What, who and when? Incorporating a discrete choice experiment into an economic evaluation

ACKNOWLEDGEMENTS: The Medman study was funded by the Department of Health for England and Wales and managed by a collaboration of the National Pharmaceutical Association, the Royal Pharmaceutical Society of Great Britain, the Company Chemist Association and the Co-operative Pharmacy Technical Panel, led by the Pharmaceutical Services Negotiating Committee. The research in this paper was undertaken while the lead author MT was undertaking a doctoral research fellowship jointly funded by the Economic and Social Research Council (ESRC) and the Medical Research Council (MRC). The Health Economics Research Unit (HERU), University of Aberdeen is funded by the Chief Scientific Office of the Scottish Government Health and Social Care Directorate.

Costs, quality of life and cost-effectiveness of open and arthroscopic repair for rotator cuff tears : economic evaluation alongside the UKUFF trial

FUNDING & ACKNOWLEDGEMENTS This project was funded by the NIHR Health Technology Assessment programme (project number 05/47/02) and is published in full in Health Technology Assessment; Vol. 19, No. 80. Further information available at: http://www.nets.nihr.ac.uk/projects/hta/054702 This paper presents independent research commissioned by the National Institute for Health Research (NIHR). The views and opinions expressed by authors in this publication are those of the authors and do not necessarily reflect those of the NHS, the NIHR, MRC, CCF, NETSCC, the HTA programme or the Department of Health. Due to the confidential nature of the trial data supporting this publication not all of the data can be made accessible to other researchers. Please contact the UKUFF study principal investigator Andrew Carr (andrew.carr@ndorms.ox.ac.uk) for more information. The authors wish to thank the UKUFF trial collaborators for their contribution in managing the conduct of the trial, and for their comments on the interim economic results: Marion Campbell and Hannah Bruhn (Centre for Healthcare Randomised Trials, HSRU, University of Aberdeen), Jonathan Rees MD and David Beard (NDORMS, University of Oxford; NIHR Oxford Biomedical Research Centre), Jane Moser (NDORMS, University of Oxford), Raymond Fitzpatrick and Jill Dawson (NDPH, University of Oxford).

Sepsis: the LightCycler SeptiFast Test MGRADE®, SepsiTest™ and IRIDICA BAC BSI assay for rapidly identifying bloodstream bacteria and fungi – a systematic review and economic evaluation

Background: Sepsis can lead to multiple organ failure and death. Timely and appropriate treatment can reduce in-hospital mortality and morbidity. Objectives: To determine the clinical effectiveness and cost-effectiveness of three tests [LightCycler SeptiFast Test MGRADE® (Roche Diagnostics, Risch-Rotkreuz, Switzerland); SepsiTest™ (Molzym Molecular Diagnostics, Bremen, Germany); and the IRIDICA BAC BSI assay (Abbott Diagnostics, Lake Forest, IL, USA)] for the rapid identification of bloodstream bacteria and fungi in patients with suspected sepsis compared with standard practice (blood culture with or without matrix-absorbed laser desorption/ionisation time-offlight mass spectrometry). Data sources: Thirteen electronic databases (including MEDLINE, EMBASE and The Cochrane Library) were searched from January 2006 to May 2015 and supplemented by hand-searching relevant articles. Review methods: A systematic review and meta-analysis of effectiveness studies were conducted. A review of published economic analyses was undertaken and a de novo health economic model was constructed. A decision tree was used to estimate the costs and quality-adjusted life-years (QALYs) associated with each test; all other parameters were estimated from published sources. The model was populated with evidence from the systematic review or individual studies, if this was considered more appropriate (base case 1). In a secondary analysis, estimates (based on experience and opinion) from seven clinicians regarding the benefits of earlier test results were sought (base case 2). A NHS and Personal Social Services perspective was taken, and costs and benefits were discounted at 3.5% per annum. Scenario analyses were used to assess uncertainty. Results: For the review of diagnostic test accuracy, 62 studies of varying methodological quality were included. A meta-analysis of 54 studies comparing SeptiFast with blood culture found that SeptiFast had an estimated summary specificity of 0.86 [95% credible interval (CrI) 0.84 to 0.89] and sensitivity of 0.65 (95% CrI 0.60 to 0.71). Four studies comparing SepsiTest with blood culture found that SepsiTest had an estimated summary specificity of 0.86 (95% CrI 0.78 to 0.92) and sensitivity of 0.48 (95% CrI 0.21 to 0.74), and four studies comparing IRIDICA with blood culture found that IRIDICA had an estimated summary specificity of 0.84 (95% CrI 0.71 to 0.92) and sensitivity of 0.81 (95% CrI 0.69 to 0.90). Owing to the deficiencies in study quality for all interventions, diagnostic accuracy data should be treated with caution. No randomised clinical trial evidence was identified that indicated that any of the tests significantly improved key patient outcomes, such as mortality or duration in an intensive care unit or hospital. Base case 1 estimated that none of the three tests provided a benefit to patients compared with standard practice and thus all tests were dominated. In contrast, in base case 2 it was estimated that all cost per QALY-gained values were below £20,000; the IRIDICA BAC BSI assay had the highest estimated incremental net benefit, but results from base case 2 should be treated with caution as these are not evidence based. Limitations: Robust data to accurately assess the clinical effectiveness and cost-effectiveness of the interventions are currently unavailable. Conclusions: The clinical effectiveness and cost-effectiveness of the interventions cannot be reliably determined with the current evidence base. Appropriate studies, which allow information from the tests to be implemented in clinical practice, are required.

Increasing the power of genome wide association studies in natural populations using repeated measures : evaluation and implementation

1. Genomewide association studies (GWAS) enable detailed dissections of the genetic basis for organisms' ability to adapt to a changing environment. In long-term studies of natural populations, individuals are often marked at one point in their life and then repeatedly recaptured. It is therefore essential that a method for GWAS includes the process of repeated sampling. In a GWAS, the effects of thousands of single-nucleotide polymorphisms (SNPs) need to be fitted and any model development is constrained by the computational requirements. A method is therefore required that can fit a highly hierarchical model and at the same time is computationally fast enough to be useful. 2. Our method fits fixed SNP effects in a linear mixed model that can include both random polygenic effects and permanent environmental effects. In this way, the model can correct for population structure and model repeated measures. The covariance structure of the linear mixed model is first estimated and subsequently used in a generalized least squares setting to fit the SNP effects. The method was evaluated in a simulation study based on observed genotypes from a long-term study of collared flycatchers in Sweden. 3. The method we present here was successful in estimating permanent environmental effects from simulated repeated measures data. Additionally, we found that especially for variable phenotypes having large variation between years, the repeated measurements model has a substantial increase in power compared to a model using average phenotypes as a response. 4. The method is available in the R package RepeatABEL. It increases the power in GWAS having repeated measures, especially for long-term studies of natural populations, and the R implementation is expected to facilitate modelling of longitudinal data for studies of both animal and human populations.

Techno-economic evaluation of building energy refurbishment processes from a life cycle perspective

427 p.

The emergent imperatives from a design-led innovation engagement within the mining industry

This research seeks a better and more detailed understanding of the processes of implementing design-led innovation in the mining equipment technology services (METS) sector, in a context where the traditional approach to manufacturing is being challenged. This longitudinal research specifically investigated the barriers to design-led innovation and opportunities that developed throughout this research, to understand how the organisation and culture of a METS company evolved, in order to progress towards design-led change. The significance of these findings is shown in the combined implementation of design imperatives leading towards design-led change at all business levels of an organisational structure.

Environmental evaluation of cogeneration scenarios in sugar industry

The development of new techniques that allow the analysis and optimization of energy systems bearing in mind environmental issues is indispensable in a world with finite natural resources and growing demand of energy. Among the energy systems that deserve special attention, cogeneration in the sugar industry must be pointed out, because it uses efficiently a common fuel for generation of useful heat and power. Within this frame, thermoeconomical optimization - 2nd Law of Thermodynamics analysis by exergy function and economic evaluation of the thermal system - gradually is taking importance as a powerful tool to assist to the decision making process. Also, the explicit consideration of environmental issues offers a better way to explore trade-offs between different aspects to support the decisions that must be made. In this work it is used the technique of Life Cycle Analysis (LCA) which allows to consider environmental matters as an integral part of the problem, in opposite to most of the environmental approaches that only reduce residuals generation , without taking into account impacts associated to other related processes. On the other hand, the consideration of environmental issues in optimization of energy systems is a novel and promissory contribution in the state of the art of energy optimization and LCA. The system under study is a sugar plant of Tucumán (Argentina) given the particular importance that this industry had inside the regional economy of the Argentinean Northwest. Although cogeneration comes being used a while ago in sugar industry, being the main objective the generation of heat and as secondary objective the electric power generation and mechanic power to cover several needs of working machineries, to the date it is no available a versatile tool that allows to analyze economical feasible alternatives bearing in mind environmental issues. At sugar plants, steam is generated in boilers using as fuel bagasse - cellulosic fiber waste obtained crushing the sugar cane- and it is used to give useful heat and shaft work to the plant, but it can also be used to generate electricity with export opportunities to the electrical network. The great number of process alternatives outlines a serious decision making problem in order to take advantage of the resources. Although the problem turns out to be a mixed non-linear problem (MINLP), the main contribution of this work is the development of a hybrid strategy to evaluate cogeneration alternatives that combines optimization approaches with environmental indicators. This powerful tool for its versatility and robustness to analyze cogeneration systems, will be of great help in the decision making process, because of their easy implementation to analyze the kind of problems presented in the sugar industry.

Evaluation of the utilization of electric vehicles for building energy management in hotels

Governments are working in new policies to slow down total energy consumption and greenhouse gases (GHG) emissions, promoting the deployment of electric vehicles (EVs) in all countries. In order to facilitate this deployment and help to reduce the final costs of their batteries, additional utilization of EVs when those are parked has been proposed. EVs can be used to minimize the total electricity cost of buildings (named vehicle to building applications, V2B). In this paper an economic evaluation of EVs in the Building Energy Management System is shown. The optimal storage capacity and its equivalent number of EVs are determined. This value is then used for determining the optimal charging schedule to be applied to the batteries. From this schedule, the total expected profit is derived for the case of a real hotel in Spain.

Desarrollo de un Procedimiento Basado en Algoritmos de Optimización para el Dimensionado de Absorbedores Puntuales Aplicados a la Conversión de Energía Undimotriz

La energía transportada por el oleaje a través de los océanos (energía undimotriz) se enmarca dentro de las denominadas energías oceánicas. Su aprovechamiento para generar energía eléctrica (o ser aprovechada de alguna otra forma) es una idea reflejada ya hace más de dos siglos en una patente (1799). Desde entonces, y con especial intensidad desde los años 70, ha venido despertando el interés de instituciones ligadas al I+D+i y empresas del sector energético y tecnológico, debido principalmente a la magnitud del recurso disponible. Actualmente se puede considerar al sector en un estado precomercial, con un amplio rango de dispositivos y tecnologías en diferente grado de desarrollo en los que ninguno destaca sobre los otros (ni ha demostrado su viabilidad económica), y sin que se aprecie una tendencia a converger un único dispositivo (o un número reducido de ellos). El recurso energético que se está tratando de aprovechar, pese a compartir la característica de no-controlabilidad con otras fuentes de energía renovable como la eólica o la solar, presenta una variabilidad adicional. De esta manera, diferentes localizaciones, pese a poder presentar recursos de contenido energético similar, presentan oleajes de características muy diferentes en términos de alturas y periodos de oleaje, y en la dispersión estadística de estos valores. Esta variabilidad en el oleaje hace que cobre especial relevancia la adecuación de los dispositivos de aprovechamiento de energía undimotriz (WEC: Wave Energy Converter) a su localización, de cara a mejorar su viabilidad económica. Parece razonable suponer que, en un futuro, el proceso de diseño de un parque de generación undimotriz implique un rediseño (en base a una tecnología conocida) para cada proyecto de implantación en una nueva localización. El objetivo de esta tesis es plantear un procedimiento de dimensionado de una tecnología de aprovechamiento de la energía undimotriz concreta: los absorbedores puntuales. Dicha metodología de diseño se plantea como un problema de optimización matemático, el cual se resuelve utilizando un algoritmo de optimización bioinspirado: evolución diferencial. Este planteamiento permite automatizar la fase previa de dimensionado implementando la metodología en un código de programación. El proceso de diseño de un WEC es un problema de ingería complejo, por lo que no considera factible el planteamiento de un diseño completo mediante un único procedimiento de optimización matemático. En vez de eso, se platea el proceso de diseño en diferentes etapas, de manera que la metodología desarrollada en esta tesis se utilice para obtener las dimensiones básicas de una solución de referencia de WEC, la cual será utilizada como punto de partida para continuar con las etapas posteriores del proceso de diseño. La metodología de dimensionado previo presentada en esta tesis parte de unas condiciones de contorno de diseño definidas previamente, tales como: localización, características del sistema de generación de energía eléctrica (PTO: Power Take-Off), estrategia de extracción de energía eléctrica y concepto concreto de WEC). Utilizando un algoritmo de evolución diferencial multi-objetivo se obtiene un conjunto de soluciones factibles (de acuerdo con una ciertas restricciones técnicas y dimensionales) y óptimas (de acuerdo con una serie de funciones objetivo de pseudo-coste y pseudo-beneficio). Dicho conjunto de soluciones o dimensiones de WEC es utilizado como caso de referencia en las posteriores etapas de diseño. En el documento de la tesis se presentan dos versiones de dicha metodología con dos modelos diferentes de evaluación de las soluciones candidatas. Por un lado, se presenta un modelo en el dominio de la frecuencia que presenta importantes simplificaciones en cuanto al tratamiento del recurso del oleaje. Este procedimiento presenta una menor carga computacional pero una mayor incertidumbre en los resultados, la cual puede traducirse en trabajo adicional en las etapas posteriores del proceso de diseño. Sin embargo, el uso de esta metodología resulta conveniente para realizar análisis paramétricos previos de las condiciones de contorno, tales como la localización seleccionada. Por otro lado, la segunda metodología propuesta utiliza modelos en el domino estocástico, lo que aumenta la carga computacional, pero permite obtener resultados con menos incertidumbre e información estadística muy útil para el proceso de diseño. Por este motivo, esta metodología es más adecuada para su uso en un proceso de dimensionado completo de un WEC. La metodología desarrollada durante la tesis ha sido utilizada en un proyecto industrial de evaluación energética preliminar de una planta de energía undimotriz. En dicho proceso de evaluación, el método de dimensionado previo fue utilizado en una primera etapa, de cara a obtener un conjunto de soluciones factibles de acuerdo con una serie de restricciones técnicas básicas. La selección y refinamiento de la geometría de la solución geométrica de WEC propuesta fue realizada a posteriori (por otros participantes del proyecto) utilizando un modelo detallado en el dominio del tiempo y un modelo de evaluación económica del dispositivo. El uso de esta metodología puede ayudar a reducir las iteraciones manuales y a mejorar los resultados obtenidos en estas últimas etapas del proyecto. ABSTRACT The energy transported by ocean waves (wave energy) is framed within the so-called oceanic energies. Its use to generate electric energy (or desalinate ocean water, etc.) is an idea expressed first time in a patent two centuries ago (1799). Ever since, but specially since the 1970’s, this energy has become interesting for R&D institutions and companies related with the technological and energetic sectors mainly because of the magnitude of available energy. Nowadays the development of this technology can be considered to be in a pre-commercial stage, with a wide range of devices and technologies developed to different degrees but with none standing out nor economically viable. Nor do these technologies seem ready to converge to a single device (or a reduce number of devices). The energy resource to be exploited shares its non-controllability with other renewable energy sources such as wind and solar. However, wave energy presents an additional short-term variability due to its oscillatory nature. Thus, different locations may show waves with similar energy content but different characteristics such as wave height or wave period. This variability in ocean waves makes it very important that the devices for harnessing wave energy (WEC: Wave Energy Converter) fit closely to the characteristics of their location in order to improve their economic viability. It seems reasonable to assume that, in the future, the process of designing a wave power plant will involve a re-design (based on a well-known technology) for each implementation project in any new location. The objective of this PhD thesis is to propose a dimensioning method for a specific wave-energy-harnessing technology: point absorbers. This design methodology is presented as a mathematical optimization problem solved by using an optimization bio-inspired algorithm: differential evolution. This approach allows automating the preliminary dimensioning stage by implementing the methodology in programmed code. The design process of a WEC is a complex engineering problem, so the complete design is not feasible using a single mathematical optimization procedure. Instead, the design process is proposed in different stages, so the methodology developed in this thesis is used for the basic dimensions of a reference solution of the WEC, which would be used as a starting point for the later stages of the design process. The preliminary dimensioning methodology presented in this thesis starts from some previously defined boundary conditions such as: location, power take-off (PTO) characteristic, strategy of energy extraction and specific WEC technology. Using a differential multi-objective evolutionary algorithm produces a set of feasible solutions (according to certain technical and dimensional constraints) and optimal solutions (according to a set of pseudo-cost and pseudo-benefit objective functions). This set of solutions or WEC dimensions are used as a reference case in subsequent stages of design. In the document of this thesis, two versions of this methodology with two different models of evaluation of candidate solutions are presented. On the one hand, a model in the frequency domain that has significant simplifications in the treatment of the wave resource is presented. This method implies a lower computational load but increased uncertainty in the results, which may lead to additional work in the later stages of the design process. However, use of this methodology is useful in order to perform previous parametric analysis of boundary conditions such as the selected location. On the other hand, the second method uses stochastic models, increasing the computational load, but providing results with smaller uncertainty and very useful statistical information for the design process. Therefore, this method is more suitable to be used in a detail design process for full dimensioning of the WEC. The methodology developed throughout the thesis has been used in an industrial project for preliminary energetic assessment of a wave energy power plant. In this assessment process, the method of previous dimensioning was used in the first stage, in order to obtain a set of feasible solutions according to a set of basic technical constraints. The geometry of the WEC was refined and selected subsequently (by other project participants) using a detailed model in the time domain and a model of economic evaluation of the device. Using this methodology can help to reduce the number of design iterations and to improve the results obtained in the last stages of the project.

Incorporating an economic model in the health impact assessment approach

The current policy decision making in Australia regarding non-health public investments (for example, transport/housing/social welfare programmes) does not quantify health benefits and costs systematically. To address this knowledge gap, this study proposes an economic model for quantifying health impacts of public policies in terms of dollar value. The intention is to enable policy-makers in conducting economic evaluation of health effects of non-health policies and in implementing policies those reduce health inequalities as well as enhance positive health gains of the target population. Health Impact Assessment (HIA) provides an appropriate framework for this study since HIA assesses the beneficial and adverse effects of a programme/policy on public health and on health inequalities through the distribution of those effects. However, HIA usually tries to influence the decision making process using its scientific findings, mostly epidemiological and toxicological evidence. In reality, this evidence can not establish causal links between policy and health impacts since it can not explain how an individual or a community reacts to changing circumstances. The proposed economic model addresses this health-policy linkage using a consumer choice approach that can explain changes in group and individual behaviour in a given economic set up. The economic model suggested in this paper links epidemiological findings with economic analysis to estimate the health costs and benefits of public investment policies. That is, estimating dollar impacts when health status of the exposed population group changes by public programmes – for example, transport initiatives to reduce congestion by building new roads/ highways/ tunnels etc. or by imposing congestion taxes. For policy evaluation purposes, the model is incorporated in the HIA framework by establishing association among identified factors, which drive changes in the behaviour of target population group and in turn, in the health outcomes. The economic variables identified to estimate the health inequality and health costs are levels of income, unemployment, education, age groups, disadvantaged population groups, mortality/morbidity etc. However, though the model validation using case studies and/or available database from Australian non-health policy (say, transport) arena is in the future tasks agenda, it is beyond the scope of this current paper.

Evaluation of the cost-effectiveness of strategies claiming to reduce the risk of surgical site infections following primary total hip arthroplasty

Background Total hip arthroplasty (THA) is a commonly performed procedure and numbers are increasing with ageing populations. One of the most serious complications in THA are surgical site infections (SSIs), caused by pathogens entering the wound during the procedure. SSIs are associated with a substantial burden for health services, increased mortality and reduced functional outcomes in patients. Numerous approaches to preventing these infections exist but there is no gold standard in practice and the cost-effectiveness of alternate strategies is largely unknown. Objectives The aim of this project was to evaluate the cost-effectiveness of strategies claiming to reduce deep surgical site infections following total hip arthroplasty in Australia. The objectives were: 1. Identification of competing strategies or combinations of strategies that are clinically relevant to the control of SSI related to hip arthroplasty 2. Evidence synthesis and pooling of results to assess the volume and quality of evidence claiming to reduce the risk of SSI following total hip arthroplasty 3. Construction of an economic decision model incorporating cost and health outcomes for each of the identified strategies 4. Quantification of the effect of uncertainty in the model 5. Assessment of the value of perfect information among model parameters to inform future data collection Methods The literature relating to SSI in THA was reviewed, in particular to establish definitions of these concepts, understand mechanisms of aetiology and microbiology, risk factors, diagnosis and consequences as well as to give an overview of existing infection prevention measures. Published economic evaluations on this topic were also reviewed and limitations for Australian decision-makers identified. A Markov state-transition model was developed for the Australian context and subsequently validated by clinicians. The model was designed to capture key events related to deep SSI occurring within the first 12 months following primary THA. Relevant infection prevention measures were selected by reviewing clinical guideline recommendations combined with expert elicitation. Strategies selected for evaluation were the routine use of pre-operative antibiotic prophylaxis (AP) versus no use of antibiotic prophylaxis (No AP) or in combination with antibiotic-impregnated cement (AP & ABC) or laminar air operating rooms (AP & LOR). The best available evidence for clinical effect size and utility parameters was harvested from the medical literature using reproducible methods. Queensland hospital data were extracted to inform patients’ transitions between model health states and related costs captured in assigned treatment codes. Costs related to infection prevention were derived from reliable hospital records and expert opinion. Uncertainty of model input parameters was explored in probabilistic sensitivity analyses and scenario analyses and the value of perfect information was estimated. Results The cost-effectiveness analysis was performed from a health services perspective using a hypothetical cohort of 30,000 THA patients aged 65 years. The baseline rate of deep SSI was 0.96% within one year of a primary THA. The routine use of antibiotic prophylaxis (AP) was highly cost-effective and resulted in cost savings of over $1.6m whilst generating an extra 163 QALYs (without consideration of uncertainty). Deterministic and probabilistic analysis (considering uncertainty) identified antibiotic prophylaxis combined with antibiotic-impregnated cement (AP & ABC) to be the most cost-effective strategy. Using AP & ABC generated the highest net monetary benefit (NMB) and an incremental $3.1m NMB compared to only using antibiotic prophylaxis. There was a very low error probability that this strategy might not have the largest NMB (<5%). Not using antibiotic prophylaxis (No AP) or using both antibiotic prophylaxis combined with laminar air operating rooms (AP & LOR) resulted in worse health outcomes and higher costs. Sensitivity analyses showed that the model was sensitive to the initial cohort starting age and the additional costs of ABC but the best strategy did not change, even for extreme values. The cost-effectiveness improved for a higher proportion of cemented primary THAs and higher baseline rates of deep SSI. The value of perfect information indicated that no additional research is required to support the model conclusions. Conclusions Preventing deep SSI with antibiotic prophylaxis and antibiotic-impregnated cement has shown to improve health outcomes among hospitalised patients, save lives and enhance resource allocation. By implementing a more beneficial infection control strategy, scarce health care resources can be used more efficiently to the benefit of all members of society. The results of this project provide Australian policy makers with key information about how to efficiently manage risks of infection in THA.