Die Anwendung von Modellierungsmethoden im Rahmen der gesundheitsökonomischen Evaluation von Impfungen in Deutschland

Damm O. Die Anwendung von Modellierungsmethoden im Rahmen der gesundheitsökonomischen Evaluation von Impfungen in Deutschland. Bielefeld: Universität Bielefeld; 2018.Entscheidungsträger im Gesundheitswesen sind zunehmend an der Einbindung gesundheitsökonomischer Analysen in den Bewertungsprozess neuer Gesundheitsleistungen interessiert, nicht zuletzt aufgrund steigender Ausgaben im Arzneimittelsektor. Gleichzeitig sind auch pharmazeutische Hersteller bemüht, zu belegen, dass ihre Produkte "good value for money" bieten. Insbesondere bei Empfehlungs- und Erstattungsentscheidungen im Impfstoffsektor gehören gesundheitsökonomische Aspekte mittlerweile in vielen Ländern zum festen Bestandteil des Kriterienkatalogs, der bei der Evidenzbewertung zur Anwendung kommt. Die entscheidungsanalytische Modellierung kann dabei helfen, die Kosteneffektivität von Impfungen zu analysieren. Sie stellt sogar eine Schlüsselmethode bei der Evaluation von Impfungen dar, da sie die Abschätzung langfristiger epidemiologischer und gesundheitsökonomischer Auswirkungen von Impfungen auf Bevölkerungsebene ermöglicht. Vor diesem Hintergrund verfolgt die Dissertationsschrift das Ziel, einen Überblick über spezifische methodische Herausforderungen der modellbasierten gesundheitsökonomischen Evaluation von Impfungen zu geben und auf Basis einer Reihe von Modellierungsstudien die langfristigen epidemiologischen und gesundheitsökonomischen Effekte verschiedener Impfungen in Deutschland zu untersuchen. Die Auswahl der evaluierten Schutzimpfungen umfasst Impfstoffe gegen Humane Papillomviren (HPV), das Varicella-Zoster-Virus (VZV) sowie saisonale Influenza. Mit der Zusammenstellung von acht in Fachzeitschriften publizierten Beiträgen unterschiedlichen Charakters leistet die vorliegende Arbeit einen wichtigen Beitrag zur Erforschung der epidemiologischen und gesundheitsökonomischen Konsequenzen von Impfungen in Deutschland. Die Arbeit stellt zugleich eine wertvolle Grundlage für den Entscheidungsfindungsprozess hinsichtlich der Entwicklung oder Überarbeitung von Impfempfehlungen dar. Die Modellanalyse zu den ökonomischen Effekten der Influenza-Impfung zeigt bspw., dass die routinemäßige Impfung von Kindern und Jugendlichen gegen Influenza aus gesellschaftlicher Perspektive eine kostensparende Intervention darstellt. Wie die in die vorliegende Arbeit eingegangenen modellbasierten Studien demonstrieren, ist die Berücksichtigung der Transmissionsdynamik von hoher Relevanz, um neben direkten Impfeffekten auch indirekte Effekte (z. B. Herdenschutzeffekte) in die Ergebnisse einzubeziehen. Die Zusammenstellung der Beiträge macht dabei ebenfalls deutlich, dass sich indirekte Effekte nicht nur positiv, sondern auch negativ auf die Beurteilung einer Impfung auswirken können. Zukünftig gilt es, die Datenbasis für entscheidungsanalytische Modelle in Deutschland zu verbessern und bislang unberücksichtigte Aspekte in die modellbasierte Evaluation von Impfungen zu integrieren. Dazu zählt u. a. der durch präventive Maßnahmen induzierte Antizipationsnutzen. Bevor entsprechende Effekte jedoch in Modellen berücksichtigt werden können, bedarf es zunächst weiterer Forschung zur Messung dieser Nutzenkomponente

Ein Computermodell für die Simulation von emotionalen Angleichungsprozessen in der Mensch-Roboter Interaktion

Damm O. Ein Computermodell für die Simulation von emotionalen Angleichungsprozessen in der Mensch-Roboter Interaktion. Bielefeld: Universität Bielefeld; 2014.Es gibt seit über 20 Jahren unterschiedliche Ansätze, virtuelle Agenten und humanoide Roboter sozialer und menschlicher erscheinen zu lassen. Um diesem Ziel näher zu kommen, wird in unterschiedliche Richtungen geforscht. Die künstlichen Interaktionspartner haben das Hören und Sprechen gelernt, um die Interaktion angenehmer und einfacher zu machen. Es wurden Modelle entwickelt die es möglich machen, komplexe Dialoge mit ihnen zu führen und nicht zuletzt wurden unterschiedliche Emotionsmodelle implementiert. Viele Modelle von artifiziellen Emotionen versuchen über unterschiedlichen Input einen internen emotionalen Zustand zu errechnen und diesen durch den Roboter darzustellen. Diese Modelle reichen vom diskreten OCC-Modell, bei dem Emotionen eine wertende Reaktion auf Konsequenzen von Ereignissen, Handlungen von Agenten oder Aspekte von Objekten sind, bis hin zu multidimensionalen Modellen die versuchen natürliche Emotionen zu simulieren. Für das OCC-Modell bedeutet das zum Beispiel, dass eine Handlung mehr oder weniger zu einer Emotion führt. Bei den dimensionalen Modellen wird der emotionale Zustand über einen Punkt in einem 3 dimensionalen Raum modelliert. Dieser Punkt wird durch wahrgenommene Handlungen oder Ereignisse im Raum bewegt. Die Emotionen sind unterschiedlichen Bereichen in diesem Raum zugeordnet. Das hier vorgestellte Modell basiert auf Erkenntnissen, die zuvor in mehreren empirischen Studien gewonnen wurden. Es simuliert emotionale Angleichungsprozesse, die in der Mensch-Mensch Interaktion beobachtet werden können. Es wird also nicht versucht, dem Roboter einen emotionalen Zustand zu ”geben“, vielmehr liegt der Focus auf der Interaktion und der Wirkung einer gezeigten Emotion auf eben diese. Dafür wurde ein Ebenen-Modell implementiert, das dem Roboter ermöglicht in unterschiedlichen Situationen emotional angemessen zu reagieren. Es setzt (Facial) Mimicry ein, damit der Roboter positiver wahrgenommen wird und ein Social Bonding zu etablieren. Des Weiteren werden Emotionen eingesetzt, um die Interaktion gezielt zu beeinflussen und um auf Ereignisse, die nicht direkt zur Interaktion gehören, zu reagieren

Need for nursing care support in cancer patients: Registry-linkage study in Germany

Aim: In Germany, very little is known about the need for assistance and nursing care support among cancer patients after hospitalization. The aim of this study was to describe nursing care support for cancer patients and to analyse whether these patients need more care assistance than other persons in need for care. Methods: This was a registry linkage study conducted in 2011. Cases were identified from the population-based cancer registry for the Muenster District in north-western Germany and in factually anonymised form linked by a semi-automatic probabilistic procedure (the standard procedure of the cancer registry) with medical examination records of patients applying for assistance and nursing care support from the regional statutory health insurance. The application records of 4,029 patients with colon, breast and prostate cancer were compared to a reference group of 13,104 non-cancer patients. Results: In only 41.7% of colon, 45.8% of breast and 37.4% of prostate cancer patients was the malignancy the main underlying diagnostic cause for the application of assistance and nursing care. These patients were on average younger (mean age 71.1 vs. 76.8 years) than the non-cancer reference group, required higher levels of support (79.5 vs. 58.1% “considerable” or higher level care need) and their applications were less likely to be rejected (odds ratios [ORs] 0.26, 0.28, and 0.31, respectively). By contrast, the proportion of successful applications and the level of support granted did not differ between multimorbid cancer patients with other main diagnoses as compared to non-cancer applicants. Conclusion: Patients with colon, breast or prostate cancer do not need per se more nursing care than non-cancer patients. Only if cancer is the main underlying diagnosis for nursing care support, higher levels of support are needed

Human papillomavirus (HPV) vaccination for the prevention of HPV 16/18 induced cervical cancer and its precursors

Introduction: Essential precondition for the development of cervical cancer is a persistent human papillomavirus (HPV) infection. The majority - approximately 70% - of cervical carcinomas is caused by two high-risk HPV types (16 and 18). Recently, two vaccines have been approved to the German market with the potential to induce protection against HPV 16 and HPV 18 among additional low-risk virus types. Objectives: To analyse whether HPV vaccination is effective with regard to the reduction of cervical cancer and precursors of cervical carcinoma (CIN), respectively? Does HPV vaccination represent a cost-effective alternative or supplement to present screening practice? Are there any differences concerning cost-effectiveness between the two available vaccines? Should HPV vaccination be recommended from a health economic point of view? If so, which recommendations can be conveyed with respect to a (re)organization of the German vaccination strategy? Which ethical, social and legal implications have to be considered? Methods: Based on a systematic literature review, randomized controlled trials (RCT) looking at the effectiveness of HPV vaccination for the prevention of cervical carcinoma and its precursors - cervical intraepithelial neoplasia - have been identified. In addition, health economic models were identified to address the health economic research questions. Quality assessment of medical and economic literature was assured by application of general assessment standards for the systematic and critical appraisal of scientific studies. Results: Vaccine efficacy in prevention of CIN 2 or higher lesions in HPV 16 or HPV 18 negative women, who received all vaccination doses, ranges between 98% and 100%. Side effects of the vaccination are mainly associated with injection site reactions (redness, turgor, pain). No significant differences concerning serious complications between the vaccination- and the placebo-groups were reported. Results of base case scenarios in the identified health economic modeling analyses range from approximately 3,000 Euro to 40,000 Euro per additional QALY (QALY = Quality-adjusted life year) and approximately 9,000 Euro to 65,000 Euro per additional life year (LYG), respectively. Discussion: The included studies show that both available HPV vaccines are effective in preventing HPV 16 and HPV 18 infections and probable resulting premalignant lesions of the cervix. However, the duration of protection is currently unclear. With regard to side effects, the vaccination can be considered as secure. Nevertheless, the number of cases within the clinical studies is not sufficient to determine the occurrence of rarely occurring (severe) adverse events in a reliable way. A reduction in the incidence and induced mortality through cervical cancer in Germany is not only depending on the vaccine’s clinical efficacy. Effects of the new technology on the overall participation rate in screening programs and the resulting vaccination rate and immunization status are also important factors. The results of identified health economic models vary substantially due to the heterogeneity of methodological approaches as well as chosen input parameters. However, almost all model-based analyses reached the conclusion that the implementation of a vaccination with lifelong protection can be considered as cost-effective, if the present screening practice continues. A comparison of the two vaccines shows, that the cost effectiveness ratios are more favorable with the quadrivalent vaccine than with the bivalent alternative when considering QALY as primary outcome parameter. The reason for this finding might be that in the case of the quadrivalent vaccine the prevention of genital warts can also be incorporated into the analysis. Variations of the duration of protection as well as the discounting rate were identified as the primary influencing factors of cost-effectiveness results. Conclusion: Implementation of HPV vaccination might lead to a reduction of cervical cancer in immunized women. However, uptake of immunization should be accompanied by further studies in order to assess long-term effectiveness and safety aiming at an optimization of possible implementation processes. High numbers of participants are of particular importance regarding immunization. This has to be backed up by programs to optimize early detection – as this affects even those women who already underwent immunization. Since cost-effectiveness evidence might be significantly affected by the unclear duration of protective benefits, a final verdict on the vaccination’s cost-effectiveness in the German setting is not possible. Hence, risk-sharing-agreements between third-party payers and manufacturers would pose an option to balance the consequences of uncertainty towards the duration of protection on cost-effectiveness

Epidemiology and cost of seasonal influenza in Germany - a claims data analysis

Background Seasonal influenza contributes substantially to the burden of communicable diseases in Europe, especially among paediatric populations and the elderly. The aim of the present study was to estimate the incidence of seasonal influenza in Germany, the probabilities of related complications and the economic burden of influenza per case and on a population level for different age groups. Methods Claims data from 2012 to 2014 from > 8 million insured of a large German sick-ness fund were analysed. A matched case control study was used on a sub-sample of 100,000 influenza cases to calculate complication rates for ear infections/acute otitis media (AOM) and community-acquired pneumonia (CAP) as well as resource use and costs for seven age groups. Results Incidence of seasonal influenza varies between the years and is highest among infants and children 2 to 5 years of age. AOM is more likely in the younger age groups with up to 14% more patients in the influenza group than in the control group. CAP is more frequently observed in the younger age groups and in influenza patients 60 years and older. The manifestation of one influenza complication (AOM or CAP) significantly in-creases the occurrence of a second complication (AOM or CAP). The economic burden per case is highest in infants (€251.91) and persons over 60 years of age (€131.59). Conclusion The burden of influenza is highest among infants and young children, which is also reflected in the economic burden. Influenza related costs per case are nearly double for infants compared to persons over 60 years of age.Peer Reviewe

Epidemiology and economic burden of measles, mumps, pertussis, and varicella in Germany: a systematic review

Damm O, Witte J, Wetzka S, et al. Epidemiology and economic burden of measles, mumps, pertussis, and varicella in Germany: a systematic review. INTERNATIONAL JOURNAL OF PUBLIC HEALTH. 2016;61(7):847-860.Despite the availability of vaccines and the existence of public vaccination recommendations, outbreaks of vaccine-preventable childhood diseases still cause public health debate. The objective of this systematic review was to provide an overview of the current epidemiology and economic burden of measles, mumps, pertussis, and varicella in Germany. We systematically reviewed studies published since 2000. The literature search was conducted using PubMed and EMBASE. Also, we used German notification data to give an up-to-date overview of the epidemiology of the four diseases under consideration. Thirty-six studies were included in our review. Results suggest that there is still considerable morbidity due to childhood diseases in Germany. Studies providing cost estimates are scarce. Comparative analyses of different data sources (notification data vs. claims data) revealed a potential underestimation of incidence estimates when using notification data. Furthermore, several studies showed regional differences in incidence of some of the diseases under consideration. Our findings underline the need for improved vaccination and communication strategies targeting all susceptible age and risk groups on a national and local level

Population size and self-reported characteristics and sexual preferences of men-who-have-sex-with-men (MSM) in Germany based on social network data.

BACKGROUND: In the absence of detailed information about the population size and behaviour data of men-who-have-sex-with-men (MSM), the estimation of prevalence rates of sexually transmitted infections (STIs) and the design of public health interventions become difficult. The aim of the present study is to estimate the lower boundary of age-specific population sizes and retrieve self-reported information from this population. METHODS: We used publicly accessible data from a large online dating and social network website for MSM in Germany to retrieve data on the age and regional distribution of profiles. The profiles were also stratified by their information on the preferred position during anal intercourse, safer sex, and sexual identity. RESULTS: A total of 464,873 user profiles correspond to an average 15.2 profiles per 1,000 male inhabitants in Germany, varying between 7.6 and 45.6 across federal states. Although the information on the absolute numbers for different age groups is limited by the search engine, age-specific relative frequencies were found to increase from 12.9 in the age group of 18 to 20 year olds to 24.6 profiles per 1,000 male inhabitants in the 28 to 30 year olds. The data shows age-specific trends for safer sex with an increasing easiness of reporting "never" engaging in safer sex or stating that safer sex "needs discussion" with increasing age. Around one third of profile owners stated to be versatile with respect to the preferred position in anal intercourse. All other options ("only bottom", "more bottom", "only top", "more top") were preferred equally likely by roughly 10% of profile owners, respectively. CONCLUSIONS: Online social network or dating sites can provide some information about specific populations in the absence of other data sources. The presented results are the first to report age-specific rates of MSM per 1,000 male inhabitants in Germany and may be useful to estimate age-specific prevalence or incidence rates as well as to inform health promotion activities and modelling studies for MSM in Germany

Can electromagnetic fields influence the structure and enzymatic digest of proteins? A critical evaluation of microwave-assisted proteomics protocols

AbstractThis study reevaluates the putative advantages of microwave-assisted tryptic digests compared to conventionally heated protocols performed at the same temperature. An initial investigation of enzyme stability in a temperature range of 37–80°C demonstrated that trypsin activity declines sharply at temperatures above 60°C, regardless if microwave dielectric heating or conventional heating is employed. Tryptic digests of three proteins of different size (bovine serum albumin, cytochrome c and β-casein) were thus performed at 37°C and 50°C using both microwave and conventional heating applying accurate internal fiber-optic probe reaction temperature measurements. The impact of the heating method on protein degradation and peptide fragment generation was analyzed by SDS-PAGE and MALDI-TOF-MS. Time-dependent tryptic digestion of the three proteins and subsequent analysis of the corresponding cleavage products by MALDI-TOF provided virtually identical results for both microwave and conventional heating. In addition, the impact of electromagnetic field strength on the tertiary structure of trypsin and BSA was evaluated by molecular mechanics calculations. These simulations revealed that the applied field in a typical laboratory microwave reactor is 3–4 orders of magnitude too low to induce conformational changes in proteins or enzymes