Maria Kubin

Epidemiology of erectile dysfunction

This review of the current epidemiological literature on erectile dysfunction (ED) suggests that approximately 5–20% of men have moderate-to-severe ED. Different definitions of ED, age distributions and concomitant medical conditions, as well as methodological differences, may explain much of the variance in reported prevalence rates. Various chronic disorders are associated with elevated rates of ED including depression, diabetes, and cardiovascular and neurological diseases. Such disorders are more common in the elderly, which may partially explain the elevated prevalence of ED in men over 60 y of age. Currently, up to 70% of men with ED are not treated. However, so many men experience considerable distress from their condition, that the increasing awareness of ED as well as the availability of noninvasive treatments may result in a greater proportion of patients seeking treatment, and eventually regaining satisfaction with their sex life.

German Recommendations on Health Economic Evaluation: Third and Updated Version of the Hanover Consensus

The second revision of the German Guidelines for Health Economic Evaluation provides a structured, broadly consented, scientific contri- bution to the ongoing methodological discus- sion in Germany. It provides the reader with guidance on different issues, i.e. study design, study perspective, study forms, selection of al- ternatives within a study, validity and data sources, cost assessment, assessment of out- comes, time horizon, discounting, sensitivity analyses, presentation and discussion of out- comes as well as publication of study results.

A Comparative Review of Health-Related Quality-of-Life Measures for Use in HIV/AIDS Clinical Trials

With the advent of highly active antiretroviral therapy (HAART), HIV-infected patients are living longer and are concerned not only with a treatment’s ability to extend their life but also with the quality of the life they are able to lead. Regulatory authorities are also paying closer attention to the use of health-related quality-of-life (HR-QOL) measures in clinical trials and to the subsequent claims that are made based on the results. This paper reviews existing HR-QOL measures reported in the HIV/AIDS literature since 1990 and identifies those most worthy of consideration for use in future clinical trials.A comprehensive review following predefined selection criteria was conducted. Generic and HIV-targeted measures were assessed for content and practicality for the clinical trial setting. The generic measures were additionally reviewed for the ability to produce preference-based index scores and for the existence of normative general population data. Three generic and six HIV-targeted measures met these selection criteria and were then assessed more fully in terms of their development (HIV-targeted measures), psychometric properties and appropriateness for use in clinical trials.It was determined that each of the selected generic measures (i.e. Medical Outcomes Study [MOS] 36-Item Short Form Survey Instrument [SF-36], EQ-5D, Health Utilities Index [HUI]) could serve as a useful adjunct to an HIV-targeted measure in a trial. The Functional Assessment of HIV Infection (FAHI) and MOS-HIV health survey were deemed the two most appropriate HIV-targeted measures. Each of the measures can be self-administered in ≤10 minutes and there was ample evidence of their excellent psychometric properties. However, they would not be optimal in all HIV-infected subgroups (e.g. treatment naive vs advanced; adolescents vs older adults) targeted for clinical trial interventions.Although there is no one best HR-QOL measure for use in HIV/AIDS clinical trials, based on our review criteria we identified three generic and two HIVtargeted candidate measures. However, these measures have their limitations and it is clear that greater consensus needs to develop regarding more effective and efficient approaches to HR-QOL measurement in HIV/AIDS clinical trials. Along with the increasingly complex HR-QOL measurement task resulting from changes in the HIV-infected population and shifts in the HR-QOL burden associated with HIV infection and its treatment over the past 25 years, it is increasingly important that HR-QOL outcomes become viable endpoints in HIV/AIDS clinical trials.

A Multi-Country Economic Evaluation of Low-Dose Aspirin in the Primary Prevention of Cardiovascular Disease

BackgroundLow-dose aspirin (acetylsalicylic acid) is standard care in patients with a history of cardiovascular disease (CVD). The use of low-dose aspirin in primary prevention is not yet fully established, although meta-analyses and US and European guidelines support its use in people at increased risk of CVD. The primary objective of this study was to assess the economic consequences of the use of low-dose aspirin in the primary prevention of CVD in four European countries (UK, Germany, Spain and Italy).MethodsBased on results (benefits and harms) reported in meta-analyses, a state-transition model was developed to predict the cost effectiveness of low-dose aspirin in the primary prevention of CVD. The model consists of five health states: no history of CVD, history of stroke, history of myocardial infarction (MI), history of stroke and MI, and death. A 10-year time horizon and 1-year cycles were used. Secondary prevention data were derived from the aspirin arm of the CAPRIE (Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events) study.Direct costs from the public healthcare payer’s perspective were used (€, 2003 values). Effects were expressed in life-years (LY) and QALYs gained. Quality weights were obtained from published data.Country-specific discounting was applied on effects and costs (3.5% for the UK, 5% for Germany and 3% for Spain and Italy). Univariate sensitivity analysis and Monte Carlo simulation were performed to assess uncertainty in the results.ResultsFor patients with an annual risk of coronary heart disease (CHD) of 1.5%, the model resulted in 10-year savings with low-dose aspirin of on average €201 (95% CI 81, 331), €281 (95% CI 141, 422), €797 (95% CI 301, 1331) and €427 (95% CI 122, 731) per patient in the UK, Germany, Spain and Italy, respectively. Average total cost was almost 3- to 4-fold higher in Spain and Italy than in the UK and Germany. Savings (non-significant) start in the first year of treatment in all countries.Sensitivity analyses on cost of complications, utility, discounting, stroke rate and gastrointestinal bleeding rate showed the robustness of the results. From an annual risk of CHD of 0.236% for the UK, 0.324% for Germany, 0.244% for Spain and 0.560% for Italy, low-dose aspirin was cost saving compared with placebo. Monte Carlo analysis showed aspirin dominance in about 97% of cases for the three studied annual risks of CHD (0.6%, 1.0% and 1.5%) in the UK, Germany and Spain. In Italy, aspirin dominance in >95% of cases was seen at annual risks of 1% and 1.5%.ConclusionsAdministering low-dose aspirin to patients with an annual risk of CHD of ≥1% appears to be significantly cost saving from the healthcare payer’s perspective in all countries analysed. Sensitivity analyses (CHD risk and bleedings) suggested the results were robust.

Which patients should receive aspirin for primary prevention of cardiovascular disease? An economic evaluation

Low‐dose aspirin is a standard care for secondary prevention of cardiovascular disease (CVD). Its use in primary prevention is less widely accepted, however, despite recent meta‐analyses and US and European guidelines supporting its use in individuals at increased CVD risk. The aim of this study was to define which patients should receive aspirin for primary prevention of CVD using data from four European countries. Based on the clinical data from two meta‐analyses, a state‐transition model was developed to compare the costs and effects of no treatment and low‐dose aspirin as primary prevention for CVD over 10 years. The model was applied to patients at different 10‐year risks (2–5%) of fatal CVD according to the SCORE equation. Direct costs from the perspective of the healthcare payer were used (base year 2003). Country‐specific discounting was applied. Treating patients with a 10‐year risk of fatal CVD of 2% or higher with low‐dose aspirin resulted in lower total costs and more quality‐adjusted life‐years gained in the UK, Germany and Spain. In Italy, savings started at a 10‐year fatal CVD risk of 3%. This difference was due to the higher cost of gastrointestinal bleeding in Italy. Monte Carlo analysis showed that aspirin was dominant in more than 90% of patients at a 10‐year risk of 4% and 5% in the four countries. In conclusion, low‐dose aspirin treatment becomes cost‐saving at a very low 10‐year risk of fatal CVD. The cost of gastrointestinal bleeding defines the level at which low‐dose aspirin becomes cost‐saving.

Evaluación económica del tratamiento con ácido acetilsalicílico en dosis bajas en la prevención primaria de enfermedades cardiovasculares

Introduccion y objetivos El acido acetilsalicilico (AAS) en dosis bajas es un tratamiento estandar en pacientes con antecedentes de enfermedades cardiovasculares (ECV); se discute su empleo en prevencion primaria. Recientes estudios apoyan su uso en personas de alto riesgo y sin antecedentes de ECV. Se evaluo la repercusion economica del uso de AAS en la prevencion primaria de ECV en Espana. Metodos Se desarrollo un modelo para estimar la relacion coste/efectividad del tratamiento con AAS a dosis bajas en la prevencion primaria de ECV a los 10 anos. Se estudiaron los costes directos desde la perspectiva del Sistema Nacional de Salud (SNS) espanol. Los resultados se expresaron como coste por anos de vida ganados y por anos de vida ajustados por calidad. Resultados La administracion de AAS en dosis bajas a personas con riesgo de enfermedad coronaria (EC) ≥ 15% a los 10 anos produce un ahorro neto medio de 797 euros (intervalo de confianza [IC] del 95%, 263-1.331 euros), que empieza el primer ano. A partir de un riesgo annual ≥ 0,24%, este tratamiento ahorra costes al SNS. El tratamiento con AAS a toda la poblacion espanola con riesgo produciria un ahorro de 26,5 millones de euros en servicios sanitarios desde el primer ano. Conclusiones El tratamiento con AAS en dosis bajas de individuos con riesgo de EC ≥ 15% a los 10 anos produciria un ahorro de costes significativo al SNS. Los analisis de sensibilidad prueban la robustez de los resultados.

[Health economic evaluation of low-dose acetylsalicylic acid in the primary prevention of cardiovascular disease].

INTRODUCTION AND OBJECTIVES Low-dose aspirin is standard treatment for patients with a history of cardiovascular disease. Its use in primary prevention is more controversial. However, recent studies also support the use of aspirin in high-risk individuals with no history of cardiovascular disease. This study investigated the health economic implications of using low-dose aspirin in the primary prevention of cardiovascular disease in Spain. METHODS A model was developed to predict the cost-effectiveness of low-dose aspirin in the primary prevention of cardiovascular disease over a period of 10 years. The direct costs used were those of the Spanish National Health Service (NHS). Results were expressed as cost per life-year gained and per quality-adjusted life-year gained. RESULTS Administering low-dose aspirin to an individual with a 10-year risk of coronary heart disease > or =15% resulted in an average net saving of e 797 (95% CI, e 263-1331) over the 10-year period, with savings starting in the first year. For an annual risk > or =0.24%, this form of treatment would reduce NHS costs. Treating all at-risk individuals in the Spanish population with aspirin would save e 26.5 million from the healthcare budget, starting in the first year. CONCLUSIONS Administering low-dose aspirin to individuals with a 10-year risk of coronary heart disease > or =15% would result in significant cost savings for the Spanish NHS. Sensitivity analysis confirmed the robustness of these findings.

PRS4 THE COST-EFFECTIVENESS OF DRUG THERAPY IN COMMUNITY-ACQUIRED PNEUMONIA AND THE IMPACT OF ANTIMICROBIAL RESISTANCE IN GERMANY

multiplied with 2004 UK unit cost. A total of 1505 COPD patients with post FEV1% pred < = 50% were included (roflumilast 755, placebo 750). 62% were taking inhaled corticosteroids. RESULTS: In the total group, COPD-related costs from a societal perspective were €1635 (roflumilast) and €1400 (placebo). From a payer’s perspective this was €1385 and €1253, respectively. The overall rate of mod/sev COPD exacerbations in the trial was low and no differences existed between roflumilast (0.96) and placebo (1.06). In a subgroup of patients with very severe COPD (n = 223), placebo was associated with a high exacerbation rate (1.7 exacerbations/patient/year) and roflumilast was associated with 35% fewer exacerbations. This lower exacerbation rate was associated with €1001 lower COPD-related treatment costs. In the subgroup of patients with high health care resource use prior to the study (n = 549) the roflumilast group showed 0.41 fewer exacerbations per patient per year, which translated into an ICER of €804 per mod/sev exacerbation avoided. CONCLUSION: These data suggest that roflumilast, like many newly introduced therapies, increases the overall cost of therapy for COPD; however, this increase was partly offset by savings. Furthermore, in this study, roflumilast was found to be cost saving in very severe patients.

Eine gesundheitsökonomische Evaluation zu Aspirin in der Primärprävention kardiovaskulärer Erkrankungen aus Sicht der Gesetzlichen Krankenversicherungen

ObjectiveAspirin® is standard care in patients with a history of cardiovascular disease (CVD), but its use is more controversial in primary prevention. Recent metaanalyses as well as US and European guidelines support the use of Aspirin® in persons at risk of CVD, but who have no prior history. This study assessed the health economic consequences of the use of Aspirin® in primary prevention of CVD in Germany from the perspective of the Statutory Health Insurance (SHI) system.MethodsBased on the results reported in 2 recent meta-analyses, a model was developed to predict the cost-effectiveness of Aspirin® in comparison to placebo for patients with an increased risk for coronary heart disease (CHD) over 10 years (10-year risk 15 %). To calculate cost-effectiveness, the difference in total costs between both treatment groups was divided by the difference in efficacy, expressed in quality-adjusted life years (QALYs). Sensitivity analyses supported the robustness of the results.ResultsFrom the SHI perspective, the use of Aspirin® in patients with a 10-year risk of CHD of 15 %, results in net savings of around € 281 (95 % CI: € 141–422) per patient over 10 years in comparison to placebo. Savings start from the first year of treatment. For patients whose 10-year CHD risk is at least 3%, the cost of Aspirin® is completely compensated by savings from avoided cardiovascular events. Aspirin® treated patients gained a survival benefit of 1 week in QALY units.ConclusionFor the German population, the use of Aspirin® in patients with a moderately increased risk of CHD (10-year risk: 15 %) would result in overall savings of € 71 million from the SHI perspective after only one year of therapy. This economic evaluation supports the recommendations of US and European guidelines regarding Aspirin® for the primary prevention of CHD.

PIN4 COST-EFFECTIVENESS ANALYSIS OF ALTERNATIVE ANTIMICROBIAL TREATMENTS FOR COMMUNITY-ACQUIRED PNEUMONIA (CAP)

OBJECTIVES: To evaluate, in daily practice, the benefits of drotrecogin alfa (DA) in the treatment of severe septic patients with multiple organ failure and optimum intensive care support. METHODS: In this prospective, observational pre-post study, the clinicians were free to include any patient meeting DA’s inclusion criteria before and after DA’s marketing. An optimal propensity score matching technique was used to reduce recruitment bias. Survival was modeled using a Cox proportional hazards model with a shared frailty term to account for the clustering of patients within the intensive care units. The number of bleeding events measured DA’s safety. RESULTS: Respectively 509 and 587 patients were included in the before and after groups. There is strong evidence of recruitment bias: patients in the after group are younger, more frequently ventilated, have less comorbidities but more organ failures. After propensity score matching, 840 patients were retained in the analysis, with a better balance between the groups. The use of a frailty model improves significantly the variance explained by the survival model, showing a non-negligible cluster effect. When considering the whole sample of patients, without adjustments, survival is improved in the after (i.e. with DA) group (p = 2.5%), with a hazard ratio (HR) of 0.805. In the matched sample, there are no significant survival differences (HR = 0.900, p = 35.0%). However, after stratifying by the LODS severity score quartiles, significance is reached (HR = 0.795, p = 4.8%). In the matched sample, a negative binomial model best described bleeding events. In this model, patients in the after group have a higher mean of bleeding events (p = 2.0%). CONCLUSION: This observational study confirms DA’s clinical trial results in the real practice setting. However, the use of the propensity score cannot replace randomization to assure perfect balance for all patient characteristics, measured and unmeasured. The results should therefore be considered with caution.