Background: Presenteeism is an economic concept that is difficult to identify, measure, and value. Rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are three chronic auto-immune conditions that increase levels of presenteeism. Workplace interventions (WPIs) help individuals to manage their health condition at work. Existing methods used to quantify the impact of presenteeism are unable to adequately inform the employer of the productive benefits of WPIs. The overall aim of this thesis was to appraise current methods used to quantify presenteeism and to develop methods to value the impact of presenteeism suitable for use in economic evaluations (EE) of WPIs. Methods: Two systematic reviews were conducted: 1) to assess the extent to which self-report measure of presenteeism were underpinned by economic theory; and 2) to explore if, and how, productivity was quantified and included in EE of WPIs for musculoskeletal conditions (MSDs). Thematic analysis methods were used to analyse qualitative data collected from working individuals with RA, AS or PsA (n=22) that explored the extent to which measures of health status (EQ5D; SF6D) and capability (ICECAP-A) capture the impact on ability to work caused by RA, AS or PsA. Econometric methods were used to specify prediction models that included measures of health status, capability and presenteeism, using a sample of 542 working people with RA and AS. Results The first systematic review identified 24 self-report measures of presenteeism; all, except one measure were not underpinned by economic theory. The second systematic review identified 20 EE of WPIs for MSDs. Absenteeism was included in all studies (n=20); however, presenteeism was included in only four. The qualitative data confirmed measures of health status and capability had the ability to capture those aspects of RA, AS and PsA that impact an individual’s ability to work. The best performing prediction model used an OLS specification including SF6D, age and gender to predict presenteeism measured by the WPAI. Conclusion: The results suggest that HRQoL measures, specifically the SF6D, can be used to capture and predict levels of presenteeism caused by RA, AS and PsA.

The focus of this thesis is on the application of decision models to the economic evaluation of health care technologies. The primary objective addresses the correct choice of modelling technique, as the attributes of the chosen technique could have a significant impact on the process, as well as the results, of an evaluation. Separate decision models, a Markov process and a discrete event simulation (DES) model are applied to a case study evaluation comparing alternative adjuvant therapies for early breast cancer. The case study models are built and analysed as stochastic models: whereby probability distributions are specified to represent the uncertainty about the true values of the model input parameters. Three secondary objectives are also specified. Firstly, the empirical application of the alternative decision models requires the specification of a 'modelling process' that is not well defined in the health economics literature. Secondly, a comparison of alternative methods for specifying probability distributions to describe the uncertainty in the model's input parameters is undertaken. The final secondary objective covers the application of methods for valuing the collection of additional information to inform the resource allocation decision. The empirical application of the two relevant modelling techniques clarifies the potential advantages derived from the increased flexibility provided by DES over Markov models. The thesis concludes that the use of DES should be strongly considered if either of the following issues appear relevant: model parameters are a function of the time spent in particular states, or the data describing the timing of events are not in the form of transition probabilities. The full description of the modelling process provides a resource for health economists wanting to use decision models. No definitive process is established, however, as there exist competing methods for various stages of the modelling process. The main conclusion from the comparison of methods for specifying probability distributions around the input parameters is that the theoretically specified distributions are most likely to provide a common baseline for comparisons between evaluations. The central question that remains to be addressed is which method is the most theoretically correct? The application of a Vol analysis provides useful insights into the methods employed and leads to the identification of particular methodological issues requiring future research in this area.

Factorial randomised controlled trials (RCTs) evaluate two or more interventions simultaneously, enabling assessment of interactions between treatments. This thesis presents literature reviews, methodological reviews, simulation studies and applied case studies that explore methods for assessing cost-effectiveness based on factorial RCTs. My systematic review suggests that factorial RCTs account for around 3% of trial-based economic evaluations, although there is currently no guidance or methodological work indicating the most appropriate methods. Around 40% of published studies assumed no interaction between treatments and many were poorly-reported. Various mechanisms are likely to produce large interactions within economic endpoints such as costs, quality-adjusted life-years (QALYs) and net benefits. Failing to take account of interactions can introduce bias and prevent efficient allocation of healthcare resources. I developed the opportunity cost of ignoring interactions as a measure of the implications of this bias. However, allowing for small, chance interactions is inefficient, potentially leading to over-investment in research if trial-based evaluations are used to inform decisions about subsequent research. Nonetheless, analyses on simulated trial data suggest that the opportunity cost of adopting a treatment that will not maximise health gains from the healthcare budget is minimised by including all interactions regardless of magnitude or statistical significance. Different approaches for conducting economic evaluations of factorial RCTs (including regression techniques, extrapolation using patient-level simulation, and considering different components of net benefit separately) are evaluated within three applied studies, including both full and partial factorials with 2x2 and 2x2x2 designs. I demonstrate that within both trial-based and model-based economic evaluation, efficient allocation of healthcare resources requires consideration of interactions between treatments, and joint decisions about interacting treatments based on incremental cost-effectiveness evaluated “inside-the-table” on a natural scale. I make recommendations for the design, analysis and reporting of factorial trial-based economic evaluations based on the results of this thesis.

L’endométriose est devenue un problème de santé important du fait de sa prévalence (près d'une femme sur dix), des multiples complications engendrant un coût notable pour la société. Le coût de la maladie est aussi le coût de ses conséquences : traitements de l'infertilité mais aussi perte de productivité des femmes et de leur entourage, et ne sont encore pas clairement identifiés. Ces conséquences sont d'autant plus importantes qu'il existe un retard diagnostique (délai diagnostique moyen supérieur à 6 ans), or plus celui-ci est long, plus la maladie est découverte à un stade sévère et les patientes à un stade sévère ont davantage de complications, nécessitent une prise en charge plus lourde et plus coûteuse, ce à quoi il faut ajouter l’errance médicale et les traitements inadéquats. La volonté d'une meilleure connaissance et reconnaissance de la maladie a abouti à des actions du monde associatif, relayées. L’évaluation économique des prises en charge, à partir d’études de cas, est un outil important d’optimisation les choix pour améliorer le sort des patientes. Cette thèse se décompose en cinq chapitres : dans le premier chapitre nous nous intéressons aux aspects théoriques de l’évaluation économique en santé et méthodologiques de l’évaluation de coût social de la maladie. Le second chapitre traite de la maladie de l’endométriose en détails et de la méthodologie adoptée dans les études de cas qui sont présentés dans les chapitres trois, quatre et cinq. Le troisième chapitre présente une étude multicentrique sur les coûts et la qualité de vie des femmes souffrant des symptômes associés à l’endométriose en Europe. Le quatrième chapitre étudie prospectivement le coût sociétal de l’endométriose en France. Enfin, le cinquième chapitre est consacré à une étude rétrospective sur la persistance des coûts associés à l’endométriose dans le temps.Cette thèse montre l’importance de l’endométriose sur le système de soins en termes de coût (€ 10,6 milliards par an en France) et illustre la nécessité d'améliorer la prise en charge en direction d’interventions plus précoces et de recours plus rapides à des centres de compétence. A une efficacité constante, il est possible d’estimer la réduction de coûts liés à une politique plus productive. Améliorer la qualité des diagnostics et des prises en charge permette aussi de maximiser l’utilité affectée aux femmes en termes de qualité de vie. / Endometriosis becomes an increasingly major health problem because of its prevalence (nearly one woman out of ten), multiple complications leading to a significant cost on the society. The cost of the disease is also the cost of its consequences which are the treatments of infertility and also the loss of productivity of women and their entourage that are not yet clearly identified. These consequences are more important when there is a delay in the diagnosis (the average delay of diagnosis is longer than 6 years), but the longer the period of diagnosis is, the more the disease will be detected in a more severe stage. The patients at this severe stage have more complications, requiring more expensive care, to which must be added the medical wandering and the inadequate treatment.The desire for a better knowledge and recognition of the disease has resulted in associative actions all around the world. The economic evaluation of health care, based on case studies, is an important tool to optimize the choices to improve the situation of the patients. This thesis is divided into five chapters : the first chapter attempts to elucidate framework of health economic evaluation and the evaluation of the social cost of illness. The second chapter focuses on the endometriosis disease in detail and the methodology used in the case studies presented in Chapter Three, Four and Five. The third chapter presents a multicenter study on the costs and quality of life of women suffering from symptoms associated with endometriosis in Europe. The fourth chapter is concerned with a prospective study on the societal cost of endometriosis in France. The fifth chapter is devoted to a retrospective study on the persistence of costs associated with endometriosis over time.This thesis shows the importance of endometriosis on the health care system in terms of cost (€ 10.6 billion per year) and illustrates the need to improve care in favor of earlier interventions and an earlier refer to competence centers. With constant efficiency, it is possible to estimate the cost reduction linked to a more productive policy. Improving the quality of diagnosis and management also maximizes the affected usefulness of women in terms of quality of life.