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Over the course of human life, health care decision-making is often interdependent. In this article, we use "interdependence" to refer to patients' engagement of nonclinicians-for example, family members or trusted friends-to reach health care decisions. Interdependence, we suggest, is common for patients in all stages of life, from early childhood to late adulthood. This view contrasts with the common bioethical assumption that medical decisions are either wholly independent or dependent and that independence or dependence is tightly coupled with a person's decision-making capacity. In this article, we array various approaches to decision-making along a continuum of interdependence. An appreciation of this continuum can empower patients and elucidate ethical challenges that arise when people transition between different kinds of interdependence across the life span.

Well before patient-centered or patient-controlled research became trendy, and earlier than calls to preferentially refer to research subjects as participants, Bob Veatch wrote "The Patient as Partner" Veatch presciently argued that research patients should not be thought of as passive subjects nor material from which to obtain data, but rather as partners in discovery. In this manuscript, I will explore Veatch's conception of patient as partner in research and how that idea has evolved and been implemented over time and consider some of the remaining challenges. Complexities of patient partnership include: clarifying the types of research in which patient partnership is most appropriate, recognizing the various possible levels of patient engagement in each case, avoiding tokenism and striving for respectful partnership, and keeping in mind the appropriate implementation of protections and safeguards. Bob Veatch would be pleased with the progress that has been made in creating research partnerships with patients, while also undoubtedly pushing us to continue to do better.

After decades of setbacks, gene therapy (GT) is experiencing major breakthroughs. Five GTs have received US regulatory approval since 2017, and over 900 others are currently in development. Many of these GTs target rare pediatric diseases that are severely life-limiting, given a lack of effective treatments. As these GTs enter early-phase clinical trials, specific ethical challenges remain unresolved in three domains: evaluating risks and potential benefits, selecting participants fairly, and engaging with patient communities. Drawing on our experience as clinical investigators, basic scientists, and bioethicists involved in a first-in-human GT trial for an ultrarare pediatric disease, we analyze these ethical challenges and offer points to consider for future GT trials.

The COVID-19 pandemic continues to disrupt every society as SARs-CoV-2 variants surge among the populations. Health care providers are exhausted, becoming ill themselves, and in some instances have died. Indeed, hospitals are struggling to find staff to care for critically ill patients most in need. Previous work has reported on the unending work-related conditions that hospital staff are laboring under and their subsequent mental and physical health strains. Health care providers need support, but it is not clear where that support is to come from. While much research has reported on the COVID-19-related fears of nurses and physicians, fewer studies have focused on supportive features of the hospital work environment and how it may provide relief to front-line health care providers.This purpose of this study was to explore an often-overlooked resource within hospital systems across the United States-clinical ethicists-and examine their many roles during COVID-19 and the types of ethical issues they addressed with nurses, physicians, administrators, and others.This was a primary analysis of semi-structured, qualitative interviews with 23 clinical ethicists across the United States. The interviews were conducted from November 2020-April 2021 and were audiotaped, transcribed verbatim, and de-identified; both inductive and deductive analyses were used to identify qualitative themes.Five major themes were identified: ethical issues that were increasingly more complex, moral distress that was "endemic," shifting ethical paradigms from the focus on the individual to the population, fostering a supportive environment, and organizational ethics: variation in the value, roles, and policy input of clinical ethicists.Our findings report on the integral and expanded role of clinical ethicists at an unprecedented time in our nation, and how they stepped forward to support front-line clinicians in hospitals across the country.

New fetal therapies offer important prospects for improving health. However, having to consider both the fetus and the pregnant woman makes the risk-benefit analysis of fetal therapy trials challenging. Regulatory guidance is limited, and proposed ethical frameworks are overly restrictive or permissive. We propose a new ethical framework for fetal therapy research. First, we argue that considering only biomedical benefits fails to capture all relevant interests. Thus, we endorse expanding the considered benefits to include evidence-based psychosocial effects of fetal therapies. Second, we reject the commonly proposed categorical risk and/or benefit thresholds for assessing fetal therapy research (e.g., only for life-threatening conditions). Instead, we propose that the individual risks for the pregnant woman and the fetus should be justified by the benefits for them and the study’s social value. Studies that meet this overall proportionality criterion but have mildly unfavorable risk-benefit ratios for pregnant women and/or fetuses may be acceptable.

OBJECTIVE: Fetal therapy trials pose complex ethical challenges because risks and benefits to both fetuses and pregnant persons must be considered. Existing regulatory guidance is limited and many proposed ethical frameworks have unnecessarily restrictive criteria that would block the development and implementation of important new fetal therapies. We aimed to develop a new ethical framework for assessing the risks and benefits of fetal therapy trials. METHODS: We reviewed existing regulatory and ethical guidance on fetal therapy trials. We used conceptual analysis to design a new ethical framework, which is grounded in general ethical principles for clinical research. RESULTS: We propose a new framework for assessing the risks and benefits of fetal therapy trials. We suggest that the potential benefits of a fetal therapy trial – for the fetus, the pregnant person, and society – should outweigh the risks for the fetus and the pregnant person. Furthermore, the risk-benefit profile for just the fetus and the risk-benefit profile for just the pregnant person should be appropriate. CONCLUSIONS: We hope that this new framework will permit important studies while protecting pregnant persons and fetuses from disproportionate harms.

One way of conceptualizing the principal achievements and failures of human research is to consider to what extent research has contributed value to society. Research is generally considered to have value if it has the prospect of producing knowledge that can be used toward improvements in health or well-being. The authors selected nine case studies of research during the twentieth and twenty-first centuries that illustrate multiple ways research has achieved or failed to achieve value. Included in the “highs” of research are the development of antiretroviral therapy for HIV, Michael Marmot’s Whitehall studies, and the evaluation of hormone replacement therapy, among others. The authors’ cases of “lows” include genetic research on the etiology of homosexuality, the US Public Health Service’s Guatemala sexually transmitted disease experiments, and the gene transfer experiment that Jesse Gelsinger participated in, among others. A retrospective analysis of how research has and hasn’t contributed value may inform more thoughtful assessments of value in future research.

Registered nurses are an essential workforce group across the globe. They use their expertise and skill sets every day in clinical practice to protect, promote, and advocate on behalf of patients and families under their care. In this article we discuss the physical, emotional, and moral stresses that nurses are experiencing in their day-to-day practice settings created by the novel coronavirus. We consider the demands placed on nurses by unexpected patient surges within hospital environments and inadequate personal protective equipment and other critical resources, challenging nurses’ ability to meet their professional and ethical obligations. We also share our thoughts on supporting nurses and others now, and ideas for needed healing for both individuals and organizations as we move forward. Finally, we argue for the need for substantive reform of institutional processes and systems that can deliver quality care in the future when faced with another devastating humanitarian and public health crises. “Nursing is not just evaluating patient symptoms, dressing wounds, lab work, and value-based care—nursing impacts the soul in each of us. In our weakest places, in our most vulnerable areas of life, nursing has literally opened the door to the most painful, but most rewarding moments in the lives of others. The dying, the hurt, the raw, emotional places of life: nurses have the privilege to walk in these spaces and provide a comforting hand, a compassionate touch, and a life-changing presence.”— Love et al., 2021 , 87

From its inception, the NIH Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, an ambitious project focused on understanding the human brain, has made a concerted effort to integrate neuroethics into its science. In the past five years, the BRAIN Initiative has given rise to powerful tools and neurotechnologies capable of probing deeply into the brain circuits in animal models. As these tools mature and move to human applications they will raise a host of important neuroethical considerations not just for the medical community but for society as a whole. Now marks a pivotal moment to assess the status and consider the future of the BRAIN Initiative's neuroethics efforts. Here we describe core issues of neuroscience advances, the state of neurotechnologies in human neuroscience, and how ethics will be incorporated into the BRAIN Initiative as this ten-year project enters its second phase. BRAIN Initiative neurotechnologies have immense potential to transform the way we diagnose and treat neurological disease; therefore, they may become more commonplace in research, medicine, and society. We also discuss future global efforts to ensure continued guidance and open dialogue surrounding neuroethics.

BACKGROUND: Potentially curative but high-risk trials of gene therapy or stem cell transplantation (PBSCT) for Sickle Cell Disease (SCD) pose new opportunities for adults with SCD, many of whom experience significant disease burden and complications with few treatment options, as well as stigma and disparities in care. We explored motivations and decision-making processes of enrollees and decliners of such trials. METHODS: Semi-structured interviews with a purposive sample of 20 enrollees and 6 decliners. Interviews explored participants’ SCD experiences, motivations and decision-making about trial participation, understanding of research-related information, and retrospective reflections. Interviews were analyzed with content analysis. RESULTS: Most identified the purpose of research, risks, and uncertainties of participation. Both enrollees and decliners described deliberative weighing of study risks and potential benefits (especially the prospect of a cure), with heavy factoring of their SCD status, experiences, and desire for a better life. Despite the influence of spirituality/religion and support of family and friends, all described the decision about participation as their own. In some patients, the primary outcome status defined by the trial did not match the patients’ perceived outcomes. Patients with negative experiences expressed a desire for greater emphasis on risks and possible outcomes during informed consent. CONCLUSIONS: This cohort of adults with SCD were thoughtfully deliberative in their decisions about gene therapy or PBSCT trials. Future participants’ decision-making may be enhanced by emphasizing that ‘successful’ scientific outcomes can still involve complications or symptoms and be facilitated by referrals to former research participants and anticipatory discussions.

Ethically challenging situations routinely arise in the course of illness and healthcare. However, very few studies have surveyed patients and family members about their experiences with ethically challenging situations. To address this gap in the literature, we surveyed patients and family members at three hospitals. We conducted a content analysis of their responses to open-ended questions about their most memorable experience with an ethical concern for them or their family member. Participants (

Background and ObjectivesIn the neurosciences, significant opportunities for sharing individual-level data are underexploited. Commentators suggest various barriers to data sharing, which may need to be addressed. Investigators' perspectives on the main barriers are unclear. Furthermore, bioethicists have raised concerns about the potential misuse of neuroscience data, although discussions are hampered by uncertainty about the potential risks. It is unclear how common sensitive data are obtained and whether investigators judge them as sensitive.MethodsAn online survey was disseminated among 1,190 principal investigators (PIs) of active National Institute of Neurological Disorders and Stroke, National Institute of Mental Health, or NIH Brain Research Through Advancing Innovative Neurotechnologies Initiative grants involving human subject research.ResultsA total of 397 investigators responded to the survey (response rate 33%). Most investigators (84%) support efforts to increase sharing of deidentified individual-level data. However, investigators perceive many barriers to data sharing. The largest barriers were costs and time; limited interpretation of the data without understanding the context of data collection; lack of incentives; limited standardization and norms for data acquisition, formatting, and description; and heterogeneity of data types. Several types of data described as sensitive in the literature are common among neuroscience studies, for example, neural correlates of behavior, emotions, or decision making (71%) and/or predictive data (54%). Although most investigators consider it unlikely or extremely unlikely for their research data to be misused to harm individual research participants (82%), the majority were at least slightly concerned about potential harm to individuals if their research data were misused (65%). Investigators with more easily reidentifiable data, data from vulnerable groups, and neural data were more concerned about the likelihood of misuse and/or magnitude of harm of misuse of their research data.DiscussionWe hope these data help prioritize the development of tools and strategies to overcome the main barriers to data sharing. Furthermore, these data provide input on what may be sensitive data for which additional safeguards should be considered.

Lynch and colleagues (2021) describe positive and cautionary lessons learned from recent extraordinary research efforts to develop COVID-19 vaccines and therapeutics and consider whether some of th...

A nurse honors her husband's legacy.

Background Limited information exists about the design of placebo-controlled cancer trials. Through a systematic review of trials published in 2013, we describe placebo use in randomized trials testing anticancer agents and analyze strategies that increase exposure to the experimental regimen. Methods Trials were classified as add-on (placebo in combination with standard treatment) or placebo-only. Strategies to allow more than half of the participants to receive the experimental regimen were reviewed. The risk–benefit ratio of receiving the experimental agent was considered favorable if the difference in primary outcome was significant (p ≤ 0.05), neutral if there was no significant difference in the primary outcome and the experimental agent did not add substantial toxicity, and unfavorable otherwise. Results Eighty trials were included (32,694 participants). Most trials were add-on (69%). The risk–benefit outcome was favorable, neutral, and unfavorable to the experimental agent in 52%, 32%, and 16% of placebo-only trials and 25%, 53%, and 22%, respectively, of add-on trials. Four strategies increased exposure to the experimental regimen: one-way crossover (23%), uneven randomization (21%), three-arms (13%), and randomized discontinuation design (4%); these strategies were used more often in placebo-only trials. Conclusion A minority of participants received placebo alone and strategies to increase experimental exposure were used commonly. Fewer than half of the studies had favorable outcomes, thus defending the use of placebo controls, when there is no established treatment. Strategies that increase patient exposure to experimental agents rather than placebo may expose them to non-beneficial, sometimes toxic, experimental agents.

Pregnant individuals are often excluded from research without clear justification, even when the research poses minimal risk of harm to the fetus. Little is known about institutional review board (IRB) decision-making practices when reviewing such research. We conducted a survey of current and former IRB personnel in the United States to elicit their interpretations of "minimal risk"-a formal regulatory category-and to identify factors that may influence IRB decisions to approve or disapprove research involving pregnant participants. Study results revealed some consensus among IRB members about the risk level of individual research procedures and hypothetical study vignettes. However, we uncovered important variations not only in the assessment of risk but also in the willingness of IRB members to approve minimal risk research that includes pregnant women. Based on our findings, guidance is needed to assist IRB members in characterizing risk, applying federal regulations, and appropriately ensuring the inclusion or justified exclusion of pregnant people in research.

Unexpected direct and indirect risks of participating in clinical trials have emerged during COVID-19 that investigators and institutional review boards may not be sure how to investigate. How should existing guidance and ethical frameworks for clinical trials be applied in a pandemic setting?

Some placebo-controlled trials can continue ethically after a candidate vaccine is found to be safe and efficacious

ImportanceAttrition in cancer clinical trials (CCTs) can lead to systematic bias, underpowered analyses, and a loss of scientific knowledge to improve treatments. Little attention has focused on retention, especially the role of perceived benefits and burdens, after participants have experienced the trial.ObjectivesTo examine the association between patients’ perceived benefits and burdens of research participation and CCT retention.Design, Setting, and ParticipantsThis survey study was conducted at a National Cancer Institute–designated comprehensive cancer center in the Northeast region of the US. The sample included adult patients with a cancer diagnosis participating in cancer therapeutic trials. Data were collected from September 2015 to June 2019. Analysis of study data was ongoing since November 2019 through October 2022.ExposuresSelf-reported validated survey instrument with a list of 22 benefits and 23 burdens of research participation that can be rated by patients with a 5-point Likert scale ranging from 1 (strongly disagree) to 5 (strongly agree).Main Outcomes and MeasuresA primary outcome was actual withdrawal from the CCT, and a composite outcome was composite withdrawal that included both actual withdrawal and thoughts of withdrawing. Bivariate and multivariable logistic regressions were used.ResultsAmong the 334 participants in the sample, the mean (SD) age was 61.9 (11.5) years and 174 women (52.1%) were included. Top-cited benefits included both aspirational and action-oriented goals, including helping others (94.2%), contributing to society (90.3%), being treated respectfully (86.2%), and hoping for a cure (86.0%). Worry over receiving a placebo (61.3%), rearranging one’s life (41.9%), and experiencing bothersome adverse effects (41.6%) were notable burdens. An increased burden score was associated with a higher probability of actual withdrawal (adjusted odds ratio [OR], 1.86; 95% CI, 1.1-3.17; P = .02) or composite withdrawal (adjusted OR, 3.44; 95% CI, 2.09-5.67; P P P = .03). The risk of withdrawal was even higher for the composite outcome (adjusted OR, 7.70; 95% CI, 2.76-21.48; P Conclusions and RelevanceThis survey study found that patients perceived important benefits from CCT participation, and this perception was associated with trial retention, even among those who also perceived substantial burdens. A broader dialogue among stakeholders can inform an ethical and patient-centric focus on benefits throughout the course of a CCT to increase retention.

Many of the ethical concerns that patients and family members remember best from times when they have been sick parallel the ethical concerns their health care providers recall in their clinical en...

This article describes oversight mechanisms for clinical research that have developed substantially over the last few decades, including institutional review boards and data safety and monitoring boards. LeRoy Walters and others in the 1970s in the US thoughtfully described the importance of fundamental ethical principles and the application of bioethics to clinical research. Dr. Walters's important essay and work with the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research helped identify and explain ethical principles that guide research. These principles, subsequently enunciated by the Commission in the Belmont Report, remain central to our understanding of the ethics of clinical research and are the foundation of our regulations. In this article, I review some history, successes, and challenges of IRBs and DSMBs to exemplify the significance of understanding and applying ethical principles to the design and conduct of clinical research, and to honor Dr. Walters's contributions.

After decades of setbacks, gene therapy (GT) is experiencing major breakthroughs. Five GTs have received US regulatory approval since 2017, and over 900 others are currently in development. Many of these GTs target rare pediatric diseases that are severely life-limiting, given a lack of effective treatments. As these GTs enter early-phase clinical trials, specific ethical challenges remain unresolved in three domains: evaluating risks and potential benefits, selecting participants fairly, and engaging with patient communities. Drawing on our experience as clinical investigators, basic scientists, and bioethicists involved in a first-in-human GT trial for an ultrarare pediatric disease, we analyze these ethical challenges and offer points to consider for future GT trials.

ispartof: VACCINE vol:39 issue:7 pages:1028-1029 ispartof: location:Netherlands status: published

Privacy and confidentiality of personal medical information are cornerstones of ethical clinical care and ethical research. But real-world research has challenged traditional ways of thinking about privacy and confidentiality of information. In today's world of "big data" and learning health care systems, researchers and others are combining multiple sources of information to address complex problems. We present a case study that highlights the ethical concerns that arise when a patient who is employed by an academic medical center learns through a research invitational letter that her private information was accessed at this center without her consent. We discuss the ethical challenges of balancing patient privacy with advancing clinical research and ask, what level of privacy and confidentiality can and should patients expect from their clinician providers, fellow research colleagues, and institutions?

It is widely agreed that an effective response to the coronavirus disease 2019 pandemic needs to include a vaccine that is safe and effective for minors. However, many current vaccine trials have no plans for when to enroll minors. Others have recently proposed enrolling minors as young as 12 years old. This lack of a systematic approach raises 2 concerns. Waiting too long to enroll minors could unjustly deny minors and their families the benefits of a vaccine and has the potential to delay an effective response to the pandemic by a year or longer. At the same time, enrolling minors too soon runs the risk of exposing them to excessive risks. With these concerns in mind, in the present article, we propose recommendations for when and how to enroll minors in vaccine trials for the coronavirus disease 2019.

In 2014, companies began covering the costs of egg freezing for their employees. The adoption of this benefit was highly contentious. Some argued that it offered women more reproductive autonomy, buying time to succeed in their careers and postpone childbearing. Others suggested this benefit might place inappropriate pressure on women, unduly influencing them to freeze their eggs to prioritize their career over reproduction. Although ethical problems with this benefit have been explored, there has not been research analyzing the perspectives of women working for companies that offer employer-based egg freezing. Furthermore, existing empirical studies often focus on the experiences of egg freezers rather than the young women thinking about, but not yet using, this technology.

Highlights • Quickly finding a safe and effective vaccine against SARS Co-V-2 would be of great value. • Collecting rigorous safety and efficacy data without compromising ethical and scientific norms is critical. • The best approach is accelerated individually randomized controlled trials. • Premature distribution could hamper public health and finding safe, effective SARS CoV-2 vaccines., Background A sense of urgency exists to develop vaccines against SARS CoV-2, responsible for numerous global cases and deaths, as well as widespread social and economic disruption. Multiple approaches have been proposed to speed up vaccine development, including accelerated randomized controlled trials (RCT), controlled human challenge trials (CHI), and wide distribution through an emergency use authorization after collecting initial data. There is a need to examine how best to accelerate vaccine development in the setting of a pandemic, without compromising ethical and scientific norms. Methods Trade-offs in scientific and social value between generating reliable evidence about safety and efficacy while promoting rapid vaccine availability are examined along five ethically relevant dimensions: (1) confidence in and generalizability of data, (2) feasibility, (3) speed and cost, (4) participant risks, and (5) social risks. Results Accelerated individually randomized RCTs permit expeditious evaluation of vaccine candidates using established methods, expertise, and infrastructure. RCTs are more likely than other approaches to be feasible, increase speed and reduce cost, and generate reliable data about safety and efficacy without significantly increasing risks to participants or undermining societal trust. Conclusion Ethical analysis suggests that accelerated RCTs are the best approach to accelerating vaccine development in a pandemic, and more likely than other approaches to enhance social value without compromising ethics or science. RCTs can expeditiously collect rigorous data about vaccine safety and efficacy. Innovative and flexible designs and implementation strategies to respond to shifting incidence and test vaccine candidates in parallel or sequentially would add value, as will coordinated data sharing across vaccine trials. CHI studies may be an important complementary strategy when more is known. Widely disseminating a vaccine candidate without efficacy data will not serve the public health nor achieve the goal of identifying safe and effective SARS Co-V-2 vaccines.

The Covid‐19 pandemic has highlighted many of the difficult ethical issues that health care professionals confront in caring for patients and families. The decisions such workers face on the front lines are fraught with uncertainty for all stakeholders. Our focus is on the implications for nurses, who are the largest global health care workforce but whose perspectives are not always fully considered. This essay discusses three overarching ethical issues that create a myriad of concerns and will likely affect nurses globally in unique ways: the safety of nurses, patients, colleagues, and families; the allocation of scarce resources; and the changing nature of nurses' relationships with patients and families. We urge policy‐makers to ensure that nurses' voices and perspectives are integrated into both local and global decision‐making so as to minimize the structural injustices many nurses have faced to date. Finally, we urge nurses to seek sources of support throughout this pandemic.

The COVID-19 pandemic raises difficult ethical questions for our healthcare system and its providers. Perhaps the most difficult is how to fairly distribute scarce resources, such as ICU beds and ventilators, as the answer will determine who lives and who dies. Compounding the difficulty, all of us are experiencing the dizzying newness of our socially distanced lives, and we sense that ‘things are different now.’ How do our traditional ethical principles apply to these very novel circumstances?

Background/aims Sparse literature exists on the challenges and ethical considerations of including people with limited access to healthcare, such as the uninsured and low-income, in clinical research in high-income countries. However, many ethical issues should be considered with respect to working with uninsured and low-income participants in clinical research, including enrollment and retention, ancillary care, and post-trial responsibilities. Attention to the uninsured and low-income is particularly salient in the United States due to the high rates of uninsurance and underinsurance. Thus, we conducted a scoping review on the ethical considerations of biomedical clinical research with uninsured and low-income participants in high-income countries in order to describe what is known and to pinpoint areas of needed research on this issue. Methods MEDLINE/PubMed, Embase, and Scopus databases were searched using terms that described main concepts of interest (e.g., uninsured, underinsured, access to healthcare, poverty, ethics, compensation, clinical research). Articles were included if they met four inclusion criteria: (1) English, (2) high-income countries context, (3) about research participants who are uninsured or low-income, which limits their access to healthcare, and in biomedical clinical research that either had a prospect of direct medical benefit or was offered to them on the basis of their ill health, and (4) recognizes and/or addresses challenges or ethical considerations of uninsured or low-income participants in biomedical clinical research. Results The searches generated a total of 974 results. Ultimately, 23 papers were included in the scoping review. Of 23 articles, the majority (n = 19) discussed enrollment and retention of uninsured or low-income participants. Several barriers to enrolling uninsured and low-income groups were identified, including limited access to primary or preventive care; lack of access to institutions conducting trials or physicians with enough time or knowledge about trials; overall lack of trust in the government, research, or medical system; and logistical issues. Considerably fewer articles discussed treatment of these participants during the course of research (n = 5) or post-trial responsibilities owed to them (n = 4). Thus, we propose a research agenda that builds upon the existing literature by addressing three broad questions: (1) What is the current status of uninsured research participants in biomedical clinical research in high-income countries? (2) How should uninsured research participants be treated during and after clinical research? (3) How, if at all, should additional protections for uninsured research participants affect their enrollment? Conclusions This review reveals significant gaps in both data and thoughtful analysis on how to ethically involve uninsured research participants. To address these gaps, we propose a research agenda to gather needed data and theoretical analysis that addresses three broad research questions.

Paying research participants is a widespread, long-standing, ethically acceptable, and perennially fraught practice. Although data are limited, payment is offered to participants in many research s...