This study addresses the current lack of empirical data on the experiences and attitudes of clinical research professionals towards AI-powered clinical trial management tools. Clinical research professionals affiliated with various Swiss and international clinical research networks were invited to participate in an online survey. The survey focused on nine use cases of AI-powered clinical trial management tools. Participants were asked to share their ethical considerations, and their experiences were assessed at both (...) the individual and institutional levels. Answers from 110 participants, primarily from Swiss academic institutions, were included in the data analysis. While participants generally held positive attitudes, mixed views were also common. Governmental attitudes were widely perceived as unclear or cautious, with the associated regulatory opacity possibly contributing to the limited adoption of AI in trial management observed in this study. In addition to a clear AI governance, ethical compliance and training emerged as crucial aspects. There was also broad consensus on the necessity of informing patients about tools’ uses and of ensuring an independent certification of the respective tools. The widespread adoption of AI-powered clinical trial management tools remains distant, entangled in a net of complexities that require further empirical investigation. Ethical concerns appear to play a crucial role, driven by distrust and the absence of a clear regulatory framework. Urgent actions are needed at both institutional and governmental levels, including the establishment of a governance framework and training provision. (shrink)

Pragmatic clinical trials offer important benefits, such as generating evidence that is suited to inform real-world health care decisions and increasing research efficiency. However, PCTs also present ethical challenges. One such challenge involves the management of information that emerges in a PCT that is unrelated to the primary research question, yet may have implications for the individual patients, clinicians, or health care systems from whom or within which research data were collected. We term these findings as?pragmatic clinical (...) trial collateral findings,? or?PCT-CFs?. In this article, we explore the ethical considerations associated with the identification, assessment, and management of PCT-CFs, and how these considerations may vary based upon the attributes of a specific PCT. Our purpose is to map the terrain of PCT-CFs to serve as a foundation for future scholarship as well as policy-making and to facilitate careful deliberation about actual cases as they occur in practice. (shrink)

Research and clinical trial development for rare diseases pose unique bioethical challenges. Much of the literature on rare diseases focuses on patient advocacy and drug development to manage or cu...

Diabetes self-management is a crucial part in the management of diabetic patients. Most randomized controlled clinical trials reported significant benefits by diabetes self-management education on DSM behaviors and metabolic control. Although the randomized clinical trials are the gold standard method in assessing the effectiveness of any intervention, including DSME interventions, the outcomes of these studies may reflect exaggerated effects; because in most of these studies, subjects in control group receive usual care with no any DSME. (...) The lack of such education in the control group had many drawbacks: make blindness impossible; at which non blinded studies may result in false-positive findings; it may be unethical to recruit patients for participation in DSME studies as control subjects, most of these studies with long periods of follow up, without any direct benefit to them during the study period; the lack of direct benefit to control subjects in any clinical trial may results in high attrition rate. The high attrition rate in clinical trials especially in the control group can lower the statistical power of the study results; thus, the DSME program would appear to have positive effects even if the program had no real benefit. This problem of the DSME exaggerated effects can be solved partially through providing control subjects with education about some DSM behaviors or comparing the effect of DSME through different educational approaches. (shrink)

BackgroundInternational guidelines recommend ethical and scientific quality standards for managing and reporting adverse events occurring during clinical trials to competent research ethics committees and regulatory authorities. The purpose of this study was to determine whether clinical trial protocols in Cameroon are developed in line with national requirements and international guidelines as far as detecting, reporting and investigating of adverse events is concerned.MethodsIt was a documentary review of all approved clinical trial protocols that were submitted at (...) the Cameroon National Ethics Committee for evaluation from 1997 through 2012. Data were extracted using a preconceived and validated grid. Protocol review process targeted the title, abstract, objectives, methodology, resources, and the chapter on safety.ResultsIn total, 106 clinical trial protocols were identified from 2173 protocols seen in the archive and 104 included for review. Seventy six trials did not include the surveillance of adverse events as part of their objective. A total of 91 protocols did not budget for adverse event surveillance, 76 did not have a data safety management board, 11 included insurance for participants, 47 did not include a case definition for serious adverse events, 33 described procedures to detect adverse events, 33 described procedure for reporting and 22 described procedure for investigating adverse events.DiscussionsMost clinical trial protocols in Cameroon are developed to focus on benefits and pay little attention to harms. The development of national guidelines can improve the surveillance of adverse events in clinical trial research conducted in Cameroon. Adverse events surveillance tools and a budget are critical for an adequate planning for adverse event surveillance when developing trial protocols.ConclusionClinical trial protocols submitted in the Cameroon National Ethics Committee do not adequately plan to assess adverse events in clinical trial protocols. In order to improve on the safety of participants and marketed drug, there is a need to develop national guidelines for clinical trials by the government, and to improve evaluation procedures and monitoring of ongoing trials by the ethics committee. (shrink)

BackgroundClinical trials should be as inclusive as possible to facilitate equitable access to research and better reflect the population towards which any intervention is aimed. Informed by the UK’s National Institute for Health and Care Research (NIHR) Innovations in Clinical Trial Design and Delivery for the Under-served (INCLUDE) guidance, we audited oncology trials conducted by the Clinical Trials and Statistics Unit at The Institute of Cancer Research, London (ICR-CTSU) to identify whether essential documents were overtly excluding any (...) groups and whether sufficient data were collected to assess diversity of trial participants from groups suggested by INCLUDE as under-served by research in the UK.MethodsThirty cancer clinical trials managed by ICR-CTSU and approved between 2011–2021 were audited. The first ethics approved version of each trial’s protocol, patient information sheet, and patient completed questionnaire, together with the first case report forms (CRFs) version were reviewed. A range of items aligned with the INCLUDE under-served groups were assessed, including age, sex and gender, socio-economic and health factors. The scope did not cover trial processes in participating hospitals.ResultsData relating to participants’ age, ethnic group and health status were well collected and no upper age limit was specified in any trials’ eligibility criteria. 23/30 (77%) information sheets used at least one gendered term to address patients. Most CRFs did not specify whether they were collecting sex or gender and only included male or female categories. The median reading age for information sheets was 15–16 years (IQR: 14–15 – 16–17). Socio-economic factors were not routinely collected and not commonly mentioned in trial protocols.ConclusionsNo systemic issues were identified in protocols which would explicitly prevent any under-served group from participating. Areas for improvement include reducing use of gendered words and improving readability of patient information. The challenge of fully assessing adequate inclusion of under-served populations remains, as socio-economic factors are not routinely collected because they fall beyond the data generally required for protocol-specified trial endpoint assessments. This audit has highlighted the need to agree and standardise demographic data collection to permit adequate monitoring of the under-served groups identified by the NIHR. (shrink)

BackgroundCommunity Advisory Boards (CAB) have become essential organs of involving communities in HIV clinical trials especially in developing countries. However, limited empirical evidence exists on the role of CABs in low and middle-income countries including Tanzania. This study aims at exploring the role of CABs in community-based HIV clinical trials conducted in Tanzania.MethodologyWe adopted a phenomenological approach to purposefully select HIV clinical trial stakeholders. These included CAB members, researchers and Institutional Review Board (IRB) members in Tanzania. (...) We conducted In-depth Interviews (IDIs) with ten participants and three Focus Group Discussions (FGDs) with eighteen participants. The data were thematically analyzed with the aid of MAXQDA software version 20.2.1.ResultsThe findings indicate that at every stage of implementation of a community-based HIV clinical trial, a functioning CAB is important for its success. This importance is based on contextualization of the informed consent process and protocol, managing rumours in the community, weighing trial risks and benefits, sensitizing the community, assisting participant recruitment, tracing and retention. However, being perceived as financial beneficiaries than community representatives emerged as a challenge to CAB members. ConclusionThe study empirically indicates the need for functioning CABs in every stage of implementation of community-based HIV clinical trials. The roles of which are interwoven in serving research goals and protecting the interests of the community and that of trial participants. (shrink)

To address the burden of maternal morbidity and mortality in low‐ and middle‐income countries (LMICs), research with pregnant women in these settings is increasingly common. Pregnant women in LMIC‐context may experience vulnerability related to giving consent to participate in a clinical trial. To recognize possible layers of vulnerability this study aims to identify factors that influence the decision process towards clinical trial participation of pregnant women in an urban middle‐income setting. This qualitative research used participant observation, (...) in‐depth interviews, and focus group discussion with medical staff and pregnant women eligible for trial participation, at a regional hospital in Accra, Ghana. Besides lack of familiarity with modern scientific concepts, specific factors influencing the decision‐making process were identified. These include a wide power difference between health provider and patient, and a different perception of risk through externalization of responsibility of risk management within a religious context as well as a context shaped by authority. Also, therapeutic misconception was observed. The combination of these factors ensued women to rely on the opinion of the medical professional, rather than being guided by their own motivation to participation. Although being a (pregnant) woman per se should not render the label of being vulnerable, this study shows there are factors that influence the decision process of pregnant woman towards trial participation in a LMIC context that can result in vulnerability. The identification of context‐specific factors that can create vulnerability facilitates adaptation of the design and conduct of research in a culturally competent manner. (shrink)

ABSTRACT The aim of this study is to determine how stakeholder engagement can be adapted for the conduct of COVID‐19‐related clinical trials in sub‐Saharan Africa. Nine essential stakeholder engagement practices were reviewed: formative research; stakeholder engagement plan; communications and issues management plan; protocol development; informed consent process; standard of prevention for vaccine research and standard of care for treatment research; policies on trial‐related physical, psychological, financial, and/or social harms; trial accrual, follow‐up, exit trial closure and (...) results dissemination; and post‐trial access to trial products or procedures. The norms, values, and practices of collectivist societies in Sub‐Saharan Africa and the low research literacy pose challenges to the conduct of clinical trials. Civil‐society organizations, members of community advisory boards and ethics committees, young persons, COVID‐19 survivors, researchers, government, and the private sector are assets for the implementation and translation of COVID‐19 related clinical trials. Adapting ethics guidelines to the socio‐cultural context of the region can facilitate achieving the aim of stakeholder engagement. (shrink)

BackgroundThe coronavirus disease (COVID-19) treatment must be based on scientific methods such as clinical trials. Trials involving human subjects and those requiring a risk-benefit analysis may occasionally face challenges owing to the time limitations in the pandemic. MethodologyThis study analyses the WHO's International Clinical Trials Registry Platform and clinicaltrials.gov, where most COVID-19 clinical trials are registered, according to ethical criteria including study design, conflicts of interest, enrollment of healthcare workers, study locations, site-, design-, and participant-related issues. The (...) discussion is based on three aspects: the quality of the information to be produced, the relevance to significant health problems, and the creation or evaluation of interventions, policies, or practices that promote individual or public health. ResultsThere were significant differences between the two platforms regarding the investigational medicinal product (IMP), the comparator, ethics committee/institutional review board approval, plan to share individual participant data, study phase, site, IMP, and design-related issues. Conflict of interest, sponsor information, and management of vulnerable groups were the main areas wherein both platforms lacked sufficient information. ConclusionWith this analysis, we aimed to define a minimum set of ethical criteria for clinical trial platforms to obtain standardization between these two platforms. (shrink)

This article explores some implications of the increasing reliance on clinical trials in contemporary health care, particularly health care payers’ efforts to use them in the so-called fourth hurdle decisions. How do these agencies manage medical uncertainty given the desire to produce clear guidelines for clinicians? Their solutions take account of trials in at least two ways, reflecting broader debates about the meaning of these medical experiments. Trials can be read as either ‘‘proofs of protocol’’—straightforward guides to action with (...) individual drugs in specific populations—or ‘‘proofs of principle’’— where extrapolation is made possible through an appeal to underlying biological mechanisms. These contrasting readings of trials are illustrated with reference to guidelines on heart disease prevention/cholesterol reduction using statins among the elderly in North America and the United Kingdom. Uncertainty in these cases does not lead to inertia but solutions use different fixed points to aid navigation, including both physiological principles and moral values. (shrink)

Patients have received experimental pharmaceuticals outside of clinical trials for decades. There are no industry-wide best practices, and many companies that have granted compassionate use, or ‘preapproval’, access to their investigational products have done so without fanfare and without divulging the process or grounds on which decisions were made. The number of compassionate use requests has increased over time. Driving the demand are new treatments for serious unmet medical needs; patient advocacy groups pressing for access to emerging treatments; internet (...) platforms enabling broad awareness of compelling cases or novel drugs and a lack of trust among some that the pharmaceutical industry and/or the FDA have patients’ best interests in mind. High-profile cases in the media have highlighted the gap between patient expectations for compassionate use and company utilisation of fair processes to adjudicate requests. With many pharmaceutical manufacturers, patient groups, healthcare providers and policy analysts unhappy with the inequities of the status quo, fairer and more ethical management of compassionate use requests was needed. This paper reports on a novel collaboration between a pharmaceutical company and an academic medical ethics department that led to the formation of the Compassionate Use Advisory Committee. Comprising medical experts, bioethicists and patient representatives, CompAC established an ethical framework for the allocation of a scarce investigational oncology agent to single patients requesting non-trial access. This is the first account of how the committee was formed and how it built an ethical framework and put it into practice. (shrink)

ObjectiveTo confirm the effects of a transtheoretical model based on multidimensional life management on healthy behavior in patients with polycystic ovary syndrome.MethodsIn total, eighty eligible patients were recruited from March 2021 to June 2021 and randomly assigned to either the intervention or control groups. Outcome measures include health-promoting behavior, self-efficacy, anthropometrics, and the number of unplanned outpatient admissions. Data were collected at baseline, 3, and 6 months after the intervention. The chi-square test, rank-sum test, t-test, and repeated measurement analysis (...) of variance were used to analyze the data.ResultsIn total, sixty-six participants completed the study: 35 participants in the intervention group and 31 participants in the control group. After 6 months of intervention, the healthy behavior level of patients with PCOS increased from moderate [health-promoting lifestyle profile -II score of 105.37 ± 12.57] to good in the intervention group; and there was no change observed in the control group. In addition, the total self-efficacy score, PCOS-related unplanned outpatient admissions, waist circumference, and body mass index were found to have a significant difference in the intervention group at 6 months. Meanwhile, repeated measures analysis of variance showed a significantly greater improvement in health-promoting behavior and self-efficacy over time in the intervention group than in the control group.ConclusionThe transtheoretical model based on multidimensional life management positively affected healthy behavior, self-efficacy, the number of unplanned outpatient admissions, and anthropometrics in patients with PCOS.Clinical Trial Registrationwww.chictr.org.cn, ChiCTR2000034572. (shrink)

Increasing ethical attention and debate is focusing on whether individuals who take part in clinical trials should be given access to post-trial care. However, the main focus of this debate has been upon drug trials undertaken in low-income settings. To broaden this debate, we report findings from interviews with individuals (n = 24) who participated in a clinical trial of a closed-loop system, which is a medical device under development for people with type 1 diabetes that (...) automatically adjusts blood glucose to help keep it within clinically recommended ranges. Individuals were recruited from UK sites and interviewed following trial close-out, at which point the closed-loop had been withdrawn. While individuals were stoical and accepting of the requirement to return the closed-loop, they also conveyed varying degrees of distress. Many described having relaxed diabetes management practices while using the closed-loop and having become deskilled as a consequence, which made reverting back to pre-trial regimens challenging. Participants also described unanticipated consequences arising from using a closed-loop. As well as deskilling, these included experiencing psychological and emotional benefits that could not be sustained after the closed-loop had been withdrawn and participants reevaluating their pre- and post-trial life in light of having used a closed-loop and now perceiving this life much more negatively. Participants also voiced frustrations about experiencing better blood glucose control using a closed-loop and then having to revert to using what they now saw as antiquated and imprecise self-management tools. We use these findings to argue that ethical debates about post-trial provisioning need to be broadened to consider potential psychological and emotional harms, and not just clinical harms, that may result from withdrawal of investigated treatments. We also suggest that individuals may benefit from information about potential nonclinical harms to help make informed decisions about trial participation. (shrink)

This article focuses on maternal-fetal surgery (MFS) and on the concept of clinical equipoise that is a widely accepted requirement for conducting randomized controlled trials (RCT). There are at least three reasons why equipoise is unsuitable for MFS. First, the concept is based on a misconception about the nature of clinical research and the status of research subjects. Second, given that it is not clear who the research subject/s in MFS is/are, if clinical equipoise is to be (...) used as a criterion to test the ethical appropriateness of RCT, its meaning should be unambiguous. Third, because of the multidisciplinary character of MFS, it is not clear who should be in equipoise. As a result, we lack an adequate criterion for the ethical review of MFS protocols. In our account, which is based on Chervenak and McCullough's seminal work in the field of obstetric ethics, equipoise is abandoned. and RCT involving MFS can be ethically initiated when a multidisciplinary ethics review board (ERB), having an evidence-based assessment of the risks involved, is convinced that the value of answering the research hypothesis, for the sake of the health interests of future pregnant women carrying fetuses with certain congenital birth defects, justifies the actual risks research participants might suffer within a set limit of low/manageable. (shrink)

Anecdotes have shown that some articles on profitable drugs are constructed by and shepherded through publication by pharmaceutical companies and their agents, whose influence is largely invisible to readers. This is ghost-management, the substantial but unrecognized research, analysis, writing, editing and/or facilitation behind publication. Publicly available documents suggest that these practices extremely widespread affecting up to 40% of clinical trial reports in key periods but it has been unclear how representative these documents are. This article presents the (...) results of an investigative sampling of the self-presentation of publication planning services, and presents this and other evidence of a sizable publication planning industry. Thus different lines of evidence indicate that ghost-management is a common and important phenomenon, strongly affecting the published medical literature in the service of marketing. (shrink)

Background Ethical decision‑making and behavior of nurses are major factors that can affect the quality of nursing care. Moral development of nurses to making better ethical decision-making is an essential element for managing the care process. The main aim of this study was to examine and comparison the effect of training in ethical decision-making through lectures and group discussions on nurses’ moral reasoning, moral distress and moral sensitivity. Methods In this randomized clinical trial study with a pre- and (...) post-test design, 66 nurses with moral reasoning scores lower than the average of the community were randomly assigned into three equal groups (n = 22) including two experimental groups and one control group. Ethical decision-making training to experimental groups was provided through the lectures and group discussions. While, the control group did not receive any training. Data were collected using sociodemographic questionnaire, the nursing dilemma test (NDT), the moral distress scale (MDS) and the moral sensitivity questionnaire (MSQ). Unadjusted and adjusted binary logistic regression analysis was reported using the odds ratio (OR) and 95% confidence intervals. Results Adjusted regression analysis showed that the probability of increasing the nursing principle thinking (NPT) score through discussion training was significantly higher than lecture (OR: 13.078, 95% CI: 3.238–15.954, P = 0.008), as well as lecture (OR: 14.329, 95% CI: 16.171–2.005, P < 0.001) and discussion groups compared to the control group (OR: 18.01, 95% CI: 22.15–5.834, P < 0.001). The possibility of increasing moral sensitivity score through discussion training was significantly higher than lecture (OR: 10.874, 95%CI: 6.043–12.886, P = 0.005) and control group (OR: 13.077, 95%CI: 8.454–16.774, P = 0.002). Moreover, the moral distress score was significantly reduced only in the trained group compared to the control, and no significant difference was observed between the experimental groups; lecture group vs. control group (OR: 0.105, 95% CI: 0.015–0.717, P = 0.021) and discussion group vs. control group (OR: 0.089, 95% CI: 0.015–0.547, P = 0.009). Conclusions The results of this study indicate that ethical decision-making training is effective on empowerment of ethical reasoning. Whereas the group discussion was also effective on increasing the ethical sensitivity, it is recommended the training plan provided in this study to be held as workshop for all nurses in health and treatment centers and placed in curricular plan of nursing students. Registration This randomized clinical trial was registered in Iranian Registry of Clinical Trials under code (IRCT2015122116163N5) in 02/07/2016. (shrink)

Seemingly distant practices of molecular biology and indigenous Xhosa healing have commonalities that I would like to bring into conversation in this article. The preclinical trial of an indigenous medicine brings them together in a research consortium. In this instance, both sets of experts are meant to collaborate in preparing a wild bush for it to pass the tests of the randomized clinical trial (RCT) and to potentially become a biopharmaceutical to counter the tuberculosis pandemic. I aim (...) to tease out how the two sets of actors and their respective practices converge and diverge in their healing hopes and ways of managing uncertainty. Ultimately, I am interested in understanding how the preferred process of making medicine “work” by each set of actors relies upon particular ways of knowing and not knowing life, bringing some ontologies into being, letting others wither away. The shared ways of knowing life as a movement of opening at the edges of the RCT are proposed as paths of recognition between one and the other practice. (shrink)

Current management of people with prolonged disorders of consciousness is failing patients, families and society. The causes include a general lack of concern, knowledge and expertise; a legal and professional framework which impedes timely and appropriate decision-making and/or enactment of the decision; and the exclusive focus on the patient, with no legitimate means to consider the broader consequences of healthcare decisions. This article argues that a clinical pathway based on the principles of the English Mental Capacity Act 2005 (...) and using time-limited treatment trials could greatly improve patient management and reduce stress on families. There needs to be early and continuing use of formal best interests meetings, starting between 7 and 21 days after onset of unconsciousness. The treatment options need to evolve as the clinical state and prognosis becomes more certain. A formal discussion of treatment withdrawal should occur when the upper bound of predicted recovery falls below a level the patient would have considered acceptable, and it should always be discussed when the condition is considered permanent. Any decision to stop treatment should be contingent on a formal second opinion from an independent expert who should review the clinical situation and expected prognosis, but not the best interests decision. The article also asks how, if at all, the adverse effects on the family and the resource implications of long-term care of people left in a prolonged state of unconsciousness should be incorporated in the process. (shrink)

BackgroundThe prevention of HIV remains an ongoing global concern. The safety and welfare of participants in these trials are imperative. Research Ethics Committees (RECs) review all reports of serious adverse events, adverse events and social harms arising in the course of such trials. There is little guidance for RECs on how to respond appropriately to social harm reports.MethodologyThis paper reviews the literature on social harms in HIV prevention trials and offers suggestions for RECs on how to respond appropriately to such (...) reports.ResultsThis review confirms that social harms are reported in clinical trials in South Africa and that specific guidance on managing these is minimal.ConclusionSocial harms in South African HIV prevention trials need to be more systematically researched so that ethical evidence‐based prevention, care and treatment strategies can be developed. This review makes specific suggestions for further research on social harms that can inform further consultations to develop more specific guidance for stakeholders on appropriate responses to such social harms. Such future work may also inform future versions of relevant local and international ethics guidance on HIV prevention trials. (shrink)

Over the past decade, the management of clinical trials of pharmaceuticals has become a veritable industry, as evidenced by the emergence and proliferation of contract research organizations (CROs) that co‐ordinate and monitor trials. This article focuses on work performed by one CRO involved in the introduction of new software, modelled on industrial production processes, into clinical trial practices. It investigates how this new management technique relates to the work performed in the clinic to ensure that (...) trial participants comply with the protocol. Using an analytical distinction between ‘classical’ management work and invisible work, the article contextualizes the meaning of compliance in the clinic and suggests that the work involved in producing compliance should be taken into consideration by those concerned with validity of trials, as clinical trials are put under private industrial management. The article builds on participant observation at a Swedish university hospital and interviews the nurses, dieticians, doctors and a software engineer, all part of a team involved in pharmaceutical drug trials on a potential obesity drug. (shrink)

Purpose We examine the levels of post-trial responsibility ascribed to different stakeholders, following a community-based clinical trial and how the ‘responsibility’ is understood. Methods We employed photovoice, unstructured observations and key informant interviews to gain insights into contexts of access to care following transition to the public health system post trial. We used an inductive narrative analysis to explore experiences and understandings of post-trial access. Results In their photovoice stories, many participants expressed a sense of (...) abandonment after the trial. This was viewed as a contributing factor to failing to re-engage with care available in the public health system. This led to the experiences of loss as some trial participants defaulted and died. Research investigators, department of health participants and sponsor agreed that PTA was especially important for communities in resource-limited settings. The government has an obligation towards its citizens while researchers have a responsibility to ensure a smooth transition of patients to public clinics. Sponsors have a responsibility to ensure that the trial is conducted in accordance with the protocol and post-trial agreements are in place and adhered to. Research partnerships among stakeholders were affected by power imbalances making it difficult to negotiate and plan for post-trial care responsibilities. Conclusions The research community still struggles with understanding the scope of PTA responsibilities. Power dynamics between public health actors and research sponsors need to be managed to ensure that government involvement is not tokenistic. The responsibility of trial participants and ethics committees needs to be investigated further. Data are available upon request. (shrink)

The Ebola epidemic that broke out inWest Africa West AfricaAfrica towards the end of 2013 had been brought under reasonable control by 2015. The epidemic had severely affected three countries. This case study is about a phase I/II clinical trial Phase I/II clinical trial of a candidate Ebola virus vaccine in 2015 in a sub-Saharan AfricanSub-Saharan Africa country which had not registered any cases of the Ebola virus disease. The study was designed as a randomized double-blinded (...) trialRandomized double blinded trial. It was sponsored and funded by one of the biggest Northern multinational pharmaceutical companiesPharmaceutical companies. The protocol received ethics clearance from the relevantNational Ethics Committee national ethics committeeEthics committee. The study was coordinated and managed at the local branch of a big Northern diagnostic laboratoryDiagnostic laboratory and a laboratory of a local regional hospital. The overall study was a multi-countryMulti-country, multi-siteMulti-site trial aimed at recruiting a total of 3,000 research participantsResearch participants across four or five sub-Saharan African countries. For this country, the recruitmentRecruitment sites were two big cities, each aiming to recruit 200 participants: adults at the first site and childrenChildren at the second. The target sampleSample size was almost achieved at the first site but, before the study commenced at the second site, some members of raised the alarm that the governmentGovernment was carelessly risking the health, safetySafety and lives of citizens in the cause of an unproven vaccine that could precipitate a public health disaster. The trial was immediately suspended. A commentary on this case, and on the importance of trustTrust, is provided by Katharine Browne and Doris Schroeder at the end of this chapter. It highlights differences between this case and a phase I Ebola vaccine trial in CanadaCanada in 2014. (shrink)

Despite their crucial role in the translation of pre-clinical research into new clinical applications, phase 1 trials involving patients continue to prompt ethical debate. At the heart of the controversy is the question of whether risks of administering experimental drugs are therapeutically justified. We suggest that prior attempts to address this question have been muddled, in part because it cannot be answered adequately without first attending to the way labor is divided in managing risk in clinical trials. (...) In what follows, we approach the question of therapeutic justification for phase 1 trials from the viewpoint of five different stakeholders: the drug regulatory authority, the IRB, the clinical investigator, the referring physician, and the patient. Our analysis shows that the question of therapeutic justification actually raises multiple questions corresponding to the roles and responsibilities of the different stakeholders involved. By attending to these contextual differences, we provide more coherent guidance for the ethical negotiation of risk in phase 1 trials involving patients. We close by discussing the implications of our argument for various perennial controversies in phase 1 trial practice. (shrink)

The Brazilian Federal Senate created a Parliamentary Inquiry Commission (CPI) to investigate the Bolsonaro government's irregularities in the management of the COVID-19 pandemic. One of the cases that drew attention was the research conducted by Prevent Senior, a private health insurance company, on the early treatment of COVID-19. The article analyzes the scientific validity of the research and the ethical problems related to its implementation. It is based on analysis of Prevent Senior's report of the clinical study, the (...) Brazilian and USA clinical trial registries, the Senate's CPI report, and on the information reported by the media. This case of scientific fraud and political-ideological bias exemplifies how Prevent Senior, using a questionable protocol to enhance its reputation and gain government support, was instrumental in building the “early treatment” narrative for COVID-19, and shows how it served as a basis for a government public policy that promoted the use of ineffective drugs. (shrink)

: As clinicians, researchers, bioethicists, and members of society, we face a number of moral dilemmas concerning randomized clinical trials. How we manage the starting and stopping of such trials—how we conceptualize what evidence is sufficient for these decisions—has implications for both our obligations to trial participants and for the nature and security of the resultant medical knowledge. One view of how this is to be done, "clinical equipoise," recently has been given an extended defense by Paul (...) Miller and Charles Weijer in their article "Rehabilitating Equipoise." The present paper critiques this position and Miller and Weijer's defense of it. I argue that their attempted rehabilitation fails. Their analysis suffers from a number of confusions, as well as a failure to make crucial distinctions, adequately to clarify key concepts, or to think through exactly what needs to be established to justify their claim. We are left with little reason to uphold the clinical equipoise criterion. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Informed Consent and Clinical ResearchRuth Faden (bio)Informed consent is a powerful symbol of the commitment and impact of the new, interdisciplinary field of biomedical ethics that the Kennedy Institute has been so instrumental in developing. In the early years of biomedical ethics, there was considerable discussion about the nature of the doctor-patient relationship, about how it ought to be structured, and about how competing values within that relationship (...) ought to be accommodated. By the 1970s and 1980s, the answer was for all practical purposes in. Biomedical ethics was engaged in a clearly reformist project, in step with the values of the times, to right a wrongful imbalance of power and control between physicians and patients.The agenda was clear—to establish the moral authority of the patient to participate in medical decision making by placing respect for the autonomy of patients on the moral map of the medical community. The chief strategy that biomedical ethics adopted to accomplish this agenda was, of course, informed consent. Theories of autonomous action as well as informed consent were intentionally crafted to advance this reformist agenda.In this paper, I examine how the theory of informed consent has fared in one particular realm of “the clinic” where, arguably, there has been considerable success. This is the realm of clinical research; research at the bedside where the patient is also the subject.I rely heavily on the work of President Clinton’s Advisory Committee on Human Radiation Experiments, which I chaired. The Advisory Committee was established in response to exposés in the press about alleged secret experiments during World War II and the Cold War in which patients had been injected with plutonium without their apparent knowledge or consent. As part of its work, the Advisory Committee undertook an oral history project in which we interviewed eminent physicians about the norms and practices of human research in the 1940s and 1950s.Drawing on these interviews, I argue here for two seemingly inconsistent conclusions. First, that the ethical standards for clinical research have changed dramatically in the last 50 years—particularly with respect to informed consent. Second, that despite these important changes, the human dynamics of clinical research in many respects remain unchanged.How the World of Clinical Research Has ChangedDuring the forties and fifties, duties to obtain informed consent, whether for treatment or for research, were simply not part of the doctor-patient experience. [End Page 356]As one physician told us:In 1945, ‘50, the doctor... was king or queen. It never occurred to a doctor to ask for consent for anything. Doctors weren’t in the habit of telling the patients anything (either). They were in charge and nobody questioned their authority.(Advisory Committee on Human Radiation Experiments 1996, p. 83)This unquestioned authority extended to all decisions about the management of the patient, including whether patients were to receive experimental therapies or otherwise become the subjects of research or experimentation. Physicians were trained to be concerned with risk, and harm, and benefit, in keeping with the Hippocratic tradition. But in most institutions, the permission to try something new and to take unknown risks came, not from the patient, but from the chairman of the department.In part, this broad license reflected the very newness of scientifically grounded medical practice. In the forties and fifties, many potentially therapeutic interventions were newly discovered and in this sense considered experimental, or at least innovative. The level of uncertainty about whether a treatment would work was generally high, whether the treatment was part of a research project or not. Moreover, the formalizing of medical science at the bedside was itself still in its infancy—it was not until 1948 that the first modern clinical trial in which patients were randomized to different treatment and control groups was reported in the literature. Much of the research of this period was informal and unsystematic.Thus, it is not surprising that the physician’s authority to make treatment decisions extended to treatments that were innovative or experimental, regardless of whether these innovative treatments were the subject of formal scientific investigation. What is perhaps more surprising is that physicians often acted the same way—that... (shrink)

Medication reconciliation for pediatric oncology patientparticipants enrolled in clinical trials often reveals the use of chemical complementary medicine alongside protocol therapeutic agents. Considering the blurry delineation between clinical ethics and research ethics, this paper demonstrates how complementary medicine-related protocol violations introduce ethical questions of who should be included and excluded from clinical trials and offers recommendations on how to manage physician-patient-family interactions around these challenging issues.

Introduction: Clinical policies control several aspects of clinical practice, including individual treatment and care, resource management and healthcare professionals’ etiquette. This article presents Clinical Policy Ethics Assessment Tool, an ethical assessment tool for clinical policies that could be used not only by clinical ethics committees but also by policy committees or other relevant groups. Aim: The aim of this study was to find or create a tool to identify ethical issues and/or confirm ethical validity (...) in nursing practice policies, protocols and guidelines. Methodology: The development of Clinical Policy Ethics Assessment Tool involved first a literature review, followed by modification of the Research Protocol Ethics Assessment Tool, which was created to identify research protocols’ ethical issues, and finally, a trial of Clinical Policy Ethics Assessment Tool to ensure its reliability and validity. Ethical consideration: The policies analysed trialling Clinical Policy Ethics Assessment Tool were in the public domain and did not contain any confidential information. Despite that, Clinical Policy Ethics Assessment Tool also had the approval of a research ethics committee. Results: Research Protocol Ethics Assessment Tool was chosen as the template for a Clinical Policy Ethics Assessment Tool, to which several modifications were added to adapt it to work within a nursing practice context. Clinical Policy Ethics Assessment Tool was tested twice, which resulted in a general test–retest reliability coefficient = 0.86, r = 0.84, α1 = 0.817, α2 = 0.824 and interclass correlation coefficient = 0.874. Discussion: Contemporary nursing practice in a developed country is often ruled by clinical policies. The use of Clinical Policy Ethics Assessment Tool could confirm the ethical validity of those clinical practice policies, impacting on nurses’ education, values and quality of care. Conclusion: Clinical Policy Ethics Assessment Tool has the potential to detect ethical issues and facilitate the correction and improvement of clinical policies and guidelines in a structured way. This is especially so as it has shown reliability in detecting issues in clinical policies involving human participants and in encouraging policymakers to consider common ethical dilemmas in nursing practice. (shrink)

Research to improve the health of pregnant and fetal patients presents ethical challenges to clinical investigators, institutional review boards, funding agencies, and data safety and monitoring boards. The Common Rule sets out requirements that such research must satisfy but no ethical framework to guide their application. We provide such an ethical framework, based on the ethical concept of the fetus as a patient. We offer criteria for innovation and for Phase I and II and then for Phase III (...) class='Hi'>clinical trials to improve the health of pregnant patients and of fetal patients and also criteria to responsibly manage the transition from investigation to clinical practice. Basing ethical criteria for research involving pregnant women on the ethical concept of the fetus as a patient insulates the proposed ethical framework and therefore research on pregnant women from the divisive and politicized concepts and discourses of personhood, fetal rights, and unborn child. (shrink)

It is widely maintained that a clinical trial is ethical only if some form of equipoise between the treatments being compared obtains. To be in equipoise between two treatments A and B is to be cognitively indifferent between the statement ‘A is strictly more effective than B’ and its negation. It is natural to claim that equipoise regarding A and B is necessary for randomised assignment to treatments A and B to be beneficent and non‐maleficent and is sufficient (...) for such an assignment to be fair. Cashing this out precisely is difficult, and various forms of equipoise have been discussed which consider whose equipoise is relevant to the decision. This is to make judgement of equipoise something to be managed socially, while its prima facie significance is supposedly cognitive. Recent reconstructions of equipoise‐like concepts in epistemology give clues about how to understand equipoise cognitively. In this paper I examine some of this work and discuss how successful it has been. I suggest that while this work is promising, it still has far to go, and that while equipoise remains the best theory we have of the cognitive justification for clinical trials, it is nonetheless incoherent. (shrink)

Schizophrenia is a serious mental disease whose pathogenesis has not been fully elucidated. Its clinical evaluation and diagnosis still highly depend on the clinical experience of doctors. It is of great scientific value and clinical significance to study the inducing factors and neuropathological mechanism of schizophrenia. Based on the four research problems of schizophrenia, this paper analyzes the data types that need to be stored in clinical trials and scientific research, including basic information, case report data, (...) neuropsychological and cognitive function evaluation, magnetic resonance data, electroencephalogram data, and intestinal flora data. Through the demand analysis of the system, including the data management part, data analysis part, the functional demand of the system management part, and the overall nonfunctional demand of the system, the overall architecture design, functional module division, and database table structure design of the system are completed. Adopting Browser/Server architecture and front-end and back-end separation mode and applying Java and Python programming language, based on spring framework and database, a multidimensional information management system for schizophrenia is designed and implemented, which includes four modules: data analysis, data management, system management, and security control. In addition, each functional module of the system is designed and implemented in detail, and the software operation flow of each module is illustrated with the sequence diagram. Finally, the multidimensional data of schizophrenia collected in our laboratory were used for system test to verify whether the system can meet the needs of clinical big data management of schizophrenia and the multidimensional information management system of schizophrenia can meet the needs of clinical big data management. The information management system helps schizophrenic researchers to carry out data management and data analysis. It also has advantages that are easy to use, safe, and efficient and has strong scalability in data management, data analysis, and scalability. It reflects the innovation of the system and provides a good platform for the management, research, and analysis of clinical big data of schizophrenia. (shrink)

Rita Bottino,1 Santosh Nagaraju,2 Vikas Satyananda,2 Hidetaka Hara,2 Martin Wijkstrom,2 Massimo Trucco,1 David KC Cooper2 1Institute of Cellular Therapeutics, Allegheny Health Network, 2Thomas E Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA: Diabetes mellitus is increasing worldwide. Type 1 diabetes can be treated successfully by islet allotransplantation, the results of which are steadily improving. However, the number of islets that can be obtained from deceased human donors will never be sufficient to cure more than a very (...) small percentage of patients who might benefit from transplantation. Although there are some differences in glucose metabolism between pigs and humans, the use of pigs could provide an unlimited supply of islets, and the insulin produced would undoubtedly control glucose levels. Transplantation of islets into the portal vein results in islets residing in the liver; however, an early inflammatory response and rejection remain problematic, even when the recipient is receiving immunosuppressive therapy. In the long term, immunosuppressive drugs may exhibit toxicities to patients and specifically harm the islet cells. In contrast, encapsulation techniques provide islets with a physical barrier that prevents antibodies binding to the islet graft while still allowing insulin to be released into the recipient's circulation; in theory, patients receiving encapsulated grafts might not require exogenous immunosuppressive therapy. Nonhuman primates with encapsulated pig islet transplants have remained insulin-independent for several weeks, but long-term efficacy remains uncertain. Furthermore, techniques are now available to knock out genes from the pig and/or insert human genes, thus rendering the antigenic structure of pigs closer to that of humans, and providing protection from the human immune response. Islet transplantation from genetically engineered pigs has been followed by insulin independence in a small number of nonhuman primates for greater than 1 year. Neonatal islets have some advantages over adult islets in that they are easier to isolate and culture, and have the ability to proliferate during the first few months after transplantation. In 2009, the International Xenotransplantation Association set up a group to encourage and advise on clinical trials of pig islet xenotransplantation; this group's guidelines are discussed. Clinical trials of encapsulated pig islets are already under way. Keywords: diabetes, islets, pancreatic, pig, xenotransplantation. (shrink)

The prevalence of dementia is increasing with the ever-growing population of older adults. Non-pharmacological, music-based interventions, including sensory stimulation, were reported by the Lancet Commission in 2020 to be the first-choice approach for managing the behavioural and psychological symptoms of dementia. Low frequency sinusoidal vibration interventions, related to music interventions through their core characteristics, may offer relief for these symptoms. Despite increasing attention on the effectiveness of auditory music interventions and music therapy for managing dementia, this has not included low (...) frequency vibration. This scoping review, following the JBI methodology guidelines, was conducted to investigate participants’ responses to both sound and mechanical vibration, the characteristics of the delivered interventions, methodological challenges, and the specifics of the research experiments reported. An extensive search was conducted in BMC, CINAHL, Cochrane Central Register of Controlled Trials, EMBASE, ERIC, MEDLINE, Pedro, ProQuest Central, PsycINFO, Scopus, and Web of Science. Current Controlled Trials, Clinical Trials, and Google Scholar were also searched as well as a hand search in relevant journals. Studies on adults with all types of dementia, investigating tactile low frequency sound or mechanical vibration in any context were considered. Data from eight full-length studies were extracted using the data extraction table developed by the authors and were included in the analysis and critical appraisal. Issues in quality related to, for example, control groups and blinding. Few studies addressed participants’ subjective responses to the interventions. Reporting on the intervention characteristics was unclear. It appeared more frequent sessions led to better outcomes and home-based interventions potentially addressing the issue of access and feasibility. Future research should include neuroimaging to measure and confirm the hypothesised mechanism of cerebral coherence. Standardised reporting of intervention characteristics is also needed to ensure replicability of the experiments. Higher quality research is needed to investigate the impact and effect of low frequency vibration for the symptoms of dementia and compare outcomes in meta-syntheses. (shrink)

Race or ethnic identity, despite its imprecise categorization, is a useful means of identifying population differences in mechanisms of disease and treatment effects. Therefore, race and other arbitrary demographic and physiological variables have appropriately served as a helpful guide to clinical management and to clinical trial participation. The African-American Heart Failure Trial was carried out in African-Americans with heart failure because prior data had demonstrated a uniquely favorable effect in this subpopulation of the drug combination (...) in BiDil. The remarkable effect of the drug in reducing mortality in this study has illuminated an important new mechanism of therapy for heart failure. Application of these findings need not be confined to the population studied, but the observation highlights the need for more precise ways to identify individual responsiveness to therapy. (shrink)

The Australian HREC system is experiencing increasing workloads and greater public scrutiny. Dr Dodds asks whether the system is sustainable and aims to encourage a constructive critical debate about the system. This article suggests there is a gap between the demands on the system and expectations of researchers, regulators and the community. The evolution of the HREC system reached a significant milestone of the publication of the National Statement on Ethical Conduct in Research Involving Humans. This article argues that there (...) will be increases in HREC workloads and new challenges from human genetic research, commercialisation of research and clinical trials. The Andrews Committee has recommended another independent review of the system. The system is also under review by the joint ALRC/ahec inquiry into the protection of human genetic information. (shrink)

The Food and Drug Administration authorizes the marketing of a drug only for uses that the manufacturer has demonstrated to be safe and effective, based on evidence from at least two clinical trials. However, the FDA does not regulate the practice of medicine, so physicians may prescribe drugs in any manner they choose. Prescribing drugs in ways that deviate from the uses specified in the FDA-approved drug label, package insert, and marketing authorization is referred to as off-label prescribing. This (...) occurs when physicians prescribe a drug for a therapeutic purpose other than the one approved by the FDA; treat patients in a different age cohort or gender than the population on which it was tested; or prescribe a different dose, for a different duration of use, or a different mode of administration than indicated on the label. (shrink)

Should first-in-human trials be designed to maximize the prospect of therapeutic benefit for volunteers, prioritize avoidance of unintended harms, or aim for some happy medium between the two? Perennial controversies surrounding initiation and design of early-phase trials hinge on how this question is resolved. In this paper, we build on the premise that the task of early-phase testing is to optimize various components of a potential therapy so that later, confirmatory trials have the maximal probability of informing drug development and (...) clinical care. We then explore three strategies that investigators might use to manage trial risks while optimizing a therapy, using cell therapy for Amyotrophic Lateral Sclerosis (ALS) as an example. We argue that an iterative application of maximin strategies over successive cohorts and trials, which we call the “risk-escalation model,” establishes a moral principle that should guide decision-making in early-phase trials. (shrink)

The Flash Technique of Eye Movement Desensitization and Reprocessing is widely recognized for its effectiveness in reducing the effects of emotional responses associated with traumatic memories. Using a randomized-controlled trial methodology, this study attempts to establish the efficacy of the EMDR Flash Technique. This study’s sample includes volunteers who were involved in traffic accidents and were given the randomized EMDR Flash Technique and Improving Mental Health Training for Primary Care Residents Stress management module. The participants were given a (...) socio-demographic data form, the Depression-Anxiety-Stress 21 scale, the Impact of Event Scale-Revised, and the WHOQOL Quality of Life scale. Participants were evaluated using measurements taken before and after the application, as well as a one-month follow-up. The mean age of the participants was 36.20 years and 82.1% were female. The DASS-21 Anxiety, IES-R Intrusion, Avoidance, Total, and WHOQOL-BREF Psychological score improvements of the EMDR Flash Technique group were shown to be statistically significant when compared to the mhGAP group. However, no statistically significant difference in the DASS-21 Depression, Stress, Impact of Event Scale-Revised Hyperarousal WHOQOL-BREF General Health, Physical, Social Relationships, and Environment component scores was reported between the two groups. The present study’s findings clearly demonstrate that the EMDR Flash technique, when applied to persons involved in traffic accidents, is successful in improving anxiety, intrusion, avoidance, total traumatic stress, and mental quality of life symptoms for at least 1 month. We believe that these findings will improve the reliability and applicability of the EMDR Flash Technique, which was tested for the first time in a clinical randomized-controlled trial. (shrink)

The arts provide openings for symbolic expression by engaging the sensory experience in the body they become a source of insight through embodied cognition and emotion, enabling meaning-making, and acting as a catalyst for change. This synthesis of sensation and enactive, embodied expression through movement and the arts is capitalized on in The BodyMind Approach®. It is integral to this biopsychosocial, innovative, unique intervention for people suffering medically unexplained symptoms applied in primary healthcare. The relevance of embodiment and arts practices (...) in TBMA are discussed in relation to the views of participants in the pursuit of self-management. If widely employed TBMA could have an enormous impact, reach, and significance for patients and global health services. This original pre-clinical trial of qualitative research reports on the perceptions of participant patients with generic MUS, a world-wide issue usually treated by either psychological therapy or physiotherapy. TBMA is not a therapy but a health education program founded upon the concept of an integration of psychological elements with physiological, bodily, and sensory experiences. Thematic analysis of qualitative data sets from open-ended questions in semi-structured interviews and a written questionnaire post intervention is presented. Five aspects which appear to be key to learning self-management were derived from analyzing the data: body with mind connections; importance of facilitation; potential benefits; preparedness for change; self-acceptance/compassion. This article advances the discourse on the nature of self-management for MUS through changing the mind-set and the relationship participants have with their bodily symptom/s through employing embodied methods and arts practices, challenging current, and solely verbal, psychological conceptual frameworks. Rigor lies in the method of data analysis using cross verification of credibility between reported findings and scrutiny by stakeholders. We conclude that facilitated TBMA groups employing embodied methods and arts practices can act as a method for developing the self-management of MUS and improving wellbeing. (shrink)

Research to improve the health of pregnant and fetal patients presents ethical challenges to clinical investigators, institutional review boards, funding agencies, and data safety and monitoring boards. The Common Rule sets out requirements that such research must satisfy but no ethical framework to guide their application. We provide such an ethical framework, based on the ethical concept of the fetus as a patient. We offer criteria for innovation and for Phase I and II and then for Phase III (...) class='Hi'>clinical trials to improve the health of pregnant patients and of fetal patients and also criteria to responsibly manage the transition from investigation to clinical practice. Basing ethical criteria for research involving pregnant women on the ethical concept of the fetus as a patient insulates the proposed ethical framework and therefore research on pregnant women from the divisive and politicized concepts and discourses of personhood, fetal rights, and unborn child. (shrink)

: The "difference position" holds that clinical research and therapeutic medical practice are sufficiently distinct activities to require different ethical rules and principles. The "similarity position" holds instead that clinical investigators ought to be bound by the same fundamental principles that govern therapeutic medicine—specifically, a duty to provide the optimal therapeutic benefit to each patient or subject. Some defenders of the similarity position defend it because of the overlap between the role of attending physician and the role of (...) investigator in a research trial. This overlap is maximal when the same physician occupies both roles with respect to a particular patient-subject. We address the ethical tensions inherent in that role conflict and argue that the tensions are real but manageable. The difference position provides a sound ethical framework within which to manage those tensions, while the similarity position is unsatisfactory because it seeks to deny the existence of the tensions. (shrink)

In the past few years, there have been a number of high profile incidents that have emphasized the issues associated with financial conflicts of interest. As a result, commentators and policy-makers throughout the world have been directing their attention to how financial conflicts should be addressed. Despite such activity, however, there are few policies that provide specific guidance addressing one of the most common forms of financial conflict-the provision of generous remuneration packages to clinical investigators.In this column, we explore (...) the conflict of interest issues that flow from the pharmaceutical industry paying community physicians to be investigators in clinical drug trials. In particular, we are interested in the challenges associated with the management of this complex issue by local research ethics boards. We suggest the need for more research on this topic and specific guidelines to empower these boards to address this growing concern. We recognize that this is one of many current conflict issues faced by policy-makers today. (shrink)

BackgroundWithholding and withdrawing treatment are deemed ethically equivalent by most Bioethicists, but intensivists often find withdrawing more difficult in practice. This can lead to futile treatment being prolonged. Time-limited trials have been proposed as a way of promoting timely treatment withdrawal whilst giving the patient the greatest chance of recovery. Despite being in UK guidelines, time-limited trials have been infrequently implemented on Intensive Care Units. We will explore the role of time in Intensive Care Unit decision-making and provide a UK (...) perspective on debates surrounding time-limited trials.MethodsThis qualitative study recruited 18 participants (nine doctors, nine nurses) from two Intensive Care Units in North West England for in-depth, one-to-one semi-structured interviews. A thematic analysis was performed of the data.ResultsOur findings show time is utilised by Intensive Care Unit staff in a variety of ways including managing uncertainty when making decisions about a patient’s prognosis or the reversibility of a disease, constructing relationships with patients’ relatives, communicating difficult messages to patients’ relatives, justifying resource allocation decisions to colleagues, and demonstrating compassion towards patients and their families.ConclusionsTime shifts the balance towards greater certainty in Intensive Care Unit decision-making, by demonstrating futility, and can ease the difficult transition for staff and families from active treatment to palliation. However, this requires clear and open communication, both within the Intensive Care Unit team and with the family, being prioritised when time is used in decision-making. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Narrative Symposium:Conflicting Interests in MedicineLaura Jean Bierut, Sal Cruz-Flores, Laura E. Hodges, Anthony A. Mikulec, Govind K. Nagaldinne, Erine L. Bakanas, John F. Peppin, Joel S. Perlmutter, William H. Seitz Jr., Edward Diao, Andre N. Sofair, and David M. Zientek• To Recruit or Not to Recruit for a Clinical Trial• An Unexpected Lesson• Am I on call for the entire Midwest?• Why is Medicare Wasting Away?• The (...) Downside of the Informed Consent Juggernaut• Expert Testimony at the Food and Drug Administration: Who Wants the Truth?• Crossroads: The Intersection of Personal, Professional Society, and Industry Relationships• A Change of Heart• The Evolution of Conflicts of Interest in a New Subspecialty: A Case Study of the Development of Interventional CardiologyCopyright © 2011 The Johns Hopkins University Press... (shrink)

_Background:_ Literature has documented the role of family in the outcome of chronic schizophrenia. In the light of this, family interventions (FIs) are becoming an integral component of treatment for psychosis. The First Episode of Psychosis (FEP) is the period when most of the changes in family atmosphere are observed; unfortunately, few studies on the relatives are available. _Objective:_ To explore burden of care and emotional distress at baseline and at 9-month follow-up and the levels of service satisfaction at follow-up (...) in the two groups of relatives (experimental treatment EXP vs. treatment as usual TAU) recruited in the cluster-randomized controlled GET UP PIANO trial. _Methods:_ The experimental treatment was provided by routine public Community Mental Health Centers (Italian National Health Service) and consisted of Treatment as Usual plus evidence-based additional treatment (Cognitive Behavioral Therapy for psychosis for patients, Family Intervention for psychosis, and Case Management). TAU consisted of personalized outpatient psychopharmacological treatment, combined with non-specific supportive clinical management and informal support/educational sessions for families. The outcomes on relatives were assessed by the Involvement Evaluation Questionnaire (IEQ-EU), the General Health Questionnaire (GHQ-12), and the Verona Service Satisfaction Scale (VSSS-EU). Differences within and between groups were evaluated. _Results:_ At baseline, 75 TAU and 185 EXP caregivers were assessed. In the experimental group 92% of relatives participated in at least 1 family session. At follow-up both groups experienced improvement in all IEQ and GHQ items, but caregivers belonging to the EXP arm experienced a significantly greater change in 10 IEQ items (mainly pertaining to the “Tension” dimension) and in GHQ items. Due to the low sample size, a significant effectiveness was only observed for 2 IEQ items and 1 GHQ-12 item. With respect to VSSS data at follow-up, caregivers in the EXP arm experienced significantly greater satisfaction in 8 items, almost all pertaining to the dimensions “Relatives' Involvement” and “Professionals' Skills and Behavior.” _Conclusions:_ The Family intervention for psychosis delivered in the GET UP PIANO trial reduced family burden of illness and improved emotional distress and satisfaction with services. These results should encourage to promote FIs on caregivers of first-episode psychosis patients. (shrink)

We argue that the universal recommendations against “off-label” pediatric use of approved COVID-19 issued by the FDA, CDC, and AAP are overbroad. Especially for higher-risk children, vaccination can be ethically justified even before FDA authorization or approval – and similar reasoning is relevant for even younger patients. Legal risks can also be managed, although the FDA, CDC, and Department of Health and Human Services (HHS) should move quickly to provide clarity.

The participation of vulnerable patients in clinical research poses apparent ethical dilemmas. Depending on the nature of the vulnerability, their participation may challenge the ethical principles of autonomy, non-maleficence, or justice. On the other hand, non-participation may preclude the building of a knowledge base that is a prerequisite for defining the optimal clinical management of vulnerable patients. Such clinical uncertainty may also incur substantial economic costs. We present the participation of pre-menopausal women with atrial fibrillation in (...) trials of novel oral anticoagulant drugs as a case study. Due to their non-participation in pivotal trials, it is uncertain whether for them, the risks that are associated with these drugs are outweighed by the advantages compared with conventional treatment. We addressed the question whether research of this new class of drugs in this subgroup would be appropriate from both, an ethical as well an economic perspective. We used the method of specifying norms as a wider framework to resolve the apparent ethical dilemma, while incorporating the question whether research of oral anticoagulants in premenopausal women with atrial fibrillation can be justified on economic grounds. For the latter, the results of a value-of-information analysis were used. Further clinical research on NOACs in premenopausal women with atrial fibrillation can be justified on both, ethical and economic grounds. Addressing apparent ethical dilemmas by invoking a method such as specifying norms can improve the quality of public practical reasoning. As such, the method should also prove valuable to committees that have formally been granted the authority to review trial protocols and proposals for scientific research. (shrink)