1,721,047 research outputs found
Treatment patterns and characteristics of older antipsychotic users in Germany
No full textThe aim of this study was to investigate the characteristics and treatment patterns of older antipsychotic (AP) users in Germany. We carried out a cohort study in the German Pharmacoepidemiological Research Database and identified new AP users aged at least 65 years between 2005 and 2011. Possible indications, comedication, and information on persistence and adherence, concurrent multiple use, and switch of APs were assessed. Overall, 298847 individuals were included in the cohort. Almost 70% entered the cohort with a typical antipsychotic (TAP). Melperone (23.4%) was used most frequently, followed by promethazine (18.3%), sulpiride (11.0%), and risperidone (10.3%). AP users had a low prevalence of schizophrenia and bipolar disorders in contrast to dementia. Initiators of atypical antipsychotics had more treatment episodes compared with TAPs (median 3 vs. 2), but lower median persistence (14 vs. 22 days). Persistence was also lower in patients with, rather than without, dementia. The overall percentage of concurrent multiple use and switch to other APs was low with 5.6%, but higher in patients with, rather than without, dementia. In conclusion, APs were used for a broad range of indications, mostly other than schizophrenia and bipolar disorders. Low persistence and a high number of treatment episodes suggest frequent as-needed' treatment, especially in dementia patients
Claims data-based studies on off-label use in ambulatory care
No full textIn many medical disciplines, particularly in paediatrics, psychiatry and oncology, drugs are often prescribed off-label. An off-label use is defined as the practice of prescribing drugs outside the terms of the product license, especially prescribed for an unapproved indication or age group. One problem is the impact of off-label use on drug safety in terms of adverse drug reactions associated with these drugs. In Germany, only limited data investigating the extent of off-label use in ambulatory care exist. Over the years, the use of secondary data from large administrative healthcare databases for pharmacoepidemiological and health service research increased. Drug utilisation studies based on these population-based data are valuable to explore patterns of drug use including off-label use. This thesis investigates the ambulatory off-label use of antidepressant and antiepileptic drugs in paediatric patients and the ambulatory off-label use of lenalidomide in oncology patients based on claims data of statutory health insurances. Drug utilisation studies to evaluate off-label use are closing a gap in the ascertainment of drug safety after approval. As physician's prescription behaviour is not influenced, claims data of statutory health insurances are an important data source to study off-label use, particularly in patients that are often underrepresented in clinical trials
Klinische Epidemiologie von Impfungen und impfpräventablen Erkrankungen auf Basis von Routinedaten der gesetzlichen Krankenversicherung
No full textFor centuries, infectious diseases have been among the top 10 leading causes of death. In 2015, they accounted for about 11% of 56.4 million deaths worldwide indicating a global public health relevance. Vaccines provide an opportunity to eliminate or even eradicate infectious diseases. In order to maximize the benefit of vaccines while minimizing their risks, it is important to investigate infectious disease etiology as well as to continuously monitor and evaluate direct vaccination effects as well as indirect vaccination effects through herd immunity. Since vaccines are usually administered to healthy people to prevent infectious diseases, the monitoring of the safety of vaccines is of high importance. For their evaluation, there is usually no trade-off between risk of disease and risk of its treatment as is usually the case for the treatment of severe diseases. Vaccine safety is also essential for the acceptance of vaccines in the population and thus for high vaccine uptake to enable herd immunity. Epidemiological observational studies are a powerful tool to investigate the burden of vaccine-preventable diseases, direct and indirect vaccination effects as well as the safety of vaccines in a real-world setting, meaning they provide important data as they includea often in contrast to randomized controlled trialsa older or immunocompromised people as well as children or pregnant women, which are most often the target population groups for vaccinations. Administrative data are a valuable data source for epidemiological observational studies and are increasingly used for studies on vaccines and vaccine-preventable diseases. However, a comprehensive knowledge of the healthcare system itself, including reimbursement policies, but also of the data source and the containing information depth is required. This thesis investigates different aspects of vaccines and vaccine-preventable diseases. Thus, in a first study, the burden of the vaccine-preventable disease of herpes zoster (HZ) and its complications is investigated and in a separate study, the risk of stroke complication after HZ infection. Vaccine uptake of the human papillomavirus (HPV) vaccine at the population level as well as its indirect impact after vaccine recommendation is assessed. Furthermore, this thesis discusses the nested case-control design with respect to its potential use for direct effectiveness and safety studies of vaccines. Relevant methodological challenges when using different observational study designs based on administrative healthcare data as well as methods to control confounding or to reduce bias are elucidated and discussed. Finally, this thesis gives outlook on potential challenges of future studies on vaccines and vaccine-preventable diseases, especially with regard to newly developed therapeutic vaccines for chronic diseases
Epidemiology and health services research of cardiovascular diseases based on routine data of German statutory health insurances
No full textRoutine data of statutory health insurance providers (SHI) are increasingly used in health services research. The size, the longitudinal character of the data, the largely unselected populations as well as the possibility to evaluate routine care render SHI routine data an attractive data source for health services research. Since the data is generated for reimbursement processes, SHI routine data is limited with regard to the range and depth of information. Furthermore, the validity of the data for research purposes often is unclear. The aim of this thesis is to discuss the methodological challenges regarding the use of SHI routine data in health services research arising from the limitations inherent in the data and to further outline approaches to overcome these limitations. One of the biggest challenges regarding the use of SHI routine data in health services research is the fact that information on disease severity which may represent a confounder in analytical health services research is largely lacking. In this context, advantages and disadvantages of different propensity score methods regarding their potential for confounder control are discussed in the thesis. A further challenge is related to the fact that studies are often based on data from a single or few SHIs. Since insurants covered by the various SHIs differ with regard to sociodemographic characteristics which, in turn, can be related to the morbidity risk or the probability of receiving certain health services, the external validity of study results might be limited. Concerning this matter, weighting approaches to account for these differences are discussed. To evaluate the validity of SHI routine data with an external gold standard or to enrich SHI routine data with external data due to the limited range of information, a patient-individual record linkage with another data source is required. However, such a record linkage often cannot be realized, since processing person-identifying information requires meeting very high standards of data protection. In this thesis, methods allowing a record linkage of SHI routine data with another data source based on person-identifying information are discussed. Finally, there is an outlook regarding the availability of SHI routine data for research purposes
Outpatient antibiotic therapy
No full textThe rise of antibiotic resistance is widely acknowledged to be an increasing threat to global public health. Promoting rational antibiotic prescribing patterns is one important approach to counter this development. Comprehensive analysis of patterns of antibiotic utilization and its quality in routine care is a perquisite to the design of effective tailored interventions to promote rational and judicious antibiotic prescribing. Automated health care databases facilitate the analysis of antibiotic utilization in outpatient care in large populations and can be used for international comparison of prescribing habits. In the German health care setting administrative databases of statutory health insurance companies (SHIs) capture all outpatient dispensations of prescription drugs and allow for the population-based and detailed analysis of antibiotic use in primary care. This doctoral thesis is based onone study on paediatric antibiotic use in German primary care and two studies comparing outpatient prescribing of systemic antibiotics to children and adolescents in the age group 0-18 years between Denmark, Italy, Germany, the Netherlands and the UK. These publications are complemented by a systematic review on the effectiveness of computer-aided clinical decision support systems in strengthening rational outpatient antibiotic prescribing. Here the aim is to (1) to further explore the significance of the published results in the light of the current state of research and (2) to amplify the discussion of important methodological issues and limitations. This comprises a critical review of the strengths and weaknesses of administrative data of German SHIs and comparable European databases as a basis for population-based studies of outpatient antibiotic utilization and cross-national comparison between European countries. In addition, an overview of the current state of knowledge regarding interventions to foster rational and judicious outpatient antibiotic prescribing is given and specific methodological challenges of the synthesis of evidence in this field are discussed. By allowing detailed cross-national comparisons of age- and gender-specific measures of antibiotic use, administrative data from German SHIs and similar European health care databases close an important gap in the surveillance of outpatient patterns of antibiotic use and the assessment of prescribing quality. Additional research is warranted to assess the validity of disease-specific measures of use based on German SHIs data. In recent years outpatient antibiotic use decreased in Germany, most remarkably in the paediatric setting. Nevertheless, further room for improvement exists. In particular, this concerns relatively high prescribing of broad spectrum agents as first line treatment of seasonal respiratory infections. Notably higher prescribing in contrast to other European countries such as the Netherlands, Denmark, Sweden or the UK can be seen for chinolones, cephalosporines (2nd and 3rd generation) and new macrolides. So far, a large number of international studies has been published aiming to improve quality of outpatient antibiotic prescription, mostly showing marginal to moderate intervention effects. Nevertheless, a selection of recently published studies consistently shows favourable effectiveness for some types of intervention, including the use of specific point-of-care tests
Methodological aspects relevant to conducting safety and utilization studies based on claims data
No full textAt the time of approval, the safety and utilization of drugs in routine clinical practice cannot be fully assessed. Therefore, active post-marketing surveillance including the determination of the safety but also the utilization of the drugs as part of risk management plans is required by regulatory agencies. Pharmacoepidemiological studies based on claims data from statutory health insurance (SHI) providers are increasingly used to address these questions. These studies require a comprehensive knowledge of the healthcare system including reimbursement policies as well as specifics of the data source. Based on several safety and utilization studies using claims data, this thesis discusses methodological aspects relevant to conducting these studies. Considering regulations of the German health care system, the assessment of exposure, outcomes, and confounders as well as the determination of potential indications are described. Further, this thesis discusses approaches for addressing confounders which either cannot be measured in databases or if, only inadequately. Since even large electronic healthcare databases may not provide a sufficient sample size to examine rare outcomes or rare exposures, multinational database studies including databases with different structures are conducted. This thesis characterizes challenges arising from the analysis of these different databases. Pharmacoepidemiological studies based on SHI claims data are an important instrument to assess the safety and utilization of drugs following approval. The development of pharmacoepidemiology is characterized by the implementation of suitable data sources as well as the development of methodological instruments. This thesis depicts the current status and outlines future challenges
Clinical-epidemiological research based on data from statutory health insurance companies - potential and limitations
No full textThis dissertation discusses potential and limitation of routine data of statutory health insurances for clinical-epidemiological research exemplified by five studies conducted for two different diseases (attention deficit-/hyperactivity disorder and anogenital warts). The included studies examine the burden of disease, prevalence of comorbidities, drug treatment patterns and the effectiveness of a prophylactic vaccine in the general population. The database used for these studies was the German Pharmacoepidemiological Research Database (GePaRD), which contains records of more than 14 million people from all regions of Germany. The GePaRD contains information of in- and outpatient medical services and of medications that are reimbursed by health insurance companies. For the estimation of the burden of diseases, regional variation of disease and the examination of the effectiveness of a vaccine in the general population routine data of statutory health insurances can be a very valuable data source. For research questions for which the severity of the disease, social status and lifestyle factors are important this data are not or only of limited use
Pharmakoepidemiologische Analyse zu okulärer Hypertension, Offenwinkelglaukom und Katarakt als unerwünschte Wirkungen von Glukokortikoiden
Get PDFDie vorliegende Arbeit diskutiert methodische Aspekte und Ergebnisse eigener pharmakoepdemiologischer Untersuchungen zum Risiko von okulärer Hypertension, Glaukom und Katarakt unter verschiedenen Darreichungsformen von Glukokortikoiden. Prospektive Studien der frühen 60er Jahre haben gezeigt, daß die Verabreichung topischer Glukokortikoide am Auge bei ca. einem Drittel der Bevölkerung zu einem Augeninnendruckanstieg führt. Bei langdauernder Therapie kann sich ein Kortikosteroidglaukom entwickeln, das in seiner Symptomatik und den klinischen Befunden einem primären Offenwinkelglaukom entspricht. Für orale Glukokortikoide untersuchten wir das Risiko von okulärer Hypertension und Offenwinkelglaukom in einer großen Fall-Kontroll-Studie, die 9.793 augenärztliche Patienten mit neu diagnostizierter okulärer Hypertension und Offenwinkelglaukom einschloß und 38.325 augenärztliche Kontrollpatienten ohne diese Erkrankungen. Die Einnahme oraler Glukokortikoide war mit einem Risikoanstieg von über 40% verbunden. Es zeigte sich ein deutlicher Anstieg des Risikos mit zunehmender Glukokortikoid-Tagesdosis: Für Patienten, die mehr als 80 mg Hydrokortisonäquivalent pro Tag erhalten hatten, war das Risiko über 80% erhöht. Unsere Berechnungen zeigten, daß unter solch hohen Dosen 93 zusätzliche Fälle von okulärer Hypertension oder Offenwinkelglaukom pro 10.000 Patienten und Jahr auftreten können. In derselben Fall-Kontroll-Studie analysierten wir auch das Risiko für inhalative und nasale Glukokortikoide. Zwar ist für diese Glukokortikoidformen das Risiko systemischer Glukokortikoidnebenwirkungen durch die topische Applikation deutlich reduziert, doch legen verschiedene klinisch-pharmakologische Untersuchungen nahe, daß inhalative Glukokortikoide in hoher Dosierung systemische Effekte ausüben können. Verschiedene Einzelfallberichte ließen ein erhöhtes Risiko von okulärer Hypertension und Glaukom für inhalative und nasale Glukokortikoide möglich erscheinen. Unsere Fall-Kontroll-Studie zeigte, daß inhalative Glukokortikoide, wenn sie in hohen Tagesdosen kontinuierlich über 3 Monate verabreicht werden, das Risiko von okulärer Hypertension und Offenwinkelglaukom um über 40% erhöhen. Wir beobachteten kein erhöhtes Risiko für nasale Glukokortikoide. In einer weiteren Fall-Kontroll-Studie untersuchten wir das Kataraktrisiko für inhalative Glukokortikoide. Orale Glukokortikoide sind ein etablierter Risikofaktor für eine Katarakt. Für inhalative Glukokortikoide lagen widersprüchliche Studienergebnisse vor. Während mehrere kleine Studien an Kindern kein erhöhtes Risiko gezeigt hatten, war in einer großen populationsbasierten australischen Studie ein erhöhtes Kataraktrisiko unter inhalativen Glukokortikoiden beobachtet worden. Wir konnten das Ergebnis der australischen Studie in unserer Fall-Kontroll-Studie bestätigen, die 3.677 Fallpatienten und 21.868 Kontrollpatienten einschloß. Eine Verabreichung inhalativer Glukokortikoide über mehr als 3 Jahre führte zu einer Verdreifachung des Risikos einer Kataraktextraktion. Das Risiko war nur für hohe Dosen inhalativer Glukokortikoide statistisch signifikant erhöht, nicht jedoch für niedrige bis mittlere Tagesdosen. Zusammengefaßt zeigen die Ergebnisse unserer Studien, daß inhalative Glukokortikoide in hoher Dosierung trotz topischer Applikation zu systemischen Glukokortikoidkomplikationen am Auge führen können. Dies läßt es geboten erscheinen, bei Patienten, die inhalative Glukokortikoide in hoher Dosierung erhalten, augenärztliche Kontrolluntersuchungen durchführen zu lassenThis work presents methodological aspects and results of own pharmacoepidemiologic studies investigating the risk of ocular hypertension, glaucoma and cataract for different forms of glucocorticoids.. Prospective studies of the early 60ies have shown that administration of topical glucorticoids at the eye will lead to ocular hypertension in about one third of the population. If ophthalmic glucocorticoid treatment is prolonged, a corticosteroid glaucoma may develop which closely resembles primary open-angle glaucoma.. We investigated the risk of ocular hypertension or open-angle glaucoma for oral glucocorticoids in a large case-control-study which included 9,793 ophthalmology patients with newly diagnosed ocular hypertension or open-angle glaucoma and 38,325 ophthalmology patients without these diseases (controls). Intake of oral glucocorticoids led to an increase in risk by over 40%. The risk increased markedly with the daily dose of glucocorticoid. For patients who had received more than 80 mg hydrocortisone-equivalent per day, the risk was more than 80% elevated. Our calculations showed that for such high doses, 93 additional cases of ocular hypertension or glaucoma per 10,000 patients and year may be expected. In the same case-control study, we analysed the risk of ocular hypertension and open-angle glaucoma for inhaled and nasal glucocorticoids. These forms of glucocorticoids have been developed to reduce the risk of systemic glucocorticoid complications by topical administration. Some clinical pharmacology studies have shown that high doses of inhaled glucocorticoids may cause systemic effects. Some published case reports suggested an increased risk of ocular hypertension and glaucoma for inhaled and nasal glucocorticoids. Our case-control study showed that high dose, continuous administration of inhaled glucocorticoids for more than 3 months increases the risk of ocular hypertension or open angle glaucoma by more than 40%. We did not observe an increased risk for nasal glucocorticoids. In another case-control study, we investigated the risk of cataract for inhaled glucocorticoids. Oral glucocorticoids are an established risk factor for cataract. For inhaled glucocorticoids, there have been contradictory results from several studies. Whereas some small studies in children did not show an increased risk, a population-based larger study from Australia demonstrated an elevated risk. We confirmed this increase in risk in our case-control study which included 3,677 elderly cases and 21,868 elderly controls. We observed a more than 3-fold risk of cataract extraction in patients who had been treated with inhaled glucocorticoids for more than three years. The risk was significantly increased only for high daily doses of glucocorticoids, but not for low-to-medium doses. In summary, the results of our studies show that high doses of inhaled glucocorticoids despite their topical administration may lead to systemic complications of glucocorticoids at the eye. Therefore it is recommended to have patients who are prescribed high daily doses of inhaled glucocorticoids examined by an ophthalmologist
Moeglichkeiten und Schwierigkeiten in Arzneimittelrisikostudien nach Marktzulassung Eine Betrachtung mit Fokus auf aeltere Patientinnen und Patienten
No full textIn the next decades, the number of older people will rise substantially in Germany. Likewise, drug treatment and polypharmacy will also augment due to the high prevalence of multimorbidity in this subpopulation. Since older people are often excluded from randomized controlled trials prior to drug approval, pharmacoepidemiological safety studies (PSS) based on spontaneous reporting systems and electronic healthcare databases often represent the only opportunity to investigate the safety of drugs in this population. However, these studies have specific methodological challenges related to the clinical characteristics of older patients and the nature of the data sources. Thus, the overall aim of this thesis is to (1) critically assess methodological challenges of PSS based on spontaneous reporting systems and electronic healthcare databases with a focus on older patients and (2) to define further areas of research to enhance their quality. In this context, disproportionality analyses based on spontaneous reports, cohort studies, nested case control studies, and case only designs are introduced as study designs for PSS. Confounding (e.g., by frailty), outcome and exposure misclassification as well as time related biases in PSS are illustrated as selected methodological challenges. These challenges are then discussed in the context of my research articles with a focus on older people, and opportunities to address these challenges are presented. More specifically, the role of spontaneous reporting systems in the detection of adverse drug reactions in older people is critically assessed. Afterwards, drug utilization studies as well as the application of high dimensional propensity score methods and case only designs are discussed as options to overcome the specific problem of confounding by indication and unmeasured confounding in PSS among older people. Further, a detailed review of the patienta s profile is recommended to increase the specificity of the outcome case algorithms in administrative claims databases. Moreover, it is highlighted that sensitivity analyses in drug utilization and safety studies are particularly important in the case of a as neededa treatment among older patients and if information on the prescribed daily dose is missing. Finally, it is highlighted how time related biases can be prevented in cohort and nested case control studies using a time dependent analysis and risk set sampling, respectively. In the conclusion, future research perspectives with regard to PSS in older patients are pointed out as, for instance, the use of semi automated drug safety monitoring based on electronic healthcare databases, the availability of additional medical information in the context of the German a e healtha legislation or the need for external validation studies to study the impact of outcome and drug exposure misclassification
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