Comparison of tools for assessing the methodological quality of primary and secondary studies in health technology assessment reports in Germany

Health care policy background: Findings from scientific studies form the basis for evidence-based health policy decisions. Scientific background: Quality assessments to evaluate the credibility of study results are an essential part of health technology assessment reports and systematic reviews. Quality assessment tools (QAT) for assessing the study quality examine to what extent study results are systematically distorted by confounding or bias (internal validity). The tools can be divided into checklists, scales and component ratings. Research questions: What QAT are available to assess the quality of interventional studies or studies in the field of health economics, how do they differ from each other and what conclusions can be drawn from these results for quality assessments? Methods: A systematic search of relevant databases from 1988 onwards is done, supplemented by screening of the references, of the HTA reports of the German Agency for Health Technology Assessment (DAHTA) and an internet search. The selection of relevant literature, the data extraction and the quality assessment are carried out by two independent reviewers. The substantive elements of the QAT are extracted using a modified criteria list consisting of items and domains specific to randomized trials, observational studies, diagnostic studies, systematic reviews and health economic studies. Based on the number of covered items and domains, more and less comprehensive QAT are distinguished. In order to exchange experiences regarding problems in the practical application of tools, a workshop is hosted. Results: A total of eight systematic methodological reviews is identified as well as 147 QAT: 15 for systematic reviews, 80 for randomized trials, 30 for observational studies, 17 for diagnostic studies and 22 for health economic studies. The tools vary considerably with regard to the content, the performance and quality of operationalisation. Some tools do not only include the items of internal validity but also the items of quality of reporting and external validity. No tool covers all elements or domains. Design-specific generic tools are presented, which cover most of the content criteria. Discussion: The evaluation of QAT by using content criteria is difficult, because there is no scientific consensus on the necessary elements of internal validity, and not all of the generally accepted elements are based on empirical evidence. Comparing QAT with regard to contents neglects the operationalisation of the respective parameters, for which the quality and precision are important for transparency, replicability, the correct assessment and interrater reliability. QAT, which mix items on the quality of reporting and internal validity, should be avoided. Conclusions: There are different, design-specific tools available which can be preferred for quality assessment, because of its wider coverage of substantive elements of internal validity. To minimise the subjectivity of the assessment, tools with a detailed and precise operationalisation of the individual elements should be applied. For health economic studies, tools should be developed and complemented with instructions, which define the appropriateness of the criteria. Further research is needed to identify study characteristics that influence the internal validity of studies

Willingness to provide informal care to older adults in Germany: a discrete choice experiment

As the German population is continually aging and the majority of older adults still wish to ‘age in place’, the need for informal care provided by family and friends will correspondingly continue to increase. In addition, while the need for formal (professional) care services is also likely to increase, the supply already does not meet the demand in Germany today. The aim of our study is the elicitation of people’s willingness to provide informal care by means of a discrete choice experiment. The self-complete postal survey was disseminated to a random sample of the German general population in Lower Saxony. Data cleansing resulted in a final sample size of 280 participants. A conditional logit and a latent class model were estimated. All attributes were judged as highly relevant by the respondents. The results revealed that an increase in the care hours per day had the greatest negative impact overall on the willingness to provide informal care in our sample. The marginal willingness-to-accept for 1 h of informal care was €14.54 when having to provide informal care for 8 h in reference to 2 h per day. This value is considerably higher than the national minimum wage of €9.82. A three-class latent class model revealed preference heterogeneity. While a monetary compensation is often discussed to increase the willingness and availability of informal care in a country, our results show that this statement could not be generalized within our entire sample

Lifestyle interventions for patients with non-alcoholic steato-hepatitis-Design, rationale and protocol of the study "target group-specific optimisation of lifestyle interventions for behavior change in non-alcoholic steato-hepatitis (OPTI-NASH)"

BACKGROUND: Non-alcoholic steato-hepatitis (NASH) is the inflammatory, progressive form of non-alcoholic fatty liver disease (NAFLD). A delayed diagnose interval is typical for the majority of the patients because of the asymptomatic natural course. However, serious sequelae may develop such as cirrhosis or hepatocellular carcinoma. NASH is also associated with an increased risk of metabolic diseases. Obesity developed due to a lack of exercise or a disadvantageous diet often leads to NAFLD or NASH, thereby interventions including enhanced physical activity and calorie reduction form the actual gold standard of treatment. To date, patients rarely use these. The project aims to model lifestyle interventions based on the preferences of the NASH patients. METHODS: Based on a systematic review and focus group discussions, two discrete choice experiments (DCE) will be designed, one on aspects influencing successful uptake of lifestyle interventions and one to analyses parameters contributing to long-term participation. An online survey will be used to elicit patient's preferences on program design and on motivational aspects in a cross-sectional design. The recruitment will take place in nine certified specialist practices and hospital outpatient clinics aiming to reach a sample size of n = 500 which is also required for the DCE design. DISCUSSION: The results will provide an overview of the NASH patient's preferences regarding the successful uptake and long-term implementation of lifestyle interventions. Recommendations for optimized lifestyle change programs will be derived and an intervention manual will be developed to facilitate target group-specific inclusion in programs in practice.</p

Exploring the status of and demand for palliative day-care clinics and day hospices in Germany: a protocol for a mixed-methods study

Background: To date, the establishment and development of palliative day-care clinics and day hospices in Germany have been completely unsystematic. Research is needed to gain insight into these services and to ensure their accessibility and quality. Accordingly, the ABPATITE research project aims at: (1) identifying the characteristics of palliative day-care clinics and day hospices in Germany, (2) determining demand and preferences for these services, and (3) proposing recommendations (with expert agreement) for the needs-based establishment and development of these services. Methods: The research is a multi-perspective, prospective, observational study following a mixed-methods approach across three study phases. In phase 1a, qualitative expert interviews will be conducted to capture the facility-related characteristics of palliative day-care clinics and day hospices in Germany; the results will feed into a questionnaire sent to all such institutions identified nationwide. In phase 1b, a questionnaire will be sent to local statutory health insurance providers, to gain insight into their contracts and accounting and remuneration models. In phase 2a, a service preference survey will be conducted with patients and family caregivers. In phase 2b, semi-structured interviews with management staff will explore the factors that promote and hinder the provision of service. In phase 2c, the external perspective will be surveyed via focus groups with local actors involved in hospice and palliative care. In phase 3a, focus groups with representatives from relevant areas will be conducted to develop recommendations. Finally, in phase 3b, recommendations will be agreed upon through a Delphi survey. Discussion: The empirically developed recommendations should enable the establishment and development of day hospices and palliative day-care clinics in Germany to be better managed, more oriented to actual demand, and more effectively integrated into wider health care services. Importantly, the findings are expected to optimize the overall development of hospice and palliative care services. Trial registratio

Estimating trends in working life expectancy based on health insurance data from Germany – Challenges and advantages

Against the backdrop of population aging and growing strain on pension systems, monitoring the development of Working Life Expectancy (WLE) is vital to assess whether the policies taken are effective. This is the first study investigating time trends and educational inequalities in WLE based on German health insurance data. The analyses are based on the data of the AOK Lower Saxony (N = 3,347,912) covering three time periods (2006-08, 2011-13, and 2016-18). WLE is defined as years spent in the labor force (i.e. in employment and unemployment) and was calculated for each age between 18 and 69 years for the three periods to depict changes over time using multistate life table analysis. Educational inequalities in 2011-13 are reported for two educational levels (8–11 years and 12–13 years of schooling). WLE increased in both sexes with increases being stronger among women. This holds irrespective of whether WLE at age 18 (35.8–38.3 years in men, 27.5–34.0 years in women) or the older working-age (e.g. at age 50 10.2–11.7 years in men, 7.8–10.5 years in men) is considered. Among women at all ages and men from their mid-20s onwards, WLE was higher among higher-educated individuals. Inequalities were most pronounced among women (e.g. Δ3.1 years in women, Δ1.3 years in men at age 50). The study supports previous research indicating that measures to extend working life are effective, but that noticeable inequalities in WLE exist. Health insurance data represent a valuable source for such research that has so far remained untapped. The data provide a suitable basis to investigate trends and inequalities in WLE. Future research should build on the strengths of the data by broadening the research towards a more comprehensive analysis of the development of WLE from a health perspective.Peer Reviewe

Claims data analysis on the dispensing of tricyclic antidepressants among patients with dementia in Germany

Objective: A restrictive use of tricyclic antidepressants (TCA) in patients with dementia (PwD) is recommended due to the hazard of anticholinergic side effects. We evaluated the frequency of TCA dispensing in PwD over a period of 1 year and the use of TCA before and after the incident diagnosis of dementia. Methods: This analysis was based on administrative data from a German statutory health insurance for a period of 2 years. Totally, 20,357 patients with an incident diagnosis of dementia in 2014 were included. We evaluated the dispensing of TCA in 2015. Subgroup analyses were conducted to evaluate associations between the incident diagnosis of dementia and modifications in TCA dispensing. Results: In 2015, 1,125 dementia patients (5.5%) were treated with TCA and 31% were medicated with TCA in all four quarters of 2015. Most dispensings were conducted by general practitioners (67.9%). On average, patients received 3.7 ± 2.6 dispensings per year. Amitriptyline (56.3%), doxepin (26.8%), and trimipramine (16.8%) were dispensed most often. Subgroup analyses revealed that the dispensing of TCA remained mainly unchanged following the incident diagnosis. Conclusion: A relevant number of PwD were treated with TCA. To maintain the patients' safety, an improved implementation of guidelines for the pharmaceutical treatment of PwD in healthcare institutions might be required. Since 68% of the patients suffered from depression, future studies should further evaluate the indications for TCA. Copyright © 2019 Hessmann, Zeidler, Stahmeyer, Eberhard, Vogelgsang, Abdel-Hamid, Wolff-Menzler, Wiltfang and Kis. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms

Methotrexat-Versorgung vor dem Einsatz von Biologika bei rheumatoider Arthritis: Eine Analyse der Leitliniengerechtigkeit

Background: With the introduction of biologics the treatment landscape for patients with rheumatoid arthritis (RA) has rapidly expanded; however, according to German and European treatment guidelines the use of biologic disease-modifying antirheumatic drugs (bDMARD) is only indicated after insufficient response under methotrexate (MTX) doses of at least 20 mg/week (first-line treatment). The aim of the study was to analyze the guideline compliance of MTX prescription in the outpatient sector prior to treatment with biologics. Material and methods: Claims data from the AOK Lower Saxony from 2013 to 2016 were provided for all insured patients with a diagnosis of RA and bDMARD prescription during the study period. Within a patient-specific observational period of 180 days prior to the first bDMARD prescription, the maximum prescribed MTX dosage was examined. Results: Data from 90 incident and 315 prevalent RA patients were analyzed. A maximum MTX prescription of < 20 mg/week was observed in 60.0% of incident patients and in 67.0% of prevalent patients. Men had a higher mean MTX maximum dose (17.1 ± 4.8 mg) than women (14.9 ± 5.0 mg; p < 0.0001). Of the study population 29.6% received oral only prescriptions during the observational period. In 12.4% of patients a switch to parenteral administration was made. Discussion: Targeted use of the full spectrum of therapies provided prior to initiation of bDMARD treatment may contribute to cost-effective RA care. This study showed indications for potential deficits in outpatient MTX prescription practice and can raise awareness for efficient treatment.Hintergrund: Seit vielen Jahren erweitern Biologika die Therapieoptionen bei rheumatoider Arthritis (RA). Der Einsatz dieser biologischen „disease-modifying antirheumatic drugs“ (bDMARDs) ist gemäß deutscher und europäischer Behandlungsleitlinien jedoch erst bei Ausschöpfung der Methotrexat (MTX)-Erstlinientherapie von mindestens 20 mg/Woche indiziert. Ziel der Studie ist es, die Leitliniengerechtigkeit der MTX-Verordnung im ambulanten Sektor vor der Biologikatherapie zu überprüfen. Methodik: Es wurden Routinedaten der AOK-Niedersachsen der Jahre 2013 bis 2016 für alle Versicherten zur Verfügung gestellt, die im Studienzeitraum eine RA-Diagnose sowie eine bDMARD-Verordnung aufweisen. Innerhalb eines patientenindividuellen Beobachtungszeitraums von 180 Tagen vor der ersten bDMARD-Verordnung wurde die maximal verordnete MTX-Dosierung untersucht. Ergebnisse: Die Studienpopulation umfasst 405 Patienten (90 inzident, 315 prävalent). Bei 60,0 % der inzidenten Patienten und 67,0 % der prävalenten Patienten wurde eine maximale MTX-Verordnung von < 20 mg/Woche beobachtet. Männer weisen im Mittel mit 17,1 ± 4,8 mg eine höhere MTX-Maximaldosierung als Frauen auf (14,9 ± 5,0 mg; p < 0,0001); 29,6 % der Studienpopulation erhielten im Beobachtungszeitraum ausschließlich orale Verordnungen. Umstellungen auf eine parenterale Applikationsform wurden bei 12,4 % der Patienten festgestellt. Diskussion: Ein gezielter Einsatz des gesamten vorgesehenen Therapiespektrums vor der Initiierung einer bDMARD-Therapie kann zu einer kosteneffizienten Versorgung der RA beitragen. Die Studie zeigt Indizien für mögliche Defizite in der ambulanten MTX-Verordnungspraxis auf und kann für eine effiziente Therapie sensibilisieren

Cost-effectiveness of Triple Therapy with Telaprevir for Chronic Hepatitis C Virus Patients in Germany

**Background:** About 400,000-500,000 people are infected with hepatitis C in Germany. Long-term consequences are the development of liver cirrhosis and hepatocellular carcinoma. The introduction of first generation protease inhibitors has significantly improved the treatment of hepatitis C genotype 1 patients. The aim of the study was to assess the cost-effectiveness of triple therapy with telaprevir in Germany. **Methods:** We used a Markov model on disease progression and natural history to assess the cost-effectiveness of triple therapy with telaprevir compared to standard treatment with pegylated interferon and ribavirin. Model structure and inputs were discussed with clinical experts. Deterministic and probabilistic sensitivity analyses were performed to verify the robustness of results. **Results:** The base-case analyses shows that triple therapy results in higher costs (untreated patients: €48,446 vs. €30,691; previously treated patients: €63,228 vs. €48,603) and better outcomes (untreated patients: 16.85 qualily of life years [QALYs] vs. 15.97 QALYs; previously treated patients: 14.16 QALYs vs. 12.89 QALYs). The incremental cost-effectiveness ratio (ICER) was €20,131 per QALY and €30,567 per life year gained (LYG) for previously untreated patients. ICER in treatment experienced patients was €7,664 per QALY for relapse patients, €12,506 per QALY for partial responders and €28,429 per QALY for null responders. Results were robust in sensitivity analyses. **Conclusion:** Although triple therapy with telaprevir leads to additional costs, there is a high probability of being cost-effective for different thresholds. This health economic analysis makes an important contribution to current debates on cost savings and efficient resource allocation in the German healthcare sector

Empirisch abgeleitete Empfehlungen für den Auf- und Ausbau von Tageshospizen in Deutschland – Ergebnisse einer Delphi-Befragung mit Expert:innen

Introduction: A needs-based and patient-oriented hospice and palliative care also includes day hospices as a specialised semi-inpatient care offer. The establishment and development of these facilities in Germany has been rather unsystematic. In order to ensure quality and adequacy of these structures, research is needed. Methods: A Delphi consensus study was conducted online from November 2022 to February 2023 aiming at generating recommendations for the development and expansion of day hospices in Germany. For each recommendation, the participants indicated on a four-point verbal rating scale how much they agreed upon a) the relevance and b) the feasibility of the recommendation. Items were considered consented when 80 % of the participants (strongly) agreed with the recommendation regarding both criteria. If no consensus was reached, the recommendations were revised according to the participants’ free text comments and presented in the next Delphi round. Descriptive analyses were applied. Results: A total of 64 experts participated in the first Delphi round and 44 in the second. In round 1, 34 recommendations and in round 2 six recommendations were consented. The final set contains a total of 40 recommendations: 18 on the tasks of day hospices, 13 on cooperation, 7 on funding, and 2 on public relations. Discussion: Recommendations for the development and expansion of day hospices in Germany were developed. Due to their highly rated feasibility, the recommendations should be directly transferable into care practice. It remains to be seen to what extent they will be taken into account in the renegotiation of the framework agreement for day hospices. Conclusion: The Delphi-consented recommendations provide a basis to guide action in the currently very dynamic development of hospice work and palliative care in Germany.Hintergrund: Zu einer bedarfsgerechten, patient:innenenorientierten Hospiz- und Palliativversorgung zählen auch Tageshospize als spezialisierte ambulante Versorgungsangebote. Aufbau und Entwicklung von Tageshospizen in Deutschland erfolgten bislang individuell und eigeninitiativ. Zur langfristigen Sicherstellung der Qualität und Bedarfsangemessenheit von Tageshospizen bedarf es wissenschaftlicher Erkenntnisse und Grundlagen. Methode: Von November 2022 bis Februar 2023 erfolgte eine deutschlandweite Online-Delphi-Befragung mit Expert:innen, in der Empfehlungen für den Auf- und Ausbau von Tageshospizen in Deutschland konsentiert wurden. Teilnehmende gaben zu jeder Empfehlung auf einer vierstufigen Rangskala an, wie sehr sie a) der Relevanz der Empfehlung und b) der Umsetzbarkeit der Empfehlung im Versorgungsalltag (nicht) zustimmen. Konsens wurde erreicht, wenn 80 % der Teilnehmenden einer Empfehlung in beiden Kriterien (eher) zustimmten. Wurde kein Konsens erreicht, wurden die Empfehlungen basierend auf Freitextkommentaren der Teilnehmenden angepasst und in der darauffolgenden Runde erneut zur Abstimmung gestellt. Die Analysen erfolgten deskriptiv. Ergebnisse: An der ersten Befragungsrunde beteiligten sich 64 und an der zweiten 44 Expert:innen. In Runde 1 wurden 34 und in Runde 2 sechs Empfehlungen konsentiert. Das finale Set enthält insgesamt 40 Empfehlungen: 18 zu Aufgaben, 13 zur Zusammenarbeit, 7 zur Finanzierung und 2 zur Öffentlichkeitsarbeit von Tageshospizen. Diskussion: Es konnten konkrete Empfehlungen zum Auf- und Ausbau von Tageshospizen in Deutschland entwickelt werden. Die Empfehlungen sollten aufgrund ihrer hoch bewerteten Umsetzbarkeit direkt in die Versorgungspraxis überführbar sein. Inwiefern die Empfehlungen in der Neuverhandlung der Rahmenvereinbarung für Tageshospize berücksichtigt werden, gilt es abzuwarten. Schlussfolgerung: Die vorliegenden Empfehlungen können handlungsweisend bei der aktuell sehr dynamischen Weiterentwicklung der Hospizarbeit und Palliativversorgung in Deutschland genutzt werden