This case discusses the potential dilemmas encountered by postdoctoral fellows in a research setting, discussing whether is it ethical for drug trials to offer money to participants in the study and also explores the potential problems with clinical trials and vulnerable populations.
From: Graduate Research Ethics: Cases and Commentaries - Volume 5, 2001
edited by Brian Schrag
Gary is a graduate student in history at Eastern State University. He has completed his course work, passed his qualifying exams and finished his research, and he is working on his dissertation. He has been working as a teaching assistant for Professor K, the chair of his committee, for the last three years. However, the university did not renew his TA contract for the current academic year, and he has been desperately seeking funds to finish his studies.
It is clear that Gary is in a financial bind at the end of his university career. Do universities have an obligation to support their graduate students during the long years of research and writing required to complete a dissertation? What should Gary do in this situation? What would you recommend if you were the chair of Gary's committee?
Gary spoke with his friend Anthony about his financial problems. Anthony informed him that a number of pharmaceutical companies were looking for volunteers to participate in clinical trials to evaluate new drugs in healthy individuals. Gary investigated the first clinical trial that he learned about through his conversation with Anthony. He was accepted and received $500 for his participation. The trial was to continue for one week, and he was required to take a pill each day and visit the evaluation center for tests. On the third day of the study, Gary decided to sign up for a second study, at a different center, which was paying $3000 for "volunteers." He hoped that the $3,500 would be sufficient to allow him to complete his thesis.
Signing up for the second study, the interviewer, in his haste to recruit enough volunteers before the company-imposed deadline for filling the quota, failed to ask whether Gary was involved in any other clinical trials. Gary was completely truthful during the interview, but he did not volunteer any additional information beyond what was asked. Therefore he did not disclose that he was participating in another study, or that he was regularly using herbal remedies for the treatment of chronic allergies.
Two weeks later, Gary began feeling very sick and sought medical attention at the University Hospital Emergency Department. During his hospitalization, physicians suspected that his symptoms were etiologically related to a drug interaction caused by the drug combination he was taking (the two drugs given to him during the two separate research studies, as well as the herbal remedies). Due to his hospitalization, Gary was not able to complete his dissertation or defend it in time for the university's deadline for graduation in June.
Posted 14 years and 5 months ago
Karen M. T. Muskavitch Boston College
Identification and Minimization of RiskPayment of Cash IncentivesFunding of Graduate Students
This case raises three primary issues: the funding of graduate students, the payment of cash incentives to those who volunteer to be the human subjects of research, and the identification and minimization of risk to human subjects. In a discussion of this case, one might choose to cover all or only one or two of these issues. I will consider each of these issues in the reverse order.
Researchers are responsible for identifying and minimizing risk because of beneficence, the second ethical principle identified in the Belmont Report1. "In this document, beneficence is understood . . . as an obligation. Two general rules have been formulated as complementary expressions of beneficent actions in this sense: (1) do not harm and (2) maximize possible benefits and minimize possible harms." Putting this principle into practice, the Common Rule2 that regulates government-funded research involving human subjects states that one of the criteria for IRB approval of the research is that "[r]isks to subjects are minimized: (i) by using procedures which are consistent with sound research design . . . and (ii) whenever appropriate, by using procedures already being performed on the subjects for diagnostic or treatment purposes." It also states that a potential subjects should receive "a description of any reasonably foreseeable risks or discomforts to the subject" as well as "for research involving more than minimal risk, an explanation as to whether any compensation and an explanation as to whether any medical treatments are available if injury occurs . . . ." The FDA rules3 that govern clinical trials of drugs and medical devices have the same requirements.
In this case, then, both the integrity of the research and concern about the subjects require that the research team and the IRB think creatively about possible risks. Frequently, only the potential risks that could come directly from the research protocol are considered. However, other factors in the lives of the subjects could combine with the research to produce more indirect adverse effects. Thus, even a question about the potential subjects' use of prescription drugs might not be sufficient to protect the subjects. In a case like this one, both the taking of nonprescription remedies and the illegal use of controlled substances as well as participation in other clinical trials might need to be determined before the potential risks could be truly evaluated and a person admitted to the study. The regulations make clear that the researcher is responsible for securing this information. It is not the obligation of the potential subject to guess and then volunteer any information that might be relevant.
It has long been common practice to pay people for their participation in research. Some say payment is to compensate them for their time and trouble. Others assert that payment increases subject compliance with the research protocol. Many researchers see compensation as a way to increase their recruitment of potential subjects. As Dickert and Grady note4, "this practice is one of the most controversial methods of recruitment. Despite discussions over many years, ethical issues about payment remain unresolved." Concerns about compensation arise out of two of the ethical principles of the Belmont Report1, the principles of respect for persons, and justice. Respect for persons leads to the need for informed consent. But as the Belmont Report asserts, "[a]n agreement to participate in research constitutes a valid consent only if voluntarily given. This element of informed consent requires conditions free of coercion and undue influence." Is the payment for participation in a research study an "undue influence," that is "an excessive, unwarranted, inappropriate or improper reward1"? How large does the payment have to be before it is "excessive"? That is one concern.
The other concern is that even at levels that would not be deemed "excessive" for the general population, do financial incentives induce more people of limited economic means to volunteer to be research subjects than the population at large? If so, this disparity is a problem related to the ethical principle of justice. This principle asserts that it is wrong if one group of people bears most of the burden and/or risk for scientific research while another group receives most of the benefit.
Because of concern for respect for persons and justice, the FDA regulations3 and the Common Rule2 state that "[w]hen some or all of the subjects, such as children, prisoners, pregnant women, handicapped, or mentally disabled persons, or economically or educationally disadvantaged persons, are likely to be vulnerable to coercion or undue influence additional safeguards [should be] included in the study to protect the rights and welfare of these subjects."
From the information given in this case, it appears that Gary volunteers for the clinical trials only because he is in need of money, not because he is interested in supporting the research. The case also suggests that the $3000 offered by the second trial was so large that Gary was willing to risk joining the second trial at the same time that he was participating in the first. Would he have done that if the amount offered had been smaller? We don't know, and this is the sort of question that researchers and IRB members face frequently. What is the purpose of paying research subjects? How much is too much? And is any payment of subjects ethically justifiable? These are important questions to discuss, and the Dickert and Grady article4 as well as subsequent letters and articles in the literature are good resources.
If graduate students are discussing this case, it will be difficult not to spend at least some time exploring this aspect of the case. The funding of graduate students' education is essential to their academic success - in fact to their very survival - but it has not been as frequently or thoroughly discussed as it should be. Discussions between professors and students have often been limited to purely academic topics.
This situation is changing, slowly, but now funding is a legitimate topic of discussion. Here are some examples. The Committee on Science, Engineering and Public Policy of the National Academy of Sciences, the National Academy of Engineering and the Institute of Medicine lists funding as one of the three logistical issues that faculty should discuss with predoctoral and postdoctoral candidates5. Particularly with regard to the sciences, Macrina observes that "[o]ne of the unique aspects of predoctoral mentoring is the degree to which the trainee is dependent upon the mentor. In many cases, this dependence is grounded in finances. . . ."6. For all disciplines at the University of Illinois, Urbana-Champaign, the Graduate College recommends that departments clearly communicate to graduate students the conditions for their financial support, if any, as part of its Best Management Practices for Graduate Program Improvement7. While few would assert that the university has an obligation to financially support all graduate students throughout their studies, most would agree that there is an obligation to clearly describe the support the university is willing to provide and candidly discuss all possible funding options with students. It is possible that Gary was not aware of other options open to him before he volunteered for the two clinical trials.
1. The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research, 1979. http://ohrp.osophs.dhhs.gov/humansubjects/guidance/belmont.htm
2. 45 CFR 46, http://ohrp.osophs.dhhs.gov/humansubjects/guidance/45cfr46.htm
3. 21 CFR 50 and 21 CFR 56, http://www.fda.gov/oc/gcp/preambles/53fr45678C.html
4. Dickert, Neal, and Christine Grady. "WhatÀs the Price of a Research Subject Approaches to Payment for Research Participation,"New England Journal of Medicine 341(3, 1999): 198-202.
5. Committee on Science, Engineering and Public Policy of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. Adviser, Teacher, Role Model, Friend: On Being a Mentor to Students in Science and Engineering. Washington, D.C.: National Academy Press, 1997, pp. 30-32. http://www.nap.edu/readingroom/books/mentor
6. Macrina, Francis L. Scientific Integrity: An Introductory Text with Cases. Washington, D.C., ASM Press, 1995, p. 17.
7. Graduate College, University of Illinois, Urbana-Champaign, "Best Management Practices for Graduate Program Improvement," http://www.grad.uiuc.edu/Pubs/bmp/index.html
From: Graduate Research Ethics: Cases and Commentaries - Volume 5, 2001 edited by Brian Schrag
Offering financial incentives to increase participation in clinical studies raises a series of ethical issues. For example, participation should be on a voluntary basis, inspired by the desire to help, and not for the money. In addition, when financial incentives are offered, there is a tendency to recruit from vulnerable groups such as the poor, students, intravenous drug users, alcoholics, etc. It is more likely that these marginalized people will lie about their lifestyle in order to qualify to participate and receive money.
In this case, the volunteer was using an herbal remedy, and he did not disclose that information. If the incentive is great enough, it is even more likely that candidates who are users of illegal narcotics will try to qualify. How will the interviewers guarantee that they can exclude drug users, who are unlikely to admit to drug use during the interview process?
Given these considerations, one can also question the scientific validity of such a study. Clinical investigators must be aware that by offering financial incentives they are recruiting from a population that is not representative of the general population. Therefore, the results are biased. Despite this fact, it is quite common to pay clinical study participants.
In addition, these issues raise the question of how to go about proper screening of candidates for clinical trials. It is essential to design screens in order to minimize the likelihood that a situation such as the one described in this case study occurs. It is evident that the investigators must be extremely rigorous in their questioning of potential participants, especially if they are offering cash incentives. If they fail to screen properly, are they committing the ethical equivalent of scientific fraud?
In this case, financial desperation drove the graduate student to take risks with his own health in order to pay for his studies. One may question what obligations universities have to graduate students to continue funding through the studentsÀ careers. In addition, there is a seeming discrimination, which most universities display in providing more assistantships for students in the natural sciences than students in the social sciences and humanities.