Current debates surrounding the virtues and shortcomings of randomization are symptomatic of a lack of appreciation of the fact that causation can be inferred by two distinct inference methods, each requiring its own, specific experimental design. There is a non-statistical type of inference associated with controlled experiments in basic biomedical research; and a statistical variety associated with randomized controlled trials in clinical research. I argue that the main difference between the two hinges on the satisfaction of the (...) comparability requirement, which is in turn dictated by the nature of the objects of study, namely homogeneous or heterogeneous populations of biological systems. Among other things, this entails that the objection according to which randomized experiments fail to provide better evidence for causation because randomization cannot guarantee comparability is mistaken. (shrink)

Motivated by a recent trend that advocates a reassessment of the aim of medical science and clinical practice, this paper investigates the epistemic aims of biomedical research. Drawing on contemporary discussions in epistemology and the philosophy of science, along with a recent study on scurvy, this paper (1) explores the concept of understanding as the aim of scientific inquiry and (2) establishes a framework that will guide the examination of its forms in biomedical research. Using the (...) case of Tuberculosis (TB), (3) it is argued that grasping a mechanistic explanation is crucial for reaching a threshold of understanding at which we may speak of an objectual, biomedical understanding of TB. (shrink)

In this article, we analyse how researchers use the categories of race and ethnicity with reference to genetics and genomics. We show that there is still considerable conceptual “messiness” (despite the wide-ranging and popular debate on the subject) when it comes to the use of ethnoracial categories in genetics and genomics that among other things makes it difficult to properly compare and interpret research using ethnoracial categories, as well as draw conclusions from them. Finally, we briefly reconstruct some of (...) the biases of reductionism to which geneticists (as well as other researchers referring to genetic methods and explanations) are particularly exposed to, and we analyse the problem in the context of the biologization of ethnoracial categories. Our work constitutes a novel, in-depth contribution to the debate about reporting race and ethnicity in biomedical and health research. First, we reconstruct the theoretical background assumptions about racial ontology which researchers implicitly presume in their studies with the aid of a sample of recent papers published in medical journals about COVID-19. Secondly, we use the typology of the biases of reductionism to the problem of biologization of ethnoracial categories with reference to genetics and genomics. (shrink)

The European project European and Latin American Systems of Ethics Regulation of Biomedical Research Project (EULABOR) has carried out the first comparative analysis of ethics regulation systems for biomedical research in seven countries in Europe and Latin America, evaluating their roles in the protection of human subjects. We developed a conceptual and methodological framework defining ‘ethics regulation system for biomedical research’ as a set of actors, institutions, codes and laws involved in overseeing the ethics (...) of biomedical research on humans. This framework allowed us to develop comprehensive national reports by conducting semi-structured interviews to key informants. These reports were summarised and analysed in a comparative analysis. The study showed that the regulatory framework for clinical research in these countries differ in scope. It showed that despite the different political contexts, actors involved and motivations for creating the regulation, in most of the studied countries it was the government who took the lead in setting up the system. The study also showed that Europe and Latin America are similar regarding national bodies and research ethics committees, but the Brazilian system has strong and noteworthy specificities. (shrink)

The current prevailing view is that participation in biomedical research is above and beyond the call of duty. While some commentators have offered reasons against this, we propose a novel public goods argument for an obligation to participate in biomedical research. Biomedical knowledge is a public good, available to any individual even if that individual does not contribute to it. Participation in research is a critical way to support an important public good. Consequently, all (...) have a duty to participate. The current social norm is that individuals participate only if they have a good reason to do so. The public goods argument implies that individuals should participate unless they have a good reason not to. Such a shift would be of great aid to the progress of biomedical research, eventually making society significantly healthier and longer lived. (shrink)

Business models for biomedical research prescribe decentralization due to market selection pressures. I argue that decentralized biomedical research does not match four normative philosophical models of the role of values in science. Non-epistemic values affect the internal stages of for-profit biomedical science. Publication planning, effected by Contract Research Organizations, inhibits mechanisms for transformative criticism. The structure of contracted research precludes attribution of responsibility for foreseeable harm resulting from methodological choices. The effectiveness of business (...) strategies leads to overrepresentation of profit values versus the values of the general public. These disconnects in respect to the proper role of values in science results from structural issues ultimately linked to the distinct goals of business versus applied science, and so it seems likely that disconnects will also be found in other dimensions of attempts to combine business and science. The volume and integration in the publishing community of decentralized biomedical research imply that the entire community of biomedical research science cannot match the normative criteria of community-focused models of values in science. Several proposals for changing research funding structure might successfully relieve market pressures that drive decentralization. (shrink)

In this paper, we discuss the processes of racialisation on the example of biomedical research. We argue that applying the concept of racialisation in biomedical research can be much more precise, informative and suitable than currently used categories, such as race and ethnicity. For this purpose, we construct a model of the different processes affecting and co-shaping the racialisation of an individual, and consider these in relation to biomedical research, particularly to studies on hypertension. (...) We finish with a discussion on the potential application of our proposition to institutional guidelines on the use of racial categories in biomedical research. (shrink)

A proposed plan to rescue US biomedical research from its current ‘malaise’ will not be effective as it misdiagnoses the root cause of the disease.

The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The (...) proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined. (shrink)

Health data processing fields face ethical and legal problems regarding fundamental rights. As we know, patients can benefit in the Digital Era from having health or medical information available, and medical decisions can be more effective with a better understanding of clinical histories, medical and health data thanks to the development of Artificial Intelligence, Internet of Things and other Digital technologies. However, at the same time, we need to guarantee fundamental rights, including privacy ones. The complaint about ethical and legal (...) requirements – including constitutional ones – is particularly relevant in the processing of health data. This paper is focused on the problem of the consent required to the processing of health data and the exceptions established in the new European Union General Data Regulation, which cover the processing of this special data -within other aims- for scientific, historical and statistical research as legitimate purposes, which include biomedical research. The conclusion is that these open concepts are problematic both for the protection of privacy rights and for the legal security/certainty of research. On one hand there are several interpretation problems, regarding the processing of health data and the protection of information privacy. On the other hand, professionals must follow the Multilevel legal framework and to guarantee fundamental rights in the processing of health data, so there are also problems of interpretation for researchers. Therefore, we need a clearer legal framework for biomedical research. (shrink)

Perez-Rodriguez and de la Fuente (2017) assume that although human races do not exist in a biological sense (“geneticists and evolutionary biologists generally agree that the division of humans into races/subspecies has no defensible scientific basis,” they exist only as “sociocultural constructions” and because of that maintain an illusory reality, for example, through “racialized” practices in medicine. Agreeing with the main postulates formulated in the article, we believe that the authors treat this problem in a superficial manner and have failed (...) to capture the current state of the field of knowledge in science and the humanities. In our commentary, we want to highlight two main omissions, and to notice three important implications for “a postracial medicine.”. (shrink)

The paper discusses the possibility that the benefits of pharmacogenomics will not be distributed equally and will create orphan populations. I argue that since these inequalities are not substantially different from those produced by ‘traditional’ drugs and are not generated with the intention to discriminate, their production needs not be unethical. Still, the final result is going against deep-seated moral feelings and intuitions, as well as broadly accepted principles of just distribution of health outcomes and healthcare. I thus propose two (...) provisos that would prevent the most offensive outcomes and moderate the scope of the produced inequalities. The first proviso rejects pharmacogenomics innovations that worsen existing group inequalities and aggravate the disadvantage of communities with a history of discrimination. The second proviso requires that there is a strategy in place to even out as much as possible the distribution of benefits in the future and that a system of compensations is in place for pharmacogenomic orphans. Given that only one moral problem generated by pharmacogenomics has been tackled, the list of provisos might be expanded when other issues are considered. (shrink)

The automatic integration of rapidly expanding information resources in the life sciences is one of the most challenging goals facing biomedical research today. Controlled vocabularies, terminologies, and coding systems play an important role in realizing this goal, by making it possible to draw together information from heterogeneous sources – for example pertaining to genes and proteins, drugs and diseases – secure in the knowledge that the same terms will also represent the same entities on all occasions of use. (...) In the naming of genes, proteins, and other molecular structures, considerable efforts are under way to reduce the effects of the different naming conventions which have been spawned by different groups of researchers. Electronic patient records, too, increasingly involve the use of standardized terminologies, and tremendous efforts are currently being devoted to the creation of terminology resources that can meet the needs of a future era of personalized medicine, in which genomic and clinical data can be aligned in such a way that the corresponding information systems become interoperable. (shrink)

What proper role should considerations of risk, particularly to research subjects, play when it comes to conducting research on human enhancement in the military context? We introduce the currently visible military enhancement techniques (1) and the standard discussion of risk for these (2), in particular what we refer to as the ‘Assumption’, which states that the demands for risk-avoidance are higher for enhancement than for therapy. We challenge the Assumption through the introduction of three categories of enhancements (3): (...) therapeutic, preventive, and pure enhancements. This demands a revision of the Assumption (4), alongside which we propose some further general principles bearing on how to balance risks and benefits in the context of military enhancement research. We identify a particular type of therapeutic enhancements as providing a more responsible path to human trials of the relevant interventions than pure enhancement applications. Finally, we discuss some possible objections to our line of thought (5). While acknowledging their potential insights, we ultimately find them to be unpersuasive, at least provided that our proposal is understood as fully non-coercive towards the candidates for such therapeutic enhancement trials. (shrink)

Background: Biomedical research nowadays is increasingly carried out in multinational and multicenter settings. Due to disparate national regulations on various ethical aspects, such as informed consent, there is the risk of ethical compromises when involving human subjects in research. Although the Declaration of Helsinki is the point of reference for ethical conduct of research on humans, national normative requirements may diverge from its provisions. The aim of this research is to examine requirements on informed consent (...) in biomedical research in Germany, Poland, and Russia to determine how each national regulatory framework relates to the provisions of the Declaration of Helsinki. Methods: For this analysis, we conducted a search of the legal databases “Gesetze im Internet” for Germany, “Internetowy System Aktow Prawnych” for Poland, and “ГAPAHT – Garant” for Russia. The search was complemented by a review of secondary literature contained in the databases Google Scholar, PubMed, Polish National Library, and eLibrary ru. We have identified 21 normative regulations containing provisions on informed consent in clinical research in all three countries. The content of these documents was systematically categorized and analyzed. Results: The normative framework in all three countries shows a strong commitment towards the core ethical principles of research envisaged in the Declaration of Helsinki. Nevertheless, provisions on informed consent vary between these three countries. The differences range from the method and language in which information should be provided, through the amount of information required to be disclosed, to the form of documenting consent or withdrawal. In the case of research on vulnerable groups, these differences are particularly visible. Conclusions: The identified differences can negatively impact the ethical conduct of international clinical studies. Attention needs to be paid that flexibilities within national regulations are not misused to undermine the protection of research subjects. Achieving global or regional legislative harmonization might prove impossible. Such lack of legal consensus reinforces the significance of the international ethical agreements. (shrink)

The Ontology for Biomedical Investigations (OBI) is an ontology that provides terms with precisely defined meanings to describe all aspects of how investigations in the biological and medical domains are conducted. OBI re-uses ontologies that provide a representation of biomedical knowledge from the Open Biological and Biomedical Ontologies (OBO) project and adds the ability to describe how this knowledge was derived. We here describe the state of OBI and several applications that are using it, such as adding (...) semantic expressivity to existing databases, building data entry forms, and enabling interoperability between knowledge resources. OBI covers all phases of the investigation process, such as planning, execution and reporting. It represents information and material entities that participate in these processes, as well as roles and functions. Prior to OBI, it was not possible to use a single internally consistent resource that could be applied to multiple types of experiments for these applications. OBI has made this possible by creating terms for entities involved in biological and medical investigations and by importing parts of other biomedical ontologies such as GO, Chemical Entities of Biological Interest (ChEBI) and Phenotype Attribute and Trait Ontology (PATO) without altering their meaning. OBI is being used in a wide range of projects covering genomics, multi-omics, immunology, and catalogs of services. OBI has also spawned other ontologies (Information Artifact Ontology) and methods for importing parts of ontologies (Minimum information to reference an external ontology term (MIREOT)). The OBI project is an open cross-disciplinary collaborative effort, encompassing multiple research communities from around the globe. To date, OBI has created 2366 classes and 40 relations along with textual and formal definitions. The OBI Consortium maintains a web resource providing details on the people, policies, and issues being addressed in association with OBI. (shrink)

The Protein Ontology (PRO) web resource provides an integrative framework for protein-centric exploration and enables specific and precise annotation of proteins and protein complexes based on PRO. Functionalities include: browsing, searching and retrieving, terms, displaying selected terms in OBO or OWL format, and supporting URIs. In addition, the PRO website offers multiple ways for the user to request, submit, or modify terms and/or annotation. We will demonstrate the use of these tools for protein research and annotation.

Ontology is a burgeoning field, involving researchers from the computer science, philosophy, data and software engineering, logic, linguistics, and terminology domains. Many ontology-related terms with precise meanings in one of these domains have different meanings in others. Our purpose here is to initiate a path towards disambiguation of such terms. We draw primarily on the literature of biomedical informatics, not least because the problems caused by unclear or ambiguous use of terms have been there most thoroughly addressed. We advance (...) a proposal resting on a distinction of three levels too often run together in biomedical ontology research: 1. the level of reality; 2. the level of cognitive representations of this reality; 3. the level of textual and graphical artifacts. We propose a reference terminology for ontology research and development that is designed to serve as common hub into which the several competing disciplinary terminologies can be mapped. We then justify our terminological choices through a critical treatment of the ‘concept orientation’ in biomedical terminology research. (shrink)

What proper role should considerations of risk, particularly to research subjects, play when it comes to conducting research on human enhancement in the military context? We introduce the currently visible military enhancement techniques and the standard discussion of risk for these, in particular what we refer to as the ‘Assumption’, which states that the demands for risk-avoidance are higher for enhancement than for therapy. We challenge the Assumption through the introduction of three categories of enhancements : therapeutic, preventive, (...) and pure enhancements. This demands a revision of the Assumption, alongside which we propose some further general principles bearing on how to balance risks and benefits in the context of military enhancement research. We identify a particular type of therapeutic enhancements as providing a more responsible path to human trials of the relevant interventions than pure enhancement applications. Finally, we discuss some possible objections to our line of thought. While acknowledging their potential insights, we ultimately find them to be unpersuasive, at least provided that our proposal is understood as fully non-coercive towards the candidates for such therapeutic enhancement trials. (shrink)

Ontologies describe reality in specific domains in ways that can bridge various disciplines and languages. They allow easier access and integration of information that is collected by different groups. Ontologies are currently used in the biomedical sciences, geography, and law. A Biomedical Ethics Ontology would benefit members of ethics committees who deal with protocols and consent forms spanning numerous fields of inquiry. There already exists the Ontology for Biomedical Investigations (OBI); the proposed BMEO would interoperate with OBI, (...) creating a powerful information tool. We define a domain ontology and begin to construct a BMEO, focused on the process of evaluating human research protocols. Finally, we show how our BMEO can have practical applications for ethics committees. This paper describes ongoing research and a strategy for its broader continuation and cooperation. (shrink)

The pathbreaking scientific advances of recent years call for a new philosophical consideration of the fundamental categories of biology and its neighboring disciplines. Above all, the new information technologies used in biomedical research, and the necessity to master the continuously growing flood of data that is associated therewith, demand a profound and systematic reflection on the systematization and classification of biological data. This, however, demands robust theories of basic concepts such as kind, species, part, whole, function, process, fragment, (...) sequence, expression, boundary, locus, environment, system, and so on. Concepts which belong to the implicit stock of knowledge of every biologist. They amount to a dimension of biological reality which remains constant in the course of biological evolution and whose theoretical treatment requires contemporary analogues of the tools developed in traditional Aristotelian metaphysics. To provide the necessary theories and definitions is a task for philosophy, which is thus called upon to play an important role as intermediary between biology and informatics. (shrink)

The fourth amendment to the German Medicinal Products Act (Arzneimittelgesetz) states that nontherapeutic research in incompetent populations is permissible under the condition that potential research participants expressly declare their wish to participate in scientific research in an advance research directive. This article explores the implementation of advance research directives in Germany against the background of the international legal and ethical framework for biomedical research. In particular, it addresses a practical problem that arises from (...) the disclosure requirement for advance research directives. We show that, if the disclosure standard for advance research directives is set at a token level, nontherapeutic research in incompetent populations becomes practically impossible. To resolve this issue, we suggest the disclosure standard be set at a type level. (shrink)

As biological and biomedical research increasingly reference the environmental context of the biological entities under study, the need for formalisation and standardisation of environment descriptors is growing. The Environment Ontology (ENVO) is a community-led, open project which seeks to provide an ontology for specifying a wide range of environments relevant to multiple life science disciplines and, through an open participation model, to accommodate the terminological requirements of all those needing to annotate data using ontology classes. This paper summarises (...) ENVO’s motivation, content, structure, adoption, and governance approach. (shrink)

The National Center for Biomedical Ontology is now in its seventh year. The goals of this National Center for Biomedical Computing are to: create and maintain a repository of biomedical ontologies and terminologies; build tools and web services to enable the use of ontologies and terminologies in clinical and translational research; educate their trainees and the scientific community broadly about biomedical ontology and ontology-based technology and best practices; and collaborate with a variety of groups who (...) develop and use ontologies and terminologies in biomedicine. The centerpiece of the National Center for Biomedical Ontology is a web-based resource known as BioPortal. BioPortal makes available for research in computationally useful forms more than 270 of the world's biomedical ontologies and terminologies, and supports a wide range of web services that enable investigators to use the ontologies to annotate and retrieve data, to generate value sets and special-purpose lexicons, and to perform advanced analytics on a wide range of biomedical data. (shrink)

1. Biomedical sciences are fast-growing fields with unprecedented speed of research outputs, especially in the quantities of papers. Philosophers aiming to study ongoing biomedical changes face cha...

The goal of the OBO (Open Biomedical Ontologies) Foundry initiative is to create and maintain an evolving collection of non-overlapping interoperable ontologies that will offer unambiguous representations of the types of entities in biological and biomedical reality. These ontologies are designed to serve non-redundant annotation of data and scientific text. To achieve these ends, the Foundry imposes strict requirements upon the ontologies eligible for inclusion. While these requirements are not met by most existing biomedical terminologies, the latter (...) may nonetheless support the Foundry’s goal of consistent and non-redundant annotation if appropriate mappings of data annotated with their aid can be achieved. To construct such mappings in reliable fashion, however, it is necessary to analyze terminological resources from an ontologically realistic perspective in such a way as to identify the exact import of the ‘concepts’ and associated terms which they contain. We propose a framework for such analysis that is designed to maximize the degree to which legacy terminologies and the data coded with their aid can be successfully used for information-driven clinical and translational research. (shrink)

Much of contemporary research ethics was developed in the latter half of the twentieth century as a response to the unethical treatment of human beings in biomedical research. Research ethical considerations have subsequently been extended to cover topics in the sciences and technology such as data handling, precautionary measures, engineering codes of conduct, and more. However, moral issues in the humanities have gained less attention from research ethicists. This article proposes an ethical principle for reading (...) for research purposes: Respect the author. (shrink)

Publication ethics is an important aspect of both the research and publication enterprises. It is particularly important in the field of biomedical science because published data may directly affect human health. In this article, we examine publication ethics policies in biomedical journals published in Central and Eastern Europe. We were interested in possible differences between East European countries that are members of the European Union (Eastern EU) and South-East European countries (South-East Europe) that are not members of (...) the European Union.The most common ethical issues addressed by all journals in the region were redundant publication, peer review process, and copyright or licensing details. Image manipulation, editors’ conflicts of interest and registration of clinical trialswere the least common ethical policies. Three aspects were significantly morecommon in journals published outside the EU: statements on the endorsement of international editorial standards, contributorship policy, and image manipulation.On the other hand, copyright or licensing information were more prevalent in journals published in the Eastern EU. The existence of significant differences amongbiomedical journals’ ethical policies calls for further research and active measuresto harmonize policies across journals. On the other hand, copyright or licensing information were more prevalent in journals published in the Eastern EU. The existence of significant differences among biomedical journals’ ethical policies calls for further research and active measures to harmonize policies across journals. (shrink)

The Human Genome Project is regarded by many as one of the major scientific achievements in recent science history, a large-scale endeavour that is changing the way in which biomedical research is done and expected, moreover, to yield considerable benefit for society. Thus, since the completion of the human genome sequencing effort, a debate has emerged over the question whether this effort merits to be awarded a Nobel Prize and if so, who should be the one to receive (...) it, as no more than three individuals can be selected. In this article, the HGP is taken as a case study to consider the ethical question to what extent it is still possible, in an era of big science, of large-scale consortia and global team work, to acknowledge and reward individual contributions to important breakthroughs in biomedical fields. Is it still viable to single out individuals for their decisive contributions in order to reward them in a fair and convincing way? Whereas the concept of the Nobel prize as such seems to reflect an archetypical view of scientists as solitary researchers who, at a certain point in their careers, make their one decisive discovery, this vision has proven to be problematic from the very outset. Already during the first decade of the Nobel era, Ivan Pavlov was denied the Prize several times before finally receiving it, on the basis of the argument that he had been active as a research manager rather than as a researcher himself. The question then is whether, in the case of the HGP, a research effort that involved the contributions of hundreds or even thousands of researchers worldwide, it is still possible to “individualise” the Prize? The “HGP Nobel Prize problem” is regarded as an exemplary issue in current research ethics, highlighting a number of quandaries and trends involved in contemporary life science research practices more broadly. (shrink)

This paper critically assesses the model of evaluation of scientific research for democratic societies defended by Philip Kitcher. The “significant truth” approach proposes a viable alternative to two classic images of science: that of the “critics”, who believe that science always serves the interests of the powerful and that of the “faithful”, who argue that the pursuit of scientific knowledge is always valuable and necessary. However, the democratic justification of Kitcher’s proposal is not compatible with the ethical problems generated (...) by the international biomedical research in developing countries. To overcome this problem, I revise the national democratic framing of the significant truth approach in light of the theory of justice of John Rawls. (shrink)

The growing commercialization of scientific research has raised important concerns about industry bias. According to some evidence, so-called industry bias can affect the integrity of the science as well as the direction of the research agenda. I argue that conceptualizing industry’s influence in scientific research in terms of bias is unhelpful. Insofar as industry sponsorship negatively affects the integrity of the research, it does so through biasing mechanisms that can affect any research independently of the (...) source of funding. Talk about industry bias thus offers no insight into the particular epistemic shortcomings at stake. If the concern is with the negative effects that industry funding can have on the research agenda, conceptualizing this influence as bias obscures the ways in which such impact is problematic and limits our ability to offer solutions that can successfully address the concerns raised by the growing role of private funding in science. (shrink)

Background Genomic research on neurodevelopmental disorders (NDDs), particularly involving minors, combines and amplifies existing research ethics issues for biomedical research. We performed a review of the literature on the ethical issues associated with genomic research involving children affected by NDDs as an aid to researchers to better anticipate and address ethical concerns. Results Qualitative thematic analysis of the included articles revealed themes in three main areas: research design and ethics review, inclusion of research (...) participants, and communication of research results. Ethical issues known to be associated with genomic research in general, such as privacy risks and informed consent/assent, seem especially pressing for NDD participants because of their potentially decreased cognitive abilities, increased vulnerability, and stigma associated with mental health problems. Additionally, there are informational risks: learning genetic information about NDD may have psychological and social impact, not only for the research participant but also for family members. However, there are potential benefits associated with research participation, too: by enrolling in research, the participants may access genetic testing and thus increase their chances of receiving a (genetic) diagnosis for their neurodevelopmental symptoms, prognostic or predictive information about disease progression or the risk of concurrent future disorders. Based on the results of our review, we developed an ethics checklist for genomic research involving children affected by NDDs. Conclusions In setting up and designing genomic research efforts in NDD, researchers should partner with communities of persons with NDDs. Particular attention should be paid to preventing disproportional burdens of research participation of children with NDDs and their siblings, parents and other family members. Researchers should carefully tailor the information and informed consent procedures to avoid therapeutic and diagnostic misconception in NDD research. To better anticipate and address ethical issues in specific NDD studies, we suggest researchers to use the ethics checklist for genomic research involving children affected by NDDs presented in this paper. (shrink)

Important advances in biomedical and behavioral research ethics have occurred over the past few decades, many of them centered on identifying and eliminating significant harms to human subjects of research. Comprehensive attention has not been paid to the totality of harms experienced by animal subjects, although scientific and moral progress require explicit appraisal of these harms. Science is a public good and the prioritizing within, conduct of, generation of, and application of research must soundly address questions (...) about which research is morally defensible and valuable enough to support through funding, publication, tenure, and promotion. Likewise, educational pathways of re-imagined science are critical. (shrink)

Background Several jurisdictions, including Singapore, Australia, New Zealand and most recently Ireland, have a public interest or public good criterion for granting waivers of consent in biomedical research using secondary health data or tissue. However, the concept of the public interest is not well defined in this context, which creates difficulties for institutions, institutional review boards and regulators trying to implement the criterion. Main text This paper clarifies how the public interest criterion can be defensibly deployed. We first (...) explain the ethical basis for requiring waivers to only be granted to studies meeting the public interest criterion, then explore how further criteria may be set to determine the extent to which a given study can legitimately claim to be in the public interest. We propose an approach that does not attempt to measure magnitude of benefit directly, but rather takes into account metrics that are more straightforward to apply. To ensure consistent and justifiable interpretation, research institutions and IRBs should also incorporate procedural features such as transparency and public engagement in determining which studies satisfy the public interest requirement. Conclusion The requirement of public interest for consent waivers in secondary biomedical research should be guided by well-defined criteria for systematic evaluation. Such a criteria and its application need to be periodically subject to intra-committee and intra-institution review, reflection, deliberation and amendment. (shrink)

The goals and tasks of neuroethics formulated by Farahany and Ramos (2020) link epistemological and methodological issues with ethical and social values. The authors refer simultaneously to the social significance and scientific reliability of the BRAIN Initiative. They openly argue that neuroethics should not only examine neuroscientific research in terms of “a rigorous, reproducible, and representative neuroscience research process” as well as “explore the unique nature of the study of the human brain through accurate and representative models of (...) its function and dysfunction”, but also its responsibilities or social consequences. In our commentary, we would like to concentrate on problem selection, which is shortly noticed by Farahany and Ramos, and by BRAIN Initiative’s Neuroethics Report itself. The document raises an important issue related to problem selection, which is strengthening or perpetuating existing prejudices and biases by choosing a research subject: “scientists are prompted to consider how the questions they choose to study in the laboratory might amplify existing biases.” This leads to several further problems: what constitutes bias?; how biases may be embedded in the selection of research programs?; is it possible to conduct completely unbiased research?; who should be a gatekeeper in the case of research that may amplify biases? We try to notice possible answers to these questions in the context of the research on differences (e.g., cognitive, medical, behavioral) between human populations. (shrink)

In a recent commentary, Kim and colleagues argued that minimal-risk research should be deregulated so that such studies do not require review by an institutional review board. They claim that regulation of minimal-risk studies provides no adequate counterbalancing good and instead leads to a costly human subjects oversight system. We argue that the counterbalancing good of regulating minimal-risk studies is that oversight exists to ensure that respect for persons and justice requirements are satisfied when they otherwise might not be.

Knowledge-making practices in biology are being strongly affected by the availability of data on an unprecedented scale, the insistence on systemic approaches and growing reliance on bioinformatics and digital infrastructures. What role does theory play within data-intensive science, and what does that tell us about scientific theories in general? To answer these questions, I focus on Open Biomedical Ontologies, digital classification tools that have become crucial to sharing results across research contexts in the biological and biomedical sciences, (...) and argue that they constitute an example of classificatory theory. This form of theorizing emerges from classification practices in conjunction with experimental know-how and expresses the knowledge underpinning the analysis and interpretation of data disseminated online. (shrink)

The context of international health research involving human subjects, and this should appear obvious, is the human community. As such, basic questions of how human beings should be treated by other human beings, particularly in situations of unequal power – e.g., in the form of control, choice, or opportunity – lay at the foundations of related ethical discourse when ethics are discussed at all. I trace a narrative that follows upon a recent revision process of international guidelines for (...) class='Hi'>biomedical research involving human subjects. I focus in particular upon the issue of a standard of care. In the second section, I draw upon philosophers John Rawls, Claudia Card, and Allen Buchanan to discuss concerns regarding the 'least advantaged members of society' in the context of global inequality. The paper includes reflections upon pedagogy in courses focused upon international health research involving human subjects. (shrink)

Background: Exposomics, the study of the exposome, is flourishing, but the field is not well defined. The term “exposome” refers to all environmental influences and associated biological responses throughout the lifespan. However, this definition is very similar to that of the term “environment”—the external elements and conditions that surround and affect the life and development of an organism. Consequently, the exposome seems to be nothing more than a synonym for the environment, and exposomics a synonym for environmental research. As (...) a result, some have rebranded their “standard” environmental health research with the neologistic exposome term, whereas others ignore or seek to abandon the seemingly redundant concept of the exposome. -/- Objectives: We argue that exposomics needs to sharpen its mission focus to counteract this apparent redundancy. Exposomics should be defined as a research program in environmental health aimed at enabling a comprehensive and discovery-driven approach to identifying environmental determinants of human health. Similar to the aim of the Human Genome Project, exposomics aims to analyze the complete complexity of exposures and their corresponding biological responses. Exposomics’ primary premise is that the existence of undiscovered, potentially interconnected, nongenetic (environmental) risk factors for health necessitates a comprehensive discovery-driven analysis approach. -/- Discussion: We argue that exposomics researchers should adopt our reconceptualization of exposomics and focus on the productiveness and integrity of their research program: its purpose and principles. We suggest that exposomics researchers should coordinate the writing of reviews that assess the program’s productiveness and integrity, as well as provide a platform for exposomics researchers to define their vision for the field. (shrink)

A wide variety of scientific research projects include public participation in roles going beyond the classic use of subjects in human subjects research. “Participatory research” is an umbrella term for such projects. In this chapter, we begin by surveying the variety of participatory research approaches across fields. We examine what goals participatory research projects seek to achieve, both of social and scientific value. Next, we apply this theoretical framework to challenges that participatory research faces. (...) We then survey three typologies of participatory research projects, each of which can illuminate and guide decisions in project development. We end with a look at participatory research approaches in health contexts, applying the theoretical resources we introduced earlier in the chapter. (shrink)

Introduction In 2013, Dr. J. Muizelaar and Dr. R. Schrot, two neurosurgeons at the University of California Davis Medical Center (UCDMC), were found guilty of research misconduct due to failure to comply with institutional policies as well as Food and Drug Administration (FDA) regulations governing human subjects research. At issue here, however, is the difference between research and innovative therapy in the clinical setting of patient care where clinical judgment is reasonably to be privileged. Methods The UCDMC (...) investigative document is reviewed along with standard literature on clinical ethics and clinical data about glioblastoma multiforme (GBM) cancer. Results In this paper I argue that, by tendentiously focusing on policies, regulations, and procedures governing human subjects research, the UCDMC investigation failed to account for the centrality of clinical judgment and clinical ethics pertinent to judicious review of this matter, especially given the unique clinical context of terminally ill patients having exhausted standard care treatment options for glioblastoma multiforme (GBM) cancer. Conclusions The UCDMC investigation raises serious problems for clinicians who are engaged in innovative therapy in the clinical setting, requiring a regulatory framework separate from the normal Institutional Review Board (IRB) process. (shrink)

Our philosophical understanding of mental illness is being shaped by neuroscience. However, it has the paradoxical effect of igniting two radically opposed groups of philosophical views. On one side, skepticism and denialism assume that, lacking clear biological mechanisms and etiologies for most mental illnesses, we should infer they are constructions best explained by means of social factors. This is strongly associated with medical nihilism: it considers psychiatry more harmful than benign. On the other side of the divide, naturalism and reductionism (...) are on the look for failures in the biological functioning of the organism whenever a genuine mental illness occurs. Psychiatry as currently practiced, accordingly, exhibits the gaps of an ongoing research programme; a yet to be completed neuroscience would link mental illnesses with identifiable biological mechanisms. Both sides of this divide claim to be fostered by scientific discoveries and advances in neuroscience, when taken at face value. Against this background, we argue instead for a modest view. To that end, we draw attention to some nuances in the scientific realism debate. While contending that neuroscientific theories and models aim to provide true representations of their target systems, and can justifiably claim to have attained some, we argue that our confidence should not be placed beforehand in specific features of these scientific representations. Hence, it would be unwarranted to extract morals for psychiatry from posits (or their absence) in neuroscientific explanations of mental illnesses. To illustrate our position, we examine some recent discoveries in neuroscience concerning bipolar disorder. We conclude by linking our topic to a broader issue in the philosophy of medicine: insofar as psychiatry is a biomedical specialty, its classifications of health and disease are guided by pragmatic concerns, as well as by scientific discoveries. (shrink)

The distinction between clinical research and clinical practice directs how we partition medicine and biomedical science. Reasons for a sharp distinction date historically to the work of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, especially to its analysis of the “boundaries” between research and practice in the Belmont Report (1978). Belmont presents a segregation model of the research-practice distinction, according to which research and practice form conceptually (...) exclusive sets of activities and interventions. This model is still the standard in federal regulations today. However, the Commission’s deliberations and conclusions about the boundaries are more complicated, nuanced, and instructive than has generally been appreciated. The National Commission did not conclude that practice needs no oversight comparable to the regulation of research. It debated the matter and inclined to the view that the oversight of practice needed to be upgraded, though the Commission stopped short of proposing new regulations for its oversight, largely for prudential political reasons. (shrink)

The COVID-19 pandemic prompted immense work on the investigation of the SARS-CoV-2 virus. Rapid, accurate, and consistent interpretation of generated data is thereby of fundamental concern. Ontologies––structured, controlled, vocabularies––are designed to support consistency of interpretation, and thereby to prevent the development of data silos. This paper describes how ontologies are serving this purpose in the COVID-19 research domain, by following principles of the Open Biological and Biomedical Ontology (OBO) Foundry and by reusing existing ontologies such as the Infectious (...) Disease Ontology (IDO) Core, which provides terminological content common to investigations of all infectious diseases. We report here on the development of an IDO extension, the Virus Infectious Disease Ontology (VIDO), a reference ontology covering viral infectious diseases. We motivate term and definition choices, showcase reuse of terms from existing OBO ontologies, illustrate how ontological decisions were motivated by relevant life science research, and connect VIDO to the Coronavirus Infectious Disease Ontology (CIDO). We next use terms from these ontologies to annotate selections from life science research on SARS-CoV-2, highlighting how ontologies employing a common upper-level vocabulary may be seamlessly interwoven. Finally, we outline future work, including bacteria and fungus infectious disease reference ontologies currently under development, then cite uses of VIDO and CIDO in host-pathogen data analytics, electronic health record annotation, and ontology conflict-resolution projects. (shrink)

Rationale, aims, and objectives: One of the sectors challenged by the COVID-19 pandemic is medical research. COVID-19 originates from a novel coronavirus (SARSCoV- 2) and the scientific community is faced with the daunting task of creating a novel model for this pandemic or, in other words, creating novel science. This paper is the first part of a series of two papers that explore the intricate relationship between the different challenges that have hindered biomedical research and the generation (...) of scientific knowledge during the COVID-19 pandemic. Methods: During the early stages of the pandemic, research conducted on hydroxychloroquine (HCQ) was chaotic and sparked several heated debates with respect to the scientific methods used and the quality of knowledge generated. Research on HCQ is used as a case study in both papers. The authors explored biomedical databases, peer-reviewed journals, pre-print servers, and media articles to identify relevant literature on HCQ and COVID-19, and examined philosophical perspectives on medical research in the context of this pandemic and previous global health challenges. Results: This paper demonstrates that a lack of prioritization among research questions and therapeutics was responsible for the duplication of clinical trials and the dispersion of precious resources. Study designs, aimed at minimising biases and increasing objectivity, were, instead, the subject of fruitless oppositions. The duplication of research works, combined with poor-quality research, has greatly contributed to slowing down the creation of novel scientific knowledge. Conclusions: The COVID-19 pandemic presented challenges in terms of (1) finding and prioritising relevant research questions and (2) choosing study designs that are appropriate for a time of emergency. (shrink)

This project considers whether and how research ethics can contribute to the provision of cost-effective medical interventions. Clinical research ethics represents an underexplored context for the promotion of cost-effectiveness. In particular, although scholars have recently argued that research on less-expensive, less-effective interventions can be ethical, there has been little or no discussion of whether ethical considerations justify curtailing research on more expensive, more effective interventions. Yet considering cost-effectiveness at the research stage can help ensure that (...) scarce resources such as tissue samples or limited subject popula- tions are employed where they do the most good; can support parallel efforts by providers and insurers to promote cost-effectiveness; and can ensure that research has social value and benefits subjects. I discuss and rebut potential objections to the consideration of cost-effectiveness in research, including the difficulty of predicting effectiveness and cost at the research stage, concerns about limitations in cost-effectiveness analysis, and worries about overly limiting researchers’ freedom. I then consider the advantages and disadvantages of having certain participants in the research enterprise, including IRBs, advisory committees, sponsors, investigators, and subjects, consider cost-effectiveness. The project concludes by qualifiedly endorsing the consideration of cost-effectiveness at the research stage. While incorporating cost-effectiveness considerations into the ethical evaluation of human subjects research will not on its own ensure that the health care system realizes cost-effectiveness goals, doing so nonetheless represents an important part of a broader effort to control rising medical costs. (shrink)

The COVID-19 pandemic prompted immense work on the investigation of the SARS-CoV-2 virus. Ontologies – structured, controlled, vocabularies – are designed to support consistency of interpretation, and thereby to prevent the development of data silos. This paper describes how ontologies are serving this purpose in the virus research domain, following the principles of the Open Biological and Biomedical Ontology (OBO) Foundry and drawing on the resources of the Infectious Disease Ontology (IDO) Core. We report the development of the (...) Virus Infectious Disease Ontology (VIDO), a reference ontology extending IDO Core covering viral infectious diseases. We examine newly minted terms, showcase ontology term reuse, and illustrate the use of VIDO by annotating selections from recent life science research on SAR-CoV-2, in the interest of supporting machine learning projects. (shrink)

PURPOSE—A substantial fraction of the observations made by clinicians and entered into patient records are expressed by means of negation or by using terms which contain negative qualifiers (as in “absence of pulse” or “surgical procedure not performed”). This seems at first sight to present problems for ontologies, terminologies and data repositories that adhere to a realist view and thus reject any reference to putative non-existing entities. Basic Formal Ontology (BFO) and Referent Tracking (RT) are examples of such paradigms. The (...) purpose of the research here described was to test a proposal to capture negative findings in electronic health record systems based on BFO and RT. METHODS—We analysed a series of negative findings encountered in 748 sentences taken from 41 patient charts. We classified the phenomena described in terms of the various top-level categories and relations defined in BFO, taking into account the role of negation in the corresponding descriptions. We also studied terms from SNOMED-CT containing one or other form of negation. We then explored ways to represent the described phenomena by means of the types of representational units available to realist ontologies such as BFO. RESULTS—We introduced a new family of ‘lacks’ relations into the OBO Relation Ontology. The relation lacks_part, for example, defined in terms of the positive relation part_of, holds between a particular p and a universal U when p has no instance of U as part. Since p and U both exist, assertions involving ‘lacks_part’ and its cognates meet the requirements of positivity. CONCLUSION—By expanding the OBO Relation Ontology, we were able to accommodate nearly all occurrences of negative findings in the sample studied. (shrink)

This is the first volume of the Encyclopedia of Neutrosophic Researchers, edited from materials offered by the authors who responded to the editor’s invitation. The authors are listed alphabetically. The introduction contains a short history of neutrosophics, together with links to the main papers and books. Neutrosophic set, neutrosophic logic, neutrosophic probability, neutrosophic statistics, neutrosophic measure, neutrosophic precalculus, neutrosophic calculus and so on are gaining significant attention in solving many real life problems that involve uncertainty, impreciseness, vagueness, incompleteness, inconsistent, and (...) indeterminacy. In the past years the fields of neutrosophics have been extended and applied in various fields, such as: artificial intelligence, data mining, soft computing, decision making in incomplete / indeterminate / inconsistent information systems, image processing, computational modelling, robotics, medical diagnosis, biomedical engineering, investment problems, economic forecasting, social science, humanistic and practical achievements. (shrink)

This is the fourth volume of the Encyclopedia of Neutrosophic Researchers, edited from materials offered by the authors who responded to the editor’s invitation. The authors are listed alphabetically. The introduction contains a short history of neutrosophics, together with links to the main papers and books. Neutrosophic set, neutrosophic logic, neutrosophic probability, neutrosophic statistics, neutrosophic measure, neutrosophic precalculus, neutrosophic calculus and so on are gaining significant attention in solving many real life problems that involve uncertainty, impreciseness, vagueness, incompleteness, inconsistent, and (...) indeterminacy. In the past years the fields of neutrosophics have been extended and applied in various fields, such as: artificial intelligence, data mining, soft computing, decision making in incomplete / indeterminate / inconsistent information systems, image processing, computational modelling, robotics, medical diagnosis, biomedical engineering, investment problems, economic forecasting, social science, humanistic and practical achievements. (shrink)