Ethics and Epistemology in Big Data Research

Biomedical innovation and translation are increasingly emphasizing research using “big data.” The hope is that big data methods will both speed up research and make its results more applicable to “real-world” patients and health services. While big data research has been embraced by scientists, politicians, industry, and the public, numerous ethical, organizational, and technical/methodological concerns have also been raised. With respect to technical and methodological concerns, there is a view that these will be resolved through sophisticated information technologies, predictive algorithms, and data analysis techniques. While such advances will likely go some way towards resolving technical and methodological issues, we believe that the epistemological issues raised by big data research have important ethical implications and raise questions about the very possibility of big data research achieving its goals.     

Challenges in Translational Research: The Views of Addiction Scientists

Objectives

To explore scientists'' perspectives on the challenges and pressures of translating research findings into clinical practice and public health policy.

Methods

We conducted semi-structured interviews with a purposive sample of 20 leading scientists engaged in genetic research on addiction. We asked participants for their views on how their own research translates, how genetic research addresses addiction as a public health problem and how it may affect the public''s view of addiction.

Results

Most scientists described a direct translational route for their research, positing that their research will have significant societal benefits, leading to advances in treatment and novel prevention strategies. However, scientists also pointed to the inherent pressures they feel to quickly translate their research findings into actual clinical or public health use. They stressed the importance of allowing the scientific process to play out, voicing ambivalence about the recent push to speed translation.

Conclusions

High expectations have been raised that biomedical science will lead to new prevention and treatment modalities, exerting pressure on scientists. Our data suggest that scientists feel caught in the push for immediate applications. This overemphasis on rapid translation can lead to technologies and applications being rushed into use without critical evaluation of ethical, policy, and social implications, and without balancing their value compared to public health policies and interventions currently in place.     

The role of modern biology and medicine in drug development in academia and industry

This symposium addresses careers in drug development in industry; the performance of translational research by academia, industry, and both; and numerous factors pertinent to alliances essential to drug discovery and development. Drug development is a complex process that regularly involves effective collaborations between academic and physician scientists and industry. There are specific occupational factors affecting recruitment of scientists and physicians in drug development programs in industry; ideal backgrounds for successful applicants for positions in industry in drug development; ethical and regulatory considerations particularly germane to the performance of scientists and physicians in drug development programs in industry and at universities; and particular gratifications available to scientists in industry working on drug development. Both similarities and differences characterize the performance of translational research in industry compared with academia. In industry, logistic, operational, and scientific oversight is complex, especially because it often involves relationships with clinical enterprises outside of the corporation. The process is long and arduous from formulation of a good idea in discovery to acceptance of a novel drug in the marketplace. Collaborations and partnerships by industry often involving academia and confrontation of multiple issues are pivotal.     

The treatable intellectual disability APP www.treatable-id.org: A digital tool to enhance diagnosis & care for rare diseases

ABSTRACT: BACKGROUND: Intellectual disability (ID) is a devastating and frequent condition, affecting 2-3% of the population worldwide. Early recognition of treatable underlying conditions drastically improves health outcomes and decreases burdens to patients, families and society. Our systematic literature review identified 81 such inborn errors of metabolism, which present with ID as a prominent feature and are amenable to causal therapy. The WebApp translates this knowledge of rare diseases into a diagnostic tool and information portal. Methods & Results: Freely available as a WebApp via www.treatable-id.org and mid 2012 via the App store, this diagnostic tool is designed for all specialists evaluating children with global delay / ID and laboratory scientists. Information on the 81 diseases is presented in different ways with search functions: 18 biochemical categories, neurologic and non-neurologic signs & symptoms, diagnostic investigations (metabolic screening tests in blood and urine identify 60% of all IEMs), therapies & effects on primary (IQ/developmental quotient) and secondary outcomes, and available evidence For each rare condition a 'disease page' serves as an information portal with online access to specific genetics, biochemistry, phenotype, diagnostic tests and therapeutic options. As new knowledge and evidence is gained from expert input and pubmed searches this tool will be continually updated. The WebApp is an integral part of a protocol prioritizing treatability in the work-up of every child with global delay / ID. A 3-year funded study will enable an evaluation of its effectiveness. CONCLUSIONS: For rare diseases, a field for which financial and scientific resources are particularly scarce, knowledge translation challenges are abundant. With this WebApp technology is capitalized to raise awareness for rare treatable diseases and their common presenting clinical feature of ID, with the potential to improve health outcomes. This innovative digital tool is designed to motivate health care providers to search actively for treatable causes of ID, and support an evidence-based approach to rare metabolic diseases. In our current -omics world with continuous information flow, the effective synthesis of data into accessible, clinical knowledge has become ever more essential to bridge the gap between research and care.     

Prioritising African perspectives in psychiatric genomics research: Issues of translation and informed consent

Psychiatric genomics research with African populations comes with a range of practical challenges around translation of psychiatric genomics research concepts, procedures, and nosology. These challenges raise deep ethical issues particularly around legitimacy of informed consent, a core foundation of research ethics. Through a consideration of the constitutive function of language, the paper problematises like‐for‐like, designative translations which often involve the ‘indigenization’ of English terms or use of metaphors which misrepresent the risks and benefits of research. This paper argues that effective translation of psychiatric genomics research terminology in African contexts demands substantive engagement with African conceptual schemas and values. In developing attenuated forms of translational thinking, researchers may recognise the deeper motivational reasons behind participation in research, highlighting the possibility that such reasons may depart from the original meaning implied within informed consent forms. These translational issues might be ameliorated with a critical re‐examination of how researchers develop and present protocols to institutional ethics review boards.     

Artificial womb technology and clinical translation: Innovative treatment or medical research?

In 2017 and 2019, two research teams claimed ‘proof of principle’ for artificial womb technology (AWT). AWT has long been a subject of speculation in bioethical literature, with broad consensus that it is a welcome development. Despite this, little attention is afforded to more immediate ethical problems in the development of AWT, particularly as an alternative to neonatal intensive care. To start this conversation, I consider whether experimental AWT is innovative treatment or medical research. The research–treatment distinction, pervasive in regulation worldwide, is intended to isolate research activities and subject them to a greater degree of oversight. I argue that there is a tendency in the literature to conceptualize AWT for partial ectogenesis as innovative treatment. However, there are sufficiently serious ethical concerns with experimental AWT that mean that it must not be first used on humans on the basis that it is a ‘beneficial treatment’. First, I outline the prospects for translation of AWT animal studies into treatment for human preterms. Second, I challenge the conceptualizations of experimental AWT as innovative treatment. It must be considered medical research to reflect the investigatory nature of the process and guarantee sufficient protections for subjects. Identifying that AWT is research is crucial in formulating further ethico-legal questions regarding the experimental use of AWT. Third, I demonstrate that clinical trials will be a necessary part of the clinical translation of AWT because of requirements laid out by regulators. I consider the justification for clinical trials and highlight some of the crucial ethical questions about the conditions under which they should proceed.     

转化医学研究中生命伦理学辩护的现况分析与前瞻思考

转化医学作为一门新兴学科,运用多学科交叉策略来推动医学发展,从临床实践中发现问题,将其凝练成科学问题进行基础医学研究,再将研究成果应用到疾病诊断、治疗和预防过程中,使其真正发挥作用,是一个从基础医学到临床应用的双向进程。转化医学已逐步融入各个学科,并在干细胞研究、生物标志物、细胞信号转导、药物及器具研发及个体化医学等各个领域发挥重要作用。随着转化医学研究深入,一些临床试验势必对人体存在一定伤害和潜在危险,存在各种伦理问题。虽说科学研究与伦理道德是一对相互冲击的矛盾,但两者在总体上又是一致的,共同决定着社会前进步伐。科研的重大进步必然会对伦理道德提出更高要求,而伦理道德的高标准又规范、引导、促进科学研究朝着正确方向迈进,两者相辅相成。鉴于伦理辩护对于转化医学研究强有力的支撑,建议在转化医学研究中能进一步完善伦理监管体系,发挥机构伦理委员会的功效,持续加大伦理培训的力度,强化研究人员的伦理道德修养,从而为转化医学的发展夯实人文基础。     

The Medawar Lecture 1998 is science dangerous?

The idea that science is dangerous is deeply embedded in our culture, particularly in literature, yet science provides the best way of understanding the world. Science is not the same as technology. In contrast to technology, reliable scientific knowledge is value-free and has no moral or ethical value. Scientists are not responsible for the technological applications of science; the very nature of science is that it is not possible to predict what will be discovered or how these discoveries could be applied. The obligation of scientists is to make public both any social implications of their work and its technological applications. A rare case of immoral science was eugenics. The image of Frankenstein has been turned by the media into genetic pornography, but neither cloning nor stem cells or gene therapy raise new ethical issues. There are no areas of research that are so socially sensitive that research into them should be proscribed. We have to rely on the many institutions of a democratic society: parliament, a free and vigorous press, affected groups and the scientists themselves. That is why programmes for the public understanding of science are so important. Alas, we still do not know how best to do this.     

SysFinder:A customized platform for search,comparison and assisted design of appropriate animal models based on systematic similarity

Animal models are increasingly gaining values by cross-comparisons of response or resistance to clinical agents used for patients.However,many disease mechanisms and drug effects generated from animal models are not transferable to human.To address these issues,we developed SysFinder(http://lifecenter.sgst.cn/SysFinder),a platform for scientists to find appropriate animal models for translational research.SysFinder offers a "topic-centered" approach for systematic comparisons of human genes,whose functions are involved in a specific scientific topic,to the corresponding homologous genes of animal models.Scientific topic can be a certain disease,drug,gene function or biological pathway.SysFinder calculates multi-level similarity indexes to evaluate the similarities between human and animal models in specified scientific topics.Meanwhile,SysFinder offers species-specific information to investigate the differences in molecular mechanisms between humans and animal models.Furthermore,SysFinder provides a userfriendly platform for determination of short guide RNAs(sgRNAs) and homology arms to design a new animal model.Case studies illustrate the ability of SysFinder in helping experimental scientists.SysFinder is a useful platform for experimental scientists to carry out their research in the human molecular mechanisms.     

The randomized controlled trial in studies using biomarkers

The randomized controlled trial (RCT) is a scientific experiment during which observations on the effects of therapy or a preventive action are conducted by the researcher under rigorous control. The purpose of the experiment is to clear the uncertainties surrounding a clinical/research issue and involves isolating the 'treatment' and 'end result' variables from external influences. RCTs therefore make use of scientific method standards: measuring, which includes the possibility of reproducing observations; controlling factors unconnected to the cause-effect relationship of interest; and the external verification or 'falsification' of the cause-effect relationship. Many RCTs are now including biomarkers to answer scientific questions in a more accurate way. In the present methodological paper, the main aspects involved in the design and conduction of a trial are discussed, with special emphasis on the use of biomarkers. Aspects that are often overlooked by scientists involved in the design of trials include multiple comparisons, subgroup analysis, the duration of the observations, the use of surrogate endpoints, and ethical issues. This review summarizes the main issues that should be addressed in a protocol, and illustrates these with an example.     

Realizing the promise of population biobanks: a new model for translation

The promise of science lies in expectations of its benefits to societies and is matched by expectations of the realisation of the significant public investment in that science. In this paper, we undertake a methodological analysis of the science of biobanking and a sociological analysis of translational research in relation to biobanking. Part of global and local endeavours to translate raw biomedical evidence into practice, biobanks aim to provide a platform for generating new scientific knowledge to inform development of new policies, systems and interventions to enhance the public’s health. Effectively translating scientific knowledge into routine practice, however, involves more than good science. Although biobanks undoubtedly provide a fundamental resource for both clinical and public health practice, their potentiating ontology—that their outputs are perpetually a promise of scientific knowledge generation—renders translation rather less straightforward than drug discovery and treatment implementation. Biobanking science, therefore, provides a perfect counterpoint against which to test the bounds of translational research. We argue that translational research is a contextual and cumulative process: one that is necessarily dynamic and interactive and involves multiple actors. We propose a new multidimensional model of translational research which enables us to imagine a new paradigm: one that takes us from bench to bedside to backyard and beyond, that is, attentive to the social and political context of translational science, and is cognisant of all the players in that process be they researchers, health professionals, policy makers, industry representatives, members of the public or research participants, amongst others.     

Human genome project: pharmacogenomics and drug development

Now that all 30,000 or so genes that make up the human genome have been deciphered, pharmaceutical industries are emerging to capitalize the custom based drug treatment. Understanding human genetic variation promises to have a great impact on our ability to uncover the cause of individual variation in response to therapeutics. The study of association between genetics and drug response is called pharmacogenomics. The potential implication of genomics and pharmacogenomics in clinical research and clinical medicine is that disease could be treated according to the interindividual differences in drug disposition and effects, thereby enhancing the drug discovery and providing a stronger scientific basis of each patient's genetic constitution. Sequence information derived from the genomes of many individuals is leading to the rapid discovery of single nucleotide polymorphisms or SNPs. Detection of these human polymorphisms will fuel the discipline of pharmacogenomics by developing more personalized drug therapies. A greater understanding of the way in which individuals with a particular genotype respond to a drug allows manufacturers to identify population subgroups that will benefit most from a particular drug. The increasing emphasis on pharmacogenomics is likely to raise ethical and legal questions regarding, among other things, the design of research studies, the construction of clinical trials and the pricing of drugs.     

Ethical issues in translational research

The translation of biomedical research knowledge to effective clinical treatment is essential to the public good and is a main focus of current health policy. However, recent health policy initiatives intended to foster the translation of basic science into clinical and public health advances must also consider the unique bioethical issues raised by the increased focus on translational research. Safety of study participants and balancing of risk due to treatment with the potential benefits of the research is tantamount. This article synthesizes theory from clinical ethics, operational design, and philosophy to provide a bioethical framework for the health policy of translational research.     

The randomized controlled trial in studies using biomarkers

The randomized controlled trial (RCT) is a scientific experiment during which observations on the effects of therapy or a preventive action are conducted by the researcher under rigorous control. The purpose of the experiment is to clear the uncertainties surrounding a clinical/research issue and involves isolating the 'treatment' and 'end result' variables from external influences. RCTs therefore make use of scientific method standards: measuring, which includes the possibility of reproducing observations; controlling factors unconnected to the cause-effect relationship of interest; and the external verification or 'falsification' of the cause-effect relationship. Many RCTs are now including biomarkers to answer scientific questions in a more accurate way. In the present methodological paper, the main aspects involved in the design and conduction of a trial are discussed, with special emphasis on the use of biomarkers. Aspects that are often overlooked by scientists involved in the design of trials include multiple comparisons, subgroup analysis, the duration of the observations, the use of surrogate endpoints, and ethical issues. This review summarizes the main issues that should be addressed in a protocol, and illustrates these with an example.     

Ethical muscle and scientific interests: a role for philosophy in scientific research

Ethics, a branch of philosophy, has a place in the regulatory framework of human subjects research. Sometimes, however, ethical concepts and arguments play a more central role in scientific activity. This can happen, for example, when violations of research norms are also ethical violations. In such a situation, ethical arguments can be marshaled to improve the quality of the scientific research. I explore two different examples in which philosophers and scientists have used ethical arguments to plead for epistemological improvements in the conduct of research. The first example deals with research dishonesty in pharmaceutical development. The second example is concerned with neuropsychological research using fMRI technology.     

Are Phase 1 Trials Therapeutic? Risk,Ethics, and Division of Labor

Despite their crucial role in the translation of pre‐clinical research into new clinical applications, phase 1 trials involving patients continue to prompt ethical debate. At the heart of the controversy is the question of whether risks of administering experimental drugs are therapeutically justified. We suggest that prior attempts to address this question have been muddled, in part because it cannot be answered adequately without first attending to the way labor is divided in managing risk in clinical trials. In what follows, we approach the question of therapeutic justification for phase 1 trials from the viewpoint of five different stakeholders: the drug regulatory authority, the IRB, the clinical investigator, the referring physician, and the patient. Our analysis shows that the question of therapeutic justification actually raises multiple questions corresponding to the roles and responsibilities of the different stakeholders involved. By attending to these contextual differences, we provide more coherent guidance for the ethical negotiation of risk in phase 1 trials involving patients. We close by discussing the implications of our argument for various perennial controversies in phase 1 trial practice.     

Ethical implications of genetic analysis of individual susceptibility to diseases

Ethics can be regarded as a reflection or reconsideration of existing moral codes in the search of good and goes beyond moral conduct. This means that ethics is a never-ending process, which in science must develop with the development of science itself. Thus, the process of seeking better ethics is as integral within science as the development of new methods. Along these lines of thought it can be argued that (1) poor science cannot be ethically sound, (2) every scientist has a personal responsibility to develop ethics in his area of expertise, (3) the development of solid ethical background in science requires education in ethics as well as in methodology and scientific thinking and (4) research ethics cannot develop in solitude, but needs input from other scientists, other fields (including philosophy) and society. Several burning questions can be identified within genetic analysis for individual susceptibility. These ethical aspects can be viewed from three different perspectives: practice of research, patient/research subject personally and long-term implications in society. This paper tries more to awaken thoughts than give clear answers.     

Interpreting evidence: why values can matter as much as science

Despite increasing awareness of the ways in which non-epistemic values play roles in science, many scientists remain reluctant to acknowledge values at stake in their own work. Even when research clearly relates to risk assessment and establishing public policy, contexts in which the presence of values is less likely to be contentious, scientists tend to present such research as merely involving empirical questions about what the evidence is. As a result, debates over policy-related science tend to be framed as purely epistemic debates over the state of the evidence. We argue that this neglects the important ways that ethical and social values play legitimate roles in judgments about what we take to be evidence for a particular policy. Using the case of recent disputes about the relative safety of home birth, we argue that although the debate has been framed as a purely scientific one about the empirical evidence for home birth, it actually involves disagreements about underlying value assumptions. If our claims are correct, then in order to move the debate forward, scientists will need to engage in a critical discussion about the values at stake.     

Unconventional allies: interdisciplinary approaches to science policy and funding

Scientific research is an often misunderstood, undervalued and yet essential activity. Many nonscientists think that research is quick and easy, and that science is a compilation of established facts rather than rigorous conclusions based on available evidence. In addition, many nonscientists, and perhaps many scientists as well, forget that our social and financial investment is small relative to the massive and expensive problems that we all want scientific research to solve. Using biomedical research in the United States as an example, I will argue that countering this underinvestment in science will require broadening perspectives in the scientific community as well as coupling expanded individual advocacy and education efforts to an interdisciplinary advocacy approach. This approach is in many ways analogous to the unique solutions that emerge when scientists working in different disciplines leave their intellectual silos and work together.     

Cybrid human embryos--warranting opportunities to augment embryonic stem cell research

The recent vote in the British Parliament allows scientists in principle to create hybrid embryos by transferring human somatic cell nuclei into animal oocytes. This vote opens a fascinating new area of research with the central aim of generating interspecific lines of embryonic stem cells (ESCs) that could potentially be used to understand development, differentiation, gene expression and genomic compatibility. It will also promote human cell therapies, as well as the pharmaceutical industry's search for new drug targets. If this approach is to be successful, many biological questions need to be answered and, in addition, some moral and ethical aspects must be taken into account.