Trust in early phase research: therapeutic optimism and protective pessimism
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Bioethicists have long been concerned that seriously ill patients entering early phase (‘phase I’) treatment trials are motivated by therapeutic benefit even though the likelihood of benefit is low. In spite of these concerns, consent forms for phase I studies involving seriously ill patients generally employ indeterminate benefit statements rather than unambiguous statements of unlikely benefit. This seeming mismatch between attitudes and actions suggests a need to better understand research ethics committee members’ attitudes toward communication of potential benefits and risks of early phase studies to potential subjects. We surveyed the members of two U.S. research ethics committees using a phase I gene transfer study scenario, and compared the results to a previous survey of potential subjects’ perceptions and attitudes toward benefit and risk for the same protocol. The results show that there is indeed a gap between the subjects’ perceptions and the committee members’ views on what is appropriate to be communicated to research subjects. This discrepancy is the product of both the commonly assumed optimism of the subjects and to a “protective pessimism” of the research ethics committee members. We discuss this discrepancy using “frameworks of trust” and demonstrate the need to incorporate these frameworks into the existing model of informed consent.
- Agrawal, M., and E.J. Emanuel. 2003. Ethics of phase 1 oncology studies: Reexamining the arguments and data. JAMA: The Journal of the American Medical Association 290: 1075–1082. CrossRef
- Cheng, J., J. Hitt, B. Koczwara, K.A. Schulman, C.B. Burnett, D.J. Gaskin, J.H. Rowland, and N.J. Meropol. 2000. Impact of quality of life on patient expectations regarding Phase I clinical trials. Journal of Clinical Oncology 18: 421–428.
- Churchill, L.R., D.K. Nelson, G.E. Henderson, N.M. King, A.M. Davis, E. Leahey, and B.S. Wilfond. 2003. Assessing benefits in clinical research: Why diversity in benefit assessment can be risky. IRB: A Review of Human Subjects Research 25: 1–8.
- De Vries, R.G., and C.P. Forsberg. 2002. What do IRBs look like? What kind of support do they receive? Accountability in Research 9: 199–216.
- Henderson, G.E., A.M. Davis, N.M.P. King, M.M. Easter, C.R. Zimmer, B.B. Rothschild, B.S. Wilfond, D.K. Nelson, and L.R. Churchill. 2004. Uncertain benefit: Investigators’ views and communications in early phase gene transfer trials. Molecular Therapy 10: 225–231. CrossRef
- Henderson, G.E., M.M. Easter, C. Zimmer, N.M.P. King, A.M. Davis, B.B. Rothschild, L.R. Churchill, B.S. Wilfond, and D.K. Nelson. 2006. Therapeutic misconception in early phase gene transfer trials. Social Science & Medicine 62: 239–253. CrossRef
- Horng, S., E.J. Emanuel, B. Wilfond, J. Rackoff, K. Martz, and C. Grady. 2002. Descriptions of benefits and risks in consent forms for phase I oncology trials. New England Journal of Medicine 347: 2134–2140. CrossRef
- Joffe, S., and J.C. Weeks. 2002. Views of American oncologists about the purposes of clinical trials. Journal of the National Cancer Institute 94: 1847–1853.
- Jonsen, A.R. 1998. The birth of bioethics. New York: Oxford University Press.
- Kim, S.Y.H., S. Frank, R. Holloway, C. Zimmerman, R. Wilson, and K. Kieburtz. 2005. Science and ethics of sham surgery: A survey of Parkinson disease clinical researchers. Archives of Neurology 62: 1357–1360. CrossRef
- Kim, S., R. Holloway, S. Frank, C. Beck, C. Zimmerman, R. Wilson, and K. Kieburtz. 2006. Volunteering for early phase gene transfer research in Parkinson disease. Neurology 66: 1010–1015. CrossRef
- Kimmelman, J. 2005. Recent developments in gene transfer: Risk and ethics. BMJ 330: 79–82. CrossRef
- King, N.M.P. 2000. Defining and describing benefit appropriately in clinical trials. Journal of Law, Medicine & Ethics 28: 332–343. CrossRef
- King, N., G. Henderson, L. Churchill, A. Davis, S.C. Hull, D.K. Nelson, P. Parham-Vetter, B. Rothschild, M. Easter, and B. Wilfond. 2005. Consent forms and the therapeutic misconception. IRB Ethics & Human Research 27: 1–8. CrossRef
- Kipnis, K. 2003. Seven vulnerabilities in the pediatric research subject. Theoretical Medicine and Bioethics 24: 107–120. CrossRef
- Kodish, E., C. Stocking, M. Ratain, A. Kohrman, and M. Siegler. 1992. Ethical issues in phase I oncology research: A comparison of investigators and institutional review board chairpersons. Journal of Clinical Oncology 10: 1810–1816.
- Priest, S.H., H. Bonfadelli, and M. Rusanen. 2003. The “trust gap” hypothesis: Predicting support for biotechnology across national cultures as a function of trust in actors. Risk Analysis 23: 751–766. CrossRef
- Shah, S., A. Whittle, B. Wilfond, G. Gensler, and D. Wendler. 2004. How do institutional review boards apply the federal risk and benefit standards for pediatric research? JAMA 291: 476–482. CrossRef
- van Luijn, H.E.M., N.K. Aaronson, R.B. Keus, and A.W. Musschenga. 2006. The evaluation of the risks and benefits of phase II cancer clinical trials by institutional review board (IRB) members: A case study. Journal of Medical Ethics 32: 170–176. CrossRef
- van Luijn, H.E.M., A.W. Musschenga, R.B. Keus, W.M. Robinson, and N.K. Aaronson. 2002. Assessment of the risk/benefit ratio of phase II cancer clinical trials by Institutional Review Board (IRB) members. Annals of Oncology 13: 1307–1313. CrossRef
- Weinfurt, K.P. 2004. Discursive versus information-processing perspective on a bioethical problem: The case of ‘unrealistic’ patient expectations. Theory and Psychology 14: 191–203. CrossRef
- Trust in early phase research: therapeutic optimism and protective pessimism
Medicine, Health Care and Philosophy
Volume 11, Issue 4 , pp 393-401
- Cover Date
- Print ISSN
- Online ISSN
- Springer Netherlands
- Additional Links
- Therapeutic misconception
- Early phase research
- Gene transfer
- Research ethics
- Trust in research
- Survey of IRBs
- Industry Sectors
- Author Affiliations
- 1. Department of Psychiatry, The Bioethics Program, The Center for Behavioral and Decision Sciences in Medicine, University of Michigan, 300 North Ingalls Street, 7C27, Ann Arbor, MI, 48109, USA
- 2. Department of Neurology, University of Rochester, Rochester, NY, USA
- 3. Department of Neurology, Boston University, Boston, MA, USA