Case that discusses issues of researcher obligations, the role of informed consent, developmental factors; and options of action available to researchers who discover that minors may be in jeopardy.
From: Graduate Research Ethics: Cases and Commentaries - Volume 3, 1999
edited by Brian Schrag
Dr. Morris Swakowski, a tenured epidemiologist, is working with Beatriz Piacere, a post-doctoral fellow, on a research project involving asthma and wheezing in African-American and white adolescents. They have just completed a school-based study in which they found a very high prevalence of diagnosed asthma and wheezing in eighth graders.
In the literature, the most current research is investigating the association of asthma with exposure and allergies to dust mites and cockroaches. Dr. Swakowski and Beatriz want to find out whether asthma and wheezing are associated with exposure and sensitivity to dust mites and cockroaches in their research population - an urban/suburban community in the South with high humidity, which provides a favorable environment for dust mites. They also want to evaluate several low-cost interventions that could reduce the children's exposure to these two allergens.
This research is being conducted in collaboration with the large public school administration of the city. The school population is 40 percent African-American, and 28 percent of the children are on the free school lunch program.
The researchers decided to address the following questions:
The two investigators agree on the sampling strategy: children who, in the previous school-based study, self reported either 1) diagnosed asthma 2) wheezing symptoms with no asthma diagnosis, and 3) no wheezing symptoms and no asthma diagnosis. After parents have given their informed consent, the children will be brought to the health clinic, enrolled, and given a skin prick test for twelve different allergens. Skin prick tests are done to determine whether the children are allergic to specific allergens including cockroaches and dust mites, which may be triggers for their wheezing attacks. Dust mite and cockroach allergen levels also will be measured in their homes.
Half the participants will receive the environmental interventions at the start of the study, and the rest will receive the interventions at the end of the study. The interventions are plastic bedcovers to reduce the dust mite population and cockroach motels to reduce the number of cockroaches.
In discussing the research design with the pediatrician and the nurse working on the project, the researchers become aware of the issue of anaphylactic shock. The risk of anaphylactic shock from the skin prick test is 1 in 1 million in the general population. Although the risk to the child occurs only at the time the test is conducted, possible consequences include death. If a child begins to go into shock, the standard treatment is immediate administration of epinephrine, which will stop the reaction if a sufficient dose is given. However, the administration of epinephrine is best done by trained staff in a hospital setting.
The nurse in the study is very concerned about this risk of anaphylactic shock. However, she considers that the study might benefit the symptomatic children. If some children have unknown allergies that trigger their asthma or wheezing, this study would benefit them by identifying the allergens that trigger their wheezing attacks. However, the risk of anaphylactic shock is a risk for the control group to be used to answer the first question. Children in the control group will gain little from participating in the research, and it will actually put them at risk. The researchers must consider whether it is necessary to drop the control group.
Posted 13 years and 2 months ago
Brian Schrag Association for Practical and Professional Ethics
Special ethical and regulatory considerations are involved in investigator design and IRB review of research on children. I will focus on these special concerns.
One step is to identify which of four categories of research the study belongs to: 1) research that does not involve greater than minimal risk to children; 2) research involving greater than minimal risk but presenting the prospect of direct benefit to the individual child-subject; 3) research involving greater than minimal risk and no prospect of benefit to the child; 4) research not otherwise approvable under one of the above categories, but the IRB determines that the study presents a reasonable opportunity to further the understanding, prevention or alleviation of a serious problem affecting the health or welfare of children. (OPRR Reports 1981)
The study in this case calls for eighth graders to take a skin prick test of 12 different allergens including those for cockroaches and dust mites. The children are divided into three groups for the purpose of the experiment based on the following characteristics. 1) children who have self reported a diagnosis of asthma; 2) children who have wheezing but have not been diagnosed with asthma, and 3) children who have neither wheezing nor asthma.
The first category of research does not involve greater than "minimal risk" to children. Minimal risk means "the probability of and magnitude harm or discomfort anticipated in the research are not greater in and of themselves that those ordinarily encountered in daily life or during performance of routine physical or psychological tests." Allergy scratch tests are included in the category of minimal risk. (Office of Human Subjects Research 1993, p. 3) There is a possibility that a child will go into anaphylactic shock from the skin prick tests. Anaphylactic shock can lead to death in minutes if not treated. The probability in the general population of anaphylactic shock from the skin prick tests is 1 in 1 million; the magnitude of harm is great, but the probability is small.
However, the aim of the research is to determine whether asthma and wheezing are associated with exposure and sensitivity to cockroaches and dust mites. If that turns out to be the case, then there is a possibility that children in groups 1) and 2), who have asthma or wheezing, may have already developed a sensitivity to these allergens. Hence, the probability of anaphylactic shock may be higher for them. That probability is, presumably, unknown. The probability of risk for subjects in these two groups may thus be higher than for the general population and those in the control group who do not have asthma or wheezing. However, the risk for those in the two experimental groups is no higher than it would be if their parents had decided, because of the children's symptoms, to take them in for allergy testing on their own. The control group, on the other hand, might not otherwise undergo the scratch tests and hence incur the 1 in 1 million risk of the scratch test.
It is also the case that the tests will be conducted in a setting prepared to deal with such reactions and perhaps with heightened awareness to the possibility of reactions. Does this set of experimental conditions move the research subjects to a category higher than minimal risk? It is not clear that it does.
There are some direct material benefits for all participants from participating in the program. 1) All participants would receive a free allergy test. 2) All participants would receive free assessment of levels of these allergens in their homes. 3) All would receive some inexpensive materials for control of dust mites and cockroaches.
Who stands to benefit from results of this research? If it should turn out that asthma and wheezing in children in groups 1) and 2) is caused by dust mites or cockroaches or both, then children in these two groups would presumably benefit significantly and directly from the findings since the source of their problem will have been identified and thus may be alleviated. For them, this study falls in the category of therapeutic research. The population of all children who are at risk when exposed to these elements also may benefit significantly from this knowledge. Recent publicity suggests that the number of children with wheezing and asthma is substantial and increasing and may be linked to allergies to dust mites and cockroaches. The benefits to the two experimental groups may well be said to offset the risks.
The results presumably would not directly benefit those in the control group who are resistant to these allergens, unless, of course, even they could become sensitized given high enough allergen levels. Children in the control group might have siblings who are sensitive to these allergens, and the siblings might benefit directly from the research results. The benefits for the control group are minimal. Children in the control group will be exposed to the risk of anaphylactic shock, which they would presumably not otherwise incur, but that risk is deemed minimal.
A second consideration in the study is the process of obtaining voluntary, informed consent. The case does not indicate the socioeconomic level of the participants. If they are from a low socioeconomic and educational background, there is a possibility that they will be unduly swayed by the offer of free allergy tests and modest environmental interventions. That possibility must be taken into consideration.
Human subjects research guidelines for children require that the permission of parents or guardians must be obtained, since children are considered unable to give legally valid informed consent. However, the children in this case are in the eighth grade and are capable of providing assent. Hence, they should be asked if they assent to participating in the research.
The information given to subjects and parents should certainly include the purpose of the experiment and the risks and benefits involved. In the case of the control group, it should be made clear to both parents and children that their involvement is not for their own benefit but for the benefit of others.
The information must be made available in a manner easily understood by both parents and children, particularly if they are from a disadvantaged population. It would be appropriate to include some general educational information on problems associated with asthma and allergies so all can understand the significance of the research and, in the case of groups 1) and 2), they can learn something about the conditions they have.
If a participant experiences anaphylactic shock at some point during the allergy tests, it would be appropriate to inform the other participants and give them the option of withdrawing from the experiment.
From: Graduate Research Ethics: Cases and Commentaries - Volume 3, 1999 edited by Brian Schrag
The researchers have carefully considered the risks and benefits of the study. If a death from anaphylactic shock were likely to occur, there would be little moral justification for the research. This research poses a very low initial risk to the children: 1 in 1 million.
There are several aspects of the research that the investigators can address. First is the issue of respect, which would include informing the parents and children of the potential risk and requesting informed consent. In addition, the researchers will try to maximize the benefit to the participants by dropping the nonsymptomatic control group because these children have much less to gain from participating than children who have respiratory symptoms. Only symptomatic children, who would have more to gain from the skin testing, will be recruited.
If one child enrolled in the study developed anaphylactic shock, the consequences could be devastating - the death of the child; the loss to family and friends; anger and fear in the community directed at the researchers, the school administration and the public health department. A child's death would also affect the research policies of the school administration and the public health department. It is likely that more conservative policies would be adopted, which would limit the ability to identify disease in at-risk subpopulations and implement measures to reduce disease.
The researchers should take several steps to prevent a death from anaphylactic shock. First, they should have trained staff who know what to do immediately if a child begins to go into shock. Second, they can conduct the research in a medical clinic with quick access to medical expertise if the emergency epinephrine does not work. With these measures in place, the researchers will have maximized the benefits to the participants and minimized the risks.
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In the Tuskegee research, investigators deceived members of the African-American community and enrolled them in a study to follow the natural history of untreated syphilis. These men were allowed to remain untreated for syphilis for forty years, from the 1930s to the 1970s, even though treatment became available in the 1940s with the dissemination of penicillin. With the legacy of the Tuskegee experiment, the African-American community has had much less trust in governmental institutions and outside investigators conducting research in their community.
Issues of respect, beneficence and justice do not change; they are universal principles in our society. However, we as researchers can learn from the past. Clearly the Tuskegee study violated the three tenets published in the Belmont Report. People who participate in research are entitled to respect, beneficence and justice.
Little respect was shown for the African-American men who participated in the Tuskegee experiment. They were treated like children or experimental lab animals; they did not give informed consent; crucial information about the experiment was withheld from them. Nor was there much concern for the welfare of participants in the 40- year duration of the experiment.
The participants did not obtain any benefits from taking part in the study. Although the men received a few free meals and palliative treatment for some of their symptoms, these were of negligible benefit compared to the harm they experienced as the disease progressed to advanced stages. Nor were they told they had syphilis. The men did not benefit from being under medical surveillance. In fact, they were placed at higher risk from procedures such as lumbar punctures to test for neural syphilis. Justice was not served by research conducted at the expense of a subpopulation of African-American men to obtain information designed to benefit the entire U. S. population. Moreover, there were no clear benefits to the population of all syphilitics.
Researchers in today's environment can ensure that they take the Belmont Report's tenets into account when planning and conducting research. In the asthma study, parents and children who are invited to participate in the study receive a clear explanation of the risks and benefits that would be incurred with participation. The informed consent forms are written in easily understood language with little jargon. Moreover, only children who seem to be at risk of asthma or wheezing are invited to participate because they are the children most likely to benefit from the study. They will learn what potential allergens they are allergic to, as well as receiving information on how to reduce their exposure or deal with asthma. They will also be enrolled in the medical clinic and have better access to care for their wheezing symptoms. In addition, all participants will receive the plastic bed covers and cockroach traps.
In considering the tenet of justice, the question stated in the Belmont Report is, "Who ought to receive the benefits of research and bear its burdens?" In the case of the asthma research, the intervention is low cost, specifically targeted for families with little money or time to spend. Thus, the subjects are being systematically selected for reasons directly related to the problem being studied rather than their easy availability or their manipulability. (National Commission,1979) Moreover, these subjects are recruited from a pool of children who were found to have wheezing symptoms, so they would benefit greatly from a reduction in allergen levels.