A Q methodology study on divergent perspectives on CRISPR-Cas9 in the Netherlands.

BACKGROUND: CRISPR-Cas9, a technology enabling modification of the human genome, is developing rapidly. There have been calls for public debate to discuss its ethics, societal implications, and governance. So far, however, little is known about public attitudes on CRISPR-Cas9. This study contributes to a better understanding of public perspectives by exploring the various holistic perspectives Dutch citizens have on CRISPR-Cas9. METHODS: This study used Q methodology to identify different perspectives of Dutch citizens (N = 30) on the use of CRISPR-Cas9. The Q-sort method aims at segmenting audiences based on the structural characteristics of their perspectives. Participants individually ranked 32 statements about CRISPR-Cas9 and discussed their rankings in small groups. By-person factor analysis was performed using PQMethod. Participants' contributions to the discussions were used to further make sense of the audience segments identified. RESULTS: Five perspectives on CRISPR-Cas9 were identified: (1) pragmatic optimism (2) concerned scepticism; (3) normative optimism; (4) enthusiastic support; and (5) benevolent generalism. Each perspective represents a unique position motivated by different ranking rationales. Sorting rationales included improving health, preventing negative impacts on society, and fear of a slippery slope. Overall, there is broad, but not universal support for medical uses of CRISPR-Cas9. CONCLUSIONS: Research on CRISPR-Cas9 should prioritise the broadly supported applications of the technology. Research and public debates on CRISPR-Cas9, its uses, its broader implications, and the governance of CRISPR-Cas9 are recommended. A discourse that includes all perspectives can contribute to the embedding of future uses of CRISPR-Cas9 in society. This study shows that Q methodology followed by group discussions enables citizens to contribute meaningfully to discourses about research.

The ethics of innovation for Alzheimer's disease: the risk of overstating evidence for metabolic enhancement protocols.

Medical practice is ideally based on robust, relevant research. However, the lack of disease-modifying treatments for Alzheimer's disease has motivated "innovative practice" to improve patients' well-being despite insufficient evidence for the regular use of such interventions in health systems treating millions of patients. Innovative or new non-validated practice poses at least three distinct ethical questions: first, about the responsible application of new non-validated practice to individual patients (clinical ethics); second, about the way in which data from new non-validated practice are communicated via the scientific and lay press (scientific communication ethics); and third, about the prospect of making new non-validated interventions widely available before more definitive testing (public health ethics). We argue that the authors of metabolic enhancement protocols for Alzheimer's disease have overstated the evidence in favor of these interventions within the scientific and lay press, failing to communicate weaknesses in their data and uncertainty about their conclusions. Such unmeasured language may create false hope, cause financial harm, undermine informed consent, and frustrate the production of generalizable knowledge necessary to face the societal problems posed by this devastating disease. We therefore offer more stringent guidelines for responsible innovation in the treatment of Alzheimer's disease.

Moral residue and health justice for the global south: Addressing past issues through current interventions and research.

This paper introduces the concept of moral residue to global health, and shows how its presence undermines crucial interventions and research, especially in the global south. Lingering feelings of anxiety, anger, blame or frustration often exist among local populations, where previous interventions or research have left traces of harm and/or exploitation. The existence of such feelings reflects the presence of moral residue, recognizing the moral experiences of epistemic injustices, which in turn undermines critical interventions and research through outright rejection or passive non-compliance among affected populations. While such situations have been variously interpreted and relevant strategies developed to address the issues, little to no consideration is made on the implications of moral residue experiences in global health contexts and how to address them. This paper demonstrates the presence of moral residue in global health and proffers an African ethical approach, a harmony framework, for addressing moral residue issues, as part of a holistic approach towards tackling population health crises without compromising health gains for affected populations in the global south.

Los comités de investigación en salud: su autoridad, responsabilidad fundamental y necesidad de que se sometan a auditorías periódicas.

Research ethics must include theoretical and practical dimensions. The first one is structured by regulations and policies, and the second dimension refers to how the committee interprets and applies those regulations and policies. This article analyses the operation of the committees at a practical level. Given that the evaluation and judgement of research protocols is a process that requires full awareness, its omission entails important implications for health research.

La ética de la investigación debe incluir las dimensiones teórica y práctica. La primera la conforman regulaciones y directrices y la segunda alude a la forma cómo los comités de ética y ética de la investigación interpretan y aplican esas regulaciones y directrices. En este artículo se analiza la operación de los comités a nivel práctico. Dado que la evaluación y el dictamen de los protocolos de investigación es un proceso que requiere consciencia plena, la omisión de esta conlleva importantes implicaciones para la investigación en salud.

Los comités de investigación en salud: su autoridad, responsabilidad fundamental y necesidad de que se sometan a auditorías periódicas / Health research committees: their authority, fundamental responsibility and the need for them to undergo periodic audits

Resumen La ética de la investigación debe incluir las dimensiones teórica y práctica. La primera la conforman regulaciones y directrices y la segunda alude a la forma cómo los comités de ética y ética de la investigación interpretan y aplican esas regulaciones y directrices. En este artículo se analiza la operación de los comités a nivel práctico. Dado que la evaluación y el dictamen de los protocolos de investigación es un proceso que requiere consciencia plena, la omisión de esta conlleva importantes implicaciones para la investigación en salud.

Abstract Research ethics must include theoretical and practical dimensions. The first one is structured by regulations and policies, and the second dimension refers to how the committee interprets and applies those regulations and policies. This article analyses the operation of the committees at a practical level. Given that the evaluation and judgement of research protocols is a process that requires full awareness, its omission entails important implications for health research.

An IQ Consortium Perspective on The Scientific Committee on Health, Environmental and Emerging Risks Final Opinion on the Need for Nonhuman Primates in Biomedical Research, Production and Testing of Products and Devices (Update 2017).

The recent Scientific Committee on Health, Environmental and Emerging Risks Final Opinion on "The need for nonhuman primates in biomedical research, production and testing of products and devices" (2017 SCHEER) highlights approaches that could significantly contribute to the replacement, reduction, and refinement of nonhuman primate (NHP) studies. Initiatives that have the potential to affect NHP welfare and/or their use are expected to be appropriate, fair, and objective and publicly disseminated information focused on NHPs in biomedical research, which includes toxicologic and pathologic research and testing, should be objectively evaluated by stakeholder scientists, researchers, and veterinarians. Thus, IQ Consortium member companies convened to develop an informed and objective response, focusing on identifying areas of agreement, potential gaps, or missing information in 2017 SCHEER. Overall, the authors agree that many positions in the 2017 SCHEER Opinion generally align with industry views on the use of NHPs in research and testing, including the ongoing need of NHPs in many areas of research. From the perspective of the IQ Consortium, there are several topics in the 2017 SCHEER that merit additional comment, attention, or research, as well as consideration in future opinions.

Ethical issues associated with HIV phylogenetics in HIV transmission dynamics research: A review of the literature using the Emanuel Framework.

The reduced costs of DNA sequencing and the use of such data for HIV-1 clinical management and phylogenetic analysis have led to a massive increase of HIV-1 sequences in the last few years. Phylogenetic analysis has shed light on the origin, spread and characteristics of HIV-1 epidemics and outbreaks. Phylogenetic analysis is now also being used to advance our knowledge of the drivers of HIV-1 transmission in order to design effective interventions. However, HIV phylogenetic analysis presents unique ethical challenges, which have not been fully explored. This review presents an analysis of what appear to be key ethical issues in HIV phylogenetics in the hope of stimulating further conceptual and empirical work in this rapidly emerging area. We structure the review using the Emanuel Framework, a systematic, holistic framework, which has been adapted for use in developing countries, which bear the brunt of the HIV-1 pandemic.

[The Japanese legal system and the applicability of laws and regulations on private information protection and research ethics relating to medical research].

Objectives　To clarify the structure, applicability, and objectives of the current Japanese legislation for private information protection and research ethics and to examine the clauses of the related laws/regulations for academic research purposes.Methods　The research design is a descriptive study based on a systematic literature review. Using the "e-Gov" database, the laws/regulations relating to private information protection and research ethics that apply to medical research involving human subjects and human genome/gene analysis research were included in the research. The Drugs Law (Law No. 145 of 1960) and related GCP/GPSP regulations and laws/regulations on administrative organizations, management, and procedures were excluded. Furthermore, the guidelines and Q&A relating to these laws/regulations and all 47 prefectural regulations on private information protection have been selected from the websites of the related ministries, government organizations, and prefectures.Results　Our study demonstrated that the current legal system on private information protection consists of three layers and that the applicability of the laws/regulations in this area varies according to the type of research organization. Additionally, the applicability of the laws/regulations on research ethics is different depending on the research area. While the Private Information Protection Law (PIPL) for the private sector contains two objectives, PIPL for administrative organizations and PIPL for independent administrative organizations both include three objectives. For academic research purposes, PIPL for the private sector sets out a holistic exemption clause, whereas the other two PIPLs stipulate three specific exemption clauses. Furthermore, our research revealed that the clauses of the prefectural regulations demonstrated many variances.Conclusion　This study suggests that the current Japanese legal system relating to private information protection could be defined as a "mixed model," wherein the laws/regulations concerned are not necessarily consistent. The protection of medical information is solely regulated by a few specific laws with a narrow scope of application; the ethical guidelines are not directly based on any laws; and identifying applicable laws/regulations, depending on the category of research organization, is complicated, especially in the case of collaborative research involving researchers from various organizations. Therefore, in the larger framework of legislation, it is indispensable to reconsider the protection of private medical information and its effective use, including the ethics of this process because of the sensitive and useful nature of private medical information.

Scientific iconoclasm and active imagination: synthetic cells as techno-scientific mandalas.

Metaphors allow us to come to terms with abstract and complex information, by comparing it to something which is structured, familiar and concrete. Although modern science is "iconoclastic", as Gaston Bachelard phrases it (i.e. bent on replacing living entities by symbolic data: e.g. biochemical and mathematical symbols and codes), scientists are at the same time prolific producers of metaphoric images themselves. Synthetic biology is an outstanding example of a technoscientific discourse replete with metaphors, including textual metaphors such as the "Morse code" of life, the "barcode" of life and the "book" of life. This paper focuses on a different type of metaphor, however, namely on the archetypal metaphor of the mandala as a symbol of restored unity and wholeness. Notably, mandala images emerge in textual materials (papers, posters, PowerPoints, etc.) related to one of the new "frontiers" of contemporary technoscience, namely the building of a synthetic cell: a laboratory artefact that functions like a cell and is even able to replicate itself. The mandala symbol suggests that, after living systems have been successfully reduced to the elementary building blocks and barcodes of life, the time has now come to put these fragments together again. We can only claim to understand life, synthetic cell experts argue, if we are able to technically reproduce a fully functioning cell. This holistic turn towards the cell as a meaningful whole (a total work of techno-art) also requires convergence at the "subject pole": the building of a synthetic cell as a practice of the self, representing a turn towards integration, of multiple perspectives and various forms of expertise.

Undisclosed conflicts of interest among biomedical textbook authors.

BACKGROUND: Textbooks are a formative resource for health care providers during their education and are also an enduring reference for pathophysiology and treatment. Unlike the primary literature and clinical guidelines, biomedical textbook authors do not typically disclose potential financial conflicts of interest (pCoIs). The objective of this study was to evaluate whether the authors of textbooks used in the training of physicians, pharmacists, and dentists had appreciable undisclosed pCoIs in the form of patents or compensation received from pharmaceutical or biotechnology companies. METHODS: The most recent editions of six medical textbooks, Harrison's Principles of Internal Medicine (HarPIM), Katzung and Trevor's Basic and Clinical Pharmacology (KatBCP), the American Osteopathic Association's Foundations of Osteopathic Medicine (AOAFOM), Remington: The Science and Practice of Pharmacy (RemSPP), Koda-Kimble and Young's Applied Therapeutics (KKYAT), and Yagiela's Pharmacology and Therapeutics for Dentistry (YagPTD), were selected after consulting biomedical educators for evaluation. Author names (N = 1,152, 29.2% female) were submitted to databases to examine patents (Google Scholar) and compensation (ProPublica's Dollars for Docs [PDD]). RESULTS: Authors were listed as inventors on 677 patents (maximum/author = 23), with three-quarters (74.9%) to HarPIM authors. Females were significantly underrepresented among patent holders. The PDD 2009-2013 database revealed receipt of US$13.2 million, the majority to (83.9%) to HarPIM. The maximum compensation per author was $869,413. The PDD 2014 database identified receipt of $6.8 million, with 50.4% of eligible authors receiving compensation. The maximum compensation received by a single author was $560,021. Cardiovascular authors were most likely to have a PDD entry and neurologic disorders authors were least likely. CONCLUSION: An appreciable subset of biomedical authors have patents and have received remuneration from medical product companies and this information is not disclosed to readers. These findings indicate that full transparency of financial pCoI should become a standard practice among the authors of biomedical educational materials.

Recommended standards for conducting and reporting ethnopharmacological field studies.

ETHNOPHARMACOLOGICAL RELEVANCE: What are the minimum methodological and conceptual requirements for an ethnopharmacological field study? How can the results of ethnopharmacological field studies be reported so that researchers with different backgrounds can draw on the results and develop new research questions and projects? And how should these field data be presented to get accepted in a scientific journal such as the Journal of Ethnopharmacology? The objective of this commentary is to create a reference that covers the basic standards necessary during planning, conducting and reporting of field research. MATERIALS AND METHODS: We focus on conducting and reporting ethnopharmacological field studies on medicinal plants or materia medica and associated knowledge of a specific people or region. The article highlights the most frequent problems and pitfalls, and draws on published literature, fieldwork experience, and extensive insights from peer-review of field studies. RESULTS: Research needs to be ethical and legal, and follow local and national regulations. Primary ethnopharmacological field data need to be collected and presented in a transparent and comprehensible way. In short this includes: 1) Relevant and concise research questions, 2) Thorough literature study encompassing all available information on the study site from different disciplines, 3) Appropriate methods to answer the research questions, 4) Proper plant use documentation, unambiguously linked to voucher specimens, and 5) Qualitative and quantitative analyses of the collected data, the latter relying on use-reports as basic units. CONCLUSION: Although not exhaustive, we provide an overview of the necessary main issues to consider for field research and data reporting including a list of minimal standards and recommendations for best practices. For methodological details and how to correctly apply specific methods, we refer to further reading of suggested textbooks and methods manuals.

Ethical stumbling blocks in uncovering folate deficiency as a preventable cause of spina bifida.

The year 2016 witnessed the anniversaries of several key events related to the prevention of neural tube defects (NTD) with folate supplementation. However, the road leading up to this achievement was full of stumbling blocks, both in terms of research ethics and researcher ethics. First, the decisions of ethics review boards differed with respect to allowing placebo groups in folate trials, thus reducing the level of evidence obtained from the earliest studies. Second, statisticians insisted on analysing the outcome of a trial by intention-to-treat - which turned out to be non-significant - rather than by treatment received, which was statistically significant. Third, the recognition of positive results was stymied by the reluctance of some researchers to recognise and quote others' contributions. All this needlessly delayed the recognition of the NTD-preventive effects of folate by a decade. The story of the prevention of NTD thus offers insights into research inadequacies that have the potential to impede the advance of medical science, with the ethical aspects having the most immediate impact. Efficient ethics review boards play a major role worldwide and if they play safe, they may risk disallowing high-quality studies of great public health import.

The Ethics of Clinical Care and the Ethics of Clinical Research: Yin and Yang.

The Belmont Report's distinction between research and the practice of accepted therapy has led various authors to suggest that these purportedly distinct activities should be governed by different ethical principles. We consider some of the ethical consequences of attempts to separate the two and conclude that separation fails along ontological, ethical, and epistemological dimensions. Clinical practice and clinical research, as with yin and yang, can be thought of as complementary forces interacting to form a dynamic system in which the whole exceeds the sum of its parts. Just as effective clinical practice cannot exist without clinical research, meaningful clinical research requires the context of clinical practice. We defend this thesis by triangulation, that is, by outlining how multiple investigators have reached this conclusion on the basis of varied theoretical and applied approaches. More confidence can be placed in a result if different methods/viewpoints have led to that result.

Ethical considerations in clinical research on herbal medicine for prevention of cardiovascular disease in the ageing.

BACKGROUND: Cardiovascular disease (CVD) in the ageing is a major public health problem worldwide. The nature of most CVD is subclinical with pathological processes that can span over years. Use of preventive measures could be an appropriate approach to prevailing over CVD in the ageing, and herbal medicine is one of the promising preventive approaches and is currently of interest among medical societies. In the evidence-based era, herbal medicine is, however, often underestimated and approached with skepticism, mainly due to the paucity of scientific evidence. Properly designed clinical trials on herbal medicine for prevention of CVD in a geriatric population are thus of importance and of clinical value. PURPOSE: To review ethical issues and discuss considerations when such research is proposed. CHAPTERS/SECTIONS: Four ethical issues, including the scientific validity of research, risk-benefit assessments, subject selection and vulnerability, and informed consent, are structured and extensively discussed in this article. CONCLUSIONS: Ethical core considerations of prevention research of CVD on herbal medicine involve particular attention on the scientific validity of research, risk-benefit assessments, subject selection and vulnerability, and informed consent. These issues and considerations are keys, although they must be adapted to an individual research setting in which a clinical study is proposed.

A Trust-Based Pact in Research Biobanks. From Theory to Practice.

Traditional Informed Consent is becoming increasingly inadequate, especially in the context of research biobanks. How much information is needed by patients for their consent to be truly informed? How does the quality of the information they receive match up to the quality of the information they ought to receive? How can information be conveyed fairly about future, non-predictable lines of research? To circumvent these difficulties, some scholars have proposed that current consent guidelines should be reassessed, with trust being used as a guiding principle instead of information. Here, we analyse one of these proposals, based on a Participation Pact, which is already being offered to patients at the Istituto Europeo di Oncologia, a comprehensive cancer hospital in Milan, Italy.