Empirical studies on how ethical recommendations are translated into practice: a cross-section study on scope and study objectives.

BACKGROUND: Empirical research can become relevant for bioethics in at least two ways. First, by informing the development or refinement of ethical recommendations. Second, by evaluating how ethical recommendations are translated into practice. This study aims to investigate the scope and objectives of empirical studies evaluating how ethical recommendations are translated into practice. METHODS: A sample of the latest 400 publications from four bioethics journals was created and screened. All publications were included if they met one of the following three criteria: (1) evaluative empirical research, (2) non-evaluative empirical research and (3) borderline cases. For all publications categorized as evaluative empirical research we analyzed which objects (norms and recommendations) had been evaluated. RESULTS: 234 studies were included of which 54% (n = 126) were categorized as non-evaluative empirical studies, 36% (n = 84) as evaluative empirical studies, and 10% (n = 24) as borderline cases. The object of evaluation were aspirational norms in 5 of the 84 included evaluative empirical studies, more specific norms in 14 (16%) studies and concrete best practices in 65 (77%) studies. The specific best practices can be grouped under five broader categories: ethical procedures, ethical institutions, clinical or research practices, educational programs, and legal regulations. CONCLUSIONS: This mapping study shows that empirical evaluative studies can be found at all stages in the translational process from theory to best practices. Our study suggests two intertwined dimensions for structuring the field of evaluative/translational empirical studies in bioethics: First, three broader categories of evaluation objects and second five categories for types of best practices. TRIAL REGISTRATION: The methodology used was described in a study protocol that was registered publicly on the Open Science Framework ( https://osf.io/r6h4y/ ).

Implementation of data access and use procedures in clinical data warehouses. A systematic review of literature and publicly available policies.

BACKGROUND: The promises of improved health care and health research through data-intensive applications rely on a growing amount of health data. At the core of large-scale data integration efforts, clinical data warehouses (CDW) are also responsible for data governance, managing data access and (re)use. As the complexity of the data flow increases, greater transparency and standardization of criteria and procedures are required in order to maintain objective oversight and control. Therefore, the development of practice oriented and evidence-based policies is crucial. This study assessed the spectrum of data access and use criteria and procedures in clinical data warehouses governance internationally. METHODS: We performed a systematic review of (a) the published scientific literature on CDW and (b) publicly available information on CDW data access, e.g., data access policies. A qualitative thematic analysis was applied to all included literature and policies. RESULTS: Twenty-three scientific publications and one policy document were included in the final analysis. The qualitative analysis led to a final set of three main thematic categories: (1) requirements, including recipient requirements, reuse requirements, and formal requirements; (2) structures and processes, including review bodies and review values; and (3) access, including access limitations. CONCLUSIONS: The description of data access and use governance in the scientific literature is characterized by a high level of heterogeneity and ambiguity. In practice, this might limit the effective data sharing needed to fulfil the high expectations of data-intensive approaches in medical research and health care. The lack of publicly available information on access policies conflicts with ethical requirements linked to principles of transparency and accountability. CDW should publicly disclose by whom and under which conditions data can be accessed, and provide designated governance structures and policies to increase transparency on data access. The results of this review may contribute to the development of practice-oriented minimal standards for the governance of data access, which could also result in a stronger harmonization, efficiency, and effectiveness of CDW.

Involving patients and the public in medical and health care research studies: An exploratory survey on participant recruiting and representativeness from the perspective of study authors.

Research on patient and public involvement so far concentrates on defining involvement, describing its methods, and analyzing involvement practices in various individual research disciplines. There is little empirical data on the process of and aims for selecting (lay) PPI participants, and to what extend they can and should be representative of the population at large. To explore practices and perceptions on these issues and on future PPI conduct more generally, we sent an electronic survey to authors who published involvement activities as part of their studies in medical and social science journals. We identified such authors with a systematic search of five databases and applied descriptive statistics for analysis. Of those who returned the survey (n = 127 of 315; 40%), most had previously conducted involvement activities (73%). 45% reported more than one type of involvement, e.g. consultation and deliberation and participation (14%) and to have recruited more than one type of participant for their PPI activity (56%), e.g. 'lay publics' and 'expert publics' (33% of 71). Representativeness was often seen as a crucial objective when selecting PPI participants, while less than half found it very easy (9%) or rather easy (34%) to select participants. Many respondents considered achieving good representativeness difficult (52%) or very difficult (17%). They identified significant respective challenges and desired more guidance on various aspects of planning and conducting PPI (56%). 55% thought that the concept of "involvement" should be changed or improved. We conclude that recruiting lay people for PPI activities and deciding about and handling representativeness are controversial in current PPI practice, given the manifold challenges mentioned by the survey respondents. Our findings may inform further research particularly regarding-the potentially many cases of-unpublished PPI.

Practice evaluation of biobank ethics and governance: current needs and future perspectives.

BACKGROUND: Biobank research faces many ethical challenges. Ethics research aims to develop standards for governance to meet these challenges by elaborating overarching normative principles of medical ethics in the context of biobanking. Most ethical standards are widely agreed on among biobank stakeholders and entail specific governance solutions, for example, adoption of consent procedures. In order to fully meet its goal, every governance solution needs to be implemented, evaluated and, if necessary, adapted and improved in practice. This study reviews the scientific literature on biobank ethics and governance in order to identify studies that specifically focus on practice evaluation of biobank governance. METHODS: A PubMed search was carried out. Retrieved literature was categorised and thematically clustered. All studies that focus on practice evaluation were reviewed and their objectives, results, and recommendations for practice summarised. RESULTS: The findings show that the majority of studies on biobank ethics and governance are theoretical; only 25 out of 922 studies empirically evaluate biobank governance in practice. The majority of these (14; 59%) focused on informed consent. Six studies (24%) addressed practice evaluation of sample and data access; the rest focused on public involvement, ethics reporting and incidental findings. Other relevant governance areas such as ethics review, priority setting and sample ownership were not addressed. CONCLUSION: In order to fulfil the ethical goals, more empirical research is needed that provides information on how governance mechanisms perform in practice and what improvements are needed.

Preclinical efficacy in therapeutic area guidelines from the U.S. Food and Drug Administration and the European Medicines Agency: a cross-sectional study.

BACKGROUND AND PURPOSE: Therapeutic area guidelines (TAGs) published by the EMA and the FDA offer guidance in planning the launch of a trial in a certain indication. We assessed and compared the guidance on preclinical efficacy of all available TAGs from EMA and FDA. EXPERIMENTAL APPROACH: EMA and FDA websites and databases were searched for all TAGs. A mixed deductive and inductive approach was applied to analyse and cluster content for preclinical efficacy. KEY RESULTS: A total of 114 EMA and 120 FDA TAGs were identified, covering 126 indications. Our core finding is that 75% of EMA TAGs and 58% from the FDA TAGs do not offer any guidance on preclinical efficacy. TAGs varied widely on the extent, nature and detail of guidance. CONCLUSIONS AND IMPLICATIONS: Guidance on preclinical efficacy in a consistent, comprehensive and explicit way that still allows for justified deviations is an important but neglected aspect of transparency for drug development. This transparency would help sponsors in designing preclinical studies and in negotiating more efficiently with regulators.

Current practices for access, compensation, and prioritization in biobanks. Results from an interview study.

Human biological materials and related data stored in biobanks are valuable resources for biomedical research. Transparent, effective, and efficient governance structures and procedures for access, compensation, and priority setting are needed, but recent debates indicate challenges in the practical application of such governance processes. This study aimed to assess the practical experiences and attitudes of biobank experts regarding the governance of biosample access, prioritization, and compensation. Qualitative, semi-structured telephone interviews were conducted with 20 biobank directors from eight countries. Respondents highlighted the need for sound governance structures in order to ensure acceptance by all stakeholders (patients/donors, researchers, research funders, public, and others). They stressed practical difficulties in trying to make best use of biomaterials. As biobanks often form part of larger academic and clinical settings, the different and sometimes conflicting interests of researchers, clinicians, patients, funders, and biobank staff currently affect the governance of access decisions. Investments such as intellectual input, financial, and human resources need to be compensated adequately. Biobanks thereby have a dual role stewarding the hosted biosamples and acting as a service provider for local researchers from universities or hospitals. In order to facilitate efficient use of human biological materials, greater harmonization of at least minimum standards for access and compensation are required at both a national and an international level.

The spectrum of ethical issues in a Learning Health Care System: a systematic qualitative review.

PURPOSE: To determine systematically the spectrum of ethical issues that is raised for stakeholders in a 'Learning Health Care System' (LHCS). DATA SOURCES: The systematic review was conducted in PubMed and Google Books between the years 2007 and 2015. STUDY SELECTION: The literature search retrieved 1258 publications. Each publication was independently screened by two reviewers for eligibility for inclusion. Ethical issues were defined as arising when a relevant normative principle is not adequately considered or two principles come into conflict. DATA EXTRACTION: A total of 65 publications were included in the final analysis and were analysed using an adapted version of qualitative content analysis. A coding frame was developed inductively from the data, only the highest-level categories were generated deductively for a life-cycle perspective. RESULTS OF DATA SYNTHESIS: A total of 67 distinct ethical issues could be categorized under different phases of the LHCS life-cycle. An overarching theme that was repeatedly raised was the conflict between the current regulatory system and learning health care. CONCLUSION: The implementation of a LHCS can help realize the ethical imperative to continuously improve the quality of health care. However, the implementation of a LHCS can also raise a number of important ethical issues itself. This review highlights the importance for health care leaders and policy makers to balance the need to protect and respect individual participants involved in learning health care activities with the social value of improving health care.

Tracking the timely dissemination of clinical studies. Characteristics and impact of 10 tracking variables.

Background: Several meta-research studies and benchmarking activities have assessed how comprehensively and timely, academic institutions and private companies publish their clinical studies. These current "clinical trial tracking" activities differ substantially in how they sample relevant studies, and how they follow up on their publication. Methods: To allow informed policy and decision making on future publication assessment and benchmarking of institutions and companies, this paper outlines and discusses 10 variables that influence the tracking of timely publications. Tracking variables were initially selected by experts and by the authors through discussion. To validate the completeness of our set of variables, we conducted i) an explorative review of tracking studies and ii) an explorative tracking of registered clinical trials of three leading German university medical centres. Results: We identified the following 10 relevant variables impacting the tracking of clinical studies: 1) responsibility for clinical studies, 2) type and characteristics of clinical studies, 3) status of clinical studies, 4) source for sampling, 5) timing of registration, 6) determination of completion date, 7) timeliness of dissemination, 8) format of dissemination, 9) source for tracking, and 10) inter-rater reliability. Based on the description of these tracking variables and their influence, we discuss which variables could serve in what ways as a standard assessment of "timely publication". Conclusions: To facilitate the tracking and consequent benchmarking of how often and how timely academic institutions and private companies publish clinical study results, we have two core recommendations. First, the improvement in the link between registration and publication, for example via institutional policies for academic institutions and private companies. Second, the comprehensive and transparent reporting of tracking studies according to the 10 variables presented in this paper.

Access policies in biobank research: what criteria do they include and how publicly available are they? A cross-sectional study.

Access policies of biobanks specify the governance of sample and data sharing. Basic guidance on relevant access criteria exists, but so far little is known about their public availability and what criteria for access and prioritization they actually include. Access policies were gathered by hand searching the websites of biobanks identified via registries (eg, BBMRI and P3G), and by additional search strategies. Criteria for access and prioritization were synthesized by thematic analysis. Of 523 biobank websites screened, 9% included a publicly available access policy. With all applied search strategies, we finally retrieved 74 access policies. Thematic analysis resulted in 62 different access criteria in three main categories: (a) scientific quality, (b) value and (c) ethical soundness. 'Scientific quality' criteria were mentioned in 70% of all policies, 'value' criteria in 33% and 'ethical soundness' criteria in 73%. Criteria for prioritization were specified in 27% of all policies. Access policies differed broadly in number, specification and operationalization of the included access criteria. In order to make biobank research more effective, efficient and trustworthy, access policies should be more available to the public. Furthermore, access policies should aim for precise and more harmonized wording of access criteria. From a public and governance perspective, the issue of how to prioritize access to scarce samples should form part of access policies.

Input analysis for two public consultations on the EU Clinical Trials Regulation.

BACKGROUND: The European Union's (EU) Clinical Trials Directive was replaced by an EU-Regulation as of 2016. The policy revision process was subject to a formal impact assessment exercised by the European Commission (EC) from 2008 to 2014. Following the EU principles of Good Governance, deliberation with stakeholders was an integral part of this impact assessment and the policy formulation process. Hence, two public consultations (PCs) were held by the EC in 2009 and 2011, respectively. Various stakeholders contributed and submitted their written input to the EC. Though often cited in the further revision process, the input gathered in the PC was not communicated with full transparency and it is unclear how and to what extent the input has been processed and used in the policy formulation. The objective of this study was an analysis of submissions to both PCs in order to systematically present what topics have been discussed and which possible policy options have been raised by the stakeholders. METHODS: All written submissions publicly available were downloaded from the EC's homepage and assessed for stakeholder characteristics. Thematic text analysis was applied to assess the full text of a random sample of 33% of these submissions. RESULTS: A total of 198 different stakeholders from the EU and the United States of America contributed to one or both of the two PCs. In total, 44 various themes have been addressed that could be clustered under 24 main themes, including the articulation of problems as well as possible policy solutions to face these problems. CONCLUSION: The two PCs on the Clinical Trials Directive were highly appreciated by the various stakeholders and their input allowed an in-depth view on their particular interests. This input provided a rich source of information for all stakeholders in the field of clinical trials as well as to the EC's impact assessment. Although the EC obviously gathered a large quantity of expert knowledge on practical implications of trials legislation by consulting stakeholders, it remained unclear how this input was used in the development of the new regulation. For the sake of transparency, it is recommended that in future PCs the EC uses better standardized methods for a more transparent analysis and presentation of results.