Important note: Information in this article was accurate in August/September 1999. The state of the art may have changed since the publication date. | The online version of HEPP News displays the main article only, to view the entire newsletter download the following PDF:
|
Prisoners, because of their relatively stable environments and availability, have historically been attractive, if not preferred, research subjects. Phase I drug toxicity studies, malaria treatment trials and radiation exposure experiments have notoriously been conducted utilizing prison inmates (1-3). However, with the evolution of research ethics and subsequent regulations, investigations involving prisoners have undergone fundamental changes over the past three decades.
Many advancements in establishing ethical standards for research conduct have stemmed from landmark events such as the Nuremberg "doctors' trials" of 1946; the 1964 statement by the World Medical Association (WMA), commonly known as the Declaration of Helsinki, and the convening by the U.S. Department of Health, Education and Welfare of the Belmont Commission in 1976 (4-6). While these events have set forth fundamental protection of human research subjects in general, each has also significantly impacted the use of prisoners in research.
At the heart of all attempts to codify ethical research practices is the concept of in-formed and voluntary consent. The major codes and commission reports require that research subjects must agree to participate in studies free from "coercion," "constraint," "duress" or "elements of force." However, many argue that the prison setting is inherently coercive and severely limits the autonomy of prisoners to make a free choice. An opposing perspective argues that prisoners should not be denied the opportunity to make informed decisions to volunteer for properly designed research protocols.
The Belmont Commission Report recognizes the difficult balance between avoiding overt and subtle coercion of inmates as study subjects and allowing inmates the choice to participate. According to the authors of the Belmont Report, "On the one hand, it would seem that the principle of respect for persons requires that prisoners not be deprived of the opportunity to volunteer for research. On the other hand, under prison conditions they may be subtly coerced or unduly influenced to engage in research activities, for which they would not otherwise volunteer. Respect for persons would then dictate that prisoners be protected." Whether to allow prisoners to "volunteer" or to "protect" them presents a dilemma, the report states (6).
The presence of unethical influence over inmates to enter clinical trials may be overt; for example, the awarding of special privileges or a sentence reduction. However, coercion can also be subtle. Increased access to medical care and opportunities to interact with others during study-related activities might constitute undue inducement.
The institutional review board’s (IRB) role is to be vigilant in determining if coercion is present. The IRB Guidebook, published in 1993 by the National Institutes of Health (NIH), charges IRBs with determining whether advantages received by prisoner subjects are sufficient to impair the inmate's ability to freely choose to enroll (7).
Federal policy mandates that only certain kinds of research are appropriate for prisoner participation. These studies present no more than a minimal risk to the subject. Minimal risk is defined as "risk of physical or psychological harm that is no greater than that encountered in the routine lives of healthy persons."(8) Research considered appropriate for prisoner participation includes studies of criminal behavior, prison life, conditions affecting prisoners as a class and therapies likely to benefit the prisoner subject. Therefore, phase I and II treatment trials are not appropriate in correctional settings.
In general, prisoners should not be selected for research when other, less vulnerable and burdened populations can address the scientific question being posed. This issue of distribution of the burden of research is addressed in the Belmont Report:
"Social justice requires that distinction be drawn between classes of subjects that ought, and ought not, to participate in any particular kind of research, based on the ability of members of that class to bear burdens, and on the appropriateness of placing further burdens on already burdened persons.
Thus, it can be considered a matter of social justice that there is an order of preference in the selection of classes of subjects (e.g., adults before children), and that some classes of potential subjects (e.g., the institutionalized mentally infirm or prisoners) may be involved as research subjects, if at all, only on certain conditions." (6)
The use of placebos must also be applied in an ethical manner when research in-volves vulnerable populations. In the wake of the Tuskegee syphilis study, where poor African American men were not informed that they were part of an infected natural history cohort, it is imperative that all pro-cedures and treatments be known and understood by the subject. Placebos can be used as part of a control group only in special circumstances and almost never when administered alone without a concomitant active agent. Use of placebos or inclusion of an untreated control group requires approval of the Department of Health and Human Services if the research is federally supported (7).
Protecting the privacy of prisoners is difficult even when they are not part of a clinical trial. Simply being moved from a cell to a clinic can make an inmate conspicuous to others.
In addition, there are breaches of confidentiality when non-medical staff have access to medical records. Study activity that in-creases the frequency of clinic visits or risks confidentiality in other ways must be minimized. Maintaining confidentiality for inmates may involve elaborate safeguards and protections such as storing study related documents separately from the medical record, integrating study visits with routine clinic visits and carefully labeling any medication dispensed.
The primary responsibility for review and oversight of clinical research is the IRB. All research involving prisoners should be evaluated by an IRB. The board should meet the requirements specified in the Code of Federal Regulations [45 CFR 46.304].
A disproportionate number of persons incarcerated in the United States are mem-bers of racial minorities. As such, research in correctional settings may place a particularly unfair burden on minority prisoners despite the efforts of the investigators to fairly select subjects. Historically, the opposite has generally been true; white prisoners have usually been over-represented in research. This may have been due to biased selection, allowing white inmates to benefit from the privileges that were historically associated with participation in research trials (9).
However, as more members of racial and ethnic minority groups are incarcerated and the coercive inducements for study enrollment are eliminated, there is a potential for minorities to be disproportionately represented in clinical research in prisons.
While individual institutions or investigators may not be able to resolve a problem that is pervasive in their social setting, they can consider distributive justice in selecting research subjects. This may be accomplished by attempting to have the racial make-up of the study population reflect that of the population affected by the disease being studied. For research investigating conditions specific to prisoners, the disproportionate inclusion of racial minorities may be justified as representative of the composition of the prison population.
Prisoners need to be protected from research that is exploitative and which can pose undue risks. Inmates must not be included in research solely because they are part of a convenient and readily accessible population. When undue coercion and influence are minimized to the greatest degree possible, prisoners may be able to make an informed decision regarding participation.
It is incumbent upon investigators and IRBs to be familiar with the regulations guiding research in correctional settings and to determine if the proposed research is suitable for prisoner participation. When designed and implemented correctly, research involving prisoners is likely to benefit inmates as a class, and become an asset to research in general.
Please note: DHHS Has Elevated the Office for Protection from Research Risks (OPRR) to become the Office of Human Research Protections (OHRP) within OPHS, DHHS
http://ohrp.osophs.dhhs.gov/*Speaker's Bureau: Roche, Bristol-Myers Squibb, Glaxo, and Roxane
1.Procedures Used at Stateville Penitentiary for the Testing of Potential Antimalarial Agents. JClin Invest. 27, no. 3 (part 2) (1948): 2-5.
2. Jessica Mitford, "Experiments Behind Bars: Doctors, Drug Companies, and Prisoners," Atlantic Monthly. 23, January 1973, 64-73
3. U.S. Department of Energy: Advisory Committee on Human Radiation Experiments, http://tis.eh.doe.gov/ohre/roadmap/achre/index.html
4. Shuster E. "Fifty years later: the significance of the Nuremberg Code." N Engl J Med 1997 Nov 13;337(20):1436-40
5. Medical Ethics Committee. Proposed revision of the World Medical Association Declaration of Helsinki. Ferney-Voltaire, France: World Medical Association, 1999.
6. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. Belmont Report: Ethical principles and guidelines for the protection of human subjects of research. Washington, D.C.: Government Printing Office, 1983 http://ohrp.osophs.dhhs.gov/humansubjects/guidance/belmont.htm
7. The IRB Guidebook - 1993. Office for Protection from Research Risks - NIH, http://www.nih.gov/grants/oprr/irb/irb_chapter6.htm#gt.
8. Code of Federal Regulations, title 45, part 46: 45 CFR 46.305 and 45 CFR 46.306, 1991.
9. Jon M. Harkness, "Vivisectors and Vivishooters: Medical Experiments on American Prisoners before 1950," paper presented at "Regulating Human Experimentation in the United States: The Lessons of History," Columbia College of Physicians and Surgeons, New York, 23 February 1995.
1999-0710
HEPP1999-0701
©1997,1998,1999,2000. The recently formed HIV Education Prison Project (HEPP) is a medical education program that targets a growing population, inmates in correctional facilities, that has been underserved in HIV care. It is part of the Brown University AIDS Program. Permission to use and reproduce portions of this newsletter is hereby granted provided that author and publication are fully credited and both copyright and permission notice appear with reprinted material. Inquiries may be directed to heppnews@brown.edu. Website: HIV Education Prison Project.
ÆGiS is made possible through unrestricted grants from Boehringer Ingelheim, Elton John AIDS Foundation, iMetrikus, Inc., the National Library of Medicine, and donations from users like you. Always watch for outdated information. This article first appeared in 2000. This material is designed to support, not replace, the relationship that exists between you and your doctor.
ÆGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.
Copyright ©1990, 2000. ÆGiS & the Sisters of Saint Elizabeth of Hungary. All materials appearing on ÆGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of ÆGIS and the Sisters of Saint. Elizabeth of Hungary, or the party credited as the provider of the content.
