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Big: National Children's Study faces full-grown questions, ethical issues
"When does it ratchet up to something more complicated?"
In planning the recently launched National Children's Study (NCS), researchers knew that ethical and IRB issues would be front and center. The federally funded observational cohort study will follow more than 100,000 U.S. children from the womb to age 21, looking at the effects of environment, genetics and other factors on childhood diseases and conditions that include childhood obesity, diabetes, autism, asthma and mental health problems.
While the study has been deemed to be minimal risk, it still raises a number of ethical issues, including collection of biospecimens and use of genetic information, confidentiality and the distribution of results to participants and their communities.
John Santelli, MPH, MD, an adolescent medicine specialist at Columbia University in New York City, served on the NCS ethics working group during the planning stages of the study in the early 2000s.
"We looked at a broad range of issues – genetics testing, stored samples, when do you consent, when do you reconsent, how do you deal with community involvement in a multisite study?" Santelli says. "Is this study really minimal risk? None of the individual procedures are particularly dangerous, but we had a lot of minimal risk data collection going on – when does it ratchet up to something more complicated?"
The scope of the project – subjects will be recruited at 105 study centers across the United States, and many study centers have multiple institutions involved – only added to the challenge of coordinating IRB approval.
Study director Peter C. Scheidt, MD, MPH, says planners determined early on they would be unable to use a centralized IRB for this project, although the IRB for the National Institute of Child Health and Human Development is serving as the IRB of reference.
"We met with various study center IRBs' representatives, had several planning meetings and came to the conclusion that IRBs would not likely completely defer to a central IRB, so we would have to address that on a local level," he says.
But he says the project has gone more smoothly than he at first had feared. So far, nearly all the IRBs have classified the study as minimal risk and no study center has had problems with IRB approvals.
Scheidt says that with this type of long-term study, not every potential ethical issue can be resolved ahead of time – it's not yet possible to know what all those issues will be.
"The way we decided to address bioethical issues in general is to create mechanisms to deal with them as they come along," he says. "We understand that this is a moving target. Take the genetics issue: What is both available and viewed as genetic information today will be changing rapidly over the next two to five years.
"We need the ability to constantly reevaluate these issues and to respond to the specific problems that occur as a result of it as the study goes forward."
Stages of consent
The longitudinal nature of the study creates challenges for giving continuing, useful informed consent. Although pregnant women are initially recruited, their children will be asked to give assent when they are 7 years old, and consent when they reach adolescence, Scheidt says.
During that time, the mother and child will participate in periodic interviews, and will be asked to give blood and other biospecimens. Researchers also will take environmental samples from participants' homes.
As a result, says Julia Slutsman, a bioethicist with the study's program office, the informed consent process has multiple phases and documents.
"The informed consent process starts with a series of advance letters and materials to potential participants explaining the study for them and what ramifications of participation might mean for them and for their children," Slutsman says. "When women first come in contact with study staff in the field, they receive a general consent booklet that explains in plain, very accessible language the research procedures, the purpose of the study and the risks to participants.
"There's a separate informed consent form for the collection of environmental specimens and for biological samples," she says. "And it's very clear that they can choose to participate in certain elements of the study but not in others."
Slutsman says one unique feature of the informed consent process is a series of documents called visit information sheets, which are given to participants at every interaction they have with a representative of the study.
"There is a description of the particular research procedure that is to be done in that visit and they can then indicate whether they choose to participate in those procedures or not – they can refuse any aspect," she says. "So the informed consent process is designed to be tailored to the participants in the study and to give numerous opportunities to explain the procedures and to allow participants to choose not to participate in particular pieces."
Handling, distributing information
Among the major ethical issues that have arisen during the development of the study is the question of when and if to return individual information to participants, Scheidt says.
"We're collecting a great deal of information and just determining what's appropriate and especially what's inappropriate to share has been a big issue," he says.
As an example, he points to one analysis, which will look whether certain environmental exposures trigger expression of autism in children. Based on statistics, Scheidt says the study expects to find about 600 of its participants are eventually diagnosed with autism.
Specimens may be taken from a baby and its home and then not analyzed until years later, when the child is diagnosed.
Decisions about when to reveal information will be made by an Independent Study Monitoring and Oversight Committee, which functions as the study's data and safety monitoring board.
"Its primary responsibility is to advise the study on what information should be revealed to participants and to communities," Scheidt says. "It's an independent committee, comprised of experts and scientists, bioethicists and community representatives."
Another mechanism in use in the NCS is a Data Access and Confidentiality Committee, which handles questions regarding what data can and should be released to study investigators, in public data sets and to other entities.
A Sample Oversight Group looks at all proposals that involve the use of biological specimens and environmental samples to ensure they are being used appropriately.
In addition to community representation on committees and on the overall study advisory board, a local community advisory board will be set up at every study center.
Scheidt says engaging the communities involved in the study is vital to its success.
"Awareness and a positive view of the study are going to be absolutely essential to enrollment and retention," he says. "So we're approaching this as not only a national study, but very much a study in 105 communities."