Concerns over risk to pediatric participants lead to study's end
Concerns over risk to pediatric participants lead to study’s end
Review by four IRBs didn’t smooth the path for observational study
A controversial pesticide exposure study involving Florida babies and toddlers has been canceled in the wake of criticism that it targeted lower-income families, offered too much financial compensation, and exposed children to too high a risk of harm.
The Environmental Protection Agency (EPA) defended the Children’s Health Environmental Exposure Research Study (CHEERS) as a means of helping understand how children are exposed to pesticides used in the home.
But acting EPA administrator Stephen Johnson announced the cancellation in April, saying the agency "must conduct quality credible research in an atmosphere absent of gross misrepresentation and controversy."
Johnson’s own career path became a part of the debate. The announcement of the study’s cancellation came only a few days after two U.S. senators, Barbara Boxer (D-CA) and Bill Nelson (D-FL), announced they would halt Johnson’s bid to be named EPA administrator unless the study was canceled.
In defending the CHEERS study, Johnson argued that it had been reviewed by four IRBs to ensure the study was designed in an ethical way.
The EPA first announced the details of the planned study in 2003. The two-year field measurement study would recruit families in the Duval County, FL, area, seeking a total of 60 children from two age groups: infants recruited into the study soon after birth and children recruited at about 12 months old.
The families would be asked about their use of pesticides during the eligibility screening process, and a field technician would inventory all pesticides being stored in the home.
Field staff would visit families accepted into the study five or six times over the two-year period, collecting air samples, surface wipes from various locations in the home, dust samples, and soil. In addition, parents would have to collect a urine sample, usually in a diaper, and put a piece of clothing on the child that would be examined later for traces of chemicals used in the home.
Parents also would have to provide duplicates of food eaten by the child over a 24-hour period, keep a diary of the child’s activities during a five-day period, have the child wear an activity monitor for the five-day period, videotape their child, and keep monthly logs of pesticide use and cleaning habits.
Participating families would receive payments as part of each visit, with families who participating throughout the two-year period receiving up to a total of $970. They also would be able to keep the video cameras provided for monitoring.
Compensation, education questioned
When the details of the study became public, several criticisms were raised about the study’s design, including:
• Study population — Critics charged that the families being recruited were predominately lower income. EPA officials stated that CHEERS advertising was being conducted throughout the county, including in private pediatricians’ offices, magnet schools, and private schools.
Peter Preuss, PhD, director of the EPA’s National Center for Environmental Assessment, says the goal was to recruit a representative group from people living in the area. "But it is a low-income area," he adds.
• High payments — The EPA defended the $970 payment to families, noting that they were being asked to perform very labor-intensive tasks as part of their participation.
But others, including an EPA toxicologist who had raised concerns about the study, say that even if the compensation was appropriate for the tasks required, it still was too high an inducement for lower-income families.
"You’re offering them a job in their own home — an appropriately paid one," argues Suzanne Wuerthele, PhD, EPA’s regional toxicologist in Denver. "Even though it was an appropriate amount of money, it was an amount of money they wouldn’t normally get."
She also objected to the offer of a video camera for parents who might not otherwise be able to afford one.
• Pesticides education — Wuerthele says she was very concerned that participants in the study wouldn’t get enough information about preventing their children from pesticide exposure.
The EPA fact sheet for the study states that a member of the research team would inventory any pesticides in a home, explain the importance of following label directions, and be sure participants were only using pesticides that were registered for use indoors. If participating children were found to have elevated exposures based on their urine samples, the EPA immediately would step in to investigate the cause and correct the problem.
But Wuerthele says the agency has an obligation to go further — to explain to participants that pesticides are neurotoxicants, and that they should minimize their children’s exposure to them.
"Literally, there’s no risk to be in the study, but there’s a whole lot of risk if you use pesticides around your baby," she says.
• Study funding — News reports stated that about $2 million of the $9 million cost of the study was to be provided by the American Chemical Council, raising criticism from environmental groups.
The design of the study does raise ethical issues, says Harold Y. Vanderpool, PhD, ThM, a professor of history and philosophy of medicine at the Institute for the Medical Humanities at the University of Texas Medical Branch in Galveston.
Vanderpool, who reviewed the CHEERS study design published on the EPA web site, says that because participation in the study wouldn’t increase the risk to the children involved, it wouldn’t fall under the federal guidelines regarding research involving children. But he says that researchers also are bound to look to general ethical principles, including the principle of a "duty to warn" a person of risk of harm.
"In this case, what you have is research going on with babies and toddlers that could very likely indicate that some of the pesticides used around them are anything from neurologically damaging to growth limiting, maybe even affects their brightness mentally — who knows what all these effects of pesticides might be?"
R. Alta Charo, BA, JD, professor of law and bioethics at the University of Wisconsin Law School in Madison, compares the situation to a study that looks at people at risk for HIV. Those participants must be warned about the necessity of using condoms, even if they choose not to use them.
"I think you want to be very sure you want to explain to people in the course of enrollment, that there are these concerns about exposure to pesticides among children," she says. "We don’t have all the answers — that’s why we’re doing the study. Certainly many people think that it’s better to simply avoid exposure for the children if at all possible. [Participants] would be encouraged to do exactly that."
Vanderpool says there’s nothing the study design that indicates that the EPA would intervene if children were shown to be harmed by their exposure to pesticides — specifically, removing them from the study. In fact, he says, the structure of the payments provides a strong incentive to continue.
"They have a two-year protocol that has increasingly large payments, designed to do what? Designed to keep them in the study for two years," Vanderpool says. "One could say that any observational study that observes that the subjects are being harmed should certainly have the duty to warn, and the duty to cease the study and begin educating."
Charo says the issue of monetary compensation for research subjects is always tricky.
"We understand that the nature of the incentives should be such that it does not cause people to abandon their own good judgment," she says. "So you’re walking a fine line between attracting people without making the offer so overwhelmingly tempting that a person of ordinary character would be unable to resist the temptation."
Vanderpool says the study design posted by the EPA doesn’t contain information about existing animal and human studies that would justify or mitigate the need for this particular study.
"Were I serving on the IRB that looked at this protocol, I would say, We defer this until the researchers come back and talk about the validity of this research, which freezes in place the lifestyle of these kids for two years and does it with the clincher of increasingly large payments to their families to keep them in the protocol,’" he says. "Does the scientific validity outweigh that? And I suspect it would not, but I don’t know."
Vanderpool says if his IRB had decided to allow such a study to go forward, he would have wanted a much smaller monetary compensation for participants.
EPA contracts with IRBs
Preuss, who is the EPA’s human subjects research official, says the agency doesn’t have an IRB of its own, but contracts with IRBs to review human research conducted by the agency or using agency grant money. All studies also must be approved by him. Four IRBs reviewed the CHEERS study:
— Battelle Memorial Institute, a Columbus, OH-based private company that was the contractor for the study;
— the University of North Carolina, which has a standing relationship with the EPA’s Human Studies Division, located on its campus;
— two IRBs at the Florida Department of Health and the University of Florida, because of the location of the study.
Battelle officials declined comment for this article, referring questions to the EPA.
UNC’s director of the Office of Research Ethics, Daniel Nelson, MS, says his board did not review the entire CHEERS study, but only a neurodevelopmental questionnaire that was to be used with parents in the study.
Jeff Goldhagen, MD, director of the Duval County Health Department, says approval had been received from the University of Florida IRB and was pending from the state Department of Health IRB when his agency decided to terminate its involvement in the study, based on the information that it was funded in part by industry.
Preuss says he sees no reason to change the current system of relying on outside IRBs for reviews of EPA human studies. "I think we are very comfortable with the work that the IRBs do — I don’t see any change in that at all."
The controversy over the CHEERS study played out against the backdrop of another debate over how to deal with so-called third-party studies conducted by outside entities, often chemical manufacturers seeking to loosen EPA restrictions on their products by offering new research that shows lesser risk.
Preuss says the EPA is currently developing a policy that could subject such studies to closer scrutiny, including ensuring that the research has complied with the Common Rule.
Charo, who was the review coordinator of a National Academy of Sciences (NAS) report on the use of pesticides in research, says she believes the third-party debate has helped drive the controversy over the CHEERS study.
She says many opposing the use of third-party data were suspicious of the motives of the manufacturers, and skeptical of their claims that the research could benefit public health.
"In the NAS report, you’ll see that committee struggling with this and finally concluding that there may very well be situations in which the public health and protection of the environment really is enhanced by a more accurate and nuanced appreciation of the way in which pesticide residues remain and the effects they have on people," Charo explains. "And on that basis, they came to the conclusion that this is research that should be done, where it is justified and properly controlled.
"I do think it is this underlying hostility that is part of why people are reacting as strongly as they are to [the CHEERS study], the most benign kind of study that is done on humans, which is a naturalist observational experiment."
Asked if he would have been comfortable had the EPA gone ahead with the CHEERS study in its original design, Preuss hesitates. "I think that’s really hard to answer with a yes’ or no,’" he replies. "Given the issues that have been raised, we might try to see now if there would be a different study design that would allow us to accomplish the same thing."
He points to the issues of compensation and selection of participants as areas where he might seek changes to the design.
Preuss says the debate served to sensitize the agency to some of the ethical issues surrounding such studies, despite his belief that much of the controversy was based on incorrect information.
He also contends the issues raised in the CHEERS study are useful for IRBs to contemplate.
"They also need to be sensitive about these kinds of public concerns, even without arguing whether they’re correct or not," Preuss says. "The fact that there are these kinds of concerns is important for IRBs to be aware of, so they can look over these kinds of studies with an eye toward these kinds of issues."
A controversial pesticide exposure study involving Florida babies and toddlers has been canceled in the wake of criticism that it targeted lower-income families, offered too much financial compensation, and exposed children to too high a risk of harm.Subscribe Now for Access
You have reached your article limit for the month. We hope you found our articles both enjoyable and insightful. For information on new subscriptions, product trials, alternative billing arrangements or group and site discounts please call 800-688-2421. We look forward to having you as a long-term member of the Relias Media community.