disclosure under the following justifications: “In all cases of research involving incomplete disclosure, such research is justified only if it is clear that (1) incomplete disclosure is truly necessary to accomplish the goals of the research, (2) there are no undisclosed risks to subjects that are more than minimal, and (3) there is an adequate plan for debriefing subjects, when appropriate, and for dissemination of research results to them.” Nonetheless, these statements are followed by another, which specifically declares that risks should never be withheld for the purpose of eliciting subjects, and fully honest answers should always be given to questions asked of the researchers by the subjects.
2 Comprehension refers to the requirement of adaptable manner and context in which information is presented to the subject based on their ability to understand, which may be variable, considering level of intelligence, rationality, maturity, and language. The Belmont Report requires that it is the investigators’ responsibility and obligation to determine that the subject fully understands the information given to him/her and that special provision be given when comprehension may be limited.
3 Finally, voluntariness refers to the agreement of the subject to participate in the research with the requirement that such consent is valid only if voluntarily given, free of coercion, undue influence, and after the first two elements of the first principle Respect for Persons are met.
The second principle of beneficence is an assessment of the risks and benefits of the clinical research. This includes an examination of the experimental design and whether the risks to the subjects participating in the research are justified, taking into account several considerations listed in the report. The first two of these considerations are that “brutal or inhumane treatment of human subjects is never morally justified; and that risks should be reduced to those necessary to achieve the research objective. It should be determined whether it is in fact necessary to use human subjects at all.” Beneficence is also an obligation of the subjects themselves to determine. They must assess for themselves whether the research is of sufficient benefit to them or the community and, thus, whether they should participate.
The final principle required in the Belmont Report is that of justice, which refers to the specific selection of subjects to participate in the clinical research. Two levels are required to be considered in the selection of subjects: the social level and the individual level. Researchers must be fair in that they should not choose patients who are “in their favor” for beneficial research, or “undesirable” patients to take part in research that may carry a higher risk. On the social level, justice requires distinction between classes of subjects in order to not place a further burden on already burdened classes of subjects. This requires, for example, that the class of “adults” should be chosen for participation in a study before “children.”
Today, the Belmont Report serves as the main reference for U.S. institutional review boards, which were established in compliance with the Declaration of Helsinki.
Conclusion
Based originally on the three documents described above, the seven main principles now in practice in all research on human subjects are that the clinical trials research must have each of the following:
Social and clinical value
Scientific validity
Fair subject selection
Favorable risk-benefit ratio
Independent review
Informed consent
Respect for potential and enrolled subjects
An additional ethical requirement of clinical trials is collaborative partnership, meaning that the clinical research must involve the community in which it occurs. The community should participate in planning, conducting, and overseeing research, and in integrating the results of the research into the community health system. The way that this is achieved is through community advisory boards in which patient advocates participate, as well as advocates for research funding.
Astra I. Chang
University of California, Davis
See Also: Clinical Trials (Adult Cells), Ethics of; Clinical Trials Outside the United States.
Further Readings
“The Belmont Report.” Office of the Secretary. Ethical Principles and Guidelines for the Protection of Human Subjects of Research. The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (April 18, 1979). http://www.hhs.gov/ohrp/humansubjects/guidance/belmont.html (Accessed May 2014).
Carlson, R. V., K. M. Boyd, and D. J. Webb. “The Revision of the Declaration of Helsinki: Past, Present and Future.” British Journal of Clinical Pharmacology, v.57/6 (2004).
Emanuel, E. J., D. Wendler, and C. Grady. “What Makes Clinical Research Ethical?” Journal of the American Medical Association, v.283/20 (May 24, 2000).
Riis, P. “Perspectives on the Fifth Revision of the Declaration of Helsinki.” Journal of the American Medical Association, v.284 (2000).
Shuster, Evelyne. “Fifty Years Later: The Significance of the Nuremberg Code.” New England Journal of Medicine, v.337 (November 13, 1997).
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The development of induced pluripotent stem cells (iPSC) and of induced adult stem cells (iASC) has dramatically quelled the debate surrounding stem cell research and therapeutic treatment by removing human embryos from the equation. However, stem cell therapy (SCT) and iASC for therapeutic treatment is still in its infancy and remains many clinical trials away from mainstream use.
As with all human clinical trials, ethical concerns for safety, efficacy, and human integrity dominate. Unlike other trials, studies involving stem cells as treatment come with a unique set of ethical concerns. This article is an amalgam addressing many differing viewpoints on the ethics of clinical trials involving adult stem cells. In the interest of fairness, viewpoints are presented without evaluation.
Origins of Stem Cells
Stem cells are precursors to the somatic cells that make up functional adult tissue types, and are classified by their plasticity. Totipotent cells are found in embryonic tissue and are capable of giving rise to an entire organism and all of its various tissue types. Pluripotent cells can also mature into any tissue type but cannot result in a complete organism, whereas multipotent cells (aka adult stem cells) develop into only a very specific set of tissue types and are usually found only within that existing tissue type.
iPSC and iASC are adult stem cells that have been induced from a multipotent state to a pluripotency and are themselves subclassified by origin. Totipotent stem cells can be created in the lab by use of somatic cell nuclear transfer (SCNT), where the complete genetic material of an adult donor cell is inserted into the nucleus of an egg (oocyte). The use of SCNT remains volatile as some argue the implanted oocyte becomes a viable, independent embryo and defeats many of the ethical benefits of iASC.
Allogeneic iASC are cells collected from a donor, with the best-known being those collected from neonate umbilical cords and cord blood. When used therapeutically, the same precautions against immune rejection must be taken as with organ transplants. Conversely, autologous stem cells (or syngeneic stem cells) are collected and induced directly from the receiving patient’s own body or from an identical twin (respectively). Because they do not require immune suppressive therapy after implantation, and skirt