Optimal subscription models to pay for antibiotics.

Novel subscription payment schemes are one of the approaches being explored to tackle the threat of antimicrobial resistance. Under these schemes, some or all of the payment is made via a fixed "subscription" payment, which provides a funder unlimited access to the treatment for a specific duration, rather than relying purely on a price per pill. Subscription-based schemes guarantee pharmaceutical firms income that incentivises investment in developing new antibiotics, and can promote responsible stewardship. From the pharmaceutical perspective, revenue is disassociated from sales, removing benefits from push marketing strategies. We investigate this from the funder perspective, and consider that the funder plays a key role in promoting responsible antibiotic stewardship by choosing the price per pill for providers such that this encourages appropriate antibiotic use. This choice determines the payment structure, and we investigate the impact of this choice through the lens of social welfare. We present a mathematical model of subscription payment schemes, explicitly featuring fixed and volume-based payment components for a given treatment price. Total welfare returned at a societal level is then estimated (incorporating financial costs and monetised benefits). We consider a practical application of the model to development of novel antibiotic treatment for Gonorrhoea, and examine the optimal treatment price under different parameterisations. Specifically, we analyse two contrasting scenarios - one where a new antibiotic's prioritised role is reducing transmission, and one where a more pressing requirement is conserving the antibiotic as an effective last defence. Critically, this analysis demonstrates that effective roll-out of a subscription payment scheme for a new antibiotic requires a comprehensive assessment of the benefits gained from treatment. We discuss the insights this work presents on the nature of these payment schemes, and how these insights can enable decision-makers to take the first steps in determining effective structuring of subscription payment schemes.

Reference Case Methods for Expert Elicitation in Health Care Decision Making.

BACKGROUND: The evidence used to inform health care decision making (HCDM) is typically uncertain. In these situations, the experience of experts is essential to help decision makers reach a decision. Structured expert elicitation (referred to as elicitation) is a quantitative process to capture experts' beliefs. There is heterogeneity in the existing elicitation methodology used in HCDM, and it is not clear if existing guidelines are appropriate for use in this context. In this article, we seek to establish reference case methods for elicitation to inform HCDM. METHODS: We collated the methods available for elicitation using reviews and critique. In addition, we conducted controlled experiments to test the accuracy of alternative methods. We determined the suitability of the methods choices for use in HCDM according to a predefined set of principles for elicitation in HCDM, which we have also generated. We determined reference case methods for elicitation in HCDM for health technology assessment (HTA). RESULTS: In almost all methods choices available for elicitation, we found a lack of empirical evidence supporting recommendations. Despite this, it is possible to define reference case methods for HTA. The reference methods include a focus on gathering experts with substantive knowledge of the quantities being elicited as opposed to those trained in probability and statistics, eliciting quantities that the expert might observe directly, and individual elicitation of beliefs, rather than solely consensus methods. It is likely that there are additional considerations for decision makers in health care outside of HTA. CONCLUSIONS: The reference case developed here allows the use of different methods, depending on the decision-making setting. Further applied examples of elicitation methods would be useful. Experimental evidence comparing methods should be generated.

Antimicrobial Resistance: Is Health Technology Assessment Part of the Solution or Part of the Problem?

Antimicrobial resistance is a serious challenge to the success and sustainability of our healthcare systems. There has been increasing policy attention given to antimicrobial resistance in the last few years, and increased amounts of funding have been channeled into funding for research and development of antimicrobial agents. Nevertheless, manufacturers doubt whether there will be a market for new antimicrobial technologies sufficient to enable them to recoup their investment. Health technology assessment (HTA) has a critical role in creating confidence that if valuable technologies can be developed they will be reimbursed at a level that captures their true value. We identify 3 deficiencies of current HTA processes for appraising antimicrobial agents: a methods-centric approach rather than problem-centric approach for dealing with new challenges, a lack of tools for thinking about changing patterns of infection, and the absence of an approach to epidemiological risks. We argue that, to play their role more effectively, HTA agencies need to broaden their methodological tool kit, design and communicate their analysis to a wider set of users, and incorporate long-term policy goals, such as containing resistance, as part of their evaluation criteria alongside immediate health gains.

Health systems, population and patient challenges for achieving universal health coverage for hypertension in Ghana.

Ghana has signed on to the United Nations Sustainable Development Goal to achieve universal health coverage (UHC), ensuring that all individuals receive the health care they require without financial hardship. Achieving that goal is a difficult task in any setting. The challenges are further exacerbated by a changing disease landscape, as the burden of non-communicable diseases (NCDs) is increasing and creating a dual burden along with infectious diseases. This study explores the existing health system for delivering hypertension care and the challenges of delivering UHC for hypertension in Ghana. Document analysis of national health reports, policies and legislations along with a review of research articles was conducted to explore the challenges of delivering UHC for NCDs in Ghana, and hypertension in particular. The main themes and indicators related to the challenges of delivering UHC for hypertension were mapped and analysed. The main challenges to delivering UHC for hypertension can be grouped into population and patient, on the one hand, and health system factors, on the other. Population and patient factors include (1) unhealthy lifestyles overburdening the health system, (2) poor health-seeking behaviour and (3) poor adherence to medication, which has led to uncontrolled cases and poor clinical outcomes even among treated patients with hypertension. Health system factors include (1) inadequate health system capacity for early diagnosis due to an increasing number of patients, (2) inequitable distribution of health care facilities affecting access, (3) financial sustainability of the National Health Insurance Scheme and delays in reimbursement of claims to facilities that affect the health system's ability to provide timely management of hypertension and (4) health care facilities and practitioners' use of non-standardized and uncalibrated blood pressure measuring equipment. Ghana therefore will need to make important decisions to overcome operational and financial challenges on its path to UHC.

Developing a reference protocol for structured expert elicitation in health-care decision-making: a mixed-methods study.

BACKGROUND: Many decisions in health care aim to maximise health, requiring judgements about interventions that may have higher health effects but potentially incur additional costs (cost-effectiveness framework). The evidence used to establish cost-effectiveness is typically uncertain and it is important that this uncertainty is characterised. In situations in which evidence is uncertain, the experience of experts is essential. The process by which the beliefs of experts can be formally collected in a quantitative manner is structured expert elicitation. There is heterogeneity in the existing methodology used in health-care decision-making. A number of guidelines are available for structured expert elicitation; however, it is not clear if any of these are appropriate for health-care decision-making. OBJECTIVES: The overall aim was to establish a protocol for structured expert elicitation to inform health-care decision-making. The objectives are to (1) provide clarity on methods for collecting and using experts' judgements, (2) consider when alternative methodology may be required in particular contexts, (3) establish preferred approaches for elicitation on a range of parameters, (4) determine which elicitation methods allow experts to express uncertainty and (5) determine the usefulness of the reference protocol developed. METHODS: A mixed-methods approach was used: systemic review, targeted searches, experimental work and narrative synthesis. A review of the existing guidelines for structured expert elicitation was conducted. This identified the approaches used in existing guidelines (the 'choices') and determined if dominant approaches exist. Targeted review searches were conducted for selection of experts, level of elicitation, fitting and aggregation, assessing accuracy of judgements and heuristics and biases. To sift through the available choices, a set of principles that underpin the use of structured expert elicitation in health-care decision-making was defined using evidence generated from the targeted searches, quantities to elicit experimental evidence and consideration of constraints in health-care decision-making. These principles, including fitness for purpose and reflecting individual expert uncertainty, were applied to the set of choices to establish a reference protocol. An applied evaluation of the developed reference protocol was also undertaken. RESULTS: For many elements of structured expert elicitation, there was a lack of consistency across the existing guidelines. In almost all choices, there was a lack of empirical evidence supporting recommendations, and in some circumstances the principles are unable to provide sufficient justification for discounting particular choices. It is possible to define reference methods for health technology assessment. These include a focus on gathering experts with substantive skills, eliciting observable quantities and individual elicitation of beliefs. Additional considerations are required for decision-makers outside health technology assessment, for example at a local level, or for early technologies. Access to experts may be limited and in some circumstances group discussion may be needed to generate a distribution. LIMITATIONS: The major limitation of the work conducted here lies not in the methods employed in the current work but in the evidence available from the wider literature relating to how appropriate particular methodological choices are. CONCLUSIONS: The reference protocol is flexible in many choices. This may be a useful characteristic, as it is possible to apply this reference protocol across different settings. Further applied studies, which use the choices specified in this reference protocol, are required. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 37. See the NIHR Journals Library website for further project information. This work was also funded by the Medical Research Council (reference MR/N028511/1).

BACKGROUND: Decisions in health care aim to maximise health, requiring judgements about treatments. The evidence used to make these judgements is typically uncertain. In these situations, the experience of experts is essential. Structured expert elicitation collects beliefs from experts. There are different guidelines available for structured expert elicitation; however, it is not clear if any of these be can be used in health-care decision-making, for example in considering if a treatment should be made available in the NHS. This project aimed to develop a guidance for structured expert elicitation to inform health-care decision-making. METHODS: Reviews and experimental techniques were used to gather a list of methods to conduct structured expert elicitation. The suitability of these choices in health-care decision-making was then determined by comparing these with a set of standards that support the use of structured expert elicitation in health-care decision-making. RESULTS: Different guidelines prefer different approaches to conduct structured expert elicitation. There is a lack of evidence available to determine which of these methods is most appropriate across the whole of health-care decision-making. It is possible to define reference protocol methods that could be used in a particular type of health-care decision-making, health technology assessment. This includes gathering experts with knowledge of the clinical area, asking experts about things that they observe in clinical practice and asking experts individually for their beliefs. For decision-makers working outside health technology assessment, for example at a local level, or for treatments that are not yet available to patients, these choices may not be appropriate. CONCLUSIONS: This flexibility of this guidance is a useful feature. It is possible for different decision-makers in health care to interpret the reference protocol for their own circumstances.

How Should the Value Attributes of Novel Antibiotics Be Considered in Reimbursement Decision Making?

Antibiotics have revolutionized the treatment of bacterial infections. However, it is widely held that there is underinvestment in antibiotics research and development relative to the socially optimal level for a number of reasons. In this article, we discuss whether existing health technology assessment procedures recognize the full economic and societal value of new antibiotics to patients and society when making reimbursement decisions. We present three recommendations for modelling the unique attributes of value that are specific to novel antibiotics. We find, based on a review of the literature, that some of the value elements proposed by our framework have previously been discussed qualitatively by health technology assessment bodies when evaluating antibiotics, but are not yet formally captured via modelling. We present a worked example to show how it may be possible to capture these dimensions of value in a more quantitative manner. We conclude by answering the question of the title as follows: the unique attributes of novel antibiotics should be considered in reimbursement decision making, in a way that captures the full range of benefits these important technologies bring to patients, health care systems, and society.

Health and economic benefits of public financing of epilepsy treatment in India: An agent-based simulation model.

OBJECTIVE: An estimated 6-10 million people in India live with active epilepsy, and less than half are treated. We analyze the health and economic benefits of three scenarios of publicly financed national epilepsy programs that provide: (1) first-line antiepilepsy drugs (AEDs), (2) first- and second-line AEDs, and (3) first- and second-line AEDs and surgery. METHODS: We model the prevalence and distribution of epilepsy in India using IndiaSim, an agent-based, simulation model of the Indian population. Agents in the model are disease-free or in one of three disease states: untreated with seizures, treated with seizures, and treated without seizures. Outcome measures include the proportion of the population that has epilepsy and is untreated, disability-adjusted life years (DALYs) averted, and cost per DALY averted. Economic benefit measures estimated include out-of-pocket (OOP) expenditure averted and money-metric value of insurance. RESULTS: All three scenarios represent a cost-effective use of resources and would avert 800,000-1 million DALYs per year in India relative to the current scenario. However, especially in poor regions and populations, scenario 1 (which publicly finances only first-line therapy) does not decrease the OOP expenditure or provide financial risk protection if we include care-seeking costs. The OOP expenditure averted increases from scenarios 1 through 3, and the money-metric value of insurance follows a similar trend between scenarios and typically decreases with wealth. In the first 10 years of scenarios 2 and 3, households avert on average over US$80 million per year in medical expenditure. SIGNIFICANCE: Expanding and publicly financing epilepsy treatment in India averts substantial disease burden. A universal public finance policy that covers only first-line AEDs may not provide significant financial risk protection. Covering costs for both first- and second-line therapy and other medical costs alleviates the financial burden from epilepsy and is cost-effective across wealth quintiles and in all Indian states.

Health and economic benefits of scaling up a home-based neonatal care package in rural India: a modelling analysis.

Approximately 900 000 newborn children die every year in India, accounting for 28% of neonatal deaths globally. In 2011, India introduced a home-based newborn care (HBNC) package to be delivered by community health workers across rural areas. We estimate the disease and economic burden that could be averted by scaling up the HBNC in rural India using IndiaSim, an agent-based simulation model, to examine two interventions. In the first intervention, the existing community health worker network begins providing HBNC for rural households without access to home- or facility-based newborn care, as introduced by India's recent programme. In the second intervention, we consider increased coverage of HBNC across India so that total coverage of neonatal care (HBNC or otherwise) in the rural areas of each state reaches at least 90%. We find that compared with a baseline of no coverage, providing the care package through the existing network of community health workers could avert 48 [95% uncertainty range (UR) 34-63] incident cases of severe neonatal morbidity and 5 (95% UR 4-7) related deaths, save $4411 (95% UR $3088-$5735) in out-of-pocket treatment costs, and provide $285 (95% UR $200-$371) in value of insurance per 1000 live births in rural India. Increasing the coverage of HBNC to 90% will avert an additional 9 (95% UR 7-12) incident cases, 1 death (95% UR 0.72-1.33), and $613 (95% UR $430-$797) in out-of-pocket expenditures, and provide $55 (95% UR $39-$72) in incremental value of insurance per 1000 live births. Intervention benefits are greater for lower socioeconomic groups and in the poorer states of Chhattisgarh, Uttarakhand, Bihar, Assam and Uttar Pradesh.

Analysis of the Universal Immunization Programme and introduction of a rotavirus vaccine in India with IndiaSim.

BACKGROUND AND OBJECTIVES: India has the highest under-five death toll globally, approximately 20% of which is attributed to vaccine-preventable diseases. India's Universal Immunization Programme (UIP) is working both to increase immunization coverage and to introduce new vaccines. Here, we analyze the disease and financial burden alleviated across India's population (by wealth quintile, rural or urban area, and state) through increasing vaccination rates and introducing a rotavirus vaccine. METHODS: We use IndiaSim, a simulated agent-based model (ABM) of the Indian population (including socio-economic characteristics and immunization status) and the health system to model three interventions. In the first intervention, a rotavirus vaccine is introduced at the current DPT3 immunization coverage level in India. In the second intervention, coverage of three doses of rotavirus and DPT and one dose of the measles vaccine are increased to 90% randomly across the population. In the third, we evaluate an increase in immunization coverage to 90% through targeted increases in rural and urban regions (across all states) that are below that level at baseline. For each intervention, we evaluate the disease and financial burden alleviated, costs incurred, and the cost per disability-adjusted life-year (DALY) averted. RESULTS: Baseline immunization coverage is low and has a large variance across population segments and regions. Targeting specific regions can approximately equate the rural and urban immunization rates. Introducing a rotavirus vaccine at the current DPT3 level (intervention one) averts 34.7 (95% uncertainty range [UR], 31.7-37.7) deaths and $215,569 (95% UR, $207,846-$223,292) out-of-pocket (OOP) expenditure per 100,000 under-five children. Increasing all immunization rates to 90% (intervention two) averts an additional 22.1 (95% UR, 18.6-25.7) deaths and $45,914 (95% UR, $37,909-$53,920) OOP expenditure. Scaling up immunization by targeting regions with low coverage (intervention three) averts a slightly higher number of deaths and OOP expenditure. The reduced burden of rotavirus diarrhea is the primary driver of the estimated health and economic benefits in all intervention scenarios. All three interventions are cost saving. CONCLUSION: Improving immunization coverage and the introduction of a rotavirus vaccine significantly alleviates disease and financial burden in Indian households. Population subgroups or regions with low existing immunization coverage benefit the most from the intervention. Increasing coverage by targeting those subgroups alleviates the burden more than simply increasing coverage in the population at large.