Med 255C: Responsible Conduct of Research for Clinical Researchers
Section 1: Clinical Research versus Clinical Care



What distinguishes research from clinical care?
Therapeutic misconception (IRB, subject, investigator): What is it? Where does it originate? How
to mitigate? Can the investigator explain the concept?
What are concrete steps that he or she can take at all research stages to minimize role confusion?
Readings:
1. Belsky. Medical researchers' ancillary clinical care responsibilities. BMJ (2004) vol. 328 (7454)
pp. 1494-1496
2. Emanuel et al. What makes clinical research ethical? JAMA (2000) vol. 283 (20) pp. 2701-11.
3. Gail Henderson et al. “Clinical Trials and Medical Care: Defining the Therapeutic
Misconception,” PLoS Medicine, 2007.
Additional Reading:
1. Apostolos Tsapas and David R. Matthews, Using N-of-1 Trials in Evidence-Based Clinical
Practice, JAMA ;301(10):1022-1023 (2009)
2. Peter D. Jacobson and Wendy E. Parmet, A New Era of Unapproved Drugs: The Case of Abigail
Alliance v Von Eschenbach, JAMA. 2007;297:205-208.
3. Frank Miller and Steven Joffe, “Evaluating the Therapeutic Misconception,” Kennedy Institute
of Ethics Journal, 2006.
Potential Cases:
1. Lysosomal storage (BECS)
2. Innovation in the Off-Label use of Drug (Eaton and Kennedy)
3. Innovative Surgery (Eaton and Kennedy)
Section 2: Protecting Human Subjects: Informed Consent, IRB, and their limitations



Basic Protections: IRB etc
Informed consent generally
Emergency informed consent
Readings:
1. Emanuel et al, “Oversight of Human Participants Research: Identifying Problems
To Evaluate Reform Proposals,” Annals of Internal Medicine, 2004.
Additional Readings:
1. Regulatory Basics (HRPP, DSMB, IRB, SCRO, Safety, Scientific Review Committees)
Potential Cases:
1. Polyheme
2. Gelsinger – gene therapy Penn; lesser harms Halpern. Nothing to do with consent. Problem is
is it a good idea? Leroy Walters
3. Grimes
1
Section 3: Conflicts of Interest
Readings:
1. Thompson, D. “Understanding Financial Conflicts of Interest,” NEJM, Vol. 329, Number 8,
(August 19, 1993) pp. 573-576.
Additional Readings:
1. Justin E. Bekelman; Yan Li; Cary P. Gross, “Scope and Impact of Financial Conflicts of
Interest in Biomedical Research: A Systematic Review”, JAMA, 2003.
Potential Cases:
1. Vioxx story with detailed accounting and Cox 1 and 2
2. Joseph Biederman
Section 4: Returning Research Results and Incidental Findings
Readings:
1. Wolf et al. Managing incidental findings in human subjects research: analysis and
recommendations. The Journal of Law, Medicine & Ethics (2008) vol. 36 (2) pp. 219-248
Additional Readings:
1. Miller, Mello, and Joffee. Incidental Findings in Human Subjects Research: What Do
Investigators Owe Research Participants? The Journal of Law, Medicine & Ethics (2008) vol. 36
(2) pp. 1-9
2. Cho. Understanding incidental findings in the context of genetics and genomics. The Journal
of Law, Medicine & Ethics (2008) vol. 36 (2) pp. 280-5, 212
Potential Cases:
1. Hallmeyer from Teneille
2. Terry Klein – just error, healthy sample, storage disease, lifesaving
3. Imaging?
4. Starbucks Case
5. Hereditary cardiomyopathy case
Section 5: Human Biological Materials and Biobanking



Labelling; Stanford policy on labeling and links to personal information
Data integrity
Informed consent places limitations on use; when is re-consent required; what about consent for
biobanks when tissues are to be used broadly?
Readings:
1. “Common Consent,” Nature, 460 (7258), 20 August 2009.
2. Salvaterra et al. 2008. Banking together: A unified model of informed consent for biobanking,
EMBO Reports, pp. 307-313.
2
Additional Readings:
1. Beskow et al. 2001.. Involving Genetics: Informed Consent for Population-Based Research,
JAMA 2001;286(18):2315-2321.
2. Ormond et al. Assessing the Understanding of Biobank Participants, American Journal of
Medical Genetics 2009: 188-198.
Potential Cases:
1. Catalona
2. Greenberg
3. Moore – Jon Merz who owns life
Section 6: Community Consent and Recruitment
 Choice of appropriate community for research vs. further stigmatization
Readings:
1. Tindana et al. Grand Challenges in Global Health: Community Engagement in Research in
Developing Countries. Plos Med (2007) vol. 4 (9) pp. e273
2. Weijer. ETHICS: Protecting Communities in Biomedical Research. Science (2000) vol. 289
(5482) pp. 1142-1144.
3. Rosas LG, Stafford RS. Practical research strategies for reducing social and racial/ethnic
disparities in obesity. Int J Obesity (London), 2012; 2[suppl]: S16-S22. PMID: 23667289.
Potential Cases:
1. Havasupai
2. Tischkoff
3. Nuu-chah-nulth (Nootka)
Section 7: Placebo versus Active Control Trials
Readings:
1. Emanuel and Miller, “The Ethics of Placebo-Controlled Trials—A Middle Ground,” NEJM,
345(12):915-919, 2001.
2. Seth Glickman et al, “Ethical and Scientific Implications of the Globalization of Clinical
Research, NEJM, 360(8) 2009: 816-823.
3. Stafford RS, Wagner TH, Lavori PW. Perspective: New, but not improved? Incorporating
comparative-effectiveness information into FDA labeling. N Engl J Med; 2009; 361: 1230-3.
PMID: 19675326.
Additional Readings:
1. Franklin G. Miller and Howard Brody, “What Makes Placebo-Controlled Trials Unethical?”
American Journal of Bioethics, Volume 2, Issue 2 Spring 2002 , pages 3 – 9.
Potential Cases:
1. AZT
2. Depression or schizophrenia - ok placebo control trial
3