Cefiderocol for treating severe aerobic Gram-negative bacterial infections: technology evaluation to inform a novel subscription-style payment model.

Background: To limit the use of antimicrobials without disincentivising the development of novel antimicrobials, there is interest in establishing innovative models that fund antimicrobials based on an evaluation of their value as opposed to the volumes used. The aim of this project was to evaluate the population-level health benefit of cefiderocol in the NHS in England, for the treatment of severe aerobic Gram-negative bacterial infections when used within its licensed indications. The results were used to inform the National Institute for Health and Care Excellence guidance in support of commercial discussions regarding contract value between the manufacturer and NHS England. Methods: The health benefit of cefiderocol was first derived for a series of high-value clinical scenarios. These represented uses that were expected to have a significant impact on patients' mortality risks and health-related quality of life. The clinical effectiveness of cefiderocol relative to its comparators was estimated by synthesising evidence on susceptibility of the pathogens of interest to the antimicrobials in a network meta-analysis. Patient-level costs and health outcomes of cefiderocol under various usage scenarios compared with alternative management strategies were quantified using decision modelling. Results were reported as incremental net health effects expressed in quality-adjusted life-years, which were scaled to 20-year population values using infection number forecasts based on data from Public Health England. The outcomes estimated for the high-value clinical scenarios were extrapolated to other expected uses for cefiderocol. Results: Among Enterobacterales isolates with the metallo-beta-lactamase resistance mechanism, the base-case network meta-analysis found that cefiderocol was associated with a lower susceptibility relative to colistin (odds ratio 0.32, 95% credible intervals 0.04 to 2.47), but the result was not statistically significant. The other treatments were also associated with lower susceptibility than colistin, but the results were not statistically significant. In the metallo-beta-lactamase Pseudomonas aeruginosa base-case network meta-analysis, cefiderocol was associated with a lower susceptibility relative to colistin (odds ratio 0.44, 95% credible intervals 0.03 to 3.94), but the result was not statistically significant. The other treatments were associated with no susceptibility. In the base case, patient-level benefit of cefiderocol was between 0.02 and 0.15 quality-adjusted life-years, depending on the site of infection, the pathogen and the usage scenario. There was a high degree of uncertainty surrounding the benefits of cefiderocol across all subgroups. There was substantial uncertainty in the number of infections that are suitable for treatment with cefiderocol, so population-level results are presented for a range of scenarios for the current infection numbers, the expected increases in infections over time and rates of emergence of resistance. The population-level benefits varied substantially across the base-case scenarios, from 896 to 3559 quality-adjusted life-years over 20 years. Conclusion: This work has provided quantitative estimates of the value of cefiderocol within its areas of expected usage within the NHS. Limitations: Given existing evidence, the estimates of the value of cefiderocol are highly uncertain. Future work: Future evaluations of antimicrobials would benefit from improvements to NHS data linkages; research to support appropriate synthesis of susceptibility studies; and application of routine data and decision modelling to assess enablement value. Study registration: No registration of this study was undertaken. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment Policy Research Programme (NIHR award ref: NIHR135591), conducted through the Policy Research Unit in Economic Methods of Evaluation in Health and Social Care Interventions, PR-PRU-1217-20401, and is published in full in Health Technology Assessment; Vol. 28, No. 28. See the NIHR Funding and Awards website for further award information.

This project tested new methods for estimating the value to the NHS of an antimicrobial, cefiderocol, so its manufacturer could be paid fairly even if very little drug is used in order to reduce the risk of bacteria becoming resistant to the product. Clinicians said that the greatest benefit of cefiderocol is when used for complicated urinary tract infections and pneumonia acquired within hospitals caused by two types of bacteria (called Enterobacterales and Pseudomonas aeruginosa), with a resistance mechanism called metallo-beta-lactamase. Because there were no relevant clinical trial data, we estimated how effective cefiderocol and alternative treatments were by doing a systematic literature review of studies that grew bacteria from infections in the laboratory and tested the drugs on them. We linked this to data estimating the long-term health and survival of patients. Some evidence was obtained by asking clinicians detailed questions about what they thought the effects would be based on their experience and the available evidence. We included the side effects of the alternative treatments, some of which can cause kidney damage. We estimated how many infections there would be in the UK, whether they would increase over time and how resistance to treatments may change over time. Clinicians told us that they would also use cefiderocol to treat intra-abdominal and bloodstream infections, and some infections caused by another bacteria called Stenotrophomonas. We estimated how many of these infections there would be, and assumed the same health benefits as for other types of infections. The total value to the NHS was calculated using these estimates. We also considered whether we had missed any additional elements of value. We estimated that the value to the NHS was £18­71 million over 20 years. This reflects the maximum the NHS could pay for use of cefiderocol if the health lost as a result of making these payments rather than funding other NHS services is not to exceed the health benefits of using this antimicrobial. However, these estimates are uncertain due to limitations with the evidence used to produce them and assumptions that had to be made.

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.

Percutaneous Revascularization for Ischemic Left Ventricular Dysfunction: Cost-Effectiveness Analysis of the REVIVED-BCIS2 Trial.

BACKGROUND: Percutaneous coronary intervention (PCI) is frequently undertaken in patients with ischemic left ventricular systolic dysfunction. The REVIVED (Revascularization for Ischemic Ventricular Dysfunction)-BCIS2 (British Cardiovascular Society-2) trial concluded that PCI did not reduce the incidence of all-cause death or heart failure hospitalization; however, patients assigned to PCI reported better initial health-related quality of life than those assigned to optimal medical therapy (OMT) alone. The aim of this study was to assess the cost-effectiveness of PCI+OMT compared with OMT alone. METHODS: REVIVED-BCIS2 was a prospective, multicenter UK trial, which randomized patients with severe ischemic left ventricular systolic dysfunction to either PCI+OMT or OMT alone. Health care resource use (including planned and unplanned revascularizations, medication, device implantation, and heart failure hospitalizations) and health outcomes data (EuroQol 5-dimension 5-level questionnaire) on each patient were collected at baseline and up to 8 years post-randomization. Resource use was costed using publicly available national unit costs. Within the trial, mean total costs and quality-adjusted life-years (QALYs) were estimated from the perspective of the UK health system. Cost-effectiveness was evaluated using estimated mean costs and QALYs in both groups. Regression analysis was used to adjust for clinically relevant predictors. RESULTS: Between 2013 and 2020, 700 patients were recruited (mean age: PCI+OMT=70 years, OMT=68 years; male (%): PCI+OMT=87, OMT=88); median follow-up was 3.4 years. Over all follow-ups, patients undergoing PCI yielded similar health benefits at higher costs compared with OMT alone (PCI+OMT: 4.14 QALYs, £22 352; OMT alone: 4.16 QALYs, £15 569; difference: -0.015, £6782). For both groups, most health resource consumption occurred in the first 2 years post-randomization. Probabilistic results showed that the probability of PCI being cost-effective was 0. CONCLUSIONS: A minimal difference in total QALYs was identified between arms, and PCI+OMT was not cost-effective compared with OMT, given its additional cost. A strategy of routine PCI to treat ischemic left ventricular systolic dysfunction does not seem to be a justifiable use of health care resources in the United Kingdom. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01920048.

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.

Economic evaluation of self-help group interventions for health in LMICs: a scoping review.

This scoping review aims to identify and critically appraise published economic evaluations of self-help group (SHG) interventions in low- and middle-income countries (LMICs) that seek to improve health and potentially also non-health outcomes. Through a systematic search of MEDLINE ALL (Ovid), EMBASE Ovid, PsychINFO, EconLit (Ovid) and Global Index Medicus, we identified studies published between 2014 and 2020 that were based in LMICs, included at least a health outcome, estimated intervention costs and reported the methods used. We critically analysed whether the methods employed can meaningfully inform decisions by ministries of health and other sectors, including donors, regarding whether to fund such interventions, and prioritized the aspects of evaluations that support decision-making and cross-sectoral decision-making especially. Nine studies met our inclusion criteria. Randomized controlled trials were the most commonly used vehicle to collect data and to establish a causal effect across studies. While all studies clearly stated one or more perspectives justifying the costs and effects that are reported, few papers clearly laid out the decision context or the decision maker(s) informed by the study. The latter is required to inform which costs, effects and opportunity costs are relevant to the decision and should be included in the analysis. Costs were typically reported from the provider or health-care sector perspective although other perspectives were also employed. Four papers reported outcomes in terms of a generic measure of health. Contrary to expectation, no studies reported outcomes beyond health. Our findings suggest limitations in the extent to which published studies are able to inform decision makers around the value of implementing SHG interventions in their particular context. Funders can make better informed decisions when evidence is presented using a cross-sectoral framework.

Using Age-Specific Values for Pediatric HRQoL in Cost-Effectiveness Analysis: Is There a Problem to Be Solved? If So, How?

Value sets for the EQ-5D-Y-3L published to date appear to have distinctive characteristics compared with value sets for corresponding adult instruments: in many cases, the value for the worst health state is higher and there are fewer values < 0. The aim of this paper is to consider how and why values for child and adult health differ; and what the implications of that are for the use of EQ-5D-Y-3L values in economic evaluations to inform healthcare resource allocation decisions. We posit four potential explanations for the differences in values: (a) The wording of severity labels may mean the worst problems on the EQ-5D-Y-3L are descriptively less severe than those on the EQ-5D-5L; (b) Adults may genuinely consider that children are less badly affected than adults by descriptively similar health issues. That is, for any given health problem, adult respondents in valuation studies consider children's overall health-related quality of life (HRQoL) on average to be higher than that for adults; (c) Values are being sought by eliciting adults' stated preferences for HRQoL in another person, rather than in themselves (regardless of whether the 'other person' concerned is a child); and (d) The need to elicit preferences for child HRQoL that are anchored at dead = 0 invokes special considerations regarding children's survival. Existing evidence does not rule out the possibility that (c) and (d) exert an upward bias in values. We consider the implications of that for the interpretation and use of values for pediatric HRQoL. Alternative methods for valuing children's HRQoL in a manner that is not 'age specific' are possible and may help to avoid issues of non-comparability. Use of these methods would place the onus on health technology assessment bodies to reflect any special considerations regarding child quality-adjusted life-year gains.

Randomised trial of stable chest pain investigation: 3-year clinical and quality of life results from CE-MARC 2.

AIMS: Guidelines for suspected cardiac chest pain have used historical risk stratification tools, advocating invasive coronary angiography (ICA) first-line in those at highest risk. We aimed to determine whether different strategies to manage suspected stable angina affected medium-term cardiovascular event rates and patient-reported quality of life (QoL) measures. METHODS: CE-MARC 2, a three-arm parallel group trial, randomised patients with suspected stable cardiac chest pain and a Duke Clinical pretest likelihood of coronary artery disease between 10% and 90%. Patients were randomised to either first-line cardiovascular magnetic resonance (CMR), single-photon emission computed tomography (SPECT) or the UK National Institute for Health and Care Excellence (NICE) CG95 (2010) guidelines-directed care. For the three arms, 1-year and 3-year first major adverse cardiovascular event (MACE) rates and QoL assessed by the Seattle Angina Questionnaire, Short Form 12 (V.12) Questionnaire and EuroQol-5 Dimension Questionnaire were recorded. RESULTS: 1202 patients were randomised to CMR (n=481), SPECT (n=481) and NICE (n=240). Forty-two patients (18 CMR, 18 SPECT, 6 NICE) experienced one or more MACEs. The percentage rates (95% CIs) of MACE in the CMR, SPECT and NICE groups at 3 years were 3.7% (2.4%, 5.8%), 3.7% (2.4%, 5.8%) and 2.1% (0.9%, 4.8%), respectively. QoL scores did not significantly differ across domains. CONCLUSION: Despite a fourfold increase in referrals for ICA, the NICE CG95 (2010) guidelines risk-stratified care strategy did not significantly reduce 3-year MACE or improve QoL, as compared with functional imaging with CMR or SPECT. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT01664858).

A qualitative study on the feasibility and acceptability of institutionalizing health technology assessment in Malawi.

OBJECTIVE: The objective of this study was to assess the feasibility and acceptability of institutionalizing Health Technology Assessment (HTA) in Malawi. METHODS: This study employed a document review and qualitative research methods, to understand the status of HTA in Malawi. This was complemented by a review of the status and nature of HTA institutionalization in selected countries.Qualitative research employed a Focus Group Discussion (FGD ) with 7 participants, and Key Informant Interviews (KIIs) with12 informants selected based on their knowledge and expertise in policy processes related to HTA in Malawi.Data extracted from the literature was organized in Microsoft Excel, categorized according to thematic areas and analyzed using a literature review framework. Qualitative data from KIIs and the FGD was analyzed using a thematic content analysis approach. RESULTS: Some HTA processes exist and are executed through three structures namely: Ministry of Health Senior Management Team, Technical Working Groups, and Pharmacy and Medicines Regulatory Authority (PMRA) with varyingdegrees of effectiveness.The main limitations of current HTA mechanisms include limited evidence use, lack of a standardized framework for technology adoption, donor pressure, lack of resources for the HTA process and technology acquisition, laws and practices that undermine cost-effectiveness considerations. KII and FGD results showed overwhelming demand for strengthening HTA in Malawi, with a stronger preference for strengthening coordination and capacity of existing entities and structures. CONCLUSION: The study has shown that HTA institutionalization is acceptable and feasible in Malawi. However, the current committee based processes are suboptimal to improve efficiency due to lack of a structured framework. A structured HTA framework has the potential to improve processes in pharmaceuticals and medical technologies decision-making.In the short to medium term, HTA capacity building should focus on generating demand and increasing capacity in cost-effectiveness assessments. Country-specific assessments should precede HTA institutionalization as well as recommendations for new technology adoptions.

Developing a Modeling Framework for Quantifying the Health and Cost Implications of Antibiotic Resistance for Surgical Procedures.

Background. Antimicrobial resistance (AMR) is a global public health threat. The wider implications of AMR, such as the impact of antibiotic resistance (ABR) on surgical procedures, are yet to be quantified. The objective of this study was to produce a conceptual modeling framework to provide a basis for estimating the current and potential future consequences of ABR for surgical procedures in England. Design. A framework was developed using literature-based evidence and structured expert elicitation. This was applied to populations undergoing emergency repair of the neck of the femur and elective colorectal resection surgery. Results. The framework captures the implications of increasing ABR by allowing for higher rates of surgical site infection (SSI) as the effectiveness of antibiotic prophylaxis wanes and worsened outcomes following SSIs to reflect reduced antibiotic treatment effectiveness. The expert elicitation highlights the uncertainty in quantifying the impact of ABR, reflected in the results. A hypothetical SSI rate increase of 14% in a person undergoing emergency repair of the femur could increase costs by 39% (-2% to 108% credible interval [CI]) and decrease quality-adjusted life-years by 11% (0.4% to 62% CI) over 15 y. Conclusions. The modeling framework is a starting point for addressing the implication of ABR on the outcomes and costs of surgeries. Due to clinical uncertainty highlighted in the expert elicitation process, the numerical outputs of the case studies should not be focused on but rather the framework itself, illustration of the evidence gaps, the benefit of expert elicitation in quantifying parameters with limited data, and the potential magnitude of the impact of ABR on surgical procedures. Implications. The framework can be used to support research surrounding the health and cost burden of ABR in England. Highlights: The modeling framework is a starting point for assessing the health and cost impacts of antibiotic resistance on surgeries in England.Formulating a framework and synthesizing evidence to parameterize data gaps provides targets for future research.Once data gaps are addressed, this modeling framework can be used to feed into overall estimates of the health and cost burden of antibiotic resistance and evaluate control policies.

Assessing the potential of HTA to inform resource allocation decisions in low-income settings: The case of Malawi.

Health technology assessment (HTA) offers a set of analytical tools to support health systems' decisions about resource allocation. Although there is increasing interest in these tools across the world, including in some middle-income countries, they remain rarely used in low-income countries (LICs). In general, the focus of HTA is narrow, mostly limited to assessments of efficacy and cost-effectiveness. However, the principles of HTA can be used to support a broader series of decisions regarding new health technologies. We examine the potential for this broad use of HTA in LICs, with a focus on Malawi. We develop a framework to classify the main decisions on health technologies within health systems. The framework covers decisions on identifying and prioritizing technologies for detailed assessment, deciding whether to adopt an intervention, assessing alternative investments for implementation and scale-up, and undertaking further research activities. We consider the relevance of the framework to policymakers in Malawi and we use two health technologies as examples to investigate the main barriers and enablers to the use of HTA methods. Although the scarcity of local data, expertise, and other resources could risk limiting the operationalisation of HTA in LICs, we argue that even in highly resource constrained health systems, such as in Malawi, the use of HTA to support a broad range of decisions is feasible and desirable.

Estimating the global demand curve for a leishmaniasis vaccine: A generalisable approach based on global burden of disease estimates.

BACKGROUND: A pressing need exists to develop vaccines for neglected diseases, including leishmaniasis. However, the development of new vaccines is dependent on their value to two key players-vaccine developers and manufacturers who need to have confidence in the global demand in order to commit to research and production; and governments (or other international funders) who need to signal demand based on the potential public health benefits of the vaccine in their local context, as well as its affordability. A detailed global epidemiological analysis is rarely available before a vaccine enters a market due to lack of resources as well as insufficient global data necessary for such an analysis. Our study seeks to bridge this information gap by providing a generalisable approach to estimating the commercial and public health value of a vaccine in development relying primarily on publicly available Global Burden of Disease (GBD) data. This simplified approach is easily replicable and can be used to guide discussions and investments into vaccines and other health technologies where evidence constraints exist. The approach is demonstrated through the estimation of the demand curve for a future leishmaniasis vaccine. METHODOLOGY/PRINCIPAL FINDINGS: We project the ability to pay over the period 2030-2040 for a vaccine preventing cutaneous and visceral leishmaniasis (CL / VL), using an illustrative set of countries which account for most of the global disease burden. First, based on previous work on vaccine demand projections in these countries and CL / VL GBD-reported incidence rates, we project the potential long-term impact of the vaccine on disability-adjusted life years (DALYs) averted as a result of reduced incidence. Then, we apply an economic framework to our estimates to determine vaccine affordability based on the abilities to pay of governments and global funders, leading to estimates of the demand and market size. Based on our estimates, the maximum ability-to-pay of a leishmaniasis vaccine (per course, including delivery costs), given the current estimates of incidence and population at risk, is higher than $5 for 25-30% of the countries considered, with the average value-based maximum price, weighted by quantity demanded, being $5.7-6 [$0.3 - $34.5], and total demand of over 560 million courses. CONCLUSION/SIGNIFICANCE: Our results demonstrate that both the quantity of vaccines estimated to be required by the countries considered as well as their ability-to-pay could make a vaccine for leishmaniasis commercially attractive to potential manufacturers. The methodology used can be equally applied to other technology developments targeting health in developing countries.

Using Economic Evaluation to Inform Responses to the Opioid Epidemic in the United States: Challenges and Suggestions for Future Research.

Background: Several aspects of the opioid epidemic and of public health care organization in the United States (US) make the conduct of economic evaluation and the design of policies to respond to this crisis particularly challenging. Objectives: This commentary offers suggestions for how economic evaluation may address and overcome four key features of the opioid epidemic: 1) its magnitude and geographical distribution, 2) its intersection with multiple epidemics, 3) its rapidly changing dynamics, 4) its multi-sectoral causes and consequences. Results: We first offer pragmatic suggestions to address the difficulties in delivering a coordinated response given the fragmented nature of health care in the US. In view of the broad suite of responses required to address opioid use disorder and its associated comorbidities, we highlight the need for economic evaluations which consider interventions throughout the continuum of care (i.e. primary, secondary and tertiary levels of prevention). We examine how the use of predictive modelling alongside economic evaluation might be adopted to address the rapidly evolving situation affecting distinct populations and geographic areas and encourage investments in epidemic preparedness. Finally, we propose methods to capture the interdependence of various sectors of government affected by the opioid crisis in economic evaluations to ensure optimal levels of investment towards a comprehensive response. Conclusions: The opioid epidemic in the US represents an unprecedented public health challenge, but sound epidemiological modelling and economic analysis can help to guide use of limited resources committed to addressing it in ways that can have greatest impact in limiting its adverse consequences.

Program Evaluation of Population- and System-Level Policies: Evidence for Decision Making.

BACKGROUND: Policy evaluations often focus on ex post estimation of causal effects on short-term surrogate outcomes. The value of such information is limited for decision making, as the failure to reflect policy-relevant outcomes and disregard for opportunity costs prohibits the assessment of value for money. Further, these evaluations do not always consider all relevant evidence, other courses of action, or decision uncertainty. METHODS: In this article, we explore how policy evaluation could better meet the needs of decision making. We begin by defining the evidence required to inform decision making. We then conduct a literature review of challenges in evaluating policies. Finally, we highlight potential methods available to help address these challenges. RESULTS: The evidence required to inform decision making includes the impacts on the policy-relevant outcomes, the costs and associated opportunity costs, and the consequences of uncertainty. Challenges in evaluating health policies are described using 8 categories: 1) valuation space; 2) comparators; 3) time of evaluation; 4) mechanisms of action; 5) effects; 6) resources, constraints, and opportunity costs; 7) fidelity, adaptation, and level of implementation; and 8) generalizability and external validity. Methods from a broad set of disciplines are available to improve policy evaluation, relating to causal inference, decision-analytic modeling, theory of change, realist evaluation, and structured expert elicitation. LIMITATIONS: The targeted review may not identify all possible challenges, and the methods covered are not exhaustive. CONCLUSIONS: Evaluations should provide appropriate evidence to inform decision making. There are challenges in evaluating policies, but methods from multiple disciplines are available to address these challenges. IMPLICATIONS: Evaluators need to carefully consider the decision being informed, the necessary evidence to inform it, and the appropriate methods.[Box: see text].

Developing the EQ-5D-5L Value Set for Uganda Using the 'Lite' Protocol.

OBJECTIVE: A 'lite' version of the EQ-5D-5L valuation protocol, which requires a smaller sample by collecting more data from each participant, was proposed and used to develop an EQ-5D-5L value set for Uganda. METHODS: Adult respondents from the general Ugandan population were quota sampled based on age and sex. Eligible participants were asked to complete 20 composite time trade-off tasks in the tablet-assisted personal interviews using the offline EuroQol Portable Valuation Technology software under routine quality control. No discrete choice experiment task was administered. The composite time trade-off data were modelled using four additive and two multiplicative regression models. Model performance was evaluated based on face validity, prediction accuracy in cross-validation and in predicting mild health states. The final value set was generated using the best-performing model. RESULTS: A representative sample (N = 545) participated in this study. Responses to composite time trade-off tasks from 492 participants were included in the primary analysis. All models showed face validity and generated comparable prediction accuracy. The Tobit model with constrained intercepts and corrected for heteroscedasticity was considered the preferred model for the value set on the basis of better performance. The value set ranges from - 1.116 (state 55555) to 1 (state 11111) with 'pain/discomfort' as the most important dimension. CONCLUSIONS: This is the first EQ-5D-5L valuation study using a 'lite' protocol involving composite time trade-off data only. Our results suggest its feasibility in resource-constrained settings. The established EQ-5D-5L value set for Uganda is expected to be used for economic evaluations and decision making in Uganda and the East Africa region.

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.

Estimating the shares of the value of branded pharmaceuticals accruing to manufacturers and to patients served by health systems.

Previous studies have estimated that patients served by health systems accrue 59-98% of the value generated by new pharmaceuticals. This has led to questions about whether sufficient returns accrue to manufacturers to incentivize socially optimal levels of R&D. These studies have not, however, fully reflected the health opportunity costs imposed by payments for branded pharmaceuticals. We present a framework for estimating how the value generated by new branded pharmaceuticals is shared. We quantify value in net health effects and account for benefits and health opportunity costs in the patent period and post-patent period when generic/biosimilar products become available. We apply the framework to 12 National Institute for Health and Care Excellence appraisals and show that realized net health effects range from losses of 160%, to gains of 94%, of the potential net health benefits available. In many cases, even in the long run, the benefits of new medicines are not sufficient to offset the opportunity costs of payments to manufacturers, and approval is expected to reduce population health. This cannot be dynamically efficient as it incentivizes future innovation at prices which will also reduce population health. Further work should consider how to reflect these findings in reimbursement policies.

Jointly Modelling Economics and Epidemiology to Support Public Policy Decisions for the COVID-19 Response: A Review of UK Studies.

COVID-19 in the UK has had a profound impact on population health and other socially important outcomes, including on education and the economy. Although a range of evidence has guided policy, epidemiological models have been central. It is less clear whether models to support decision making have sought to integrate COVID-19 epidemiology with a consideration of broader health, wellbeing and economic implications. We report on a rapid review of studies seeking to integrate epidemiological and economic modelling to assess the impacts of alternative policies. Overall, our results suggest that few studies have explored broader impacts of different COVID-19 policies in the UK. Three studies looked only at health, capturing impacts on individuals with and without COVID-19, with various methods used to model the latter. Four models considered health and wider impacts on individuals' economic outcomes, such as wages. However, these models made no attempt to consider the dynamic impacts on economic outcomes of others and the wider economy. The most complex analyses sought to link epidemiological and dynamic economic models. Studies compared a wide range of policies, although most were defined in general terms with minimal consideration of their granular specifications. There was minimal exploration of uncertainty, with no consideration in half the studies. Selecting appropriate models to inform decisions requires careful thought of factors relevant to the decision options under consideration such as the outcomes of interest, sectors likely to be impacted and causal pathways. In summary, better linking epidemiological and economic modelling would help to inform COVID-19 policy.

Methodological issues in economic evaluations of emergency transport systems in low-income and middle-income countries.

A recent systematic review identified few papers on the economic evaluation of systems for emergency transport of acutely ill or injured patients. In addition, we found no articles dealing with the methodological challenges posed by such studies in low-income or middle-income countries. We therefore carried out an analysis of issues that are of particular salience to this important topic. This is an intellectual study in which we develop models, identify their limitations, suggest potential extensions to the models and discuss priorities for empirical studies to populate models. First, we develop a general model to calculate changes in survival contingent on the reduced time to treatment that an emergency transport system is designed to achieve. Second, we develop a model to estimate transfer times over an area that will be served by a proposed transfer system. Third, we discuss difficulties in obtaining parameters with which to populate the models. Fourth, we discuss costs, both direct and indirect, of an emergency transfer service. Fifth, we discuss the issue that outcomes other than survival should be considered and that the effects of a service are a weighted sum over all the conditions and severities for which the service caters. Lastly, based on the above work, we identify priorities for research. To our knowledge, this is the first study to identify and frame issues in the health economics of acute transfer systems and to develop models to calculate survival rates from basic parameters, such as time delay/survival relationships, that vary by intervention type and context.