What do international ethics guidelines say in terms of the scope of medical research ethics?

BACKGROUND: In research ethics, the most basic question would always be, "which is an ethical issue, which is not?" Interestingly, depending on which ethics guideline we consult, we may have various answers to this question. Though we already have several international ethics guidelines for biomedical research involving human participants, ironically, we do not have a harmonized document which tells us what these various guidelines say and shows us the areas of consensus (or lack thereof). In this manuscript, we attempted to do just that. METHODS: We extracted the imperatives from five internationally-known ethics guidelines and took note where the imperatives came from. In doing so, we gathered data on how many guidelines support a specific imperative. RESULTS: We found that there is no consensus on the majority of the imperatives and that in only 8.2% of the imperatives were there at least moderate consensus (i.e., consensus of at least 3 of the 5 ethics guidelines). Of the 12 clusters (Basic Principles; Research Collaboration; Social Value; Scientific Validity; Participant Selection; Favorable Benefit/Risk Ratio; Independent Review; Informed Consent; Respect for Participants; Publication and Registration; Regulatory Sanctions; and Justified Research on the Vulnerable Population), Informed Consent has the highest level of consensus and Research Collaboration and Regulatory Sanctions have the least. CONCLUSION: There was a lack of consensus in the majority of imperatives from the five internationally-known ethics guidelines. This may be partly explained by the differences among the guidelines in terms of their levels of specification as well as conceptual/ideological differences

Continuous deep sedation at the end of life:a qualitative interview-study among health care providers on an evolving practice

Background:Continuous deep sedation (CDS) can be used for patients at the end of life who suffer intolerably from severe symptoms that cannot be relieved otherwise. In the Netherlands, the use of CDS is guided by an national guideline since 2005. The percentage of patients for whom CDS is used increased from 8% of all patients who died in 2005 to 18% in 2015. The aim of this study is to explore potential causes of the rise in the use of CDS in the Netherlands according to health care providers who have been participating in this practice. Methods: Semi-structured interviews were conducted and thematically analysed. Participants were Dutch health care providers (HCPs), working at patients’ homes, hospices, elderly care facilities and in hospitals and experienced in providing CDS, who were recruited via purposeful sampling. Results: 41 Health care providers participated in an interview. For these HCPs the reason to start CDS is often a combination of symptoms resulting in a refractory state. HCPs indicated that symptoms of non-physical origin are increasingly important in the decision to start CDS. Most HCPs felt that suffering at the end of life is less tolerated by patients, their relatives, and sometimes by HCPs; they report more requests to relieve suffering by using CDS. Some HCPs in our study have experienced increasing pressure to perform CDS. Some HCPs stated that they more often used intermittent sedation, sometimes resulting in CDS. Conclusions: This study provides insight into how participating HCPs perceive that their practice of CDS changed over time. The combination of a broader interpretation of refractory suffering by HCPs and a decreased tolerance of suffering at the end of life by patients, their relatives and HCPs, may have led to a lower threshold to start CDS. Trial registration: The Research Ethics Committee of University Medical Center Utrecht assessed that the study was exempt from ethical review according to Dutch law (Protocol number 19–435/C).</p

Experiences and perceptions of continuous deep sedation:An interview study among Dutch patients and relatives

Background: The incidence of continuous deep sedation (CDS) has more than doubled over the last decade in The Netherlands, while reasons for this increase are not fully understood. Patients and relatives have an essential role in deciding on CDS. We hypothesize that the increase in CDS practice is related to the changing role of patients and relatives in deciding on CDS. Objective: To describe perceptions and experiences of patients and relatives with regard to CDS. This insight may help professionals and policymakers to better understand and respond to the evolving practice of CDS. Methods: Qualitative interviews were held with patients and relatives who had either personal experience with CDS as a relative or had contemplated CDS for themselves. Results: The vast majority of respondents appreciated CDS as a palliative care option, and none of the respondents reported (moral) objections to CDS. The majority of respondents prioritized avoiding suffering at the end of life. The patients and families generally considered CDS a palliative care option for which they can choose. Likewise, according to our respondents, the decision to start CDS was made by them, instead of the physician. Negative experiences with CDS care were mostly related to loss of sense of agency, due to insufficient communication or information provision by healthcare professionals. Lack of continuity of care was also a source of distress. We observed a variety in the respondents' understanding of the distinction between CDS and other end-of-life care decisions, including euthanasia. Some perceived CDS as hastening death. Conclusion: The traditional view of CDS as a last resort option for a physician to relieve a patient's suffering at the end of life is not explicit among patients and relatives. Instead, our results show that they perceive CDS as a regular palliative care option. Along with this normalization of CDS, patients and relatives claim a substantial say in the decision-making and are mainly motivated by a wish to avoid suffering and exercise control at the end of life. These distinct views on CDS of patients, their relatives and healthcare providers should be reconciled in guidelines and protocols for CDS. Patient or Public Contribution: One of the authors in our team (G. H.) has experience with CDS as a relative and ensured that the patient/relative viewpoint was adequately reflected in the design and conduct of our study. In the preliminary phase of our study, G. H. adjusted the topic list so it was better adapted to the current practice of CDS. During the data analysis, G. H. read several interviews and took part in the open and critical discussion on central themes and core concepts as an important member of the author team, thereby guaranteeing the central position of the patient/relative perspective in our final research outcome.</p

Learning accountable governance: Challenges and perspectives for data-intensive health research networks

Current challenges to sustaining public support for health data research have directed attention to the governance of data-intensive health research networks. Accountability is hailed as an important element of trustworthy governance frameworks for data-intensive health research networks. Yet the extent to which adequate accountability regimes in data-intensive health research networks are currently realized is questionable. Current governance of data-intensive health research networks is dominated by the limitations of a drawing board approach. As a way forward, we propose a stronger focus on accountability as learning to achieve accountable governance. As an important step in that direction, we provide two pathways: (1) developing an integrated structure for decision-making and (2) establishing a dialogue in ongoing deliberative processes. Suitable places for learning accountability to thrive are dedicated governing bodies as well as specialized committees, panels or boards which bear and guide the development of governance in data-intensive health research networks. A continuous accountability process which comprises learning and interaction accommodates the diversity of expectations, responsibilities and tasks in data-intensive health research networks to achieve responsible and effective governance

A cross-sectional survey on the early impact of COVID-19 on the uptake of decentralised trial methods in the conduct of clinical trials

BACKGROUND: The COVID-19 pandemic significantly impacted the conduct of clinical trials through delay, interruption or cancellation. Decentralised methods in clinical trials could help to continue trials during a pandemic. This paper presents the results of an exploratory study conducted early in the pandemic to gain insight into and describe the experiences of organisations involved in clinical trials, with regard to the impact of COVID-19 on the conduct of trials, and the adoption of decentralised methods prior to, and as mitigation for the impact, of COVID-19. METHODS: A survey with 11 open-ended and four multiple choice questions was conducted in June 2020 among member organisations of the public-private “Trials@Home” consortium. The survey investigated (1) the impact and challenges of COVID-19 on the continuation of ongoing clinical trials, (2) the adoption of decentralised methods in clinical trials prior to and as a mitigation strategy for COVID-19, (3) the challenges of conducting clinical trials during COVID-19, (4) the expected permanency of COVID-19-driven changes to the adoption of decentralised methods in clinical trials, and (5) lessons learned from conducting clinical trials during the COVID-19 pandemic. A thematic, inductive analysis of open survey questions was performed, complemented with descriptive statistics (frequencies and distributions). RESULTS: The survey had a response rate of 81%. All organisations included in the analysis (n = 18) implemented (some) decentralised methods in their clinical trials prior to COVID-19, and 15 (83%) implemented decentralised methods as mitigation for COVID-19. Decentralised methods for IMP supply, patient-health care provider interaction and communication, clinic visits and source document verification were used more often as mitigation strategies than they were used prior to COVID-19. Many respondents expect to maintain those decentralised methods they implemented during COVID-19 in ongoing trials, as well as implement them in future trials. CONCLUSIONS: Decentralised methods are a widely implemented mitigation strategy for trial conduct in the face of the COVID-19 pandemic. The results of this survey show that there is an interest to continue the use of decentralised methods in future trials, but important points of attention have been identified that need solutions to help guide the transition from the traditional trial model to a more decentralised trial model. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-022-06706-x

Developments in euthanasia practice in the Netherlands: Balancing professional responsibility and the patient’s autonomy

In 2015, euthanasia accounted for 4.5% of deaths in the Netherlands, of which 93% were performed by a GP. Historically, a conflict of physician’s duties—to alleviate unbearable suffering and at the same time preserve the patient’s life—is central to the justification of euthanasia practice in the Netherlands. However, there seems to be a shift towards a greater emphasis on the patient’s autonomous wish as the primary basis for euthanasia. This shift has consequences for the role and interpretation of the physician’s duties in end-of-life care. This paper aims to describe these developments in euthanasia practice and end-of-life decision-making. We describe important relevant developments and look into the role and the meaning of two dimensions of the concept of ‘patient autonomy’ regarding end-of-life decisions, in particular, the euthanasi

Toward responsible clinical n-of-1 strategies for rare diseases

N-of-1 strategies can provide high-quality evidence of treatment efficacy at the individual level and optimize evidence-based selection of off-label treatments for patients with rare diseases. Given their design characteristics, n-of-1 strategies are considered to lay at the intersection between medical research and clinical care. Therefore, whether n-of-1 strategies should be governed by research or care regulations remains a debated issue. Here, we delineate differences between medical research and optimized clinical care, and distinguish the regulations which apply to either. We also set standards for responsible optimized clinical n-of-1 strategies with (off-label) treatments for rare diseases. Implementing clinical n-of-1 strategies as defined here could aid in optimized treatment selection for such diseases

Euthanasia and Physician-Assisted Suicide in Patients with Multiple Geriatric Syndromes

Importance: The Dutch Regional Euthanasia Review Committees (RTEs) reviewed and reported an increasing number of cases of euthanasia and physician-Assisted suicide (EAS) requested by older people with multiple geriatric syndromes (MGS). Knowledge of the characteristics of cases of EAS for MGS is important to facilitate societal debat