Background If trials of therapeutic interventions are to serve society's interests, they must be of high methodological quality and must satisfy moral commitments to human subjects. The authors set out to develop a clinical - trials compendium in which standards for the ethical treatment of human subjects are integrated with standards for research methods. Methods The authors rank-ordered the world's nations and chose the 31 with >700 active trials as of 24 July 2008. Governmental and other authoritative entities of (...) the 31 countries were searched, and 1004 English-language documents containing ethical and/or methodological standards for clinical trials were identified. The authors extracted standards from 144 of those: 50 designated as ‘core’, 39 addressing trials of invasive procedures and a 5% sample of the remainder. As the integrating framework for the standards we developed a coherent taxonomy encompassing all elements of a trial's stages. Findings Review of the 144 documents yielded nearly 15 000 discrete standards. After duplicates were removed, 5903 substantive standards remained, distributed in the taxonomy as follows: initiation, 1401 standards, 8 divisions; design, 1869 standards, 16 divisions; conduct, 1473 standards, 8 divisions; analysing and reporting results, 997 standards, four divisions; and post-trial standards, 168 standards, 5 divisions. Conclusions The overwhelming number of source documents and standards uncovered in this study was not anticipated beforehand and confirms the extraordinary complexity of the clinical trials enterprise. This taxonomy of multinational ethical and methodological standards may help trialists and overseers improve the quality of clinical trials, particularly given the globalisation of clinical research. (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)

Statistics play a critical role in biological and clinical research. However, most reports of scientific results in the published literature make it difficult for the reader to reproduce the statistical analyses performed in achieving those results because they provide inadequate documentation of the statistical tests and algorithms applied. The Ontology of Biological and Clinical Statistics (OBCS) is put forward here as a step towards solving this problem. Terms in OBCS, including ‘data collection’, ‘data transformation in statistics’, ‘data (...) visualization’, ‘statistical data analysis’, and ‘drawing a conclusion based on data’, cover the major types of statistical processes used in basic biological research and clinical outcome studies. OBCS is aligned with the Basic Formal Ontology (BFO) and extends the Ontology of Biomedical Investigations (OBI), an OBO (Open Biological and Biomedical Ontologies) Foundry ontology supported by over 20 research communities. We discuss two examples illustrating how the ontology is being applied. In the first (biological) use case, we describe how OBCS was applied to represent the high throughput microarray data analysis of immunological transcriptional profiles in human subjects vaccinated with an influenza vaccine. In the second (clinical outcomes) use case, we applied OBCS to represent the processing of electronic health care data to determine the associations between hospital staffing levels and patient mortality. Our case studies were designed to show how OBCS can be used for the consistent representation of statistical analysis pipelines under two different research paradigms. By representing statistics-related terms and their relations in a rigorous fashion, OBCS facilitates standard data analysis and integration, and supports reproducible biological and clinical research. (shrink)

I. EXECUTIVE SUMMARY The MRCT Center Post-trial Responsibilities: Continued Access to an Investigational Medicine Framework outlines a case-based, principled, stakeholder approach to evaluate and guide ethical responsibilities to provide continued access to an investigational medicine at the conclusion of a patient’s participation in a clinical trial. The Post-trial Responsibilities (PTR) Framework includes this Guidance Document as well as the accompanying Toolkit. A 41-member international multi-stakeholder Workgroup convened by the Multi-Regional Clinical Trials Center of Brigham and Women’s Hospital and (...) Harvard University (MRCT Center) developed this Guidance and Toolkit. Project Motivation A number of international organizations have discussed the responsibilities stakeholders have to provide continued access to investigational medicines. The World Medical Association, for example, addressed post-trial access to medicines in Paragraph 34 of the Declaration of Helsinki (WMA, 2013): “In advance of a clinical trial, sponsors, researchers and host country governments should make provisions for post-trial access for all participants who still need an intervention identified as beneficial in the trial. This information must also be disclosed to participants during the informed consent process.” This paragraph and other international guidance documents converge on several consensus points: • Post-trial access (hereafter referred to as “continued access” in this Framework [for terminology clarification – see definitions]) is the responsibility of sponsors, researchers, and host country governments; • The plan for continued access should be determined before the trial begins, and before any individual gives their informed consent; • The protocol should delineate continued access plans; and • The plan should be transparent to potential participants and explained during the informed consent process. -/- However, there is no guidance on how to fulfill these responsibilities (i.e., linking specific responsibilities with specific stakeholders, conditions, and duration). To fill this gap, the MRCT Center convened a working group in September of 2014 to develop a framework to guide stakeholders with identified responsibilities. This resultant Framework sets forth applicable principles, approaches, recommendations and ethical rationales for PTR regarding continued access to investigational medicines for research participants. (shrink)

Since its introduction just over two decades ago, evidence-based medicine (EBM) has come to dominate medical practice, teaching, and policy. There are a growing number of textbooks, journals, and websites dedicated to EBM research, teaching, and evidence dissemination. EBM was most recently defined as a method that integrates best research evidence with clinical expertise and patient values and circumstances in the treatment of patients. There have been debates throughout the early 21st century about what counts as good research evidence (...) between EBM proponents and philosophical critics and even within the EBM community itself. Similar controversy arises about the relative worth of patient values and clinical expertise (and how these can be integrated). EBM has also evolved in ways that have come under scrutiny. Specifically, policymakers have used EBM research methodology to increase the relative importance of clinical guidelines that some clinicians have argued are tyrannical. Philosophers have addressed all of these controversies, and with very few exceptions have been critical of EBM. In addition most philosophical attention has been on the epistemic role of Randomization and evidence hierarchies, with relatively little attention being paid to the role of Diagnosis, expertise, patient values, and Systematic Reviews within EBM. (shrink)

The public health crisis is started with emergence of new coronavirus on 11 February 2020 which triggered as coronavirus disease-2019 (COVID-19) pandemics. The causative agent in COVID-19 is made up of positively wrapped single-stranded RNA viruses ~ 30 kb in size. The epidemiology, clinical features, pathophysiology, and mode of transmission have been documented well in many studies, with additional clinical trials are running for several antiviral agents. The spreading potential of COVID-19 is faster than its two previous families, (...) the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV). Apart from clinical manifestation, comorbid status is playing key role for prevalence of COVID-19 infection and mortalities. The comorbid effects associated with COVID-19 are diabetes, cardiovascular, digestive, hepatitis-B, cerebrovascular, hypertension, liver injury, coronary heart disease, cancer, rheumatoid arthritis, and neurological impairment. Antimalarial drugs (chloroquine and hydroxychloroquine), remdesivir, Tocilizumab, clopinavir/ritonavir, convalescent plasma therapy, spike protein-angiotensin-converting enzyme 2 (ACE2) inhibitors, human monoclonal antibodies, mRNA-1273, mesenchymal stem cells, Indian and Chinese traditional medicine, small molecules antioxidant, natural products and dietary supplements, high doses of vitamin-E, -C, -D, minerals, flavonoids,and IFN-beta are therapeutic intervention running to develop treatment against COVID-19. Although clinical usage of these therapeutic agents against COVID-19 is well documented, cytokine storms, absence of appropriate animal model have limited its therapeutic use. This review explores the clinical information currently available on COVID-19 on the mechanisms of infection, prevention, management, comorbid status, and current drug treatment options. (shrink)

The International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 dataset is one of the largest international databases of prospectively collected clinical data on people hospitalized with COVID-19. This dataset was compiled during the COVID-19 pandemic by a network of hospitals that collect data using the ISARIC-World Health Organization Clinical Characterization Protocol and data tools. The database includes data from more than 705,000 patients, collected in more than 60 countries and 1,500 centres worldwide. Patient data are available (...) from acute hospital admissions with COVID-19 and outpatient follow-ups. The data include signs and symptoms, pre-existing comorbidities, vital signs, chronic and acute treatments, complications, dates of hospitalization and discharge, mortality, viral strains, vaccination status, and other data. Here, we present the dataset characteristics, explain its architecture and how to gain access, and provide tools to facilitate its use. (shrink)

Semantic interoperability requires the use of standards, not only for Electronic Health Record (EHR) data to be transferred and structurally mapped into a receiving repository, but also for the clinical content of the EHR to be interpreted in conformity with the original meanings intended by its authors. Accurate and complete clinical documentation, faithful to the patient’s situation, and interoperability between systems, require widespread and dependable access to published and maintained collections of coherent and quality-assured semantic resources, including (...) models such as archetypes and templates that would (1) provide clinical context, (2) be mapped to interoperability standards for EHR data, (3) be linked to well specified, multi-lingual terminology value sets, and (4) be derived from high quality ontologies. Wide-scale engagement with professional bodies, globally, is needed to develop these clinical information standards. (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)

Decision-making by a Data and Safety Monitoring Board (DSMB) regarding clinical trial conduct and termination is intricate and largely limited by cases and rules. Decision-making by legal jury is also intricate and largely constrained by cases and rules. In this paper, I argue by analogy that legal decision-making, which strives for a balance between competing demands of conservatism and innovation, supplies a good basis to the logic behind DSMB decision-making. Using the doctrine of precedents in legal reasoning as my (...) central analog will lead us to a decision-theoretic analogy for much more systematic documentation of decisions in clinical trials. My conclusion is twofold: every DSMB decision should articulate a clear general principle (a ratio decidendi) that gives reason for the decision; and all such decisions should be made public. I use Bartha’s (2010) theory of analogical arguments to both frame and assess my argument by analogy. (shrink)

Most regulations and guidelines require that potential research participants be told a great deal of information during the consent process. Many of these documents, and most of the scholars who consider the consent process, assume that all this information must be disclosed because it must all be understood. However, a wide range of studies surveying apparently competent participants in clinical trials around the world show that many do not understand key aspects of what they have been told. The standard (...) view of the conditions for valid consent therefore implies that these people have failed to give valid consent to research participation. In this paper we argue that the standard view is false. The primary function of the requirement that researchers disclose information about a study is the avoidance of illegitimate control over someone’s consent decision, which is a form of fraud.We derive the content and manner of appropriate disclosure by analysing the ways in which the manipulation of information can invalidate consent. Our analysis shows that the informational requirements for valid consent are conceptually distinct and thus unlikely to have identical contents. This implies that consent can be valid when not everything that ought to be disclosed by the person asking for consent is understood by the person who proffers it. (shrink)

Obsessive-compulsive disorder is a commonly occurring neuropsychiatric condition characterized by bothersome intrusive thoughts and urges that frequently lead to repetitive dysfunctional behaviours such as excessive handwashing. There are well-documented alterations in cerebral function which appear to be closely related to the manifestation of these symptoms. Controlled studies of cognitive-behavioural therapy techniques utilizing the active refocusing of attention away from the intrusive phenomena of OCD and onto adaptive alternative activities have demonstrated both significant improvements in clinical symptoms and systematic changes (...) in the pathological brain circuitry associated with them. Careful investigation of the relationships between the experiential and putative neurophysiological processes involved in these changes can offer useful insights into volitional aspects of cerebral function. (shrink)

An increasing number of European research projects return, or plan to return, individual genomic research results (IRR) to participants. While data access is a data subject’s right under the General Data Protection Regulation (GDPR), and many legal and ethical guidelines allow or require participants to receive personal data generated in research, the practice of returning results is not straightforward and raises several practical and ethical issues. Existing guidelines focusing on return of IRR are mostly project-specific, only discuss which results to (...) return, or were developed outside Europe. To address this gap, we analysed existing normative documents identified online using inductive content analysis. We used this analysis to develop a checklist of steps to assist European researchers considering whether to return IRR to participants. We then sought feedback on the checklist from an interdisciplinary panel of European experts (clinicians, clinical researchers, population-based researchers, biobank managers, ethicists, lawyers and policy makers) to refine the checklist. The checklist outlines seven major components researchers should consider when determining whether, and how, to return results to adult research participants: 1) Decide which results to return; 2) Develop a plan for return of results; 3) Obtain participant informed consent; 4) Collect and analyse data; 5) Confirm results; 6) Disclose research results; 7) Follow-up and monitor. Our checklist provides a clear outline of the steps European researchers can follow to develop ethical and sustainable result return pathways within their own research projects. Further legal analysis is required to ensure this checklist complies with relevant domestic laws. (shrink)

Objective: To examine the current ethical review process of ethics committees in a non-pharmacological trial from the perspective of a clinical investigator.Design: Prospective collection of data at the Study Centre of the German Surgical Society on the duration, costs and administrative effort of the ERP of a randomised controlled multicentre surgical INSECT Trial between November 2003 and May 2005.Setting: Germany.Participants: 18 ethics committees, including the ethics committee handling the primary approval, responsible overall for 32 clinical sites throughout Germany. (...) 8 ethics committees were located at university medical schools and 10 at medical chambers. Duration was measured as days between submission and receipt of final approval, costs in euros and administrative effort by calculation of the product of the total number of different types of documents and the mean number of copies required .Results: The duration of the ERP ranged from 1 to 176 days. The median duration was 26 days at MSUs compared with 34 days at medical chambers. The total cost was €2947. 1 of 8 ethics committees at universities and 8 of 10 at medical chambers charged a median fee of €162 . The administrative effort for primary approval was 30. Four ethics committees required a higher administrative effort for secondary approval .Conclusion: The ERP for non-pharmacological multicentre trials in Germany needs improvement. The administrative process has to be standardised: the application forms and the number and content of the documents required should be identical or at least similar. The fees charged vary considerably and are obviously too high for committees located at medical chambers. However, the duration of the ERP was, with some exceptions, excellent. A centralised ethics committee in Germany for multicentre trials such as the INSECT Trial can simplify the ERP for clinical investigators in and outside the country. (shrink)

Resumen Ésta es la primera traducción al español de las guías “Atención después de la investigación: un marco para los comités de ética de investigación del National Health Service (NHS) (borrador versión 8.0)”. El documento afirma que existe una fuerte obligación moral de garantizar que los participantes enfermos de un estudio clínico hagan una transición después del estudio hacia una atención de la salud apropiada. Con “atención de la salud apropiada” se hace referencia al acceso para los participantes a la (...) atención de la salud, proporcionada principalmente por el National Health Service (en adelante NHS), el sistema de salud del Reino Unido, y/o a la intervención en estudio, también llamada producto o tratamiento en investigación. Las guías “Atención después de la investigación” están dirigidas principalmente a los miembros de los 79 comités de ética de investigación del NHS y a quienes presentan sus estudios de investigación ante estos comités. Se trata de un documento borrador muy avanzado, trabajado en numerosas reuniones, durante más de 3 años, que ha sido discutido por participantes de estudios y miembros de la comunidad, miembros y presidentes de comités de ética de investigación del Reino Unido, especialistas internacionales en ética de la investigación, representantes de la industria y otras partes interesadas. La redacción de las guías es producto de la colaboración de Neema Sofaer y Penney Lewis, ambas investigadoras del King’s College London, en el Centre of Medical Law and Ethics del Dickson Poon School of Law, y Hugh Davies, Asesor en Ética de la Investigación de la Health Research Authority (HRA) del NHS. El traductor del presente documento, Ignacio Mastroleo, participó del workshop en la Fundación Brocher (Ginebra, Suiza, diciembre de 2011) donde se revisó el borrador versión 7.0 y contribuyó en la revisión del borrador de la versión 8.0 durante el 2012. -/- Abstract This is the first Spanish translation of the guidelines “Care after research: a framework for NHS RECs (8th draft)”. The document states that there is a strong moral obligation to ensure that participants in a clinical study who are ill transition after the study to appropriate healthcare. The terms "appropriate healthcare" refer to participants’ access to health care, mainly provided by the National Health Service (NHS), the health system in the UK, and/or to the intervention study also named investigational treatment or product. The guides "Care after research" are mainly directed to members of the 79 NHS committees of research ethics (RECs) and to those who submit their research to these committees. This is a very advanced draft document, worked in several meetings, for more than three years, that has been discussed with study participants and community members, members and chairs of RECs in the UK, international specialists in research ethics, industry representatives and other stakeholders. The drafting of the guidelines is the result of the collaboration of Neema Sofaer and Penney Lewis, both researchers at King's College London, at the Centre of Medical Law and Ethics of Dickson Poon School of Law, and Hugh Davies, Research Ethics Advisor of the Health Research Authority (HRA) of the NHS. The translator of this document, Ignacio Mastroleo, attended the workshop at the Brocher Foundation (Geneva, Switzerland, December 2011) where draft version 7.0 was revised and contributed in the revision of draft version 8.0 during 2012. (shrink)

Background: In prevalence studies of sexually transmitted infections (STIs), investigators often provide syndromic management for symptomatic participants, but may not provide specific treatment for asymptomatic individuals with positive laboratory test results due to the delays between sample collection and availability of results as well as logistical constraints in recontacting study participants. Methods: To characterize the extent of this issue, 80 prevalence studies from the World Health Organization’s Report on global sexually transmitted infection surveillance, 2018, were reviewed. Studies were classified as (...) to whether clinically relevant positive results were returned or if this was not specified. Results: More than half (56%) of the cited studies did not specify if participants were notified of clinically relevant positive STI test results. The percentages were similar for low- and middle-income country populations (57%) and high-income country populations (53%). Conclusions: The absence of documentation of the provision of test results raises the possibility that in some instances, results may not have been communicated, with potential negative effects for participants, their sexual partners, and newborns. From an ethical perspective, clinically relevant results should be returned to study participants and treating clinicians in a timely fashion to ensure appropriate management of identified infections. Study authors should document if they returned test results to study participants and report on numbers lost to follow-up. (shrink)

Despite the recent advances in information and communication technology that have increased our ability to store and circulate information, the task of ensuring that the right sorts of information gets to the right sorts of people remains. We argue that the many efforts underway to develop efficient means for sharing information across healthcare systems and organizations would benefit from a careful analysis of human action in healthcare organizations. This in turn requires that the management of information and knowledge within healthcare (...) organizations be combined with models of resources and processes of patient care that are based on a general ontology of social interaction. The Health Level 7 (HL7) is one of several ANSI-accredited Standards Developing Organizations operating in the healthcare arena. HL7 has advanced a widely used messaging standard that enables healthcare applications to exchange clinical and administrative data in digital form. HL7 focuses on the interface requirements of the entire healthcare system and not exclusively on the requirements of one area of healthcare such as pharmacy, medical devices, imaging or insurance transactions. This has inspired the development of a powerful abstract model of patient care called the Reference Information Model (RIM). The present paper begins with an overview of the core classes of the HL7 (Version 3) RIM and a brief discussion of its “actcentered” view of healthcare. Central to this account is what is called the life cycle of events. A clinical action may progress from defined, through planned and ordered, to executed. These modalities of an action are represented as the mood of the act. We then outline the basis of an ontology of organizations, starting from the theory of speech Acts, and apply this ontology to the HL7 RIM. Special attention is given to the sorts of preconditions that must be satisfied for the successful performance of a speech act and to the sorts of entities to which speech acts give rise (e.g. obligations, claims, commitments, etc.). Finally we draw conclusions for the efficient communication and management of medical information and knowledge within and between healthcare organizations, paying special attention to the role that medical documents play in such organizations. (shrink)

Background: A better understanding of the pattern of epidemic-related referrals to healthcare centers might allow the identification of vulnerabilities and the required changes that the healthcare management system should undergo. Objectives: This study aimed to investigate the COVID-19 referral pattern and the role of media and health management planning in changing the trends. Methods: Data extracted from the electronic medical database of Imam Khomeini Hospital Complex (IKHC), located in Tehran, Iran, from February 20 to June 4, 2020 were examined. Individuals (...) were divided into two groups, COVID-19 positive and negative. We used Google Trends to evaluate Google Internet search queries and also available policy documents, programs, and official news related to COVID-19 in Iran during the mentioned period. Results: In this study, 8647 individuals aged 46.05 ± 16.5 years were referred to IKHC. Approximately 57% were male, and 70% were COVID-19 positive. The most clinical symptoms were dyspnea, fever, cough, and myalgia. Chronic kidney disease (CKD) and type 2 diabetes mellitus were the most common underlying health conditions. In the first two weeks, the percentage of negative cases was higher than positive cases and then the pattern was reversed, when people searched for information about COVID-19 in media. Conclusions: Proper and timely information and education to people through the media and health management measures can be effective in reducing unnecessary visits to health centers, preventing the exhaustion of medical staff, and controlling the disease during epidemics. (shrink)

This topic focuses on the problems that arise in providing medical care to the population during armed conflict or martial law. Under such conditions, hospitals, clinics, and other healthcare facilities have to work in challenging circumstances with limited resources and reduced security for medical personnel. This topic explores such issues as how martial law affects the work of medical institutions, what problems arise in providing medical care to the population in war, how war affects the health of the people, and (...) what consequences it may have in the long term. Research in this area will help to understand how to organize better and prepare medical facilities to work in war conditions and ensure high-quality medical care to the population in emergencies. The methods used to write this article were analysis, synthesis, generalization, explanation, and data qualification. The primary and fundamental sources for writing an article may vary depending on the topic, but generally, the following sources can be recommended. Academic studies: these can be scholarly articles, monographs, dissertations, conference papers, and other materials related to the topic of your article. These sources can help you find information about the latest research in the field and allow you to see the approaches and methodologies used in the studies. Official sources: These can be legal documents, reports, regulations, guidelines, and other materials issued by government agencies, ministries, and other departments. These sources can help you understand the rules and regulations governing your article's topic. Expert reviews: these can be interviews with experts in the field, articles, and other materials written by well-known specialists. These sources can help you understand the views and opinions of well-known experts on the issues related to your paper. (shrink)

In order to achieve the World Health Organization’s Millennium Development Goal of reducing maternal mortality by three quarters by 2015, a strong global commitment is needed to address this issue in low-income nations where the risk to women is greatest. A comprehensive international effort must include provision of obstetric and general medical care as well as community-based interventions, with an emphasis on the latter in nations where the majority of women deliver babies at home without a trained attendant. Methods: This (...) systematic analysis evaluates interventions published in Medline and CINAHL whose outcome measure is maternal mortality. Analysis includes components of the intervention, nation and maternal death rates. Results: Nine studies documented the effectiveness of various clinical and community-based interventions, including specific drug regimens and procedures, in reducing the risk of maternal death. Six studies reported interventions that did not significantly alter maternal mortality outcomes, and the intervention in one study demonstrated increased risk of maternal death. Conclusion: The dearth of evidence highlights the need for increased focus on translational research that bridges the gap between medical advances and community-based interventions that are feasible in low-income nations. This cannot be accomplished without a stronger commitment to reducing maternal mortality by global health practitioners and researchers. (shrink)

A previously atypical symptom report of a hospitalized patient experiencing unusual visual broadcasting has been documented but has received minimal attention in the research and clinical field of psychiatry. A preliminary hypothesis is proposed of an implicit mechanism of motivation for action and emotional relief functional significance of elevated cortisol and dopamine correlation, that is loosely based on the concept of stress-induced psychosis and which could have led to a concurrent "visual and thought" psychotic episode. In addition, the implication (...) of the effect of increased dopamine on intracranial pressure and indirectly on cerebral perfusion pressure is briefly discussed. A follow-up on the insight and comprehensive understanding of such atypical and novel symptom as an extension of schizophrenia is warranted. (shrink)

If we already had a periodic table of mental illness in hand, there would be less need for a book of this type. Although some psychiatrists do think of themselves as chemists, the analogy is without warrant. Not only does psychiatry lack an analogue of the periodic table, its principal tool -- the Diagnostic and Statistical Manual of Mental Disorders (DSM) -- is a contentious document. Even subsequent to the publication of DSM-III in 1980, which was intended to serve as (...) an operational guideline for clinical practice, it and its heirs (DSM-V was published in 2013) have often fueled rather than quelled controversy. Although beginning with that third major revision of DSM a concerted effort has been made to ensure greater consistency in diagnoses, psychiatry remains beset by concerns that it is insufficiently scientific, unduly influenced by the pharmaceutical industry, indecisive as to whether it should focus on the mind or the brain, incapable of distinguishing among types of diseases, inclined to expand illness criteria without adequate justification, overly reliant on subjective judgments, wont to conflate clinical and ethical judgments, and engaged in indiscriminate use of psychoactive drugs. These worries concerning its scientific and ethical status are among the reasons that psychiatry attracts the attention of philosophers. (shrink)

CLE aims and clients’ needs conflict where students’ interests are put beyond clients’ needs. Students have interests in gaining employment, impressing instructors and supervisors, and experiencing the active application of law. Where the clients’ service-needs are subordinated to students’ interests, the relationship between the two—the ‘tension’—is tilted in a manner in which the clients are disserved through the fulfilment of students’ interests. This may be exacerbated by faulty institutional cultures where clinical faculty are treated differently, or as less accomplished (...) or ‘worthwhile’ than their ‘traditional’ counterparts. This also emphasizes that it is the clinical law faculty who may exacerbate or assuage the tension, as it is for clinical faculty to assure that clients’ needs are met on ethical grounds,20 and to equate the practice of law with excellence before students. (shrink)

The theory of granular partitions (TGP) is a new approach to the understanding of ontologies and other classificatory systems. The paper explores the use of this new theory in the treatment of task-based clinical guidelines as a means for better understanding the relations between different clinical tasks, both within the framework of a single guideline and between related guidelines. We used as our starting point a DAML+OIL-based ontology for the WHO guideline for hypertension management, comparing this with related (...) guidelines and attempting to show that TGP provides a flexible and highly expressive basis for the manipulation of ontologies of a sort which might be useful in providing more adequate Computer Interpretable Guideline Models (CIGMs) in the future. (shrink)

The article presents the advantages and limitations of adaptive clinical trials for assessing the effectiveness of medical interventions and specifies the conditions that contributed to their development and implementation in clinical practice. I advance two arguments by discussing different cases of adaptive trials. The normative argument is that responsible adaptation should be taken seriously as a new way of doing clinical research insofar as a valid justification, sufficient understanding, and adequate operational conditions are provided. The second argument (...) is historical. The development of adaptive trials can be related to lessons learned from research in cases of urgency and to the decades-long efforts to end the productivity crisis of pharmaceutical research, which led to the emergence of translational, personalized, and, recently, precision medicine movements. (shrink)

The theory of document acts is an extension of the more traditional theory of speech acts advanced by Austin and Searle. It is designed to do justice to the ways in which documents can be used to bring about a variety of effects in virtue of the fact that, where speech is evanescent, documents are continuant entities. This means that documents can be preserved in such a way that they can be inspected and modified at successive points in time and (...) grouped together into enduring document complexes. We outline some components of a theory of document acts, and show how it can throw light on certain problems in Searle’s ontology of social reality. (shrink)

In this paper, we argue that there are reasons to believe that an implicit bias for normalcy influences what are considered medically necessary treatments in psychiatry. First, we outline two prima facie reasons to suspect that this is the case. A bias for ‘the normal’ is already documented in disability studies; it is reasonable to suspect that it affects psychiatry too, since psychiatric patients, like disabled people, are often perceived as ‘weird’ by others. Secondly, psychiatry's explicitly endorsed values of well-being (...) and function are hard to measure directly, which is why we see simpler box-ticking conceptions of recovery used in large research studies. This need not be problematic, but might lead to researchers and clinicians focusing too much on treatments that promote easy-to-measure proxies for recovery, instead of what actually matters to psychiatric patients themselves. Next, we provide examples of treatments and treatment decisions within two areas – self-injury and psychosis – which are hard to explain unless we assume that an implicit and harmful normalcy bias is at work. We conclude with some suggestions for clinicians and future research. (shrink)

There are two important ways in which, when dealing with documents, we go beyond the boundaries of linear text. First, by incorporating diagrams into documents, and second, by creating complexes of intermeshed documents which may be extended in space and evolve and grow through time. The thesis of this paper is that such aggregations of documents are today indispensable to practically all complex human achievements from law and finance to orchestral performance and organized warfare. Documents provide for what we can (...) think of as a division of intellectual, instructional, and deontic labour, allowing plans, orders, and obligations to be enmeshed together in a way that often involves the use of diagrammatic elements, as for example in a musical score. (shrink)

Psychiatry has witnessed a new wave of approaches to clinical phenotyping and the study of psychopathology, including the National Institute of Mental Health’s Research Domain Criteria, clinical staging, network approaches, the Hierarchical Taxonomy of Psychopathology, and the general psychopathology factor, as well as a revival of interest in phenomenological psychopathology. The question naturally emerges as to what the relationship between these new approaches is – are they mutually exclusive, competing approaches, or can they be integrated in some way (...) and used to enrich each other? In this opinion piece, we propose a possible integration between clinical staging and phenomenological psychopathology. Domains identified in phenomenological psychopathology, such as selfhood, embodiment, affectivity, etc., can be overlaid on clinical stages in order to enrich and deepen the phenotypes captured in clinical staging (‘high resolution’ clinical phenotypes). This approach may be useful both ideographically and nomothetically, in that it could complement diagnosis, enrich clinical formulation, and inform treatment of individual patients, as well as help guide aetiological, prediction, and treatment research. The overlaying of phenomenological domains on clinical stages may require that these domains are reformulated in dimensional rather than categorial terms. This integrative project requires assessment tools, some of which are already available, that are sensitive and thorough enough to pick up on the range of relevant psychopathology. The proposed approach offers opportunities for mutual enrichment: clinical staging may be enriched by introducing greater depth to phenotypes; phenomenological psychopathology may be enriched by introducing stages of severity and disorder progression to phenomenological analysis. (shrink)

Existing social disparities in the United States are inconsistent with the promise of democracy; therefore, there was a need for critical conceptualization of the first principles that undergird American democracy and the genesis of democratic social change in America. This constructivist grounded theory study aimed to construct a grounded theory that provides an understanding of the process of American democratic social change as it emerged from the nation’s founding documents. A post hoc polytheoretical framework including Foucault’s, Bourdieu’s, and Marx and (...) Engels’s theories of power was used to understand power dynamics. The research question focused on understanding the process of democratic social change in America. The sample comprised the Articles of Confederation, the U.S. Declaration of Independence, The Federalist Papers, and the U.S. Constitution. The documents were retrieved from the National Archives and Library of Congress. The data analysis plan incorporated successive comparison, situational and dramaturgical analysis, deconstruction, and perspective taking as strategies. The result was the construction of a democratic social change process theory preceded by five grounded theories: (a) first principles of democracy, (b) first principles of democracy conceptual framework, (c) socio-ethical principles of democracy, (d) demoralizing process, and (e) either-or approach to democracy. Positive social change implications include applying a democratic social change process to future social change endeavors across domains and levels of analysis, a normative framework for a republican form of government, and a tool to analyze and minimize the latent consequences of social justice policies. (shrink)

This article addresses two areas of continuing controversy about consent in clinical research: the question of when consent to low risk research is necessary, and the question of when consent to research is valid. The article identifies a number of considerations relevant to determining whether consent is necessary, chief of which is whether the study would involve subjects in ways that would (otherwise) infringe their rights. When consent is necessary, there is a further question of under what conditions consent (...) is valid or successful in waiving a right. The most influential account of validity conditions is non-moralized, in the sense that the conditions make no essential reference to whether the researcher soliciting consent has obtained it in a way that wrongs the subject. The article examines the implications of this account, and compares it with recent accounts that moralize some of the validity conditions. -/- . (shrink)

The principle of clinical equipoise has been variously characterized by ethicists and clinicians as fundamentally flawed, a myth, and even a moral balm. Yet, the principle continues to be treated as the de facto gold standard for conducting randomized control trials in an ethical manner. Why do we hold on to clinical equipoise, despite its shortcomings being widely known and well-advertised? This paper reviews the most important arguments criticizing clinical equipoise as well as what the most prominent (...) proposed alternatives are. In the process, it evaluates the justification for continuing to use clinical equipoise as the gold standard for randomized control trials. (shrink)

Clinical guidelines are special types of plans realized by collective agents. We provide an ontological theory of such plans that is designed to support the construction of a framework in which guideline-based information systems can be employed in the management of workflow in health care organizations. The framework we propose allows us to represent in formal terms how clinical guidelines are realized through the actions of are realized through the actions of individuals organized into teams. We provide various (...) levels of implementation representing different levels of conformity on the part of health care organizations. Implementations built in conformity with our framework are marked by two dimensions of flexibility that are designed to make them more likely to be accepted by health care professionals than standard guideline-based management systems. They do justice to the fact 1) that responsibilities within a health care organization are widely shared, and 2) that health care professionals may on different occasions be non-compliant with guidelines for a variety of well justified reasons. The advantage of the framework lies in its built-in flexibility, its sensitivity to clinical context, and its ability to use inference tools based on a robust ontology. One disadvantage lies in its complicated implementation. (shrink)

Clinical Ethics Consultations are an important tool for physicians in solving difficult cases. They are extremely common in North America and to a lesser extent also present in Europe. However, there is little data on this practice in Poland. We present results of a survey of 521 physicians practising in Poland concerning their opinion on CECs and related practices. We analysed the data looking at such issues as CECs’ perceived availability, use of CECs, and perceived usefulness of such support. (...) Physicians in our study generally encounter hard ethics cases, even—surprisingly—those who do not work in hospitals. Most physicians have no CEC access, and those that do still do not employ CECs. However, physicians perceive this form of support as useful—even more so among actual users of CECs. We compared these findings with similar studies from other European countries and the North America. We point out peculiarities of our results as compared to those in other countries, with some possible explanations. We hope the results may encourage regulatory debate on the need to formally introduce CECs into the Polish healthcare system. (shrink)

Many extant theories of placebo focus on their causal structure wherein placebo effects are those that originate from select features of the therapy (e.g., client expectations or “incidental” features like size and shape). Although such accounts can distinguish placebos from standard medical treatments, they cannot distinguish placebos from everyday occurrences, for example, when positive feedback improves our performance on a task. Providing a social-epistemological account of a treatment context can rule out such occurrences, and furthermore reveal a new way to (...) distinguish clinical placebos from standard medical treatments. (shrink)

We argue that charging people to participate in research is likely to undermine the fundamental ethical bases of clinical research, especially the principles of social value, scientific validity, and fair subject selection.

Machine learning algorithms may radically improve our ability to diagnose and treat disease. For moral, legal, and scientific reasons, it is essential that doctors and patients be able to understand and explain the predictions of these models. Scalable, customisable, and ethical solutions can be achieved by working together with relevant stakeholders, including patients, data scientists, and policy makers.

The desideratum of semantic interoperability has been intensively discussed in medical informatics circles in recent years. Originally, experts assumed that this issue could be sufficiently addressed by insisting simply on the application of shared clinical terminologies or clinical information models. However, the use of the term ‘ontology’ has been steadily increasing more recently. We discuss criteria for distinguishing clinical ontologies from clinical terminologies and information models. Then, we briefly present the role clinical ontologies play in (...) two multicentric research projects. Finally, we discuss the interactions between these different kinds of knowledge representation artifacts and the stakeholders involved in developing interoperational real-world clinical applications. We provide ontology engineering examples from two EU-funded projects. (shrink)

Outcomes research in healthcare has been a topic much addressed in recent years. Efforts in this direction have been supplemented by work in the areas of guidelines for clinical practice and computer-interpretable workflow and careflow models.In what follows we present the outlines of a framework for understanding the relations between organizations, guidelines, individual patients and patient-related functions. The derived framework provides a means to extract the knowledge contained in the guideline text at different granularities, in ways that can help (...) us to assign tasks within the healthcare organization and to assess clinical performance in realizing the guideline. It does this in a way that preserves the flexibility of the organization in the adoption of the guidelines. (shrink)

Context-sensitive expressions appear ill suited to the purpose of sharing content across contexts. Yet we regularly use them to that end (in regulations, textbooks, memos, guidelines, laws, minutes, etc.). This paper describes the utility of the concept of a metacontext for understanding cross-contextual content-sharing with context-sensitive expressions. A metacontext is the context of a group of contexts: an infrastructure that can channel non-linguistic incentives on content ascription so as to homogenize the content ascribed to context-sensitive expressions in each context in (...) the group. Documents composed of context-sensitive expressions can share content across contexts when supported by an appropriate metacontext. The bible has its church, the textbook its education system, the form its bureaucracy, and the manifesto its social movement. Some metacontexts support cross-contextual content-sharing. Some don’t. A promising research programme (one with practical importance) would take metacontexts as its unit of analysis. (shrink)

This is a supplementary document to my "Why I am not an Absolutist (Or a First-Orderist)", which is forthcoming in a volume on higher-order logic edited by Peter Fritz and Nick Jones.

Abstract: In this article, we explore what are ethical forms of holding service users responsible in mental health care contexts. Hanna Pickard has provided an account of how service users should be held responsible for morally wrong or seriously harmful conduct within contexts of mental health care, called the clinical stance. From a clinical stance one holds a person responsible for harm, but refrains from emotionally blaming the person and only considers the person responsible for this conduct in (...) a detached sense. Her account is based on what are considered best practices in the treatment of people with borderline personality disorder and addiction. We ask if this account generalizes across different diagnostic criteria and different clinical contexts. To begin to answer this question, we compare the clinical stance to an account of what are considered best practices in the treatment of service users at a specialized clinic for people with autism spectrum disorder in the Netherlands. We refer to this alternative account as the nurturing stance and highlight relevant similarities and differences between the clinical stance and the nurturing stance. We conclude with suggestions for further research and theorizing. (shrink)

Ontological realism aims at the development of high quality ontologies that faithfully represent what is general in reality and to use these ontologies to render heterogeneous data collections comparable. To achieve this second goal for clinical research datasets presupposes not merely (1) that the requisite ontologies already exist, but also (2) that the datasets in question are faithful to reality in the dual sense that (a) they denote only particulars and relationships between particulars that do in fact exist and (...) (b) they do this in terms of the types and type-level relationships described in these ontologies. While much attention has been devoted to (1), work on (2), which is the topic of this paper, is comparatively rare. Using Referent Tracking as basis, we describe a technical data wrangling strategy which consists in creating for each dataset a template that, when applied to each particular record in the dataset, leads to the generation of a collection of Referent Tracking Tuples (RTT) built out of unique identifiers for the entities described by means of the data items in the record. The proposed strategy is based on (i) the distinction between data and what data are about, and (ii) the explicit descriptions of portions of reality which RTTs provide and which range not only over the particulars described by data items in a dataset, but also over these data items themselves. This last feature allows us to describe particulars that are only implicitly referred to by the dataset; to provide information about correspondences between data items in a dataset; and to assert which data items are unjustifiably or redundantly present in or absent from the dataset. The approach has been tested on a dataset collected from patients seeking treatment for orofacial pain at two German universities and made available for the NIDCR-funded OPMQoL project. (shrink)

Our culture is dominated by digital documents in ways that are easy to overlook. These documents have changed our worldviews about science and have raised our expectations of them as tools for knowledge justification. This article explores the complexities surrounding the digital document by revisiting Michael Polanyi’s theory of tacit knowledge—the idea that “we can know more than we can tell.” The theory presents to us a dilemma: if we can know more than we can tell, then this means that (...) the communication of science via the document as a primary form of telling will always be incomplete. This dilemma presents significant challenges to the open science movement. (shrink)

The UN Convention against Torture defines torture as “any act by which severe pain or suffering, whether physical or mental, is intentionally inflicted on a person” by someone acting in an official capacity for purposes such as obtaining a confession or punishing or intimidating that person.1 It is unethical for healthcare professionals to participate in torture, including any use of medical knowledge or skill to facilitate torture or allow it to continue, or to be present during torture.2-7 Yet medical participation (...) in torture has taken place throughout the world and was a prominent feature of the US interrogation practice in military and Central Intelligence Agency (CIA) detention facilities in the years after the attacks of 11 September 2001.8-11 Little attention has been paid, however, to how a regime of torture affects the ability of health professionals to meet their obligations regarding routine clinical care for detainees. -/- The 2016 release of previously classified portions of guideline from the CIA regarding medical practice in its secret detention facilities sheds light on that question. These show that the CIA instructed healthcare professions to subordinate their fundamental ethical obligations regarding professional standards of care to further the objectives of the torturers. (shrink)

The desideratum of semantic interoperability has been intensively discussed in medical informatics circles in recent years. Originally, experts assumed that this issue could be sufficiently addressed by insisting simply on the application of shared clinical terminologies or clinical information models. However, the use of the term ‘ontology’ has been steadily increasing more recently. We discuss criteria for distinguishing clinical ontologies from clinical terminologies and information models. Then, we briefly present the role clinical ontologies play in (...) two multicentric research projects. Finally, we discuss the interactions between these different kinds of knowledge representation artifacts and the stakeholders involved in developing interoperational real-world clinical applications. We provide ontology engineering examples from two EU-funded projects. (shrink)

Regarding the appropriateness of deception in clinical practice, two (apparently conflicting) claims are often emphasised. First, that ‘clinicians should not deceive their patients.’ Second, that deception is sometimes ‘in a patient’s best interest.’ Recently, Hardman has worked towards resolving this conflict by exploring ways in which deceptive and non-deceptive practices extend beyond consideration of patients’ beliefs. In short, some practices only seem deceptive because of the (common) assumption that non-deceptive care is solely aimed at fostering true beliefs. Non-deceptive care, (...) however, relates to patients’ non-doxastic attitudes in important ways as well. As such, Hardman suggests that by focusing on belief alone, we sometimes misidentify non-deceptive care as ‘deceptive’. Further, once we consider patients’ beliefs and non-doxastic attitudes, identifying cases of deception becomes more difficult than it may seem. In this essay, I argue that Hardman’s reasoning contains at least three serious flaws. First, his account of deception is underdeveloped, as it does not state whether deception must be intentional. The problem is that if intention is not required, absurd results follow. Alternatively, if intention is required, then identifying cases of deception will be much easier (in principle) than Hardman suggests. Second, Hardman mischaracterises the ‘inverse’ of deceptive care. Doing so leads to the mistaken conclusion that common conceptions of non-deceptive care are unjustifiably narrow. Third, Hardman fails to adequately separate questions about deception from questions about normativity. By addressing these issues, however, we can preserve some of Hardman’s most important insights, although in a much simpler, more principled way. (shrink)

As is well known, speech acts such as acts of promising can have ontological consequences. For example an act of promising can give rise to a mutually correlated claim and obligation. Increasingly, speech acts in the narrow sense are being augmented by the use of documents of multiple different sorts. In this paper we analyze the results of this augmenta-tion from the ontological point of view, considering especially the domains of law and com-merce. We show how document acts are not (...) isolated phenomena, but rather form large and complex systems with other entities, including occurrent entities such as acts of signing and inspecting, as well as speech acts for example of instructing people to sign or complete a doc-ument. The paper concludes with a consideration of some of the special problems associated with the use of digital documents, for example as concerns issues of security and provenance. (shrink)

Introduction: Clinical practice guidelines (CPGs) are an important source of justification for clinical decisions in modern evidence-based practice. Yet, we have given little attention to how they argue their evidence. In particular, how do CPGs argue for treatment with long-term medications that are increasingly prescribed to older patients? Approach and rationale: I selected six disease-specific guidelines recommending treatment with five of the medication classes most commonly prescribed for seniors in Ontario, Canada. I considered the stated aims of these (...) CPGs and the techniques employed towards those aims. Finally, I reconstructed and logically analysed the arguments supporting recommendations for pharmacotherapy. Analysis: The primary function of CPGs is rhetorical, or persuasive, and their means of persuasion include both a display of their credibility and their argumentation. Arguments supporting pharmacotherapy recommendations for the target population follow a common inductive pattern: statistical generalization from randomized controlled trial (RCT) and meta-analysis evidence. Two of the CPGs also argue their treatment recommendations for older patients in this style, while three fail to justify pharmacotherapy specifically for the older population. Discussion: The arguments analysed lack the auxiliary assumptions that would warrant making a generalization about the clinical effectiveness of medications for the older population. Guidelines reason using simple induction, while ignoring important inferential gaps. Future guidelines should aspire to be well-reasoned rather than simply evidence-based; argue from a plurality of evidence; be wary of hasty inductions; appropriately limit the scope of their recommendations; and avoid making law-like, prescriptive generalizations. (shrink)

The once animated efforts in medical phenomenology to integrate the art and science of medicine (or to humanize scientific medicine) have fallen out of philosophical fashion. Yet the current competing medical discourses of evidencebased medicine and patient-centered care suggest that this theoretical endeavor requires renewed attention. In this paper, I attempt to enliven the debate by discussing theoretical weaknesses in the way the “lived body” has operated in the medical phenomenology literature—the problem of the absent body—and highlight how evidence-based medicine (...) has refigured medical phenomenology’s historical nemesis, “biomedicine.” What we now need is a phenomenology of the embodied subject in the age of evidence-based medicine. (shrink)