Cost-effectiveness of air pollution control: Improving quantification methods and estimating QALY gains and health care resource impacts in England

This thesis is about the economic evaluation of interventions for air pollution control. It is structured around three major components. First, a critical analysis of current methods for health impact quantification in the environmental health literature. Second, the development of a Markov model of the health impacts of long-term exposure to air pollution, using the quality-adjusted life year as health metric, in order to evaluate the cost-effectiveness of reducing air pollution in England. Third, evidence synthesis and COPD incidence estimation by severity stage, in order to parameterise the model developed. I demonstrate that the current approach to quantifying the health benefits from air pollution reduction leads to substantially biased estimates. By ignoring interactions between morbidity and mortality impacts, including differential susceptibility to risk by health status, it overestimates the change in morbidity cases and underestimates life expectancy effects. I also show that current European guidelines for uncertainty analysis in assessments of air pollution control interventions underestimate decision uncertainty and may misguide air quality strategies. My Markov model fully captures, for the first time, the lifetime impact of air pollution exposure on individuals' quality and length of life, and identifies the joint health care budget impact of a reduction in chronic morbidity and premature death. Air quality improvement has important health implications. In London, investing up to £500 million to reduce fine particulate concentrations by 1 ug/m3 (i.e. by 7%) is highly likely to be cost-effective, whether the investment is funded by the NHS or through taxation. If this improvement were to cost more than that, however, funding through taxation is more likely to be cost-effective than funding via the NHS, since consumer willingness to pay for a QALY is higher than the estimated NHS expenditure required to deliver one QALY. The optimal level of pollution reduction, as well as the decision about whether and for how long to delay investments, is therefore expected to depend on the source of financing

Economic evaluations of the health impacts of weather-related extreme events : A scoping review. International Journal of Environmental Research and Public Health

The frequency and severity of extreme events is expected to increase under climate change. There is a need to understand the economic consequences of human exposure to these extreme events, to underpin decisions on risk reduction. We undertook a scoping review of economic evaluations of the adverse health effects from exposure to weather-related extreme events. We searched PubMed, Embase and Web of Science databases with no restrictions to the type of evaluations. Twenty studies were included, most of which were recently published. Most studies have been undertaken in the U.S. (nine studies) or Asia (seven studies), whereas we found no studies in Africa, Central and Latin America nor the Middle East. Extreme temperatures accounted for more than a third of the pool of studies (seven studies), closely followed by flooding (six studies). No economic study was found on drought. Whilst studies were heterogeneous in terms of objectives and methodology, they clearly indicate that extreme events will become a pressing public health issue with strong welfare and distributional implications. The current body of evidence, however, provides little information to support decisions on the allocation of scarce resources between risk reduction options. In particular, the review highlights a significant lack of research attention to the potential cost-effectiveness of interventions that exploit the capacity of natural ecosystems to reduce our exposure to, or ameliorate the consequences of, extreme events

Practical metrics for establishing the health benefits of research to support research prioritisation

Introduction : We present practical metrics for estimating the expected health benefits of specific research proposals. These can be used by research funders, researchers, and health-care decision makers within low- and middle-income countries (LMICs) to support evidence-based research prioritisation. Methods : The methods require three key assessments: (1) the current level of uncertainty around the endpoints the proposed study will measure; (2) how uncertainty impacts on the health benefits and costs of health-care programmes; and (3) the health opportunity costs imposed by programme costs. Research is valuable because it can improve health by informing the choice of which programmes should be implemented. We provide a Microsoft Excel tool to allow readers to generate estimates of the health benefits of research studies based on these three assessments. The tool can be populated using clinical studies, existing cost-effectiveness models and expert opinion. Where such evidence is not available, the tool can quantify the value of research under different assumptions. Estimates of the health benefits of research can be considered alongside research costs, and the consequences of delaying implementation until research reports, to determine whether research is worthwhile. We illustrate the method using a case study of research on HIV self-testing programmes in Malawi. This analysis combines data from the literature with outputs from the HIV synthesis model. Results : For this case study we found a costing study that could be completed and inform decision making within one year offered the highest health benefits (67,000 DALYs averted). Research on outcomes improved population health to a lesser extent (12,000 DALYs averted) and only if carried out alongside programme implementation. Conclusion : Our work provides a method for estimating the health benefits of research in a practical and timely fashion. This can be used to support accountable use of research funds

Concomitant health benefits package design and research prioritisation : development of a new approach and an application to Malawi

Health benefits packages (HBPs) are increasingly used in many countries to guide spending priorities on the path towards universal health coverage. Their design is, however, informed by an uncertain evidence base but research funds available to address this are limited. This gives rise to the question of which piece of research relating to the cost-effectiveness of interventions would most contribute to improving resource allocation. We propose to incorporate research prioritisation as an integral part of HBP design. We have, therefore, developed a framework and a freely available companion stand-alone tool, to quantify in terms of net disability-adjusted life-years (DALYs) averted, the value of research for the interventions considered for inclusion in a package. Using the tool, the framework can be implemented using sensitivity analysis results typically reported in cost-effectiveness studies. To illustrate the framework, we applied the tool to the evidence base that informed the Malawi Health Sector Strategic Plan 2017-2022. Out of 21 interventions considered, 8 investment decisions were found to be uncertain and three showed strong potential for research to generate large health gains: 'male circumcision', 'community-management of acute malnutrition in children' and 'isoniazid preventive therapy in HIV +individuals', with a potential to avert up to 65 762, 36 438 and 20 132 net DALYs, respectively. Our work can help set research priorities in resource-constrained settings so that research funds are invested where they have the largest potential to impact on the population health generated via HBPs

Pollen Processing Behavior of Heliconius Butterflies: A Derived Grooming Behavior

Pollen feeding behaviors Heliconius and Laparus (Lepidoptera: Nymphalidae) represent a key innovation that has shaped other life history traits of these neotropical butterflies. Although all flower visiting Lepidoptera regularly come in contact with pollen, only Heliconius and Laparus butterflies actively collect pollen with the proboscis and subsequently take up nutrients from the pollen grains. This study focused on the behavior of pollen processing and compared the movement patterns with proboscis grooming behavior in various nymphalid butterflies using video analysis. The proboscis movements of pollen processing behavior consisted of a lengthy series of repeated coiling and uncoiling movements in a loosely coiled proboscis position combined with up and down movements and the release of saliva. The proboscis-grooming behavior was triggered by contamination of the proboscis in both pollen feeding and non-pollen feeding nymphalid butterflies. Proboscis grooming movements included interrupted series of coiling and uncoiling movements, characteristic sideways movements, proboscis lifting, and occasionally full extension of the proboscis. Discharge of saliva was more pronounced in pollen feeding species than in non-pollen feeding butterfly species. We conclude that the pollen processing behavior of Heliconius and Laparus is a modified proboscis grooming behavior that originally served to clean the proboscis after contamination with particles

Economic Evaluation of Environmental Interventions: Reflections on Methodological Challenges and Developments

Evaluation of the costs and outcomes associated with environmental policies and interventions is often required to inform public policy and allocate scarce resources. Methods to conduct assessments of cost-effectiveness have been developed in the context of pharmaceuticals, but have more recently been applied in public health, diagnostics, and other more complex interventions. The suitability of existing economic evaluation methodology has been explored in many contexts, however, this is yet to be undertaken for interventions and policies pertaining to the natural environment, such as urban green spaces and strategies to reduce indoor and outdoor air pollution. To make significant inroads into the evaluation of interventions and policies relating to the natural environment requires an understanding of the challenges faced in this context. Many of these challenges may be practical (data-related), however, a number are also methodological, and thus have implications for the appropriate framework for economic evaluation. This paper considers some of the challenges faced when conducting cost-effectiveness analyses in this context and explores what solutions have been proposed thus far. The intention is to help pave the way for consideration of which existing framework is most appropriate for the evaluation of natural environment (NE) interventions, or if a distinct framework is required. Environmental policies and interventions relating to the built environment, for example, housing, are not explicitly included here

Non-invasive imaging software to assess the functional significance of coronary stenoses : a systematic review and economic evaluation

Background: QAngio® XA 3D/QFR® (three-dimensional/quantitative flow ratio) imaging software (Medis Medical Imaging Systems BV, Leiden, the Netherlands) and CAAS® vFFR® (vessel fractional flow reserve) imaging software (Pie Medical Imaging BV, Maastricht, the Netherlands) are non-invasive technologies to assess the functional significance of coronary stenoses, which can be alternatives to invasive fractional flow reserve assessment. Objectives: The objectives were to determine the clinical effectiveness and cost-effectiveness of QAngio XA 3D/QFR and CAAS vFFR. Methods: We performed a systematic review of all evidence on QAngio XA 3D/QFR and CAAS vFFR, including diagnostic accuracy, clinical effectiveness, implementation and economic analyses. We searched MEDLINE and other databases to January 2020 for studies where either technology was used and compared with fractional flow reserve in patients with intermediate stenosis. The risk of bias was assessed with quality assessment of diagnostic accuracy studies. Meta-analyses of diagnostic accuracy were performed. Clinical and implementation outcomes were synthesised narratively. A simulation study investigated the clinical impact of using QAngio XA 3D/QFR. We developed a de novo decision-analytic model to estimate the cost-effectiveness of QAngio XA 3D/QFR and CAAS vFFR relative to invasive fractional flow reserve or invasive coronary angiography alone. Scenario analyses were undertaken to explore the robustness of the results to variation in the sources of data used to populate the model and alternative assumptions. Results: Thirty-nine studies (5440 patients) of QAngio XA 3D/QFR and three studies (500 patients) of CAAS vFFR were included. QAngio XA 3D/QFR had good diagnostic accuracy to predict functionally significant fractional flow reserve (≤ 0.80 cut-off point); contrast-flow quantitative flow ratio had a sensitivity of 85% (95% confidence interval 78% to 90%) and a specificity of 91% (95% confidence interval 85% to 95%). A total of 95% of quantitative flow ratio measurements were within 0.14 of the fractional flow reserve. Data on the diagnostic accuracy of CAAS vFFR were limited and a full meta-analysis was not feasible. There were very few data on clinical and implementation outcomes. The simulation found that quantitative flow ratio slightly increased the revascularisation rate when compared with fractional flow reserve, from 40.2% to 42.0%. Quantitative flow ratio and fractional flow reserve resulted in similar numbers of subsequent coronary events. The base-case cost-effectiveness results showed that the test strategy with the highest net benefit was invasive coronary angiography with confirmatory fractional flow reserve. The next best strategies were QAngio XA 3D/QFR and CAAS vFFR (without fractional flow reserve). However, the difference in net benefit between this best strategy and the next best was small, ranging from 0.007 to 0.012 quality-adjusted life-years (or equivalently £140–240) per patient diagnosed at a cost-effectiveness threshold of £20,000 per quality-adjusted life-year. Limitations: Diagnostic accuracy evidence on CAAS vFFR, and evidence on the clinical impact of QAngio XA 3D/QFR, were limited. Conclusions: Quantitative flow ratio as measured by QAngio XA 3D/QFR has good agreement and diagnostic accuracy compared with fractional flow reserve and is preferable to standard invasive coronary angiography alone. It appears to have very similar cost-effectiveness to fractional flow reserve and, therefore, pending further evidence on general clinical benefits and specific subgroups, could be a reasonable alternative. The clinical effectiveness and cost-effectiveness of CAAS vFFR are uncertain. Randomised controlled trial evidence evaluating the effect of quantitative flow ratio on clinical and patient-centred outcomes is needed. Future work: Studies are required to assess the diagnostic accuracy and clinical feasibility of CAAS vFFR. Large ongoing randomised trials will hopefully inform the clinical value of QAngio XA 3D/QFR. Study registration: This study is registered as PROSPERO CRD42019154575. Funding: This project was funded by the National Institute for Health Research (NIHR) Evidence Synthesis programme and will be published in full in Health Technology Assessment; Vol. 25, No. 56. See the NIHR Journals Library website for further project information

Patterns and predictors of e-cigarette, cigarette and dual use uptake in UK adolescents: Evidence from a 24-month Prospective Study

Background and Aims: To assess prevalence and predictors of e-cigarettes/cigarettes patterns of use in adolescents in England. Design: Prospective study with 24-month follow-up of e-cigarette/cigarette ever/regular use with data from an intervention evaluation. Setting: Forty-five schools in England (Staffordshire and Yorkshire). Participants: 3,210 adolescents who, at baseline, were aged 13-14 years and had never used e-cigarettes/cigarettes. Measurements: Based on e-cigarette/cigarette ever use at follow-up, six groups were created: (a) never user, (b) e-cigarette only, (c) cigarette only, (d) dual use – order of use unclear, (e) dual use – e-cigarettes used first, (f) dual use – cigarettes used first. Baseline measures were: gender, ethnicity, socioeconomic status, impulsivity, family plus friend smoking, and smoking-related beliefs (attitude and perceived behavioural control). Findings: In groups (a) through (f), there were 71·5%, 13·3%, 3·3%, 5·7%, 2·9%, and 3·4% adolescents, respectively. Among groups using cigarettes, regular smoking was more prevalent in group (f) (dual use – cigarettes used first) (17·6%, 95%CI 10·4, 24·8) than in groups (c), (d) and (e) combined (7·3%, 95%CI 4·7, 9·9). Among groups using e-cigarettes, regular use was less prevalent in group (b) (e-cigarette only) (1·9%, 95%CI 0·6, 3·2) than in groups (d), (e) and (f) combined (12·2%, 95%CI 8·9, 15·5). Higher impulsivity plus friends and family smoking were predictive of being in groups (b) to (f) compared with group (a) (never users). Males were more likely to be in group (b) compared to group (a); females were more likely to be in groups (c) to (f) compared to group (a). Conclusions: Regular use of e-cigarettes/cigarettes varies across groups defined by ever use of e-cigarettes/cigarettes. Interventions targeted at tackling impulsivity or adolescents whose friends and family members smoke may represent fruitful avenues for future research

QALY gain and health care resource impacts of air pollution control: A Markov modelling approach

This paper proposes a novel complementary approach to evaluate the public health benefits of air pollution control, where the joint impact on individuals’ quality and length of life is fully quantified using Markov modelling. A Markov model which captures, for the first time: (i) air pollution's influence on population individuals’ quality of life and life expectancy at baseline and (ii) dynamics in individuals’ susceptibility to air pollution exposure, is developed. In order to represent the body of epidemiological evidence on the cardio-respiratory effects of long-term exposure to fine particulate air pollution, the model is structured around three diseases: chronic obstructive pulmonary disease, coronary heart disease and lung cancer. Application of the model provides the first estimates of age and gender-specific quality-adjusted life years (QALY) gains from air quality improvement in the UK. Reducing mean PM2.5 concentrations by 1 μg/m3 in London and in England and Wales is expected to yield more than 63,000 and 540,000 QALYs respectively, to adults aged 40 and above over their remaining lifetime, discounting at 3.5% p.a. At a WTP value for a QALY of £65,000, which is in line with recommendations for the UK, the expected discounted monetary benefit of the intervention amounts to £4 billion in London and £34 billion in England and Wales

An intervention to support stroke survivors and their carers in the longer term (LoTS2Care): study protocol for a cluster randomised controlled feasibility trial

Background Despite the evidence that many stroke survivors report longer term unmet needs, the provision of longer term care is limited. To address this, we are conducting a programme of research to develop an evidence-based and replicable longer term care strategy. The developed complex intervention (named New Start), which includes needs identification, exploration of social networks and components of problem solving and self-management, was designed to improve quality of life by addressing unmet needs and increasing participation. Methods/Design A multicentre, cluster randomised controlled feasibility trial designed to inform the design of a possible future definitive cluster randomised controlled trial (cRCT) and explore the potential clinical and cost-effectiveness of New Start. Ten stroke services across the UK will be randomised on a 1:1 basis either to implement New Start or continue with usual care only. New Start will be delivered by trained facilitators and will be offered to all stroke survivors within the services allocated to the intervention arm. Stroke survivors will be eligible for the trial if they are 4–6 months post-stroke and residing in the community. Carers (if available) will also be invited to take part. Invitation to participate will be initiated by post and outcome measures will be collected via postal questionnaires at 3, 6 and 9 months after recruitment. Outcome data relating to perceived health and disability, wellbeing and quality of life as well as unmet needs will be collected. A ‘study within a trial’ (SWAT) is planned to determine the most acceptable format in which to provide the postal questionnaires. Details of health and social care service usage will also be collected to inform the economic evaluation. The feasibility of recruiting services and stroke survivors to the trial and of collecting postal outcomes will be assessed and the potential for effectiveness will be investigated. An embedded process evaluation (reported separately) will assess implementation fidelity and explore and clarify causal assumptions regarding implementation. Discussion This feasibility trial with embedded process evaluation will allow us to gather important and detailed data regarding methodological and implementation issues to inform the design of a possible future definitive cRCT of this complex intervention. Trial Registration ISRCTN38920246. Registered 22 June 2016