[Research Data Center on Health - Vision for Further Development from the Research Perspective]. / Forschungsdatenzentrum Gesundheit ­ Vision für eine Weiterentwicklung aus Sicht der Forschung.

The German research data center for health will provide claims data of statutory health insurances. The data center was set up at the medical regulatory body BfArM pursuant to the German data transparency regulation (DaTraV). The data provided by the center will cover about 90% of the German population, supporting research on healthcare issues, including questions of care supply, demand and the (mis-)match of both. These data support the development of recommendations for evidence-based healthcare. The legal framework for the center (including §§ 303a-f of Book V of the Social Security Code and two subsequent ordinances) leaves a considerable degree of freedom when it comes to organisational and procedural aspects of the center's operation. The present paper addresses these degrees of freedom. From the point of view of researchers, ten statements show the potential of the data center and provide ideas for its further and sustainable development.

Causal analyses with target trial emulation for real-world evidence removed large self-inflicted biases: systematic bias assessment of ovarian cancer treatment effectiveness.

BACKGROUND AND OBJECTIVES: Drawing causal conclusions from real-world data (RWD) poses methodological challenges and risk of bias. We aimed to systematically assess the type and impact of potential biases that may occur when analyzing RWD using the case of progressive ovarian cancer. METHODS: We retrospectively compared overall survival with and without second-line chemotherapy (LOT2) using electronic medical records. Potential biases were determined using directed acyclic graphs. We followed a stepwise analytic approach ranging from crude analysis and multivariable-adjusted Cox model up to a full causal analysis using a marginal structural Cox model with replicates emulating a reference randomized controlled trial (RCT). To assess biases, we compared effect estimates (hazard ratios [HRs]) of each approach to the HR of the reference trial. RESULTS: The reference trial showed an HR for second line vs. delayed therapy of 1.01 (95% confidence interval [95% CI]: 0.82-1.25). The corresponding HRs from the RWD analysis ranged from 0.51 for simple baseline adjustments to 1.41 (95% CI: 1.22-1.64) accounting for immortal time bias with time-varying covariates. Causal trial emulation yielded an HR of 1.12 (95% CI: 0.96-1.28). CONCLUSION: Our study, using ovarian cancer as an example, shows the importance of a thorough causal design and analysis if one is expecting RWD to emulate clinical trial results.

Treatment Patterns and Healthcare Resource Utilization Among Patients with Atopic Dermatitis: A Retrospective Cohort Study Using German Health Claims Data.

INTRODUCTION: Atopic dermatitis (AD) is a common inflammatory skin disease. Many patients are initiating a systemic therapy, if the disease is not adequately controlled with topical treatment only. Currently, there is little real-world evidence on the AD-related medical care situation in Germany. This study analyzed patient characteristics, treatment patterns, healthcare resource utilization and costs associated with systemically treated AD for the German healthcare system. METHODS: In this descriptive, retrospective cohort study, aggregated anonymized German health claims data from the InGef research database were used. Within a representative sample of four million insured individuals, patients with AD and systemic drug therapy initiation (SDTI) in the index year 2017 were identified and included into the study cohort. Systemic drug therapy included dupilumab, systemic corticosteroids (SCS) and systemic immunosuppressants (SIS). Patients were observed for one year starting from the date of SDTI in 2017. RESULTS: 9975 patients were included (57.8% female, mean age 39.6 years [SD 25.5]). In the one-year observation period, the most common systemic drug therapy was SCS (> 99.0%). Administrations of dupilumab (0.3%) or dispensations of SIS were rare (cyclosporine: 0.5%, azathioprine: 0.6%, methotrexate: 0.1%). Median treatment duration of SCS, cyclosporine and azathioprine was 27 days, 102 days, and 109 days, respectively. 2.8% of the patients received phototherapy; 41.6% used topical corticosteroids and/or topical calcineurin inhibitor. Average annual costs for medications amounted to € 1237 per patient. Outpatient services were used by 99.6% with associated mean annual costs of € 943; 25.4% had at least one hospitalization (mean annual costs: € 5836). 5.3% of adult patients received sickness benefits with associated mean annual costs of € 5026. CONCLUSIONS: Despite unfavorable risk-benefit profile, this study demonstrated a common treatment with SCS, whereas other systemic drug therapy options were rarely used. Furthermore, the results suggest a substantial economic burden for patients with AD and SDTI.

Preferences for and use of oral anticoagulants for stroke prevention in atrial fibrillation under real-world conditions in Germany: A survey among physicians.

In Germany, there is little real-world evidence on physicians' choice of oral anticoagulants (OACs). Our study aimed at assessing preferences for and prescribing patterns of treatment options for stroke prevention in atrial fibrillation in clinical practice in Germany. We conducted a nationwide quantitative online survey among office-based physicians in Germany. Physicians were asked about their preference for and use of treatment options as well as factors influencing their choice of a specific OAC. A total of n = 953 physicians was surveyed in September and October 2020 (general physicians: 36.0%; internists: 37.3%; cardiologists: 23.7%; neurologists: 10.5%; multiple specialties possible). Preference and use were highest for non-vitamin K oral anticoagulants (NOACs); followed by vitamin K antagonists (VKAs). Most preferred OACs were apixaban (39.3%), rivaroxaban (28.5%) and edoxaban (14.7%). Most used OACs were apixaban (24.3%), rivaroxaban (21.2%) and phenprocoumon (21.4%). NOACs were preferred more often than used (85.6% > 68.6%). VKAs were preferred less often than used (9.6% < 23.5%). OAC attributes and patient characteristics related to efficacy and safety, as well as patients' kidney function were most important when selecting a specific OAC. Federal and regional governance instruments likely influenced treatment decision-making. We found a high divergence between preferences for and use of available treatment options in clinical practice. Further exploration of the importance of OAC attributes, patient characteristics as well as federal and regional governance instruments for physicians' choice of a specific OAC may help to further optimize the healthcare of patients with atrial fibrillation in the long-term.

[What do We Mean by Secondary Data? - A Keynote Contribution to the Terminological Classification and Definition]. / Was verstehen wir unter Sekundärdaten? ­ Ein Grundsatzbeitrag zur terminologischen Einordnung und Definition.

Data are both material and product for health services research. As a "substrate" or starting point for health-related analyses, they have gained immense importance in recent decades. Data are an essential raw material for the assessment of services in the health care system, for its control and development. In everyday scientific life and in research work that uses this raw material, the meaning of the term "data" - especially "secondary data" - is often neglected. This article aims to shed more light on the context of meaning of the two terms and to attempt to classify the term "secondary data" terminologically.

[Now is the Time to Establish an Efficient Health Research Data Centre]. / Jetzt die Weichen stellen für ein leistungsfähiges Forschungsdatenzentrum Gesundheit.

Based on sections 303a to 303f social code book V, the course is currently being set for an innovative and high-performance national information and data platform. This requires short-term provision of current and relevant data on the health care system, especially process data on statutory health insurance and other social insurance carriers, using established methodological standards as well as taking into account data protection regulations. From the point of view of future users, expectations regarding an "ideal" research health data centre are formulated in ten recommendations. The present article is an offer from health services researchers intended to support decision-makers in the field of politics and self-administration in the German health system in their task of establishing and further development of a research health data centre.

[Dementia prevention and primary care: Estimation of the target population]. / Demenzprävention und hausärztliche Versorgung: Schätzung der Zielpopulation.

BACKGROUND: The prevention of dementia, especially the cardiovascular prevention of cognitive disorders, is increasingly coming into the focus of health services research. The aim of this study is to determine the possible target population for dementia prevention approaches as well as frequency of health examinations (HE) in individual general practitioner offices (GP). METHOD: 987 GP practices, which are covered by the nationwide IMS Disease Analyzer database (IQVIA) have been investigated for the prevalence of the following diagnoses, which are considered risk factors for the development of dementia Hypertension, obesity, hearing loss in each age group 45-65 and diabetes and depression in the age group 65 and older. In addition, it was recorded how many of these patients received a HE). RESULTS: In a sample of 2,398,405 patients receiving primary care, the target population relevant for dementia prevention measures in 2018 consisted of 191,883 patients with hypertension, 23,308 with obesity, 5,059 with hearing loss, 120,200 with diabetes and 43,233 with depression. More than a quarter of these patients have already had a HE. In 2018, patients with hypertension (N=51), diabetes (N=30.5) and depression (N=11.3) were the most frequently treated patients, less frequently patients with obesity (N=8.2) and hearing loss (N=1.6). CONCLUSION: On the basis of defined diagnoses in certain phases of life, a manageable group of patients can be identified who are eligible for specific dementia preventive interventions. The implementation of dementia preventive interventions in practices will be more difficult for the less frequent treatment diagnoses obesity and hearing loss than for the much more frequent treatment diagnoses hypertension, diabetes and depression.

The patient journey of patients with Fabry disease, Gaucher disease and Mucopolysaccharidosis type II: A German-wide telephone survey.

BACKGROUND: Lysosomal Storage Diseases (LSD) are rare and multisytemic diseases which are caused by lysosomal enzyme deficiencies leading into accumulation of waste products due to an interruption in the decomposition process. Due to the low prevalence and therefore limited disease awareness as well as the fact that LSD patients present with unspecific symptoms the final diagnosis is often made after a long delay. The aim of this German-wide survey was to characterize the period between onset of symptoms and final diagnosis regarding e.g. self-perceived health, symptom burden and false diagnoses for patients with selected LSDs (Fabry disease (FD), Gaucher disease (GD) and Mucopolysaccharidosis type II (MPS II). METHODS: The study was conducted as a telephone based cross-sectional survey. All patients living in Germany with a confirmed diagnosis of FD, GD or MPS II were eligible to participate. The questionnaire was provided in advance in order to enable the participants to prepare for the interview. Only descriptive analyses were carried out. Single analyses were not carried out for all three patient groups due low case numbers. RESULTS: Of the overall population, 39 patients have been diagnosed with FD, 19 with GD and 11 with MPS II with the majority of patients being index patients. The majority of FD patients reported their current health status as "satisfactory" or better (79.5%). Self-perceived health status was observed to be at least stable or improving for the majority of FD patients compared to the year prior to diagnosis. The most frequently reported symptoms for patients with FD were paraesthesias (51.3%), whereas patients with GD reported a tendency for bleeding, blue spots or coagulation disorder (63.2%) as well as hepatomegaly and/or splenomegaly (63.2%) as the most commonly appearing symptoms. The number of patients reporting misdiagnoses was n = 5 (13.5%) for patients with FD and n = 5 (27.8%) for patients with GD. The median duration of the diagnostic delay was 21.0 years for FD, 20.0 years for GD and 2.0 years for MPS II. CONCLUSIONS: This study showed that self-perceived status of health for patients might improve once the final correct diagnoses has been made and specific treatment was available. Furthermore, it was observed that diagnostic delay is still high in Germany for a relevant proportion of affected patients. Further challenges in the future will still be to increase awareness for these diseases across the entire healthcare sector to minimize the diagnostic delay.

A Germany-wide survey study on the patient journey of patients with hereditary angioedema.

BACKGROUND: Hereditary angioedema (HAE) is a rare genetic disease and characterized by clinical features such as paroxysmal, recurrent angioedema of the skin, the gastrointestinal tract, and the upper airways. Swelling of the skin occurs primarily in the face, extremities and genitals. Gastrointestinal attacks are accompanied by painful abdominal cramps, vomiting and diarrhea. Due to the low prevalence and the fact that HAE patients often present with rather unspecific symptoms such as abdominal cramps, the final diagnosis is often made after a long delay. The aim of this German-wide survey was to characterize the period between occurrence of first symptoms and final diagnosis regarding self-perceived health, symptom burden and false diagnoses for patients with HAE. RESULTS: Overall, 81 patients with HAE were included and participated in the telephone-based survey. Of those, the majority reported their current health status as "good" (47.5%) or "very good" (13.8%), which was observed to be a clear improvement compared to the year before final diagnosis ("good" (16.3%), "very good" (11.3%)). Edema in the extremities (85.2%) and in the gastrointestinal tract (81.5%) were the most currently reported symptoms and occurred earlier than other reported symptoms (mean age at onset 18.1 and 17.8 years, respectively). Misdiagnoses were observed in 50.6% of participating HAE patients with appendicitis and allergy being the most frequently reported misdiagnoses (40.0 and 30.0% of those with misdiagnosis, respectively). Patients with misdiagnosis often received mistreatment (80.0%) with pharmaceuticals and surgical interventions as the most frequently carried out mistreatments (65.6 and 56.3% of those with mistreatment, respectively). The mean observed diagnostic delay was 18.1 years (median 15.0 years). The diagnostic delay was higher in older patients and index patients. CONCLUSIONS: This study showed that self-perceived status of health for patients is much better once the final correct diagnosis has been made and specific treatment was available. Further challenge in the future will still be to increase awareness for HAE especially in settings which are normally approached by patients at occurrence of first symptoms to assure early referral to specialists and therefore increase the likelihood of receiving an early diagnosis.

Epidemiology, characteristics and treatment of patients with relapsing remitting multiple sclerosis and incidence of high disease activity: Real world evidence based on German claims data.

BACKGROUND: Multiple Sclerosis (MS) is a chronic inflammatory, immune mediated disease of the central nervous system, with Relapsing Remitting MS (RRMS) being the most common type. Within the last years, the status of high disease activity (HDA) has become increasingly important for clinical decisions. Nevertheless, little is known about the incidence, the characteristics, and the current treatment of patients with RRMS and HDA in Germany. Therefore, this study aims to estimate the incidence of HDA in a German RRMS patient population, to characterize this population and to describe current drug treatment routines and further healthcare utilization of these patients. METHODS: A claims data analyses has been conducted, using a sample of the InGef Research Database that comprises data of approximately four million insured persons from around 70 German statutory health insurances (SHI). The study was conducted in a retrospective cohort design, including the years 2012-2016. Identification of RRMS population based on ICD-10 code (ICD-10-GM: G35.1). For identification of HDA, criteria from other studies as well as expert opinions have been used. Information on incidence, characteristics and current treatment of patients with RRMS and HDA was considered. RESULTS: The overall HDA incidence within the RRMS population was 8.5% for 2016. It was highest for the age group of 0-19 years (29.4% women, 33.3% men) and lowest for the age group of ≥ 50 years (4.3% women, 5.6% men). Mean age of patients with RRMS and incident HDA was 38.4 years (SD: 11.8) and women accounted for 67.8%. Analyses of drug utilization showed that 82.4% received at least one disease-modifying drug (DMD) in 2016. A percentage of 49.8% of patients received drugs for relapse therapy. A share of 55% of RRMS patients with HDA had at least one hospitalization with a mean length of stay of 13.9 days (SD: 18.3 days) in 2016. The average number of outpatient physician contacts was 28.1 (SD: 14.0). CONCLUSIONS: This study based on representative Germany-wide claims data from the SHI showed a high incidence of HDA especially within the young RRMS population. Future research should consider HDA as an important criterion for the quality of care for MS patients.

[Linkage of Clinical and Claims Data in the Evaluation of Post-Stroke Care - SeDaStro: Experiences from the Tyrolian StrokeCard Program]. / Linkage von klinischen Primärdaten und Krankenkassenabrechnungsdaten in der Evaluation der Schlaganfallversorgung ­ SeDaStro: Erfahrungen aus dem Tiroler StrokeCard-Programm.

AIMS AND OBJECTIVES: Data linkage is of paramount importance in the evaluation of treatment regimens for chronic diseases where different health care sectors are involved. A comprehensive picture of long-term treatment effects and, in particular, the cost-effectiveness ratio of treatment approaches can only be drawn when data from various sources are merged and analyzed together. METHODOLOGICAL PROBLEMS AND CHALLENGES: Regarding post-acute stroke care, the present study gives an example of an exact deterministic data linkage procedure including clinical patient records and claims data of TGKK, the main Tyrolean statutory health insurance fund. Typical problems known from other data linkage projects also emerged in the so-called StrokeCard program conducted at the Medical University of Innsbruck. Distinctive Austrian features (the majority of the Austrian population benefits from a mandatory social insurance system without freedom of choice) facilitated the feasibility of the data linkage procedures. RESULTS: Over the recruitment period 01/2014-12/2015, 540 patients could be assigned to the operative dataset. Of these, 367 patients were part of the StrokeCard group (i. e. the treatment group), and 173 belonged to the usual care group (i. e. the control group); 11 patients did not complete the one-year follow-up period (7 treatment group patients vs. 4 control group patients); 7 of them died during the study (5 treatment group patients vs. 2 control group patients). For all 540 patients, TGKK claims data were available for the time-frames of one year before recruitment and one year after discharge from the University hospital. All data could be used in the health-economic evaluation of the StrokeCard program. CONCLUSIONS: The linking of clinical patient records with data collected by SHI funds opens a window of opportunities for analyses of medical care. Counter-intuitively, Austrian health services research activities have limited experience in data linkage approaches, alhough studies based on the linkage of clinical patient records and claims data are indispensable for the evaluation of complex multi-sectoral treatment schemes. The current project proves the feasibility of data linkage mechanisms in the Austrian context. This should be regarded as an impetus for extending data linkage principles to evaluation studies in the future.