Advance Consent in Acute Stroke Trials: Survey of Canadian Stroke Physicians.

Advance consent presents a potential solution to the challenge of obtaining informed consent for participation in acute stroke trials. Clinicians in stroke prevention clinics are uniquely positioned to identify and seek consent from potential stroke trial participants. To assess the acceptability of advance consent to Canadian stroke clinic physicians, we performed an online survey. We obtained 58 respondents (response rate 35%): the vast majority (82%) expressed comfort with obtaining advance consent and 92% felt that doing so would not be a significant disruption to clinic workflow. These results support further study of advance consent for acute stroke trials.

Advance Consent in Acute Stroke Trials: Survey of Canadian Research Ethics Board Chairs.

Advance consent could allow individuals at high risk of stroke to provide consent before they might become eligible for enrollment in acute stroke trials. This survey explores the acceptability of this novel technique to Canadian Research Ethics Board (REB) chairs that review acute stroke trials. Responses from 15 REB chairs showed that majority of respondents expressed comfort approving studies that adopt advance consent. There was no clear preference for advance consent over deferral of consent, although respondents expressed significant concern with broad rather than trial-specific advance consent. These findings shed light on the acceptability of advance consent to Canadian ethics regulators.

Inference to the best action and its basis in clinical expertise.

Can contemporary cognitive science explain clinical expertise? We argue that the answer could be "no." In support of this, we provide an analysis of two of the most essential expressions of clinical expertise in nursing and medicine, the ability to run a code blue and the ability to diagnose congestive heart failure. We show how it makes sense to treat both as examples of what we call inference to the best action, and we then argue that two of the standard explanatory paradigms of cognitive science - the Humean and Bayesian paradigms - are unable to provide a plausible analysis of inference to the best action.

Ethical evaluation in acute stroke decision-making.

RATIONALE: The evidentiary standards and epistemic models of clinical care, especially those of evidence-based medicine, are dissimilar to those used in philosophy and examination of how the two systems intersect may help clinicians make more informed treatment decisions. AIMS AND OBJECTIVES: This paper examines the use of ethical frameworks in routine clinical decision-making, using the example of acute stroke treatment decisions to demonstrate that ethical evaluation is integral to clinical practice. METHOD: Utilising acute stroke care as a lens through which to examine the phenomenon of ethical evaluation in medical practice, we offer a philosophical analysis of the presence of ethical evaluation in medicine. RESULTS AND CONCLUSION: We find that the medical establishment should embrace ethical evaluation as intrinsic to medical practice and that medical training and treatment guidelines should reflect this reality. Patients deserve clarity and transparency about how physicians make determinations about their treatment, and physicians should be prepared to offer explanations for those decisions.

Nursing science as the study of how to reconcile behavioral messiness with clinical norms and ideals.

There is no settled definition of nursing science that describes how this field of scientific research is unique. This paper attempts to correct this problem. It uses a combination of historical analysis and abductive argument to support the thesis that nursing science is a sui generis social science that studies how to reconcile clinical ideals or norms that are applicable to practice in nursing with the messiness of human behavior.

What do we talk about when we talk about "equipoise"? Stakeholder interviews assessing the use of equipoise in clinical research ethics.

INTRODUCTION: Equipoise, generally defined as uncertainty about the relative effects of the treatments being compared in a trial, is frequently referenced as an ethical standard for the conduct of randomized clinical trials. However, it seems to be defined in several different ways and may be used differently by different individuals. We explored how clinical researchers, chairs of research ethics boards, and philosophers of science define and reason with this term. METHODS: We completed semi-structured interviews about clinical trial ethics with 15 clinical researchers, 15 research ethics board chairs, and 15 philosophers of science/bioethicists. Each participant was asked a standardized set of 10 questions, 4 of which were specifically about equipoise. All interviews were conducted telephonically and transcribed. Responses were grouped and analysed via a modified grounded theory method. RESULTS: Forty-three respondents defined equipoise in 7 logically distinct ways, and 2 respondents could not explicitly define it. The most common definition, offered by 14 respondents (31%), defined "equipoise" as a disagreement at the level of a community of physicians. There was significant variability in definitions offered between and within groups. When asked how they would "operationalize" equipoise - i.e. check or test for its presence - respondents provided 7 alternatives, the most common being in relation to a literature review (15/45, 33%). The vast majority of respondents (35/45, 78%) felt the concept was helpful, though many acknowledged that the lack of a clear definition or operationalization was problematic. CONCLUSION: There is significant variation in definitions of equipoise offered by respondents, suggesting that parties within groups and between groups may be referring to different concepts when they reference "equipoise". This non-uniformity may impact fairness and transparency and opens the door to potential ethical problems in the evaluation of clinical trials - for instance, a patient may understand equipoise very differently than the researchers enrolling her in a trial, which could cause her agreement to participate to be based upon false premises.

Protocol for Deferral of Consent in Acute Stroke Trials.

The challenges of conducting hyperacute stroke research and obtaining informed consent have been increasingly recognized within the stroke research community in recent years. Deferral of consent, in which a patient is enrolled in a trial and then provides consent at some point thereafter, is increasingly used to enroll patients into hyperacute stroke trials in Canada and Europe, although it is not permitted in the United States. Deferral of consent offers several potential advantages-quicker door-to-randomization, increased enrolment, decreased selection bias-but these must be balanced against the risk of enrolling patients against their wishes. We seek to minimize the attendant risks of deferral of consent by offering practical guidance regarding how to conduct acute stroke trials using deferral of consent. Building on existing guidelines and recent experiences with deferral of consent in acute stroke trials, we have developed a protocol for the use of deferral of consent that aims to maximize patient involvement while minimizing ethical and scientific risks.

How are randomized clinical trials ethically justified? A systematic scoping review and thematic analysis of reasons that ethically justify randomized clinical trials.

OBJECTIVES: We set out to identify and count the types of reasons that are used in contemporary scholarship about the ethical permissibility of randomized trials, with the goal of developing a finer grained taxonomy of reasons than what is currently used by most participants in this literature. Because of its central role in justifying normative conclusions about randomized clinical trials (RCTs), we paid particular attention to both uses of the keyword "equipoise" and to the different concepts associated with it. METHODS: We conducted a scoping review to identify articles that included arguments that were likely to express reasons justifying RCTs. Text excerpts that expressed reasoning about the ethical permissibility of RCTs were extracted from relevant papers, and our data were generated by coding these excerpts using a mixed-methods protocol that fused elements of a grounded analysis and thematic coding. In our study, each theme corresponded to a specific type of reason that was contentful and stable when applied to our corpus of text extracts. RESULTS: Our search, screening, and text extraction process yielded 1,335 unique text excerpts, which then formed the basis of our coding. Although we found that 16 themes were sufficient to saturate this corpus, slightly less than 100% of our excerpts were covered by just 10 themes. We also tracked uses of 16 keywords in the text excerpts to explore whether there was any relationship between the keywords and our themes and found that keywords frequently did not cooccur with the presence of our themes. CONCLUSIONS: Our data and analysis support the conclusion that there is significant diversity in the types of reasons offered to justify RCTs; 10 themes effectively captured all the text excerpts we analyzed, and these themes cannot be reduced to the occurrence of relevant keywords. This result highlights how individuals and organizations may use different reasons to consider randomized trials to be justified and even when they use similar language the concepts they are referencing may not be consistent.

A Longitudinal Study of the Impact of Personal and Professional Resources on Nurses' Work Engagement: A Comparison of Early-Career and Mid-Later-Career Nurses.

To predict and ensure a healthy and high-performing nursing workforce, it is necessary to identify the antecedents that promote work engagement, especially among early-career nurses. To date no study has focused on this. This longitudinal survey, administered to 1204 nurses working in seven general hospitals with 200 or more beds in four prefectures in Japan at two different times in 2019, aims to examine the causal relationship between the personal and professional resources for nurses to work vigorously (PPR-N) and work engagement among nurses in the early stages of their careers, considering time as a key mediating factor. The analysis of structural equation modeling using the cross-lagged effect model supported that PPR-N had significant and positive effects on work engagement after 3 months among early-career nurses with less than 10 years of nursing experience. The PPR-N is a reliable antecedent of work engagement, which is typical of early-career nurses. These results may be provided guidance for managers in overseeing the work environment to ensure a thriving sustainable nursing workforce.

Identifying sex-specific differences in the carotid revascularisation literature: findings from a scoping review.

OBJECTIVE: No systematic review of the literature has dedicated itself to looking at the management of symptomatic carotid stenosis in female patients. In this scoping review, we aimed to identify all randomised controlled trials (RCTs) that reported sex-specific outcomes for patients who underwent carotid revascularisation, and determine whether sufficient information is reported within these studies to assess short-term and long-term outcomes in female patients. DESIGN, SETTING AND PARTICIPANTS: We systematically searched Medline, Embase, Pubmed and Cochrane libraries for RCTs published between 1991 and 2020 that included female patients and compared either endarterectomy with stenting, or any revascularisation (endarterectomy or stenting) with medical therapy in patients with symptomatic high-grade (>50%) carotid stenosis. RESULTS: From 1537 references examined, 27 eligible studies were identified. Sex-specific outcomes were reported in 13 studies. Baseline patient characteristics of enrolled female patients were reported in 2 of those 13 studies. Common outcomes reported included stroke and death, however, there was significant heterogeneity in the reporting of both periprocedural and long-term outcomes. Sex-specific differences relating to the degree of stenosis and time from index event to treatment are largely limited to studies comparing endarterectomy to medical therapy. Adverse events were not reported by sex. CONCLUSIONS: Only half of the previously published RCTs and systematic reviews report sex-specific outcomes. Detailed analyses on the results of carotid artery intervention for female patients with symptomatic stenosis are limited.

Rationalisations for women-only randomised controlled trials in conditions that affect both sexes: a scoping review protocol.

INTRODUCTION: Women have historically been under-represented in randomised controlled trials (RCTs), including many landmark RCTs that established standards of care. In light of this fact, some modern researchers are calling for replication of earlier landmark trials with women only. This approach is ethically concerning, in that it would require some enrolled women to be deprived of treatments that are currently considered standard of care. OBJECTIVE: In an attempt to better understand the justification of a women-only approach to designing clinical trials, this study looks to systematically categorise the number of women-only RCTs for conditions that affect both men and women and the reasons given within the medical and philosophical literatures to perform them. METHODOLOGY: This scoping review of the literature will search, screen and select articles based on predetermined inclusion/exclusion criteria, after which a grounded theory approach will be used to synthesise the data. It is expected that there will be a variety of reasons given for why a women-only trial may be justified. Electronic databases that will be searched include MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Clinical Trials Register, Web of Science Proceedings, ClinicalTrials.gov, Philosopher's Index, Phil Papers, JSTOR, Periodicals Archive Online, Project MUSE and the National Reference Centre for Bioethics. SIGNIFICANCE: The scope of this study is to determine published rationales used to justify women-only randomised trials, both in the case of new trials and in the repetition of landmark trials. ETHICS AND DISSEMINATION: Research ethics board approval is not required for this study as there is no participant involvement. Results will be published as a stand-alone manuscript and will inform a larger project related to the ethics of a women-only RCT of carotid intervention for women with symptomatic high-grade carotid stenosis.

The productive mind: Creativity as a source of abstract mental representations.

Explanations of how the brain makes successful predictions should refer to abstracta. But, the mind/brain system is for more than prediction alone. Creativity also plays an important role in supply the mind/brain system with abstracta that serve a number of valuable ends over and above prediction.

Benefit of carotid revascularisation for women with symptomatic carotid stenosis: protocol for a systematic review.

INTRODUCTION: Carotid intervention in the form of endarterectomy or stenting is the current standard of care for the majority of patients with symptomatic high-grade carotid stenosis. However, some randomised controlled trials (RCT) have demonstrated that women benefited significantly less from intervention than men. It is unclear if this is a true phenomenon or a study sampling artefact, as women were severely under-represented in all RCTs of carotid revascularisation. A systematic review is needed to summarise the existing data and to answer the question of whether a women-only trial for symptomatic patients with ipsilateral carotid stenosis is scientifically necessary and ethically permissible. METHODS AND ANALYSIS: We will systematically search Medline, Embase, PubMed and the Cochrane libraries for all studies with data from RCTs that included women and compared either endarterectomy with stenting or revascularisation (by means of endarterectomy or stenting) with medical therapy in patients with symptomatic carotid stenosis. Search dates will be restricted to 1991-2018. Two reviewers will conduct screening search results, study selection, data extraction and quality assessment. We will include all studies reporting outcomes of interest. Planned subgroup analysis based on revascularisation technique, degree of stenosis and timing of intervention from the index event will be conducted with enough data. ETHICS AND DISSEMINATION: This research is exempt of ethics approval as no primary data will be collected. The results will be published in peer-reviewed journals and disseminated through national and international-level conferences and scientific meetings. The result of this comprehensive review will provide useful information on whether further RCTs are required to study a women-only population with symptomatic carotid disease. PROSPERO REGISTRATION NUMBER: CRD42019134967.

Protocol for a systematic scoping review of reasons given to justify the performance of randomised controlled trials.

INTRODUCTION: Randomised controlled trials (RCTs) are widely viewed to generate the most reliable medical knowledge. However, RCTs are not always scientifically necessary and therefore not always ethical. Unfortunately, it is not clear when an RCT is not necessary or how this should be established. This study seeks to systematically catalogue justifications offered throughout the medical and ethics literature for performing randomisation within clinical trials. METHODS AND ANALYSIS: We will systematically search electronic databases of the medical literature including MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Clinical Trials Register, Web of Science Proceedings, ClinicalTrials.gov; databases of philosophical literature including Philosopher's Index, Phil Papers, JSTOR, Periodicals Archive Online, Project MUSE, National Reference Centre for Bioethics; the library catalogue at the University of Ottawa; bibliographies of retrieved papers; and the grey literature. We will also pursue suggestions from experts in the fields of medical ethics, philosophy and clinical trial methodology. Article screening, selection and data extraction will be performed by two independent reviewers based on prespecified inclusion/exclusion criteria. A third reviewer will be consulted to resolve any discrepancies. We will then extract the reasons given to justify randomisation using methodology established to extract data in a defensible, systematic manner. We will track the reasons given, their frequency of use and changes over time. Finally, using grounded theory, we will combine the reasons into broader themes. These themes will form the foundation of our subsequent analysis from qualitative and quantitative perspectives. This review will map existing arguments that clinicians, ethicists and philosophers use to ethically justify randomisation in clinical trials. ETHICS AND DISSEMINATION: No research ethics board approval is necessary because we are not examining patient-level data. This protocol complies with the reported guidance for conducting systematic scoping reviews. The findings of this paper will be disseminated via presentations and academic publication. In a subsequent phase of this research, we hope to engage with stakeholders and translate any recommendations derived from our findings into operational guidelines.

Many randomized clinical trials may not be justified: a cross-sectional analysis of the ethics and science of randomized clinical trials.

OBJECTIVE: We have proposed that three scientific criteria are important for the ethical justification of randomized clinical trials (RCTs): (1) they should be designed around a clear hypothesis; (2) uncertainty should exist around that hypothesis; (3) that uncertainty should be as established through a systematic review. We hypothesized that the majority of a sample of recently published RCTs would not explicitly incorporate these criteria, therefore rendering them potentially unjustified on scientific grounds. STUDY DESIGN AND SETTING: Cross-sectional analysis of all RCTs published in the New England Journal of Medicine and the Journal of the American Medical Association in 2015. Each article and protocol was reviewed for: (1) a clearly stated central hypothesis; (2) references to "equipoise," or "consensus;" (3) some indication of evidentiary uncertainty; (4) a meta-analysis or systematic review surrounding the hypothesis or study question. RESULTS: We included 208 RCT articles and 199 protocols. Among combined articles and protocols, 76% had a clearly stated hypothesis, 99% referenced some form of uncertainty, and 54% cited a relevant systematic review or meta-analysis. Only 44% of combined texts contained all three scientific criteria. There were few references to "equipoise" (10%) or "consensus" (11%), and those references to equipoise were most often inconsistent with accepted definitions. CONCLUSION: The majority of RCTs (56%) did not meet the three scientific criteria described previously and therefore may be scientifically and therefore ethically unjustified. We recommend that "equipoise," "clinical equipoise," and "lack of consensus" be abandoned as scientific criteria for RCTs and be replaced by an expectation that RCTs have a clearly stated, meaningful hypothesis around which uncertainty has been established through a systematic review of the literature.