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08/25/2016

Do the EPA Exposure Studies Violate Do No Harm and Informed Consent?

by Craig Klugman, Ph.D

A government agency recruits elderly and sick patients for an important research study. In a controlled environment, subjects are exposed to airborne pollutants at levels many times higher than found in the real world. Some pollutants are considered so dangerous that the FDA considers any exposure to be dangerous.

Such a scenario may sound like a historical case study of human subjects abuse, but such studies are actually the subject of an 18-month review by the EPA on ethical conduct of research. Such studies are not a secret. In fact, a 2000 article in the journal Environmental Health Perspectives talks about the benefit of exposing people to pollutants at controlled doses in controlled environments. The last meeting of the review committee was August 24, 2016.

Subjects are consented to participate in the experiments, but the EPA’s own inspector general has questioned whether potential subjects truly understood the risks and whether researchers immediately and properly reported all adverse events. Specifically, the inspector general refers to a study of 81 subjects, exposing them to airborne particles and diesel exhaust fumes in 2010 and 2011. The concerns range from lack of review board approval and notification of study modifications, to addressing risks differently to different subjects in the same study, to a lack of procedures for reporting and acting on adverse events.

The public health benefits of this research are important for answering how much exposure is safe as well as what are the effects of exposure at various levels to a diverse pool of people (based on age, ethnicity, health status). The results can help guide regulations and policies that affect us all. When one considers solidarity—minimizing morbidity and mortality of a community—then these studies seem justified. But from the perspective of do no harm, and respecting human life, the answer is not so clear. Consider the concerns that have been place on such historical experiments as Tuskegee, Nazi wartime experiments, and the US radiation experiments, one wonders whether a government should ever expose vulnerable populations to such potential harms.

In 2009, David Resnik published in Accountability in Research that the public health benefits of these studies outweighed the risks if 5 conditions were met: “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 the those encountered in a typical Phase I drug study.”

Steve Milloy of JunkScience.com and a Senior Legal Fellow at the Energy & Environmental Legal Institute testified before the EPA committee. He shows that the EPA violated its own exposure safety rules by subjecting vulnerable people to pollutants at levels it already considered dangerous. I am not an environmental scientist so cannot attest to the accuracy of his presentation (you can see his slides here). However, if there is any truth to what he is saying, then the studies are concerning. One of the criticisms of Tuskegee was that the study replicated research that had already been done in Sweden, thus unnecessarily exposing subjects to risk. It is possible that the same claim could be made about the EPA studies. Referring to Resnik’s 5 criteria, is it possible to minimize a risk when any exposure is dangerous?

Criteria 4, that the subject must “receive some benefits, such as medical evaluations” seems like a very light standard. If the medical evaluation were part of the study and data was being used for the study, would it be a benefit? I have always viewed a benefit as something that is aimed to help the subject, not the research. In the IRBs in which I have been involved, this is why receiving a study drug is not considered a benefit because it’s not intended to benefit the subject (but to gather data).

Criteria 5 is also concerning. Phase 1 trials are usually done with a small number of sick patients suffering from a disease who have often exhausted all approved treatment options. In the EPA studies, no potential therapy was being tested. Exposure to the pollutants were not intended to make people better and were given to see how much sicker they would get. Thus, this criterion is problematic because the analogy between a clinical trial and environmental exposure does not hold. And in a clinical trial there is a remote possibility (even if unintended) that a person might be helped whereas an exposure trial holds no such hope. An asthmatic or COPD patient has no potential benefit from exposure only risk.

In a 2014 comment on EPA’s stricter guidelines for research with vulnerable subjects, Resnik criticizes the EPA for not being in line with the looser Common Rule standards. He states that since vulnerable populations are exposed to these environmental pollutants anyway, that it’s acceptable to conduct research on them. However, this does not address why the EPA would condone studies that (a) violate it’s own rules and (b) that the exposure during testing is higher and more concentrated than that experienced in the real world leading one to question whether such tests even have real world validity. If this last point were true, then these studies are an unnecessary exposure to harm.

On the side of permitting these studies, Stanley Young, a statistician has found that the existing study data does not support the idea that exposure to some of these pollutants increases the risk of mortality. His ideas are not without controversy as he generally is against EPA regulations and has stated that there are benefits to rising CO2 levels in the atmosphere.

What were subjects told? The inspector general’s report says that subjects were not told when new findings may have changed the risk-benefit ratio and that different subjects in the same study were given different information on the risks. Such an inconsistent process is a violation of informed consent as a continuing process.

The results of the current committee hearings will hopefully lend insight into the science of these sorts of studies. Since good ethics begins with good facts, that will enable a better ethical analysis of the studies. As they have been described, however, these studies are concerning since they echo back to some classic cases of human research subject abuse. Most of the classic cases find fault with a lack of informed consent for potential subjects and a lack of voluntariness. The former concern is also found in this EPA case.

Beyond the irregular administrative and paperwork questions raised in the EPA studies, there is a larger issue of whether a subject should ever be placed in the situation to be part of a study that can only make her or his health worse? Are there studies where a person should not be permitted to volunteer because the risks are too high? Are there simply some studies that should never be done on human beings, even if that knowledge is valuable?

Answering these questions and analyzing this case must be done carefully and with a scholarly rigor. Already, information outlets are calling this a failure of government and have labeled the experiments as “evil.” Any similar experiments should be put on hold while the investigation continues to figure out what went wrong and what can be done to correct this in the future. But placing sensationalizing labels might draw eyes to websites but won’t do anything to protect human subjects or improve the system of ethical review.

 

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