Experiences and needs of women in vulnerable situations receiving additional interventions in maternity care: a qualitative study.

BACKGROUND: Tailoring an intervention to the needs and wishes of pregnant women in vulnerable situations (e.g., socioeconomic disadvantages) can reduce the risk of adverse outcomes and empower these women. A relatively high percentage of pregnant women in the North of the Netherlands are considered vulnerable to adverse pregnancy outcomes because of their low socioeconomic status and the intergenerational transmission of poverty. In order to improve perinatal and maternal health, next to standard prenatal care, various interventions for pregnant women in vulnerable situations have been developed. We do not know to what extent these additional interventions suit the needs of (pregnant) women. Therefore, the aim of this study is to gain insight into the experiences and needs of women in vulnerable situations who receive additional maternity care interventions in the Northern Netherlands. METHODS: Qualitative research was performed. We used a phenomenological framework, which is geared towards understanding people's experiences in the context of their everyday lives. In-depth semi-structured interviews were conducted with 17 pregnant women in vulnerable situations living in the Northern Netherlands. A thematic analysis was carried out. RESULTS: We found three themes that reflect the experiences and needs of pregnant women in vulnerable situations in relation to the intervention they receive. These themes relate to the care provided by health professionals, to the impact of being offered an intervention, and to practical issues related to receiving an additional intervention. We found that the needs of pregnant women in vulnerable situations who received an additional maternity care intervention varied. This variation in needs was mainly related to practical issues. Women also expressed common needs, namely the desire to have control over their situation, the wish to receive tailor-made information about the intervention, and the wish for the intervention to be specifically tailored to their circumstances. CONCLUSIONS: Living in vulnerable situations and being offered additional care evoked diverse reactions and emotions from pregnant women. We recommend that health professionals ensure open and clear communication with women, that they ensure continuity of care and relationship-centered care, and that they become aware of the process of stigmatization of women in vulnerable situations.

Moral obligations in conducting stem cell-based therapy trials for autism spectrum disorder.

Unregulated patient treatments and approved clinical trials have been conducted with haematopoietic stem cells and mesenchymal stem cells for children with autism spectrum disorder (ASD). While the former direct-to-consumer practice is usually considered rogue and should be legally constrained, regulated clinical trials could also be ethically questionable. Here, we outline principal objections against these trials as they are currently conducted. Notably, these often lack a clear rationale for how transplanted cells may confer a therapeutic benefit in ASD, and thus, have ill-defined therapeutic outcomes. We posit that ambiguous and unsubstantiated descriptions of outcome from such clinical trials may nonetheless appeal to the lay public as being based on authentic scientific findings. These may further fuel caregivers of patients with ASD to pursue unregulated direct-to-consumer treatments, thus exposing them to unnecessary risks. There is, therefore, a moral obligation on the part of those regulating and conducting clinical trials of stem cell-based therapeutic for ASD minors to incorporate clear therapeutic targets, scientific rigour and reporting accuracy in their work. Any further stem cell-based trials for ASD unsupported by significant preclinical advances and particularly sound scientific hypothesis and aims would be ethically indefensible.

Family experiences with non-therapeutic research on dying patients in the intensive care unit.

Experiences of substitute decision-makers with requests for consent to non-therapeutic research participation during the dying process, including to what degree such requests are perceived as burdensome, have not been well described. In this study, we explored the lived experiences of family members who consented to non-therapeutic research participation on behalf of an imminently dying patient.We interviewed 33 family members involved in surrogate research consent decisions for dying patients in intensive care. Non-therapeutic research involved continuous physiological monitoring of dying patients prior to and for 30 min following cessation of circulation. At some study centres participation involved installation of bedside computers. At one centre electroencephalogram monitoring was used with a subset of participants. Aside from additional monitoring, the research protocol did not involve deviations from usual end-of-life care.Thematic analysis of interviews suggests most family members did not perceive this minimal-risk, non-therapeutic study to affect their time with patients during the dying process, nor did they perceive research consent as an additional burden. In our analysis, consenting for participation in perimortem research offered families of the dying an opportunity to affirm the intrinsic value of patients' lives and contributions. This opportunity may be particularly important for families of patients who consented to organ donation but did not proceed to organ retrieval.Our work supports concerns that traditional models of informed consent fail to account for possible benefits and harms of perimortem research to surviving families. Further research into consent models which integrate patient and family perspectives is needed.

Non-static framework for understanding adaptive designs: an ethical justification in paediatric trials.

Many drugs used in paediatric medicine are off-label. There is a rising call for the use of adaptive clinical trial designs (ADs) in responding to the need for safe and effective drugs given their potential to offer efficiency and cost-effective benefits compared with traditional clinical trials. ADs have a strong appeal in paediatric clinical trials given the small number of available participants, limited understanding of age-related variability and the desire to limit exposure to futile or unsafe interventions. Although the ethical value of adaptive trials has increasingly come under scrutiny, there is a paucity of literature on the ethical dilemmas that may be associated with paediatric adaptive designs (PADs). This paper highlights some of these ethical concerns around safety, scientific/social value and caregiver/guardian comprehension of the trial design. Against this background, the paper develops a non-static conceptual lens for understanding PADs. It shows that ADs are epistemically open and reduce some of the knowledge-associated uncertainties inherent in clinical trials as well as fast-track the time to draw conclusions about the value of evaluated drugs/treatments. On this note, the authors argue that PADs are ethically justifiable given they (1) have multiple layers of safety, exposing enrolled children to lesser potential risks, (2) create social/scientific value generally and for paediatric populations in particular, (3) specifically foster the flourishing of paediatric populations and (4) can significantly improve paediatric trial efficiency when properly designed and implemented. However, because PADs are relatively new and their regulatory, ethical and logistical characteristics are yet to be clarified in some jurisdictions, the cooperation of various public and private stakeholders is required to ensure that the interests of children, their caregivers and parents/guardians are best served while exposing paediatric research subjects to the most minimal of risks when they are enrolled in paediatric trials that use ADs.

The impact of Ibero-American science on global bioethical thinking.

The bioethics research conducted in Ibero-American countries has been very much restricted to its own realm. The aim of this study was to perform a bibliometric evaluation of bioethics papers by authors affiliated with Ibero-American institutions, and to determine how their work influences global bioethics literature. We performed a literature search in the Web of Science Core Collection (WoS CC) and Scopus. We identified a total of 5,975 documents, of which 84.3% were articles, 11.6% reviews and 4.1% book chapters. The median number of citations per paper was higher in English-language journals. Only 10 articles published between 2010 and 2019 in peer-reviewed bioethics journals and produced exclusively by authors from Ibero-American institutions garnered more than 15 citations. Our study suggests that if researchers from Ibero-American institutions want to influence global bioethical thinking, they must make the required leap in quality to be able to publish in high-quality bioethics and mainstream journals.

Research abuses against people of colour and other vulnerable groups in early psychedelic research.

There is a growing resurgence in the study of psychedelic medicines for the treatment of mental health and substance use disorders. However, certain early investigations are marred by questionable research methods, abuses against research participants, and covert Central Intelligence Agency financial involvement. The purpose of this study was to understand how and to what extent people of colour and other vulnerable populations, specifically, individuals who were incarcerated or incapacitated due to mental health issues (inpatients with psychotic disorders), were exploited during the first wave of psychedelic research in the USA (1950-1980). To do so, we reviewed available empirical publications according to current ethical standards. Variables of interest included race and ethnicity of participants, population vulnerability, drug administration conditions, informed consent and undue influence. Our findings draw attention to the history of research abuses against people of colour in Western psychedelic research. In light of these findings, we urge a call-to-action to current psychedelic researchers to prioritise culturally inclusive and socially responsible research methods in current and future studies.

Reflections of methodological and ethical challenges in conducting research during COVID-19 involving resettled refugee youth in Canada.

Research involving migrant youth involves navigating and negotiating complex challenges in order to uphold their rights and dignity, but also all while maintaining scientific rigour. COVID-19 has changed the global landscape within many domains and has increasingly highlighted inequities that exist. With restrictions focusing on maintaining physical distancing set in place to curb the spread of the virus, conducting in-person research becomes complicated. This article reflects on the ethical and methodological challenges encountered when conducting qualitative research during the pandemic with Syrian migrant youth who are resettled in Canada. The three areas discussed from the study are recruitment, informed consent and managing the interviews. Special attention to culture as being part of the study's methodology as an active reflexive process is also highlighted. The goal of this article is to contribute to the growing understanding of complexities of conducting research during COVID-19 with populations which have layered vulnerabilities, such as migrant youth. This article hopes that the reflections may help future researchers in conducting their research during this pandemic by being cognizant of both the ethical and methodological challenges discussed.

Ethical considerations of recruiting migrant workers for clinical trials.

Migrant workers in dormitories are an attractive source of clinical trial participants. However, they are a vulnerable population that has been disproportionately affected by the COVID-19 pandemic. Guidelines on recruiting vulnerable populations (such as prisoners, children or the mentally impaired) for clinical trials have long been established, but ethical considerations for migrant workers have been neglected. This article aims to highlight and explain what researchers recruiting migrant workers must be cognizant of, and offers recommendations to address potential concerns. The considerations raised in this article include: three types of illiteracy, power dynamics, the risks associated with communal living and potential benefits to the migrant workers as well as researchers.

Controlled human infection with SARS-CoV-2 to study COVID-19 vaccines and treatments: bioethics in Utopia.

A number of papers have appeared recently arguing for the conclusion that it is ethically acceptable to infect healthy volunteers with severe acute respiratory syndrome coronavirus 2 as part of research projects aimed at developing COVID-19 vaccines or treatments. This position has also been endorsed in a statement by a working group for the WHO. The papers generally argue that controlled human infection (CHI) is ethically acceptable if (1) the risks to participants are low and therefore acceptable, (2) the scientific quality of the research is high, (3) the research has high social value, (4) participants give full informed consent, and (5) there is fair selection of participants. All five conditions are necessary premises in the overall argument that such research is ethically acceptable. The arguments concerning risk and informed consent have already been critically discussed in the literature. This paper therefore looks specifically at the arguments relating to condition 3 'high social value' and condition 5 'fair selection of participants' and shows that whereas they may be valid, they are not sound. It is highly unlikely that the conditions that are necessary for ethical CHI trials to take place will be fulfilled. Most, if not all, CHI trials will thus be well intentioned but unethical.

Human infection challenge studies in endemic settings and/or low-income and middle-income countries: key points of ethical consensus and controversy.

Human infection challenge studies (HCS) involve intentionally infecting research participants with pathogens (or other micro-organisms). There have been recent calls for more HCS to be conducted in low-income and middle-income countries (LMICs), where many relevant diseases are endemic. HCS in general, and HCS in LMICs in particular, raise numerous ethical issues. This paper summarises the findings of a project that explored ethical and regulatory issues related to LMIC HCS via (i) a review of relevant literature and (ii) 45 qualitative interviews with scientists and ethicists. Among other areas of consensus, we found that there was widespread agreement that LMIC HCS can be ethically acceptable, provided that they have a sound scientific rationale, are accepted by local communities and meet usual research ethics requirements. Unresolved issues include those related to (i) acceptable approaches to trade-offs between the scientific aim to produce generalisable results and the protection of participants, (iii) the sharing of benefits with LMIC populations, (iii) the acceptable limits to risks and burdens for participants, (iv) the potential for third-party risk and whether the degree of acceptable third-party risk is different in endemic settings, (v) the conditions under which (if any) it would be appropriate to recruit children for disease-causing HCS, (v) appropriate levels of payment to participants and (vi) appropriate governance of (LMIC) HCS. This paper provides preliminary analyses of these ethical considerations in order to (i) inform scientists and policymakers involved in the planning, conduct and/or governance of LMIC HCS and (ii) highlight areas warranting future research. Insofar as this article focuses on HCS in (endemic) settings where diseases are present and/or widespread, much of the analysis provided is relevant to HCS (in HICs or LMICs) involving pandemic diseases including COVID19.

Paediatric xenotransplantation clinical trials and the right to withdraw.

Clinical trials of xenotransplantation (XTx) may begin early in the next decade, with kidneys from genetically modified pigs transplanted into adult humans. If successful, transplanting pig hearts into children with advanced heart failure may be the next step. Typically, clinical trials have a specified end date, and participants are aware of the amount of time they will be in the study. This is not so with XTx. The current ethical consensus is that XTx recipients must consent to lifelong monitoring. While this presents challenges to the right to withdraw in the adult population, additional and unanswered questions also linger in the paediatric population. In paediatric XTx, parents or guardians consent not only to the initial treatment of the child but also to lifelong monitoring, thus making a decision whose consequences will remain present as the child develops the capacity for assent, and finally the capacity for informed consent or refusal. This article presents and evaluates unanswered paediatric ethical questions in regard to the right to withdraw from XTx follow-up in the paediatric population.

Disclosure of non-recent (historic) childhood sexual abuse: What should researchers do?

Non-recent (historic) childhood sexual abuse is an important issue to research, though often regarded as taboo and frequently met with caution, avoidance or even opposition from research ethics committees. Sensitive research, such as that which asks victim-survivors to recount experiences of abuse or harm, has the propensity to be emotionally challenging for both the participant and the researcher. However, most research suggests that any distress experienced is usually momentary and not of any clinical significance. Moreover, this type of research offers a platform for voices which have often been silenced, and many participants report the cathartic effect of recounting their experiences in a safe, non-judgemental space. With regard to the course of such research, lines of inquiry which ask adult participants to discuss their experiences of childhood sexual abuse may result in a first-time disclosure of that abuse by the victim-survivor to the researcher. Guidance about how researchers should respond to first-time disclosure is lacking. In this article, we discuss our response to one research ethics committee which had suggested that for a qualitative study for which we were seeking ethical approval (investigating experiences of pregnancy and childbirth having previously survived childhood sexual abuse), any disclosure of non-recent (historic) childhood sexual abuse which had not been previously reported would result in the researcher being obliged to report it to relevant authorities. We assess this to be inconsistent with both law and professional guidance in the United Kingdom; and provide information and recommendations for researchers and research ethics committees to consider.

Constructing authentic decisions: proxy decision making for research involving adults who lack capacity to consent.

Research involving adults who lack capacity to consent relies on proxy (or surrogate) decision making. Proxy decisions about participation are ethically complex, with a disparity between normative accounts and empirical evidence. Concerns about the accuracy of proxies' decisions arise, in part, from the lack of an ethical framework which takes account of the complex and morally pluralistic world in which proxy decisions are situated. This qualitative study explored the experiences of family members who have acted as a research proxy in order to develop an understanding of the ethical concepts involved, and the interactions between those concepts. Proxies described a complex process of respecting the wishes and preferences of the person they represented, whist integrating preferences with what they viewed as being in the interests of the person. They aimed to make a decision that was 'best' for the person and protected them from harm; they also aimed to make the 'right' decision, viewed as being authentic to the person's values and life. Decisions were underpinned by the relationship between the person and their proxy, in which both trust and trustworthiness were key. Proxies' decisions, based both on respect for the person and the need to protect their interests, arose out of their dual role as both proxy and carer. The findings raise questions about accounts which rely on existing normative assumptions with a focus on accuracy and discrepancy, and which fail to take account of the requirement for proxies to make authentic decisions that arise out of their caring obligations.

Donor-funded research: permissible, not perfect.

Donor-funded research is research funded by private donors in exchange for research-related benefits, such as trial participation or access to the trial intervention. This has been pejoratively referred to as 'pay to play' research, and criticised as unethical. We outline three models of donor-funded research, and argue for their permissibility on the grounds of personal liberty, their capacity to facilitate otherwise unfunded health research and their consistency with current ethical standards for research. We defend this argument against objections that donor-funded research is wrongly exploitative, unfair and undermines the public good of medical research. Our conclusion is that, like all human subjects research, donor-funded research should be regulated via standard health research legislation/guidelines and undergo Research Ethics Committee/Institutional Review Board and scientific peer-review. We expect that, measured against these standards, some donor-funded research would be acceptable.

Reporting suspected abuse or neglect in research involving children.

In this article, we explore the ethical issues related to the reporting of suspected abuse or neglect in research involving children. Ethical dilemmas related to reporting child maltreatment are often complex because the rights of children and their adult caregivers may conflict and determinations of abuse or neglect are socially constructed judgments that depend on particular circumstances. We argue that when reporting is legally mandated, investigators must follow the law and report their suspicions to Child Protective Services. When reporting is not legally mandated, investigators still have an ethical obligation to report to help prevent additional maltreatment and allow children to obtain access to services needed to recover from abuse or neglect. We also argue that investigators should include plans and procedures in the research protocol for making reports and training research staff in recognising evidence of child abuse or neglect. Although investigators should report evidence of abuse or neglect that is discovered incidentally, they have no mandate to actively search for such evidence when it is not related to the study's objectives. Investigators should also inform parents and children about their obligations to report suspected abuse or neglect.

Addressing ethical challenges in HIV prevention research with people who inject drugs.

Despite recent advances in HIV prevention and treatment, high HIV incidence persists among people who inject drugs (PWID). Difficult legal and political environments and lack of services for PWID likely contribute to high HIV incidence. Some advocates question whether any HIV prevention research is ethically justified in settings where healthcare system fails to provide basic services to PWID and where implementation of research findings is fraught with political barriers. Ethical challenges in research with PWID include concern about whether research evidence will be translated into practice; concerns that research might exacerbate background risks; and ethical challenges regarding the standard of HIV prevention in research. While these questions arise in other research settings, for research with PWID, these questions are especially controversial. This paper analyses four ethical questions in determining whether research could be ethically acceptable: (1) Can researchers ensure that research does not add to the burden of social harms and poor health experienced by PWID? (2) Should research be conducted in settings where it is uncertain whether research findings will be translated into practice? (3) When best practices in prevention and care are not locally available, what standard of care and prevention is ethically appropriate? (4) Does the conduct of research in settings with oppressive policies constitute complicity? We outline specific criteria to address these four ethical challenges. We also urge researchers to join the call to action for policy change to provide proven safe and effective HIV prevention and harm reduction interventions for PWID around the world.

Vulnerability of pregnant women in clinical research.

BACKGROUND: Notwithstanding the need to produce evidence-based knowledge on medications for pregnant women, they remain underrepresented in clinical research. Sometimes they are excluded because of their supposed vulnerability, but there are no universally accepted criteria for considering pregnant women as vulnerable. Our aim was to explore whether and if so to what extent pregnant women are vulnerable as research subjects. METHOD: We performed a conceptual and empirical analysis of vulnerability applied to pregnant women. ANALYSIS: A conceptual analysis supports Hurst's definition of vulnerability. Consequently, we argue that pregnant women are vulnerable if they encounter an identifiably increased likelihood of incurring additional or greater wrong. According to the literature, this increased likelihood could exist of four alleged features for pregnant women's vulnerability: (i) informed consent, (ii) susceptibility to coercion, (iii) higher exposure to risk due to lack of knowledge, (iv) vulnerability of the fetus. DISCUSSION: Testing the features against Hurst's definition demonstrates that they all concern the same issue: pregnant women are only vulnerable because a higher exposure to risk due to lack of scientific knowledge comprises an increased wrong. Research Ethics Committees have a responsibility to protect the vulnerable, but a higher exposure to risk due to lack of scientific knowledge is a much broader issue and also needs to be addressed by other stakeholders. CONCLUSIONS: The only reason why pregnant women are potentially vulnerable is to the extent that they are increasingly exposed to higher risks due to a lack of scientific knowledge. Accordingly, the discussion can advance to the development of practical strategies to promote fair inclusion of pregnant women in clinical research.

Cure research and consent: the Mississippi Baby, Barney Clark, Baby Fae and Martin Delaney.

Trials using children as subjects are much more problematic from an informed consent perspective than trials on competent adults, although the 'therapeutic misconception' is a central concern in both. The role of famous experiments and the use of one individual's experience to designate and justify a whole category of research have always threatened to undermine the validity of informed consent to research by making it seem to be a validated therapy. In research, the unintended consequence of 'naming' based on goals ('cure') or specific individuals (like the Mississippi Baby) tends to subvert informed consent when the famous case is a 'success', and to prematurely end a line of research if the named subject dies. Names, including the Mississippi Baby, Barney Clark, Baby Fae and even Martin Delaney, are more suggestive of fantasy than science. The word 'cure' should not be used in obtaining consent for HIV 'cure trials', and names of people involved in past experiments should be avoided in the informed consent process. These two modest proposals should reduce the risks of the therapeutic misconception in 'cure research'.

Feasibility of conducting prospective observational research on critically ill, dying patients in the intensive care unit.

Studying patients during the end of life is important, as it has the potential to lead to improvements in care for the dying. For patients who die after a controlled withdrawal of life-sustaining therapies in the intensive care unit, information about the natural history of death and the process of removing life support has additionally led to advances in practice for deceased organ donation. However, this unique population of severely critically ill and imminently dying patients has been difficult to study, largely due to assumptions made by research teams and ethics boards alike about the logistical difficulties of obtaining consent and completing research procedures before or during the process of withdrawal of life-sustaining therapies. In this paper, we describe the ethics substudy of the first prospective observational research study in Canada to obtain consent and collect clinical data on patients during the process of withdrawal of life-sustaining therapies in the intensive care unit. We describe in detail the process of protocol development, review by five institutional research ethics boards and bedside staff satisfaction with the study. We conclude that prospective research on a critically ill and imminently dying population is feasible and can be conducted in an ethical manner. Further information is needed about the experiences and motivations of families and substitute decision makers who provide consent for research on critically ill intensive care unit patients at the end of life.

Prisoners as research participants: current practice and attitudes in the UK.

The use of prisoners as research participants is controversial. Efforts to protect them in response to past exploitation and abuse have led to strict regulations and reluctance to involve them as participants. Hence, prisoners are routinely denied the opportunity to participate in research. In the absence of comprehensive information regarding prisoners' current involvement in research, we examined UK prisoners' involvement through review of research applications to the UK National Research Ethics Service. We found that prisoners have extremely limited access to research participation. This analysis was augmented by a survey of those involved in research and research governance (UK researchers and Research Ethics Committee members). Our results suggest that pragmatic concerns regarding the perceived burden of including prisoners are far more prominent in motivating their exclusion than ethical concerns or knowledge of regulations. While prisoners may remain a vulnerable research population due to constraints upon their liberty and autonomy and the coercive nature of the prison environment, routine exclusion from participation may be disadvantageous. Rigorous ethical oversight and the shift in the prevailing attitude towards the risks and benefits of participation suggest that it may be time for research to be more accessible to prisoners in line with the principle of equivalence in prison healthcare. We suggest the necessary first step in this process is a re-examination of current guidance in the UK and other countries with exclusions.