Healthy Volunteers as Model Organisms

September 5, 2017

Comparative Research Ethics and Policy for Phase I Trials

Principal Investigators: Jill A. Fisher and Rebecca L. Walker

This project addresses the need for a novel evidence-based approach to the protection of Phase I healthy volunteers. Phase I clinical trials test the safety of investigational drugs that eventually may be used in affected patients. These trials have distinctive features that may undermine the validity of data gathered and lead to ethics and policy gaps in protecting healthy volunteers. One such feature is that healthy volunteers must stay in the clinic during the trial where they are given a prescribed diet and experience other restrictions. Another feature of Phase I trials is they rely on repeat volunteers who do not mirror the health or sociodemographic characteristics of typical patient populations. Given these unique features of Phase I trials, we contend that valuable insights may be gained through a comparison with non-human animal “model organism” research. We will investigate this comparison and generate new ethics and policy guidance that addresses the problems of risk, subject selection, validity, and translation that are particular to healthy volunteer trials.

To do so, this project has 3 primary aims:

  1. Describe and normatively evaluate the limitations of current research oversight in Phase I trials by analyzing data on healthy volunteers’ perceptions of clinical trials, including through a non-human animal research “model organism” lens;
  2. Compare the ways in which Phase I researchers, non-human animal researchers, bioethicists and policymakers, regulatory and research oversight staff, and healthy volunteers conceptualize: a.) similarities and differences between healthy volunteer and non-human animal research and b.) ethical, policy, and translational science problems particular to each arena; and
  3. Develop ethics and policy guidance for Phase I healthy volunteer research that a.) extrapolates from the model organism framework in Specific Aims 1 and 2, b.) is attentive to the structural features of Phase I research, and c.) is vetted by expert stakeholders.

This 4-year project is a renewal of our current longitudinal R01 study of 180 healthy volunteers (the HealthyVOICES Project). To address the new aims, we will analyze the current grant’s dataset to identify ethics and policy gaps and generate empirically-grounded points of comparison between Phase I trials and animal research (Aim 1). We will also conduct 60 interviews and 300 surveys with expert informants from Phase I healthy volunteer research, animal studies, and bioethics and regulatory perspectives about the key ethical, policy, and translational issues at stake (Aim 2). Finally, we will develop ethics and policy guidance to protect Phase I subjects and improve the translational science pipeline. Four stakeholder forums across the US will provide a vetting process for our draft guidance and initiate dissemination for our final recommendations (Aim 3). We expect the contribution of the proposed project to be significant because it will generate ethics and policy guidance that can provide advances in healthy volunteer welfare and the translational efficacy of Phase I trials.

Ethics of HIV-Related Research Involving Adolescents in Kenya

August 7, 2017

Despite the high social value of adolescent HIV prevention research in sub-Saharan Africa, investigators are reluctant to involve adolescents in studies with HIV testing and disclosure of results because of ethical concerns about the risks of their participation. This study examines four inter-related ethical issues essential to adolescent HIV research: the effects of disclosure of HIV test results on adolescent psychosocial well-being, health-seeking, or risk behavior; minimizing harms in the recruitment of adolescents; comprehension of informed consent among parents, children, and adolescents 18 years and older; and the appropriate use of compensatory payments for youth and parent participation. The study setting is Siaya County in western Kenya.

Specific Aims

  1. To examine the effects of HIV testing and disclosure on adolescent behavior and psychosocial well-being in the context of a research study.  About 4,200 adolescents aged 15-19 will participate in an empirical study of HIV testing and disclosure per the standard of care to inform ethical guidelines.
  2. To examine stakeholder perceptions about adolescent HIV research methods for recruitment, informed consent, HIV testing and disclosure of results, and compensation/inducements for study participation.
  3. To develop guidelines for the ethical conduct of adolescent HIV research and to refine them in consultation with key stakeholders. Findings from Aims 1 and 2 will be used to develop preliminary guidelines for conducting ethical adolescent HIV research. Perceptions about the guidelines from the Kenya advisory boards, and from comparable focus group participants and local ethicists from two additional sub-Saharan countries will be analyzed and used to refine the guidelines and assess their generalizability.

Principal Investigator

  • Winfred Luseno, PhD, Pacific Institute for Research and Evaluation (PIRE)

Co-Investigators

  • Stuart Rennie, PhD, University of North Carolina at Chapel Hill
  • Denise Hallfors, PhD, PIRE
  • Hyunsan Cho, PhD, PIRE
  • Daniel Kwaro, MBChB, MPH, Kenya Medical Research Institute (KEMRI)
  • Amek Nyaguara, PhD, KEMRI
  • David Ayuku, PhD, Moi University
  • Muhammed Afolabi, PhD, Gambia, Medical Research Council
  • Arthur Caplan, PhD, New York University

Funder

  • NIH-National Institute of Mental Health (R01 MH102125, 9/1/2014 – 8/31/2019)

 

Exploring Moral Distress Within the Context of Our Health Care System

July 27, 2017

This study employs survey, focus group and interview data to examine moral distress among clinicians. Moral distress was first described within the context of nursing in the 1980s as a situation in which “one knows the right thing to do, but institutional constraints make it nearly impossible to pursue the right course of action” (Jameton 1984). Moral distress is increasingly recognized within a wide variety of contexts. Studies suggest that moral distress is experienced by various health care professionals including nurses, respiratory therapists, physicians, and trainees. Left unaddressed, moral distress in health care can erode inter- and intra- personal relationships and lead to provider burnout, thereby compromising patient care.

The goal of this project is to develop more effective metrics to define and characterize moral distress amongst the diverse health care professionals within the UNC Health Care System. Our collaborative will utilize data obtained with these tools to develop targeted interventions for responding to moral distress at the institutional level.

Team Members

Using Simulation to Assess Ethical Skills in the Context of ACGME Residency Milestones

July 27, 2017

This project is funded through an AHEC Campus Innovation Grant and is a collaborative project by members of the Center for Bioethics, the Hospital Ethics Committee, and the School of Medicine’s Clinical Skills and Patient Simulation Center. It uses simulation to assess ethical skills as framed in the ACGME professionalism milestones for pediatric residencies. While the use of an objective structured clinical exam (OSCE), via simulation, is a well-developed tool in other parts of medical education, there is limited data on the use of OSCEs at the resident level for assessing ethical skills and professionalism. Simulation allows for a more objective and informed milestone determination in these challenging areas. We will create OSCEs sensitive to the ethical skills captured in professionalism milestones in pediatrics. Our model of simulation will permit pediatric residents to demonstrate, and preceptors to evaluate, competencies in ethical practice as prescribed by the professionalism milestones. Our ultimate product will be an ethics simulation module containing cases, assessment forms, and an instruction guide. This ethics module will be translatable to other residency groups beyond pediatrics. We will also promote the module and make it easily available to AHEC faculty throughout North Carolina.

Team Members

  • PI: Arlene Davis, JD, Center for Bioethics, Department of Social Medicine
  • Jean Cadigan, PhD; Center for Bioethics, Dept. of Social Medicine
  • Benny L. Joyner, Jr., MD, MPH; Dept. of Pediatrics and Clinical Co-director of the Clinical Skills and Patient Simulation Center
  • Margaret Waltz, PhD; Department of Social Medicine
  • Kimberly Blasius, MD; Dept. of Anesthesiology
  • Melissa Smith, MD; Dept. of Pediatrics
  • Gene Hobbs, BA; Dept. of Pediatrics and Simulation Lab Director
  •  Research Assistance from Warren Whipple, Dept of Social Medicine, Elizabeth Brassfield, UNC MD/PhD program, and Rohit Jaswaney, MS2, NY Medical College

Acute Infection: Lived Experiences and Ethical Challenges in HIV Research

February 6, 2017

A better understanding of acute HIV infection is essential to public health, impacting both HIV transmission and potential advances in HIV cure clinical research. Acute HIV infection refers to the earliest stages of HIV infection, the short window of time right after a person becomes infected when they are most infectious. Individuals diagnosed and treated during acute infection are an important population for HIV cure research.

Early phase HIV cure research protocols are both novel (and potentially riskier) to participants. Research done with this population presents a unique set of challenges as an acute diagnosis in itself may contribute to strong emotional and behavioral responses. Faced with new HIV-positive identities and increased transmission risk to their sex partners, acutely diagnosed patients may face greater stress and confusion as they navigate decisions related to medical care and research participation. This intersection of public health interest, HIV cure scientific value, and patients’ personal challenges indicates a compelling need to consider whether acute HIV experiences merit special ethical guidance for research.

The aims of this project are three-fold:

  1. Examine the experiences of acutely infected research participants involved in HIV treatment and cure-related studies using anthropological methods.
  2. Compare perceptions of risks and benefits of clinical HIV trial participation between acute and chronic HIV diagnosed research subjects.
  3. Develop a set of ethical recommendations that address specific challenges related to identifying, recruiting, and retaining AHI diagnosed individuals in HIV clinical (especially cure) research.

This project is conducted at three sites: the University of North Carolina at Chapel Hill, Duke University Medical Center, and Guy’s and St Thomas’ Hospital, London, UK.

Research team members:

  • Stuart Rennie (Principal Investigator), Assistant Professor, UNC Center for Bioethics, Department of Social Medicine, UNC-Chapel Hill
  • Adam Gilbertson (Co-Principal Investigator) Postdoctoral Research Fellow, UNC Center for Bioethics, Department of Social Medicine, UNC-Chapel Hill
  • Joe Tucker (Co-investigator) Assistant Professor of Medicine and Director of UNC Project-China, Department of Medicine, UNC-Chapel Hill
  • Julie Fox (Co-Investigator) HIV Consultant, King’s College London and Guy’s and St Thomas’ Hospital, London, United Kingdom
  • Audrey Pettifor (Co-investigator) Associate Professor, Dept. of Epidemiology, UNC-Chapel Hill
  • JoAnn Kuruc (Co-investigator) Clinical Program Director, UNC HIV Cure Center at the UNC-Chapel Hill
  • Kate MacQueen (Consultant) Senior Social Scientist, Global Health Research, FHI 360
  • Kara McGee (Consultant) Physician Assistant, Duke University Medical Center
  • Alice Sharp (Research Manager) Guy’s and St Thomas’s Hospital London, UK
  • Liz Kelly (Graduate Research Assistant) UNC-Chapel Hill

Funded by NIAID, the National Institute of Allergy and Infectious Diseases.
Grant number 1R21AI120549-01A1.

 

Re-Engaging Ethics: Ethical Issues in Engaged Research

January 30, 2017
Clockwise starting at top-left: Giselle Corbie-Smith, Al Richmond, Mysha Wynn, and Stuart Rennie

Project Description

Re-Engaging Ethics is a project that is funded by the Greenwall Foundation. The purpose of this project is to create and disseminate recommendations for the review and conduct of community-engaged research, by engaging a diverse set of stakeholders in dialogue about the unique ethical concerns that arise in this emerging scientific approach to public health and biomedical research. While there has been some conceptual work in the peer-reviewed literature on the ethical issues that arise in engaged scholarship, the field is so new that there hasn’t been a comprehensive examination of these issues, nor have there been clear recommendations for review. In addition, much of what has been written has been from the perspective of the investigator or ethicist; few include the perspectives of community members as authors, and even fewer bring all of these perspectives to bear in one set of recommendations. Our project seeks to remedy these issues by soliciting the varied perspectives of community, academic and ethics scholars through in depth interviews, questionnaires, workshops, and literature reviews, and developing a set of recommendations that address ethical issues in engaged scholarship.

Research Team

Real World Narratives Wanted!

The Re-Engaging Ethics team seeks narratives in the following topic areas: equitable and just research, relationship dynamics, community informed risk/benefit assessment, and accountability. Visit this page to learn more about submitting a narrative.

Strengthening Bioethics Capacity and Justice in Health

January 27, 2017
Kinshasa School of Public Health
Kinshasa School of Public Health

Francophone African countries are among the most resource-constrained in the world. Citizens in these regions commonly struggle with a wide variety of health problems related to poverty, political conflict and social upheaval. Those involved in local efforts to improve health, in clinical medicine, biomedical research or public health initiatives, often find themselves in difficult situations of moral conflict. Managing these conflicts is challenging, partly because local health professionals may come to them unprepared due to bioethics typically not forming an explicit part of the medical curriculum and having little presence in common culture.

This training project, entitled Strengthening Bioethics Capacity and Justice in Health, seeks to increase awareness of ethical issues in biomedicine in Francophone Africa, and contribute to locally relevant bioethics education and practice in this region. Our project conducts workshops, organizes conferences, provides training in bioethics for local collaborators and interested scholars, publishes peer-reviewed articles on bioethical issues in Francophone Africa, and integrates bioethics content into existing curricula in key educational institutions. The target countries for our initiatives are the Democratic Republic of Congo (DRC) and Madagascar. Strengthening Bioethics Capacity and Justice in Health is a collaborative project among leading health institutions in the United States, Belgium, Madagascar and the DRC.

Site leaders

Key investigators

Funding

Vermont Study on Aid in Dying

January 11, 2017

Vermont SAID

Lee Farm, Woodstock, Vermont

The Vermont Study of Aid-in-Dying (Vermont SAID) investigates the implementation and cultural impact of Vermont’s “Patient Choice and Control at End of Life” Act (Act 39), enacted in May 2013. Due to the recent enactment of Act 39, and Vermont’s small size and the geographic proximity of key institutions, Vermont offers an unparalleled setting for documenting emergent responses to the law across multiple sites and actors (e.g. patients, caregivers, medical providers and administrators, activists, legislators). The study will yield descriptive information about how the legalization of assisted dying affects death, dying, and end-of-life care. It will also describe ethical challenges that assisted dying raises for clinical communication about end-of-life care and the patient-provider relationship. Ultimately, the goal of the study is to 1) provide information that can be used to enhance end-of-life communication and policymaking, and 2) contribute to anthropological understandings of the biomedical management of death.

Research Team

mara-buchbinder-tileDr. Mara Buchbinder is the Principal Investigator on the project and a medical anthropologist specializing in the culture of medicine in the United States. Her recent work has explored how patients, families, and healthcare providers navigate social and ethical challenges raised by new developments in medical technology, public health policy, and law. She is especially interested in the role of language in medicine and in the relationships among patients, families, and clinicians in managing illness and healthcare. Dr. Buchbinder is an Associate Professor in the UNC Department of Social Medicine and core faculty in the UNC Center for Bioethics.

dragana-lassiterDragana Lassiter is the study research assistant and a PhD candidate in the UNC Department of Anthropology.

Study Participation

Over the past two years, Dr. Buchbinder has interviewed 78 clinicians, advocates and legislators, and family members/caregivers. In addition to these groups, we would also like to understand the perspectives of people who have been diagnosed with a serious or life-threatening medical condition. We hope to capture a variety of perspectives on the issue, including the voices of patients on either side of the debate, as well as those who don’t have a strong stance or don’t feel affected by the law. Interviews are typically an hour long and include questions about: your background, perspectives on the law, and ideas about what constitutes a good death. The study will run through the end of 2017. If you would like to participate, we would love to hear from you! (mara_buchbinder@med.unc.edu)

Frequently Asked Questions

  • Who is funding the study?
    The study has been funded by the National Science Foundation and the Greenwall Foundation.
  • Should I expect any benefits from participating in the study?
    There is no financial compensation for participating in the study. However, sharing your perspectives and experiences might help advance the conversation about aid-in-dying in Vermont.
  • What does participation entail?
    Participation entails an hour long recorded interview at an agreed-upon location.
  • How will my privacy be protected?
    Once we transcribe the interviews, all personal information is removed. This generally includes all personal names, institution names, and names of towns and other geographical landmarks. We also work hard to remove any contextual information that could be identifying, such as one’s unique professional role or position within an institution.
  • What is your stance on physician aid-in-dying?
    We do not advocate for or against aid-in-dying. Instead, we are interested in the way legislating AID shapes end-of-life care and cultural perceptions of death and dying.

Contact

Mara Buchbinder, PhD
Associate Professor
Department of Social Medicine
University of North Carolina at Chapel Hill
333 S. Columbia Street
341A MacNider Hall
Chapel Hill, NC 27599-7240

phone: 216.402.0498

email: mara_buchbinder@med.unc.edu

Project Website

vermontsaid.web.unc.edu

Second Wave Initiative

January 11, 2017

 

Each year, hundreds of thousands of pregnant women in the US face significant medical illness during their pregnancies, and many more do so worldwide. Diabetes and hypertension complicate 40,000+ pregnancies; psychiatric illness complicates an estimated 500,000; cancer and autoimmune diseases are not uncommon. Yet we have surprisingly little data about how to safely and effectively treat these conditions. The costs of ignorance are significant: the pregnant body can substantially change the ways in which drugs are metabolized; concerns about the safety of taking medication must be balanced against the medical risks — to woman and fetus alike — of undertreating significant medical disease. Without information to guide these decisions, pregnant women and the children they bear face risks of under-treatment, ineffective treatment, and short-and long term health consequences.

Co-Principal Investigators

Current Projects

joint-logo-header

PHASES: Pregnancy & HIV/AIDS: Seeking Equitable Study

  • Principal Investigator: Anne Lyerly
  • The multi-year project funded by the U.S. National Institutes of Health seeks ethical solutions to advance research at the intersection of women’s reproduction and HIV prevention, treatment, and management.
  • hivpregnancyethics.org

Zika and Beyond: Pregnancy, Research, and Public Health Emergencies

  • Co-principal investigators: Anne Lyerly and Ruth Faden
  • The multi-year project funded by the United Kingdom’s Wellcome Trust seeks ethical solutions to ensure that the health needs of pregnant women and their offspring are appropriately included in research efforts addressing emerging public health crises
  • zika.pregnancyethics.org

History of the Second Wave Initiative

Nearly a decade ago, Anne Lyerly partnered with Ruth Faden (Johns Hopkins Berman Institute of Bioethics) and Maggie Little (Georgetown Kennedy Institute for Ethics) to move forward responsible inclusion of pregnant women in research. The Second Wave Initiative, launched in 2009, is a collaborative academic effort to identify, develop and advance ethically and scientifically responsible solutions for increasing our knowledge base for the treatment of pregnant women who face medical illness. The initiative took shape in April of 2009, when 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. Supported by a Reflective Engagement grant from Georgetown, the outcome of the workshop identified barriers, articulated the costs of ignorance, and proposed consensus proposals that can immediately begin to make a difference in pregnant women’s health. Second Wave advocates have also worked with Members of Congress and their staffs to raise awareness of the issue. Those efforts resulted in inclusion of language in the House Committee Report accompanying the Fiscal 2010 Appropriations for the Departments of Labor, Health and Human Services and Education. Their research and scholarship in the area are ongoing, with empirical studies aimed at understanding what matters to pregnant women considering enrollment in studies, conceptual work to help guide responsible research with pregnant women in the future, and two large projects to develop concrete guidance for ethically responsible inclusion of pregnant women in pressing health contexts, including HIV, Zika, as well as other public health emergencies.

Project Twitter: @pregnancyethics

Second Wave Initiative Project Website: secondwaveinitiative.org