The Role of Medical Humanism in Clinical Research

1. The Role of Medical Humanism in Clinical Research Paula Bistak, D.MH, RN, MS, CIP, CHRC Executive Director, Human Subjects Protection Program Chris Asmann-Finch, D.MH, MS Program Development Specialist, Human Subjects Protection Program

2. Human Subjects Protection Program The mission of HSPP is to support the University's research enterprise by ensuring the protection of individuals who participate in research; ensuring compliance with all pertinent federal and state laws and regulations; fostering the ethical conduct of human subjects research; and providing education and other services to the University's researchers regarding regulatory requirements and best practices. Components: Education (research community) Support IRB committees in moral deliberations Community Outreach Compliance (Quality Assurance)

4. Poetry SUBJECT I feel the blankness of meaningless combinations of letter and numbers Which say who I am according to them No woman No person A count A number of cells A lack of antibodies A statistic A textbook case No one wants to help me To me to help To help They want me To help Them To make discoveries To write research papers To make them famous They don’t even want to know my name To know at all That those counts of cells Belong to a body Who is a person Who has suffered and is tired Tired of all this poking and testing and number counting Who is just tired — Anonymous, August 1987 (McNeill, Paul M. The Ethics and Politics of Human Experimentation. Cambridge: Cambridge UP. 1993, p 178)

5. Clinicians most conflicted Researcher/Scientist versus Physician/Caregiver

6. Learning Objectives • Symposium attendees recognize that ethical conduct and humanistic practice are necessary in the conduct of clinical research, just as they are necessary in the delivery of medical care. • Symposium attendees are able to identify areas where Medical Humanities efforts contribute to ethical conduct and humanistic practices in clinical research and oversight activities.

7. Session Overview • Review current applications of Medical Humanities in therapeutic medicine; • Outline similarities and differences between therapeutic medicine and human subjects research and highlight need for professional conduct and humanistic practices in both; and • Identify current applications of Medical Humanities in Human Subject Protection Programs to support and nurture professional conduct and humanistic practices in human subjects research.

8. Therapeutic Medicine • Medicine is the “science or practice of diagnosing, treating and/or preventing disease”. (Oxford Dictionary) • “I will prescribe regimens for the good of my patients according to my ability and my judgment and never do harm to anyone.” (Hippocratic Oath)

9. Medical Ethics and Humanities: A Foundation for Medical Professionalism • Association of American Medical Colleges (AAMC) • Education in argument-based reasoning in medical ethics, narrative-based reasoning in literature, creative reasoning in the fine arts, and historical reasoning in learning • Accreditation Council for Graduate Medical Education (ACGME) • Demonstrate respect, compassion, integrity, commitment to ethical principles, sensitivity and responsiveness to patients’ culture, age, gender and disabilities • Liaison Committee on Medical Education (LCME) • Education must include medical ethics and human values, communication….to exhibit scrupulous ethical principles in caring for patients and in relating to patients’ families and to other involved in patient care See Doukas, D., et al. 2012. “Medical Education in Medical Ethics and Humanities as the foundation for Developing Medical Professionalism.” Academic Medicine 87(3): 1-8.

10. Medical Humanities… • an interdisciplinary study of humanities (literature, philosophy, ethics, history and religion), social science (anthropology, cultural studies, psychology, sociology), and the arts (literature, theater, film, and visual arts) as a form of moral development and which concepts are applied to better understand notions of health, disease and medical policy and practice; • employs the methods, concepts and content from one or more of the disciplines to investigate illness, pain, disability, suffering, healing, therapeutic relationships, and other aspects of medicine and health care practice;

11. Medical Humanities (continued) • activities nurture collaboration among scholars, professionals, healers, and patients to design humane health care practices and systems; • demands that we never lose sight of the complexity and beauty of our humanity, especially in times of illness. See also: Brody, Howard. 2011. “Defining the Medical Humanities: Three Conceptions and Three Narratives.” Journal of Medical Humanities 32(1): 1-7. Drew University Medical Humanities Program Committee. 2011. “Medical Humanities for Primary Care Providers.” Shapiro, Johanna, et al., 2009. “Medical Humanities and Their Discontents: Definitions, Critiques, and Implications.” Academic Medicine 84(2):192-198.

12. Applications of Medical Humanities in Therapeutic Medicine Engaging with the humanities, social sciences and art aids: -Medical students to develop skills of observation, communication, analysis, empathy and self-reflection and by this sharpen diagnostic skills, develop respect for patients and enhance the quality of the clinical encounter; • Medical ethics committees to develop narrative competence skills in order to attend more carefully to the details—nuances and complexities—and to strengthen moral imagination in order to identify who and what is at stake in ethical dilemmas; • Health policy makers and interested publics to analyze how the stories, as told, inform how policy is formed and with what consequences; and • Patients to find ways to express their suffering and, through that expression, facilitate healing.

13. Clinical Research • Definition of research: a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge. 45 CFR 46.102(d)

14. Differences between therapeutic medicine and clinical research • Therapeutic Medicine prioritizes needs and interests of patient. Research prioritizes the needs of the experiment. • Therapeutic Medicine strives for specific knowledge to benefit the patient. Research strives for generalizable knowledge to benefit society.

15. Challenges Unique to Clinical Research • Communicating Adequately with Subject • Weighing/Balancing Interests of Subject with that of Science • Just Inclusion on a Shoestring Budget

16. How Research is Similar to Therapeutic Medicine Researcher competency/skills Responsible Conduct of Research/Good Clinical Practice (GCP) Collaborative Institutional Training Initiative (CITI) Researcher Professionalism Ethical Conduct of Research Truth-telling Adequate information Understanding diverse values and beliefs Empathy

17. Examples of High Profile Problematic Research • Tuskegee Syphilis Study (truth-telling) • Havasupi v University of Arizona (communication/understanding health beliefs) • Abney v Amgen, Inc. (empathy/moral imagination)

18. Tuskegee Syphilis Study

19. Havasupi Tribe Members Recover Specimens for Burial

20. Abney v Amgen, Inc. • No picture!

21. Nurturing Humanism in Research Practices Ethical research can yield better science Individuals grounded in medical humanism can be better researchers

22. Consent Process Informed consent is an application of the principle of Respect for Persons To be a truly informed consent: Information Comprehension Voluntariness

23. Purpose of the Consent Process Assist the potential subject in making a decision about their participation in a research study Language impacts the experience of illness (research)

24. Medical Humanist Scientist • Information • Communicating adequately with the subject • Comprehension • Weighing/balancing the interests of the subject with that of science • Voluntariness • Just (fair) inclusion in research

25. Using Medical Humanities to Strengthen IRB Deliberations • Develop moral imagination • Finding stories • Critical reflection on the ways we deliberate

26. Medical Humanities and IRB Deliberations Primary function of an IRB: “An IRB is a committee that performs ethical review of proposed research.” U.S. Department of Health and Human Services

27. GENERAL ETHICAL PRINCIPLES Respect for Persons (Principle of Autonomy): • Acknowledging the value and decision-making rights of persons by enabling them to act autonomously and respecting their autonomously made decisions. Principle of Beneficence: • We should do no harm and act in ways that promote the welfare of other people. Principle of Justice: • Benefits and burdens of research ought to be distributed in ways that are fair and just.

28. IRB Deliberations Application of ethical principles difficult because information about subjects is NOT regularly available for IRB Review • Patients’ and/or Subjects’ Stories • Experience living with disease • Experience in clinical trials • Community Stories • Identifying what is important to research • Experience with research and/or researchers • Other Evidence • Periodic stopping points in research to assess expectations/problems (not even for studies conducted by PIs with history of problematic conduct) • Satisfaction surveys at end of study • Comparative Effectiveness Research

29. Narrative Exercise: Phase III: Pharmacokinetics, Safety and Tolerability of Zavesca (Miglustat) in Patients with Infantile Onset Gangliosidosis [Tay-Sachs]: Single and Steady State Oral Doses The primary objective of the study is to investigate the pharmacokinetics of ZAVESCA (miglusatat, OGT918), when given as a single dose and a steady state, in infantile patients with GM2 gangliosidosis. The secondary objectives are to evaluate the tolerability and safety of single and multiple doses of miglustat and to monitor disease progress using physical and developmental assessments and disease-specific biomarkers. Endpoints: • Biomarkers (level of GM2 ganglioside, chitotriosidase activity, anti-GM2 antibodies) in plasma, serum and CSF will be measured at initial visit (run-in period), Week 13, and Week 25. • Neurophysiologic Assessment – EEG and BEAR tests will be done at initial visit (run-in period), Week 13, and Week 25. • Ophthalmology Assessment – comparison of the “cherry-red” macula changes will be made at initial visit (run-in period) and Week 25. ClinicalTrials.gov; Trial #NCT00672022

31. A Parent’s Story Ronan [our son] has given us a terrible freedom from expectations, a magical world where there are no goals, no prizes to win, no outcomes to monitor, discuss, compare….Our son won’t prosper or succeed in the way we have come to understand this term in our culture; he will never walk or say ‘Mama’, and I will never be a tiger mom… Our goals are simple and terrible: to help our [son] live with minimal discomfort and maximum dignity. […the day-to-day is often peaceful, even blissful…cuddling, feeding naps. He can watch television if he wants to; he can have pudding and cheesecake for every meal…The only task here is to love…]. We will not launch our [child] into a bright and promising future, but see [him] into [an] early [grave]. We will prepare to lose [him] and then, impossibly to live on after that gutting loss. This requires a new ferocity, a new way of thinking, a new animal. We are dragon parents: fierce and loyal and loving as hell. Our experiences have taught us how to parent for the here and now, for the sake of parenting, for the humanity implicit in the act itself…. Rapp, Emily. “Opinion: Notes From a Dragon Mom.” New York Times Sunday Review, October 16, 2011. pg. 12.

32. Problems Result When IRBs Fail to Imagine the Other • Biology becomes a ‘superfact” in deliberations • Application of Ethical Principles distorted • Good science does not guarantee an ethical study

33. A Problem with Stories • …there are so many of them! 2,405,000 people in clinical trials in 2006 alone: 775,000 govt.-funded trials 880,000 pharma-funded I-III 750,000 pharma-funded post-marketing CISCRP

34. Need to Develop Deliberative Reflexivity (narrative competence) • Who are the “stakeholders” narrated in the proposed research? Are there other important stakeholders we need to know about? If so, who and why? What is at stake for each? • How does the story, and the particular way it is told, define or redefine those stakes, raising or lowering them? • How does the story change our sense of what is possible, what is permitted, and what is responsible or irresponsible? • How will the study alleviate suffering? See Frank, A. 2010. Letting Stories Breathe: A Socio-Narratology. U of Chicago Press. pp. 74-5.

35. Application of Medical Humanities in Clinical Research Engaging with the humanities, social sciences and art aids: - Clinical Researchers to develop skills of communication, analysis, empathy, community engagement and self-reflection and by this sharpen research skills, develop respect for research subjects and enhance the quality of the research encounter; and - Research ethics committees (IRBs) to develop narrative competence to attend more carefully to the details—nuances and complexities—and strengthen moral imagination in order to identify who and what is at stake in proposed clinical research.

36. The Goal of Medical Humanities Activities Regardless of context, be it medical practice or clinical research, we endeavor to never lose sight of the complexity and beauty of our humanity, especially in times of illness.