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 most stem cell controversies, this is where much of the current research is focused.
Ethical Concerns in Clinical Trials
All clinical trials present ethical concerns that must be balanced against research value. Patient safety is paramount; however, there is always risk and the acceptable amount is often determined by how devastating the illness to be treated is. Patients must be presented with the full facts about risk and benefit (both to themselves and others) in order to make an “informed consent” of participation.
To ensure study viability, placebo groups are often used, which, in and of itself, introduces ethical concerns as patients must decide if the potential benefits of the experimental treatment are outweighed by the possibility of being in the placebo group and receiving no treatment at all. In the case of severe illnesses, the placebo group is often replaced by a comparison of the trial results against traditional treatments. Risk/benefit analysis and informed consent are of special concern with iASC studies due to an ongoing controversy surrounding cancer studies in the 1990s.
Human integrity and provider conflicts of interest are real concerns, but difficult to quantify. In this discussion human integrity refers to protecting the patient’s rights and dignity throughout the course of the trial, including property rights and the use of an individual’s tissues for purposes outside the study. These concerns can frequently lead to conflicts of interest within the medical and research communities.
Of particular concern with technologies such as iASC, which show high profit potential, is the dual role held by doctors as care providers and researchers. Patients with serious illness are a vulnerable population and depend heavily on the guidance of their caregiver. Even the best-intentioned professionals can find themselves swayed by their personal enthusiasm for a project, as well as other pressures, to place candidates into a study when they might objectively be better served by traditional treatments.
Studies for “last chance” therapies are especially susceptible to human integrity violations by both physicians and patients. These studies involve patients suffering life-threatening illnesses who have not responded (or not responded well) to traditional treatments. The temptation of “new hope” can be coercing to patients and providers alike when palliative end-of-life care may realistically offer the greatest dignity
