Above and Beyond: Four Ethical Considerations for IRBs
For partial credit in
MHE 602 Section I: Research Ethics – Spring 2010
Robert C. Baker
In the past 70 years, notorious ethical infractions have necessitated the development of principles and frameworks to protect individual participants from research abuse. Generally, the Nuremberg Doctors’ Trial (1946-47), which focused on Nazi medical atrocities (1) and led to the development of the ten-point Nuremberg Code (2), is cited as the first example of such a development. The Tuskegee Syphilis Study (1932-72), a project directed by the U.S. Public Health Service to chart the progression of the disease in over 400 socially- and economically-deprived black men in Alabama (3), eventually gave rise to the Belmont Report (4) (1979) and, subsequently in 1991, 45 CFR 46 (“the Common Rule”) (5). Other ethical standards for research that have developed in response to abuse include the Declaration of Helsinki, adopted the World Medical Association’s General Assembly in 1964 (6), and the International Ethical Guidelines for Biomedical Research Involving Human Subjects, drafted by the Council for International Organizations of Medical Sciences in 1982 (7).
While each of these guidelines enunciate ethical principles, many of which overlap, in this brief paper I will argue that four ethical considerations–scientific validity, right to privacy, informed consent, and equitable recruitment of subjects–should be incorporated into the overall purpose, structure, and design of clinical research involving human participants. As such, they will be an important part of the consideration of institutional review boards (IRBs), which are required by U.S. federal law to provide ethical guidance and accountability to clinical trials. While none of these considerations are new or exclusive, they do embody decades of accepted ethical reflection that culminated after clear examples of ethical abuse, have been incorporated in numerous ethical frameworks and, in most instances, have become established in law. Finally, I will relate the four ethical considerations to IRBs in order to prove the ongoing need for quality ethical reflection above and beyond codified ethical principle.
Four Ethical Considerations
Scientific Validity
“The value of research depends upon the integrity of study results.” (8) The Institutional Review Board Guidebook points to a general, underlying assumption regarding research: In order to be scientific, research should be ethical. Research abuses exposed during or after the Nuremberg Doctors’ Trail, the Tuskegee Syphilis Study, and the Jewish Chronic Disease Hospital Case (9), among others, provide conclusive evidence that discrimination against, and the mental and physical abuse of, research participants based on race, ethnicity, socio-economic condition, lack of power, or any other condition of vulnerability not only violate ethical values, but also invalidates the status of such research projects as “science.” Emanuel et al. (2008) go so far as to suggest that “science and ethics do not conflict” (10, p. 127). That is not to suggest that experiments cannot be unethical. Rather, the presumption is that in order for research to qualify as science, it must be ethical. The scope and focus of a clinical study, the way in which the study is carried out, the ethical principles involved, the manner of record keeping, retention, and review, the selection of participants, the choice of investigator, and IRB membership–all require the utmost attention in order for ethical research to be carried out. As Emanuel et al. note, while some contend that science and ethics to not mix, in practice both should work in tandem (10, p. 127). This requires, for example, that IRBs concern themselves not only with ethical guidelines and federal regulations, but also seek to ensure that the research being conducted is good, principled science.
Right to Privacy
Another ethical consideration pertains to participants’ right to privacy, which encompasses the use and handling of personal records and identifiable information. Generally, previously existing public or private records obtained prior to the inception of research may be exempted by an IRB (8). However, if personally identifiable information is to be recorded within the context of research, IRBs are obligated to establish controls and procedures to protect such information (8). While the right to privacy can be considered a subset of autonomy rights, it also raises issues related to participant respect and informed consent. For example, Emanuel et al. suggest that a benchmark of well-being supports the principle of respect for participants. As such, it could be argued that sloppy record-keeping during the course of research, which results in a leak of personally-identifiable and potentially-damaging information such as a criminal record, harms participants (10, p. 126) both in the short and long run. Likewise, such a privacy violation could be classified as failure of informed consent if participants had been promised record privacy and had consented to participate in research based on that promise.
Informed Consent
A third ethical consideration is the principle of informed consent. Informed consent well-established, universal, and likewise is derived from a principle of personal autonomy (10, p. 130). While this ethical consideration is important in all studies involving human participants, it should receive a special emphasis in randomized clinical trials, or RCTs (8, 11). Subjects participating in RCTs must be informed if they are likely to receive experimental treatment, especially if that treatment may include a placebo as part of research (8). The risk for therapeutic misconception, or the misunderstanding by research participants that the clinical trial is designed to cure them rather than to cure future patients, must be minimized. In their own language and context, patients should understand and should be able to describe, using their own words, their participation in research. For example, it would not suffice for a Spanish-only-speaking person to sign a Spanish-language consent form without being able to describe, at least orally to someone on the research team who understands Spanish, what the participant’s role would be in the trial. In such a case, while researchers may be seek to demonstrate valid informed consent by the presentation of the signed form, IRBs should realize that the way the consent was obtained is unethical.
Equitable Recruitment of Participants
A final ethical consideration is the equitable recruitment of participants, also known as fair participant selection (12). Given the history of injustices against vulnerable groups in favor of persons of privilege (10, p. 128), equitable recruitment of research participants is an integral part of the design of any clinical research protocol. In recruitment, the right to privacy should be preserved, especially in those instances where valid and ethical informed consent has not or cannot be obtained. Advertising or payment for participation should be reviewed by IRBs for accuracy and to ensure that participants are not misinformed, coerced, or unduly influenced by solicitations or monetary award (8). While attitudes toward equitable recruitment of participants has evolved during the past twenty years (12, p. 378), participants, researchers, and institutions would be well-served by IRBs being familiar with the underlying tensions between protecting today’s participants in view of serving tomorrow’s research beneficiaries. Thus, within federal guidelines, it may be advantageous in the whole for an IRB to consider approval for a study that investigates a disease among a vulnerable population, say, an disenfranchised ethnic minority, particularly if competent, recognized representatives of that population petition for a study in order to expedite the discovery of a cure benefitting that population.
The Continuing Ethical Responsibilities of IRBs
Institutional review boards are established to protect “the rights and welfare” of research participants (13). Given that, within federal research guidelines, IRBs have considerable leeway in interpreting research design and evaluating the ethical basis of all aspects of clinical research, their role cannot be underestimated. While the Common Rule criteria for IRB approval of research contains additional such as minimized participant risk and reasonable participant risk in relation to anticipated benefits (13), these considerations could be subsumed under the consideration of scientific validity as discussed above. The Common Rule mandates technical and baseline requirements such as IRB membership and boards’ functions and duties. However, this federal guideline and perfect adherence to records and reporting management alone cannot ensure that clinical research involving human participants is ethical. What is needed is IRB members, who are committed not only to the ethical considerations scientific validity, the right to privacy, informed consent, and the equitable recruitment of participants, but also to the underlying value of human life.
1. Weindling, PJ. The Nazi Medical Experiments. In: The Oxford Textbook of Clinical Research Ethics. NY: Oxford University Press; 2008:18-30.
2. Annas GJ, and Grodin MA. The Nuremberg Code. In: The Oxford Textbook. Pp.136-40.
3. Jones JH. The Tuskegee Syphilis Experiment. In: The Oxford Textbook. Pp. 86-96.
4. Beauchamp TL. The Belmont Report. In: The Oxford Textbook. Pp. 149-55.
5. Porter JP, and Koski G. Regulations for the Protection of Humans in Research in the United States: The Common Rule. In: The Oxford Textbook. Pp. 156-157.
6. Ashcroft Richard E. The Declaration of Helsinki. In: The Oxford Textbook. Pp. 141-48.
7. Idanpaan-Heikkila JE, and Fluss SS. International Ethical Guidance from the Council for International Organizations of Medical Sciences. In: The Oxford Textbook. Pp. 168-73.
8. U.S. Department of Health and Human Services. The Institutional Review Board Guidebook. Available at: http://www.hhs.gov/ohrp/irb/irb_chapter4.htm. Accessed January 27, 2010.
9. Arras JD. The Jewish Chronic Disease Hospital Case. In: The Oxford Textbook. Pp. 73-79.
10. Emanuel EJ, Wendler D, and Grady C. An Ethical Framework for Biomedical Research. In: The Oxford Textbook. Pp. 123-135.
11. Miller FG. The Ethics of Placebo-controlled Trials. In: The Oxford Textbook. Pp. 261-72.
12. Meltzer LA, and Childress JF. What Is Fair Participant Selection? In: The Oxford Textbook. Pp. 377-85.
13. Office of Human Subjects Research. National Institutes of Health. 45 CRF 46: Protection of Human Subjects. Available at: http://ohsr.od.nih.gov/guidelines/45cfr46.html. Accessed January 27, 2010.
