Medication Adherence and Healthcare Costs in Chronically Ill Patients Using German Claims Data.

BACKGROUND AND OBJECTIVE: Despite the importance of medication adherence for chronically ill patients and the vast literature on its relationship to costs, this field suffers from methodological limitations. These are caused, amongst others, by the lack of generalizability of data sources, varying definitions of adherence, costs, and model specification. We aim to address this with different modeling approaches and to contribute evidence on the research question. METHODS: We extracted large cohorts of nine chronic diseases (n = 6747-402,898) from German claims data of stationary health insurances between 2012 and 2015 (t0-t3). Defined as the proportion of days covered by medication, we examined the relationship of adherence using several multiple regression models at baseline year t0 with annual total healthcare costs and four sub-categories. Models with concurrent, and differently time-lagged measurements of adherence and costs were compared. Exploratively, we applied non-linear models. RESULTS: Overall, we found a positive association between the proportion of days covered by medication and total costs, a weak association with outpatient costs, positive with pharmacy costs, and frequently negative with inpatient costs. There were major differences by disease and its severity but little between years, provided adherence and costs were not measured concurrently. The fit of linear models was mainly not inferior to that of non-linear models. CONCLUSIONS: The estimated effect on total costs differed from most other studies, which highlights concerns about generalizability, although effect estimates in sub-categories were as expected. Comparison of time lags indicates the importance of avoiding concurrent measurement. A non-linear relationship should be considered. These methodological approaches are valuable in future research on adherence and its consequences.

Identification of target groups and individuals for adherence interventions using tree-based prediction models.

Background: In chronically ill patients, medication adherence during implementation can be crucial for treatment success and can decrease health costs. In some populations, regression models do not show this relationship. We aim to estimate subgroup-specific and personalized effects to identify target groups for interventions. Methods: We defined three cohorts of patients with type 1 diabetes (n = 12,713), type 2 diabetes (n = 85,162) and hyperlipidemia (n = 117,485) from German claims data between 2012 and 2015. We estimated the association of adherence during implementation in the first year (proportion of days covered) and mean total costs in the three following years, controlled for sex, age, Charlson's Comorbidity Index, initial total costs, severity of the disease and surrogates for health behavior. We fitted three different types of models on training data: 1) linear regression models for the overall conditional associations between adherence and costs, 2) model-based trees to identify subgroups of patients with heterogeneous adherence effects, and 3) model-based random forests to estimate personalized adherence effects. To assess the performance of the latter, we conditionally re-estimated the personalized effects using test data, the fixed structure of the forests, and fixed effect estimates of the remaining covariates. Results: 1) our simple linear regression model estimated a positive adherence effect, that is an increase in total costs of 10.73 Euro per PDC-point and year for diabetes type 1, 3.92 Euro for diabetes type 2 and 1.92 Euro for hyperlipidemia (all p ≤ 0.001). 2) The model-based tree detected subgroups with negative estimated adherence effects for diabetes type 2 (-1.69 Euro, 24.4% of cohort) and hyperlipidemia (-0.11 Euro, 36.1% and -5.50 Euro, 5.3%). 3) Our model-based random forest estimated personalized adherence effects with a significant proportion (4.2%-24.1%) of negative effects (up to -8.31 Euro). The precision of these estimates was high for diabetes type 2 and hyperlipidemia patients. Discussion: Our approach shows that tree-based models can identify patients with different adherence effects and the precision of personalized effects is measurable. Identified patients can form target groups for adherence-promotion interventions. The method can also be applied to other outcomes such as hospitalization risk to maximize positive health effects of an intervention.

Treatment Costs of Colorectal Cancer by Sex and Age: Population-Based Study on Health Insurance Data from Germany.

Objective: Evidence on the cost-effectiveness of screening for colorectal cancer (CRC) in the German general population remains scarce as key input parameters, the costs to treat CRC, are largely unknown. Here, we provide detailed estimates on CRC treatment costs over time. Methods: Using insurance claims data from the Vilua healthcare research database, we included subjects with newly diagnosed CRC and subjects who died of CRC between 2012 and 2016. We assessed annualized CRC-related inpatient, outpatient and medication costs for up to five years after first diagnosis and prior to death, stratified by sex and age. Findings: We identified 1748 and 1117 subjects with follow-up data for at least 1 year after diagnosis and prior to death, respectively. In those newly diagnosed, average costs were highest in the first year after diagnosis (men, EUR 16,375−16,450; women, EUR 10,071−13,250) and dropped steeply in the following years, with no consistent pattern of differences with respect to age. Costs prior to death were substantially higher as compared to the initial phase of care and consistently on a high level even several years before death, peaking in the final year of life, with strong differences by sex and age (men vs. women, <70 years, EUR 34,351 vs. EUR 31,417; ≥70 years, EUR 14,463 vs. EUR 9930). Conclusion: Once clinically manifest, CRC causes substantial treatment costs over time, particularly in the palliative care setting. Strong differences in treatment costs by sex and age warrant further investigation.

[Prevalence of Rheumatoid Arthritis in Germany: Analysis of Longitudinal Data of Statutory Health Insurance]. / Prävalenz der Rheumatoiden Arthritis in Deutschland: Analyse von Längsschnittdaten der Gesetzlichen Krankenversicherung.

BACKGROUND: Rheumatoid arthritis (RA) is a progressive chronic inflammatory systemic autoimmune disease with destructive joint changes. Data on prevalence in adult patients are only available to a limited extent in Germany. METHODOLOGY: Anonymised diagnosis and prescription data for 2008-2013 were evaluated at patient level for approximately 2.3 million insured adults (total data set; status 2013) and approx. 1.2 million insured adults (smaller data set with additional information such as treatment by a specialist; status 2013) from 7 different statutory health insurance companies. RA was diagnosed if the code M05 (seropositive chronic polyarthritis) or M06 (other chronic polyarthritis) was present (diagnosis group M0[5,6]) and if the patient was either an outpatient at least twice (in 2 different quarters) or at least once an inpatient within a calendar year (according to the BVA criteria, inpatient diagnoses were thus classified as more reliable). The data were extrapolated to the SHI-insured and total population in Germany for 2013. RESULTS: The prevalence of RA in the total data set was 1.26% on average over all years (2008-2013). More than 90% of the diagnosis was based on the diagnosis code M06. In 88% of the cases, the classification was based exclusively on outpatient diagnoses. Taking into account a diagnosis by a specialist based on a smaller data set containing this additional information to determine a "reliable" RA diagnosis, the average RA rate for 2011-2013 was about 0.99%. Related to the diagnosis group M0[5,6] in the total data set, the prevalence of RA in 2013 was about 1.8% of women and about 0.8% of men. Only about 40% of diagnosed patients were treated with DMARDs. CONCLUSIONS: The prevalence estimates for RA derived from the larger data set correspond to those of previous surveys with partially different methodological approaches. Based on the analysis of the health insurance data presented, the prevalence of diagnosed RA in adults in Germany is 1.26%, which is within the range of 0.81-1.62% that can be found in the literature. This represents about 721,000 adult SHI-insured persons. The low rate of DMARD prescriptions may indicate inadequate care of these patients.

Burden and epidemiology of status epilepticus in infants, children, and adolescents: A population-based study on German health insurance data.

OBJECTIVE: Status epilepticus (SE) is an important medical emergency condition with particularly unfavorable outcome in refractory and superrefractory SE (SRSE). The economic impact of SE and especially of SRSE in the pediatric population remains unclear. We aimed to determine the burden of illness of SE in a pediatric patient population. METHODS: Insurance records for patients aged 0-18 years admitted between 2008 and 2015 were selected from a nationwide insurance research database utilizing International Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) codes for SE (G41), epilepsy (G40), or febrile convulsions (R56). Patients were further classified based on admission to the intensive care unit and use of mechanical ventilation. RESULTS: The algorithm identified 11 693 seizure-related admissions and classified 4% as SE. Of these cases, 282 (60.4%) were classified by the algorithm as nonrefractory SE (NRSE), 125 (26.8%) as refractory SE (RSE), and 60 (12.8%) as SRSE. The crude SE incidence was 17.6/100 000, with NRSE being 11.4/100 000, RSE 3.9/100 000, and SRSE 2.3/100 000. SRSE incidence peaked in the 0- to 1-year-old age subgroup accounting for 48.3% of all pediatric SRSE admissions. The median length of stay (LOS) for all SE cases was 7 days, with median 44.5 days in SRSE, 5 days in NRSE, and 12 days in RSE. Mean admission costs for total SE were €15 880, with a mean expense for SRSE of €75 358, for NRSE of €4119, and for RSE of €13 864. The mean LOS for non-SE epilepsy admissions was 3 days, with mean costs of €2697 for epilepsy and €1614 for febrile convulsion admissions. There were no deaths in non-SE and NRSE admissions, whereas the overall mortality for SE was 3%, with 5.6% in RSE and 11.7% in SRSE. SIGNIFICANCE: Although cases classified as SE represented 4% of the seizure-associated admissions, they accounted for 22% of the overall costs. These costs were disproportionately represented by SRSE cases, which accounted for 62% of all SE-associated costs.

Costs, length of stay, and mortality of super-refractory status epilepticus: A population-based study from Germany.

OBJECTIVE: Super-refractory status epilepticus (SRSE) is a severe condition in which a patient in status epilepticus (SE) for ≥24 h does not respond to first-, second-, or third-line therapy. The economic impact of SRSE treatment remains unclear. A health insurance research database was used for a population-based estimation of SRSE-associated inpatient costs, length of stay, and mortality in Germany. METHODS: An algorithm using International Classification of Diseases, 10th Edition coding and treatment parameters identified and classified patients in a German statutory health insurance database covering admissions from 2008 to 2013 as having refractory SE (RSE) or SRSE. Admissions data in our study refer to these classifications. Associated patient data included costs, procedures, and demographics. RESULTS: The algorithm identified 2,585 (all type) SE admissions, classified as 1,655 nonrefractory SE (64%), 592 (22.9%) RSE, and 338 (13.1%) SRSE, producing database incidence rates of 15.0 in 100,000, 5.2 in 100,000, and 3.0 in 100,000 per year, respectively. Median cost per admission was €4,063 for nonrefractory SE, €4,581 (p < 0.001) for RSE, and €32,706 (p < 0.001) for SRSE. Median length of stay varied significantly between 8 days (mean = 13.6) in nonrefractory SE, 14 days in RSE, and up to 37 days in SRSE. Discharge mortality increased from 9.6% in nonrefractory SE to 15.0% (p < 0.001) in RSE and 39.9% (p < 0.001) in SRSE. SIGNIFICANCE: This study evaluated the hospital treatment costs associated with admissions classified by the algorithm as SRSE in Germany. SRSE represented 13% of all SE admissions, but resulted in 56% of all SE-related costs. The lack of approved treatments and limited number of evidence-based treatment guidelines highlight the need for further evaluations of the SRSE burden of illness and the potential for further optimization of treatments for SRSE.

Impact of chronic ischemic heart disease on the health care costs of COPD patients - An analysis of German claims data.

OBJECTIVES: Chronic Obstructive Pulmonary Disease (COPD) has a substantial impact on health care systems worldwide. Particularly, cardiovascular diseases such as ischemic heart disease (IHD) are frequent in individuals with COPD, but the economic consequences of combined COPD and IHD are by large unknown. Therefore, our study has the objective to investigate excess costs of IHD in COPD patients. METHODS: Out of German Statutory Health Insurance claims data we identified 26,318 COPD patients with and 10,287 COPD patients without IHD based on ICD-10 codes (COPD J44; IHD I2[0,1,2,5]) of the year 2011 and matched 9986 of them in a 1:1 ratio based on age and gender. Then, we investigated health care service expenditures in 2012 via Generalized Linear Models. Moreover, we evaluated a potential non-linear association between health care expenditures and age in a gender-stratified Generalized Additive Model. RESULTS: The prevalence of IHD in individuals with COPD increases with rising age up to a share of 50%. COPD patients with IHD cause adjusted mean annual per capita health care service expenditures of ca. €7400 compared with ca. €5800 in COPD patients without IHD. Moreover, excess costs of IHD have an inverse u-shape, peaking in the early (men) respectively late seventies (women). CONCLUSIONS: IHD in COPD patients is associated with excess costs of ca. € 1,500, with the exact amount varying age- and gender-dependently. Subgroups with high excess costs indicate medical need that calls for efficient care strategies, considering COPD and IHD together particularly between 70 and 80 years of age.

Guideline conform initial monotherapy increases in patients with focal epilepsy: A population-based study on German health insurance data.

PURPOSE: To examine the implementation of the clinical practice guideline "first epileptic seizure and epilepsy in adulthood" published in 2008 to patients with newly diagnosed epilepsy between 2008 and 2014. METHOD: This retrospective, population-based analysis was performed on patient data of 4.1 million insurants from the German statutory health insurance. Prevalent and incident cases in adults were identified based on ICD-10 codes, using a hierarchical diagnosis selection algorithm. The first anticonvulsive agent in a newly diagnosed epilepsy patient was validated against the clinical practice guideline. RESULTS: We determined an annual crude prevalence rate in adults between 0.946% and 1.090% and incidence rates of at least 156 per 100,000. A significant increase in guideline compliant monotherapy was found in patients with a focal epilepsy syndrome, while, among patients with idiopathic generalised epilepsies, the share of guideline noncompliant monotherapy increased. Both changes are likely due to the overall increase in prescription of levetiracetam from 19.6% in 2008 to 58.9% in 2014 in all newly treated patients. Overall, the proportion of enzyme-inducing anticonvulsants fell significantly from 20.7% in 2008 to 4.3% in 2014 (p<0.001). The likelihood to receive non-enzyme-inducing antiepileptic drugs was 5.82 (95% CI 4.62-7.33) higher in 2014 than in 2008. CONCLUSION: Initial monotherapy for focal epilepsy is in line with current clinical practice guidelines and mainly implemented by prescription of levetiracetam. Further evaluations should address the question of whether patients treated in line with the guidelines have a favorable outcome, compared to patients not treated in line with current guidelines.