Research Ethics Literature Research Articles

Policy equipoise and interventional superiority

ABSTRACT According to the norm of policy equipoise, it is permissible to randomly assign participants to two or more interventions in a public policy randomised controlled trial (RCT) when there is meaningful uncertainty among the relevant expert community regarding which intervention is superior. While this norm is gaining traction in the research ethics literature, the idea of interventional superiority remains unclear. Is one intervention superior to another if it is reasonably expected to more effectively realise one outcome of interest, even though there is uncertainty regarding other outcomes of interest? Or, must an intervention be reasonably expected to more effectively realise all outcomes of interest? I address this question in this paper. My aim is to develop and defend an account of interventional superiority for policy RCTs that are authorised, funded, or conducted by government institutions. I defend the greatest value view, according to which one intervention is superior to another if and only if it is reasonably expected to more effectively realise a set of outcomes with greater value.

Structural Influences on Consent Decisions in Participatory Health Research in Eswatini.

Recognition that structural factors influence participation decisions and have potential to coerce participation, emerged relatively recently in research ethics literature. Empirical evidence to elucidate the nature of "structural" coercion and influence is needed to optimise respect for autonomy through voluntary informed consent. We present findings from ethnographic data about community co-researchers' experiences designing and implementing demographic and health survey consent procedures in participatory health research in Eswatini. Informed by Bourdieu's sociological theory of multiple types of capital/power, our findings detail structural influences on research participation decisions, highlight the inherently power-laden dynamics of consent interactions, and suggest that to be optimally ethical, research ethics principles and practices should consider and account for structural power dynamics.

When is it impractical to ask informed consent? A systematic review.

BackgroundInformed consent is one of the cornerstones of biomedical research with human subjects. Research ethics committees may allow for a modification or a waiver of consent when the research has social value, involves minimal risk, and if consent is impractical to obtain. While the conditions of social value and minimal risk have received ample attention in research ethics literature, the impractical condition remains unclear. There seem to be different interpretations of the meaning of impractical within academic literature. To address this lack of clarity, we performed a systematic review on the interpretation of impractical.MethodsFirst, we examined international research ethics guidelines on their usage and interpretation of impractical. Next, we used international ethical guidelines to identify synonyms of the term “impractical.” Accordingly, PubMed, Embase, and Web of Science were searched for articles that included “informed consent” and “impractical” or one of its synonyms.ResultsWe found that there were only a few international ethics guidelines that described what could be considered impractical. Out of 2329 identified academic articles, 42 were included. Impractical was used to describe four different conditions: (1) obtaining informed consent becomes too demanding for researchers, (2) obtaining informed consent leads to invalid study outcomes, (3) obtaining informed consent harms the participant, and (4) obtaining informed consent is meaningless for the participant.ConclusionThere are conditions that render conventional informed consent truly impractical, such as untraceable participants or harm for participants. At the same time, researchers have a moral responsibility to design an infrastructure in which consent can be obtained, even if they face hardship in obtaining consent. In addition, researchers should seek to minimize harm inflicted upon participants when harm may occur as a result of the consent procedure. Invalidity of research due to consent issues should not be regarded as impractical but as a condition that limits the social value of research. Further research is essential for when a waiver of informed consent based on impractical is also reasonable.

Community-Level Vulnerabilities and Political Field Experiments

Most research ethics literature on vulnerability focuses on the vulnerability of individuals and populations defined by the potential vulnerability of their members (such as adults with intellectual disabilities or prisoners). However, research involving human participants does not always take the individual as the unit of analysis: political experiments may apply an intervention to a community as a whole. This paper argues that community-level vulnerability is not reducible to the sum of the vulnerabilities of community members, and that there is thus a need to consider vulnerability at the community level of analysis when analyzing the ethical implications of political field experiments. I first review ethical literature on community intervention research and the emerging scholarship on the ethics of political field experiments. I then highlight key accounts of the concept of vulnerability at an individual level. Drawing on Whitfield’s concept of “collective wrongs,” I argue that communities can be negatively affected in ways that are distinct from harms to individual community members, and that variation in susceptibility to such wrongs at the community level is largely consistent with existing conceptualizations of vulnerability. I suggest questions that researchers should consider when designing political field experiments to ensure that community-level vulnerabilities are taken into account.

Accounting for research fatigue in research ethics.

How to account for participants' psychological and emotional exhaustion with research has been under-explored in the research ethics literature. Research fatigue, as it is known, has significant impacts on patients' well-being and their ongoing and future participation in studies. From the perspective of researchers and researched communities, research fatigue also creates selection bias and opportunity costs, negatively impacting the collective scientific enterprise. Institutional Review Boards should systematically consider research fatigue during the research approval process and strive to mitigate it.

Making Autism Research Inclusive by Attending to Intersectionality: a Review of the Research Ethics Literature

Growth in autism research necessitates corresponding attention to autism research ethics, including ethical and meaningful inclusion of diverse participants. This paper presents the results of a review of research ethics literature, strengthened by consultation with a task force involving autism professionals, family members, and self-advocates on the spectrum. It reviews research ethics concerns around sex and gender; level of support needs; communication modes; race, ethnicity, geography, and language; socioeconomic status; and age. The exclusion of marginalized subgroups of people with autism is a major ethical concern. Researchers can facilitate inclusion by using inclusive terminology, developing accessible communication strategies, or traveling to meet participants. A person-oriented research ethics framework described in this paper structures the advice offered in the literature to create inclusive and supportive research environments.

Judging the Social Value of Health-Related Research: Current Debate and Open Questions.

On the occasion of the 40th anniversary of the Belmont Report-one of the foundational documents of modern research ethics-this article reviews the ethical debate about the social value of health-related research with human participants. It shows that the Belmont Report discusses the social value of research only cursorily, much like most of the research ethics literature until recently. The article then reviews the current debate and open questions about the social value of health-related research, organized around three questions: (1) is social value a necessary ethical requirement for health-related research with human participants? (2) if so, how should a social value requirement should be specified? and (3) how should such a requirement be implemented in practice?

Ethical Consistency and Experience: An Attempt to Influence Researcher Attitudes Toward Questionable Research Practices Through Reading Prompts.

Over the past couple of decades, the apparent widespread occurrence of Questionable Research Practices (QRPs) in scientific research has been widely discussed in the research ethics literature as a source of concern. Various ways of reducing their use have been proposed and implemented, ranging from improved training and incentives for adopting best practices to systematic reforms. This article reports on the results of two studies that investigated the efficacy of simple, psychological interventions aimed at changing researcher attitudes toward QRPs. While the interventions did not significantly modify researchers' reactions to QRPs, they showed differential efficacy depending on scientists' experience, suggesting complexities in researcher psychology and the ethics of QRPs that merit further study.

Improving dissemination of study results: perspectives of individuals with cystic fibrosis

The practice of communicating research findings to participants has been identified as important in the research ethics literature, but little research has examined empirically how this occurs and what research participants’ views are in this regard. We interviewed 21 adults with cystic fibrosis who had previously participated in research and 2 research coordinators at a cystic fibrosis clinic. We aimed to better understand research participants’ views on receiving research results, types of findings they are interested in, how they would like to receive this information, and the impact this might have on future participation. Participants reported that they do not generally recall receiving study findings, though many reported that they would like to receive them. While some participants were not interested in receiving results, all participants felt that these results should be provided when desired by participants and believed that receiving study findings would support future participation. Participants felt that an accessible format, such as a lay summary, would be most helpful. This study supports calls to make study findings available to participants, though the format in which they are provided requires consideration. Participants rarely recalled receiving findings despite the clinic in which this study was conducted returning them regularly. Therefore, questions pertaining to the provision of study findings must focus less on whether to share the findings and more on how to share them with participants most effectively. The logistics of providing study findings may be challenging in some cases, but participant support for the practice highlights its importance.

A Tale of Two Capacities: Including Children and Decisionally Vulnerable Adults in Biomedical Research.

The participation of individuals who lack decision-making capacity is essential for advancing genomics research and neuroscience, but raises ethical and legal challenges relating to vulnerability, consent, and exclusion. Capacity differences between populations and individuals, the dynamics of capacity over time, and evolving legal consent and capacity regimes all raise uncertainty for researchers, institutional review boards, and policy makers. We review international ethical and legal best practices for including children and decisionally vulnerable adults in health research. Research ethics norms and literature tend to split such groups into narrow silos, which results in inconsistency and conceptual confusion, or to lump them together, which fails to take into account morally relevant differences. Through a narrative review of international norms, we identify challenges common to both groups, while drawing out distinctions reflecting their opposite capacity trajectories. Our comparison between these two populations clarifies underlying ethical concepts and offers opportunities for critique. Children need protection to foster their long-term autonomy, while decisionally vulnerable adults need to be provided with support in order to exercise their autonomy. This leads to differences in how researchers determine who lacks capacity, who has authority to consent, and what criteria guide such decision-making. We also consider how capacity issues color contemporary research governance debates over broad consent, data protection compliance, data sharing, and the return of individual research results and incidental findings.

Ethical considerations for HIV cure-related research at the end of life

BackgroundThe U.S. National Institute of Allergies and Infectious Diseases (NIAID) and the National Institute of Mental Health (NIMH) have a new research priority: inclusion of terminally ill persons living with HIV (PLWHIV) in HIV cure-related research. For example, the Last Gift is a clinical research study at the University of California San Diego (UCSD) for PLWHIV who have a terminal illness, with a prognosis of less than 6 months.DiscussionAs end-of-life (EOL) HIV cure research is relatively new, the scientific community has a timely opportunity to examine the related ethical challenges. Following an extensive review of the EOL and HIV cure research ethics literature, combined with deliberation from various stakeholders (biomedical researchers, PLWHIV, bioethicists, and socio-behavioral scientists) and our experience with the Last Gift study to date, we outline considerations to ensure that such research with terminally ill PLWHIV remains ethical, focusing on five topics: 1) protecting autonomy through informed consent, 2) avoiding exploitation and fostering altruism, 3) maintaining a favorable benefits/risks balance, 4) safeguarding against vulnerability through patient-participant centeredness, and 5) ensuring the acceptance of next-of-kin/loved ones and community stakeholders.ConclusionEOL HIV cure-related research can be performed ethically and effectively by anticipating key issues that may arise. While not unique to the fields of EOL or HIV cure-related research, the considerations highlighted can help us support a new research approach. We must honor the lives of PLWHIV whose involvement in research can provide the knowledge needed to achieve the dream of making HIV infection curable.

Government Policy Experiments and Informed Consent

Abstract Governments are increasingly making use of field experiments to evaluate policy interventions in the spheres of education, public health and welfare. However, the research ethics literature is largely focused on the clinical context, leaving investigators, institutional review boards and government agencies with few resources to draw on to address the ethical questions they face regarding such experiments. In this article, we aim to help address this problem, investigating the conditions under which informed consent is required for ethical policy research conducted or authorized by government. We argue that investigators need not secure participants' informed consent when conducting government policy experiments if: (i) the government institution conducting or authorizing the experiment possesses a right to rule over the spheres of policy targeted by the research; and (ii) data collection does not involve the violation of participants' autonomy rights.

Clinical Equipoise and Adaptive Clinical Trials

Ethically permissible clinical trials must not expose subjects to risks that are unreasonable in relation to anticipated benefits. In the research ethics literature, this moral requirement is typically understood in one of two different ways: (1) as requiring the existence of a state of clinical equipoise, meaning a state of honest, professional disagreement among the community of experts about the preferred treatment; or (2) as requiring an equilibrium between individual and collective ethics. It has been maintained that this second interpretation makes it mandatory to minimize the number of patients receiving the treatment that will eventually be shown to be inferior by the trial. This requirement has led to the development of adaptive trials, i.e., trials in which treatment allocation is determined by data accumulated during interim analysis. Many statisticians argue that in some circumstances—typically with potentially high benefits, as in the much discussed ECMO trial—adaptive design is the only ethically permissible experimental design. Nevertheless, some proponents of clinical equipoise argue that adaptive trials are neither ethically required nor permissible. More specifically, they argue that clinical trials using adaptive designs fail to meet the moral requirement of clinical equipoise, since these trials presuppose an epistemic state that is incompatible with a physician’s duty of care to her subjects. This paper emphasizes that the debate is to a large extent resting on an epistemological confusion. Specifically, I argue that this response conflates two different conceptions of statistical evidence (i.e., frequentist and Bayesian), and that recognizing this distinction elucidates an epistemological framework in which adaptive trials are both consistent with and recommended by the moral requirement of clinical equipoise.

Informed consent in cluster randomised trials: new and common ethical challenges

Cluster randomised trials are an increasingly important methodological tool in health research but they present challenges to the informed consent requirement. In the relatively limited literature on the ethics of...

Research in Pregnancy: The Ethics of Risk-Benefit Tradeoffs Between Woman, Fetus, and Future Child [21G

INTRODUCTION: In contrast to many areas of health research, the field of HIV/AIDS has pursued research with pregnant women as a key component of its research agenda. Several large trials have made vivid a number of critical ethical questions for research with pregnant women broadly--including how risks and benefits can and should be traded off between the woman, the fetus, and the future child--offering an important opportunity for building an adequate ethical framework for research in pregnancy, more generally. METHODS: As a part of a multidisciplinary research project addressing barriers and opportunities to conducting research with pregnant women (the PHASES project--Pregnancy and HIV/AIDS: Seeking Equitable Study), we examined several large HIV network studies conducted in the last five years that required risk/benefit tradeoffs between woman, fetus and future child in conjunction with U.S. research regulations and the research ethics literature. Selected studies were analyzed in conjunction with U.S. research regulations and the research ethics literature. RESULTS: We describe three challenging tradeoff scenarios encountered in HIV network studies and develop an approach that is consistent with US regulations governing research with pregnant women. CONCLUSION: The inclusion of pregnant women in clinical research can be justified based on 1) the prospect of direct and indirect benefit to fetus; 2) the imposition of no more than minimal risk for studies involving no prospect of benefit to fetus; or 3) a reasonable ratio of maternal benefit to fetal risk. Tradeoffs between the fetus and the future child risk should be responsive to potential participants’ values.

Embracing qualitative research: a visual model for nuanced research ethics oversight

The research ethics review systems within universities evolved from the positivist biomedical model but have expanded to include all non-clinical research involving human subjects. However, the application of the biomedical paradigm to qualitative research often creates significant problems. This article highlights the fundamental differences between biomedical and humanities and social science (HSS) research, illustrating that one size does not fit all when it comes to research ethics review. Recognising the resource constraints faced by many higher level education institutions, we develop a model which encompasses the traditional research ethics concepts without requiring separate oversight procedures. After its original construction based on extent research ethics literature, the model was evolved based on findings from qualitative interviews carried out with expert members of research ethics committees. The model can be adapted to multiple contexts through the application of different levels of tolerance in each domain. Our contribution is twofold: (1) to synthesise from the literature an explicit rationale for differentiating research contexts when it comes to research ethics oversight; and (2) to provide research ethics committees with a workable visual model that can be used to aid decision making in diverse research domains.

The ethics of ethical debates in peace and conflict research: Notes towards the development of a research covenant

This article outlines the case for peace and conflict researchers to formulate a research covenant to better shape their ethical obligations and responsibilities. This is an urgent necessity given that ethical debates have in some proponents become emotive and are not conducted in an ethical manner. In coming to this assessment, the article reviews trends in the research ethics literature and draws out some of the generic issues addressed in a review of the personal reflexivity that an assortment of individual peace and conflict researchers have engaged in when recounting their fieldwork experiences. These generic issues are reformulated in an attempt to codify appropriate ethical practice in peace and conflict research, and they go towards determining the contents of the research covenant. It is suggested that the research covenant is a more ethical way to debate the ethics of peace and conflict research.

What Factors Influence the Production of Orthopaedic Research in East Africa? A Qualitative Analysis of Interviews

Research addressing the burden of musculoskeletal disease in low- and middle-income countries does not reflect the magnitude of the epidemic in these countries as only 9% of the world's biomedical resources are devoted to addressing problems that affect the health of 90% of the world's population. Little is known regarding the barriers to and drivers of orthopaedic surgery research in such resource-poor settings, the knowledge of which would help direct specific interventions for increasing research capacity and help surgeons from high-income countries support the efforts of our colleagues in low- and middle-income countries. We sought to identify through surveying academic orthopaedic surgeons in East Africa: (1) barriers impeding research, (2) factors that support or drive research, and (3) factors that were identified by some surgeons as barriers and others as drivers (what we term barrier-driver overlap) as they considered the production of clinical research in resource-poor environments. Semistructured interviews were conducted with 21 orthopaedic surgeon faculty members at four academic medical centers in Ethiopia, Kenya, Tanzania, and Uganda. Qualitative content analysis of the interviews was conducted using methods based in grounded theory. Grounded theory begins with qualitative data, such as interview transcripts, and analyzes the data for repeated ideas or concepts which then are coded and grouped into categories which allow for identification of subjects or problems that may not have been apparent previously to the interviewer. We identified and quantified 19 barriers to and 21 drivers of orthopaedic surgery research (mentioned n=1688 and n=1729, respectively). Resource, research process, and institutional domains were identified to categorize the barriers (n=7, n=5, n=7, respectively) and drivers (n=7, n=8, n=6, respectively). Resource barriers (46%) were discussed more often by interview subjects compared with the research process (26%) and institutional barriers (28%). Drivers of research discussed at least once were proportionally similar across the three domains. Some themes such as research ethics boards, technology, and literature access occurred with similar frequency as barriers to and drivers of orthopaedic surgery research. The barriers we identified most often among East African academic orthopaedic faculty members focused on resources to accomplish research, followed by institutional barriers, and method or process barriers. Drivers to be fostered included a desire to effect change, collaboration with colleagues, and mentorship opportunities. The identified barriers and drivers of research in East Africa provide a targeted framework for interventions and collaborations with surgeons and organizations from high-resource settings looking to be involved in global health.

Balancing research interests and patient interests: a qualitative study into the intertwinement of care and research in paediatric oncology.

Traditionally, in ethical guidelines and in research ethics literature, care and research are clearly separated based on their different objectives. In contrast, in paediatric oncology, research and care are closely combined. Currently, it is unknown how relevant actors in paediatric oncology perceive this combination of research and care. We conducted a qualitative study into the experiences of those involved in Dutch paediatric oncology with the intertwinement of research and care and the dual role of paediatric oncologists as researchers and treating physicians. A qualitative study approach, using two focus groups and 19 semi-structured, in-depth interviews with paediatric oncologists, research coordinators, parents of children with cancer, and adolescents with cancer. Four themes characterize how actors experience the intertwinement of research and care in paediatric oncology. First, research is considered of major importance, and paediatric oncology professionals convey this message to patients and their parents. Second, there is ambiguity about categorization of studies into cancer therapy as either research or treatment. Third, role conflicts appear within the work of the paediatric oncologists. Finally, the various benefits of combining treatment with research are emphasized. Research is regarded as a fundamental and indispensable characteristic of paediatric oncology practice. Paediatric oncology professionals, parents, and patients have a very positive outlook on combining research and care, but they may not be sufficiently critical with respect to potential conflicts. Increased reflection on how to optimally combine research and care could serve as an important protection of the interests of children with cancer and their parents.

What are fair study benefits in international health research? Consulting community members in Kenya.

BackgroundPlanning study benefits and payments for participants in international health research in low- income settings can be a difficult and controversial process, with particular challenges in balancing risks of undue inducement and exploitation and understanding how researchers should take account of background inequities. At an international health research programme in Kenya, this study aimed to map local residents' informed and reasoned views on the effects of different levels of study benefits and payments to inform local policy and wider debates in international research.Methods and FindingsUsing a relatively novel two-stage process community consultation approach, five participatory workshops involving 90 local residents from diverse constituencies were followed by 15 small group discussions, with components of information-sharing, deliberation and reflection to situate normative reasoning within debates. Framework Analysis drew inductively and deductively on voice- recorded discussions and field notes supported by Nvivo 10 software, and the international research ethics literature. Community members' views on study benefits and payments were diverse, with complex contextual influences and interplay between risks of giving ‘too many’ and ‘too few’ benefits, including the role of cash. While recognising important risks for free choice, research relationships and community values in giving ‘too many’, the greatest concerns were risks of unfairness in giving ‘too few’ benefits, given difficulties in assessing indirect costs of participation and the serious consequences for families of underestimation, related to perceptions of researchers' responsibilities.ConclusionsProviding benefits and payments to participants in international research in low-income settings is an essential means by which researchers meet individual-level and structural forms of ethical responsibilities, but understanding how this can be achieved requires a careful account of social realities and local judgment. Concerns about undue inducement in low-income communities may often be misplaced; we argue that greater attention should be placed on avoiding unfairness, particularly for the most-poor.