BackgroundResearch misconduct and questionable research practices have been the subject of increasing attention in the past few years. But despite the rich body of research available, few empirical works also include the perspectives of non-researcher stakeholders.MethodsWe conducted semi-structured interviews and focus groups with policy makers, funders, institution leaders, editors or publishers, research integrity office members, research integrity community members, laboratory technicians, researchers, research students, and former-researchers who changed career to inquire on the topics of success, integrity, and responsibilities in science. (...) We used the Flemish biomedical landscape as a baseline to be able to grasp the views of interacting and complementary actors in a system setting.ResultsGiven the breadth of our results, we divided our findings in a two-paper series with the current paper focusing on the problems that affect the integrity and research culture. We first found that different actors have different perspectives on the problems that affect the integrity and culture of research. Problems were either linked to personalities and attitudes, or to the climates in which researchers operate. Elements that were described as essential for success were often thought to accentuate the problems of research climates by disrupting research culture and research integrity. Even though all participants agreed that current research climates need to be addressed, participants generally did not feel responsible nor capable of initiating change. Instead, respondents revealed a circle of blame and mistrust between actor groups.ConclusionsOur findings resonate with recent debates, and extrapolate a few action points which might help advance the discussion. First, the research integrity debate must revisit and tackle the way in which researchers are assessed. Second, approaches to promote better science need to address the impact that research climates have on research integrity and research culture rather than to capitalize on individual researchers’ compliance. Finally, inter-actor dialogues and shared decision making must be given priority to ensure that the perspectives of the full research system are captured. Understanding the relations and interdependency between these perspectives is key to be able to address the problems of science.Study registrationhttps://osf.io/33v3m. (shrink)

As thousands of healthy research participants are being included in small and large imaging studies, it is essential that dilemmas raised by the detection of incidental findings are adequately handled. Current ethical guidance indicates that pathways for dealing with incidental findings should be in place, but does not specify what such pathways should look like. Building on an interview study of researchers’ practices and perspectives, we identified key considerations for the set-up of pathways for the detection, management and communication of (...) incidental findings in imaging research. We conducted an interview study with a purposive sample of researchers at research facilities across the Netherlands. Based on a qualitative analysis of these interviews and on existing guidelines found in the literature, we developed a prototype ethical framework, which was critically assessed and fine-tuned during a two-day international expert meeting with bioethicists and representatives from large population-based imaging studies from the United Kingdom, Germany, Sweden and Belgium. Practices and policies for the handling of incidental findings vary strongly across the Netherlands, ranging from no review of research scans and limited feedback to research participants, to routine review of scans and the arrangement of clinical follow-up. Respondents felt that researchers do not have a duty to actively look for incidental findings, but they do have a duty to act on findings, when detected. The principle of reciprocity featured prominently in our interviews and expert meeting. We present an ethical framework that may guide researchers and research ethics committees in the design and/or evaluation of appropriate pathways for the handling of incidental findings in imaging studies. The framework consists of seven steps: anticipation of findings, information provision and informed consent, scan acquisition, review of scans, consultation on detected abnormalities, communication of the finding, and further clinical management and follow-up of the research participant. Each of these steps represents a key decision to be made by researchers, which should be justified not only with reference to costs and/or logistical considerations, but also with reference to researchers’ moral obligations and the principle of reciprocity. (shrink)

This interview study investigates the short- and long-term implications of incidental findings detected through brain imaging on research participants’ lives and their surroundings. For this study, nine participants of the Rotterdam Scan Study with an incidental finding were approached and interviewed. When examining research participants’ narratives on the impact of the disclosure of incidental findings, the authors identified five sets of tensions with regard to motivations for and expectations of research participation, preferences regarding disclosure, short- and long-term impacts and impacts (...) on self and others. The paper shows: that the impact of incidental findings may be greater than participants at first let on; incidental findings can have significant effects on participants’ social environment; and participants may not feel prepared for disclosure even if incidental findings have been discussed during the informed consent process. The authors call for investigators to be aware of research participants’ experiences and these short- and long-term impacts when designing suitable courses of action for the detection and management of incidental findings in research settings. (shrink)

The participation of minors in clinical trials is essential to provide safe and effective medical care to children. Because few drugs have been tested in children, pediatricians are forced to prescribe medications off-label with uncertain efficacy and safety. In this article, we analyze how the enrollment of minors in clinical trials is negotiated within relationships of mutual trust between clinicians, minors, and their parents. After a brief description of the problems associated with involving minors in clinical research, we consider how (...) existing “relationships of trust” can be used as a place where the concerns of research subjects can be more fully discussed and addressed. Building on the tacit recognition of trust found in The European Clinical Trials Directive we make policy recommendations that allow for clearer, more ethically informed guidelines for enrolling minors in clinical research. (shrink)

For a significant number of patients, there exists no, or only little, interest in developing a treatment for their disease or condition. Especially with regard to rare diseases, the lack of commercial interest in drug development is a burning issue. Several interventions have been made in the regulatory field in order to address the commercial disinterest in these conditions. However, existing regulations mainly focus on the provision of incentives to the sponsors of clinical trials of orphan drugs, and leave unanswered (...) the overarching question about the rightful place of orphan drugs in resource allocation systems. In this article, we analyse the ethical aspects of funding research and development in the field of rare diseases. We then propose an ethical framework that can help health policy makers move forward in the difficult matter of fairly allocating resources for the prevention, diagnosis and treatment of rare diseases. (shrink)

ABSTRACTThe quality of medicines is generally adequately assured by manufacturers and regulatory authorities for well-resourced settings, while the implementation of existing quality standards is challenged in many low- and middle-income countries. This situation of multiple pharmaceutical standards raises the question whether it could ever be ethically justified to compromise on the quality assurance of medicines depending on what individuals, communities, or societies can afford. In this paper, we contend that ethically, any unjustified exceptions to medicines’ quality assurance represents a violation (...) of the principles of beneficence and non-maleficence. Exceptions are only acceptable in exceptional and temporary circumstances, if based on a meaningful quality risk assessment, guided by a rigorous ethical framework built on the principles of independence, technical competence, transparency, and accountability. We also discuss how such exceptional and temporary circumstances should be defined/justified.... (shrink)

Patients who search for a better treatment, an increased quality of life, or even a chance to preserve life itself may claim to have an interest in accessing investigational medicinal products (IMP), particularly when no validated treatment for their disease or condition exists. For many, awaiting the uncertain and time-consuming process of converting an IMP into an approved drug may not appear a realistic option, as prognoses may be grim and a dramatic outcome may seem hard to avert. Gaining access (...) to an IMP, however, often proves to be a difficult enterprise with a highly uncertain outcome. In addition, the process of seeking access to IMP is surrounded by various ethical issues that will be explored in this article. This paper explores the ethical concerns in two potential tracks of seeking access to IMP for minors: on an individual basis, or collectively, as a patient organisation. In this discourse, several unique ethical and regulatory concerns related to the direct negotiation of access to IMP for minor patients are identified, with a focus on product safety, the recruitment of research subjects, the unnoticed entry of market mechanisms in the recruitment of research subjects, and the sidelining of third parties in the recruitment process. The paper concludes with a concise reflection on the way forward. The quest for access to investigational drugs is particularly relevant to paediatric practice, in which a significant share of the drugs prescribed has never been tested in children or labelled for use in the paediatric population. (shrink)