Irb.2011

Editor's Notes

• #3: There have been many uplifting and morally upright chapters written in the history of the State of Alabama. However, one of them was not the infamous Tuskegee Syphilis Experiment which took place in East Alabama town of Tuskegee with the full knowledge of the government of the United States and at least the acquiescence of the State of Alabama. As you will remember from your history, beginning in 1932 and continuing until 1972, a 600 black men, 399 of whom were identified as being infected with syphilis and 201 without, who rather than being treated, were instead surreptitiously monitored to see what the long term consequences would be. In the 1970s, the truth, as it always does, began to out and the consequences of this very bad idea were many and far-reaching. By the end of the study, only 74 of the test subjects were still alive. Twenty-eight of the men had died directly of syphilis, 100 were dead of related complications, 40 of their wives had been infected, and 19 of their children had been born with congenital syphilis. As part of a settlement of a class action lawsuit subsequently filed by NAACP, nine million dollars and the promise of free medical treatment were given to surviving participants and surviving family members who had been infected as a consequence of the study. The Tuskegee experiment represents an abuse of power by physicians in the face of illiterate minority patients. One attorney who represented the patients and their survivors commented on the illiteracy of the patients' descendants, which he discovered while attempting to identify potential beneficiaries of the legal settlement: Perhaps the most distressing thing [attorneys] Gray and Carter encountered was the lack of social and economic mobility among the heirs. “There were more people who had to execute document by making marks than I'll ever see the rest of my life,” Carter recalled. “It didn't matter whether they had gone to Cleveland or stayed right here, so many of them were illiterate and uneducated .”
• #4: One good consequence of the Experiment was the push within the then Department of Health, Education and Welfare (HEW) to study the ethical principles involved in such human experimentation and to issue guidelines applicable to all institutions proposing perform such research. A blue ribbon commission was established by HEW and was directed to consider:           the boundaries between biomedical and behavioral research and the accepted and routine practice of medicine,           the role of assessment of risk-benefit criteria in the determination of the appropriateness of research involving human subjects,           appropriate guidelines for the selection of human subjects for participation in such research and           the nature and definition of informed consent in various research settings.   The report was finished on April 18, 1979 and gets its name from the Belmont Conference Center where the document was drafted. Belmont, which at one time belonged to the Smithsonian Institution, is located in Elkridge, Maryland, close to Baltimore.
• #5: The Tuskegee Experiment was not the first widely publicized abuse of human subjects to draw widespread attention and to beg corrective action. In the wake of atrocious tales of human experimentation by the infamous Dr. Mengele for Hitler in World War II, the Nuremberg Code was written to set standards for the judging of the ex post facto conduct of physicians and scientists in the war. The Nuremberg Code, though a retrospective, nevertheless became the “prototype” for several later codes that had a prospective application. The Nuremberg Code divided the field into three broad areas of scope: boundaries between practice and research; basic ethical principle; and practice. Building upon the Nuremberg foundation, the World Medical Associated in 1964 drafted the Declaration of Helsinki. Named for the meeting place, Helsinki, Finland, the Declaration established informed consent as the ethical standard in research while allowing for “surrogate” consent in appropriate cases. The Declaration also enunciated the principle that research should only be performed when it is “necessary to promote the health of the population represented.” The Helsinki Declaration laid the foundation for the establishment by the Belmont Report of Institutional Review Boards. The Belmont Report builds upon this base and continues it placing the general principles more in utilitarian categories.
• #6: In 1991, fourteen federal agencies joined HHS in adopting the uniform set of guidelines for human research and the protection of human subjects. This today is known as the “Common Rule,” and is the standard for all agencies and institutions performing such research. Boundaries between practice and research - According to Belmont, “practice” refers to interventions designed to “enhance the well-being” of the individual while “research” applies to the process to test an hypothesis, permit the drawing of conclusions therefrom and thus contribute to generalizable knowledge. This definition needs to be borne in mind as the place of the research has changed over the years. Research is no longer carried on only in teaching institutions and academic medical facilities. One author estimates that there are as many as 19,000,000 individuals participating in research in a given year. The Heart of our consideration herein is the second portion of Belmont as informed by Nuremberg – ethical principles. These principle, though specifically applicable to research involving human subjects sounds very much like basic human rights statements – and so they are. Belmont renders three basic principles: respect for persons, beneficence and justice.
• #14: Respect for persons is an eagle with two wings. First that persons should be treated as autonomous agents and second that persons with diminished capability for autonomy must be protected by society. Autonomous persons have the right to have their opinion consulted in matters that relate to themselves. To make a fair judgment about such decisions, they must be given accurate information and must not be pressured into making decisions. One of the first things our IRB looks at in an IRB submittal is the “informed consent.” Is there one? Is it really “informed,” does it give enough information, and is it understandable to the group under consideration. A further aspect of this is the requirement that this consent be periodically tested to make sure the subject still understands and still consents.
• #15: Beneficence requires the investigator to not only make sure there is continuing knowing consent, but to look out for the broader good of the subject. The investigator starts with a borrowing from Hippocrates and “does no harm” and then move past this to attempting to maximize the benefit to the individual subject. In other words, this principle requires the investigator not stop at merely doing no harm because as the research progresses, what is considered “harm” can change based on facts learned. A thorny ethical controversy involves questions of whether it is a valid subject of beneficent research where there is little or minimal risk to the subject balanced against substantial benefit to generalizable knowledge or even to identifiable groups.
• #16: The Principle of Justice applies to the allocation of risk and benefit the subjects and to the expected served populations. To explain, it can be said that there are several formulations for distributing the benefits and burdens of research: to each person an equal share, to each person according to his or her need, to each person according to societal contributions past and future or to each person according to merit. An example of the justice principle is the question of how the researcher goes about selecting the subjects for the research. Are these welfare patients, from a particular socio-economic or ethic background, confined populations such as prisoners? If so, the selection process of the subjects would give me pause as an IRB chair. The reverse application of the principle is true for the recipients of the benefit of the research. Is it going to benefit only a member of one of these groups or is it going to exclude systematically members of one of these or other groups?
• #17: As these principles work themselves out in the mechanics of application, there must be an informed consent, a detailed analysis of the risk to benefit ratio and an analysis of the criteria for selection of the subjects of the research. There are occasions when the revelation of the subject of the research would invalidate the outcome. In that case informed consent requires three things: 1) incomplete disclosure must really be necessary, 2) there would be no undisclosed risks that are more tan minimal to the subject and 30 there is an adequate plan for debriefing subjects after the conclusion of the project. The laying out of the risk to benefit ratio concerns itself with probabilities and “magnitude” of possible harm and anticipated benefits. Harm, of course can be more than merely physical, consideration must also be given to psychological, legal, social and economic elements of the possible risk. These must then be balanced. To a great extent, the “balancing” is subjective but should be governed by a full knowledge of the ethical principles which underlie research itself. The selection of subjects is accomplished principally according to the justice of the matter. This obtains on a social and an individual level. Individually, researchers should be fair with the subjects, telling the truth to them and not offering inflated goals or promises. Neither should promises or recruitment statements be used to encourage or discourage particular subjects.
• #18: Special care must be taken with confined or disadvantaged populations so as not to continue the over-burdening of such populations. In recruiting especially prisoners, special attention must be given to whether or not the “volunteers” are really volunteers. The same can apply to service men and women. If they are allowed to perceive that they get a special benefit such as light duty or excuse from exercises because they participate, one should look carefully at the justice of such promises.
• #28: Questions?
• #29: See “Closed Pods” - downloads on Slideshare © http://www.slideshare.net/jwible