Achieving dynamic efficiency in pharmaceutical innovation: Identifying the optimal share of value and payments required.

It has been argued that cost-effectiveness analysis of branded pharmaceuticals only considers static efficiency, neglects dynamic effects and undermines incentives for socially valuable innovation. We present a framework for designing pharmaceutical pricing policy to achieve dynamic efficiency. We develop a coherent framework that identifies the long-term static and dynamic benefits and costs of offering manufacturers different levels of reward. The share of value that would maximise long-term population health depends on how the quantity and quality of innovation responds to payment. Using evidence of the response of innovation to payment, the optimal share of value of new pharmaceuticals to offer to manufacturers is roughly 20% (range: 6%-51%). Reanalysis of a sample of NICE technology appraisals suggests that, in most cases, the share of value offered to manufacturers and the price premium paid by the English NHS were too high. In the UK, application of optimal shares would offer considerable benefits under both a public health objective and a broader view of social welfare. We illustrate how an optimal share of value can be delivered through a range of payment mechanisms including indirect price regulation via the use of different approval norms by an HTA body.

We need to talk about values: a proposed framework for the articulation of normative reasoning in health technology assessment.

It is acknowledged that health technology assessment (HTA) is an inherently value-based activity that makes use of normative reasoning alongside empirical evidence. But the language used to conceptualise and articulate HTA's normative aspects is demonstrably unnuanced, imprecise, and inconsistently employed, undermining transparency and preventing proper scrutiny of the rationales on which decisions are based. This paper - developed through a cross-disciplinary collaboration of 24 researchers with expertise in healthcare priority-setting - seeks to address this problem by offering a clear definition of key terms and distinguishing between the types of normative commitment invoked during HTA, thus providing a novel conceptual framework for the articulation of reasoning. Through application to a hypothetical case, it is illustrated how this framework can operate as a practical tool through which HTA practitioners and policymakers can enhance the transparency and coherence of their decision-making, while enabling others to hold them more easily to account. The framework is offered as a starting point for further discussion amongst those with a desire to enhance the legitimacy and fairness of HTA by facilitating practical public reasoning, in which decisions are made on behalf of the public, in public view, through a chain of reasoning that withstands ethical scrutiny.

Is extending eligibility for adult social care better than investing more in existing users in England? A cross-sectional evidence for multiple financial years.

OBJECTIVES: Publicly funded adult social care (ASC) in England aims to improve quality of life through the provision of services for individuals with care needs due to physical and/or mental impairment or illness. Access to these services, however, is often restricted to contain public expenditure. With a fast-growing care need, information on whether extending eligibility is good value for money becomes policy-relevant. PRIMARY AND SECONDARY OUTCOME MEASURES: This study investigates the effect of extending ASC eligibility on user care-related quality of life (CRQoL), a policy-relevant measure of quality of life. DESIGN: We use English cross-sectional survey data from 2017/2018 to 2019/2020 on users receiving publicly funded long-term support including domiciliary and other community-based social care, as well as residential and nursing care from local authorities responsible for ASC. We employ the two-stage least square method to estimate the impact of ASC expenditure on CRQoL at various levels of ASC expenditure in each financial year. This includes the CRQoL effect of increasing expenditure from zero to some level, which captures the effect of extending ASC eligibility to new users. RESULTS: We find that publicly funded ASC improves the CRQoL of both existing and newly eligible users, although the latter are likely to experience greater CRQoL gains. Moreover, from 2017/2018 to 2019/2020, spending as much as an average user for a newly eligible user costs between £54 224 and £77 778 per social care-quality-adjusted life year (SC-QALY) gained. These results are statistically significant at the 5% level. Compared with this finding, increasing expenditure for an existing user has always a higher cost per SC-QALY gained. CONCLUSIONS: Extending ASC eligibility to new users is likely to be more cost-effective compared with using the same resources to increase expenditure for existing users.

How Uncertainty Matters Under Risk Neutrality.

It is typical in cost-effectiveness analysis to invoke a normative decision-making framework that assumes, as a starting point, that "a quality-adjusted life-year (QALY) is a QALY is a QALY." The implication of this assumption is that the decision maker is risk neutral and that expected values could be considered sufficiently informative for a given "approve or reject" decision. Nevertheless, it seems intuitive that less uncertainty should be desirable and this has led some to incorporate "real" risk aversion (RA) into cost-effectiveness analysis. We illustrate in this article that RA is not always necessary to justify choosing more over less certain options. We show that for a risk neutral decision maker, greater uncertainty can make the approval of technology less likely in the presence of (1) model nonlinearities, (2) nonlinear opportunity costs, and (3) irreversible costs. We call these cases of "apparent" RA. Incorporating explicit risk preferences into decision making can be challenging; nevertheless, as we show here, it is not necessary to justify caring about uncertainty in approval decisions.

The impact of different types of NHS expenditure on health: Marginal cost per QALY estimates for England for 2016/17.

English data from 2003 to 2012 suggests that it costs the NHS £10,000 to generate an additional quality-adjusted life year (QALY).  This estimate relates to all NHS expenditure and no attempt was made to explore possible heterogeneity within this total.  Different types of expenditure - such as secondary care, primary care and specialized commissioning - may have different productivities and estimates of these may help policymakers decide where additional investment is most beneficial.  We use the two-stage least squares estimator and data for 2016 to explore the mortality response to three types of healthcare expenditure.  Three specifications are estimated for each type of expenditure: backward selection and regularized regression are used to identify parsimonious specifications, and a full specification with all covariates is also estimated.  The regression results are combined with information about survival and morbidity disease burden to calculate the marginal cost per QALY for each type of expenditure: the most conservative results suggest that this is about £8,000 for locally (CCG) commissioned services, while estimates for specialized commissioning and primary care are more uncertain.  When this heterogeneity is taken into account, the estimated marginal cost per QALY for all NHS expenditure increases slightly, from about £6,000 to £7,000.  Our results suggest that additional investment is likely to be most productive in primary care and in locally commissioned services.

Informing a cost-effectiveness threshold for Saudi Arabia.

BACKGROUND: Saudi Arabia's Vision 2030 aims to reform health care across the Kingdom, with health technology assessment being adopted as one tool promising to improve the efficiency with which resources are used. An understanding of the opportunity costs of reimbursement decisions is key to fulfilling this promise and can be used to inform a cost-effectiveness threshold. This paper is the first to provide a range of estimates of this using existing evidence extrapolated to the context of Saudi Arabia. METHODS AND MATERIALS: We use four approaches to estimate the marginal cost per unit of health produced by the healthcare system; drawing from existing evidence provided by a cross-country analysis, two alternative estimates from the UK context, and based on extrapolating a UK estimate using evidence on the income elasticity of the value of health. Consequences of estimation error are explored. RESULTS: Based on the four approaches, we find a range of SAR 42,046 per QALY gained (48% of GDP per capita) to SAR 215,120 per QALY gained (246% of GDP per capita). Calculated potential central estimates from the average of estimated health gains based on each source gives a range of SAR 50,000-75,000. The results are in line with estimates from the emerging literature from across the world. CONCLUSION: A cost-effectiveness threshold reflecting health opportunity costs can aid decision-making. Applying a cost-effectiveness threshold based on the range SAR 50,000 to 75,000 per QALY gained would ensure that resource allocation decisions in healthcare can in be informed in a way that accounts for health opportunity costs. LIMITATIONS: A limitation is that it is not based on a within-country study for Saudi Arabia, which represents a promising line of future work.

Healthcare in Saudi Arabia is undergoing wide-ranging reform through Saudi Arabia's Vision 2030. One aim of these reforms is to ensure that money spent on healthcare generates the most improvement in population health possible. To do this requires understanding the trade-offs that exist: funding one pharmaceutical drug means that same money is not available to fund another pharmaceutical drug. This is relevant whether the new drug would be funded from within the existing budget for healthcare or from an expansion of it. If the drugs apply to the same patient population and have the same price, the question is simply, "which one generates more health?" In reality, we need to compare pharmaceutical drugs for different diseases, patient populations, and at a range of potential prices to understand whether the drug in question would generate more health per riyal spent than what is currently funded by the healthcare system. This paper provides the first estimates of the amount of health, measured in terms of quality adjusted life years (QALYs), generated by the Saudi Arabian healthcare system. We find that the healthcare system generates health at a rate of one QALY produced for every 50,000­75,000 riyals spent (58­86% of GDP per capita). Using the range we estimate to inform cost-effectiveness threshold can aid decision-making.

Economic Evaluation Evidence for Resource-Allocation Decision Making: Bridging the Gap for Local Decision Makers Using English Case Studies.

Best-practice economic evaluation methods for health-related decision making at a national level in England are well established, and as a first principle generally involve attempting to maximise the amount of health generated from the health system's budget. Such methods are applied in ways that are broadly transparent and accountable, often at arm's length from explicit political pressures. At local levels of decision making, however, decision making is arguably less likely to be applied according to established overarching principles, is less transparent and is more subject to political pressures. This may be owing to a multiplicity of reasons, for example, undesirability/inappropriateness of such methods, or a failure to make the methods clear to local decision makers. We outline principles for economic evaluations and break down these methods into their component parts, considering their relevance in the English local context. These include taxonomies of decision-making frameworks, budgets, costs, outcome, and characterisations of cost effectiveness. We also explore the role of broader factors, including the relevance of assuming a single fixed budget, pressures resulting from political and budgetary cycles and affordability. We consider the data requirements to inform such deliberations. By setting out principles for economic evaluation methods in a clear language aimed at local decision making, a potential role for such methods can be established, which to date has failed to emerge. While the extent to which these methods can and should be applied are a matter for continued debate, the establishment of such a mutual understanding may assist in the improvement of methods for such decision making and the outcomes resulting from their application.

Health Inequalities: To What Extent are Decision-Makers and Economic Evaluations on the Same Page? An English Case Study.

Economic evaluations have increasingly sought to understand how funding decisions within care sectors impact health inequalities. However, there is a disconnect between the methods used by researchers (e.g., within universities) and analysts (e.g., within publicly funded commissioning agencies), compared to evidence needs of decision makers in regard to how health inequalities are accounted for and presented. Our objective is to explore how health inequality is defined and quantified in different contexts. We focus on how specific approaches have developed, what similarities and differences have emerged, and consider how disconnects can be bridged. We explore existing methodological research regarding the incorporation of inequality considerations into economic evaluation in order to understand current best practice. In parallel, we explore how localised decision makers incorporate inequality considerations into their commissioning processes. We use the English care setting as a case study, from which we make inference as how local commissioning has evolved internationally. We summarise the recent development of distributional cost-effectiveness analysis in the economic evaluation literature: a method that makes explicit the trade-off between efficiency and equity. In the parallel decision-making setting, while the alleviation of health inequality is regularly the focus of remits, few details have been formalised regarding its definition or quantification. While data development has facilitated the reporting and comparison of metrics of inequality to inform commissioning decisions, these tend to focus on measures of care utilisation and behaviour rather than measures of health. While both researchers and publicly funded commissioning agencies are increasingly putting the identification of health inequalities at the core of their actions, little consideration has been given to ensuring that they are approaching the problem in a consistent way. The extent to which researchers and commissioning agencies can collaborate on best practice has important implications for how successful policy is in addressing health inequalities.

How Responsive is Mortality to Locally Administered Healthcare Expenditure? Estimates for England for 2014/15.

BACKGROUND: Research using local English data from 2003 to 2012 suggests that a 1% increase in healthcare expenditure causes a 0.78% reduction in mortality, and that it costs the NHS £10,000 to generate an additional quality-adjusted life year (QALY). In 2013, the existing 151 local health authorities (Primary Care Trusts) were abolished and replaced with 212 Clinical Commissioning Groups (CCGs). CCGs retained responsibility for secondary care and pharmaceuticals, but responsibility for primary care and specialised commissioning returned to central administrators. OBJECTIVES: The aim was to extend and apply existing methods to more recent data using a new geography and expenditure base, while improving covariate selection and examining the responsiveness of mortality to expenditure across the mortality distribution. METHODS: Instrumental variable regression is used to quantify the relationship between mortality and local expenditure. Backward selection and regularised regression are used to identify parsimonious specifications. These results are combined with information about survival and morbidity disease burden to calculate the marginal cost per QALY. Unconditional quantile regression (UQR) is used to examine the response of mortality to expenditure across the mortality distribution. RESULTS: Backward selection and regularised regression both suggest that the marginal cost per QALY in 2014/15 was about £7000 for locally commissioned services. The UQR results suggest that additional expenditure generates larger health benefits in high-mortality areas and that, if anything, the average size of this heterogeneous response is larger than the response at the mean. CONCLUSIONS: The new healthcare geography and expenditure base can be used to update estimates of the health opportunity costs associated with additional expenditure. The variation in the mortality response across the mortality distribution suggests that the use of the response at the mean will, if anything, underestimate the health opportunity costs associated with a national policy or nationally mandated guidance on the use of new technologies. The health opportunity costs of such policies are likely to be greater (lower) in areas of higher (lower) mortality, increasing health inequalities.

The Relevance of Including Future Healthcare Costs in Cost-Effectiveness Threshold Calculations for the UK NHS.

BACKGROUND AND OBJECTIVE: The supply-side threshold for the UK National Health Service has been empirically estimated as the marginal returns to healthcare spending on health outcomes. These estimates implicitly exclude future healthcare costs, which is inconsistent with the objective of making the most efficient use of healthcare resources. This paper illustrates how empirical estimates of the threshold within healthcare can be adjusted to account for future healthcare costs. METHODS: Using cause-deleted life tables and previous work on future costs in England and Wales, we illustrate how such estimates can be adjusted. RESULTS: While the effect of including future healthcare costs can have substantial effects on incremental cost-effectiveness ratios of specific life-extending interventions, we find that including future costs has relatively little impact (an increase of £743 per quality-adjusted life-year) on the threshold estimate. CONCLUSIONS: For some life-extending interventions the impact of including future costs on whether an intervention is deemed cost effective may be considerable.

Empirical Estimates of the Marginal Cost of Health Produced by a Healthcare System: Methodological Considerations from Country-Level Estimates.

Many health technology assessment committees have an explicit or implicit reference value (often referred to as a 'threshold') below which new health technologies or interventions are considered value for money. The basis for these reference values is unclear but one argument is that it should be based on the health opportunity costs of funding decisions. Empirical estimates of the marginal cost per unit of health produced by a healthcare system have been proposed to capture the health opportunity costs of new funding decisions. Based on a systematic search, we identified eight studies that have sought to estimate a reference value through empirical estimation of the marginal cost per unit of health produced by a healthcare system for England, Spain, Australia, The Netherlands, Sweden, South Africa and China. We review these eight studies to provide an overview of the key methodological approaches taken to estimate the marginal cost per unit of health produced by the healthcare system with the aim to help inform future estimates for additional countries. The lead author for each of these papers was invited to contribute to the current paper to ensure all the key methodological issues encountered were appropriately captured. These included consideration of the key variables required and their measurement, accounting for endogeneity of spending to health outcomes, the inclusion of lagged spending, discounting and future costs, the use of analytical weights, level of disease aggregation, expected duration of health gains, and modelling approaches to estimating mortality and morbidity effects of health spending. Subsequent research estimates for additional countries should (1) carefully consider the specific context and data available, (2) clearly and transparently report the assumptions made and include stakeholder perspectives on their appropriateness and acceptability, and (3) assess the sensitivity of the preferred central estimate to these assumptions.

Avoiding Opportunity Cost Neglect in Cost-Effectiveness Analysis for Health Technology Assessment.

Despite being a fundamental tenet of economic analysis there is a lack of clarity regarding the relevance of opportunity costs to cost-effectiveness analysis for health technology assessment. We argue that this is due, in part, to the importance of the decision context in understanding the nature of opportunity costs. Taking the example of the National Institute of Health and Care Excellence (NICE) on behalf of the National Health Service (NHS) in England and Wales, we explore the implications of existing discrepancies between policy thresholds and emerging empirical evidence of health opportunity costs. In particular, we consider analysts communicating the results of cost-effectiveness analysis, and recommend that analysts provide analysis according to both the policy threshold and the latest empirical evidence until the discrepancies are better understood or resolved. A number of conceptually related, but distinct, issues are discussed and clarified.

Accounting for country- and time-specific values in the economic evaluation of health-related projects relevant to low- and middle-income countries.

Economic evaluation of health-related projects requires principles and methods to address the various trade-offs that need to be made between costs and benefits, across sectors and social objectives, and over time. Existing guidelines for economic evaluation in low- and middle-income countries embed implicit assumptions about expected changes in the marginal cost per unit of health produced by the healthcare sector, the consumption value of health and the appropriate discount rates for health and consumption. Separating these evaluation parameters out requires estimates for each country over time, which have hitherto been unavailable. We present a conceptual economic evaluation framework that aims to clarify the distinct roles of these different evaluation parameters in evaluating a health-related project. Estimates for each are obtained for each country and in each time period, based on available empirical evidence. Where existing estimates are not available, for future values of the marginal cost per unit of health produced by the healthcare sector, new estimates are obtained following a practical method for obtaining projected values. The framework is applied to a simple, hypothetical, illustrative example, and the results from our preferred approach are compared against those obtained from other approaches informed by the assumptions implicit within existing guidelines. This exposes the consequences of applying such assumptions, which are not supported by available evidence, in terms of potentially sub-optimal decisions. In general, we find that applying existing guidelines as done in conventional practice likely underestimates the value of health-related projects on account of not allowing for expected growth in the marginal cost per unit of health produced by the healthcare sector.

Causal impact of social care, public health and healthcare expenditure on mortality in England: cross-sectional evidence for 2013/2014.

OBJECTIVES: The first objective is to estimate the joint impact of social care, public health and healthcare expenditure on mortality in England. The second objective is to use these results to estimate the impact of spending constraints in 2010/2011-2014/2015 on total mortality. METHODS: The impact of social care, healthcare and public health expenditure on mortality is analysed by applying the two-stage least squares method to local authority data for 2013/2014. Next, we compare the growth in healthcare and social care expenditure pre-2010 and post-2010. We use the difference between these growth rates and the responsiveness of mortality to changes in expenditure taken from the 2013/2014 cross-sectional analysis to estimate the additional mortality generated by post-2010 spending constraints. RESULTS: Our most conservative results suggest that (1) a 1% increase in healthcare expenditure reduces mortality by 0.532%; (2) a 1% increase in social care expenditure reduces mortality by 0.336%; and (3) a 1% increase in local public health spending reduces mortality by 0.019%. Using the first two of these elasticities and data on the change in spending growth between 2001/2002-2009/2010 and 2010/2011-2014/2015, we find that there were 57 550 (CI 3075 to 111 955) more deaths in the latter period than would have been observed had spending growth during this period matched that in 2001/2002-2009/2010. CONCLUSIONS: All three forms of public healthcare-related expenditure save lives and there is evidence that additional social care expenditure is more than twice as productive as additional healthcare expenditure. Our results are consistent with the hypothesis that the slowdown in the rate of improvement in life expectancy in England and Wales since 2010 is attributable to spending constraints in the healthcare and social care sectors.

How Effective is Marginal Healthcare Expenditure? New Evidence from England for 2003/04 to 2012/13.

BACKGROUND: The endogenous nature of healthcare expenditure means that instruments are often used when estimating the relationship between expenditure and mortality. Previous English studies of this relationship have largely relied on statistical tests to justify their instruments. A recent paper proposed that exogenous components of the resource allocation formula, used to distribute the national healthcare budget to local health authorities, be used as instruments. OBJECTIVES: To estimate the relationship between healthcare expenditure and mortality by disease area for England from 2003/4 to 2012/13 using exogenous elements from the resource allocation formula as instruments for expenditure. To use these disease-specific estimates to calculate the marginal cost per quality-adjusted life year (QALY) for English NHS expenditure. To compare these estimates with those that relied on statistical tests to justify their instruments. METHODS: The two-stage least squares estimator is used to determine the annual relationship between mortality and healthcare expenditure by disease area across 151 local authorities. These disease-specific outcome elasticities are combined with information about survival and morbidity disease burden in different disease areas to calculate the marginal cost per QALY for English National Health Service (NHS) expenditure. RESULTS: The results suggest an annual marginal cost per QALY of between £5000 and £10,000. This is similar to that reported previously by studies that used statistical tests to justify their instruments. CONCLUSION: These cost per QALY estimates are much lower than the threshold currently used by the UK's National Institute for Health and Care Excellence (NICE) (£20,000 to £30,000) to assess whether a new pharmaceutical product should be funded by the NHS. Our estimates suggest that guidance issued by NICE is likely to do more harm than good, reducing health outcomes overall for the NHS. There may be legitimate reasons why such harms are deemed appropriate, but it is only through the type of empirical analysis in this paper that the reasons for these 'harms' are likely to be articulated and explicitly justified.

Does public long-term care expenditure improve care-related quality of life of service users in England?

Public long-term care (LTC) systems provide services to support people experiencing difficulties with their activities of daily living. This study investigates the marginal effect of changes in public LTC expenditure on care-related quality of life (CRQoL) of existing service users in England. The public LTC program for people aged 18 or older in England is called Adult Social Care (ASC) and it is provided and managed by local authorities. We collect data on the outcomes and characteristics of public ASC users, on public ASC expenditure, and on the characteristics of local authorities across England in 2017/18. We employ an instrumental variable approach using conditionally exogenous elements of the public funding system to estimate the effect of public ASC expenditure on user CRQoL. Our findings show that by increasing public ASC expenditure by £1000 per user, on average, local authorities increase user CRQoL by 0.0030. These results suggest that public ASC is effective in increasing users' quality of life but only to a relatively small extent. When combined with the other potential effects of LTC expenditure (e.g., on informal carers, mortality), this study can inform policy makers in the United Kingdom and internationally about whether social care provides good value for money.

A Health Opportunity Cost Threshold for Cost-Effectiveness Analysis in the United States.

BACKGROUND: Cost-effectiveness analysis is an important tool for informing treatment coverage and pricing decisions, yet no consensus exists about what threshold for the incremental cost-effectiveness ratio (ICER) in dollars per quality-adjusted life-year (QALY) gained indicates whether treatments are likely to be cost-effective in the United States. OBJECTIVE: To estimate a U.S. cost-effectiveness threshold based on health opportunity costs. DESIGN: Simulation of short-term mortality and morbidity attributable to persons dropping health insurance due to increased health care expenditures passed though as premium increases. Model inputs came from demographic data and the literature; 95% uncertainty intervals (UIs) were constructed. SETTING: Population-based. PARTICIPANTS: Simulated cohort of 100 000 individuals from the U.S. population with direct-purchase private health insurance. MEASUREMENTS: Number of persons dropping insurance coverage, number of additional deaths, and QALYs lost from increased mortality and morbidity, all per increase of $10 000 000 (2019 U.S. dollars) in population treatment cost. RESULTS: Per $10 000 000 increase in health care expenditures, 1860 persons (95% UI, 1080 to 2840 persons) were simulated to become uninsured, causing 5 deaths (UI, 3 to 11 deaths), 81 QALYs (UI, 40 to 170 QALYs) lost due to death, and 15 QALYs (UI, 6 to 32 QALYs) lost due to illness; this implies a cost-effectiveness threshold of $104 000 per QALY (UI, $51 000 to $209 000 per QALY) in 2019 U.S. dollars. Given available evidence, there is about 14% probability that the threshold exceeds $150 000 per QALY and about 48% probability that it lies below $100 000 per QALY. LIMITATIONS: Estimates were sensitive to inputs, most notably the effects of losing insurance on mortality and of premium increases on becoming uninsured. Health opportunity costs may vary by population. Nonhealth opportunity costs were excluded. CONCLUSION: Given current evidence, treatments with ICERs above the range $100 000 to $150 000 per QALY are unlikely to be cost-effective in the United States. PRIMARY FUNDING SOURCE: None.

Valuing health outcomes: developing better defaults based on health opportunity costs.

BACKGROUND: Current health economic analysis guidelines emphasize the importance of using nationally appropriate cost and valuation inputs. However, some countries lack national data, and some analyses focus on interventions with costs and benefits at regional or global scales. METHODS: Recognizing the need for better estimates of appropriate values for application at these levels than those used in the past, we characterize population-weighted dollar per disability-adjusted life year (DALY) averted by World Bank Income Level based on available national estimates of the marginal productivity of the healthcare system. RESULTS: The defaults suggested here reflect health opportunity costs across countries more consistent with existing evidence than those previously used or recommended. As countries change income levels and healthcare spending, and as additional or updated marginal productivity of healthcare expenditure estimates become available, we expect the defaults to change. CONCLUSION: The best option for informing decisions around resource allocation in health care such that they improve health outcomes overall remains the use of time-appropriate country-specific estimates of the marginal productivity of the healthcare system. Instead of single, time-invariant defaults, health economists should seek to develop valuation inputs that better account for health opportunity costs and do so over time.