Do Physicians Have a Duty to Support Secondary Use of Clinical Data in Biomedical Research? An Inquiry into the Professional Ethics of Physicians.

Secondary use of clinical data in research or learning activities (SeConts) has the potential to improve patient care and biomedical knowledge. Given this potential, the ethical question arises whether physicians have a professional duty to support SeConts. To investigate this question, we analyze prominent international declarations on physicians' professional ethics to determine whether they include duties that can be considered as good reasons for a physicians' professional duty to support SeConts. Next, we examine these documents to identify professional duties that might conflict with a potential duty of physicians to support SeConts.

[Nationally standardized broad consent in practice: initial experiences, current developments, and critical assessment]. / National standardisierter Broad Consent in der Praxis: erste Erfahrungen, aktuelle Entwicklungen und kritische Betrachtungen.

BACKGROUND: The digitalization in the healthcare sector promises a secondary use of patient data in the sense of a learning healthcare system. For this, the Medical Informatics Initiative's (MII) Consent Working Group has created an ethical and legal basis with standardized consent documents. This paper describes the systematically monitored introduction of these documents at the MII sites. METHODS: The monitoring of the introduction included regular online surveys, an in-depth analysis of the introduction processes at selected sites, and an assessment of the documents in use. In addition, inquiries and feedback from a large number of stakeholders were evaluated. RESULTS: The online surveys showed that 27 of the 32 sites have gradually introduced the consent documents productively, with a current total of 173,289 consents. The analysis of the implementation procedures revealed heterogeneous organizational conditions at the sites. The requirements of various stakeholders were met by developing and providing supplementary versions of the consent documents and additional information materials. DISCUSSION: The introduction of the MII consent documents at the university hospitals creates a uniform legal basis for the secondary use of patient data. However, the comprehensive implementation within the sites remains challenging. Therefore, minimum requirements for patient information and supplementary recommendations for best practice must be developed. The further development of the national legal framework for research will not render the participation and transparency mechanisms developed here obsolete.

Physicians' attitudes towards secondary use of clinical data for biomedical research purposes in Germany. Results of a quantitative survey.

BACKGROUND: For biomedical data-driven research purposes, secondary use of clinical data carries great but largely untapped potential. Physicians' attitudes and their needs towards secondary data use are essential to inform its practical and ethically sound implementation but are currently understudied. OBJECTIVE: Therefore, the objectives of the study are to assess physicians' (i) general attitudes and concerns, (ii) willingness to adapt workflows and to make data available for secondary use, (iii) group-specific conditions toward implementation of secondary use and associated concerns of physician-scientists and purely clinical physicians. METHODS: We developed an online survey based on a literature review and an expert interview study. Physicians in private practice and at two large German university hospitals were surveyed from May 2021 until January 2022. RESULTS: In total, 446 physicians participated in the survey. 96% [380/397] of all physicians reported a positive attitude towards secondary use; 87% [31/397] are in-principle willing to support secondary use of clinical data along with a small proportion of physicians with fundamental reservations. Secondly, the most important conditions for adapting workflows were funding of additional time and effort for research-adequate documentation (71% [286/390]) and the most important condition for providing patients' clinical data was reliable protection of patients' privacy (67% [254/382]). Thirdly, physician-scientists were more likely than purely clinical physicians to request additional funding for research-adequate documentation as a precondition for support (83% vs 69%, P = .002) and the privilege to conduct research with their own patients' clinical data before other researchers are allowed to (43% vs 11%, P < .001); while purely clinical physicians more frequently require reliable protection of patient privacy (76% vs 62%, P = .007) and monetary compensation (45% vs 25%, P < .001). CONCLUSION: Since this study presents high in-principle willingness of physicians to support secondary use along with little general concerns, it seems essential to address physicians' group-specific conditions toward secondary use in order to gain their support.

German funders' data sharing policies-A qualitative interview study.

BACKGROUND: Data sharing is commonly seen as beneficial for science but is not yet common practice. Research funding agencies are known to play a key role in promoting data sharing, but German funders' data sharing policies appear to lag behind in international comparison. This study aims to answer the question of how German data sharing experts inside and outside funding agencies perceive and evaluate German funders' data sharing policies and overall efforts to promote data sharing. METHODS: This study is based on sixteen guided expert interviews with representatives of German funders and German research data experts from stakeholder organisations, who shared their perceptions of German' funders efforts to promote data sharing. By applying the method of qualitative content analysis to our interview data, we categorise and describe noteworthy aspects of the German data sharing policy landscape and illustrate our findings with interview passages. RESULTS: We present our findings in five sections to distinguish our interviewees' perceptions on a) the status quo of German funders' data sharing policies, b) the role of funders in promoting data sharing, c) current and potential measures by funders to promote data sharing, d) general barriers to those measures, and e) the implementation of more binding data sharing requirements. DISCUSSION AND CONCLUSION: Although funders are perceived to be important promoters and facilitators of data sharing throughout our interviews, only few German funding agencies have data sharing policies in place. Several interviewees stated that funders could do more, for example by providing incentives for data sharing or by introducing more concrete policies. Our interviews suggest the academic freedom of grantees is widely perceived as an obstacle for German funders in introducing mandatory data sharing requirements. However, some interviewees stated that stricter data sharing requirements could be justified if data sharing is a part of good scientific practice.

Patient data for commercial companies? An ethical framework for sharing patients' data with for-profit companies for research.

BACKGROUND: Research using data from medical care promises to advance medical science and improve healthcare. Academia is not the only sector that expects such research to be of great benefit. The research-based health industry is also interested in so-called 'real-world' health data to develop new drugs, medical technologies or data-based health applications. While access to medical data is handled very differently in different countries, and some empirical data suggest people are uncomfortable with the idea of companies accessing health information, this paper aims to advance the ethical debate about secondary use of medical data generated in the public healthcare sector by for-profit companies for medical research (ReuseForPro). METHODS: We first clarify some basic concepts and our ethical-normative approach, then discuss and ethically evaluate potential claims and interests of relevant stakeholders: patients as data subjects in the public healthcare system, for-profit companies, the public, and physicians and their healthcare institutions. Finally, we address the tensions between legitimate claims of different stakeholders in order to suggest conditions that might ensure ethically sound ReuseForPro. RESULTS: We conclude that there are good reasons to grant for-profit companies access to medical data if they meet certain conditions: among others they need to respect patients' informational rights and their actions need to be compatible with the public's interest in health benefit from ReuseForPro.

What is data stewardship? Towards a comprehensive understanding.

Data stewardship is a term that is understood in heterogenous ways. In recent organisational developments and efforts to build infrastructures and hire professional staff for research data management in various scientific fields in Europe, data stewardship is understood as mainly aiming at optimising data management in line with the FAIR principles (findability, accessibility, interoperability, reusability) forpurposes of reuse in the interests of the scientific community and the public. In addition, especially in the health and biomedical sciences some understandings of data stewardship mainly focus on the responsibility to respect the informational rights of data subjects. Following on from these different understandings and from recent developments to include ever more stakeholders in data stewardship, we propose a comprehensive understanding of data stewardship. According to this comprehensive understanding, data stewardship includes responsibilities towards all pertinent stakeholders and to equally consider and respect their legitimate rights and interests in order to build and maintain an efficient, trusted and fair data ecosystem. We also point out some of the practical challenges implied in such a comprehensive understanding.

[Data infrastructures for health research : Ethical framework and legal implementation]. / Dateninfrastrukturen für die Gesundheitsforschung : Ethische Rahmenbedingungen und rechtliche Umsetzung.

The role of data infrastructures for health research is not limited to acting as a service or interface for data exchange between data producers and data users. Rather, the infrastructure itself is an actor in the process of data sharing and therefore also bears responsibility for this process.This applies first of all to the lawfulness of personal data processing. If data processing is based on the consent of the data subject, the infrastructure must also ensure that all data processing is covered by this consent. If the data processing is based on a statutory basis, the infrastructure must ensure the highest possible level of data protection, in particular through technical and organizational measures. In addition, the infrastructure is also responsible for implementing the rights of data subjects, such as the right to information, rectification or erasure of data, and dealing with incidental or additional findings.The question of how researchers regard their involvement in infrastructure projects and how private companies should be involved in such projects must be based on the principle of public welfare. This is accompanied by the obligation of infrastructures to take into account the principles of participation, transparency, and scientific communication as far as possible. Observing all these ethical and legal aspects is especially important because only by doing so can the trust of all stakeholders be established and thus the central basis for the successful construction and operation of data infrastructures be provided.

Neither carrots nor sticks? Challenges surrounding data sharing from the perspective of research funding agencies-A qualitative expert interview study.

BACKGROUND: Data Sharing is widely recognised as crucial for accelerating scientific research and improving its quality. However, data sharing is still not a common practice. Funding agencies tend to facilitate the sharing of research data by both providing incentives and requiring data sharing as part of their policies and conditions for awarding grants. The goal of our article is to answer the following question: What challenges do international funding agencies see when it comes to their own efforts to foster and implement data sharing through their policies? METHODS: We conducted a series of sixteen guideline-based expert interviews with representatives of leading international funding agencies. As contact persons for open science at their respective agencies, they offered their perspectives and experiences concerning their organisations' data sharing policies. We performed a qualitative content analysis of the interviews and categorised the challenges perceived by funding agencies. RESULTS: We identify and illustrate six challenges surrounding data sharing policies as perceived by leading funding agencies: The design of clear policies, monitoring of compliance, sanctions for non-compliance, incentives, support, and limitations for funders' own capabilities. However, our interviews also show how funders approach potential solutions to overcome these challenges, for example by coordinating with other agencies or adjusting grant evaluation metrics to incentivise data sharing. DISCUSSION AND CONCLUSION: Our interviews point to existing flaws in funders' data sharing policies, such as a lack of clarity, a lack of monitoring of funded researchers' data sharing behaviour, and a lack of incentives. A number of agencies could suggest potential solutions but often struggle with the overall complexity of data sharing and the implementation of these measures. Funders cannot solve each challenge by themselves, but they can play an active role and lead joint efforts towards a culture of data sharing.

Patients' Willingness to Provide Their Clinical Data for Research Purposes and Acceptance of Different Consent Models: Findings From a Representative Survey of Patients With Cancer.

BACKGROUND: Secondary use of clinical data for biomedical research purposes holds great potential for various types of noninterventional, data-driven studies. Patients' willingness to support research with their clinical data is a crucial prerequisite for research progress. OBJECTIVE: The aim of the study was to learn about patients' attitudes and expectations regarding secondary use of their clinical data. In a next step, our results can inform the development of an appropriate governance framework for secondary use of clinical data for research purposes. METHODS: A questionnaire was developed to assess the willingness of patients with cancer to provide their clinical data for biomedical research purposes, considering different conditions of data sharing and consent models. The Cancer Registry of the German federal state of Baden-Württemberg recruited a proportionally stratified random sample of patients with cancer and survivors of cancer based on a full census. RESULTS: In total, 838 participants completed the survey. Approximately all participants (810/838, 96.7%) showed general willingness to make clinical data available for biomedical research purposes; however, they expected certain requirements to be met, such as comparable data protection standards for data use abroad and the possibility to renew consent at regular time intervals. Most participants (620/838, 73.9%) supported data use also by researchers in commercial companies. More than half of the participants (503/838, 60%) were willing to give up control over clinical data in favor of research benefits. Most participants expressed acceptance of the broad consent model (494/838, 58.9%), followed by data use by default (with the option to opt out at any time; 419/838, 50%); specific consent for every study showed the lowest acceptance rate (327/838, 39%). Patients expected physicians to share their data (763/838, 91.1%) and their fellow patients to support secondary use with their clinical data (679/838, 81%). CONCLUSIONS: Although patients' general willingness to make their clinical data available for biomedical research purposes is very high, the willingness of a substantial proportion of patients depends on additional requirements. Taking these perspectives into account is essential for designing trustworthy governance of clinical data reuse and sharing. The willingness to accept the loss of control over clinical data to enhance the benefits of research should be given special consideration.

Data protection-compliant broad consent for secondary use of health care data and human biosamples for (bio)medical research: Towards a new German national standard.

BACKGROUND: The secondary use of deidentified but not anonymized patient data is a promising approach for enabling precision medicine and learning health care systems. In most national jurisdictions (e.g., in Europe), this type of secondary use requires patient consent. While various ethical, legal, and technical analyses have stressed the opportunities and challenges for different types of consent over the past decade, no country has yet established a national consent standard accepted by the relevant authorities. METHODS: A working group of the national Medical Informatics Initiative in Germany conducted a requirements analysis and developed a GDPR-compliant broad consent standard. The development included consensus procedures within the Medical Informatics Initiative, a documented consultation process with all relevant stakeholder groups and authorities, and the ultimate submission for approval via the national data protection authorities. RESULTS: This paper presents the broad consent text together with a guidance document on mandatory safeguards for broad consent implementation. The mandatory safeguards comprise i) independent review of individual research projects, ii) organizational measures to protect patients from involuntary disclosure of protected information, and iii) comprehensive information for patients and public transparency. This paper further describes the key issues discussed with the relevant authorities, especially the position on additional or alternative consent approaches such as dynamic consent. DISCUSSION: Both the resulting broad consent text and the national consensus process are relevant for similar activities internationally. A key challenge of aligning consent documents with the various stakeholders was explaining and justifying the decision to use broad consent and the decision against using alternative models such as dynamic consent. Public transparency for all secondary use projects and their results emerged as a key factor in this justification. While currently largely limited to academic medicine in Germany, the first steps for extending this broad consent approach to wider areas of application, including smaller institutions and medical practices, are currently under consideration.

Secondary Use of Clinical Data in Data-Gathering, Non-Interventional Research or Learning Activities: Definition, Types, and a Framework for Risk Assessment.

BACKGROUND: The secondary use of clinical data in data-gathering, non-interventional research or learning activities (SeConts) has great potential for scientific progress and health care improvement. At the same time, it poses relevant risks for the privacy and informational self-determination of patients whose data are used. OBJECTIVE: Since the current literature lacks a tailored framework for risk assessment in SeConts as well as a clarification of the concept and practical scope of SeConts, we aim to fill this gap. METHODS: In this study, we analyze each element of the concept of SeConts to provide a synthetic definition, investigate the practical relevance and scope of SeConts through a literature review, and operationalize the widespread definition of risk (as a harmful event of a certain magnitude that occurs with a certain probability) to conduct a tailored analysis of privacy risk factors typically implied in SeConts. RESULTS: We offer a conceptual clarification and definition of SeConts and provide a list of types of research and learning activities that can be subsumed under the definition of SeConts. We also offer a proposal for the classification of SeConts types into the categories non-interventional (observational) clinical research, quality control and improvement, or public health research. In addition, we provide a list of risk factors that determine the probability or magnitude of harm implied in SeConts. The risk factors provide a framework for assessing the privacy-related risks for patients implied in SeConts. We illustrate the use of risk assessment by applying it to a concrete example. CONCLUSIONS: In the future, research ethics committees and data use and access committees will be able to rely on and apply the framework offered here when reviewing projects of secondary use of clinical data for learning and research purposes.

Do patients and research subjects have a right to receive their genomic raw data? An ethical and legal analysis.

BACKGROUND: As Next Generation Sequencing technologies are increasingly implemented in biomedical research and (translational) care, the number of study participants and patients who ask for release of their genomic raw data is set to increase. This raises the question whether research participants and patients have a legal and moral right to receive their genomic raw data and, if so, how this right should be implemented into practice. METHODS: In a first step we clarify some central concepts such as "raw data"; in a second step we sketch the international legal framework. The third step provides an extensive ethical analysis which comprehends two parts: an evaluation of whether there is a prima facie moral right to receive one's raw data, and a contextualization and discussion of the right in light of potentially conflicting interests and rights of the data subject herself and third parties; in a last fourth step we emphasize the main practical consequences of the ethical analyses and propose recommendations for the release of raw data. RESULTS: In several legislations like the new European General Data Protection Regulation, patients do in principle have the right to receive their raw data. However, the procedural implementation of this right and whether it involves genetic counselling is at the discretion of the Member States. Even more questions remain with respect to the research context. The ethical analysis suggests that patients and research subjects have a moral right to receive their genomic raw data and addresses aspects which are also of relevance for the legal discussion such as the costs of release of raw data and its impact on academic freedom. CONCLUSION: Taking into account the specific nature and implications of genomic raw data and the contexts of research and health care, several concerns and potentially conflicting interests of the data subjects themselves and involved researchers, physicians, biomedical institutions and relatives arise. Instead of using them to argue in favor of restrictions of the data subjects' legal and moral right to genomic raw data, the concerns should be addressed through provision of information and other measures. To this end, we propose relevant recommendations.

Trust and responsibility in molecular tumour boards.

Molecular tumour boards (MTBs) offer recommendations for potentially effective, but potentially burdensome, molecularly targeted treatments to a patient's treating physician. In this paper, we discuss the question of who is responsible for ensuring that there is an adequate evidence base for any treatments recommended to a patient. We argue that, given that treating oncologists cannot usually offer a robust evaluation of the evidence underlying an MTB's recommendation, members of the MTB are responsible for ensuring that the evidence level is adequate. We explore two models for how to share responsibility between MTB members. According to the first model, each MTB member, as well as the treating physician, should be held maximally and equally responsible for the recommendations. We argue that this insufficiently accounts for differences in roles and expertise of MTB members. We propose instead that responsibility is delegated via relationships of trust. We argue if these relationships of trust are to be instances of reasonable trust, (a) MTBs should offer a clinical representative to whom a treating physician may delegate the responsibility of ensuring there is sufficient evidence for treatment recommendations, (b) the relationships of trust between the representative and the other MTB members should be clearly defined, and (c) MTB members should be carefully selected. Treating oncologists retain a responsibility to consider general limitations of the evidence for targeted treatments in assessing whether the treatment recommendation offered by an MTB's representative is adequate for a given clinical situation.

'Your DNA, Your Say': global survey gathering attitudes toward genomics: design, delivery and methods.

Our international study, 'Your DNA, Your Say', uses film and an online cross-sectional survey to gather public attitudes toward the donation, access and sharing of DNA information. We describe the methodological approach used to create an engaging and bespoke survey, suitable for translation into many different languages. We address some of the particular challenges in designing a survey on the subject of genomics. In order to understand the significance of a genomic result, researchers and clinicians alike use external databases containing DNA and medical information from thousands of people. We ask how publics would like their 'anonymous' data to be used (or not to be used) and whether they are concerned by the potential risks of reidentification; the results will be used to inform policy.

Key Implications of Data Sharing in Pediatric Genomics.

Accurate clinical interpretation of children's whole-genome and whole-exome sequences relies on comparing the patient's linked genomic and phenotypic data with variant reference databases of both healthy and affected patients. The robustness of such comparisons, in turn, is made possible by sharing pediatric genomic and associated clinical data. Despite this, sparse ethical-legal policy attention has been paid to making such sharing routine in practice. The interdisciplinary Paediatric Task Team of the Global Alliance for Genomics and Health considered in detail the current ethical, legal, and social implications of sharing genomic and associated clinical data involving children. An initial set of points to consider was presented at a meeting of the Paediatric Task Team at the 4th Plenary of the Global Alliance for Genomics and Health. The Key Implications for Data Sharing (KIDS) framework for pediatric genomics was developed based on feedback from this group and was supplemented by findings from a critical appraisal of the data-sharing literature. The final points to consider that comprise the KIDS framework are categorized into the following 4 primary themes: children's involvement, parental consent, balancing benefits and risks, and data protection and release requirements.

Applying systems biology to biomedical research and health care: a précising definition of systems medicine.

BACKGROUND: Systems medicine has become a key word in biomedical research. Although it is often referred to as P4-(predictive, preventive, personalized and participatory)-medicine, it still lacks a clear definition and is open to interpretation. This conceptual lack of clarity complicates the scientific and public discourse on chances, risks and limits of Systems Medicine and may lead to unfounded hopes. Against this background, our goal was to develop a sufficiently precise and widely acceptable definition of Systems Medicine. METHODS: In a first step, PubMed was searched using the keyword "systems medicine". A data extraction tabloid was developed putting forward a means/ends-division. Full-texts of articles containing Systems Medicine in title or abstract were screened for definitions. Definitions were extracted; their semantic elements were assigned as either means or ends. To reduce complexity of the resulting list, summary categories were developed inductively. In a second step, we applied six criteria for adequate definitions (necessity, non-circularity, non-redundancy, consistency, non-vagueness, and coherence) to these categories to derive a so-called précising definition of Systems Medicine. RESULTS: We identified 185 articles containing the term Systems Medicine in title or abstract. 67 contained at least one definition of Systems Medicine. In 98 definitions, we found 114 means and 132 ends. From these we derived the précising definition: Systems Medicine is an approach seeking to improve medical research (i.e. the understanding of complex processes occurring in diseases, pathologies and health states as well as innovative approaches to drug discovery) and health care (i.e. prevention, prediction, diagnosis and treatment) through stratification by means of Systems Biology (i.e. data integration, modeling, experimentation and bioinformatics). Our study also revealed the visionary character of Systems Medicine. CONCLUSIONS: Our insights, on the one hand, allow for a realistic identification of actual ethical as well as legal issues arising in the context of Systems Medicine and, in consequence, for a realistic debate of questions concerning its matter and (future) handling. On the other hand, they help avoiding unfounded hopes and unrealistic expectations. This especially holds for goals like improving patient participation which are intensely debated in the context of Systems Medicine, however not implied in the concept.

So rare we need to hunt for them: reframing the ethical debate on incidental findings.

Incidental findings are the subject of intense ethical debate in medical genomic research. Every human genome contains a number of potentially disease-causing alterations that may be detected during comprehensive genetic analyses to investigate a specific condition. Yet available evidence shows that the frequency of incidental findings in research is much lower than expected. In this Opinion, we argue that the reason for the low level of incidental findings is that the filtering techniques and methods that are applied during the routine handling of genomic data remove these alterations. As incidental findings are systematically filtered out, it is now time to evaluate whether the ethical debate is focused on the right issues. We conclude that the key question is whether to deliberately target and search for disease-causing variations outside the indication that has originally led to the genetic analysis, for instance by using positive lists and algorithms.

Stakeholders' perspectives on biobank-based genomic research: systematic review of the literature.

The success of biobank-based genomic research is widely dependent on people's willingness to donate their tissue. Thus, stakeholders' opinions should be considered in the development of best practice guidelines for research and recruiting participants. We systematically analyzed the empirical literature describing different stakeholders' views towards ethical questions with regard to type of consent, data sharing and return of incidental findings. Patients are more open to one-time general consent than the public. Only a small proportion desires recontact if the research aim changed. A broad consent model would prevent only a small proportion of patients from participating in research. Although professionals are concerned about a risk of reidentification, patients and the public support data sharing and find that the benefit of research outweighs the potential risk of reidentification. However, they desire detailed information about the privacy protection measures. Regarding the return of incidental findings, the public and professionals focus on clinically actionable results, whereas patients are interested in receiving as much information as possible. For professionals, concrete guidelines that help managing the return of incidental findings should be warranted. For this it would be helpful addressing the different categories - actionable, untreatable and inheritable diseases - upfront with patients and public.