ClinicalTrials.gov (NCT01972321). Between April-June 2014, 7679 households were surveyed; 2806 children were found with malaria, diarrhoea, or pneumonia symptoms in the last one month. Appropriate treatment was 11% higher in the mHealth compared to the control arm (risk ratio [RR] 1.11, 95% CI 1.02, 1.21; p = 0.018). The largest effect was on appropriate treatment for diarrhoea (RR 1.39; 95% CI 0.90, 2.15; p = 0.134). The VHC intervention increased appropriate treatment by 9% (RR 1.09; 95% CI 1.01, 1.18; p = 0.059), again with largest effect on treatment of diarrhoea (RR 1.56, 95% CI 1.04, 2.34, p = 0.030). CHWs provided the highest levels of appropriate treatment compared to other providers. However, improvements in appropriate treatment were observed at health facilities and pharmacies, with CHW appropriate treatment the same across the arms. The rate of CHW attrition in both intervention arms was less than half that of the control arm; adjusted risk difference mHealth arm -4.42% (95% CI -8.54, -0.29, p = 0.037) and VHC arm -4.75% (95% CI -8.74, -0.76, p = 0.021). Appropriate treatment by CHWs was encouragingly high across arms. The inSCALE mHealth and VHC interventions have the potential to reduce CHW attrition and improve the care quality for sick children, but not through improved CHW management as we had hypothesised. Trial Registration:ClinicalTrials.gov (NCT01972321).