Intentional Exposure Studies of Environmental Agents on Human Subjects: Assessing Benefits and Risks∗

In this article, I assess the benefits and risks of studies that intentionally expose research subjects to environmental agents. I describe these types of studies, identify their benefits and risks, compare them to other research methods that can be used to investigate the relationship between environmental exposures and disease, and discuss some issues related to research design and risk minimization. I argue that the benefits of intentional environmental exposure studies outweigh the risks when 1) the knowledge gained is likely to improve our understanding of the relationship between environmental exposure and disease, 2) this knowledge cannot be obtained by other methods, 3) the experiments are well designed, 4) the subjects will receive some benefits, such as medical evaluations, 5) risks are minimized, and 6) the risks to human subjects are less than those encountered in a typical Phase I drug study. Only in rare circumstances (i.e., when an intentional environmental exposure study is needed to implement an important environmental or public health intervention or regulation) may such studies expose research subjects to risks as high as those encountered in a typical Phase I drug trail.     

Research on environmental health interventions: ethical problems and solutions

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.     

Medical school guidelines for investigating misconduct and fraud in science

Institutional review boards (IRBs) are legally required to determine whether the balance between the risks and benefits (the risk-benefit ratio or RBR) of a proposed study is “reasonable” or “proportional”. This obligation flows from their duty to protect the interests of research subjects. It has been argued that it is difficult, perhaps even impossible for IRBs to determine the RBR of studies, because the risks and benefits are not only heterogeneous, but also incommensurable. After arguing that the relevant meaning of incommensurability is incomparability, we discuss whether the risks of participating in a trial and the benefits are comparable. We conclude that at least the risks and the benefits to participants are comparable. In the last section we show that the main problem of RBR analyses is that of interpersonal incompensability. IRBs have to assume that risks to research subjects be compensated by benefits to others. The question is: To what extent? When does it become unreasonable to ask that patients accept the risks of participating in a trial for the benefit of science and/or future patients?     

Are risks and benefits of oncological research protocols both incommensurable and incompensable?

Institutional review boards (IRBs) are legally required to determine whether the balance between the risks and benefits (the risk-benefit ratio or RBR) of a proposed study is "reasonable" or "proportional". This obligation flows from their duty to protect the interests of research subjects. It has been argued that it is difficult, perhaps even impossible for IRBs to determine the RBR of studies, because the risks and benefits are not only heterogeneous, but also incommensurable. After arguing that the relevant meaning of incommensurability is incomparability, we discuss whether the risks of participating in a trial and the benefits are comparable. We conclude that at least the risks and the benefits to participants are comparable. In the last section we show that the main problem of RBR analyses is that of interpersonal incompensability. IRBs have to assume that risks to research subjects be compensated by benefits to others. The question is: To what extent? When does it become unreasonable to ask that patients accept the risks of participating in a trial for the benefit of science and/or future patients?     

Comparing risk preferences over financial and environmental lotteries

This paper investigates whether preferences over environmental risks are best modeled using probability-weighted utility functions or can be reasonably approximated by expected utility (EU) or subjective EU models as is typically assumed. I elicit risk attitudes in the financial and environmental domains using multiple-price list experiment. I examine how subjects?? behavioral, attitudinal, and demographic characteristics affect their probability weighting functions first for financial risks, then for oil-spill risks. I find that most subjects tend to overweight extreme positive outcomes relative to expected utility in both the environmental and financial domains. Subjects are more likely to overemphasize low probability, extreme environmental outcomes than low probability, extreme financial outcomes, leading subjects to offer more support for mitigating environmental gambles than financial gambles with the same odds and equivalent outcomes. I conclude that EU models are likely to underestimate subjects?? willingness to pay for environmental cleanup programs or policies with uncertain outcomes.     

Research on Environmental Health Interventions: Ethical Problems and Solutions

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.     

The Role of Intuition in Risk/Benefit Decision-Making in Human Subjects Research

One of the key principles of ethical research involving human subjects is that the risks of research to should be acceptable in relation to expected benefits. Institutional review board (IRB) members often rely on intuition to make risk/benefit decisions concerning proposed human studies. Some have objected to using intuition to make these decisions because intuition is unreliable and biased and lacks transparency. In this article, I examine the role of intuition in IRB risk/benefit decision-making and argue that there are practical and philosophical limits to our ability to reduce our reliance on intuition in this process. The fact that IRB risk/benefit decision-making involves intuition need not imply that it is hopelessly subjective or biased, however, since there are strategies that IRBs can employ to improve their decisions, such as using empirical data to estimate the probability of potential harms and benefits, developing classification systems to guide the evaluation of harms and benefits, and engaging in moral reasoning concerning the acceptability of risks.     

When RIP means research in progress--the use of brain dead subjects in medical research

Recent research reported in a number of medical journals highlights some of the problems associated with performing experiments with human subjects who have been declared dead using the brain death criteria of death. These reports provide interesting illustrations of some of the real dilemmas involved in the regulation of human subjects experimentation. In particular, the traditional method of balancing risks and benefits in determining the ethical acceptability of research on human subjects is thrown into question. It is suggested that there should be a moratorium on the use of brain-dead subjects in research until some of the issues can be clarified and appropriate guidelines for the conduct of this research can be prepared.     

Physician duties in the conduct of human subject research

In this article, I examine a skeptical argument against the possibility of ethically justifying risky human subject research (rHSR). That argument asserts that such research is unethical because it holds the possibility of wronging subjects who are harmed and whose consent to participate was less than fully voluntary. I conclude that the skeptical argument is not in the end sufficient to undermine the ethical foundation of rHSR because it fails to take account of the special positive duty researchers owe their clients and future patients. Although the skeptical argument is defeated, it exacts certain novel concessions from the pro-research position. Of particular importance are the admissions (a) that researchers presumptively owe a fiduciary duty to research subjects, (b) that because the most important risks of rHSR are unknown and unquantifiable that duty must be explicitly waived by all subjects before they participate in any protocol, and (c) that such waivers must be made by individuals who satisfy objective criteria of competence for giving fully voluntary consent. The implementation of procedures responsive to these concerns might have a dampening effect on the conduct of research. However, the article concludes with a consideration of the likely benefits to researchers and society of a more cautious ethical regime.     

Scientific evidence and the judicial system

Research involving the vulnerable sick raises difficult challenges for investigators and Institutional Review Boards. Exactly who among the ill counts as vulnerable is a matter of judgement, and involves consideration of susceptibility to harm and capacity to provide free and informed consent. A balanced approach is required when protections are considered, and the benefits as well as the risks of research participation must be carefully weighed. A variety of protections for the vulnerable sick in research are available, including enrolling subjects in a study only with a strong justification, ensuring that consent is free and comprehending, and setting limits on the risk to which they may be asked to endure. Discussion of three contemporary controversies, placebo‐controlled trials in the psychiatric setting, phase I clinical trials and oncology patients, and emergency room research involving patients incapable of giving consent, highlights the little recognized prominence of risk‐benefit issues in the clinical studies in the vulnerable sick.     

Physician duties in the conduct of human subject research

In this article, I examine a skeptical argument against the possibility of ethically justifying risky human subject research (rHSR). That argument asserts that such research is unethical because it holds the possibility of wronging subjects who are harmed and whose consent to participate was less than fully voluntary. I conclude that the skeptical argument is not in the end sufficient to undermine the ethical foundation of rHSR because it fails to take account of the special positive duty researchers owe their clients and future patients. Although the skeptical argument is defeated, it exacts certain novel concessions from the pro‐research position. Of particular importance are the admissions (a) that researchers presumptively owe a fiduciary duty to research subjects, (b) that because the most important risks of rHSR are unknown and unquantifiable that duty must be explicitly waived by all subjects before they participate in any protocol, and (c) that such waivers must be made by individuals who satisfy objective criteria of competence for giving fully voluntary consent. The implementation of procedures responsive to these concerns might have a dampening effect on the conduct of research. However, the article concludes with a consideration of the likely benefits to researchers and society of a more cautious ethical regime.     

The monamine hypothesis,placebos, and problems of theory construction in psychology and psychiatry

Can there be scientific theories in psychology, medicine or psychiatry? I approach this question through an in-depth analysis of a typical experiment for clinical depression involving the monoamine hypothesis, drug action, and placebos. I begin my discussion with a reconstruction of Adolf Grünbaum’s conceptual analysis of what a placebo is. I then use his notion of “intentional placebo” to discuss a typical experiment using the monoamine hypothesis, two drugs, and a placebo. I focus on the theoretical aspects of the experiment, especially on the notion of causal explanation. I then raise five conceptual and methodological problems for theory construction. These problems focus on questions of the causal efficacy of placebos and drugs; ad hoc versus ceteris paribus explanations in biomedicine and psychology; and the falsifiability of the monoamine hypothesis. I conclude by pointing out the need for further, rigorous philosophical analysis concerning the possibility of theory construction in psychology, medicine or psychiatry.     

A review essay: recent literature on cognitive science

Can there be scientific theories in psychology, medicine or psychiatry? I approach this question through an in-depth analysis of a typical experiment for clinical depression involving the monoamine hypothesis, drug action, and placebos. I begin my discussion with a reconstruction of Adolf Grünbaum’s conceptual analysis of what a placebo is. I then use his notion of “intentional placebo” to discuss a typical experiment using the monoamine hypothesis, two drugs, and a placebo. I focus on the theoretical aspects of the experiment, especially on the notion of causal explanation. I then raise five conceptual and methodological problems for theory construction. These problems focus on questions of the causal efficacy of placebos and drugs; ad hoc versus ceteris paribus explanations in biomedicine and psychology; and the falsifiability of the monoamine hypothesis. I conclude by pointing out the need for further, rigorous philosophical analysis concerning the possibility of theory construction in psychology, medicine or psychiatry.     

Who's Minding the Kids? Pollucion,Public Schools,and Environmental Justice in Los Angeles

Objective . Although previous environmental justice research has focused on analysis of the disproportionate burden of environmental hazards on minority residents, few studies have examined demographic inequities in health risks among children. This article evaluates the demographic distribution of potentially hazardous facilities and health risks associated with ambient air toxics exposures among public schoolchildren in the Los Angeles Unified School District. Methods . We combine Geographic Information System analysis with multivariate statistics to compare enrollment and demographic information for students who attend district schools with the spatial pattern of land use, locations of toxic emissions and facilities, and calculated indices of estimated lifetime cancer risk and respiratory hazards associated with exposures to toxic air emissions. Results . District schools are more likely to be located in census tracts containing potentially hazardous facilities; however, these tracts actually have slightly lower cancer and respiratory health risks associated with air toxics when compared to other tracts in the district. Demographic comparisons among school sites indicate that minority students, especially Latinos, are more likely to attend schools near hazardous facilities and face higher health risks associated with outdoor air toxics exposure. Conclusions . These patterns of hazard exposure and health risk should be considered both in the process of siting new schools to house the rapidly growing regional student population and in remediation efforts at existing schools.     

Ethics and research assessing the relative roles of genes and the environment

Research on the interaction of genes and the environment is revealing that many human diseases have both genetic and environmental components. Even traditional "environmental" diseases, such as infections, appear to interact with genetic components in the human host. Environmental genetics research will inevitably increase understanding of individual susceptibilities to toxic exposures in the environment and harmful side effects of medications; therefore, it has great promise for improving the prevention and treatment of human diseases. However, realizing the benefits of this research requires careful attention to ethical issues that are particularly relevant in this context. This article reviews some of the most pressing issues related to research design and methods, as well as from the application of research results (e.g., workplace genetic screening and legal toxic torts, personal medical responsibility, and the relationship between genetics and public health measures).     

Ethics and Research Assessing the Relative Roles of Genes and the Environment*

Research on the interaction of genes and the environment is revealing that many human diseases have both genetic and environmental components. Even traditional “environmental” diseases, such as infections, appear to interact with genetic components in the human host. Environmental genetics research will inevitably increase understanding of individual susceptibilities to toxic exposures in the environment and harmful side effects of medications; therefore, it has great promise for improving the prevention and treatment of human diseases. However, realizing the benefits of this research requires careful attention to ethical issues that are particularly relevant in this context. This article reviews some of the most pressing issues related to research design and methods, as well as from the application of research results (e.g., workplace genetic screening and legal toxic torts, personal medical responsibility, and the relationship between genetics and public health measures).     

Effects of Disease Type and Latency on the Value of Mortality Risk

We evaluate the effects of disease type and latency on willingness to pay (WTP) to reduce environmental risks of chronic, degenerative disease. Using contingent-valuation data collected from approximately 1,200 respondents in Taiwan, we find that WTP declines with latency between exposure to environmental contaminants and manifestation of any resulting disease, at a 1.5 percent annual rate for a 20 year latency period. WTP to reduce the risk of cancer is estimated to be about one-third larger than WTP to reduce risk of a similar chronic, degenerative disease. The value of risk reduction also depends on the affected organ, environmental pathway, or payment mechanism: estimated WTP to reduce the risk of lung disease due to industrial air pollution is twice as large as WTP to reduce the risk of liver disease due to contaminated drinking water.     

Smoker-Nonsmoker Conflict: Using a Social Psychological Framework to Understand aCurrent Social Controversy

Over the past two decades, state and federal restrictions of public smoking have become increasingly common. The resulting controversy has generally focused on the research evidence regarding the physiological effects of second-hand smoke while ignoring relevant psychological aspects of smoker-nonsmoker conflict. In this article I review the literature on the psychological consequences of smoker-nonsmoker interaction, interpreting these results from the framework of social psychological research on inter-group conflict. From this review I conclude that: a) smoker-nonsmoker conflict shares many characteristics of other ingroup-outgroup interactions; b) both groups are served by the legislated separation of these groups; and c) such separation can be successfully accomplished only when close attention is paid to subtle environmental cues. Finally, theoretical benefits of studying smoker-nonsmoker conflict from a social psychological perspective are discussed.     

The Inappropriate Use of Risk-Benefit Analysis in the Risk Assessment of Experimental Trauma-Focused Research

A large body of research has explored the impact of questioning participants about traumatic experiences. To determine the level of risk, these studies have relied, to various degrees, upon a risk-benefit calculus, whereby risks are weighed against the benefits that an individual can receive from participating. In the case of trauma-focused studies this approach is erroneous. The procedures involved in trauma-focused studies do not meet the criteria to be considered therapeutic, and the benefits associated with these procedures do not carry the moral weight to offset risk. Applying the risk-benefit calculus to non-therapeutic procedures inevitably leads to inaccurate risk assessments and ethically problematic claims, examples of which can be found throughout traumatic stress literature. This article outlines how the standard approach to risk assessment in trauma-focused studies is fallacious, and presents an established alternative model that researchers can use to accurately assess the risks of asking participants about their traumatic experiences.     

Chemical Accidents in the United States, 1990–1996

Objective. Much of the empirical work on environmental justice centers on the geographic distribution of potential chronic health risks (e.g., planned toxic releases or treatment storage and disposal facilities). Far less attention has been devoted to the geographic distribution of acute health risks that cause immediate harm. The purpose of this work is to examine environmental justice in terms of potential acute health risks by examining the distribution of serious chemical accidents across diverse subpopulations. Methods. We draw upon 1990 census data for the United States to study the relationship between the racial, ethnic, and economic characteristics of census block groups ( N = 226,398) and the presence or absence of chemical accidents that caused at least one injury, death, or evacuation for the time period of 1990–1996. The data used to map the location of the chemical accidents were obtained from the Environmental Protection Agency's Accidental Release Information Program (ARIP) database. Results. Our results indicate that the acute risk associated with chemical accidents at fixed facilities is greater for individuals living in low–income census block groups, especially when comparisons are made within the counties where the chemical accidents occur. Our results concerning race and ethnicity are less consistent and somewhat weaker. Conclusions. Although these results do not show large and dramatic effects, as have often been found in the study of the social distribution of chronic environmental risk, they do stand as one of a relatively few social analyses of social variation in exposure to acute environmental risk.