Research Ethics

Factors Affecting Healthy Volunteers’ Long-Term Participation in Clinical Trials

Jill Fisher (PI

Social Medicine Collaborators: Arlene Davis, Malika Roman Isler, and Rebecca Walker (CIs)

Funded by the National Institute of General Medical Sciences (NIH) as an R01, this project investigates healthy volunteers’ patterns of participation in Phase I clinical trials, with particular attention to the differences among minority groups. The majority of healthy volunteers in clinical trials are serial participants, meaning that they enroll repeatedly in studies, so the research has a longitudinal design to understand volunteers’ patterns of participation in clinical trials. The project has four primary aims: (1) Assess how participants’ perceptions of the risks and benefits of Phase I participation change over time; (2) Examine how participants make decisions regarding their participation in clinical trials – including continuing serial participation – and assess the consistency of their choices over time; (3) Document how participants’ self-reported behaviors (a) affect the validity of clinical trials and (b) increase and/or mitigate harm that could come from serial participation, including behaviors that have health benefits; and (4) Compare participants’ perceptions, decisions, and behaviors across racial and ethnic groups.

The Second Wave Initiative

Anne Lyerly, Ruth Faden (Johns Hopkins University), Margaret Little (Georgetown University) (PIs)

Launched in 2009, the Second Wave Initiative is a collaborative academic effort to advocate for, and help find, ethically and scientifically responsible solutions for increasing our knowledge base for the treatment of pregnant women who face medical illness. In April of 2009, scholars from Georgetown, Johns Hopkins, and Duke held a two-day workshop to make progress in this challenging area. Participation included leaders from the NIH, FDA, as well as from leading academic medical centers and identified barriers, articulated the costs of ignorance, and proposed consensus proposals to immediately begin to improve pregnant women’s health. Second Wave advocates have also worked over the summer with Members of Congress and their staffs to raise awareness of the issue. Those efforts resulted inclusion of language in the House Committee Report accompanying the Fiscal 2010 Appropriations for the Departments of Labor, Health and Human Services and Education. We have published our work for academia and the public, including two op-eds in the New York Times [link to:]. Research and scholarship in the area are ongoing, with empirical studies aimed at understanding what matters to pregnant women considering enrollment in studies, what are the challenges faced by researchers, clinicians and policy makers; and conceptual work to help guide responsible research with pregnant women in the future.

Central IRB Pilot Project

Daniel Nelson

Oversight of multicenter clinical trials is complicated by the traditional approach of replicate, sometimes contradictory, review of the identical protocol by multiple local IRBs for each site. Academic institutions are increasingly relying on central IRBs for these scenarios, but there are few data to guide their decisions. We are conducting a randomized, controlled comparison of local versus central IRB review, assessing both the efficiency and quality of review processes. The results of this novel project will be shared with institutions across the country, as well as used to inform local policy decisions at UNC-Chapel Hill.

Dual Parental Consent for Pediatric Research

Daniel Nelson

When research involving children is determined to present greater than minimal risk but no potential for direct benefit, permission is required from both parents, unless one is not reasonably available. These requirements are variably understood and applied, and guidance is lacking for investigators, IRBs and institutional legal counsel. We examined availability of parents to participate in the consent process for a research project on newborn screening, participation rates among couples, and factors that influenced the process.

Advancing Research Ethics Training in Southern Africa (ARESA)

Stuart Rennie (Co-PI)

Social Medicine Collaborator: Eric Juengst (CI)

This 5-year NIH-Fogarty International Center funded capacity building program—a collaboration between UNC Bioethics Center and the University of Stellenbosch—focuses on education in bioethics and research ethics for health care professionals in Southern Africa. A cohort of 10-12 trainees follow three 2-week intensive modules at the University of Stellenbosch during the calendar year and conduct a mentored research assignment in order to obtain a Postgraduate Diploma in Health Research Ethics. The aim of the program is to strengthen the bioethics capacity in the home institutions of the trainees, given that research-poor countries in Southern Africa are increasingly regarded as attractive venues for health research. The project has its own trainee-driven ARESA newsletter that is published biannually, and the project is establishing a Southern Africa research ethics committee member network.

Building Bioethics Capacity and Justice in Health

Stuart Rennie (Co-PI)

This program, funded by NIH-Fogarty International Center since 2004, has a mission to promote responsible research in the Democratic Republic and in Francophone Africa. It has established the Center Interdisciplinaire de Bioéthique pour l’Afrique Francophone (CIBAF) at the Kinshasa School of Public Health (KSPH) and has leveraged CIBAF’s resources to enhance ethics capacity locally, regionally and internationally. Through this project, the University of North Carolina (UNC) and KSPH strengthen CIBAF’s ongoing research, educational, consultation and network-building activities by broadening its current repertoire of research ethics, clinical ethics and public health ethics curricula; integrating ethics modules into a new MPH at KSPH with concentration in public health and bioethics; supporting short-term study visits at UNC; creating required research ethics modules for all doctorate degrees at KSPH; strengthening CIBAF members skills in grant and manuscript writing, research design methodology and English. The project has conducted numerous bioethics capacity workshops within the DR Congo, as well as Brazzaville (Republic of Congo) and Bujumbura (Burundi). The program also continues to provide training and support for a new bioethics unit at the Institut Nationale de Santé Publique et Communautaire (INSPC) in Antananarivo, Madagascar.

Virtue Ethics and Animal Research: Of Mice and Primates

Rebecca Walker

Does a researcher or lab technician who develops relationships with her animal subjects owe them a greater duty of care than one who does not? What is the moral significance of the positive or negative psychological effects on the researcher of doing animal research? Can, or should, a rhesus macaque monkey live a life that is a good one for its kind when it is housed in a research facility? What about a genetically modified mouse? These questions are of critical importance for a virtue-ethical assessment of animal research practices. Virtue ethics emphasizes the role of an agent’s character in determining the moral value of an action, focuses on habit and practice in developing good character traits, and places significant value on a well-lived life. Yet questions such as those posed above are rarely addressed by the two most common moral frameworks for assessing animal research (and the two rival philosophical accounts of morality to virtue ethics): duty-based and welfare-based accounts. This philosophical project brings these questions to the forefront in changing the moral discussion regarding animal research. The major product will be a book.

Clinical Ethics

The Complex Patient Project

Arlene Davis

Social Medicine Collaborator: Deborah Love

This clinical ethics pilot study examines the non-medical contributors to extended hospital lengths of stay and the strategies used by physicians, hospital staff and patients/families to contend with both medical decision-making and discharge planning decisions in these cases. The data in this mixed method study include medical records, clinical ethics consult records, policy review, and in-depth interviews. Special focus will be given to the roles played by hospitalists and clinical case managers who must balance the individual patient needs and institutional interests invoked by payer policies. In addition, we will analyze a hospital data set that includes all patients during a two-year period who experienced at least one length of stay of fifteen days or greater. Following this pilot study and building on its findings, our long-term goals are to (1) enhance clinicians’ ability to appreciate the ethical tensions that arise when clinical judgments, values and preferences differ from the beliefs, values and preferences of patients and their families, particularly in the context of institutional practices and demands; (2) identify opportunities for earlier identification of factors contributing to extended lengths of stay; and (3) development of educational interventions to address (1) and (2) with the aim of mitigating the non-medical contributors to hospital lengths of stay.

North Carolina Clinical Genomic Evaluation by NextGen Exome Sequencing (NC Genes)

Gail Henderson (PI for Project 3)

Social Medicine Collaborators: Giselle Corbie-Smith, Eric Juengst, Arlene Davis, Dan Nelson

Awarded in 2011, NCGENES is part of a U01 consortium funded by NHGRI to explore the clinical application of next generation sequencing. NCGENES Project 3 employs a theoretically-grounded multi-method approach to address the ethical, psychosocial, and behavioral implications of the production of diagnostic and incidental information through whole exome sequencing (WES) in a clinical setting. We use qualitative and quantitative methods to identify benefits and harms of providing WES diagnostic and incidental findings to patients, and employ a randomized longitudinal design for adult participants to investigate what types of WES results patients wish to receive, and assess the impact of being offered a choice to receive incidental findings or not. Inclusion of adults and children with a range of medical conditions and inclusion of medically underserved populations enhances the generalizability of results to clinical practice. We utilize ethnographic observational methods to track the development of the WES results classification system and how it is communicated and used from the lab to the clinician and patient.

Anticipating Personalized Genomic Medicine: Impact and Implications

Eric Juengst, Jennifer Fishman (McGill University), Richard Settersten (Oregon State University) (PIs)

“Personalized Genomic Medicine”(PGM) has become a banner which unites a very wide array of scientific, clinical, and commercial initiatives, from medical sequencing and pharmacogenomics research to medical school curricula, public health interventions, nutritional regimes, and direct-to-consumer “recreational” genome scanning. Across this spectrum, the virtues of PGM as a goal for translational genomic medicine and a new paradigm for health care are interpreted in different ways, with different implications for where this banner leads. In this study, researchers are examining the ways in which five sets of key interpreters understand PGM as a biomedical goal, in order to anticipate the ethical and social challenges they could provoke: individual scientists and labs who invoke the goal in NIH grant applications; the institutional sponsors and public policy proponents of the concept, including patient advocacy groups; PGM’s funding, regulatory, and editorial gatekeepers, medical educators and clinicians already working under this rubric, and the “early adopters” of PGM services amongst consumers and patients. There has been a good bit of discussion of the challenges involved in attempting to roll out PGM within the social context of our health care system. This R01 study, funded by the National Human Genome Research Institute, is aimed at exploring the challenges that could flow from the intrinsic axiological commitments of PGM itself, i.e. the values that drive and shape the enterprise.

The Good Birth Project

Anne Lyerly

The Good Birth Project is a major ongoing initiative aimed at describing what constitutes a “good birth” from the perspectives of birthing women themselves. Analogous to what others have observed about the other bookend of life, we lack a language and conceptual framework for describing the “good” at life’s beginning. To redress this lacuna, I have conducted a large series of in-depth interviews with a diverse sample of women, partners and providers who have given or attended births in diverse settings across the US. These data are the basis of a book (to be published with the Penguin Group, 2013) which will present a rich account of the good birth and considers the implications of that account for the polarized debate about and approaches to maternity care. I also plan to expand research efforts toward exploring these issues across cultures, and developing quality measurement tools that will inform public policy and practice around maternity care in the US and abroad.

Justice Considerations in the Use of Psychosocial Criteria for Organ Allocation

Rebecca Walker

Potential organ recipients are screened for medical appropriateness for transplant, but also “psychosocial” (PS) factors that may impact post-transplant outcomes. These factors may include behavioral and psychological issues (“substance” use, psychiatric disorder or intellectual capacity), relationships and support networks, financial resources, and environmental circumstances (ability to travel, proximity to health care resources). When such screening is used to assess eligibility for transplant (rather than to provide potential recipients with additional services and support to meet their deficits or needs) several justice-based questions are raised: 1. What are the implications of the use of PS factors for disparities in health care access across race and social class? 2. How do PS factors relate to the problematic use of “social values” in the allocation of scarce health care resources? 3. What justifies using PS factors to determine eligibility for transplant rather than as a factor in the distribution of organs? 2. From the point of view of procedural justice, how are transparency and uniformity taken into account? This philosophical project will address these justice questions in a series of articles for biomedical and bioethics audiences.