[Quality of life and treatment satisfaction in patients being treated with long-acting insulin analogues]. / Lebensqualität und Behandlungszufriedenheit unter Therapie mit langwirksamen Analoginsulinen.

BACKGROUND AND OBJECTIVES: The purpose of this study was to review studies reporting on quality of life and treatment satisfaction of patients with diabetes mellitus being treated with long-acting insulin analogues. MATERIAL AND METHODS: A systematic literature search was made of trials published between January 1, 2000 and June 28, 2007. Retrieved studies were analysed, using predefined inclusion criteria as well as methodological and quality aspects. RESULTS: Twelve studies were included, all of them dealing with insulin glargine as the trial drug or for comparison. With regard to treatment satisfaction, insulin glargine was superior in one head-to-head comparison with NPH (neutral protamine Hagedorn) and one head-to-head comparison with NPH as an add-on to oral glimepiride. There was no difference in comparisons with continuous subcutaneous insulin infusion (CSII), insulin aspart or exenatide. Regarding health related quality of life (HRQoL), insulin glargine was shown to be superior to rosiglitazone as an add-on to metformin and sulfonylurea. Again, there were no differences in comparisons with NPH, CSII or exenatide. CONCLUSION: There are only a limited number of high quality studies showing that insulin glargine is superior regarding treatment satisfaction and HRQoL of patients with diabetes mellitus. There are fewer publications with good evidence of patient-reported outcomes than those reporting well-established outcomes using HbA1c levels or the incidence of hypoglycaemia.

[Contribution of leflunomide to the cost effectiveness of sequential DMARD therapy of rheumatoid arthritis in Germany]. / Wirtschaftlichkeit von Leflunomid bei sequentieller Basistherapie der rheumatoiden Arthritis in Deutschland.

Since November 1999, leflunomide (LEF), an innovative disease-modifying antirheumatic drug (DMARD), is available in Germany for treatment of rheumatoid arthritis (RA). LEF slows radiographic disease progression and improves functional capacity as well as healthrelated quality of life of RA patients. Resources for health care of the patients are limited in Germany as in all other countries. The purpose of the analysis therefore was to compare the cost effectiveness of the following alternatives: LEF in sequential monotherapy with other DMARDs versus sequential monotherapy of other DMARDs. The target variables of this cost-effectiveness comparison were additional direct costs per ACR20-response year (ACR20RY) gained and per quality-adjusted life year (QALY) gained, respectively, each after three years of treatment. The cost-effectiveness comparison was carried out using a modeling study after secondary analysis of relevant data. Oral methotrexate (MTX), sulphasalazine (SSZ), antimalarials (CQ/HCQ), intramuscular gold (IMG), and azathioprine (AZA) were selected as "other" DMARDs representing the current status of sequential monotherapy. Based on health care regulation in Germany-Guidelines on the Prescription of Drugs amended by the Federal Commission of Medical Practitioners and Health Insurance Funds on 10 December 1999-LEF was exclusively considered second within a DMARD sequence. Direct costs were given by outpatient and inpatient treatment, long-term care, and rehabilitation treatment. Prices relate to the period of 1998 to 2001 and were converted to Euro (euro), according to the official exchange rate of 1 euro = 1.95583 DM (1 euro approximately 0.90 US dollars; 2001 values). The comparative cost-effectiveness analysis covered a treatment period of more than one year. To estimate the net present value of future costs and effectiveness, a discount rate of 5% per year was applied. In the case of DMARD-naïve patients with RA, the sequence MTX, LEF, SSZ, IMG, AZA, CQ/HCQ was the most cost effective with direct costs of 7297 euro per ACR20RY and 6499 euro per QALY. In order to estimate the consequences of introducing LEF into the prescribing practice in Germany, the distribution of RA patients by individual DMARD in rheumatological care in 1998 was considered. This distribution was taken from the National Database of the German Collaborative Arthritis Centres. Though the sequences comprising LEF incurred 3% higher direct costs, they led to a higher effectiveness of 6% and 3% in the case of ACR20RYs and QALYs, respectively. Choosing sequences comprising LEF, there were additional direct costs of 5004 euro per ACR20RY gained and 8301 euro per QALY gained, as compared to the corresponding sequences without LEF. In comprehensive sensitivity analyses, the robustness of the model and its results was shown. The contribution of LEF to the cost effectiveness of sequential DMARD therapy is obvious. The modeling study revealed advantages for the patients and the cost carriers. Though there were initially higher medication costs of the sequences comprising LEF, these costs were nearly compensated to remaining excess costs of just 3% after three years. This was caused by cost savings in other sectors of the health care system due to the higher effectiveness of the sequences comprising LEF.

Cost effectiveness of ramipril in patients with non-diabetic nephropathy and hypertension: economic evaluation of Ramipril Efficacy in Nephropathy (REIN) Study for Germany from the perspective of statutory health insurance.

BACKGROUND: In the Ramipril Efficacy In Nephropathy (REIN) trial, ramipril significantly lowered the rate of reaching the combined end-point of doubling of baseline serum creatinine levels or end-stage renal failure (ESRF). OBJECTIVE: To determine the additional cost per patient-year of chronic (long term) dialysis avoided (PYCDA) when the ACE inhibitor, ramipril, was added to conventional treatment of patients with non-diabetic nephropathy and hypertension. STUDY PERSPECTIVE: Statutory Health Insurance (SHI) provider in Germany. DESIGN AND SETTING: Data from the REIN Study were used in a cost-effectiveness analysis (CEA). A modelling approach was used, which was based on secondary analysis of published data, and costs were those incurred by the SHI provider (i.e. SHI expenses). In the base-case analysis, average case-related SHI expenses were applied and PYCDA were quantified using the cumulative incidence of ESRF as observed in the REIN trial. MAIN OUTCOME MEASURES AND RESULTS: The incremental cost-effectiveness ratios (ICERs) of ramipril varied between about -76,700 deutschmarks (DM) and -DM81,900 per PYCDA (DM 1 approximately equals 0.55 US dollars; 1999 values), according to the treatment periods of 1 year and 3 years, respectively. In the sensitivity,analysis, the robustness of the model and its results were shown when the extent of influence of different model variables on the base-case results was investigated. First, probabilities of ESRF and PYCDA were estimated according to the Weibull method. Second, the influence of the model variables on the target variable was quantified using a deterministic model. Third, the dependency of the target variable (ICER) on random variables was described in a simulation. The cost for chronic dialysis had by far the greatest impact on the target variable, which was 28 times greater than the impact of clinical effectiveness of ramipril, i.e. the number of PYCDA. There were net savings per PYCDA with ramipril treatment after 1, 2 and 3 years: 95% of the 10,000 simulation steps resulted in savings of between DM69 500 and D94,600 per PYCDA after 3 years. CONCLUSIONS: Results from this evaluation show that ramipril offers enormous savings from the perspective of the SHI provider (third-party payer) in Germany when added to the conventional treatment of patients with non-diabetic nephropathy and hypertension.

Economic evaluation of specific immunotherapy versus symptomatic treatment of allergic rhinitis in Germany.

OBJECTIVE: To use published data to compare the economic consequences of specific immunotherapy (SIT) lasting 3 years with those of continuous symptomatic treatment in patients with either pollen or mite allergy. DESIGN AND SETTING: The evaluation was conducted from the following 3 perspectives in Germany: (i) society; (ii) healthcare system; and (iii) statutory health insurance (SHI) provider. A modelling approach was used which was based on secondary analysis of existing data. The follow-up period was 10 years. The break-even point of cumulated costs, their difference per patient and the additional cost per additional patient free from asthma symptoms [incremental cost-effectiveness ratio (ICER)] were used as target variables, each from the viewpoint of SIT. The types of costs were direct and indirect (society), direct (healthcare system) and those incurred by SHI (i.e. expenses). In the base-case analysis, the average values of the clinical parameters and average case-related costs/expenses were applied. MAIN OUTCOME MEASURES AND RESULTS: The break-even point was reached between year 6 and year 8 after the start of therapy, resulting in net savings of between 650 and 1190 deutschmarks (DM) per patient after 10 years. The ICERs of SIT were between -DM3640 and -DM7410, depending on study perspective and nature of the allergy (1990 values for symptomatic treatment and treatment of asthma, 1995 values for SIT; DM1 approximately $US0.58). The sensitivity analysis demonstrated the robustness of the model and its results. First, all the independent variables of the model were varied. Secondly, the influence of the model variables was quantified using a deterministic model. SIT was more likely to result in net savings than in additional costs. An economic parameter (cost for symptomatic treatment) had the highest influence on the results. CONCLUSIONS: This evaluation showed that SIT for 3 years is economically advantageous in patients who are allergic to pollen or mites and whose symptoms are inadequately controlled by continuous symptomatic treatment. After 10 years, the administration of SIT leads to net savings from the perspectives of society, the healthcare system and SHI (third-party payer) in Germany.

The cost effectiveness of acamprosate in the treatment of alcoholism in Germany. Economic evaluation of the Prevention of Relapse with Acamprosate in the Management of Alcoholism (PRAMA) Study.

Alcoholism places a considerable economic burden on society. The rate of relapse of previously weaned alcoholics has been shown to decrease following treatment with acamprosate. Therefore, this study investigated the cost effectiveness of acamprosate in the treatment of alcoholism in Germany from the perspective of the German healthcare system. In this retrospective analysis of clinical data, the additional direct medical costs per additional abstinent alcoholic incurred by adjuvant acamprosate therapy of previously weaned alcoholics were quantified. In the base-case analysis, average case-related direct costs were applied. The cost-effectiveness ratio was -2600 deutschmarks (DM) per additional abstinent patient. Thus, the administration of acamprosate is cost saving. The cost benefit of acamprosate was also shown in a sensitivity analysis. The variance of the target variable under 'real world' conditions was simulated and the impact of the model variables on the target variable was quantified using a deterministic model. The variance was broad and the rate of abstinence under acamprosate was the independent variable with the greatest impact on the target variable. From the perspective of both the German healthcare system (i.e. direct medical costs) and the Statutory Health Insurance expenses, adjuvant acamprosate therapy led to net savings, while at the same time improved the patient's state of health. Based on the naturalistic design of the underlying clinical trial and on this economic evaluation, it can be concluded that adjuvant acamprosate therapy leads to net savings under 'real world' conditions.

Cost-effectiveness analysis of ramipril in heart failure after myocardial infarction. Economic evaluation of the Acute Infarction Ramipril Efficacy (AIRE) study for Germany from the perspective of Statutory Health Insurance.

OBJECTIVE: Data from the Acute Infarction Ramipril Efficacy (AIRE) study were used in a cost-effectiveness analysis to determine the incremental cost per life-year gained (LYG) when the ACE inhibitor ramipril was added to conventional treatment in patients with heart failure after acute myocardial infarction. In the AIRE trial, the addition of ramipril significantly lowered rates of total mortality and rehospitalisation due to heart failure. DESIGN AND SETTING: The cost-effectiveness analysis was conducted from the perspective of the Statutory Health Insurance (SHI) provider in Germany. A modelling approach was used which was based on secondary analysis of existing data, and costs were those incurred by SHI (i.e. expenses of SHI). In the base-case analysis, average case-related expenses of SHI were applied and LYG were quantified by the method of Kaplan and Meier. MAIN OUTCOME MEASURES AND RESULTS: The incremental cost-effectiveness ratios of ramipril varied between 2500 and 8300 deutschmarks (DM) per LYG (1993 values for inpatient and 1995 values for outpatient treatment; DM1 approximately $US0.70), according to the treatment periods of 3.8 years and 1 year, respectively. In the sensitivity analysis, the robustness of the model and its results was shown when the extent of influence of different model variables on the base-case results was investigated. First, survival probability and LYG were estimated according to the Weibull method. Second, the dependency of the target variable (i.e. incremental cost per LYG) on random variables was described in a simulation. Third, the influence of the model variables on the target variable was quantified using a deterministic model. The variance of the target variable was broad and the hospitalisation impact of adding ramipril to conventional treatment was an independent variable with much greater influence on the target variable than the parameter of clinical effectiveness, i.e. the number of LYG. CONCLUSION: Results of this evaluation showed that ramipril has a favourable incremental cost-effectiveness ratio for the treatment of heart failure in post myocardial infarction patients and can be considered an economical therapeutic agent from the perspective of SHI (third-party payer) in Germany.

Economic evaluation of the Cardiac Insufficiency Bisoprolol Study for the Federal Republic of Germany.

The Cardiac Insufficiency Bisoprolol Study (CIBIS) demonstrates that, for patients with heart failure of different aetiologies, administration of the beta 1-adrenoceptor blocker bisoprolol as an adjuvant to the standard therapy leads to a significant avoidance of hospital admissions. A pharmacoeconomic analysis of the results of the CIBIS was conducted for the Federal Republic of Germany, and was restricted to direct costs only. The costs of bisoprolol medication and inpatient treatment of heart failure were considered, the latter forming the major part of costs incurred. Per 1000 patient-years, adjuvant bisoprolol therapy resulted in overall cost savings of Deutschmarks (DM)157,272. Statutory Health Insurance had a net saving of DM186,719 in 1000 patient-years, while patients experienced additional net expenses of DM17,760 over 1000 patient-years. The economic advantage of adjuvant bisoprolol treatment was also borne out in the sensitivity analysis. Adjuvant therapy with bisoprolol was not only clinically beneficial for the patient with heart failure but was also economically advantageous.

[Cost effectiveness of bisoprolol in heart failure. Economic evaluation of the Cardiac Insufficiency Bisoprolol Study (CIBIS) for Germany]. / Wirtschaftlichkeit von Bisoprolol bie Herzinsuffizienz. Okonomische Bewertung der Cardiac Insufficiency Bisoprolol Study (CIBIS) für die Bundesrepublik Deutschland.

BACKGROUND: The Cardiac Insufficiency Bisoprolol Study (CIBIS) demonstrates that, for patients with heart failure of different etiologies, the administration of the beta(1)-adrenoceptor blocker bisoprolol adjuvant to the standard therapy leads to a significant avoidance of hospital admissions. PHARMACOECONOMIC EVALUATION: The results of the CIBIS were evaluated pharmacoeconomically for the Federal Republic of Germany, and were restricted to direct costs only. The costs of bisoprolol medication and in-patient treatment of heart failure were considered, the latter forming the major part of costs incurred. CONCLUSION: Adjunctive therapy with bisoprolol is not only clinically beneficial to the patient with heart failure, but also economically advantageous.

[Cost-effectiveness analysis of prevention of reinfarction using low-dose acetylsalicylic acid; model calculation]. / Kosten-Wirksamkeits-Analyse der Reinfarktprophylaxe mit niedrig dosierter Acetylsalicylsäure: Modellrechnung.

The purpose of this study is to estimate the potential of savings which can be achieved by prophylaxis of myocardial reinfarction with low-dose acetylsalicylic acid (ASA) at 75 mg per day over a treatment period of two years. After secondary analysis of published data, the effectiveness of low-dose ASA is compared to placebo by a model calculation. The difference in the effectiveness between the prophylaxis with ASA and placebo is taken from an international meta-analysis. The economic valuation of this difference is carried out by a cost-effectiveness analysis applying disease costs per case. According to the model calculation, 5535 DM can be saved per patient with a history of myocardial infarction with 75 mg ASA a day over a treatment period of two years. In 1991 there were around 740,000 patients with a history of myocardial infarction in the age group of 25-64 in the Old Bundesländer of the Federal Republic of Germany. The application of the results of the model calculation would lead to considerable savings. Even in the sensitivity analysis with different assumptions regarding costs incurred by hospital treatment and costs incurred by premature retirement, the cost advantage of the ASA-prophylaxis remains. Due to the cautious and conservative assumptions in the model calculation the potential of savings is likely underestimated. Nevertheless, there is a distinct advantage for the prophylaxis with low-dose ASA which already occurs in direct costs thus leading to advantages also for cost carriers.

Alcoholism. The cost of illness in the Federal Republic of Germany.

The purpose of this study was to estimate the direct and indirect costs of alcoholism in the Federal Republic of Germany. Direct costs comprised treatment costs, while indirect costs consisted mainly of costs incurred as a result of work time lost, as well as costs related to premature retirement and premature mortality. The costs of alcoholism were estimated using the aggregated statistics of several social security organisations and official statistics. For the purposes of this study, alcoholism was defined as alcohol dependence syndrome [9th revision of the International Classification of Diseases code (ICD) 303], alcoholic chronic liver disease and cirrhosis (ICD 571.0 to 571.3), and alcoholic psychoses (ICD 291). The reference period consisted of the years 1985 to 1991. All statistics and all analyses were limited to the so-called old states of Germany, within the boundaries as they were before 3rd October 1990. The overall monetary burden (in 1990 Deutschemarks) of alcoholism in the western part of Germany in 1990 was estimated to be DM5975 million. Alcoholism is associated with considerably more indirect costs (DM4422 million) than direct costs (DM1553 million). The predominance of indirect costs is mainly the result of the very high premature mortality of patients with alcoholism. Thus, the cost of premature mortality makes up more than half of the indirect costs of alcoholism (DM2284 million), while about a quarter of the indirect costs (DM1150 million) are associated with inability to work. Early retirement accounts for a similar amount (DM988 million). The majority of direct costs is accounted for by treatment in acute hospitals (DM869 million). Costs incurred as a result of rehabilitation treatment (DM373 million) and ambulatory care (DM331 million) are also considerable.

Self-sufficiency--20 years on.

The opening paper of this symposium discusses the theme [European self-sufficiency and haemophilia prophylaxis: achievable goals or idealistic concepts?' from four aspects: (a) the meaning and interpretation of self-sufficiency in the European Community; (b) a summary of the facts, discussions and developments of the last 20 years; (c) a description of future aims and objectives; and (d) a discussion of what this symposium hopes to achieve. The author suggests that one most important point is to find an adequate definition of the term [self-sufficiency' in this context.

[Quality of event data in detection of unwanted drug side-effects in general practice of established physicians]. / Qualität von Ereignisdaten bei der Erfassung unerwünschter Arzneimittelwirkungen in Praxen niedergelassener Arzte.

Since 1986, the Federal Health Office (BGA) has supported the model project "Monitoring Adverse Drug Reactions (ADRs) in the Surgeries of Office-Based Physicians". The project itself is being carried out by the Institute for Health Systems Research in Kiel. The aim of the project is to develop a method for the systematic monitoring of the risks involved with selected new drugs. This should also facilitate the determining of the incidence rate of ADRs as well as reveal as yet unknown ADRs. Several conclusions can be drawn when examining the quality of event data when monitoring ADRs through office-based physicians. The documentation quality of the transferred data fluctuates from surgery to surgery. In order to obtain valid outcomes, the data should be thoroughly examined and checked by consulting the participating surgery. When quantifying known events with a suspected ADR, the Sentinel approach leads to reliable results. When monitoring drug therapies through office-based physicians, risk situations can be monitored and assessed more easily under everyday conditions. When assessing the quality of event data with regard to disclosing hitherto unknown, potential ADRs, the character of the individual surgery is of utmost importance. The object of the research project is to examine cause-effect associations which have nothing whatsoever to do with the participating physicians themselves but which reflect interactions between drugs and patients.