April 2002 Study Assembly Meeting Summary Minutes

April 9, 2002
Sheraton Premiere Tysons Corner
Vienna, VA

This meeting was held in conjunction with the National Children’s Study, which is led by a consortium of federal agency partners: the U.S. Department of Health and Human Services (including the National Institute of Child Health and Human Development [NICHD] and the National Institute of Environmental Health Sciences [NIEHS] , two parts of the National Institutes of Health , and the Centers for Disease Control and Prevention [CDC] ) and the  U.S. Environmental Protection Agency (EPA) .

Welcome and Introduction

Peter Scheidt, M.D., M.P.H., director of the National Children’s Study Program Office at the NICHD and co-chair of the Study’s Interagency Coordinating Committee (ICC), welcomed participants to the plenary session for the Study Assembly. Dr. Scheidt noted that a major milestone in the Study was achieved during the 3-day Study Assembly meeting, when the federally chartered Advisory Committee (NCSAC) met for the first time. He welcomed the NCSAC and its chair, Donald Mattison, M.D., to the Study Assembly.

Overview of Progress

ICC member Carole Kimmel, Ph.D., of the EPA, presented a brief history of the planning phase of the Study and an overview of progress to date.

Beginnings of the Planning Phase

Dr. Kimmel explained that the idea for the Study was generated by the President’s Task Force on Environmental Health Risks and Safety Risks to Children, which was established in 1997. Planning for the Study began in late 1999. The first event was a consultation meeting held in January 2000, where the directors of 10 major cohort studies discussed lessons learned and the feasibility of conducting a large longitudinal study. The key message from this first event was to move forward and be bold in planning the Study. In October 2000, Congress passed the Children’s Health Act of 2000, which called for a large-scale, national longitudinal study on children’s health and charged the director of the NICHD with directing the study, in concert with other federal agencies, such as EPA and the CDC.

A second consultation was held in December 2000 to gather input from 300 stakeholders. At this event, participants provided direction and feedback on Study design, hypotheses, ethics, community participation, and various aspects of information technology.

The Children’s Health Act of 2000 called for the Study to be conducted as an open, public process involving organizations and individuals from both the private sector and federal agencies. To meet this charge, the Study began to establish Working Groups that included both federal and non-federal experts. Dr. Kimmel added that the Study currently was supported by 22 Working Groups, with more than 275 members representing 62 universities, agencies, and organizations.

In 2001, the Study launched a Web site and listserv. The Study also established a Federal Consortium, which included representatives from 7 agencies within the DHHS, 5 other Departments, and 20 NIH Institutes or Centers, to provide input on a policy level to the NICHD Director. The charter for the NCSAC was granted to NIH in 2001.

The planning phase has involved giving informational presentations to and soliciting feedback from scientific and professional societies, industry groups, children’s health groups, and other organizations.

Study Organizational Structure

Dr. Kimmel provided an overview of the organizational structure (see Figure 1) for the planning phase of the Study and described certain components in more detail.

• Study Assembly. The Study Assembly is the community of individuals interested in the Study, including the Working Group members. Meetings of the Study Assembly are open to all interested parties. They provide an overview of the Study planning process, updates on the Working Group efforts, and an opportunity for feedback from the Study Assembly members and the public. The first such meeting was held on October 16, 2001.
  
  
• Working Groups. The Working Groups provide input in the form of findings to the NCSAC. The Working Groups include federal and non-federal co-chairs, approximately 15 to 20 core members, and at-large members who can serve as expert consultants or reviewers.
  
  The Working Groups include Cross-Cutting/Integrative Working Groups that address overarching issues, such as Study design, ethics, information technology, repositories, community outreach, and communications. A recruitment and retention Working Group is also being planned. There are also Focused Working Groups that address the following types of topics:
  
  
  • Endpoint-specific —for example, asthma; birth defects; immunity, infections, and vaccines; injuries; development and behavior; nutrition; and growth and pubertal development
    
    
  • Exposure-related —for example, exposures to chemical agents; physical exposures; medicine and pharmaceuticals; and gene-environment interactions
    
    
  • Life-stage specific —for example, fertility and early pregnancy; pregnancy and the infant; and the early origins of adult health
    
    
  • Social issues —for example, health disparities and environmental justice; health services; and social environment.

Dr. Kimmel added that each Working Group was developing its charge, timeline, and expected outcomes. Final Working Group reports would be available on the Study Web site following NCSAC review; interim reports would be available online following public meetings.

• NCSAC. The NCSAC makes recommendations to the ICC and the NICHD Director. The NCSAC is chartered under the Federal Advisory Committee Act (FACA) to review and advise the NICHD Director regarding the design and conduct of the Study. It also enables the Study Working Groups to function by receiving and reviewing their reports. Another important role of the NCSAC is to ensure that the science conducted under the Study is of high quality and that the recommendations to the federal government are fair and unbiased.
  
  
• ICC. The ICC and NICHD Director are responsible for final decisions about the Study. The ICC consists of representatives from the lead federal agencies involved in the Study. The committee serves several functions in the planning of the Study. It works with the Program Office to oversee and carry out the planning process, acts as liaisons to the Working Groups, and organizes methods development and pilot study activities to prepare for the actual Study.
  
  
• Federal Consortium. The Federal Consortium is chaired by the NICHD Director and gives input at a policy level.
  
  
• Program Office. A Program Office housed at the NICHD provides oversight and administrative support for the Study; this office works closely with the ICC.

Dr. Kimmel outlined strategies for facilitating interaction among Working Groups, the ICC, and the NCSAC. Web-based portal technology was being used to provide e-rooms for Working Groups, as well as common areas to allow interaction and information sharing among Working Group chairs and ICC members. In addition, each Working Group had an ICC liaison to help coordinate activities.

Dr. Kimmel also described the considerations that informed the design of the Study logo and tag line. She noted that the logo was designed to be recognizable and relevant throughout the life of the Study. The current tagline of "Health, Growth, Environment" can change over time to evolve with the Study.

Accomplishments

Dr. Kimmel reported on the following accomplishments, completed as of the meeting date:

• Nearly all of the Study’s Working Groups had been formed.
• Two meetings of the Study Assembly had been convened.
• The Federal Consortium had been established and was beginning to function as a group.
• The NCSAC had been chartered and had met for the first time.
• Strategic planning was ongoing and included the development of guidelines for participation and publication, discussion of ethical issues, the development of plans for community outreach and participation, and consideration of ways to improve public-private partnerships.
• Several methods development and pilot studies were underway:
  • Systematic review of core and potential hypotheses
  • Review and comparative analysis of sampling strategies for participants in the Study
  • Low-cost, low-burden exposure monitoring strategies that can be used in a large study
  • Systematic evaluation of personal exposure measures
  • Temporal exposure variability and efficient exposure measurement design
  • Subject recruitment and retention methods
  • Development of a database of biomarkers for chemical exposures and outcomes
  • Collection and storage methods for genetic testing
  • Review of emerging technologies applicable to the Study.
  
  Other studies would be proposed by Working Groups and implemented over the next two years.

General Progress and Future Direction

Woodie Kessel, M.D., M.P.H., Senior Child Health Science Advisor to the Office of the Secretary, DHHS, co-director of the President’s Task Force on Environmental Health Risks and Safety Risks to Children, and ICC member, began by noting a concept he learned from a tribe in Africa. He stated that the Masai had a greeting, Kasserian Ingera, which meant, "How are the children?" He explained that this concept emphasized the importance of children in society and implied that it was everyone’s job to help children stay well. He added that this greeting summarized the reason behind the investment of human, capital, and intellectual resources in the Study. Dr. Kessel reported that DHHS Secretary Tommy Thompson and EPA Administrator Christine Whitman had indicated their commitment to this study and believed that good science was necessary for good public policy.

Dr. Kessel related facts and observations from several archival publications on health, including a study on infant mortality prepared by the Children’s Bureau in 1909 and America’s Children—Key National Indicators of Well-Being, published 100 years later, to provide an historical context for the Study. Concerns about environmental effects on children’s health were evident in these documents.

Dr. Kessel remarked that the Study would focus on expanding scientific knowledge so that critical health issues could be addressed with common sense. He noted challenges that should be considered during the process of prioritizing issues, including determining significance, explaining that most researchers focused on statistical significance, but the real goal was to determine whether the issue was important. Another consideration was to make choices based on dimensions such as caring, feelings, or justice.

Dr. Kessel concluded by stating that, in answer to the question of Kasserian Ingera, it was important to consider how to employ and collect the kind of "common sense science" that provided the evidence for what mattered and what made a difference. He added that the Study was about generating the science to enhance the common good, and that the participation of so many people in this study was a testimony to how people were taking up that challenge.

Overview of Working Groups’ Progress

Mathew Longnecker, M.D., Sc.D., and Adolfo Correa. M.D., M.P.H., members of the ICC, presented an overview of progress made by the Study Working Groups since the previous Assembly meeting in October 2001. They noted that final summary reports by the Working Groups would be submitted to the Program Office by April 15.

Selected Working Group Accomplishments

Dr. Longnecker, from NIEHS, reviewed the charges of the Working Groups: identifying priority hypotheses, pilot studies, and design issues; considering ways to interact with other Working Groups; and developing an action plan and timeline. He then summarized the activities of the six overarching Working Groups, noting that the Recruitment and Retention Working Group had not yet been formed:

• The Ethics Working Group had submitted a white paper on human subjects considerations and was close to organizing a workshop to convene investigators who had recent experience with children’s epidemiological studies.
• The Community Outreach and Communications Working Group had submitted one hypothesis.
• The Information Technology Working Group had submitted a questionnaire for other Working Groups to complete.
• The Study Design Working Group was finalizing screening and evaluation criteria to be applied to initial core hypotheses submitted by other Working Groups. It had also requested that three white papers be produced to help its members evaluate core hypotheses and make findings about the most appropriate Study design.

Dr. Longnecker reported the accomplishments of 16 topic-specific Working Groups, noting that the Physical Exposures Working Group had not yet been formed:

• The Early Origins of Adult Health Working Group had submitted eight initial hypotheses and was finalizing three others.
• The Exposures to Chemical Agents Working Group had submitted four initial hypotheses.
• The Fertility and Early Pregnancy Working Group had submitted four initial hypotheses and requested four pilot studies.
• The Gene-Environment Interactions Working Group had submitted three initial hypotheses.
• The Injury Working Group submitted five initial hypotheses and was finalizing another.
• The Social Environment Working Group submitted one position paper and proposals for three reviews and one workshop.

Dr. Longnecker explained that the Working Groups were formed at different times, which affected the groups’ ability to produce hypotheses and studies. He also indicated that it was difficult to determine what counted as hypotheses (for example, broad hypotheses could be disassembled into multiple, more specific hypotheses) and what could be categorized as "final" (that is, would be submitted within the next few weeks). Dr. Longnecker acknowledged that the brief summary could not do justice to the amount of work that had been done by the Working Groups.

Recurrent Themes in Working Group Discussions

Dr. Correa, from the CDC, presented some of the overlapping, recurrent themes gleaned from the Working Group discussions held on April 7, as well as selected findings and observations from various Working Groups.

• Ethical Issues: Several Working Groups indicated concerns about risks and benefits for Study participants, incentives for recruitment and retention, questions about informed consent and confidentiality, and the responsibility of investigators for remediation or treatment, as well as for informing subjects about the Study findings. Dr. Correa noted that the Ethics Working Group was addressing these issues and was planning a workshop to identify approaches that other investigators used to address Institutional Review Board (IRB) issues.
  
  
• Recruitment Issues: Groups expressed concerns such as how to engage communities, who should be enrolled (for example, parents only or parents and their siblings), and when participants should be recruited into the Study (for example, before or during pregnancy). Several Working Groups also cited considerations that would affect the current timeline for conducting the Study. For example, the Community Outreach and Communications Working Group commented that the considerable investment necessary to establish credibility and involve communities in the Study would take a long time to build from scratch-building on relationships already present in communities would be important. The Study Design Working Group inquired how it could evaluate detailed proposals on potential core hypotheses, which had not yet been requested, in time to present findings to NCSAC by the June 2002 meeting. Dr. Correa suggested that building additional components into the timeline would be necessary to address these concerns.
  
  
• Exposure Assessment Issues: Several Working Groups cited the unique opportunity that the Study offered to measure exposures of concern during critical periods of vulnerability. Of particular interest were transient exposures for which there may be few records. Working Groups advocated the development of a framework for exposure assessment that took into account the developmental timeframe, chemical class, and media involved. Dr. Correa reported that the Exposures to Chemical Agents Working Group had established such a framework for exposure assessment, identified data gaps for the framework, and identified pilot studies that would address these gaps. The Working Group also planned to develop an inventory of exposure assessment strategies used for longitudinal studies, a catalog of questionnaires for exposure assessment and an evaluation of their effectiveness, and a framework for air pollutants and multi-media pollutants.
  
  
• Quality Assurance and Control: Key issues included the quality assurance and control procedures that would be needed for questionnaire data collection and management; data from clinical evaluations; and specimen collection, storage, retrieval, and processing. One example of the need for quality control was indicated by Working Groups focused on specific outcomes (for example, asthma or birth defects), which identified the need to standardize methods for outcome ascertainment and definition.

The Gene-Environment Interactions Working Group developed a summary document that described the design and analyses considerations for hypotheses related to gene-gene interactions, gene-environment interactions, and exposure-exposure interactions, as well as for IRB issues that were specific to the evaluation of genetic factors and the onset of disease. The Working Group also pointed out the expertise methodology, technology (sample collection, processing), and analysis that were available among its members. Dr. Correa suggested that this document be shared with other Working Groups.

In addition, the Information Technology Forum identified the following topics for the development of standards:

• Data standards
• Automated data collection
• Use of geographic information system (GIS) data
• Storage of images or other large data sets
• Use of wireless technology and personal data systems
• Secure data transmission and access.

Selected Working Group Findings

Dr. Correa summarized some of the findings and observations that emerged from Working Group discussions.

• The Health Disparities and Environmental Justice Working Group noted the need for more diversity within the Study Working Groups and the NCSAC. Dr. Correa advised the Study Assembly that the ICC had been concerned about this issue and had made many attempts to ensure diverse representation on Working Groups and the NCSAC. He welcomed any suggestions the participants could give on how to enhance diversity.
  
  
• The Fertility and Early Pregnancy Working Group began negotiations with a journal to arrange publication of its white papers. This arrangement was held up as an example of how other Working Groups could benefit from the effort put into developing white papers.
  
  
• The Repository Working Group developed a hypothetical paradigm about the type of specimens to be collected and frequency of collection so that costs could be appreciated. Dr. Correa noted that early indications suggested that such calculations may be very informative at this stage. The group also had developed a hypothetical flow chart on how specimens might be processed and analyzed.
  
  
• The Study Design Working Group was preparing feedback on the initial core hypotheses proposed by other Working Groups. It was also preparing guidelines that would help other Working Groups submit more detailed descriptions of their proposed core hypotheses. Dr. Correa noted that the NCSAC had also has identified information that it would like to see on hypothesis proposals. Consequently, some coordination between the Study Design Working Group and NCSAC may be helpful in defining the information that Working Groups should submit about their proposed hypotheses.
  
  
• Several Working Groups would be developing joint hypotheses. Among these groups are:
  • Asthma Working Group with the Gene-Environment Interactions Working Group
  • Asthma Working Group with the Chemical Exposures Working Group
  • Birth Defects Working Group with the Chemical Exposures Working Group
  • Nutrition, Growth, and Puberty Working Group with the Early Origins of Adult Health Working Group.

Dr. Correa also observed that the Study Working Groups, as currently defined, left a few gaps with respect to potentially important outcomes. However, in at least two cases, Working Groups had submitted hypotheses to help fill these gaps. For example, the Gene-Environment Interaction Working Group submitted a hypothesis on type 1 diabetes, while the Early Origins of Adult Health Working Group submitted a hypothesis on schizophrenia.

Dr. Correa advised participants that a list of the hypotheses was submitted before the meeting, distributed to Working Group chairs, and shared with Working Group members. Specific hypotheses and more detailed observations and findings that emerged from the Working Group discussions could not be presented due to time constraints. Dr. Correa reminded the Working Groups that they were to submit two-page reports of their activities, decisions, and plans by April 15, 2002. He noted that the Working Group reports would serve as interim progress reports for the NCSAC and would be posted on the Study Web site.

Assembly Comment and Discussion on Progress to Date

ICC member Pauline Mendola, Ph.D., from the EPA, invited participants to share comments and ask questions about Study progress to date. She welcomed suggestions for the planning process, particularly ways to enhance diversity in the Working Groups and NCSAC. Dr. Scheidt reiterated that the progress reports presented by Dr. Longnecker and Dr. Correa were not final reports and should be considered as information sharing with the Assembly to familiarize participants with Working Group activities.

Participants offered the following remarks (organized by broad topic areas):

Hypotheses Issues

• Dr. Mendola provided more details on the hypotheses review process in response to questions about whether Working Groups’ proposed hypotheses were being funneled through the Study Design Working Group to the NCSAC, and whether Working Groups could have prospective criteria before revising hypotheses. It was explained that the Study Design Working Group developed suggested criteria in a survey to help it identify core hypotheses that might impact the Study design. The survey was distributed in December 2001. The NCSAC reviewed and slightly modified the survey. The struggle for the Study Design Working Group had been that the hypotheses submitted by other Working Groups did not match what was requested on the survey form. Specifically, hypotheses did not suggest that a longitudinal study of the magnitude and scope of the Study was necessary to answer the questions. As a result, the Study Design Working Group questioned the clarity of its message. Dr. Mendola stressed that the Study Design Working Group was not filtering Working Group products or neglecting to send them to the NCSAC. The products were shared among Working Groups via the portal. Now that the NCSAC was active, the hypotheses would be sent simultaneously to the NCSAC and the Study Design Working Group, with the latter continuing its integrative effort as an overarching Working Group. The number of iterations in the review process would depend on the depth and responsiveness of the products submitted by the Working Group.
  
  
• Dr. Mattison further clarified that the NCSAC wanted the proposed hypotheses to be processed within the various Working Groups at the same time that they were sent to the committee. Because the NCSAC was meeting for the first time, it could not review all the Working Group submissions. It asked for an initial meeting with Working Group chairs in June to go over their charges and a brief summary of their existing hypotheses. The NCSAC expected to give full consideration to all the hypotheses in the fall, with comments sent to the originating Working Group.
  
  
• Additional communication from the Study Design Working Group would be sent to the Working Groups to clarify what was meant by "core" hypotheses: core hypotheses would provide the rationale for why a study involving 100,000 subjects followed for 20 years was necessary. These core hypotheses did not preclude other hypotheses that did not need such a large sample size, but the core hypotheses would identify priorities with scientific and public health importance that could not be done without a study of this scope. One participant commented that some of the submitted hypotheses did address these requirements.
  
  
• It was suggested that a group of past studies involving 70,000 pregnant women was an example of a large cohort focused on children’s health. The studies looked for outcomes such as birth defects related to drugs taken during pregnancy; the rationale for the large cohort was that the size was necessary to find a few rare events (for example, a drug that caused a heart defect). It could be argued that the Study also needed to be a large study to find rare events and to look at environmental toxins, which were not part of the earlier studies. Furthermore, the conception of the earlier large studies was praised in retrospect because gathering data without specific hypotheses allowed for imposing hypotheses later, when those rare events were identified. The broad focus of the previous studies had stood the test of time, although it evoked criticism at the time the studies were initiated.
  
  
• Dr. Mendola added that although the Study was a broad study on the health and environment of children, there were probably a few burning questions that would get particular attention in terms of Study design, data collection, and other issues.

Diversity Issues

• One participant noted that, although the notion of "How are the children?" was important, so too was the question "How are the children who are in greatest need?". It was added that strategies for enhancing diversity were available and should be employed as soon as possible, but the Study needed a theme from which it could engage diverse participation. Organizations that might be helpful included the Interamerican College of Physicians and Surgeons and the National Medical Association.
  
  
• It was explained that the Health Disparities and Environmental Justice Working Group had two underlying assumptions to address based in history and science: (1) if there was no injustice historically, there would be no need for an executive order on environmental justice, and (2) ever since records have been kept on health disparities, these disparities have existed. These assumptions should constitute a foundation for design and hypotheses. But because the Study had delayed in engaging diverse participation, the Study was beginning to develop hypotheses without this input, which increased the risk that it may be rejected.
  
  
• ICC members added that health disparities were specifically mentioned in the Children’s Health Act of 2000 and were foundational to the planning of the Study. The request for the names of organizations and individuals that could help recruit diverse participation was reiterated. However, it was pointed out that credible individuals were needed to take the request to diverse organizations. These organizations had been asked for help before, but the exchange should continue.
  
  
• Another strategy described that could increase diversity was to involve more people from local health departments. These individuals could bring quality and diversity to the Study and could help the Study access populations of interest. Dr. Mendola noted that one member of the NCSAC was from a local health department.

Study Sample Issues

• Dr. Mendola raised the issue of whether the Study sample should be strictly a statistically random sample. She noted questions about whether the Study should enroll pregnant women or couples contemplating pregnancy. A strong value had been placed on ensuring that the results of the Study were in some way representative of children in the United States. Consequently, the Study had to be sufficiently large and well designed to achieve this goal. One other issue mentioned was possible oversampling of certain groups.
  
  
• One participant indicated that because 5 percent of all pregnancies occur in children under 17 years of age, the Study had to consider ethical issues related to the enrollment of minors. However, these types of pregnancies also needed to be involved in the Study because of the potential for pathologies associated with children having children.
  
  
• It was explained that many subpopulations, some of which were quite small (for example, Native Americans and people who eat marine mammals), would be of interest to the Study and generate hypotheses. Balancing the need to study these subgroups with the need to represent the general population would be a challenge. Without a reasonable facsimile of a random sample, which could be stratified and oversampled in various groups, it would be difficult to identify biases. Testing the probability of hypotheses was usually based on starting with a random sample.
  
  
• Another participant explained that a general random sample (for example, the British Birth Cohort) was not necessarily the only choice. A stratified random sample, such as the National Health and Nutrition Examination Survey (NHANES), overselected from certain critical populations but was capable of inferring back to the national population. Another possible Study design was the CARDIA study, which allowed competitive research centers to bid on the process. This approach resulted in cohorts that represented the local communities in which the research centers resided. CARDIA was a good example of a study that looked at the longitudinal effects of air pollution on the development and exacerbation of cardiovascular disease. However, because of the way the study centers were set up, the most heavily polluted community was Chicago, IL, and the gradient of exposure was lacking. The choice facing the Study was not between representative and nonrepresentative sampling, but between a stratified sampling frame imposed at the national level (for example, NHANES) or the competitive research centers approach (for example, CARDIA), which would provide cohorts in the locations of the centers that won the awards.
  
  
• It was added that the nationally representative NHANES model and the centers model were not necessarily incompatible. In the NHANES model, the sample was clustered in areas around the country. Any nationally representative sample would be clustered, and whether fewer or more clusters were involved is a design detail. Once the primary sampling units collected in the local areas were selected within an NHANES model, there could be competition for participation among centers in those areas. Most of the largest U.S. cities would probably be selected in any reasonable model, so there was potential compatibility between the two approaches. One member raised the possibility of stratifying centers by category and having competition between separate clusters (for example, have competition between centers in different rural regions).
  
  
• A participant noted that, when considering oversampling, the Study might want to think beyond region, oversample women with certain underlying chronic conditions that are of public concern for prevalence or increasing prevalence, and follow them for their children’s outcomes.
  
  
• The issue of how representative the sample should be depended on the Study’s core hypotheses. For example, if the core hypotheses dealt with the relationship of a health outcome to a certain exposure factor, then the best design was to get the widest possible range of that exposure factor. Thus, the core hypotheses would determine whether the Study required a sample that would be representative or one that would maximize the efficiency of a parameter and model.
  
  
• One person explained that the Study Design Working Group deliberately avoided discussing sampling because it waited to be driven by the research hypotheses. However, some themes had emerged. Strong arguments existed for oversampling certain subsets of the population (for example, ethnic groups, rural status, maternal risk factors, and environmental exposures), and these should be taken into account, depending on the core hypotheses.
  
  
• Another participant noted that the Study needed investigators as well as subjects, and the distribution of these groups in the United States was different. Consequently, the same sampling scheme may not work for both. Usually investigators were sampled first, each bringing their own subjects to the research. However, this was not the best design. The Study might be able to sample subjects first, determine where they were, and then identify investigators who could work with them, possibly from a distance.
  
  
• Another consideration noted was that the children, pregnant women, and couples who might enroll in the Study would not remain in the same location throughout the duration of the study. Flexibility and attention would be required to connect with subjects as they moved within or outside the country so that critical Study measures could be obtained.

Community Involvement Issues

• Dr. Mendola raised the issue of community involvement in the Study and asked for feedback on questions such as when community involvement was subject to burden and how subjects could be involved and given feedback at an appropriate level.
  
  
• One participant who worked in the area of lead exposure in children, had a study design that included significant community involvement, including community input to help design a followup study. She volunteered to be a resource on this issue.
  
  
• It was added that pilot studies could be directed to answer some questions of community involvement. The studies could be directed in a cooperative, participatory manner to provide an evidence base from which to make decisions.
  
  
• The discussion then turned to lessons about community involvement that could be learned from studies such as KIDS COUNT and its evolution. Because KIDS COUNT generated state-specific data, and in some cases city-specific data, states used the information as part of their policy and program development and were investing their own resources to supplement the study with a broader sample from within the states. The Study may have opportunities to form partnerships at the state level if there were interest in energizing more community involvement.
  
  
• A participant added that there was no need to reinvent a network to work with people at the community level. The U.S. Department of Agriculture’s Cooperative Extension Service had existed since the turn of the 20th century and reached every county and territory in the nation. Many researchers at land-grant universities and state colleges used the extension system. The volunteers and other individuals who were part of the system were all trained professionals and were increasingly involved in health issues such as cancer and diabetes.

Other Issues

• In response to a question about increasing the size of the Working Groups to augment available expertise, Dr. Scheidt explained that factors such as efficiency and support costs limited the size of the Working Groups. However, the at-large membership allowed Working Groups to use the expertise of interested, capable individuals who could provide additional primary review or serve as substitutes. Ad hoc membership in Working Groups was also feasible, and experts could be brought in for one consultation or meeting.
  
  
• A member explained that some federal agencies were negotiating with the Office of Management and Budget (OMB) about their fiscal year 2004 budgets, which had to be aligned with the projected starting date of the Study. Although birth cohort recruitment was scheduled to begin in 2004/2005, a more realistic start date was needed, given the current slippage in the Study timeline. Participants were advised that a revised timeline would be presented later in the afternoon. Dr. Mendola added that events in the wake of September 11, 2001, diverted some attention from planning efforts, which involved multiple federal agencies.

Next Steps in the Planning Process

ICC member Marshalyn Yeargin-Allsopp, M.D., of the CDC, reviewed future Study milestones and the activities associated with each step. Figure 2 highlights the next steps in the Study planning phase, beginning with the April 2002 Study Assembly meeting.

Dr. Yeargin-Allsopp noted that although the chart showed the Program Office supporting the NCSAC and the Working Groups in fiscal year 2002, the Office had actually been providing support to these groups and to the ICC for the past year.

Dr. Yeargin-Allsopp provided additional details about the planning timeline and outlined responsibilities for each step.

• The next step in planning involved selection of the Study’s core hypotheses. The milestones for this step included the following:
  • Late spring—NCSAC begins review of hypotheses
  • Early summer—Working Groups refine hypotheses
  • Mid-summer 2002—Working Groups submit refined hypotheses as findings to the NCSAC
  
  During this process, the Working Groups were responsible for proposing hypotheses as findings to the NCSAC. The Working Groups were in various stages of formation; some had already proposed hypotheses and some had yet to do so. The NCSAC would review and recommend hypotheses, and the ICC would select the core hypotheses to submit to the NICHD Director.

• The first round of methods development and pilot studies was scheduled to begin in spring 2002. The following milestones would be completed:
  • Spring 2002—Begin proposal evaluation within the Working Groups
  • Early summer 2002—Refine and consolidate ideas within the Working Groups and in the Study Design Working Group
  • Early summer 2002—The ICC and Program Office will make awards and work will begin
  
  During this step, Working Groups will develop proposals for studies; the NCSAC will review and recommend proposals; and the ICC and the Program Office will set priorities, allocate resources, match proposals to needs, and administer funding.

• The milestones for the second round of methods development and pilot studies included the following:
  • Summer 2002—Reevaluate priorities
  • Early fall 2002—Evaluate proposals and match to priorities
  • Late fall 2002—Make awards and begin work
  
  Responsibilities would be the same as those for the first round.

• Writing the Study protocol constituted the next step in planning. The following milestones would be completed during this stage.
  • Winter 2002—Finalize sampling strategy
  • Early 2003—NCSAC and Working Groups provide final Study design proposals to ICC
  • Begin writing protocol and continue writing through most of 2003
  
  To support this step, the NCSAC and the Working Groups would propose measurement needs and designs to achieve the goals of Study hypotheses. The ICC and the Program Office would synthesize information into a protocol to submit to OMB.

• The final planning step was to prepare for implementation of the full Study. Milestones included the following:
  • Winter 2003—Summer 2004—Compete for initial centers
  • Late Summer 2004—Select initial centers
  • Fall 2004—Receive core funding
  • Early 2005—Begin enrollment for Study
  
  During this step, the Program Office and ICC would translate the Study protocol to make awards and administer the funding mechanisms. The NCSAC and the Working Groups would advise and provide relevant findings. The Working Groups would provide relevant findings to the NCSAC, which would advise the ICC and Program Office.
  
  According to this timeline, enrollment in the Study would begin in 2005.

Commitment to an Open Planning Process

ICC member Kenneth C. Schoendorf, M.D., M. P. H., of the CDC, discussed the continuing commitment to an open and participatory planning process. Since the first consultation held in January 2000, Study planners had been convinced that a large-scale child health study was feasible. The following guiding principles emerged from this consultation:

• Think boldly—The Working Groups were helping to expand the boundaries of the Study.
• The allocation of new money would be necessary—The Study could not be sufficiently funded from existing research dollars.
• Extensive public/private collaboration—The mechanism necessary to ensure this type of collaboration and non-federal involvement was the formation of the NCSAC and the various Working Groups to operate as tools of the NCSAC, in adherence to FACA.

Dr. Schoendorf admitted that this inclusion process was an unprecedented mechanism for designing a research study. The typical approach was to start with a topic of interest and perceived import, proceed linearly to design a study around the topic, implement the study, and, when necessary, call on additional expertise. The Study mechanism was very inclusive, but could seem to lack direction and efficiency. However, the following benefits of the inclusive NCSAC/Working Group structure outweighed the disadvantages:

• The breadth and depth of the available scientific expertise surpassed that of any federal agency or combination of agencies or any collection of academic or industry researchers.
  
  
• A study of this magnitude could not happen without the necessary support and participation of the individuals and groups represented in the Working Groups and NCSAC. Support from academia, professional organizations, industries, and community organizations was critical to planning and implementing the study.
  
  
• The inclusive process engendered a new level of professional interaction. Novel interactions represented true collaboration between federal and non-federal professionals who operated on equal footing and were engaged in creating new work. In addition, the interaction between disciplines and people with diverse expertise was unique. The continued work of the groups involved in study planning would be a lasting contribution to child health, even if the Study was not funded.
  
  
• This project was necessary to encourage and train the next generation of child health researchers, who would not only address the general issue of child health and the environment, but would also carry on with the Study as it proceeded over decades.

Dr. Schoendorf concluded by noting that, although the inclusive process was an untried way to design a research project, the Study would not have a chance of success without the continued enthusiastic support and hard work of all the people at the Study Assembly.

Assembly Comment and Discussion on Next Steps and Future Directions

Dr. Mendola invited comments on the final portion of the ICC presentation, including aspects of the inclusive policy and the interactions between Working Groups.

• It was noted that there was a slight disconnect between the timeline presented by Dr. Yeargin-Allsopp and the current perceptions of the NCSAC. The NCSAC was just starting to learn about the Study and the steps to get the project launched. It was explained that the NCSAC members met for the first time in the past few days, and most members were just beginning to learn about the Study. The NCSAC was setting up additional meetings to satisfy FACA requirements and would meet again within 30 to 90 days to review each of the Working Groups’ charges, a brief summary of their hypotheses, and unresolved issues that they were facing. A second NCSAC meeting in October would deal more formally with submitted hypotheses.
  
  
• It was emphasized that the Study Design Working Group needed to continue reviewing the hypotheses, but the Working Groups should be aware of the NCSAC timeline. Participants anticipated that the timeline presented by Dr. Yeargin-Allsopp might need to be pushed back 6 months to accommodate the NCSAC timeline.
  
  
• Dr. Yeargin-Allsopp suggested that the timeframe for refining hypotheses might need to be moved from the summer to the fall. She acknowledged that the timeline represented goal milestones to stay on track for funding to be provided in the fall of 2004 and Study enrollment beginning in 2005.

Participants offered the following additional remarks (organized by broad topic areas):

Strategies for Building Support

• Although federal agencies were not allowed to lobby Congress, efforts to get congressional support for the Study would be necessary via other means. It was suggested that the child health advocacy community be enlisted to build the ground swell of support needed to get funding for the Study in 2004. It was acknowledged that federal agencies could not lobby, but they could provide information to Congress through briefings by legislative and public liaisons.
  
  
• Efforts to build broad-based support for the Study had already begun. It was added that the Study’s lead funding agencies initiated a series of meetings to inform the leadership about the Study from within the administration. Ensuring that the information and general support existed was an important first step before an intentional, large-scale lobbying effort from non-federal groups would be appropriate. ICC members would continue to inform people about the Study and gain support. NCSAC members would be able to talk about the Study as they became more acquainted with the work.
  
  
• Three groups that might be valuable allies were mentioned: the Children’s Environmental Health Network, the American Academy of Pediatrics, and the March of Dimes. In addition to identifying other groups that need to be involved, Study planners will need to translate the science behind the Study into language that will assist advocacy efforts.
  
  
• It was added that the involvement of the American College of Obstetricians and Gynecologists, which had a very active and successful lobbying effort, would also be crucial. A coalition of obstetricians and pediatricians would be very powerful.
  
  
• In addition to considering what key organizations should be involved, strategies for gaining support should consider states represented by members of Congress who wielded considerable influence on funding for children’s issues.
  
  
• Participants added that crucial support was also needed from Healthy People 2010 and from representatives from education communities. Other constituency groups that would be valuable included the National Association for the Education of Young Children, the National Parents and Teachers Association, and the National ARC. Representatives of specialized groups, such as the Autism Society of America, should be balanced with representatives from the general population of well children to help sell the Study to the average U.S. citizen. Additional consideration for involving the education field was the potential for taking many measurements and collecting data while children were in school. Dr. Yeargin-Allsopp reported that representation of the Department of Education was crucial to planning, and interactions had been taking place. Dr. Kimmel added that, as a member of the President’s Task Force, the Department of Education has been engaged in the Study effort since its inception.
  
  
• It was noted that to receive federal funds by fall 2004, a proposal to fully fund the Study would have to be in the hands of a congressional committee by April 2003.
  
  
• It was suggested that changing the Study tagline to Health, Development, Environment might help gather support. Educational issues were currently driving the domestic policy and were increasingly being framed as "school readiness" issues, which were tied to development. Thus, using "development" instead of "growth" in the tagline could be a stronger tie to domestic policy. However, it was pointed out that testing of the tagline resulted in "development" being replaced with "growth" because it was thought that a shorter word might stand out more on media materials.
  
  
• Participants explained that a crucial argument to justify the considerable cost of a single large study, when opponents would advocate for smaller studies on other child health issues, was that the Study was not being conducted just for the sake of science and answering important basic questions. It was important to emphasize the collateral benefits of the Study. For example, the technology that was likely to emerge from the Study, such as the instrumentation, assessments, data, and ways of analyzing and integrating data, would be useful at the state and local levels to support early childhood development programs and health and developmental improvement programs. This technology providec collateral benefits to fields other than child health, including the educational, mental health, and juvenile justice systems.
  
  
• It was noted that the well- becoming of children was a more powerful motivator for major investment than the well-being of children. Thus, the Study should be framed more clearly in terms of how it relates to what children will do and how they will add to society over the long run (for example, through a link to education).

Funding Mechanisms

• A question was raised about the mechanism that would be used to make competitive awards for the Study centers and to foster collaboration between federal scientists and the awardees. Dr. Mendola responded that, before the Study design was in place, decisions about funding mechanisms would be premature. However, there was interest in making the award process as competitive as possible. The Study would have a defined core set of measurements that would be accomplished most efficiently through a contract mechanism. However, another consideration was providing the opportunity to engage intramural scientists from a variety of agencies. Dr. Mendola added that the Study might be funded in several ways. For example, a contract mechanism might be used to fund core Study activities, while special substudies could be added through an R01 competitive process or certain types of cooperative funding streams.
  
  
• Dr. Scheidt communicated his personal vision that the centers would be funded by a mechanism (for example, contract or cooperative agreement) that would allow federal scientists involved in designing the study to use and analyze Study data, joined by the investigators collecting the data. Other mechanisms might be used to allow non-federal scientists to have similar access. Dr. Scheidt expressed interest in pursuing these possibilities.

Other Issues

• At the October 2001 Study Assembly, someone raised the issue of having a component of the Study that trained the next generation of biomedical and clinical researchers. In response to a question on whether that suggestion was still being considered, Dr. Scheidt acknowledged the need for training researchers to do this kind of work. However, the lead funding agencies had not charged ICC with addressing this issue. Therefore, the ICC could not make a commitment to funding both the Study and training programs. Dr. Mendola noted that the Children’s Health Act of 2000 contained provisions regarding training, and there was an interest in exploring training opportunities. There were only a limited number of people studying child health and environmental effects; many of the young investigators in this field went on to training programs in other areas, such as cancer.
  
  
• In response to a question about three similar millennial studies that are being launched in England, Canada, and Australia, Dr. Scheidt reported that there had been a fair amount of collaboration between Canadian investigators and the Study. There had also been discussions with Japanese, Israeli, United Kingdom, and Mexican investigators interested in similar efforts. The ICC was considering proposing an international Working Group to coordinate such efforts more explicitly. Dr. Mendola added that the ICC was also in communication with the World Health Organization and the European Union about similar studies. These activities indicated that there was a worldwide recognition of the importance of questions about child health and the environment.
  
  
• Concern was expressed that the current planning timeline did not provide a sufficient interval to analyze findings from the pilot studies that may impact the design of the Study. Moreover, there was no time allowed to revise hypotheses based on the Study design after it was released. Dr. Yeargin-Allsopp reported that the ICC recognized that continuous revisions to hypotheses (but not necessarily core hypotheses) were needed as findings from methods development and pilot studies were received. These results would not be available when the protocol is written, but the protocol would be refined as results were received. Dr. Mendola added that having goals and timelines helps planning move forward. The ICC hoped to establish core hypotheses within the given timeline; other features of the Study may be added on another parallel track.

Conclusion

Dr. Scheidt delivered closing comments to the Study Assembly. He noted that the meeting was marked by the establishment of the chartered NCSAC, the formation of 8 new Working Groups, and the development of core hypotheses by 16 Working Groups. He added that pilot studies were underway and that 206 organizations, institutions, and agencies were on the listserv for the Study Assembly, which included more than 1,300 individuals. Dr. Scheidt reported that the April 2002 meeting had 403 registered participants, a considerably larger number than the previous Study Assembly meeting in October 2001.

Dr. Scheidt anticipated that the Study Assembly would need to meet again within 6 to 12 months. He hoped that, by the next meeting, the Study would have more progressive and stable funding, a full set of core hypotheses, results of the current pilot studies, the outline of a sampling plan, and new pilot studies underway. Dr. Scheidt also expected to be able to give participants more advance notice of the meeting dates.

Dr. Scheidt urged participants to keep in touch with the Study through the following channels:

• The Study Web site at www.nichd.nih.gov/despr/cohort/
• The Study listserv
• E-mail at ncs@mail.nih.gov

He advised participants that the Study Web site was being revised and that a new site would be available in a few weeks ( www.nationalchildrensstudy.gov). The new site would offer more details on the Study and pages for each element of the Study.

Dr. Scheidt adjourned the meeting.

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