A reassessment of the cost-effectiveness of hormone replacement therapy in Sweden – results based on the Women’s Health Initiative randomised controlled trial

The cost-effectiveness of hormone replacement therapy (HRT) based on a societal perspective is reassessed based on new medical evidence found in the Women’s Health Initiative (WHI). Within a model framework using an individual state transition model the cost-effectiveness of 50-60 year old women with menopausal symptoms is assessed in Sweden. The Markov model has a 50 year time horizon divided into a cycle length of 1 year. The model consists of the following disease states: Coronary Heart Disease (CHD), Stroke, Venous thromboembolic events, breast cancer, colorectal cancer, hip fracture, vertebral fracture and wrist fracture. An intervention is modelled by its impact on the disease risks during and after the cessation of therapy. The model calculates costs and quality adjusted life years (QALYs) with and without intervention. The resulting cost per gained QALY is compared to the value of a gained QALY, which is set to SEK 600 000. The model requires data on clinical effects, risks, mortality rates, quality of life weights and costs valid for Sweden. The cost-effectiveness ratios are estimated at about SEK 10 000, which is far below the value of a gained QALY. Conditional on that HRT increases the quality of life weight more than 0.013 the therapy is cost-effective. In conclusion, given the new evidence in WHI, there is still a high probability that HRT is a cost-effective strategy for women with menopausal symptoms.cost-effectiveness analysis; hormone replacement therapy; Markov model

Cost-Effectiveness of Alendronate in the Treatment of Osteoporosis in Denmark - An Economic Evaluation Based on the Fracture Intervention Trial

Background: The Fracture Intervention Trial (FIT) showed that the bisphosphonate alendronate reduces the risk of fractures in women with low bone mass in the United States. Objective: To estimate the cost-effectiveness (cost per life-year gained and cost per quality-adjusted life-year, QALY, gained) of treating osteoporotic women in Denmark with alendronate, compared with no treatment. Design: A Markov model earlier used in the economic evaluation for Sweden was adapted using epidemiological and cost data for Denmark. In the base-case alendronate was assumed to have a fracture-risk reducing effect for ten years; a treatment duration period of 5 years followed by a 5-year period where the effect declined linearly to zero. Results: Treating a 71-year old (the mean age in the vertebral arm of the FIT) osteoporotic woman with one prior vertebral fracture with alendronate was found to be associated with a cost of DKK 52,311 per QALY gained. The cost-effectiveness ratio when treating a 69-year old woman with low bone mass and without previous vertebral fractures was higher (DKK 205,816) but still within the limits of what can be considered good value for money. Conclusions: The results of this study indicate that treatment with alendronate in Denmark is cost-effective, provided the treatment is targeted towards high-risk patients corresponding to the patient groups in the FIT study.osteoporosis; cost-effectiveness; quality of life; Markov models; acceptability curve

Cost-effectiveness of alendronate in the treatment of osteoporois in Denmark: An economic evaluation based on the fracture intervention trial

Background: The Fracture Intervention Trial (FIT) showed that the bisphosphonate alendronate reduces the risk of fractures in women with low bone mass in the United States. Objective: To estimate the cost-effectiveness (cost per life-year gained and cost per quality-adjusted life-year, QALY, gained) of treating osteoporotic women in Denmark with alendronate, compared with no treatment. Design: A Markov model earlier used in the economic evaluation for Sweden was adapted using epidemiological and cost data for Denmark. In the base-case alendronate was assumed to have a fracture-risk reducing effect for ten years; a treatment duration period of 5 years followed by a 5-year period where the effect declined linearly to zero. Results: Treating a 71-year old (the mean age in the vertebral arm of the FIT) osteoporotic woman with one prior vertebral fracture with alendronate was found to be associated with a cost of DKK 52,311 per QALY gained. The cost-effectiveness ratio when treating a 69-year old woman with low bone mass and without previous vertebral fractures was higher (DKK 205,816) but still within the limits of what can be considered good value for money. Conclusions: The results of this study indicate that treatment with alendronate in Denmark is cost-effective, provided the treatment is targeted towards high-risk patients corresponding to the patient groups in the FIT study

A reassessment of the cost-effectiveness of hormone replacement therapy in Sweden: Results based on the Women's Health Initiative randomised controlled trial

The cost-effectiveness of hormone replacement therapy (HRT) based on a societal perspective is reassessed based on new medical evidence found in the Women's Health Initiative (WHI). Within a model framework using an individual state transition model the cost-effectiveness of 50-60 year old women with menopausal symptoms is assessed in Sweden. The Markov model has a 50 year time horizon divided into a cycle length of 1 year. The model consists of the following disease states: Coronary Heart Disease (CHD), Stroke, Venous thromboembolic events, breast cancer, colorectal cancer, hip fracture, vertebral fracture and wrist fracture. An intervention is modelled by its impact on the disease risks during and after the cessation of therapy. The model calculates costs and quality adjusted life years (QALYs) with and without intervention. The resulting cost per gained QALY is compared to the value of a gained QALY, which is set to SEK 600 000. The model requires data on clinical effects, risks, mortality rates, quality of life weights and costs valid for Sweden. The cost-effectiveness ratios are estimated at about SEK 10 000, which is far below the value of a gained QALY. Conditional on that HRT increases the quality of life weight more than 0.013 the therapy is cost-effective. In conclusion, given the new evidence in WHI, there is still a high probability that HRT is a cost-effective strategy for women with menopausal symptoms

Predicting survival in cost-effectiveness analyses based on clinical trials

This paper deals with the question how to model health effects after the cessation of a randomised controlled trial (RCT). Using clinical trial data on severe congestive heart failure patients we illustrate how survival beyond the cessation of a RCT can be predicted based on parametric survival models. In the analysis we compare the predicted survival and the resulting incremental cost-effectiveness ratio (ICER) of different survival models with the actual survival/ICER. Our main finding is that the results are highly sensitive to the choice of survival model and that extensive sensitivity analysis in the CE analysis is required. We also show that adding the true survival after the end of the clinical study will underestimate the true variability

Costs and quality of life associated with osteoporosis related fractures - Results from a Swedish survey

There are few studies investigating the consequences of osteoporotic (low bone density) fractures in terms of costs and health outcomes. The purpose of this Swedish pilot study is to assess the costs and quality of life related to fractures of the hip, spine, wrist and shoulder and further to identify important cost items that should be included in future studies in this area. Data were collected using a questionnaire administered by a nurse at Malmö University Hospital. The costs are collected based on a societal perspective and include both direct and indirect costs. Health effects were measured by the EuroQol questionnaire, rating scale method and the SF-36. The total costs varied between SEK 23 000 for a wrist fracture and SEK 63 000 for a hip fracture. Although that the response rate is low the cost and quality of life related to hip fracture are close to the results presented in other studies. The major new finding is that spine fractures are associated with higher costs and lower quality of life than previously assumed. Future studies must include a sufficient number of patients in order to obtain reliable cost and health effect estimates after osteoporotic fractures in general and after spine fractures in particular. Such studies will provide important inputs for health economic evaluations assessing the cost-effectiveness of the treatment and prevention of osteoporosis.costs; fracture; osteoporosis; quality of life

The risk and burden of vertebral fractures in Sweden

The aim of this study was to determine the risk and burden of vertebral fractures judged as those coming to clinical attention and as morphometric fractures. Incidence and utility loss were computed from data from Malmo, Sweden. Clinical fractures accounted for 23% of all vertebral deformities in women and for 42% in men. The average 10-year fracture probability for morphometric fractures increased with age in men from 2.9% at the age of 50 years (7.2% in women) to 8.4 at the age of 85 years (26.7% in women). As expected, probabilities increased with decreasing T-score for hip BMD. Cumulative utility loss from a clinical vertebral fracture was substantial and was 50-62% of that due to a hip fracture depending on age. When incidence of fractures in the population was weighted by disutility, all spine fractures accounted for more morbidity than hip fracture up to the age of 75 years. We conclude that vertebral fractures have a major personal and societal impact that needs to be recognised in algorithms for assessment of risk and in health economic strategies for osteoporosis

Flavour-changing neutral currents in top quark decays to Higgs bosons in a two-Higgs-doublet model

In this thesis top quark decays to a charm quark and a (CP even) Higgs boson are investigated in a general two-Higgs-doublet model (2HDM) allowing flavour-changing neutral currents. The theory behind 2HDMs is introduced and the specific choice of 2HDM is put to test under theoretical constraints that require the potential in the Lagrangian density of the model to satisfy vacuum stability, tree-level unitarity and perturbativity. The parameter space of the specific 2HDM is also restricted by recent data from the LHC on the signal strengths of the discovered Higgs boson in the photon-photon and ZZ decay channels. In addition, constraints from a recent measurement of Br(t -> c phi) are taken into account. This puts restrictions on the values of the off-diagonal Yukawa coupling appearing in the t -> c phi decay. It is found that the commonly used Cheng-Sher ansatz regarding the order of magnitude of this flavour-changing neutral coupling is not severely constrained by the measurement.Först lite terminologi: Standardmodellen är en kvantfältteori. Sådana beskriver störningar i fält och dessa kallas för partiklar. Tänk dig svallvågorna som följer på ytan i ett badkar vari en sten släppts, fast i tre dimensioner istället för två, det är ett fält. Varje elementär partikel är en störning i ett sådant tillhörande fält (eller "kvantum" varav namnet kvantfält). Fälten kommer i två sorter: fermionska och bosonska. De förstnämnda fälten beskriver all materia vi känner till, samt lite till som kan skapas i acceleratorer men som inte är något vi stöter på till vardags. Bosonfält beskriver hur fermionfält interagerar med varandra, hur störningar i ett fält kan orsaka störningar i ett annat. Ett bekant bosonfält är det elektromagnetiska, som även är känt som ljus. Störningar i detta fält kallas för fotoner. Higgsfältet framlades som ett förslag på 60-talet för att lösa problemet med varför vissa (både fermion och boson) partiklar har massa. Cirka 50 år senare hittades en Higgsboson (störning i det bosonska Higgsfältet) med rätt egenskaper såsom förutsagda av Standardmodellen. Teorin beskriver massans ursprung på ett liknande sätt som andra interaktioner och sätter dem nästan på jämn fot. Olika fält interagerar med Higgsfältet olika mycket och detta gör att partiklarna får olika massa. De blir "tröga", som fysiker säger om partiklar med massa, av att färdas genom Higgssoppan. Att ha massa är nämligen ett annat sätt att säga "att inte färdas i ljusets hastighet". Fysiker tycker att enkelt är snyggt (och praktiskt), därför har man i Standardmodellen antagit att det bara finns ett Higgsfält som ger upphov till alla massor. Det finns dock stora anledningar att låta fler Higgsfält sköta jobbet. I den enklaste utvidgningen av teorin inför man istället två Higgsdubletter som trots namnet introducerar fem nya partiklar i teorin. Många vidare teorier som kan förklara varför laddning är kvantiserad och mörk materia (med trevliga ord som supersymmetri och storförenade teorier) kräver minst detta för att fungera. I denna uppsats har jag undersökt en konsekvens av detta "första steg mot en allmännare teori". En ny teori ska helst förklara allt som Standardmodellen förklarar och lite till, så att man kan särskilja dem med experiment. En sådan skiljelinje visar sig vid sönderfall av en toppkvark till en charmkvark\footnote{Ytterligare några fermioner: De kommer i flera smaker. Smak är faktiskt den tekniska termen. Ett topp- till charm sönderfall kallas för en smakändrande (neutral) ström.} och en (valfri)\footnote{Men elektriskt neutral, om man ska vara petig.} Higgsboson. Detta sönderfall sker nästan aldrig enligt Standardmodellen men kan göra det i två-Higgs-dublett modeller. Jag har undersökt hur vanligt förekommande detta sönderfall får och kan vara, enligt teoretiska och experimentella begränsningar. Sönderfallet är speciellt för just en viss sorts två-Higgs-dublett modell (kallad 2HDM-\RNum{3}), i alla andra varianter är det väldigt sällsynt. Om det går att hitta en signal för detta sönderfall, så skulle alltså alla andra sorters två-Higgs-dublett modeller och de teorier som bygger vidare på dessa, visa sig vara felaktiga. Många flugor i en smäll, med andra ord

Structural Modelling of Credit Spreads on the European Bond Market: An Empirical Study

This thesis empirically tests the explanatory power of structural models on the European corporate bond market. Using new evaluation methods, including LASSO and gradient boosting regression, we can provide an in-depth assessment of the models’ shortcomings. With these tools we show that the structural models tend to systematically overstate or understate the spread due to an oversensitivity to leverage ratio and asset volatility. We introduce a novel extension to the Black Cox model in order to mitigate the observed weaknesses. Our extension is calibrated to match historical default probabilities with an additional baseline default risk component attributable to all firms. This approach manages to increase the R-squared from 39 % to 47 % and at the same time reduce the residual dependencies of leverage ratio and asset volatility.In a growing global corporate bond market, insights and understanding of the markets pricing mechanisms becomes increasingly important to investors. While previous research on credit risk has mainly focused on the American bond market, European bonds remain rather unexplored in academia. In this article, we investigate the explanatory power of a family of credit risk models - called structural models - applied on the European corporate bond market. Using new methods of model evaluation on a dataset of over 50 000 observations, we derive a novel extension to existing models yielding improved explanatory power compared to the base case. WHAT IS A BOND? Companies in need of financing can besides from raising capital through bank loans, issue bonds to investors. A bond is a contractual agreement, in which a firm promises investors to receive future payments in exchange for an upfront payment at the date of issue. From the issuers point of view, a bond can finance projects and activities that are too large and risky for a single bank to fund alone. Instead capital and risk is pooled among several investors owning a smaller share of the debt. From the investors perspective, the upside of a bond investment is that the returns of promised future cash flows often exceed the interest rate of a risk-free investment. Due to the complex nature of corporate debt, the translation of bond characteristics to market price is not straightforward. Research has therefore historically focused on trying to describe prices on the market through different theoretically founded models. STRUCTURAL MODELS AND BEYOND The structural approach is by many regarded as the most successful framework thanks to its intuitive interpretation of credit risk. The general structure of the structural framework assumes that corporate debt is valued as a contingent claim depending on the total value of the issuing firm, which evolves as a stochastic process. The analogy to option pricing derives from the fact that debt holders are prioritised higher than equity holders in terms of repayment. Imagine a firm active only during one year and liquidated at the end of that year. If the firm remains solvent until liquidation, debt holders are repaid the nominal amount of debt. However, if the firm is defaulted at the year-end, debt holders are repaid the residual firm value after bankruptcy costs. Within the structural framework we have mainly fo cused on the Black Cox model, which allows the issuing firm to default not only when the bond contract is due, but at any time during the active period of the bond. Default occurs in the model if the firms value falls below a default boundary defined as a constant multiplied by the issued amount of debt. Boundary = d·(Tot. Debt), d ∈ (0,1] Using new evaluation methods, including modern machine learning algorithms, we show that the Black Cox model tends to systematically overstate or understate the bond price due to an oversensitivity with respect to the input parameters leverage ratio and asset volatility. Based on our findings we introduce the intercept calibrated leverage ratio model (ICLR) in which the default boundary is modified slightly as Boundary = m + d·(Tot. Debt), m ∈ (0,1], d ∈ (0,1] The essence of this structure is that we introduce a common risk component for all firms. This modification is in many ways intuitive since an IT-company with 20 % leverage ratio may have bonds traded at higher spreads than a highly levered real-estate company. Exploring the models oversensitivity to asset volatility we find - rather surprisingly - that only 13 % of the instantaneous asset volatility is attributable to the valuation of bond prices. As a consequence, the model performs better when assuming a constant asset volatility over time. With the original Black Cox model as base case, we improve the R-squared from 39 % to 47 % when implementing ICLR and constant asset volatility. The residuals from our final model also show decreased dependence of leverage ratio and asset volatility. However, these input parameters along with the risk-free interest rate and payout ratio remain influential. This result hints that the structural models are not fully capable of absorbing the default risk components of European corporate bond prices. Other remaining dependencies are found to originate from the bid ask spread, the size of the bond issue in relation to total debt, the US federal swap rate and the market capitalisation as a few examples. Ultimately, the dependency analysis show that other factors which are not considered in the structural models affect price levels on the European bond market. These factors are considered as non default components, which rather relate to liquidity, political, inflation and supply risks. Further research should therefore focus on finding theoretically backed models of disaggregating default and nondefault components in the observed yield spreads. This will result in other model evaluation frameworks, which can better assess and compare the explanatory ability of structural models