Do German university medical centres promote robust and transparent research? A cross-sectional study of institutional policies.

BACKGROUND: In light of replication and translational failures, biomedical research practices have recently come under scrutiny. Experts have pointed out that the current incentive structures at research institutions do not sufficiently incentivise researchers to invest in robustness and transparency and instead incentivise them to optimize their fitness in the struggle for publications and grants. This cross-sectional study aimed to describe whether and how relevant policies of university medical centres in Germany support the robust and transparent conduct of research and how prevalent traditional metrics are. METHODS: For 38 German university medical centres, we searched for institutional policies for academic degrees and academic appointments as well as websites for their core facilities and research in general between December 2020 and February 2021. We screened the documents for mentions of indicators of robust and transparent research (study registration; reporting of results; sharing of research data, code and protocols; open access; and measures to increase robustness) and for mentions of more traditional metrics of career progression (number of publications; number and value of awarded grants; impact factors; and authorship order). RESULTS: While open access was mentioned in 16% of PhD regulations, other indicators of robust and transparent research were mentioned in less than 10% of institutional policies for academic degrees and academic appointments. These indicators were more frequently mentioned on the core facility and general research websites. Institutional policies for academic degrees and academic appointments had frequent mentions of traditional metrics. CONCLUSIONS: References to robust and transparent research practices are, with a few exceptions, generally uncommon in institutional policies at German university medical centres, while traditional criteria for academic promotion and tenure still prevail.

A template for broad consent in biobank research. Results and explanation of an evidence and consensus-based development process.

BACKGROUND: Biobanks increasingly presume long-term storage of biomaterials and data that shall be used for future research projects which are today unspecified. Appropriate consent documents for sample donors must therefore explain the breadth of consent and other elements of the biobank governance framework. Recent reviews demonstrated high variability in what issues these documents mention or not and how the issues are explained. This might undermine the protection of sample donors, complicate networked biobank research, create research waste and impact on public trust. METHODS: A systematic analysis of international research guidelines and existing broad consent templates was performed. Based on this information an interdisciplinary expert group from the AKMEK (Permanent Working Party of German RECs) developed a draft template and organized a comprehensive stakeholder consultation. After revision the final template was consented by all 53 German RECs. RESULTS: This paper briefly explores the spectrum of potentially relevant issues for broad consent forms. It then elaborates the template and how it was designed to be applicable in different types of biobanks. DISCUSSION: To further improve the validity and applicability of broad consent forms in biobank and other big data research, practice evaluations are needed. We hope that in this regard the presented template supports the development of new consent forms as well as the evaluation and revision of existing ones.

The full spectrum of ethical issues in the care of patients with ALS: a systematic qualitative review.

Dealing systematically with ethical issues in amyotrophic lateral sclerosis (ALS) care requires an unbiased awareness of all the relevant ethical issues. The aim of the study was to determine systematically and transparently the full spectrum of ethical issues in ALS care. We conducted a systematic review in Medline and Google Books (restricted to English and German literature published between 1993 and 2014). We applied qualitative text analysis and normative analysis to categorise the spectrum of ethical issues in ALS care. The literature review retrieved 56 references that together mentioned a spectrum of 103 ethical issues in ALS care. The spectrum was structured into six major categories that consist of first and second-order categories of ethical issues. The systematically derived spectrum of ethical issues in ALS care presented in this paper raises awareness and understanding of the complexity of ethical issues in ALS care. It also offers a basis for the systematic development of informational and training materials for health professionals, patients and their relatives, and society as a whole. Finally, it supports a rational and fair selection of all those ethical issues that should be addressed in health policies, position papers and clinical practice guidelines. Further research is needed to identify ways to systematically select the most relevant ethical issues not only in the clinical environment, but also for the development of clinical practice guidelines.

[Rationalization and rationing at the bedside. A normative and empirical status quo analysis]. / Rationalisierung und Rationierung am Krankenbett. Normativ-empirische Analyse zum Status quo.

BACKGROUND: The topic of bedside rationing is increasingly discussed in Germany. Further need for clarification exists for the question how bedside rationing (e.g., in the area of overcare) can be justified despite coexistent inefficiencies. DISCUSSION: This paper outlines and analyses the relationship of waste avoidance and rationing from an ethical perspective. Empirical findings regarding the status quo of bedside rationing and rationalization are presented. These normative and empirical explorations will then be further specified regarding opportunities for future physician-driven activities to tackle overuse. CONCLUSION: The self-government partners in Germany should communicate more explicitly within their communities and to the public how and with which benchmarks they aim to reduce inefficient health care (overuse) in an appropriate manner. Physician-driven activities such as the "Choosing Wisely®" initiative in the USA could provide a first step to raise the awareness for overuse among physicians as well as in the public.

[Avoidance of overuse as an integral part of medical professionalism. Conceptual analysis and new perspective]. / Der Abbau von Überversorgung als Teil der ärztlichen Berufsethik. Konzeptionelle Klärung und neue Perspektive.

BACKGROUND: The topics of rationing and priority setting have been increasingly discussed over the past 5 years in Germany by physicians together with other health care stakeholders. The topic of overuse, however, has not been discussed with similar intensity and publicity. OBJECTIVES: This analysis paper outlines the relationships and differences between efficiency, priority setting, and rationing. Furthermore, it argues why and how German physicians should address the topic of overuse with more transparency and intensity. DISCUSSION: Efforts of physicians to rationalize health care mainly comprise efforts to decrease overuse. The identification of important areas of overuse includes the prioritization of indications and medical interventions. Rationing health care can be unavoidable, for example, because other strategies such as rationalization, price regulation or disinvestments are not sufficient to avoid scarcity of financial resources. In such a case, rationing health care is unavoidable and, therefore, cannot be unethical per se. However, the debate on rationing becomes more legitimate if physicians demonstrate sufficient efforts to reduce overuse sufficiently. The Choosing Wisely initiative in the USA is outlined as one interesting option of how physicians could demonstrate and prove such efforts. Additional and more effective strategies to decrease overuse might be possible. CONCLUSION: German physicians demand a more explicit communication within their communities and together with other stakeholders on the appropriateness of existing and potential future activities to decrease overuse. Such initiatives to avoid and decrease overuse should primarily be motivated through the ethical principle of beneficence, while the effect of cost containment should be considered as a welcomed side effect.

[S3 guidelines on diagnostics and therapy of bipolar disorders: development process and essential recommendations]. / S3-Leitlinie zur Diagnostik und Therapie bipolarer Störungen: Entwicklungsprozess und wesentliche Empfehlungen.

Bipolar disorders are severe psychiatric disorders with extensive individual and health economic consequences. Starting in 2007 the first German evidence and consensus based guideline for diagnostics and treatment of bipolar disorders was developed which holds the potential of increasing confidence of therapists, patients and relatives in the decision-making process and improving healthcare service experiences of patients and relatives. Apart from recommendations for diagnostics and treatment the guidelines provide those for trialogue action, knowledge transfer and self-help and for strategies for healthcare provision of this complex disorder. In the present article the methodology and essential recommendations are outlined and complemented in specific topics by corresponding articles in this special issue. Due to restrictions of the length of this presentation there is the need to refer to the comprehensive version of the guidelines at several points also regarding a detailed discussion of the limitations.

[Quality of reporting in studies on bipolar disorders: implications for the development of guidelines]. / "Quality of reporting" in Studien zur bipolaren Störung : Folgen für die Leitlinienentwicklung.

BACKGROUND: Selective publishing as well as inadequate reporting of clinical trials entail a risk of bias in clinical decision making. Therefore the CONSORT statement was introduced to improve the quality of reporting of randomized controlled trials (RCT). This study aimed to assess the quality of reporting of RCTs on pharmacological treatment of bipolar disorder in relation to publication period and endorsement of publication guidelines. METHODS: In the context of the development of the German evidence and consensus-based S3 guidelines for diagnosis and therapy of bipolar disorders a systematic literature search was carried out to identify all RCTs published between 2000 and 2010 relevant to the pharmacological treatment of bipolar disorders. An adapted checklist based on the CONSORT statement was used to assess the quality of reporting. RESULTS: A total of 134 RCTs were included in this analysis. Of the 72 checklist items, 43% were generally reported adequately (reported in ≥ 75% of all trials) and 25% inadequately (reported in < 25% of all trials). Reporting was generally poor for randomization, effect size (reported in 22%) and number needed to treat (NNT 16%). No consistent trend could be shown for improvement in quality of reporting over time or for journals that do or do not endorse the URM (uniform requirements for manuscripts submitted to biomedical journals). CONCLUSIONS: Clinical investigators as well as editors and reviewers should be further encouraged to follow publication guidelines otherwise trials have to be downgraded or excluded from systematic evaluations.

[German language physician rating sites]. / Deutschsprachige Arztbewertungsportale.

BACKGROUND: In physician rating sites (PRS), patients are able to share their experiences and indicate their satisfaction in qualitative and quantitative form. This information should support other patients in the search for a suitable physician and can serve as a form of anonymous feedback for physicians. Medical association representatives are often concerned that such reviews primarily aim at defamation. Furthermore, there are various aspects of medical work that cannot be adequately evaluated solely through the patients. In the United States of America, the majority of such previous reviews were shown to be positive. It has yet to be examined in the German and English speaking regions where distinct criteria presently allow patients to express their satisfaction through PRS. METHOD: Based on the systematic review of patient satisfaction questionnaires, a set of criteria was created that represents the dimensions of patient satisfaction. German and English language physician rating sites were systematically researched using the Internet search machines "Google" and "Yahoo". The identified PRS were then evaluated with the help of the aforementioned set of criteria. In order to survey the tendency of the amount and content of reviews, a stratified sample of members of the Panel Doctor's Association in Hamburg and Thuringia was generated. A total of 298 randomly selected physicians were searched for in 6 German-language PRS regarding potential reviews. RESULTS: Some of the key features of the relation-ship between physicians and patients, such as medical competence, information, and consultation, were surveyed by more than three-fourths of the German-speaking PRS; however, other features such as communication were only sampled by one. As opposed to formal points of view, office facilities and organisation were assessed by all PRS. General reviews on treatment success and satisfaction were displayed in more than half of the reviews. Between 75% and 98% of physicians from the random sampling could be found in one of the 6 German language physician rating sites. Of the randomly sampled physicians, between 3% and 28% were evaluated by at least one patient. On average, the ratings for the total sample (on a scale of 1=good to 3=poor) ranged from 1.1 to 1.5, which clearly represents a positive trend. There were no differences found in terms of quantity and quality of ratings, or concerning the identifiability of physicians in the cases of Thuringia and Hamburg. CONCLUSION: The various PRS vary significantly in the selection and explanation of criteria for the evaluation of medical quality and, respectively, patient satisfaction. The specific selection and explanation of certain evaluation criteria could have a lasting effect on the understanding of physician quality and patient self-conception in the case of increased utilisation of PRS. The lack of standards for medical evaluation for PRS as well as poorly differentiated reviews, since reviews were usually positive, generally speak for the need for full text comments on PRS. This would enable peer-to-peer communication amongst users, especially regarding the practical relevance of evaluation criteria. Through this interaction between PRS users, user-oriented standards can be established and the advanced use of physician rating sites can be promoted.

[The concept of the development of S3 guidelines: additional benefit compared to traditional standards, problems and solutions]. / Das Konzept der Entwicklung von S3-Leitlinien: Mehrwert gegenüber üblichen Standards, Problembereiche und Lösungsansätze.

Guidelines for the diagnosis and treatment of psychiatric disorders developed on the highest qualitative methodical standard cover reliable decision guidance and are an important instrument of quality improvement in health care. They have to be accessible with little effort and should be concise and clearly presented to be used in daily routine. Early integration of members of the different professions, patients and their care givers into the development process is essential for acceptance. The development process of a S3 guideline is complex and poses a difficult challenge to personal manpower and funding, which is met by the associations of the Association of Medical Societies in Germany. Further scientific discussion is necessary to find adequate solutions for problematic topics or potential distortion, such as the consequences of inadequate reporting of studies, insufficient recording and reporting of the risk of damage, unpublished data and lacking interest of sponsors in specific topics.

[Is there health care rationing in German hospitals? How exactly do we know and why should it not be the most important question?]. / Wird in deutschen Kliniken rationiert oder nicht? Wie genau wir es wissen und warum es nicht die wichtigste Frage sein sollte.

A questionnaire study, conducted by the authors among a representative sample of hospital doctors in Germany, showed that health care rationing in German hospitals is already a fact. But since the results were published in 2009 the validity of its findings has been questioned. This article provides empirical data to demonstrate that the findings are not biased to any significant extent by misunderstandings or political motivation of the responding doctors. There is thus an urgent need for action in support of medical professionals to make it possible for them to deal with implicit rationing and with the potential disadvantages to which vulnerable groups of patients may be exposed. Taking into account health opportunity costs, increased funding in the health sector should not be the primary demand. The availability and critical appraisal of scientific evidence on the risk/benefit ratio of medical interventions must first be improved in order to optimize the administration of scarce health care resources in a medically rational way so that it is ethically and legally acceptable as well as economically reasonable.

[Extent and impact of bedside rationing in German hospitals: results of a representative survey among physicians]. / Ausmass und Auswirkungen von Rationierung in deutschen Krankenhäusern. Arztliche Einschätzungen aus einer repräsentativen Umfrage.

BACKGROUND: Healthcare rationing is increasingly discussed among German physicians. However, in contrast to the relatively intense debates on how to prioritize and ration on the macro level of the health system, there is hardly any discussion on how doctors can make the unavoidable rationing decisions on the micro level in a medically and ethically appropriate manner. The development of both accountable and feasible guidance requires empirical evidence about the prevalence of bedside rationing and a more in-depth understanding of the practical challenges. METHODS: Based on the official German hospital registry a national survey was performed nationwide among 1,137 randomly selected physicians working in cardiology or critical care medicine. RESULTS: 68% of the respondents stated that they had already withheld from patients medical services with a potential benefit for the patient because of cost considerations. However, only few of them indicated that this happens often. The frequency of bedside rationing differed, in some cases significantly, in relation to specialty, professional status and hospital funding. The majority of clinicians describes a negative impact of cost pressure on their work satisfaction and on the patient-doctor relationship. German clinicians have become aware of only a few opportunities that would allow them to increase their efficiency with a view to avoiding healthcare rationing. Instead, more then 50 % of the doctors considered additional funding for the health care system, through higher contributions to the statutory health insurance or higher out-of-pocket spending by patients, to be an acceptable approach to dealing with scarce resources. CONCLUSION: There is a need to develop explicit methods that support physicians in making inevitable rationing decisions at the bedside. Such methods must be accompanied by consultation procedures so that a rational and fair use of scarce health care resources is achieved.

Systematic reviews of empirical bioethics.

BACKGROUND: Publications and discussions of survey research in empirical bioethics have steadily increased over the past two decades. However, findings often differ among studies with similar research questions. As a consequence, ethical reasoning that considers only parts of the existing literature and does not apply systematic reviews tends to be biased. To date, we lack a systematic review (SR) methodology that takes into account the specific conceptual and practical challenges of empirical bioethics. METHODS: The steps of systematically reviewing empirical findings in bioethics are presented and critically discussed. In particular, (a) the limitations of traditional SR methodologies in the field of empirical bioethics are critically discussed, and (b) conceptual and practical recommendations for SRs in empirical bioethics that are (c) based on the authors' review experiences in healthcare ethics are presented. RESULTS: A 7-step approach for SRs of empirical bioethics is proposed: (1) careful definition of review question; (2) selection of relevant databases; (3) application of ancillary search strategies; (4) development of search algorithms; (5) relevance assessment of the retrieved references; (6) quality assessment of included studies; and (7) data analysis and presentation. Conceptual and practical challenges arise because of various peculiarities in reviewing empirical bioethics literature and can lead to biased results if they are not taken into account. CONCLUSIONS: If suitably adapted to the peculiarities of the field, SRs of empirical bioethics provide transparent information for ethical reasoning and decision-making that is less biased than single studies.

Zuclopenthixol dihydrochloride for schizophrenia.

BACKGROUND: Zuclopenthixol dihydrochloride, given orally, is commonly used for managing the signs and symptoms of schizophrenia. OBJECTIVES: To determine the effects of zuclopenthixol dhydrochloride for treatment of schizophrenia. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group's register (December 2004). This register is compiled of methodical searches of BIOSIS, CINAHL, Dissertation abstracts, EMBASE, LILACS, MEDLINE, PSYNDEX, PsycINFO, RUSSMED, Sociofile, supplemented with hand searching of relevant journals and numerous conference proceedings. To identify further trials we also contacted a pharmaceutical company and authors of relevant studies. SELECTION CRITERIA: We included all randomised controlled trials comparing zuclopenthixol dihydrocodine with antipsychotics or with placebo (or no intervention) for treatment of schizophrenia and/or schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: We independently inspected citations and abstracts, ordered papers, re-inspected and quality assessed articles and extracted data. For dichotomous data we calculated relative risks (RR) and the 95% confidence intervals (CI) and the number needed to treat (NNT) or number needed to harm statistics. For continuous data we calculated weighted mean differences with 95% CIs for non-skewed data. MAIN RESULTS: We included eighteen trials involving 1578 people. Two trials compared zuclopenthixol with placebo and neither reported global or mental state outcomes. People allocated zuclopenthixol did have increased risk of experiencing extraparamydal symptoms compared with placebo (n=64, RR 5.37, CI 1.12 to 29.34 NNH 2 CI 2 to 31). Ten short trials (total n=478) compared zuclopenthixol with other typical antipsychotics. Risk of being unchanged or worse was decreased by allocation to zuclopenthixol (n=357, 7 RCTs, RR 0.72 CI 0.53 to 0.98, NNT 10 CI 6 to 131). No findings suggest any clear difference between zuclopenthixol and other typical antipsycotics across a whole range of adverse effects, including movement disorders (n=280, 6 RCTs, RR needing additional antiparkinsonian medication 1.07 CI 0.86 to 1.33) and general agitation (n=162, 3 RCTs, RR needing treatment with hypnotic/sedative drugs 1.09 CI 0.76 to 1.56). Fewer people allocated zuclopenthixol left in the short term compared with those given other typical antipsychotics (n=424, 22% vs 30%, 8 RCTs, RR 0.70 CI 0.51 to 0.95, NNT 12 CI 7 to 67). Three short trials (total n=233) compared zuclopenthixol with atypical antipsychotics. Zuclopenthixol was associated with no greater risk of being unchanged or worse compared with risperidone (n=98, 1 RCT, RR 1.30 CI 0.80 to 2.11). People allocated zuclopenthixol were prescribed antiparkinsonian medication more frequently compared to those treated with risperidone (n=98, 1 RCT, RR 1.92 CI 1.12 to 3.28, NNH 3 CI 3 to 17). Weight gain was equal for people allocated zuclopenthixol and those given sulpiride (n=61, 1 RCT, WMD 1.60 CI 8.35 to 5.15). Many people left these short studies early (45% zuclopenthixol vs 30% risperidone, n=159, 2 RCTs, RR 1.48 CI 0.98 to 2.22). The two isomers of zuclopenthixol, when compared in four short studies (total n=140), did not result in clearly different outcomes. AUTHORS' CONCLUSIONS: There is an indication that zuclopenthixol causes movement disorders, perhaps more so than the newer generation of drugs, though no more frequently than the older generation of antipsychotics. There is some suggestion from this review that oral zuclopenthixol may have some clinical advantage, at least in the short term, over other older drugs in terms of global state. If an older drug is going to be prescribed, zuclopenthixol dihydrochloride is a viable option but may be best taken with additional medication to offset movement disorders that occur in about half the people taking this drug. There is no information on service, functional, behavioural outcomes and important outcomes such as relapse, for such a widely used drug this would indicate the need for further studies. We feel that it should remain a choice in the treatment of those for whom older generation drugs are indicated.