Hepatocellular carcinoma after prior sorafenib treatment: incidence, healthcare utilisation and costs from German statutory health insurance claims data.

OBJECTIVE: To estimate both the number of patients with hepatocellular carcinoma (HCC) eligible annually for second-line therapy following sorafenib in Germany and the healthcare costs accrued by patients meeting eligibility criteria. METHODS: Patients with an HCC diagnosis and one or more sorafenib prescription were identified from samples of > 3 million insured persons in each of 2012, 2013 and 2014 using the anonymised Betriebskrankenkasse health insurance scheme database. Incidence rates from 2013 were extrapolated to the German population using data from the statutory health insurance system database and Robert Koch Institute. Resource use and cost data were collected for a subset of patients with follow-up data post-sorafenib. RESULTS: Between 1032 and 1484 patients with HCC in Germany (893-1390 publicly insured patients) were estimated as likely to be eligible for second-line therapy after sorafenib annually. For post-sorafenib analyses, 117 patients were identified with HCC, one or more sorafenib prescription and considered potentially eligible for second-line treatment, 15 of whom were alive after 12 months' follow-up. Total mean costs per patient accrued in the 12 months after sorafenib treatment ended were €11,152 (hospital care, €6483 [58.1%]; outpatient prescriptions, €3137 [28.1%]). CONCLUSION: The estimated number of publicly insured HCC patients annually eligible for second-line therapy in Germany was < 1400 and mean total costs accrued in the year after completion of sorafenib therapy were approximately €11,000 per patient for the German statutory healthcare system. These estimates can be used when evaluating the budgetary impact of new second-line therapies for advanced HCC in Germany.

Use of Structural Equation Modeling to Demonstrate the Differential Impact of Storage and Voiding Lower Urinary Tract Symptoms on Symptom Bother and Quality of Life during Treatment for Lower Urinary Tract Symptoms Associated with Benign Prostatic Hyperplasia.

PURPOSE: Lower urinary tract symptoms associated with benign prostatic hyperplasia typically respond well to medical therapy. While changes in total I-PSS (International Prostate Symptom Score) are generally accepted as measurement for treatment response, I-PSS storage and voiding subscores may not accurately reflect the influence of symptom improvement on patient bother and quality of life. MATERIALS AND METHODS: Structural equation modeling was done to evaluate physiological interrelationships measured by I-PSS storage vs voiding subscore questions and measure the magnitude of effects on bother using BII (Benign Prostatic Hyperplasia Impact Index) and quality of life on I-PSS quality of life questions. Pooled data from 4 randomized, controlled trials of tadalafil and placebo in 1,462 men with lower urinary tract symptoms/benign prostatic hyperplasia were used to investigate the relationship of storage vs voiding lower urinary tract symptoms on BII and quality of life. RESULTS: The final structural equation model demonstrated a sufficient fit to model interdependence of storage, voiding, bother and quality of life (probability for test of close fit <0.0001). Storage aspects had a twofold greater effect on voiding vs voiding aspects on storage (0.61 vs 0.28, each p <0.0001). The direct effect of storage on bother was twofold greater than voiding on bother (0.64 vs 0.29, each p <0.0001). Bother directly impacted quality of life by the largest magnitude of (-0.83), largely driven by storage lower urinary tract symptoms (p <0.0001). CONCLUSIONS: Total I-PSS is a reliable instrument to assess the therapeutic response in lower urinary tract symptoms/benign prostatic hyperplasia cases. However, an improvement in storage lower urinary tract symptoms is mainly responsible for improved bother and quality of life during treatment. Care should be taken when evaluating the accuracy of I-PSS subscores as indicators of the response to medical therapy.

Patient preferences for outcomes of depression treatment in Germany: a choice-based conjoint analysis study.

BACKGROUND: In general, treatment efficacy in depressed patients is evaluated mainly based on the core symptoms of depression. However, patients might consider different outcomes. This study used choice-based conjoint analysis (CBC) to evaluate patient preferences for depression treatment outcomes. METHODS: Adult subjects from Germany, currently or previously on antidepressant treatment, were presented with 18 pairs of hypothetical treatment outcome scenarios, differing in eight attributes (2-3 factor levels each): depressed mood, loss of interest and enjoyment, loss of energy/fatigue, sleep disturbance, feelings of guilt, depression-related pain, treatment duration, side effects after 2 weeks. Attributes and factor levels were defined by literature review, expert consultations, and in-depth subject interviews. Data were analyzed using multinomial logit modeling; individual part-worth utilities were estimated using hierarchical Bayes routines. RESULTS: Two hundred twenty-seven subjects (89.4% currently treated with antidepressants, 30.0% with depression-related pain) completed the survey. They valued the relative importance of outcomes as follows: loss of energy/fatigue 18.5%, side effects after 2 weeks 14.2%, loss of interest and enjoyment 13.5%, depression-related pain 12.0%, sleep disturbance 12.0%, feelings of guilt 11.5%, treatment duration 9.9%, depressed mood 8.5%. LIMITATIONS: Participants were not required to meet ICD-10 or DSM-IV criteria for depression and had heterogeneous disease severity. CONCLUSIONS: CBC analysis was able to reveal patient preferences for outcomes of depression treatment. Subjects valued the ability to cope with activities of everyday living highest. They considered being free of depression-related pain and side effects more important than being free of depressed mood. These findings should be considered when making treatment decisions.

Preferences of diabetes patients and physicians: a feasibility study to identify the key indicators for appraisal of health care values.

BACKGROUND: Evidence-based medicine, the Institute of Medicine (IOM) and the German Institute for Quality and Efficiency in Health Care (IQWiG), support the inclusion of patients' preferences in health care decisions. In fact there are not many trials which include an assessment of patient's preferences. The aim of this study is to demonstrate that preferences of physicians and of patients can be assessed and that this information may be helpful for medical decision making. METHOD: One of the established methods for assessment of preferences is the conjoint analysis. Conjoint analysis, in combination with a computer assisted telephone interview (CATI), was used to collect data from 827 diabetes patients and 60 physicians, which describe the preferences expressed as levels of four factors in the management and outcome of the disease. The first factor described the main treatment effect (reduction of elevated HbA1c, improved well-being, absence of side effects, and no limitations of daily life). The second factor described the effect on the body weight (gain, no change, reduction). The third factor analyzed the mode of application (linked to meals or flexible application). The fourth factor addressed the type of product (original brand or generic product). Utility values were scaled and normalized in a way that the sum of utility points across all levels is equal to the number of attributes (factors) times 100. RESULTS: The preference weights confirm that the reduction of body weight is at least as important for patients--especially obese patients--and physicians as the reduction of an elevated HbA1c. Original products were preferred by patients while general practitioners preferred generic products. CONCLUSION: Using the example of diabetes, the difference between patients' and physicians' preferences can be assessed. The use of a conjoint analysis in combination with CATI seems to be an effective approach for generation of data which are needed for policy and medical decision making in health care.

Expenditures of the German statutory health insurance system for patients suffering from acute coronary syndrome and treated with percutaneous coronary intervention.

Patients with acute coronary syndrome (ACS) are in need of cost-intensive treatment involving different aspects of the German Health System. Percutaneous coronary intervention (PCI) is the treatment of choice for a large proportion of cases. In the present study, an analysis of the cost impact of ACS with focus on PCI therapy was conducted across-the-board for the German Health System. Results indicated that 85% of all costs arising from treatment of ACS with a trial of PCI are due to in-patient care. Projection of results onto the entire insurant collective of the statutory health system estimated a total of Euro 954,995,603-a proportional 0.7% of all expenditure by statutory health insurance in 2005.

Diabetic retinopathy and health-related quality of life.

OBJECTIVE: To describe the impact of co-morbidities, visual acuity, diabetic retinopathy (DR) grade, and macular edema (ME) on the health-related quality of life (HRQOL) among patients with diabetic retinopathy. METHODS: Analysis of data of 207 patients with diabetic retinopathy from Germany in 2003. HRQOL assessment was done using the generic (SF-12) questionnaire. It was hypothesized that exogenous variables (co-morbidities, visual acuity impairment, DR, and ME) would have an impact on HRQOL. Using a structural equation modelling procedure, the effects of exogenous variables on endogenous variables physical component summaries (PSC) and mental component summaries (MCS) reflecting HRQOL were tested. RESULTS: The number of co-morbidities had a negative effect on visual acuity (b = -0.26, standardized) and a similar negative effect on PCS (b = -0.27). DR grade had a negative effect on visual acuity (b = -0.19) and a positive effect on the variable ME (b = 0.44). ME displayed a negative effect on visual acuity (b = -0.58) and also on MCS (b = -0.29). Visual acuity had a positive effect (b = 0.48) on PCS. CONCLUSIONS: Presence of DR and ME, visual acuity impairment and patient co-morbidities lead to significant impairment of both the physical and mental components of HRQOL.

The quality of life and economic burden of neuropathy in diabetic patients in Germany in 2002--results from the Diabetic Microvascular Complications (DIMICO) study.

OBJECTIVE: To describe the health-related quality of life (HRQOL), the resource utilization and annual costs associated with diabetic neuropathy (DN) in Germany. METHODS: In this retrospective, observational study German internists, diabetologists and general practitioners provided information on 185 adult type 1 and type 2 diabetic patients with DN. Health-related quality of life (HRQOL) was assessed using generic and disease specific questionnaires. Socio-demographic and resource use data were assessed from medical charts and through patient interviews. Based on these results, national-level cost estimates were calculated using German unit costs. RESULTS: The majority of DN patients were severely impaired with regard to general physical HRQOL. Disease specific HRQOL decreased continuously with increasing DN severity. In accordance, costs associated with DN increased as DN progressed, with costs from the societal perspective increasing about 50-fold from the lowest severity stage (patients with sensory-motor neuropathy without symptoms) (euro431) to patients with lower extremity amputation in the year 2002 (euro21,476). The German statutory health insurance covered more than two thirds of the total costs of DN. CONCLUSIONS: The results described in this report show that diabetic neuropathy in adults with type 1 or type 2 diabetes generates significant reductions in the patient's quality of life and a substantial economic burden both for society and health insurance.

Predisposing factors for early retirement in patients with schizophrenia in Germany.

Although early retirement causes major changes in the life of schizophrenic patients and is among the major cost factors to be covered by payers, the causes leading to early retirement of schizophrenic patients have not been investigated in detail. Therefore, the objective of this retrospective non-interventional case-control study was to generate hypotheses on predisposing factors for early retirement in schizophrenia. Logistic regression was used to explore potential predisposing parameters with regard to their effect on the outcome early retirement. As the study results indicate, schizophrenia severity, assistance or care in the patient's everyday life, age and antipsychotic treatment with typical antipsychotics are linked to the occurrence of early retirement. Further research should be planned to confirm or refute the hypotheses determined in this retrospective analysis and to determine whether atypical antipsychotics could help to avoid early retirement and to improve the situation of schizophrenic patients.

Constructing an Index for the Subjective Well-being Under Neuroleptics scale (SWN), short form: applying structural equation modeling for testing reliability and validity of the index.

Structural equation modeling (SEM) has been widely used in psychology and sociology for testing validity of measurement instruments. However, this statistical technique has so far played minor role in quality-of-life research. The main objective of this paper is to demonstrate the potential of SEM for constructing and testing the validity of a Subjective Well-being under Neuroleptics (SWN) index for patients with schizophrenia. For these purposes, data from the GEO study (Gesundheitsökonomische Evaluation von Olanzapin in Deutschland; Health economics study of olanzapine in the treatment of schizophrenia in Germany) were used. The GEO is a prospective, comparative, noninterventional, observational study. A total of 646 participants treated with either olanzapine (n = 416) or haloperidol (n = 230) were enrolled in the study; 360 patients were available for factor analyses. The short (20-item) form of the SWN scale was administered to assess patients' perspectives on their quality of life. The structural equation models (SEMs) were then applied to construct 5- and 10-item indexes based on SWN. The data indicate that the 5-item index is the most time-saving approach for evaluating perceptions of well-being (and thus, quality of life) among patients with schizophrenia. The application of SEM showed no appreciable loss of validity of this index.

A decision model to compare health care costs of olanzapine and risperidone treatment for schizophrenia in Germany.

Second-generation atypical antipsychotics such as clozapine, olanzapine, risperidone, quetiapine, ziprasidone, amisulpride and ariprazole offer the potential to reduce the significant health care resource demands in the treatment of schizophrenia through improved levels of initial clinical response and reduced levels of long-term acute relapse. However, the optimal sequencing of these drugs remains unclear. To consider this issue from a health economic viewpoint a decision model approach was used comparing healthcare costs and clinical outcomes when treating patients with alternative sequences of atypical antipsychotic treatment. Treated patients were assumed to be in a current acute episode with at least a 10-year history of disease and to be naive to previous atypical treatments. Treatment strategies were based on either first-line olanzapine or risperidone with switching to the alternative drug as second-line treatment following an inadequate clinical response to first-line drug therapy. Clinical response data were derived from a pivotal published comparative study of both olanzapine and risperidone. Published data on the long-term use of antipsychotic drugs where used wherever possible to populate the model for relapse rates during the maintenance phase. Health care resource data were defined for Germany based on expert clinical opinion. A treatment strategy of first-line olanzapine was shown to be cost saving over a 1-year period, with additional clinical benefits in the form of avoided relapses. The model suggests that over the first year of treatment a strategy of first-line olanzapine is associated with lower risk of additional relapse (0.33 fewer acute relapses per 100 patients per year) and with cost savings (euro 35,306 per 100 patients per year). There is a need for longer term direct in-trial comparisons of atypical antipsychotics to confirm these indicative results.

[Costs of early retirement--the case of schizophrenia]. / Kosten der Frühverrentung am Beispiel der Schizophrenie.

Schizophrenia is a severe psychic disorder that occurs at young age and often leads to a work disability. The disease not only induces direct costs in the health care system but also indirect costs that show up in the social security system. In this study, we apply statistics from the social security administration on early retirement due to disability. Over 6000-males and females per year retire with the diagnosis schizophrenia (classified as 295, ICD-9). The average retirement age is 39 for males and 42 for females. Schizophrenia is the most important single reason for early retirement before age 40. Of all male cases of disability retirement under the age of 40, 14.7 % are due to schizophrenia. The present discounted value of pensions paid out before the standard retirement age of 65 is 215 000 Euro for an average male. Moreover, the revenue loss in income taxes and payroll contributions amounts to 345 000 Euro. In the year 2000, a total of 125 000 persons under the age of 65, who originally entered retirement with the diagnosis schizophrenia, are estimated to be receiving a pension. The corresponding annual expenditures of the social security system reach 1.3 Billion Euro; the revenue loss (pay-roll plus income taxes) reaches 2 Billion Euro. Since only two thirds of the working age population is covered by the social security system, the costs of early retirement due to schizophrenia are underestimated by a factor of at least one third.

Cost-effectiveness of drotrecogin alfa (activated) for the treatment of severe sepsis in Germany.

Drotrecogin alfa (activated) (Xigris; Eli Lilly and Company, Indianapolis, IN) significantly reduced mortality in severe sepsis in the PROWESS trial. We evaluate the cost-effectiveness of drotrecogin alfa (activated) as an adjunct to standard therapy from the German healthcare payer's perspective with respect to patients with 1) severe sepsis and 2) severe sepsis and multiple organ failure the approved European indication. Hospital resource use based on PROWESS was valued using German unit costs. German life-tables and long-term survival assumptions determined life-years gained. European and German healthcare resource use data are examined in the sensitivity analysis. We assumed a unit price of euro;237.50 for drotrecogin alfa (activated). Per patient treated, drotrecogin alfa (activated) increased costs by euro;7,500, and hospital costs by euro;900 for all patients (euro;7,400 and euro;1,500 respectively for the approved indication) and survival by 0.59 life years (0.87 life years respectively for the approved indication). Thus drotrecogin alfa (activated) cost euro;14,100 (euro;17,700 discounting life years at 3%) per life year gained for all patients (euro;10,200 and euro;12,900, respectively, for the approved indication). Testing the unit cost of drotrecogin alfa (activated), pattern of resource use, and survival benefit, demonstrated that cost-effectiveness lies well within the range of other life saving interventions in Germany representing good economic value.