Use of Biologic Therapies in the Treatment of Asthma - A Comparative Real World Data Analysis on Healthcare Resource Utilization and Costs Before and After Therapy Initiation.

Background: Asthma is one of the most common chronic diseases in Germany. While many patients achieve asthma control under standard therapies, some patients still experience exacerbations and persistent airway obstructions. Thus, further pharmacological treatment is needed, and biologics could fill this gap, as they have shown clinical benefit in patients with severe asthma. Therefore, this real-world study aimed to compare healthcare resource utilization (HCRU) and associated costs before and after biologic therapy initiation. Methods: A retrospective claims data analysis has been conducted on adult asthma patients who initiated a long-term biologic therapy between January 2015 and June 2018. Patients were therapy-naïve to biologics for at least 12 months. HCRU and cost incurred by patients during 12 months before and after therapy initiation were compared. Results: Overall, 571 asthma patients initiated a biologic therapy during the observational period (316 omalizumab, 232 mepolizumab, 16 benralizumab, and 7 reslizumab). Patients had a mean age of 54.86 (62.70% female), and the majority (93.70%) received at least one follow-up prescription of their index-biologic agent within one year. During baseline, patients received on average 2.75 OCS prescriptions compared to 2.17 during follow-up. Most patients received less or the same amount of OCS after therapy initiation. Moreover, hospitalizations and asthma-related sick leave days decreased significantly. The average total costs per patient were €6618.90 during baseline and €22,832.33 during follow-up. Biologics mainly drove the increase; however, hospitalization costs were reduced significantly (€2443.37 vs €1941.93; p<0.001). Conclusion: Our study demonstrates an improved asthma control due to the initiation of a biologic therapy in terms of decreased hospitalization frequency, OCS consumption, and sick leave days. However, biologics are associated with high costs for healthcare providers during the first year after initiation. Therefore, short- and long-term clinical benefits and financial burden must be considered in the overall context of healthcare.

A novel superior medication-based chronic disease score predicted all-cause mortality in independent geriatric cohorts.

OBJECTIVES: On the basis of current treatment guidelines, we developed and validated a medication-based chronic disease score (medCDS) and tested its association with all-cause mortality of older outpatients. STUDY DESIGN AND SETTING: Considering the most prevalent chronic diseases in the elderly German population, we compiled a list of evidence-based medicines used to treat these disorders. Based on this list, a score (medCDS) was developed to predict mortality using data of a large longitudinal cohort of older outpatients (training sample; MultiCare Cohort Study). By assessing receiver-operating characteristics (ROC) curves, the performance of medCDS was then confirmed in independent cohorts (ESTHER, KORA-Age) of community-dwelling older patients and compared with already existing medication-based scores and a score using selected anatomical-therapeutic-chemical (ATC) codes. RESULTS: The final medCDS score had an ROC area under the curve (AUC) of 0.73 (95% CI 0.70-0.76). In the validation cohorts, its ROC AUCs were 0.79 (0.76-0.82, KORA-Age) and 0.74 (0.71-0.78, ESTHER), which were superior to already existing medication-based scores (RxRisk, CDS) and scores based on pharmacological ATC code subgroups (ATC3) or age and sex alone (Age&Sex). CONCLUSIONS: A new medCDS, which is based on actual treatment standards, predicts mortality of older outpatients significantly better than already existing scores.

The impact of potentially inappropriate medication on the development of health care costs and its moderation by the number of prescribed substances. Results of a retrospective matched cohort study.

BACKGROUND: In the growing population of the elderly, drug-related problems are considered an important health care safety issue. One aspect of this is the prescription of potentially inappropriate medication (PIM) which is considered to increase health care costs. OBJECTIVE: Using data from the Health Economics of Potentially Inappropriate Medication (HEPIME) study, we aimed to analyze how the number of prescribed substances moderates the association of PIM use as defined by the German PRISCUS list and health care costs applying a longitudinal perspective. METHODS: An initial number of 6,849,622 insurants aged 65+ of a large German health insurance company were included in a retrospective matched cohort study. Based on longitudinal claims data from the four separate quarters of a 12-month pre-period, 3,860,842 individuals with no exposure to PIM in 2011 were matched to 508,212 exposed individuals. Exposure effects of PIM use on health care costs and the number of prescribed substances were measured based on longitudinal claims data from the four separate quarters of the 12-month post-period. RESULTS: After successful balancing for the development of numerous matching variables during the four quarters of the pre-period, exposed individuals consumed 2.1 additional prescribed substances and had higher total health care costs of 1,237 € when compared to non-exposed individuals in the 1st quarter of the post-period. Controlling for the number of prescribed substances, the difference in total health care costs between both study groups was 401 €. The average effect of one additionally prescribed substance (other than PIM) on total health care costs was increased by an amount of 137 € for those being exposed to a PIM. In quarters 2-4 of the post-period, the differences between both study groups tended to decrease sequentially. CONCLUSIONS: PIM use has an increasing effect on the development of health care costs. This cost-increasing effect of PIM use is moderated by the number of prescribed substances.

Health Service Use, Costs, and Adverse Events Associated with Potentially Inappropriate Medication in Old Age in Germany: Retrospective Matched Cohort Study.

BACKGROUND: Drug-related problems are an important healthcare safety concern in the growing population of older people. Prescription of potentially inappropriate medication (PIM) is one aspect of this concern that is considered to increase the risk of adverse health outcomes. OBJECTIVE: The aim of the Health Economics of Potentially Inappropriate Medication (HEPIME) study was to analyze the association between the prescription of PIMs according to the German PRISCUS list and healthcare utilization, healthcare costs, and the occurrence of adverse events in old age. METHODS: Insurants of a large German health insurance company aged 65+ years were included in a retrospective matched cohort study. A total of 3,953,423 individuals with no exposure to PIM in 2011 were matched to 521,644 exposed individuals and compared in terms of outpatient healthcare utilization, healthcare costs, and the occurrence of adverse events in outpatient, hospital, and rehabilitation sectors during a 12-month follow-up. RESULTS: On average, individuals in the exposed group had additional 143 [95% confidence interval (CI) 140-146] daily defined doses of pharmaceuticals and 4.5 (95% CI 4.4-4.6) days in hospital. Mean annual total healthcare costs per individual in the exposed group exceeded those in the non-exposed group by €2321 (95% CI 2269-2372), resulting mainly from differences in hospitalization costs of €1718 (95% CI 1678-1759). Odds ratios for the occurrence of adverse events in the exposed group were 1.32 (95% CI 1.32-1.34) in the outpatient sector, 1.76 (95% CI 1.73-1.79) in the hospital sector, and 1.82 (95% CI 1.76-1.89) in the rehabilitation sector. CONCLUSIONS: Increased healthcare utilization and costs as well as an increased probability for adverse events in individuals exposed to PIM demonstrate the health economic relevance of PIM prescriptions. Whether avoiding PIM listed on the PRISCUS list may potentially improve the quality and efficiency of healthcare is currently unknown.

A Longitudinal Investigation of Willingness to Pay for Health Insurance in Germany.

OBJECTIVE: To investigate factors affecting willingness to pay (WTP) for health insurance of older adults in a longitudinal setting in Germany. DATA SOURCES: Survey data from a cohort study in Saarland, Germany, from 2008-2010 and 2011-2014 (n1  = 3,124; n2  = 2,761) were used. STUDY DESIGN: Panel data were taken at two points from an observational, prospective cohort study. DATA COLLECTION: WTP estimates were derived using a contingent valuation method with a payment card. Participants provided data on sociodemographics, lifestyle factors, morbidity, and health care utilization. PRINCIPAL FINDINGS: Fixed effects regression models showed higher individual health care costs to increase WTP, which in particular could be found for members of private health insurance. Changes in income and morbidity did not affect WTP among members of social health insurance, whereas these predictors affected WTP among members of private health insurance. CONCLUSIONS: The fact that individual health care costs affected WTP positively might indicate that demanding (expensive) health care services raises the awareness of the benefits of health insurance. Thus, measures to increase WTP in old age should target at improving transparency of the value of health insurances at the moment when individual health care utilization and corresponding costs are still relatively low.

Comparative evaluation of methods approximating drug prescription durations in claims data: modeling, simulation, and application to real data.

PURPOSE: The purpose of this study was to compare the predictive accuracy of different methods suggested for approximation of drug prescription durations in claims data. METHODS: We expanded a well-established modeling and simulation framework to compare approximated drug prescription durations with 'true' (i.e., simulated) durations. Real claims data of persons aged ≥65 years insured by the German nationwide 'Statutory Health Insurance Fund' AOK between 2010 and 2012 provided empiric input parameters that were completed with missing information on actual dosing patterns from an observational cohort. The distinct approximation methods were based on crude measures (one tablet a day), population-averaged measures (defined daily doses), or individually-derived measures (longitudinal coverage approximation of the applied dose, COV). As a proof-of-principle, we assessed the methods' performance to predict the well-characterized bleeding risks of anticoagulant, antiplatelet, and/or non-steroidal anti-inflammatory drugs. RESULTS: When applied to modeling and simulation data sets, the closest, least biased, and thus most accurate approximation was observed using the COV approximation. In a real-data example, rather similar results to an external reference were obtained for all methods. However, some of the differences between methods were meaningful, and the most reasonable and consistent results were obtained with the COV approach. CONCLUSION: Based on theoretically most accurate approximations and practically reasonable estimates, the individual COV approach was preferable over the population-averaged defined daily dose technique, although the latter might be justified in certain situations. Advantages of the COV approach are expected to be even bigger for drug therapies with particularly large dosing heterogeneity. Copyright © 2016 John Wiley & Sons, Ltd.

Associations of frailty with health care costs--results of the ESTHER cohort study.

BACKGROUND: The concept of frailty is rapidly gaining attention as an independent syndrome with high prevalence in older adults. Thereby, frailty is often related to certain adverse outcomes like mortality or disability. Another adverse outcome discussed is increased health care utilization. However, only few studies examined the impact of frailty on health care utilization and corresponding costs. The aim of this study was therefore to investigate comprehensively the relationship between frailty, health care utilization and costs. METHODS: Cross sectional data from 2598 older participants (57-84 years) recruited in the Saarland, Germany, between 2008 and 2010 was used. Participants passed geriatric assessments that included Fried's five frailty criteria: weakness, slowness, exhaustion, unintentional weight loss, and physical inactivity. Health care utilization was recorded in the sectors of inpatient treatment, outpatient treatment, pharmaceuticals, and nursing care. RESULTS: Prevalence of frailty (≥3 symptoms) was 8.0%. Mean total 3-month costs of frail participants were €3659 (4 or 5 symptoms) and €1616 (3 symptoms) as compared to €642 of nonfrail participants (no symptom). Controlling for comorbidity and general socio-demographic characteristics in multiple regression models, the difference in total costs between frail and non-frail participants still amounted to €1917; p < .05 (4 or 5 symptoms) and €680; p < .05 (3 symptoms). Among the 5 symptoms of frailty, weight loss and exhaustion were significantly associated with total costs after controlling for comorbidity. CONCLUSIONS: The study provides evidence that frailty is associated with increased health care costs. The analyses furthermore indicate that frailty is an important factor for health care costs independent from pure age and comorbidity. Costs were rather attributable to frailty (and comorbidity) than to age. This stresses that the overlapping concepts of multimorbidity and frailty are both necessary to explain health care use and corresponding costs among older adults.

Health service use and costs associated with excess weight in older adults in Germany.

BACKGROUND: excess weight is a risk factor for numerous co-morbidities that predominantly occur in later life. This study's purpose was to analyse the association between excess weight and health service use/costs in the older population in Germany. METHODS: this cross-sectional analysis used data of n = 3,108 individuals aged 58-82 from a population-based prospective cohort study. Body mass index (BMI) and waist-to-height ratio (WHtR) were calculated based on clinical examinations. Health service use was measured by a questionnaire for a 3-month period. Corresponding costs were calculated applying a societal perspective. RESULTS: 21.8% of the sample were normal weight, 43.0% overweight, 25.5% obese class 1 and 9.6% obese class ≥2 according to BMI. In 42.6%, WHtR was ≥0.6. For normal weight, overweight, obese class 1 and obese class ≥2 individuals, mean costs (3-month period) of outpatient care were 384€, 435€, 475€ and 525€ (P < 0.001), mean costs of inpatient care were 284€, 408€, 333€ and 652€ (P = 0.070) and mean total costs 716€, 891€, 852€ and 1,244€ (P = 0.013). For individuals with WHtR <0.6 versus ≥0.6, outpatient costs were 401€ versus 499€ (P < 0.001), inpatient costs 315€ versus 480€ (P = 0.016) and total costs 755€ versus 1,041€ (P < 0.001). Multiple regression analyses controlling for sociodemographic variables showed a significant effect of obesity on costs of outpatient care (class 1: +72€; class ≥2: +153€) and total costs (class ≥2: +361€) while the effect of overweight was not significant. WHtR ≥0.6 significantly increased outpatient costs by +79€ and total costs by +189€. CONCLUSIONS: excess weight is associated with increased service use and cost in elderly individuals, in particular in obese class ≥2 individuals.

Health care costs in the elderly in Germany: an analysis applying Andersen's behavioral model of health care utilization.

BACKGROUND: To analyze the association of health care costs with predisposing, enabling, and need factors, as defined by Andersen's behavioral model of health care utilization, in the German elderly population. METHODS: Using a cross-sectional design, cost data of 3,124 participants aged 57-84 years in the 8-year-follow-up of the ESTHER cohort study were analyzed. Health care utilization in a 3-month period was assessed retrospectively through an interview conducted by trained study physicians at respondents' homes. Unit costs were applied to calculate health care costs from the societal perspective. Socio-demographic and health-related variables were categorized as predisposing, enabling, or need factors as defined by the Andersen model. Multimorbidity was measured by the Cumulative Illness Rating Scale for Geriatrics (CIRS-G). Mental health status was measured by the SF-12 mental component summary (MCS) score. Sector-specific costs were analyzed by means of multiple Tobit regression models. RESULTS: Mean total costs per respondent were 889 € for the 3-month period. The CIRS-G score and the SF-12 MCS score representing the need factor in the Andersen model were consistently associated with total, inpatient, outpatient and nursing costs. Among the predisposing factors, age was positively associated with outpatient costs, nursing costs, and total costs, and the BMI was associated with outpatient costs. CONCLUSIONS: Multimorbidity and mental health status, both reflecting the need factor in the Andersen model, were the dominant predictors of health care costs. Predisposing and enabling factors had comparatively little impact on health care costs, possibly due to the characteristics of the German social health insurance system. Overall, the variables used in the Andersen model explained only little of the total variance in health care costs.

Inequalities in out-of-pocket payments for health care services among elderly Germans--results of a population-based cross-sectional study.

INTRODUCTION: In order to limit rising publicly-financed health expenditure, out-of-pocket payments for health care services (OOPP) have been raised in many industrialized countries. However, higher health-related OOPP may burden social subgroups unequally. In Germany, inequalities in OOPP have rarely been analyzed. The aim of this study was to examine OOPP of the German elderly population in the different sectors of the health care system. Socio-economic and morbidity-related determinants of inequalities in OOPP were analyzed. METHODS: This cross-sectional analysis used data of N = 3,124 subjects aged 57 to 84 years from a population-based prospective cohort study (ESTHER study) collected in the Saarland, Germany, from 2008 to 2010. Subjects passed a geriatric assessment, including a questionnaire for health care utilization and OOPP covering a period of three months in the following sectors: inpatient care, outpatient physician and non-physician services, medical supplies, pharmaceuticals, dental prostheses and nursing care. Determinants of OOPP were analyzed by a two-part model. The financial burden of OOPP for certain social subgroups (measured by the OOPP-income-ratio) was investigated by a generalized linear model for the binomial family. RESULTS: Mean OOPP during three months amounted to €119, with 34% for medical supplies, 22% for dental prostheses, 21% for pharmaceuticals, 17% for outpatient physician and non-physician services, 5% for inpatient care and 1% for nursing care. The two-part model showed a significant positive association between income (square root equivalence scale) and total OOPP. Increasing morbidity was associated with significantly higher total OOPP, and in particular with higher OOPP for pharmaceuticals. Total OOPP amounted to about 3% of disposable income. The generalized linear model for the binomial family showed a significantly lower financial burden for the wealthiest quintile as compared to the poorest one. CONCLUSIONS: This is the first study providing evidence of inequalities in OOPP in the German elderly population. Socio-economic and morbidity-related inequalities in OOPP and the resulting financial burden could be identified. The results of this study may contribute to the discussion about the mechanisms causing the observed inequalities and can thus help decision makers to consider them when adapting future regulations on OOPP.

[Tablet splitting: do discount contracts influence prescribing quality?]. / Teilung von Tabletten: Welchen Einfluss haben die Rabattverträge auf die Verordnungsqualität?

BACKGROUND: In Germany, about one fourth of all tablets are split before ingestion. Since April 2007, by German law, pharmacists are legally obligated to substitute a prescribed drug for a generic drug, provided the patients' health insurance company has made corresponding contracts with pharmaceutical companies (discount contracts). However, generic drugs may differ substantially in their splitting properties. Until now it is unknown how generic substitutions due to discount contracts will influence the prescribing quality with regard to tablet splitting. METHODS: The prescription data of 425 ambulatory patients with polymedication insured at the Allgemeine Ortskrankenkasse (AOK) were analyzed and their drugs switched according to current discount contracts. RESULTS: Altogether 24% of all tablets were split before ingestion. For 54% of these split tablets (182 of 335) existing discount contracts mandated generic substitution. In about 10% of the substitutions there was a chance of substituting a scored tablet for a dosage form not suitable for splitting (unscored tablet or capsule). BACKGROUND: Therefore, current legislation should not only aim at reducing medication cost but also safeguard both effectiveness of the drugs and handling by the patients.

Asthma patients with low perceived burden of illness: a challenge for guideline adherence.

RATIONALE AND AIMS: The reason why many patients seem to tolerate suffering from sub-optimal treated asthma remains unclear. The aim was to evaluate the guideline adherence combined with quality of life of patients with moderate to severe asthma. METHODS: 256 asthma patients from 43 primary care practices in Saxony-Anhalt filled in a questionnaire including the Asthma Quality of Life Questionnaire (AQLQ), the Patient Health Questionnaire (PHQ-D) and questions evaluating the asthma severity, medication and self-management. RESULTS: 43.4% suffered from moderate to severe asthma. Drug treatment accorded with guidelines in 36.9%, drug dosage of inhaled steroids was too low in 34.3%, and 21.5% were not treated according to guidelines. A total of 7.3% of the patients received end-of-dose therapy. AQLQ declined and depression rose with asthma severity and guideline non-adherence (P < 0.001). Only 29.1% received asthma education. However, 64.5% of the patients without education did not want to receive education. They had a higher quality of life, lower depression (P < 0.001) and lower use of steroids (P = 0.016). Higher depression scores where related with hospital admission (OR 3.29; 95% CI 1.57-6.87 for each quartile of PHQ-D) and unscheduled home visits or ambulatory care (OR 1.58; 1.07-2.33). CONCLUSION: There is a large variation of asthma severity which can partly be explained by the guideline adherence of medication and deficits of patients' management. The perceived burden of illness plays a more important role for education and self-management than the real severity of disease. Therefore, target-oriented interventions are needed to identify and motivate patients at risk.