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.

The effect of hospital spending on waiting times.

Long waiting times have been a persistent policy issue in the United Kingdom that the COVID-19 pandemic has exacerbated. This study analyses the causal effect of hospital spending on waiting times in England using a first-differences panel approach and an instrumental variable strategy to deal with residual concerns for endogeneity. We use data from 2014 to 2019 on waiting times from general practitioner referral to treatment (RTT) measured at the level of local purchasers (known as Clinical Commissioning Groups). We find that increases in hospital spending by local purchasers of 1% reduce median RTT waiting time for patients whose pathway ends with a hospital admission (admitted pathway) by 0.6 days but the effect is not statistically significant at 5% level (only at the 10% level). We also find that higher hospital spending does not affect the RTT waiting time for patients whose pathway ends with a specialist consultation (non-admitted pathway). Nor does higher spending have a statistically significant effect on the volume of elective activity for either pathway. Our findings suggest that higher spending is no guarantee of higher volumes and lower waiting times, and that additional mechanisms need to be put in place to ensure that increased spending benefits elective patients.

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.

Electroencephalography (EEG) dataset during naturalistic music listening comprising different genres with familiarity and enjoyment ratings.

The article provides an open-source Music Listening- Genre (MUSIN-G) EEG dataset which contains 20 participants' continuous Electroencephalography responses to 12 songs of different genres (from Indian folk music to Goth Rock to western electronic), along with their familiarity and enjoyment ratings. The participants include 16 males and 4 females, with an average age of 25.3 (+/-3.38). The EEG data was collected at the Indian Institute of Technology Gandhinagar, India, using 128 channels Hydrocel Geodesic Sensor Net (HCGSN) and the Netstation 5.4 data acquiring software. We provide the raw and partially preprocessed data of each participant while they listened to 12 different songs with closed eyes. The dataset also contains the behavioural familiarity and enjoyment ratings (scale of 1 to 5) of the participants for each of the songs. In this article, we further discuss the preprocessing steps which can be used on the dataset and prepare the data for analysis, as in the paper [1].

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.

Electron-induced dissociation dynamics studied using covariance-map imaging.

Recently, covariance analysis has found significant use in the field of chemical reaction dynamics. When coupled with data from product time-of-flight mass spectrometry and/or multi-mass velocity-map imaging, it allows us to uncover correlations between two or more ions formed from the same parent molecule. While the approach has parallels with coincidence measurements, covariance analysis allows experiments to be performed at much higher count rates than traditional coincidence methods. We report results from electron-molecule crossed-beam experiments, in which covariance analysis is used to elucidate the dissociation dynamics of multiply-charged ions formed by electron ionisation over the energy range from 50 to 300 eV. The approach is able to isolate signal contributions from multiply charged ions even against a very large 'background' of signal arising from dissociation of singly-charged parent ions. Covariance between the product time-of-flight spectra identifies pairs of fragments arising from the same parent ions, while covariances between the velocity-map images ('recoil-frame covariances') reveal the relative velocity distributions of the ion pairs. We show that recoil-frame covariance analysis can be used to distinguish between multiple plausible dissociation mechanisms, including multi-step processes, and that the approach becomes particularly powerful when investigating the fragmentation dynamics of larger molecules with a higher number of possible fragmentation pathways.

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.

Resonance as a Design Strategy for AI and Social Robots.

Resonance, a powerful and pervasive phenomenon, appears to play a major role in human interactions. This article investigates the relationship between the physical mechanism of resonance and the human experience of resonance, and considers possibilities for enhancing the experience of resonance within human-robot interactions. We first introduce resonance as a widespread cultural and scientific metaphor. Then, we review the nature of "sympathetic resonance" as a physical mechanism. Following this introduction, the remainder of the article is organized in two parts. In part one, we review the role of resonance (including synchronization and rhythmic entrainment) in human cognition and social interactions. Then, in part two, we review resonance-related phenomena in robotics and artificial intelligence (AI). These two reviews serve as ground for the introduction of a design strategy and combinatorial design space for shaping resonant interactions with robots and AI. We conclude by posing hypotheses and research questions for future empirical studies and discuss a range of ethical and aesthetic issues associated with resonance in human-robot interactions.

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.