National Children's Study Box Lunch Session
International Meeting on Inuit and Native American Child Health
April 29, 2005
Alan Fleischman, MD
James Jarvis, MD (Moderator)
Dr Alan Fleischman is a pediatrician and Acting Chair of the Federal Advisory Committee and Ethics Advisor to the National Children's Study at the National Institute of Child Health and Human Development, NIH. Dr Fleischman began the session by providing an overview of the National Children's Study.
The National Children's Study (NCS) will be the largest and most ambitious study of child health ever to be conducted in the US. It will be a longitudinal study of children, their families, and the environment from preconception through age 21. The study defines "environment" in a broad way to encompass chemical, biological, physical, behavioral, social, and cultural environments. The NCS plans to study a wide range of common environmental exposures and will measure the impact of the environment on children and on the genetic expression of their inherent genetic capacities.
The study has a long and mobile history that originated from a large body of epidemiological work "Framingham Study for Children". The study officially began in 1997, when President Clinton created a Task Force on Environmental Health and Safety Risks to Children. This Task Force was charged with developing strategies to reduce risk of environmental exposures to children. This was a very high-level Task Force, as the co-chairs included the US Secretary of Health and Human Services and the Administrator of the Environmental Protection Agency.� Task Force members included Cabinet officers and senior staff. This group was created because there was awareness that the annual economic burden to society for just a few child health conditions was $800 billion. This figure represents only the economic burden (does not take humanity into account) of just a few conditions.�
By 2000, the Task Force reported that children are especially vulnerable to environmental exposures, which possibly lead to serious developmental effects. They suspected that many conditions had suspected environmental contributions (ie. learning disabilities, autism, diabetes, asthma, behavioral disorders, prematurity); however, the Task Force concluded that the existing research was inadequate. They felt that a large longitudinal study was required to link multiple exposures to multiple outcomes. At first, discussions centered around environmental exposures such as chemicals (eg. pesticides), but experts indicated that there are multiple factors in a child's environment that are even more important. The need to measure all of these factors became evident, as this one would not be able to make clear inferences or associations otherwise.
In 2000, Congress passed the Children's Health Act. This legislation authorized the NICHD to conduct a national longitudinal study on environmental influences in children's health and development. Although the NICHD was identified as the lead agency, a concept central to the study was that it would integrally involve other agencies such as the National Institute of Environmental Health Sciences, the Centers for Disease Control and Prevention, and the Environmental Protection Agency. At this point, a broad-based consortium has been developed, with over 40 government agencies engaged.
There are several challenges inherent to a study of this nature:
� Biostatisticians have told them they need a minimum study cohort of 100,000 children in order to obtain a true probability sample.
o Determining sampling strategy and creating cohort
o Maintaining cohort over a long period of time
� Exposure period begins during conception and goes all the way through the life cycle.
� Genetic expression is affected by the environment and gene-gene interactions.
The NCS plans to utilize state of the art technology in all of their approaches and measurement. This will involve extensive public-private partnerships. They are committed to involving academic scientists and social scientists in this process through a center-based structure. They do not want this to be a federally implemented study, rather they would like this to be a federally funded and planned study. Public-private collaborations have already been established, with over 2,400 individuals (both federal and academic communities) involved in the planning process.� Once a dataset is created, it was also felt that scientists and social scientists could mine the public use datasets to ask and answer research questions over many decades.
It was determined that hypotheses were needed to guide the study. Hypotheses will help ensure that important questions are being asked and that the big questions are being answered. In addition, hypotheses can help to justify some costly elements to the study ? so if there were trade-offs for what was going to be measured, the hypotheses could help to guide the trade-offs that are being made. It was also felt that hypotheses were needed to know that the questions were going to be answerable with a cohort of 100,000 children.��
The NCS has developed a series of hypotheses guides. Dr Fleishman shared an example of hypotheses that have been developed related to asthma.�
� What is the relationship of maternal stress during pregnancy to asthma?
� What is the relationship of early exposure to microbial products and asthma?
� How is asthma incidence and severity influenced by incidence of early life infection and air quality?
There are also priority exposures related to asthma such as:�
� Physical environment (neighborhoods and communities, housing stock, radiation, air pollution)
� Chemical exposure (pesticides, pollution)
� Pharmaceuticals (medicines, vaccines)
� Biologic environment (infectious agents, metabolic issues)
� Genetic environment (gene environment and gene-gene issues)
� Psychosocial and Cultural Environment (social capital, social networks, social support,� communities, racism, psychosocial import to children and families)
Dr Fleischman identified several priority outcomes for the NCS. In general, they will try to gather data to determine what correlates to health and ill-health. In addition, they are committed to the development of an anonymized data set; with public data sets that are made available to the research community as soon as physically and feasibly possible. He stated that although there were other important outcomes, the following were considered the priorities:
� Neurodevelopment and Behavior
� Injury (primarily unintentional)
� Obesity/Physical Development
It is expected that children who take part in the NCS will be born by 2010. Children will be identified through the use of a national probability sample, which will therefore be representative of all children in the US. Use of a probability sample will allow the NCS to make exposure-outcome inferences, and be scientifically more powerful.
The National Center for Health Statistics at the CDC utilized a probability mechanism to select 101 sites, which are counties or clusters of counties. These sites were chosen based on metropolitan and rural status, geography across the country, average number of births/year, race, ethnicity, and percent low birth rate. There are 3 types of sites: large metropolitan areas, modest metropolitan areas, and rural areas. It was noted that at least 20% of the sample will come from rural areas. Dr Fleischman shared a map of the sites, and noted that not all states are represented. This was a chance occurrence, and part of having a random probability sample.
Centers for Excellence will also be integrally involved with conducing research at individual sites. So, sites are geographic areas; whereas centers are entities/institutions who will be conducting the study. Contracts will be established with these Centers to ensure consistency between sites, and that research is conducted in a high quality and rigorous way. Although contracts do not typically allow for much flexibility and collaboration, they are hoping for a collaborative process, where academic leaders can contribute to actual protocols. Each Center will have it's own probability sample; as there will be secondary sampling strategies at each site. Eight potential "Vanguard Centers" have been selected to help operationalize the protocols for the study. These 8 Centers will be chosen to represent a broad geographic distribution across the US.��
"Segments" (or communities) will be created within each site. Although Centers will help to define the segments and provide input, they will not determine the segments, as this too will be done using a probabilistic methodology. Researchers will conduct household enumeration to determine where there are young women in these segments. These young women will be sought out and asked to enroll in the study.
Data collection will begin pre-birth, with several interactions occurring with women. During the first year, they will be gathering data in the delivery room, and during home visits at 1 month, 6 months, and 12 months. Thereafter, they plan to observe children periodically from 18 months of age to young adulthood. Observations will take place during home visits, at child care settings, at schools ? any place that a child spends more than 30 hours/week. Overall, they are hoping to obtain a 20-25% pre-conception cohort; with the rest of cohort being recruited within the 1st trimester of pregnancy, if possible.�
There will be some incentives for families to participate in the study. They believe that families will learn a great deal about themselves and others like them and unlike them. This information will help parents make good choices. Data will be consistently given back to parents to inform them of what is being learned about their children and their environments, and efforts will be made to interpret this data for parents to help them understand what we do and don't know. Families will also receive financial compensation for their time, inconvenience, and expense. Modest gifts of appreciation will also be given.�
A lot of discussion has also taken place whether or intervene if a child or family is at risk for harm. Dr Fleischman reported that they will intervene to help families in positive ways, using community resources. They plan to ask each of the Centers to identify community partners, so that children identified as having a need can be referred. For example, if they determine that someone has no health insurance, they will tell people where more information can be obtained about health insurance; but they will not enroll people.
The study is in process. On November 16, 2004, they announced the RFP's for the Data Coordinating Center as well as for the Vanguard Centers. Many proposals were received, reviews have been completed, and contract negotiations will begin soon. By September 1, 2005, they will announce who has received the contracts. Then final protocol development will begin, so that in 2006, they will have the final protocol ready to roll out for recruitment. Recruitment will begin in 2007. They hope to have all Centers aboard by 2008. In 2010, they will have pregnancy outcome data. They plan to evaluate outcome data periodically throughout the life of the study through the year 2030.
Another RFP is currently being developed for a data repository. This repository will be necessary to save environmental and biological samples. The CDC has agreed to supervise laboratory analysis of biologic samples, and they are committed to revealing clinically relevant data to families in a timely manner. If there is a test with a clinical correlate, this test will be done in real time and test results will be given back quickly. If tests are being conducted for inferential reasons, these results will be given back more periodically. The information systems have tagged all clinically relevant red flags. If data reveal a test result outside of normal ranges, they will be able to quickly notify clinicians near the child to investigate further.
Dr Fleischman noted that Native Americans comprise a substantial but small proportion of our overall population. He showed the audience a slide revealing the distribution of sites relative to Native American populations. One predominately Native American site has been selected (Apache, AZ). This county is 71% Native American. There are also 9 regions, generally in the SW that will participate in the study and give us a proportionate view of Native American children. It was further noted that some Native American people will be represented at urban sites.�
Dr Fleischman noted that the NCS stands prepared to partner with other agencies/organizations to conduct adjunct and special studies with communities across the country. If the NCS is fully funded and has a probability sample of 100,000, there will be a methodology/platform that could be duplicated in other counties/communities; for example, as part of an IHS initiative. The NCS is prepared to share the technology and be the place that coordinates data collection for colleagues in adjunct and special studies.
The NCS is prepared to oversample some special populations as well. For example, the National Bioethics Council asked the President and Congress to study assistive reproductive technologies. They wanted to answer the question, "Does assistive reproductive technology lead to children with more health deficits?" This is unclear in the US, and the NCS is prepared to oversample women who use assistive reproductive technology.�
The total cost of the NCS will be close to $3 billion in today's dollars. The cost may increase due to inflation by completion of the study. While this cost seems large, this translates to about $100 million/year over a 25 year period, and is not that large when comparing to other federal expenditures. Dr Fleischman indicated that they have spent about $20 million in the study's planning phases; and about $69 million will be needed in the next fiscal year to kick off the Vanguard Centers. $150 million will be needed during the year that all of the sites kick off; and about $100 million will be needed in all other years. It was emphasized that those who advocate for children need to understand the power and importance of this study for the future of children.
If this study is successful, they will have answers to many hard questions. They will be able to tell absence of effects as well as effects. They will also look at causal factors that "immunize" toward health of children, and will look at early life factors that contribute to many adult conditions. The will look at health disparities issues; uncovering evidence about causation, social factors, access factors, and other factors within biology. The will attempt to close the health gaps in America's children and among the highest health priorities. If study is successful, they may continue the study into adulthood.���
Dr Fleischman urged everyone to learn more about the study and to become part of the NCS listserv. Regular updates are provided on the listserv. Additional information can be obtained by emailing firstname.lastname@example.org.
Dr Fleischman was very interested in obtaining input/feedback from participants at the International Meeting on Inuit and Native American Child Health. He posed several questions to the audience and invited participants to also ask questions of him:
� What are the most effective ways for the study to involve Native Americans?
� How can we best encourage participation?
� Are there special strategies?
� What incentives are acceptable or appropriate?
� How can we address special issues such as visiting people's home, analyzing placental tissues, looking at genetic and other biologic samples?
Leo Nolan, IHS, Rockville, MD:� Mr Nolan reported that there is a special relationship between the federal government and the 562 tribal nations; and that there are executive orders in place that state that tribal nations MUST be consulted. Mr Nolan indicated that he could share email addresses and other contact information for individuals that they can contact to begin this consultation process. Mr Nolan informed Dr Fleischman that on May 17-18, 2005, the Secretary will be holding a meeting with tribal leaders to discuss the FY 2007 budget at the Great Hall. He suggested that it might be worthwhile to come by and discuss the study. Mr Nolan asked, "Are we involved with the fathers at all in the NCS?"
Dr Fleischman:� Dr Fleischman believed that initial consultations with tribal leaders have occurred. He was pleased to hear that tribal consultation MUST occur. Regarding fathers? participation in the NCS, he stated that they are focusing on the index research participant, which is the women. They will consent for her involvement and the involvement of the child. However, because the vast majority of children are born in families, they will seek consultation and consent of fathers to participate as a subject for the study (ie. questionnaires, biologic samples). They plan to learn about families through 3 major subjects: women, children, and fathers. Dr Fleischman indicated that it was important to obtain the buy-in of fathers, as fathers could stop mothers from participating; however, there is no legal/regulatory obligation that a father must consent.
Dr Fleischman also noted that in 2005, they will spend a substantial amount of effort to create culturally sensitive materials to inform the public about the NCS. Specific information for women will also be created, encouraging them to talk with husbands, mothers, and others to discuss the study. The goal is for people to be informed about the study and fully understand the risks and burdens prior to making a decision to participate. He indicated that the NCS is a minimal risk study with modest burden. Enrollees may opt to withdraw from the NCS at any time.�
Jennie Joe, University of Arizona, Tucson, AZ:� Dr Joe wanted to give a reminder that research is not something that is welcomed in many Native communities. She stated that Native people need to be involved not only at local level, but also at Vanguard Centers and at the clinical coordinating centers. She suggested that Centers should really involve Native people on their advisory committees to help recruit participants and coordinate any interventions that need to take place. In addition, it would be beneficial to involve respected community leaders, particularly when intervention is necessary.
Dr Joe also stated that in most circumstances, utilizing a community's resources works; however, in urban settings and rural communities, resources are very limited. She noted that if IHS facilities or tribal health programs were going to be counted on to help provide follow-up testing, etc, this could put a strain on already stretched resources.� This could prove to be another barrier.�
Finally, Dr Joe expressed her concern about children's health, and her feelings that we don't do enough. She stated that we tend to look at deficits; and a greater emphasis needs to be placed on looking at strengths. She felt that if we provide this kind of message, outlining benefits, there will probably be a lot more mothers that want to participate. She also emphasized that much education needs to take place, so that mothers will understand the longer-term benefits and want to participate.
Dr Fleischman:� Dr Fleischman commented that if there is a reasonable participation rate, there will be about 2,000 Native participants in the NCS. He stated that the RFP for the Vanguard Centers included real dollars for a 1-year lead time between contract and enrollment. This lead time offers the opportunity for the Centers to obtain community involvement and engagement in meaningful ways; such as hiring community members to be part of the research enterprise. The intention of the NCS was to hire people from the communities that will be served. This was made clear in the expectations outlined for the Centers, and Dr Fleischman hopes that would be clear in reality as well. Dr Fleischman also noted that some Centers will have community boards; whereas other Centers will have structures that are fairly sophisticated. He noted that the Federal advisory committee is committed to providing technical assistance; so that each site has a real community engagement strategy.�
Finally, Dr Fleischman noted that funds have been built into the overall cost of the study; so that local sites who conduct laboratory studies, testing, etc should be able to get their costs reimbursed.
Bill Freeman: NW Indian College, past-IHS Research Director:� Dr Freeman offered his perspective and suggestions to the NCS. He stated that much could be learned from the Human Genome Diversity Project; a well-intentioned project to get specimens of Native communities throughout world that were dying - prior to their genes dying out. This went over very negatively with Native people, as taking genes and specimens was a BIG issue. Dr Freeman stated that the NCS is a very important study that can be very important to American Indians. However, he cautioned that not every well-intentioned thing gets accepted.
Dr Freeman also indicated that Native governments don't want to study the genetics of environment (gene/environment interaction) until you've taken care of all of the other things that can be corrected; and that they probably would not be in favor of this kind of study (ie. NCS) that is looking at a broad picture. He felt that we need to demonstrate how the study would benefit the community, and probably Native governments would come on board. He stated that some interventions that benefit the environment and address problems at the time of the study need to be included. He also questioned whether the Navajo Nation can add research questions to the survey that are especially useful to them.�
Finally, Dr Freeman questioned who was going to make sure that specimens from American Indians are not identified as American Indian so that research can go and search for the alcoholism gene? He stated that Native communities need to have a good understanding of who will control specimens and what this control will be like. Dr Freeman believed these things were all doable, but emphasized that these were things that people who are not familiar with working with Native communities need to address.�
Dr Fleischman stated that the Navajo Nation can add questions to the survey. He indicated that every site will have some core questions that NCS wants to gather, but that each sites will be able to add adjunct questions. These adjunct questions will go through a formal review process, because the NCS is concerned about the burden to study participants.��
Dr Fleischman also agreed that anonymization of data, particularly related to race/ethnicity/tribal status is REALLY important. They have begun conversations with some of the world's leading people who do this (de-identifying information, separating out data to maintain confidentiality), and it's a real challenge. Dr Fleischman stated that datasets that have the potential to harm the public or communities, or that cannot be adequately anonymized will not be released to the general public.��
Kristin Lujan, Turtle Mountain Community College, Belcourt, ND: Ms Lujan asked how many of the 101 sites were located on tribal lands. She also was wondering if there is a list of all counties/sites available.
Dr Fleischman:� Dr Fleischman stated that some of the counties have a fair density of American Indians; but there was one county (Apache County, AZ) that has a 70% density. He reiterated that the NCS is prepared to partner with the IHS if they wish to fund something more specific to a tribe/reservation. A list of potential sites and demographic information about the sites is available on the NCS Web site http://nationalchildrensstudy.gov/
Dr Jarvis stated that if there are tribal organizations that are interested in spinning off research from the NCS, he could be the point person, as he is on the Federal Advisory Committee for the NCS.
Don Warne, Family Physician, Arizona State University: Dr Warne stated that close to 60% of all American Indians live off-reservation in urban settings. He questioned whether there was specific outreach planned to the 34 urban Indian clinics, some of which are in the identified counties.�
Dr Fleischman:� Dr Fleischman indicated that there will be outreach to ALL health care facilities in all selected sites. Some of this outreach has already begun, as the commissioner of health, the maternal-child health office, and the Governor's office of the selected sites received information about the NCS. In 2006, the Vanguard Centers will be involved in extensive outreach efforts. They've been given a 6-12 month lead time, as they understand that this will be necessary to inform clinicians, clinics, and the community in it's broad array of community structures; from AI community/ tribal leaders/ health clinics, community churches, senior centers, child care centers, etc. They want the community assets to know about this study; so that if a mother is thinking about becoming part of the study, she will be able to ask someone in the community who is important to her about it.��
Dr Fleischman also indicated that they plan on doing broad-based media and health-based media publicity. He noted that they are beginning to do broad-based media and health-related media interactions; as they get closer to the sites, will be doing much more local, on-the-street work. It is a little early to do more on-the-street work, since the study is still about 18 months out from recruitment.�
Bill Freeman, NW Indian College, past-IHS Research Director:� Dr Freeman clarified that his previous concerns not only related to de-identifying specimens regarding the ethnicity of the individual the specimen was obtained from, but also were related to the genetic markers that were inherent in the specimen. There may be instances where a specimen cannot be completely de-identified and this is a significant issue for American Indians.�
Dr Fleischman:� Dr Fleischman agreed, but stated that there are mechanisms within the process for how you array the data, so you can still use the information in a constructive manner without identifying individuals or communities.
Melanie Nadeau, Turtle Mountain Community College, Belcourt, ND:� Ms Nadeau asked whether participants can withdraw from the study at any time. She also stated that the need for intervention may be defined differently from the Native American perspective and the researcher's perspective (ie. What is considered a need?). Ms Nadeau also stated that one thing that might help individuals to participate would be to identify who will be partners and how they can access resources that are available, instead of waiting until there is a need. Finally, Ms Nadeau stated that home visits may take much longer in Native communities.
Dr Fleishman:� Dr Fleishman stated that they hope to have sensitive research assistants out in community who are working with clear protocols. Therefore, will be no interventions without knowledge or involvement of the family. He believed that there will be instances where the family doesn't wish for intervention, and the study will not intervene unless there risk for immediate harm - that is assessed by a protocol. They very much want to work with families to see if we can optimize their ability to make choices. Each site will need to have resources available so the research assistants can help the families, by saying that "if you have these needs, here's where you might go." Dr Fleischman stated that the NCS is not prepared to solve all of the problems of US children during the study; but they hope the study will be able to impact long-term on those critical needs.