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)

This case describes an adolescent in a crisis of a chronic medical condition whose situation is complicated by substance abuse and mental illness. D. Micah Hester provides an analytic approach, teasing apart the multiple layers of medical, developmental, and moral issues at hand and describing possible responses and outcomes. Amy T. Campbell examines existing legal guidelines for adolescent decision making, arguing that greater space exists for clinical discretion in these matters than commonly thought. Cheryl D. Lew discusses the development (...) of agency in adolescent patients, the ideal of autonomous decision making in the context of impairment and chronic illness, and the obligation of healthcare teams to examine an adolescent patient’s decisions in relation to her identity. (shrink)

Nanomedicine is yielding new and improved treatments and diagnostics for a range of diseases and disorders. Nanomedicine applications incorporate materials and components with nanoscale dimensions where novel physiochemical properties emerge as a result of size-dependent phenomena and high surface-to-mass ratio. Nanotherapeutics and in vivo nanodiagnostics are a subset of nanomedicine products that enter the human body. These include drugs, biological products, implantable medical devices, and combination products that are designed to function in the body in ways unachievable at larger scales. (...) Nanotherapeutics andin vivonanodiagnostics incorporate materials that are engineered at the nanoscale to express novel properties that are medicinally useful. These nanomedicine applications can also contain nanomaterials that are biologically active, producing interactions that depend on biological triggers. Examples include nanoscale formulations of insoluble drugs to improve bioavailability and pharmacokinetics, drugs encapsulated in hollow nanoparticles with the ability to target and cross cellular and tissue membranes and to release their payload at a specific time or location, imaging agents that demonstrate novel optical properties to aid in locating micrometastases, and antimicrobial and drug-eluting components or coatings of implantable medical devices such as stents. (shrink)

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)

Book reviewed in this article: In That Case: Medical Ethics in Everyday Practice. By Alastair Campbell and Roger Higgs. Medical Genetics Casebook: A Clinical Introduction to Medical Ethics Systems Theory. By Colleen D. Clements. Cases in Bioethics from the Hastings Center Report. Edited by Carol Levine and Robert M. Veatch. Hastings‐on‐Hudson.

BackgroundAlthough patient advocates have developed templates for standard consent forms, evaluating patient preferences for first in human (FIH) and window of opportunity (Window) trial consent forms is critical due to their unique risks. FIH trials are the initial use of a novel compound in study participants. In contrast, Window trials give an investigational agent over a fixed duration to treatment naïve patients in the time between diagnosis and standard of care (SOC) surgery. Our goal was to determine the patient-preferred presentation (...) of important information in consent forms for these trials.MethodsThe study consisted of two phases: (1) analyses of oncology FIH and Window consents; (2) interviews of trial participants. FIH consent forms were analyzed for the location(s) of information stating that the study drug has not been tested in humans (FIH information); Window consents were analyzed for the location(s) of information stating the trial may delay SOC surgery (delay information). Participants were asked about their preferred placement of the information in their own trial’s consent form. The location of information in the consent forms was compared to the participants’ suggestions for placement. Results34 [17 FIH; 17 Window] of 42(81%) cancer patients approached participated. 25 consents [20 FIH; 5 Window] were analyzed. 19/20 FIH consent forms included FIH information, and 4/5 Window consent forms included delay information. 19/20(95%) FIH consent forms contained FIH information in the risks section 12/17(71%) patients preferred the same. Fourteen (82%) patients wanted FIH information in the purpose, but only 5(25%) consents mentioned it there. 9/17(53%) Window patients preferred delay information to be located early in the consent, before the “Risks” section. 3/5(60%) consents did this.ConclusionsDesigning consents that reflect patient preferences more accurately is essential for ethical informed consent; however, a one-size fits all approach will not accurately capture patient preferences. We found that preferences differed for FIH and Window trial consents, though for both, patients preferred key risk information early in the consent. Next steps include determining if FIH and Window consent templates improve understanding. (shrink)

Background Informed consent is an integral component of good medical practice. Many researchers have investigated measures to improve the quality of informed consent, but it is not clear which techniques work best and why. To address this problem, we propose developing a core outcome set to evaluate interventions designed to improve the consent process for surgery in adult patients with capacity. Part of this process involves reviewing existing research that has reported what is important to patients and doctors in the (...) informed consent process. Methods This qualitative synthesis comprises four phases: identification of published papers and determining their relevance; appraisal of the quality of the papers; identification and summary of the key findings from each paper while determining the definitiveness of each finding against the primary data; comparison of key themes between papers such that findings are linked across studies. Results Searches of bibliographic databases returned 11,073 titles. Of these, 16 studies met the inclusion criteria. Studies were published between 1996 and 2016 and included a total of 367 patients and 74 health care providers. Thirteen studies collected data using in-depth interviews and constant comparison was the most common means of qualitative analysis. A total of 94 findings were extracted from the primary papers and divided into 17 categories and ultimately 6 synthesised findings related to: patient characteristics, knowledge, communication, the model patient, trust and decision making. Conclusions This qualitative meta-aggregation is the first to examine the issue of informed consent for surgery. It has revealed several outcomes deemed important to capture by patients and clinicians when evaluating the quality of a consent process. Some of these outcomes have not been examined previously in research comparing methods for informed consent. This review is an important step in the development of a COS to evaluate interventions designed to improve the consent process for surgery. Registration The study protocol was registered on the international prospective register for systematic reviews. (shrink)

Editors of Pliny's Naturalis Historia have not had to deplore the paucity of the MS. tradition, but rather its value; while MSS. belonging to the ordo recentiorum are numerous and fairly complete, those of the ordo uetustiorum are very few, and never contain more than a few books, often with considerable gaps. They are A ii 196–vi 51, M xi–xv, P and H parts of xviii, I xxiii, xxv, B xxxii–xxxvii . There are also some scattered fragments. Detlefsen indeed claimed (...) that the restoration of the original text of the N.H. is more difficult than that of any other Latin author owing to the mutilated and defective transmission of considerable parts. (shrink)

Editors of Pliny's Naturalis Historia have not had to deplore the paucity of the MS. tradition, but rather its value; while MSS. belonging to the ordo recentiorum are numerous and fairly complete, those of the ordo uetustiorum are very few, and never contain more than a few books, often with considerable gaps. They are A ii 196–vi 51, M xi–xv, P and H parts of xviii, I xxiii, xxv, B xxxii–xxxvii. There are also some scattered fragments. Detlefsen indeed claimed that (...) the restoration of the original text of the N.H. is more difficult than that of any other Latin author owing to the mutilated and defective transmission of considerable parts. (shrink)

It may seem obvious that causing disability in another person is morally problematic in a way that removing or preventing a disability is not. This suggests that there is a moral asymmetry between causing disability and causing non-disability. This chapter investigates whether there are any differences between these two types of actions that might explain the existence of a general moral asymmetry. After setting aside the possibility that having a disability is almost always bad or harmful for a person (a (...) view that we have critiqued at length elsewhere), seven putative differences are considered. Ultimately, it is concluded that none of these seven factors can ground a general moral asymmetry between causing disability and causing non-disability, though each factor can provide some moral reason to avoid causing disability in certain particular cases. (shrink)

Using 94 published empirical articles in academic journals as a data base, this paper provides a critical review of the methodology employed in the study of ethical beliefs and behavior of organizational members. The review revealed that full methodological detail was provided in less than one half of the articles. Further, the majority of empirical research articles expressed no concern for the reliability or validity of measures, were characterized by low response rates, used convenience samples, and did not offer a (...) theoretic framework, hypotheses, or a definition of ethics. Several recommendations, including a reviewer rating form addressing methodological decisions and inclusion of methodologists on the review panel, are offered to improve methodological rigor in published ethics research. (shrink)

D. M. Armstrong is an eminent Australian philosopher whose work over many years has dealt with such subjects as: the nature of possibility, concepts of the particular and the general, causes and laws of nature, and the nature of human consciousness. This collection of essays explores the many facets of Armstrong's work, concentrating on his more recent interests. There are four sections to the book: possibility and identity, universals, laws and causality, and philosophy of mind. The contributors comprise an international (...) group of philosophers from the United States, England and Australia. An interesting feature of the volume is that Armstrong himself has written responses to each of the essays. There is also a complete bibliography of Armstrong's writings. (shrink)

Family involvement in healthcare decision-making for competent patients occurs to varying degrees in many communities around the world. There are different attitudes about who should make treatment decisions, how and why. Legal and professional ethics codes in most jurisdictions reflect and support the idea that competent patients should be enabled to make their own treatment decisions, even if others, including their healthcare professionals, disagree with them. This way of thinking contrasts with some cultural norms that put more emphasis on the (...) family as a decision-making entity, in some circumstances to the exclusion of a competent patient. Possible tensions may arise between various combinations of patient, family members and healthcare professionals, and healthcare professionals must tread a careful path in navigating family involvement in the decision-making process. These tensions may be about differences of opinion about which treatment option is best and/or on who should have a say or influence in the decision-making process. While some relevant cultural, legal and policy considerations vary from community to community, there are ethical issues that healthcare professionals need to grapple with in balancing the laws and professional codes on decision-making and the ethical principle of respecting patients and their autonomy. This paper will highlight and propose that a partial resolution to these issues may lie in relational understandings of autonomy, which in principle justify interventions by healthcare professionals and family that support patients in decision-making. (shrink)

Given an argumentation network we associate with it a modal formula representing the ‘logical content’ of the network. We show a one-to-one correspondence between all possible complete Caminada labellings of the network and all possible models of the formula.

Every quantum state can be represented as a probability distribution over the outcomes of an informationally complete measurement. But not all probability distributions correspond to quantum states. Quantum state space may thus be thought of as a restricted subset of all potentially available probabilities. A recent publication (Fuchs and Schack, arXiv:0906.2187v1, 2009) advocates such a representation using symmetric informationally complete (SIC) measurements. Building upon this work we study how this subset—quantum-state space—might be characterized. Our leading characteristic is that the inner (...) products of the probabilities are bounded, a simple condition with nontrivial consequences. To get quantum-state space something more detailed about the extreme points is needed. No definitive characterization is reached, but we see several new interesting features over those in Fuchs and Schack (arXiv:0906.2187v1, 2009), and all in conformity with quantum theory. (shrink)