The bench is closer to the bedside than we think: Uncovering the ethical ties between preclinical researchers in translational neuroscience and patients in clinical trials.

Millions of people worldwide currently suffer from serious neurological diseases and injuries for which there are few, and often no, effective treatments. The paucity of effective interventions is, no doubt, due in large part to the complexity of the disorders, as well as our currently limited understanding of their pathophysiology. The bleak picture for patients, however, is also attributable to avoidable impediments stemming from quality concerns in preclinical research that often escape detection by research regulation efforts. In our essay, we connect the dots between these concerns about the quality of preclinical research and their potential ethical impact on the patients who volunteer for early trials of interventions informed by it. We do so in hopes that a greater appreciation among preclinical researchers of these serious ethical consequences can lead to a greater commitment within the research community to adopt widely available tools and measures that can help to improve the quality of research.

The past and present of pandemic management: health diplomacy, international epidemiological surveillance, and COVID-19.

The establishment of international sanitary institutions, which took place in the context of rivalry among the great European powers and their colonial expansion in Asia, allowed for the development of administrative systems of international epidemiological surveillance as a response to the cholera epidemics at the end of the nineteenth century. In this note, I reflect on how a historical analysis of the inception of international epidemiological surveillance and pandemic management helps us to understand what is happening in the COVID-19 pandemic today.

Dynamic Consent: a potential solution to some of the challenges of modern biomedical research.

BACKGROUND: Innovations in technology have contributed to rapid changes in the way that modern biomedical research is carried out. Researchers are increasingly required to endorse adaptive and flexible approaches to accommodate these innovations and comply with ethical, legal and regulatory requirements. This paper explores how Dynamic Consent may provide solutions to address challenges encountered when researchers invite individuals to participate in research and follow them up over time in a continuously changing environment. METHODS: An interdisciplinary workshop jointly organised by the University of Oxford and the COST Action CHIP ME gathered clinicians, researchers, ethicists, lawyers, research participants and patient representatives to discuss experiences of using Dynamic Consent, and how such use may facilitate the conduct of specific research tasks. The data collected during the workshop were analysed using a content analysis approach. RESULTS: Dynamic Consent can provide practical, sustainable and future-proof solutions to challenges related to participant recruitment, the attainment of informed consent, participant retention and consent management, and may bring economic efficiencies. CONCLUSIONS: Dynamic Consent offers opportunities for ongoing communication between researchers and research participants that can positively impact research. Dynamic Consent supports inter-sector, cross-border approaches and large scale data-sharing. Whilst it is relatively easy to set up and maintain, its implementation will require that researchers re-consider their relationship with research participants and adopt new procedures.

Targeted drugs and Psycho-oncological intervention for breast cancer patients.

Personalized medicine is a new field based on molecular biology and genomics in which targeted tumor therapies are administered to patients. Psycho-oncology is a complementary approach that considers social and psychological aspects of patients as part of the treatments for cancer patients. The aim of this mini-review is to weigh clinical benefits for breast cancer patients of both treatments and possibly enhance benefits by modulating the use of both interventions. We have compared and evaluated on the one hand the use of anti Vascular Endothelial Growth Factor and, on the other hand, psycho-oncological interventions in metastatic and non-metastatic breast cancer patients.Both treatments did not increase survival of metastatic breast cancer patients, while in a selected study psycho-oncological interventions extended lifespan of non-metastatic breast cancer patients and ameliorate psychological and social factors of metastatic breast cancer patients. Because the two approaches address completely different aspects of cancer patients, if the comparison is limited to the extension of survival, the value of these two treatments cannot be assessed and compared.It is likely that by comparing patients reported outcomes, possibly by using standardized Quality of Life questionnaires, both patients and health care providers can weigh the benefits of the two treatments. It is therefore important to evaluate the use of cancer patients' quality of life measures as a mean to improve their experiences about life and treatment, and possibly to extend their survival.

Research participants' perceptions and views on consent for biobank research: a review of empirical data and ethical analysis.

BACKGROUND: Appropriate information and consent has been one of the most intensely discussed topics within the context of biobank research. In parallel to the normative debate, many socio-empirical studies have been conducted to gather experiences, preferences and views of patients, healthy research participants and further stakeholders. However, there is scarcity of literature which connects the normative debate about justifications for different consent models with findings gained in empirical research. In this paper we discuss findings of a limited review of socio-empirical research on patients' and healthy research participants' experiences and views regarding consent to biobank research in light of ethical principles for appropriate information and consent. METHODS: Review question: Which empirical data are available on research participants' perceptions and views regarding information and elicitation of consent for biobank research? Search of articles published till March 1st 2014 in Pubmed. Review of abstracts and potentially relevant full text articles by two authors independently. As categories for content analysis we defined (i) understanding or recall of information, (ii) preferences regarding information or consent, and (iii) research participants' concerns. RESULTS: The search in Pubmed yielded 337 abstracts of which 10 articles were included in this study. Approaches to information and consent varied considerably across the selected studies. The majority of research participants opted for some version of limited consent when being informed about such possibility. Among the factors influencing the type of preferred consent were information about sponsoring of biobank research by pharmaceutical industry and participants' trade-off between privacy and perceived utility. Studies investigating research participants' understanding and recall regarding the consent procedure indicated considerable lack of both aspects. Research participants' perceptions of benefits and harms differ across those studies. CONCLUSION: The knowledge, perceptions and views of research participants who have undergone a consent procedure within the context of biobank research raise several questions on the issue of how to inform and elicit consent in an ethically acceptable way. In our empirical-ethical analysis we develop suggestions on how the practice of eliciting consent in the biobank context should be improved.

Biomolecular Prospecting, Informative Gaps, and the Cancer Clinic: A Qualitative Fieldwork and an Epistemological, Historical and Ethical Analysis of Informed Consent for Clinical Trials for Monoclonal Antibodies and Biobank Research.

What happens to patients with cancer engaged in biomedical research when intellectual property regimes and ethical regimes intersect? This qualitative historical study addresses this question by situating the experiences, hopes, and reasons of patients to enter clinical trials within the historical trajectory of informed consent and monoclonal antibodies, the biotechnology underpinning many targeted drugs used in oncological clinical trials and biobank research. Based on fieldwork we undertook in a German university hospital where we interviewed patients and the medical personnel, a historical review, and an ethical analysis we inquire into the effects that financial, legal, and technological changes connected to the relevant pharmaceutical research and commerce have on cancer patients engaged in clinical trials and biobank research. We find that the controversial aspects of monoclonal antibodies, especially those related to the commercial interests at stake, enter the informed consent process mainly in the form of informative gaps. We highlight how a qualitative analysis of the clinic, especially when it is situated against the backdrop of the history of related technological advancements and patent regime, it can serve the purpose of giving voice to subjects who are silenced by regimes of an ethical, epistemic, and commercial kind while pointing to informed consent as an unhelpful device for addressing risks arising from the commercial purposes of biomedical products and infrastructure.

A historical and political epistemology of microbes.

This article traces the historical co-evolution of microbiology, bacteriology, and virology, framed within industrial and agricultural contexts, as well as their role in colonial and national history between the end of the 19th century and the first decades of the 20th century. The epistemology of germ theory, coupled with the economic interests of European colonies, has shaped the understanding of human-microbial relationships in a reductionist way. We explore a brief history of the medical and biological sciences, focusing on microbes and the difficulty of implementing germ theory outside of biology laboratories. Furthermore, we highlight the work of Lynn Margulis, who conceptualized microbes within their ecological contexts. Such research shows the active role microbes play in handling life-sustaining biological and biochemical processes. We outline how the industrial and technological advancements of the last two centuries not only impacted almost all human societies, but also changed the world on microbial, biological, and geological levels. The narration of these histories is a complex task, and depends on how national, international, and intergovernmental institutions (such as the World Health Organization) conceive of the selective environmental pressures exerted by industry and biotechnological companies.

Health, wealth and behavioural change: an exploration of role responsibilities in the wake of epigenetics.

The field of epigenetics is leading to new conceptualizations of the role of environmental factors in health and genetic disease. Although more evidence is required, epigenetic mechanisms are being implicated in the link between low socioeconomic status and poor health status. Epigenetic phenomena work in a number of ways: they can be established early in development, transmitted from previous generations and/or responsive to environmental factors. Knowledge about these types of epigenetic traits might therefore allow us to move away from a genetic deterministic perspective, and provide individuals with the opportunity to change their health status. Although this could be equated with patient empowerment, it could also lead to stigmatization and discrimination where individuals are deemed responsible for their health, even if they are not in social situations where they are able to enact change that would alter their health status. In this paper, we will explore the responsibilities of different actors in the healthcare sphere in relation to epigenetics across four different contexts: (1) genetic research, (2) clinical practice, (3) prenatal care and (4) the workplace. Within this exploration of role responsibilities, we will also discuss the potential constraints that might prevent the patient, mother-to-be, research participant or employee, from enacting any necessary steps in order to increase their health status in response to epigenetic information.

Samples and data accessibility in research biobanks: an explorative survey.

Biobanks, which contain human biological samples and/or data, provide a crucial contribution to the progress of biomedical research. However, the effective and efficient use of biobank resources depends on their accessibility. In fact, making bio-resources promptly accessible to everybody may increase the benefits for society. Furthermore, optimizing their use and ensuring their quality will promote scientific creativity and, in general, contribute to the progress of bio-medical research. Although this has become a rather common belief, several laboratories are still secretive and continue to withhold samples and data. In this study, we conducted a questionnaire-based survey in order to investigate sample and data accessibility in research biobanks operating all over the world. The survey involved a total of 46 biobanks. Most of them gave permission to access their samples (95.7%) and data (85.4%), but free and unconditioned accessibility seemed not to be common practice. The analysis of the guidelines regarding the accessibility to resources of the biobanks that responded to the survey highlights three issues: (i) the request for applicants to explain what they would like to do with the resources requested; (ii) the role of funding, public or private, in the establishment of fruitful collaborations between biobanks and research labs; (iii) the request of co-authorship in order to give access to their data. These results suggest that economic and academic aspects are involved in determining the extent of sample and data sharing stored in biobanks. As a second step of this study, we investigated the reasons behind the high diversity of requirements to access biobank resources. The analysis of informative answers suggested that the different modalities of resource accessibility seem to be largely influenced by both social context and legislation of the countries where the biobanks operate.

What Potential Donors in Research Biobanking Want to Know: A Large Population Study of the Italian Twin Registry.

Donation of human tissues for research and ELSI (ethical, legal, and social issues) of biobanking are increasingly debated issues. While several studies have highlighted patients' concerns, little is known about opinions and preferences of healthy potential donors. Further investigations in this respect may allow communication procedures tailored to participants' needs. Based on the Italian Twin Registry, a cross-sectional survey was conducted among twins who had not yet donated biological samples for research. The objective was to assess the importance these potential donors attributed to specific procedures and pieces of communication related to research biobanking. A self-administered questionnaire was constructed and validated. Items were as follows: potential agreement on use of biological samples for research; knowledge of biobanks; and importance given to privacy protection and to communication of general and individual tests results, study objectives, type and amount of participant involvement, location and duration of sample storage, and benefits and potential risks. Multivariate analysis was performed to estimate the association of these items with sociodemographic factors as well as with perceived health status and chronic or long-term diseases. The questionnaire was mailed to 4894 twins aged 18-65 (response rate 34%). One-third of subjects already knew about biobanks, 52% had some knowledge, and 20% were uninformed. A majority expressed unconditional agreement to sample use for research. Only 6% of respondents considered privacy protection not important in research biobanking. Knowledge of biobanks predicted attention to most of the issues. Higher education was associated with more frequent concern about type and amount of involvement, but less frequent concern about place and time of storage, and presence of benefits. Women were more attentive to research biobanking. This study supports the need of procedures tailored on different donors' concerns and highlights the social value of population biobanks. Furthermore, the results call for greater efforts in the promotion of research biobanking.

Feedback of Individual Genetic Results to Research Participants: Is It Feasible in Europe?

BACKGROUND: There is growing consensus that individual genetic research results that are scientifically robust, analytically valid, and clinically actionable should be offered to research participants. However, the general practice in European research projects is that results are usually not provided to research participants for many reasons. This article reports on the views of European experts and scholars who are members of the European COST Action CHIP ME IS1303 (Citizen's Health through public-private Initiatives: Public health, Market and Ethical perspectives) regarding challenges to the feedback of individual genetic results to research participants in Europe and potential strategies to address these challenges. MATERIALS AND METHODS: A consultation of the COST Action members was conducted through an email survey and a workshop. The results from the consultation were analyzed following a conventional content analysis approach. RESULTS: Legal frameworks, professional guidelines, and financial, organizational, and human resources to support the feedback of results are largely missing in Europe. Necessary steps to facilitate the feedback process include clarifying legal requirements to the feedback of results, developing harmonized European best practices, promoting interdisciplinary and cross-institutional collaboration, designing educational programs and cost-efficient IT-based platforms, involving research ethics committees, and documenting the health benefits and risks of the feedback process. CONCLUSIONS: Coordinated efforts at pan-European level are needed to enable equitable, scientifically sound, and socially robust feedback of results to research participants.

Biobank research, informed consent and society. Towards a new alliance?

With the rise of -omics disciplines and biobank research, personal data and biosamples crossing national borders pose new ethical questions. In this article, informed consent, as originally conceived, is shown as not being sufficient to address aims of research and interests of patients any more. Therefore the author has, after having scrutinised issues in biobanking, sketched a model of dynamic consent and a manner of scrutinising ethical issues through empirical data.