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. ApostolosTsapas 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

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.

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

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