Research on Environmental Health Interventions: Ethical Problems and Solutions

Abstract

This article reviews a variety of ethical issues one must consider when conducting research on environmental health interventions on human subjects. The paper uses the Kennedy Krieger Institute lead abatement study as well as a hypothetical asthma study to discuss questions concerning benefits and risks, risk minimization, safety monitoring, the duty to warn, the duty to report, the use of control groups, informed consent, equitable subject selection, privacy, conflicts of interest, and community consultation. Research on environmental health interventions can make an important contribution to our understanding of human health and disease prevention, provided it is conducted in a manner that meets prevailing scientific, ethical, and legal standards for research on human subjects.

We would like to thank Ernest Kraybill, Walter Rogan, and two anonymous reviewers for helpful comments.

Notes

We would like to thank Ernest Kraybill, Walter Rogan, and two anonymous reviewers for helpful comments.

¹The goal of the KKI study was to assess the effectiveness of different forms of lead abatement. KKI researchers enrolled 25 low-income families in the study and divided them into five different groups. Three of the groups included families living in houses where lead paint was known to be present. These three groups were randomly assigned to receive varying degrees of repair and maintenance to reduce exposure to lead. The study also included a group of families living in houses that had already undergone complete lead abatement, and a group of families living in houses that never had been painted with lead paint. The KKI study collected dust samples from these houses and measured lead levels in the blood of children living with those families to determine the effectiveness of lead abatement programs. Prior to recruiting families to participate in the study, KKI researchers reached agreements with landlords to allow their buildings to be part of the study, encouraged the landlords to rent to families with young children, and helped the landlords obtain grants to pay for lead abatement ( Grimes vs. Kennedy Krieger Institute, Inc., 2001). When the study began, the landlords were not required by law to reduce lead exposure in their buildings. Young children exposed to environmental lead are at risk for lead poisoning and permanent brain damage (Hoffman and Rothenberg, 2002). The plaintiffs sued KKI and several researchers, arguing that they did not receive adequate informed consent about the research and were not warned about dangerous lead levels in a timely fashion. The defendants moved to dismiss the case on the grounds that they did not have any legal duties to the plaintiffs that could serve as a basis for a lawsuit. The circuit court ruled in favor of the defendants, and the plaintiffs appealed this decision. The Maryland Courts of Appeals ruled in favor of the plaintiffs and remanded the case back to the lower court. The Court of Appeals said that the researchers had a legal duty to the subjects, based on the federal research regulations and the informed consent document. The court also engaged in a lengthy discussion of the duties researchers owe subjects in nontherapeutic research ( Grimes vs. Kennedy Krieger Institute, Inc., 2001). The court found that a parent or guardian may not give consent for a child’s participation in nontherapeutic research in which the subject faces any risk of damage or injury. KKI, as well as several other organizations that support biomedical research, asked the court to reconsider its ruling, on the grounds that the opinion could undermine pediatric research and was more restrictive than the federal regulations on pediatric research, which allow children to participate nontherapeutic research that constitutes only a minimal risk to subjects. Although the court did not change its ruling, it clarified its opinion and stated that children can participate in nontherapeutic research if the research poses only a minimal risk to the subjects (Nelson, 2002). Nontherapeutic research is research in which the subject has no prospect of a direct health benefit. Most commentators hold that it is morally acceptable to expose children to more than minimal risks in therapeutic research if the subjects can benefit from the research. For example, a child with cancer may participate in a study of a new cancer drug, if participation in the study offers the child medical benefits. Because the Maryland Court of Appeals focused on questions relating to Maryland’s law, the implications of Grimes for other courts and cases are unclear. Although Maryland district courts are obligated to follow Grimes, other state or federal courts could reach different conclusions. Even so, it is likely that other courts will examine Grimes to consider its legal reasoning and insight (Resnik, 2004b).

²Biologists often speak of various types of environments, such as the intracellular environment or the extracellular environment. The best way to understand this usage of the word environment is to regard the environment as a relational concept in biomedicine. One could view an organism as an environment relative to a cell within the organism; a cell as an environment relative to one of its organelles, such as the nucleus, and so on (Brandon, 1995). Indeed, it makes sense to say that there is not one environment but that there are many different types of environments at different levels of biological organization (Eldredge, 1985). Thus, the line between environmental interventions and pharmaceutical, surgical, or dietary interventions also may be blurry. For the sake of clarity, this article will focus only on those interventions occurring at the organismic level of organization, not on those occurring at lower levels.

³Some researchers recently have challenged the significance of the placebo effect in biomedicine; see Hrobjartsson and Gotzsche (2001).

⁴This hypothetical case is similar to several real cases, such as Morgan et al. (2004). We are using a hypothetical case in this article because we want to focus on the ethical issues at stake in environmental interventions, and we are not interested in criticizing any particular research study. In this case, we refer to the people who are being studied as subjects. We are aware that some writers prefer to use the term participants, but we have chosen not to use this term because we think it can obscure the fact that people who are being studied often are vulnerable and easily manipulated. Moreover, the federal regulations and other important legal documents use the term subject.

⁵It is worth noting that the duty to warn was an important issue in Grimes (Hoffman and Rothenberg, 2002). The plaintiffs alleged that the defendants failed to fulfill their duty to warn them about dangerous lead hazards in their homes in a timely fashion. During the study, the researchers from KKI collected data on lead dust in the homes, but they allegedly failed to notify subjects about these risks in a reasonable time (Grimes v. Kennedy Krieger Institute, Inc., 2001). One of the plaintiffs in Grimes, Catina Higgins, claimed that her son, Myron, suffered a learning disability, shortened attention span, reading difficulty, and hyperactivity as a result of KKI’s failure to inform her in a timely fashion about dangerous lead levels in the home and in her son’s blood (Hoffman and Rotherberg, 2002).

One important lesson that environmental health researchers should learn from Grimes is that they have a duty to warn subjects about health risks in the environment which they discover during the course of their research. Researchers undertake this duty because the relationship between researcher and subject is a fiduciary one: Researchers are entrusted with protecting the health and safety of research subjects (Veatch, 1987). Under U.S. law, a fiduciary relationship is defined as “a relationship in which one person is under a duty to act for the benefit of the other on matters within the scope of the relationship ( Black’s Law Dictionary, 1999). In an important research ethics case, the California Supreme Court found that medical researchers have fiduciary duties to their subjects/patients ( Moore v. Regents of the University of California, 1990). In this case, the researchers had patented a cell-line that they had taken from Moore following an operation to remove his spleen. The plaintiff, Moore, argued that the researchers had breached their fiduciary duties by failing to inform him about their financial interests related to their relationship.However, a recent case found that researchers do not have a fiduciary relationship with their subjects in nontherapeutic research ( Greenberg v. Miami Children’s Hospital, 2003). In this case, the subjects alleged that the researchers breached their fiduciary duties by failing to inform them about their financial interests in patenting a genetic test. The court said that the researchers did not have fiduciary duties to their subjects because they only collected tissue from their subjects and did not have a therapeutic relationship with their subjects. The court held that therapeutic research gives rise to fiduciary obligations, but not nontherapeutic research. It remains to be seen whether other courts follow the court’s opinion in Greenberg, but many ethicists have argued that the therapeutic vs. nontherapeutic distinction lacks merit (Levine, 1988). Federal research rules and guidelines, such as The Common Rule (1991) and The Belmont Report (National Commission 1979), do not make such a distinction.

⁶There is a large body of literature on clinical equipoise in medicine and stopping rules. The controversy focuses on epistemological questions concerning the evidence one needs to start or stop a study, and who makes these decision. See Miller and Weijer (2003) and Miller and Brody (2002) for a review.

⁷The problems we discuss here would be as pronounced if the hypothetical study used a crossover method. In a crossover study, one switches the intervention and experimental groups halfway through the study. Although crossover studies can allow more subjects to benefit from access to experimental therapies, they can be difficult to interpret because the control group in the second half of the study has already been exposed to the intervention.

⁸The adjective vulnerable has been applied to many others subjects besides those protected by specific regulations, including gravely ill patients, students, impoverished patients, and patients who do not speak the language of the country in which research is conducted. For further discussion, see Macklin (2003).

⁹Women, minorities, and children also have been excluded from research for practical and economic reasons. Minority patients, especially African Americans, tend to have a low level of trust in the biomedical research establishment, due to their awareness of episodes of exploitation and abuse, such as the Tuskegee study. Consequently, researchers often have difficulty recruiting patients from racial or ethnic minorities (Dresser, 2001). Additionally, pharmaceutical and biotechnology companies make research funding decisions based on profit potential. Many of these firms have decided that more profit can be gleaned from studying problems that affect rich, white men than from studying problems that affect children, minorities, or poor people (Resnik, 2001).

¹⁰One might argue that the researchers in the KKI study did not violate the federal regulations for pediatric research. Although the KKI study was probably a more than minimal risk study, it also probably resulted in direct medical benefits to children, as there were no inactive control groups in the study. All of the children lived in houses that received some type of lead abatement. If the study had recruited families and required them to live in unabated houses, this would have exposed children to more than minimal risks with no medical benefits. Critics of the KKI study, including the Maryland Court of Appeals, have argued that researchers should not have exposed children to such high levels of risk in nontherapeutic research. This argument misses the point: The federal regulations do not distinguish between therapeutic and nontherapeutic research. What matters is whether children are expected to receive direct medical benefits.

¹¹The plaintiffs in Grimes alleged that they were not adequately informed about the risks of living in a home with dangerous lead levels.

¹²Involvement of community in research can introduce bias into the study, as community members may want the results of the research to promote their interests. Although researchers should be mindful of this potential bias and should takes step to minimize it, this concern is not a sufficient reason for refusing to involve community members in research.

¹³The International Society for the Study of Environmental Epidemiology (ISEE) has developed ethics guidelines for research (ISEE, 1999; Sokolne and Light, 1996). Our paper reinforces many of the important insights contained in the ISEE’s pioneering work.

Greenberg v. Miami Children's Hospital. 264 F.Supp.2d 1064 (S.D. Fla. 2003)

Health Insurance Portability and Accountability Act. (1996). Pub. Law 104–191.

Moore v. Regents of the University of California. 51 Cal.3d 120 (1990)