Randomized controlled trial trial designs exist on an explanatory-pragmatic spectrum, depending on the degree to which a study aims to address a question of efficacy or effectiveness. As conceptualized by Schwartz and Lellouch in 1967, an explanatory approach to trial design emphasizes hypothesis testing about the mechanisms of action of treatments under ideal conditions, whereas a pragmatic approach emphasizes testing effectiveness of two or more available treatments in real-world conditions. Interest in, and the number of, pragmatic trials has grown substantially (...) in recent years, with increased recognition by funders and stakeholders worldwide of the need for credible evidence to inform clinical decision-making. This increase has been accompanied by the onset of learning healthcare systems, as well as an increasing focus on patient-oriented research. However, pragmatic trials have ethical challenges that have not yet been identified or adequately characterized. The present study aims to explore the views of key stakeholders with respect to ethical issues raised by the design and conduct of pragmatic trials. It is embedded within a large, four-year project that seeks to develop guidance for the ethical design and conduct of pragmatic trials. As a first step, this study will address important gaps in the current empirical literature with respect to identifying a comprehensive range of ethical issues arising from the design and conduct of pragmatic trials. By opening up a broad range of topics for consideration within our parallel ethical analysis, we will extend the current debate, which has largely emphasized issues of consent, to the range of ethical considerations that may flow from specific design choices. Semi-structured interviews with key stakeholders, across multiple jurisdictions, identified based on their known experience and/or expertise with pragmatic trials. We expect that the study outputs will be of interest to a wide range of knowledge users including trialists, ethicists, research ethics committees, journal editors, regulators, healthcare policymakers, research funders and patient groups. All publications will adhere to the Tri-Agency Open Access Policy on Publications. (shrink)

BackgroundRandomized controlled trials (RCTs) are often complex and expensive to perform. Less than one third achieve planned recruitment targets, follow-up can be labor-intensive, and many have limited real-world generalizability. Designs for RCTs conducted using cohorts and routinely collected health data, including registries, electronic health records, and administrative databases, have been proposed to address these challenges and are being rapidly adopted. These designs, however, are relatively recent innovations, and published RCT reports often do not describe important aspects of their methodology in (...) a standardized way. Our objective is to extend the Consolidated Standards of Reporting Trials (CONSORT) statement with a consensus-driven reporting guideline for RCTs using cohorts and routinely collected health data.MethodsThe development of this CONSORT extension will consist of five phases. Phase 1 (completed) consisted of the project launch, including fundraising, the establishment of a research team, and development of a conceptual framework. In phase 2, a systematic review will be performed to identify publications (1) that describe methods or reporting considerations for RCTs conducted using cohorts and routinely collected health data or (2) that are protocols or report results from such RCTs. An initial “long list” of possible modifications to CONSORT checklist items and possible new items for the reporting guideline will be generated based on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) and The REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) statements. Additional possible modifications and new items will be identified based on the results of the systematic review. Phase 3 will consist of a three-round Delphi exercise with methods and content experts to evaluate the “long list” and generate a “short list” of key items. In phase 4, these items will serve as the basis for an in-person consensus meeting to finalize a core set of items to be included in the reporting guideline and checklist. Phase 5 will involve drafting the checklist and elaboration-explanation documents, and dissemination and implementation of the guideline.DiscussionDevelopment of this CONSORT extension will contribute to more transparent reporting of RCTs conducted using cohorts and routinely collected health data. (shrink)

Placebo-controlled surgical trials can provide important information about the efficacy of surgical interventions. However, they are ethically contentious as placebo surgery entails the risk of harms to recipients, such as pain, scarring or anaesthetic misadventure. This has led to claims that placebo-controlled surgical trials are inherently unethical. On the other hand, without placebo-controlled surgical trials, it may be impossible to know whether an apparent benefit from surgery is due to the intervention itself or to the placebo effect.

To understand how children manage anger and engage in various forms of aggression, it is important to observe children responding to peer provocation. Observing children's anger and aggression poses serious ethical and practical challenges, especially with samples of older children and adolescents. This article describes 2 laboratory methods for observing children's responses to peer provocation: 1 involves participants playing a game with a provoking child actor, and the other involves a pair of close friends responding to an actor posing as (...) a difficult play partner. Both methods are described in detail, ethical safeguards are discussed, and evidence is presented to show that children understand their research rights in these types of investigations. (shrink)

Over 100 million Americans suffer from chronic pain, which causes more disability than any other medical condition in the United States at a cost of $560–$635 billion per year. Opioid analgesics are frequently used to treat CP. However, long term use of opioids can cause brain changes such as opioid-induced hyperalgesia that, over time, increase pain sensation. Also, opioids fail to treat complex psychological factors that worsen pain-related disability, including beliefs about and emotional responses to pain. Cognitive behavioral therapy can (...) be efficacious for CP. However, CBT generally does not focus on important factors needed for long-term functional improvement, including attainment of personal goals and the psychological flexibility to choose responses to pain. Acceptance and Commitment Therapy has been recognized as an effective, non-pharmacologic treatment for a variety of CP conditions. However, little is known about the neurologic mechanisms underlying ACT. We conducted an ACT intervention in women with chronic musculoskeletal pain. Functional magnetic resonance imaging data were collected pre- and post-ACT, and changes in functional connectivity were measured using Network-Based Statistics. Behavioral outcomes were measured using validated assessments such as the Acceptance and Action Questionnaire, the Chronic Pain Acceptance Questionnaire, the Center for Epidemiologic Studies Depression Scale, and the NIH Toolbox Neuro-QoLTM scales. Results suggest that, following the 4-week ACT intervention, participants exhibited reductions in brain activation within and between key networks including self-reflection, emotion, and cognitive control. These changes in connectivity strength were correlated with changes in behavioral outcomes including decreased depression and pain interference, and increased participation in social roles. This study is one of the first to demonstrate that improved function across the DMN, SN, and FPN may drive the positive outcomes associated with ACT. This study contributes to the emerging evidence supporting the use of neurophysiological indices to characterize treatment effects of alternative and complementary mind-body therapies. (shrink)

The controversies in Bristol, Alder Hey and elsewhere in the UK surrounding the removal and retention of human tissue and organs have led to extensive law reform in all three UK legal systems. This paper reports a short study of the reactions of a range of health professionals to these changes. Three main areas of ethical concern were noted: the balancing of individual rights and social benefit; the efficacy of the new procedures for consent; and the helpfulness for professional practice (...) of the new legislation and regulation. Recognition of these concerns may help in forging a new partnership between professionals and patients and their families. (shrink)

(No abstract is available for this citation).

The so-called Disability Paradox arises from the apparent tension between the popular view that disability leads to low well-being and the relatively high life-satisfaction reports of disabled people. Our aim in this essay is to make some progress toward dissolving this alleged paradox by exploring the relationship between disability and various “goods of life”—that is, components of a life that typically make a person’s life go better for her. We focus on four widely recognized goods of life (happiness, rewarding relationships, (...) knowledge, achievement) and four common types of disability (sensory, mobility, intellectual, and social) and systematically examine the extent to which the four disability types are in principle compatible with obtaining the four goods of life. Our findings suggest that that there is a high degree of compatibility. This undermines the widespread view that disabilities, by their very nature, substantially limit a person’s ability to access the goods of life, and it provides some guidance on how to dissolve the Disability Paradox. (shrink)

The increasing complexity of human subjects research and its oversight has prompted researchers, as well as institutional review boards, to have a forum in which to discuss challenging or novel ethical issues not fully addressed by regulations. Research ethics consultation services provide such a forum. In this article, we rely on the experiences of a national Research Ethics Consultation Collaborative that collected more than 350 research ethics consultations in a repository and published 18 challenging cases with accompanying ethical commentaries to (...) highlight four contexts in which REC can be a valuable resource. REC assists: 1) investigators before and after the regulatory review; 2) investigators, IRBs, and other research administrators facing challenging and novel ethical issues; 3) IRBs and investigators with the increasing challenges of informed consent and risk/benefit analysis; and 4) in providing flexible and collaborative assistance to overcome study hurdles, mediate conflicts within a team, or directly engage with research participants. Institutions that have established, or plan to establish, REC services should work to raise the visibility of their service and engage in open communication with existing clinical ethics consult services as well as the IRB. While the IRB system remains the foundation for the ethical review of research, REC can be a valuable service for investigators, regulators, and research participants aligned with the goal of supporting ethical research. (shrink)

Recently there has been a great deal of argument about what justifies references to representational states in explanations of behavior. I discuss Jerry Fodor's claim that it is necessary to ascribe representational states to organisms that respond to "nonnomic properties" of stimuli. Zenon Pylyshyn's (apparently equivalent) claim that it is necessary to ascribe representational states to organisms that respond to "nonprojectable properties" of stimuli and Fodor's claim that an organism's ability to respond to nonnomic properties of stimuli is a criterion (...) of its having representational states. I argue that if Fodor's account of how organisms respond to nonnomic properties of stimuli is correct, we could always replace explanations that appeal to nonnomic properties of stimuli with explanations that appeal only to nomic properties of stimuli. I also argue that, according to Fodor's account, we could not determine whether an organism is responding to nonnomic properties of stimuli unless we already knew whether the explanation of the response includes a reference to a representational state. Thus, given Fodor's account, there is no noncircular way of arguing that it is necessary to ascribe representational states to organisms because they respond to nonnomic properties of stimuli. Finally, I argue that Fodor has not actually provided an account of how organisms respond to nonnomic properties of stimuli and I discuss the prospects of a different strategy for linking the nonnomic properties of stimuli to representational states. (shrink)

Cognitive scientists routinely distinguish between controlled and automatic mental processes. Through learning, practice, and exposure, controlled processes can become automatic; however, whether automatic processes can become deautomatized – recuperated under the purview of control – remains unclear. Here we show that a suggestion derails a deeply ingrained process involving involuntary audiovisual integration. We compared the performance of highly versus less hypnotically suggestible individuals in a classic McGurk paradigm – a perceptual illusion task demonstrating the influence of visual facial movements on (...) auditory speech percepts. Following a posthypnotic suggestion to prioritize auditory input, HSIs but not LSIs manifested fewer illusory auditory perceptions and correctly identified more auditory percepts. Our findings demonstrate that a suggestion deautomatized a ballistic audiovisual process in HSIs. In addition to guiding our knowledge regarding theories and mechanisms of automaticity, the present findings pave the road to a more scientific understanding of top-down effects and multisensory integration. (shrink)

The recent Ebola outbreak in West Africa began in the spring of 2014 and has since caused the deaths of over 6,000 people. Since there are no approved treatments or prevention modalities specifically targeted at Ebola Virus Disease , debate has focused on whether unproven interventions should be offered to Ebola patients outside of clinical trials. Those engaged in the debate have responded rapidly to a complex and evolving crisis, however, and this debate has not provided much opportunity for in-depth (...) analysis. Additionally, the existing literature on access to unproven therapies has focused on contexts like HIV/AIDS and oncology, which are very different than the Ebola epidemic. In this paper, we examine the ethical issues surrounding access to unproven therapies in the context of the recent Ebola outbreak to yield new insights about this controversial and unsettled issue. We argue first that, in this context, the interests of patients in obtaining access to unproven therapies are not fully aligned.. (shrink)

In this comprehensive collection of essays, most of which appear for the first time, eminent scholars from many disciplines—philosophy, economics, sociology, political science, demography, theology, history, and social psychology—examine the causes, nature, and consequences of present-day consumption patterns in the United States and throughout the world.

Several philosophers have discussed informal versions of a "symmetry argument" that seems to show that two rational maximizers will cooperate when they are in a prisoner's dilemma. I present a more precise version of that argument and I argue that it is valid only if some crucial statements are misinterpreted as material conditionals instead of being interpreted correctly as subjunctive conditionals.

Using the Stroop paradigm, we have previously shown that a specific suggestion can remove or reduce involuntary conflict and alter information processing in highly suggestible individuals . In the present study, we carefully matched less suggestible individuals to HSIs on a number of factors. We hypothesized that suggestion would influence HSIs more than LSIs and reduce the Stroop effect in the former group. As well, we conducted secondary post hoc analyses to examine negative priming – the apparent disruption of the (...) response to a previously-ignored item. Our present findings indicate that suggestion reduces Stroop effects in HSIs. Secondary analyses show that LSIs had an NP effect at baseline and that suggestion influenced the NP condition. Thus, at least in this experimental context, suggestion seems to dampen a deeply-engrained and largely automatic process – reading – by wielding a larger influence on HSIs relative to comparable LSIs. (shrink)

Let me summarize the results of this paper in a way that seems fitting to Hume's discussion of the cosmological argument. There are some philosophers who adopt the most stringent empiricist principles. Such men and women would reject any notion of necessity that is not analytic, and for this reason they would never admit a proof of the necessary existence of anything. Other philosophers, though empiricists, are not so dogmatic. They question the need for, not the coherence of, necessary existence. (...) They believe that the material universe is nothing over and above the sum of its material parts and, thus, see no reason to conclude that a necessary being exists based on PSR. Still others are driven by a rationalist persuasion. They would gladly recognize the existence of almost anything provided it be proven by reason and argument. When they confront the cosmological argument they do indeed find it compelling but still see no reason to conclude that God, or any transcendent being, necessarily exists. The entity established need be nothing more than the universe itself. Therefore, as Hume has demonstrated, no philosopher need accept the conclusion of the cosmological argument. (shrink)

There are a limited number of neuroimaging investigations into motor control of the lumbopelvic musculature. Most investigation examining motor control of the lumbopelvic musculature utilize transcranial magnetic stimulation and focus primarily on the motor cortex. This has resulted in a dearth of knowledge as it relates to how other regions of the brain activate during lumbopelvic movement. Additionally, task-based functional connectivity during lumbopelvic movements has not been well elucidated. Therefore, we used functional magnetic resonance imaging to examine brain activation and (...) ROI-to-ROI task-based functional connectivity in 19 healthy individuals during the performance of three lumbopelvic movements: modified bilateral bridge, left unilateral bridge, and right unilateral bridge. The whole brain analysis found robust, bilateral activation within the motor regions of the brain during the bilateral bridge task, and contralateral activation of the motor regions during unilateral bridging tasks. Furthermore, the ROI-to-ROI analysis demonstrated significant connectivity of a motor network that included the supplemental motor area, bilateral precentral gyrus, and bilateral cerebellum regardless of the motor task performed. These data suggest that while whole brain activation reveals unique patterns of activation across the three tasks, functional connectivity is very similar. As motor control of the lumbopelvic area is of high interest to those studying low back pain, this study can provide a comparison for future research into potential connectivity changes that occur in individuals with LBP. (shrink)