June 2002 NCSAC Meeting 

The 2nd Meeting of the National Children’s Study Federal Advisory Committee (NCSAC)
June 13-14, 2002
Natcher Center, National Institutes of Health (NIH)
Bethesda, MD

Summary Minutes 

The National Children’s Study 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) .

The NCSAC convened for its second meeting at 9:04 a.m., on Thursday, June 13, 2002, at the NIH campus. Donald R. Mattison, M.D., a consultant to the Division of Epidemiology, Statistics, and Prevention Research at the NICHD, chaired the meeting. Unlike the first NCSAC meeting, this meeting included representatives of the National Children’s Study (the Study), the Interagency Coordinating Committee (ICC), as well as Study Working Group chairs.

Appendix A provides a list of those present at this NCSAC meeting.

June 13, 2002

I. Call to Order and Introductions

Dr. Mattison, NCSAC chair, called the meeting to order and proceeded with the official NCSAC agenda.

II. NCSAC Interactions with Legislators and Legislative Staff

Dr. Mattison introduced George Gaines and Lisa Kaeser from the NICHD Office of Program and Public Liaison. Mr. Gaines outlined the parameters for communication between individual NCSAC members and legislators, including legislative staff. Mr. Gaines then distributed a copy of the Public Policy Activity Guidelines for the NCSAC members. He added that, as special government employees, NCSAC members must adhere to these guidelines, which included: official duty periods of NCSAC members; restrictions on contact with members of congress or their staff when on official duty; approved lobbying or contact with members of congress and congressional staff; procedures for obtaining approval for, and coordination of, official congressional contacts; appropriate interaction with congress as private citizens; permissible contact with congressional staff as private citizens; coordinating interaction with officials of HHS and other federal agencies; and informing the NCSAC chair of contact with non-government organizations, groups, and key individuals.

Mr. Gaines clarified the restrictions imposed on NCSAC members, as determined by these guidelines. It was added that questions about the guidelines should be directed to the NICHD Office of Program and Public Liaison.

III. Interactions with the ICC

Dr. Mattison reported that he had asked two ad hoc committees composed of NCSAC and ICC members to address two issues: 1) The process by which recommendations from the NCSAC are forwarded to the ICC, to be addressed by Drs. Graham, Dudley, LeMasters, Kimmel, Scheidt, and Schoendorf; and 2) Institutional Review Board (IRB) processes, to be chaired by Dr. Fleischman, who will compose the committee’s membership in consultation with the Ethics Working Group co-chairs.

Dr. Mattison asked Peter Scheidt, M.D., M.P.H., to summarize the respective roles and responsibilities of the Study Working Groups and the NCSAC. Dr. Scheidt’s presentation described:

• The roles and responsibilities of the NCSAC, as outlined in the NCSAC’s charter
• The roles and responsibilities of the Working Groups in providing expertise, proposing hypotheses, and producing findings
• The rationale for having a broad and diverse range of Working Groups
• The criteria that were used in establishing Working Groups

IV. ICC Recommendations

Dr. Scheidt reported that the ICC recommended changes to two Working Groups. First, the ICC proposed that the planned Recruitment and Retention Working Group be delayed or abandoned because it could not carry out its work until the study design was developed and the sampling plan was determined. Dr. Scheidt noted that pilot projects focused on enrollment had already been initiated, and that recruitment and retention issues could be addressed by the Study Design Working Group or the NCS Program Office.

Second, the ICC proposed a restructuring of the Information Technology Working Group because the NCS data management system would be developed under contract. Instead, the group would be the Technology Working Group, and it would be composed exclusively of federal staff to eliminate the possibility of giving potential vendors a competitive edge.

V. Discussion of the Roles of the NCSAC, ICC, and the Working Groups

Dr. Scheidt explained the specific role of the Working Groups. Based on guidance from the HHS Office of General Counsel, Dr. Scheidt stated that Working Groups were responsible for gathering facts and information, performing studies, drafting reports, identifying alternatives, and allowing for the exchange of views and ideas. He added that Working Groups could not make decisions, provide consensus advice, or communicate directly with federal officials about the study.

Dr. Scheidt summarized the role of the ICC in relation to the Working Groups, specifically in regard to: providing information about the status of the Study, assisting the NCSAC with interpreting the overall structure and operation of the Study; ensuring that Working Group findings and proposals were forwarded directly to the NCSAC; ensuring that agencies consider only products generated by the Working Groups that were reviewed and forwarded by the NCSAC; facilitating smooth and productive functioning of the Working Groups; collaborating with Working Group chairs; and identifying and resolving challenges in collaboration with the NCSAC.

Dr. Scheidt noted that the NCSAC was responsible for making recommendations to the NICHD director, who had administrative responsibility for the Study, and to the ICC. Because the NICHD director could not be involved in the day-to-day management of the study planning process, Dr. Scheidt reported that the NICHD director had delegated much of his decision-making authority to the ICC. He explained that the ICC would now be responsible for reviewing hypotheses, measures, pilot findings, and other recommendations submitted by the NCSAC.

VI. NCSAC Recommendations and Discussion

It was noted that the NCSAC needed to establish its structure for making recommendations to the NICHD director and the ICC, as well as to identify a process for reviewing and commenting on agency-generated proposals, perhaps via ad hoc committees composed of NCSAC and ICC representatives.

Dr. Scheidt invited questions and comments from NCSAC members; the following issues were discussed:

• When asked about the role and duration of the NCSAC during implementation of the Study, Dr. Scheidt stated that the Study protocol would be written by scientists in the NICHD Program Office, based on Working Group findings and NCSAC recommendations. He added that the NCSAC would be integrally involved throughout the planning phase. As for how long the NCSAC would exist, he explained that the issue would be determined by the NCSAC itself and the NICHD director.
• When asked how the Working Group members benefit from participation in the Study planning process, Dr. Scheidt stated that, when data become available, it was hoped that Working Group members could participate in analyzing areas of special interest, accessing public use data sets, or conducting investigator-initiated analyses. He added that safeguards were in place to eliminate the potential for conflict of interest. It was noted that Working Group members needed to know how they could benefit from their involvement, so that the study, in turn, would benefit from engaging the best minds in planning the Study.
• One member underscored how critical the issue of recruitment was to the Study and how important it was that cutting-edge and emerging technologies be employed in the Study. Dr. Scheidt replied that the Recruitment/Retention and Technology Working Groups were established because the ICC recognized how important these issues were to the Study design.
• When asked which Working Group would be dealing with sampling strategies, Dr. Scheidt stated that the ICC saw this task as a joint effort of Study Design Working Group and the ICC, with final decisions made by the NCSAC and, ultimately, the NICHD director. It was asked that a specific statement be added to the charge of the Study Design Working Group to indicate its role in addressing sampling strategies. The meeting chair suggested that the NCSAC send a memorandum to the Study Design Working Group asking it to add this responsibility to its official charge. It was added that more information would be needed to assess the most effective ways to sample specific minority populations (e.g., focusing on a particular geographic region).
• It was proposed that the NCSAC delegate responsibility for reviewing Working Group reports to ad hoc committees.
• One member asked whether each center would examine the same exposures and outcomes, and if some portion of Study resources would be dedicated to communities or cross-community collaborations. Dr. Scheidt responded that a rigorous core Study protocol would be developed and applied throughout the study, but that there would also be some local and investigator-initiated studies.
• It was noted that communities were not currently represented on the NCSAC, and that this perspective should be addressed sooner rather than later.
• One member asked for clarification regarding the technology to be used for recording data. An ICC representative responded that the ICC had been discussing how to use technology in ways that it had not been used before. While the Technology Working Group would be composed entirely of federal staff, there would be targeted workshops and consultations to solicit new and creative ideas. Implementing those ideas would most likely involve collaborating with the Working Groups to ensure that technologies were used appropriately and accurately in collecting data, and that the full range of technologies were used to support the Study.
• One member commented on the challenges associated with ownership of data in the Study (e.g., when a child moves from one center to another and becomes part of another data set), and noted that it would be difficult to discuss recruitment, retention, and sampling issues until there was more clarification as to whether the Study was one large study, or a cluster of separate studies.
• It was suggested that the Study develop a matrix to help conceptualize the Working Group structure. On the issue of community outreach, it was noted that, when a study was observational, communities might not recognize the benefits of participation as clearly as they would for an intervention study. One member underscored the need to integrate the perspectives of communities as soon as possible. Another member added that, even if the same protocol was used across centers, different recruitment and retention strategies would be needed for different types of communities, and recommended identifying someone with expertise in tailoring recruitment strategies to advise the NCSAC.
• A question was raised about the feasibility of the Study in terms of the expense, the complicated nature of the measurements, and the burden on participants. The need to implement restrictions on the Working Groups to avoid developing a massive and impractical study was stressed.
• One member expanded on the issue of participant burden. It was noted that participants might want to receive some benefit for their participation, but an observational study did not offer an immediate benefit. Dr. Scheidt stated that the ICC was aware of the expansiveness of some proposed hypotheses. However, he added that it was possible to get a wealth of data with minimal or no increased burden on subjects.

VII. Timeline and Methods Development

Dr. Mattison introduced Pauline Mendola, Ph.D., of EPA, who presented the proposed Study timeline, a copy of which was included in the NCSAC Briefing Book. The Study hoped to begin enrolling participants in 2005, even though some modifications to the timeline may be necessary. Core hypotheses, the first step in the Study design process, were expected to be finalized in fall 2002. Secondary hypotheses with smaller samples would be identified after the core hypotheses were determined. Once the hypotheses were determined, the NICHD Program Office planned to write the Study protocol during fiscal year 2003, with Office of Management and Budget approval anticipated in fiscal year 2004.

Dr. Mendola invited questions and comments regarding the timeline. The following issues were discussed:

• One member asked how it would be possible to write the protocol when pilot studies were not yet complete. Dr. Mendola indicated that some parallel processing of tasks would take place, but stressed the importance of identifying the timeline for study planning and follow-through. It was noted that it may be necessary to accelerate the timeline, rather than to continue to delay it.
• One member expressed concern about ensuring buy-in from the investigators regarding the protocol and their opportunities to make a creative contribution to the Study. It was proposed that the Study planners seek the input of investigators to ensure that they would support and follow the protocol.
• When asked if the centers would be responsible for data collection, cleaning, coding, and analysis, Dr. Mendola stated that the coordinating center would serve as the data repository, and that plans were being made to address the information management issues.
• It was asked whether the secondary hypotheses would be investigator-initiated and localized, and if there was a possibility that the sample may not require 100,000 subjects. Dr. Mendola stated that the Study design would be structured around the core hypotheses, and that secondary hypotheses would emerge out of discussions about what else could be learned from the available sample.
• One member inquired as to which populations would be sampled and how they would be sampled. Dr. Scheidt responded that several components of the Study planning structure were dealing with these issues. The Study Design Working Group would make the initial proposal, submit it to the NCSAC, and the ICC would make a determination based on the NCSAC’s recommendation. He noted that this process would be informed by the pilot work already underway to address these issues. Dr. Mendola added that the ICC wanted the sample to be as representative as possible, so some oversampling would be required. One member suggested that the next version of the Study timeline identify a goal for completing the sampling plan because so much of the study planning process relied on it.

VIII. Information Management Systems Development

Dr. Mattison introduced Sarah Keim, M.A., of the NICHD Program Office, and member of the ICC. Ms. Keim presented the status of the information management systems to be used in the Study.

Ms. Keim outlined the various phases associated with developing the Study information management system infrastructure:

• Phase 0: planning activities; almost complete
• Phase 1: detailed architectural development
• Phase 2: infrastructure design and system building
• Phase 3: making operational the information management system

Ms. Keim stated that the ICC recognized the need to develop a system that would enable efficient collection, transmittal, storage, archiving, and retrieval of data. She added that one challenge was multiple data input points from the various centers, and that the longitudinal nature of the study itself presented several key challenges.

Ms. Keim commented on the range of technologies that may be used in the Study. She explained that it would be necessary to keep data in pristine condition, and to safeguard the security of the data, including all specimens. Once the information management systems were developed, tested, and implemented, the data collected would be a valuable tool. She noted that the key would be to maximize the potential of the data, to limit the burden on participants, to capitalize on niches of technological expertise in the private sector, to adapt to change, and to ensure that the science drives the technology (rather than having the technology drive the science). Ms. Keim noted that, after 20 years of data were collected, the information management system would require approximately 500 gigabytes, which was roughly equivalent to the amount of data contained in each United States Census.

Ms. Keim also stated that developing a system blending off-the-shelf and customized data management technologies appeared to hold the most promise, in terms of cost and feasibility. She said the ICC envisioned distributed data collection sites supported by a data management center, all of which complying with HL7 standards for coding to enhance analysis. Once designed, the system would enable data transmittal via the Internet. However, Ms. Keim noted that it would be important to launch the study using cutting-edge, scalable, and upgradeable systems and hardware, so that the system could be adapted as needed at scheduled points throughout the study.

Ms. Keim indicated that the key information technology and management questions at this point in the Study planning process were about the amount of image data, the amount of data on people other than the child, standards compliance, funding availability, the impact of new legislation on privacy rules, and managing changes to the protocol effectively.

Ms. Keim then summarized the role of the NCSAC in facilitating this process by pointing out that the committee could be most helpful by providing input on ethical and privacy issues, and by addressing persistent questions about data ownership.

IX. The ICC Pilot Studies Plan

Carole Kimmel, Ph.D., of EPA briefed the NCSAC members on the status of pilot studies that would be conducted in the coming months, and distributed the ICC’s pilot studies plan. She stated that some pilot studies began in 2000, and that the ICC was anxious to fund more pilot studies before the end of the current fiscal year. The purpose of these pilot studies, according to Dr. Kimmel, was to inform the overall Study design.

Dr. Kimmel indicated that the ICC was seeking concept clearance for three pilot studies. The first pilot study would test the feasibility of the lead sampling strategy(ies). The second would focus on the potential to use primary care sites as a uniform and available source of contact and data collection. The third pilot study would identify criteria for defining injuries throughout the Study.

To facilitate NIH approval for the pilot studies, Dr. Kimmel asked the NCSAC to review the proposals and provide feedback. In addition, she noted that the ICC was seeking the NCSAC’s permission to contact Working Group participants as needed to engage them in convening expert panels, identifying experts, and addressing other issues as they arose.

Other pilot studies included in the ICC’s pilot studies plan would focus on the following issues: assessment of fetal growth and development; standardized neonatal exams; ethics guidelines; community outreach and education; sampling strategies; utilization of technology to collect, store, archive, and analyze data; measures for evaluating cognitive development; methods for testing exposure to therapeutic agents; and repository capabilities.

Dr. Mattison invited questions and comments. The following issues were discussed:

• One member asked to what degree the pilot studies proposed by Working Groups had been incorporated into the ICC’s pilot studies plan. Dr. Kimmel indicated that, given the Study planning structure, the Working Groups were supposed to present their pilot study needs to the NCSAC, and that the NCSAC would review those proposals and make recommendations to the ICC. At this point, the ICC had not been able to interact with the Working Groups because of the Study planning structure, and because the NCSAC had not yet granted permission for such interaction.
• When asked who would conduct the pilot studies, Dr. Scheidt stated that most pilot studies would be funded via competitive procurement. One member added that pilot study proposals had not yet been coordinated because of the Study planning structure. Another member further clarified the urgency to move forward because the end of the current fiscal year was rapidly approaching, but funding for specific pilot studies had not yet been allocated.
• One NCSAC member proposed establishing NCSAC subcommittees composed of one individual to review the pilot study proposals and make a recommendation.
• It was recommended that the pilot studies be conducted by the same people who would be conducting the overall Study, and that some literature reviews might be helpful.
• One member commented on the proposal to examine the feasibility of identifying subjects through primary care sites, noting that many children and families did not have access to primary care services. It was added that ethical questions existed related to identifying potential subjects who were not in primary care, while doing nothing to get them enrolled in Medicaid. Dr. Scheidt responded that there were established, extensive, primary care research networks and resources that would be available to the Study, along with many other networks and resources. He added that the proposed pilot studies provided an opportunity to get the Study moving forward without disrupting Working Group activities. One member underscored the need to move forward as soon as possible.
• It was recognized that not all of the pilot studies were of equal importance, and that it would be necessary to prioritize activities. Further, it was noted that, for the NCSAC subcommittees to make an informed recommendation, they would need more information to provide effective feedback. Dr. Kimmel restated that the NCSAC needed to identify the pilot studies identified by the Working Groups, to review those proposals, and to make a recommendation to the ICC. It was proposed that the NCSAC ask the Working Groups to collaborate with the ICC in identifying pilot study needs and to provide the NCSAC with a description of the proposed pilot studies.
• The meeting chair stated that he would select individuals from the NCSAC to review the pilot study information. Prior to making a recommendation, the information would be circulated to all NCSAC members.
• It was proposed that the NCSAC give the ICC permission to collaborate with the Working Groups.

X. Working Group Presentations

The chair of each Working Group updated the NCSAC on the progress of that group’s activities.

• One member indicated that it would be helpful if the Working Group could begin to tackle how communities would benefit from the Study. Ms. Dennis-Flagler stated that it was important to involve communities as soon as possible to engage them in the process and to help them get a better understanding of how they could benefit from the Study.
• When asked if the Working Group had considered the unique needs of non-English speaking audiences, Ms. Dennis-Flagler indicated that the Working Group would be sending that information to the NCSAC in the near future.
• It was asked whether the Working Group had examined its pilot study needs. Ms. Dennis-Flagler indicated that the group was hoping to get some guidance from the EPA pilot study for involving communities and creating community advisory boards, and that information from large studies was obtained as part of the Working Group’s literature search.
• When asked about the discussion group sessions proposed by the Working Group, Ms. Dennis-Flagler stated that the purpose of the proposed group sessions was to better understand how communities felt about such studies. She also restated the need to involve communities and grassroots organizations that could help the study access target populations.
• One member asked how communities would be selected, or whether the centers would select communities themselves, and proposed making a center’s ability to engage community support for the Study a requirement of funding. Dr. Mattison suggested that the Working Group develop criteria for characterizing communities and asking the centers to address those criteria in their funding proposals.

B. Health Disparities and Environmental Justice

Charles Lee stated that the Working Group, based on its charge, was focusing on two areas: 1) examining how the issues of health disparities and environmental justice could be integrated into the overall Study design; and 2) ensuring these issues continued to be a priority as the Study was conducted. Mr. Lee said the Working Group hoped to establish a structure for future interaction with other Working Groups, and to have a role in ensuring that vulnerable communities were included in the Study. He added that the group had examined some of the proposed core hypotheses and was pleased that health disparity and environmental justice issues were reflected in several of the potential hypotheses.

• One member encouraged the Working Group to think about guidelines for identifying subpopulations and their relevant disparities.
• The Working Group was urged to carefully consider sampling issues, in that a national representative sample may not be consistent with the Working Group’s priorities. It was recommended that the group examine the issue of poverty and what specific measures could be used to determine poverty-related factors (e.g., poor nutrition, supplements) associated with the outcomes.
• The Working Group was encouraged to collaborate with the Ethics Working Group to address issues of mutual concern (e.g., guidelines for interventions to reduce health disparities).
• When asked how the NCSAC could support the Working Group’s efforts, Mr. Lee said the group’s most urgent need was to better understand how to integrate environmental justice and disparity concerns into the overall study design, and to get firm direction from the NCSAC.
• The NCSAC members agreed that the work of the Health Disparities/Environmental Justice Working Group was critical to the overall Study design and implementation.
• One member encouraged the Working Group to think about sampling issues and how their issues could be incorporated into the Study’s sampling strategy. When it was noted that no member of the Working Group had that kind of expertise, one member stated that the NCSAC may be able to help the Working Group acquire such expertise.
• The meeting chair suggested that the Working Group develop criteria for ensuring that its concerns were addressed by other groups in developing hypotheses.
• It was also recommended that the Working Group participate in reviewing hypotheses.

C. Social Environment

Chris Bachrach, Ph.D., of NICHD stated that the group was interested in the issues of socioeconomic status, race, ethnicity, and geographic variability, and that it viewed the broader social environment to include public policy, programs, the areas in which people live and work, and other issues. She noted that the group believed it was important to examine the role of the social environment in both child and parental development over time; therefore a subgroup of the Working Group was developing hypotheses on families, their resources, and the impact on child development. Dr. Bachrach then presented the hypotheses that had been developed thus far by the Working Group, including integrative hypotheses that were related to the activities of other Working Groups. She indicated that additional hypotheses would be developed by the Working Group in coming months.

Dr. Bachrach explained that where people were located in a social process itself must be examined, understood, and incorporated into the Study design. She added that the Working Group advocated for a probability sample, as well as some cluster sampling. Dr. Bachrach asked for direction from the NCSAC regarding how hypotheses should be presented. She concluded that the Working Group requested four pilot studies in January 2002.

The following questions and comments were noted:

• When asked to what degree the Working Group had collaborated with other Working Groups, Dr. Bachrach reported that the Working Group held conference calls with other Working Groups. However, she stated it would be necessary for people who could see the “big picture” to encourage crosscutting Working Group collaboration.
• It was asked why asthma was the focus of so much effort, rather than upper and lower respiratory diseases. Dr. Mattison answered that asthma was specifically identified by the President’s Task Force, but that the NCSAC could ask the asthma group to expand its focus to upper and lower respiratory diseases.
• The Working Group was encouraged to assume a role in identifying how much information needed to be collected, and from what sources, to accurately capture the social and physical environments. Dr. Bachrach noted that the group had discussed the idea of developing an integrated document to describe the geography of the social environment and list the key constructs to be measured. Dr. Mattison agreed that would be appropriate.

D. Exposure to Chemical Agents

Haluk Ozkaynak, Ph.D., M.S., of EPA and Larry Needham, Ph.D., of CDC stated that the Working Group developed a strategy for examining chemical exposures and the potential relationships to neurodevelopmental disorders and asthma as a framework for developing hypotheses. The Working Group had developed four proposed hypotheses to test a variety of outcomes and was looking at critical windows of exposures, as well as the feasibility of measuring exposures. They explained that the group was also trying to obtain questionnaires conducted by children’s health centers to examine the measures for reliability. The Working Group also hoped to present during the annual meeting of the Children’s Centers.

Dr. Needham discussed the proposed white paper to be developed by the Working Group that would focus on the lifecycle stages, assess preconceptional exposure, calibrate and validate questionnaire data, assess neonatal exposure, and identify critical exposure periods postnatally. He added that the challenge was to examine chemical exposures, and to collect data at critical windows of exposure, without overburdening the population.

The following comments and questions were noted:

• One member reiterated the need for more Working Group collaboration, noting that several Working Groups were developing hypotheses that focused on similar outcomes. Dr. Ozhaynak requested more guidance regarding how the Working Groups should collaborate more effectively.
• The lifecycle approach was praised, and it was noted that the Working Group could examine all of the exposures in the Study and determine which ones could be assessed preconceptionally, in utero, postnatally, and so on. It was noted that methylmercury was a very important exposure that had not been included in a longitudinal study to date.
• One member added that every exposure measured in the Study would require a great deal of time and effort, but that it was important to consider what was already known and what scientific evidence existed to support inclusion of specific exposures. It was noted that, if the Working Group proposed to measure a certain exposure, then it should also calculate the power necessary to measure the exposure.

E. Ethics

Jeffrey R. Botkin, M.D., M.P.H., of the University of Utah School of Medicine, and Diane K. Wagener, Ph.D., of the Office of Disease Prevention and Health Promotion reported that the Ethics Resource Guide, developed by the Working Group, which outlined key ethical issues with which the Study is concerned, was now available on the Study portal. They explained that the group had also developed a white paper summarizing federal regulations that may constrain the design or conduct of the Study. They added that one of the group’s main challenges was understanding how the Ethics Working Group could be more accessible to the other Working Groups. It also encouraged the NCSAC, ICC, and the NICHD Program Office to identify important ethical issues so that the Working Group could tackle the issue and develop findings.

Other key ethical concerns for the Study include the following: the ethical implications associated with conducting a non-therapeutic study; definition of minimal risk and the risk associated with certain interventions; circumstances in which minor risk was permissible; what constituted minimal risk for a fetus; recruitment issues (e.g., how to approach underserved populations who had different perceptions of “health” and where disease comes from, pregnant adolescents, or people engaged in an illegal activity); the management of research results; whether or not clinically significant results would be communicated to subjects once a potential risk was identified, perhaps many years later; responding to findings and ameliorating the impact (e.g., child abuse); informed consent; and compensation, incentives, and reimbursement.

Dr. Botkin stated that the Working Group had proposed several pilot studies, which included conducting focused, expert interviews or holding a conference. The Working Group was also interested in IRB reviews and functions, and in the potential advantages of a central IRB for the study.

After the presentation, the following questions and comments were noted:

• Because ethical issues crosscut every aspect of the study, it was proposed that the Working Group be elevated to Ethical Oversight Committee status.
• The Working Group was also invited to provide comments regarding day-to-day management of the data.

F. Health Services

Neal Halfon, M.D., M.P.H., of the University of California at Los Angeles and William F. Lawrence, M.D., M.S., of the Agency for Healthcare Research and Quality noted that Study findings could play a major role in determining how the nation invests its health resources. The Working Group planned to recommend strategies for studying the impact of health care services on child health and development, how new knowledge generated by the Study would be incorporated into health care policy and practice, and how the Study would affect future health care services design. The Working Group was in the process of developing hypotheses, which focused on the epidemiology of health care, the impact of health care on outcomes, and the timing of interventions during critical periods of development. The Working Group planned to finalize its hypotheses by October 2002, but had not proposed any pilot studies.

The following questions and comments were noted:

• It was asked whether the Working Group was planning to study the actual health encounter or the quality of care delivered by the provider. Dr. Halfon responded that those issues had been studied extensively in recent years, so the Working Group had focused its efforts on other issues that had not benefited from extensive study.
• One member posed a question about the ethical issues associated with children who had medical conditions that were not being adequately treated. Dr. Halfon stated that, while the Study could not provide case management services, there could be an opportunity to study how systems ensured that children access appropriate care. When asked about the potential to study the impact of treatments themselves, Dr. Halfon responded that the issue could be studied via secondary hypotheses.

G. Immunity, Infections, and Vaccines

Robert Yolken, M.D., of the Johns Hopkins School of Medicine and William Rodriguez, M.D., Ph.D., of the U.S. Food and Drug Administration (FDA) explained that the Working Group had developed seven hypotheses focused on infectious and chronic disease, infections in pregnancy and early childhood, autism, early onset of depression and schizophrenia, asthma and viral infections, the impact of environmental exposures on autoimmunity, and immunity and genetic disease. It had also developed two hypotheses focused on vaccines and was contemplating another hypotheses on HIV infection. The Working Group had not yet identified a need for pilot studies.

They explained that the group was struggling with how to coordinate its activities with other Working Groups with shared areas of interest. The group was also concerned with Study sampling issues and whether or not the study would treat infections diagnosed in subjects.

The following comments and questions were noted:

• It was suggested that the Study was an intervention study by nature because participants would be treated differently than if they had not participated in the Study.
• When asked whether food allergies had been discussed, Dr. Yolken stated that few hypotheses dealt with food allergies, but that the group was receptive to examining other issues of interest to the NCSAC. When one member noted that oral health had not been mentioned at all thus far, a representative from the ICC responded that a group of investigators at CDC were reviewing a hypothesis proposal that focused on oral health.

XI. Adjournment of Day One

Dr. Mattison adjourned the first day of the NCSAC meeting at 5:41 p.m., and asked the NCSAC to reconvene the following morning at 8:30 a.m.

June 14, 2002

Call to Order of Day Two

Dr. Mattison reconvened the second day of the NCSAC meeting at 8:36 a.m. He stated that the first order of business was to complete the Working Group presentations.

II. Working Group Presentations Continued from Day One

• It was noted that the Study Design Working Group had established a format for submission of hypotheses, and that the NCSAC would be providing feedback on the screening and evaluation of hypotheses later in the day.
• Many NCSAC members praised the Working Group for the quality of its work and identified its proposal as a model for other Working Groups. It was suggested that the group develop a summary table at the end of its proposal to identify outcomes and key points of exposure. The Working Group was asked to provide additional guidance regarding the sample size needed to test the hypotheses.
• It was also suggested that the group examine other risk factors for asthma attacks (e.g., salt intake) and discuss health disparities in asthma based on geographic setting, race/ethnicity, and other factors to identify high-risk groups.
• One member commented on the value of having family behaviors reflected in hypotheses.
• It was noted that the group’s ideas regarding workshops had merit, and that perhaps the workshops could be combined to save time and promote efficiency. The meeting chair encouraged NCSAC members to state whether or not pilot studies, workshops, or other activities should be funded, so that the ICC could move forward with funding such projects.

B. Early Origins of Adult Health

Matthew Gillman, M.D., S.M., of the Harvard Medical School explained that the Working Group, formerly known as the Early Markers of Adult Disease Working Group, had established subgroups needed to develop hypotheses and conduct pilot studies.

Dr. Gillman indicated that the Working Group’s deliberations were guided by a life-course approach to chronic disease (e.g., considering the range of environmental, social, behavior, and biological exposures at the preconception, fetal, infant, child, and adolescent life stages); the dynamic relationship of these exposures across the life stages; critical exposure periods; and the potential for accumulation of risk. The group’s target conditions were those that occurred in adolescence or adulthood that had a high burden of disease or risk, and those that could be measured over time or had valid intermediate markers (e.g., obesity).

Dr. Gillman explained that the group had focused largely on two key hypotheses:1) The relationship between obesity and type 2 diabetes; and 2) The early origins of schizophrenia. These outcomes were selected because of the high rates of morbidity associated with the conditions, the long-term costs associated with them, and the rapidly increasing prevalence of these conditions in childhood and adolescence. In addition, Dr. Gillman stated that these hypotheses justified a large sample size and longitudinal examination. Other hypotheses developed by the Working Group were available on the Study portal. The Working Group also proposed a series of literature reviews and pilot studies.

Dr.Gillman asked the NCSAC to provide more guidance regarding the way in which the Working Group should collaborate with other Working Groups and how actual measurements associated with these hypotheses should be presented.

The following questions and comments were noted:

• It was asked how the group was looking at various transitions in childhood and certain outcomes, such as the relationship between early pubertal development and obesity, why the group selected schizophrenia as an outcome to study instead of depression, and what the differences might be between physical environments and chemical exposures. Dr. Gillman stated that the group was very interested in the physical environment and was willing to consider any issues proposed by the NCSAC. He added, however, that the group was limited by its expertise and focused its efforts on issues that it could address completely and expertly.
• One member expressed the benefit of looking at mental illness and suggested that the group might want to collaborate with the Immunity, Infections, and Vaccines Working Group. It was also asked whether the proposed pilot studies could be combined and what their comparative urgency was. Dr. Gillman said the prenatal and postnatal growth assessment study was the most urgent, followed by the pilot study on placental pathology. It was noted that all of the proposed pilot studies had merit, and the ICC was encouraged to coordinate them with other pilot study efforts.
• The group was encouraged to examine some outcomes (e.g., Alzheimer’s Disease, Parkinson’s, etc.) where far less was known about early exposures, very late onset of disease, and the early markers associated with these outcomes. Dr. Gillman replied that the group was willing to consider issues proposed by the NCSAC, and that several members were interested in issues related to aging.
• Members asked for more information regarding the power calculations and sample size necessary to test proposed hypotheses. The issue was also raised that some public health problems, particularly obesity, may decrease in incidence over time if public education efforts proved effective an issue that should be considered in calculating the power necessary to test hypotheses. Dr. Gillman noted that the group had developed power calculations for difference sample sizes, exposures, and outcomes.
• One member noted that, because some of the group’s hypotheses dealt with late-onset illnesses that would not occur during the 21-year Study period, it would be important to make a strong case for these hypotheses. Dr. Gillman explained that the Study would provide an opportunity to identify potential intermediate markers (e.g., bone density and later onset of osteoporosis).
• In response to Dr. Gillman’s request for more guidance on how measurements should be presented, one NCSAC member suggested that hypotheses be accompanied by a matrix of measurements and timing needs for each measurement, to help Study planners begin to conceptualize the level of burden imposed on the lives of subjects. The meeting chair added that some one at some point would have to look across all hypotheses and attempt to align the measurements.

C. Study Design

Nigel Paneth, M.D., M.P.H., of Michigan State University stated that core hypotheses should drive the power calculations and inform the Study design. He added that the Working Group had also developed criteria for evaluating proposed hypotheses.

Dr. Paneth noted that submitted hypotheses were in various stages of development. The Working Group’s primary concern was that none of the proposed hypotheses adequately justified a study of the expected size and scope. He encouraged the NCSAC to review the criteria so they could be distributed to the Working Groups and suggested that a pilot study be conducted to identify critical child health outcomes to be addressed in the study. He added that the group was anxious to provide feedback to other Working Groups regarding further refinement of proposed core hypotheses.

The following comments and questions were noted:

• One member asked for clarification regarding the two sets of criteria presented in the briefing book. Dr. Paneth indicated that one set of criteria focused on screening proposals, while the other was designed to provide a structure for ranking proposals that met the screening criteria. Similarities were noted in the two sets of criteria, and it was decided that what the group really needed was agreement from the NCSAC that some level of screening was necessary. Members expressed willingness to support the process. Dr. Paneth stated that all hypotheses, including those that did not pass the screening criteria, would be submitted to the NCSAC for consideration.
• It was proposed that the screening criteria place stronger emphasis on the feasibility of the proposed hypothesis. Dr. Paneth responded that there could be ways to promote economies of scale that would enable the Study to test as many hypotheses as possible.
• When asked if the group was tackling the issue of sampling, Dr. Paneth indicated that it had discussed the issue and received input from some of the other groups, but that the sampling strategy could not be crafted until the core hypotheses were identified. According to Dr. Paneth, a pilot study at the National Center for Health Statistics was exploring some basic assumptions regarding representativeness, generalizeability, and oversampling. He then restated the need to identify core hypotheses first and determine the sampling strategy.
• Dr. Paneth affirmed one member’s assumption that the proposed screening criteria applied only to core hypotheses. It was added that the group had discussed developing a scaling system that penalized proposals in which there was already significant evidence to support the hypotheses, and rewarded proposals where little was known (e.g., if there was only evidence from animal studies and not human studies).

D. Gene-Environment Interactions

Paula Yoon, Sc.D., M.P.H., of CDC explained that the Working Group viewed its role as collaborating with other groups and outlining key issues related to genetics that should be included in the Study. Key issues for the Working Group in terms of the Study design and implementation included: gathering data on the family triad (mother, father, and infant); specimen collection, processing, and long-term storage; perceptions of genetics issues among Study participants; informed consent and ethical issues, including reporting results to participants; impact of new advances in our understanding of genetics on statistical analyses and methods; changing technological capabilities and the implications for informed consent; the potential for the Study to evolve from a purely etiologic study to an intervention study as more evidence became available.

Dr. Yoon noted that new technologies could provide less-costly means for collecting genetic samples, and added that the biggest challenge for the group was integrating its activities with those underway in the other groups that focused on specific outcomes and exposures.

The following questions and comments were noted:

• Members recommended that the group collaborate with the Community Outreach and Communications Working Group to address issues related to public perception of genetics studies.
• One member identified a role for the group in determining the feasibility of hypotheses proposed by other Working Groups.
• One member raised the issue of childhood cancer and suggested that there may be creative ways to use the sample to study this public health concern. It was added that incorporating childhood cancer into the study design might help generate more support for the Study. Dr. Yoon noted that more studies were looking at various protein expressions and identifying early markers for childhood cancer. When it was suggested that the Study may be able to identify risk factors for the development of cancer, Dr. Yoon stated that the Working Group had started to look at the issue of family history and whether it may be possible to identify people at high or moderate risk for various outcomes.
• The NCSAC encouraged the group to share its ethical concerns with the Ethics Working Group.

E. Pregnancy and the Infant

Catherine Spong, M.D., of NICHD, Gary Hankins, M.D., of the University of Texas, and Marian Willinger, Ph.D., of NICHD stated that the group’s activities were closely related to those of other Working Groups and included identifying samples, tissues, and measures for pregnancy and infancy, once the core hypotheses were developed.

Dr. Spong presented two hypotheses that the group felt justified the sample size and drove the Study design: 1) Intra-uterine exposure; and 2) Stress and genetic susceptibility. Both hypotheses were designed to capture the impact of the social environment and the family unit. The Working Group had also proposed four pilot studies to assess the fetal environment, to define and quantify maternal stress, to identify methods for fetal and newborn assessment, and to examine environmental exposures beyond the usual suspects. Dr. Spong underscored the urgency of beginning these pilot studies as soon as possible, to inform the study design and help identify the specific samples that need to be collected. If possible, the Working Group proposed enrolling women preconceptionally.

The following questions and comments were noted:

• It was noted that pre-term birth and infant and fetal factors were important public health factors that must be incorporated into the study. When asked if the group had considered the potential impact of toxicants on birthweight and term of delivery, Dr. Spong indicated that such expertise was not represented on the Working Group, but that it may be possible to collaborate with other groups that offered such expertise. Dr. Spong added that the group had developed other hypotheses, which may not be core in nature.
• It was noted that “stress” was an ambiguous term, and that other groups might be considering the impact of stress at conception. Dr. Spong replied that the group did not know if it would be able to do a pilot study on the issue of stress, but that it planned to measure both maternal and child stress. She also stated that the group advocated enrolling women preconceptionally, and working with the Fertility and Social Environment Working Groups to determine how this could be done.
• One member cautioned that there was a great deal of literature to discourage looking at cultural groups from a deficit model, and added that it would be better to recognize that negative exposures and experiences such as stress could lead to resilience and other positive outcomes.

F. Fertility and Early Pregnancy

Germaine M. Buck, Ph.D., M.S., of the NICHD and Robert Chapin, Ph.D., of Pfizer Global Research and Development summarized the group’s charge and encouraged the NCSAC to consider both maternal and paternal exposures prior to, during, and shortly after conception.

They noted that the group was preparing a series of white papers to support its rationale, to address the feasibility and utility of prospective pregnancy studies for this avenue of research, to provide practical methodological and statistical strategies for analyzing parental exposures at critical windows of human reproduction and development, and to address effective ways to communicate with study participants and clinicians. The group was is contemplating three pilot studies.

Dr. Chapin indicated that the group promoted a broad definition of the term “exposure” so that the study could extend beyond the measures typically collected. He added that enrolling participants preconceptionally held serious implications for recruiting and retaining subjects.

The following questions and comments were noted:

• The NCSAC underscored the challenges associated with enrolling subjects preconceptionally, especially those from vulnerable populations, and suggested that a pilot study may be necessary to determine the feasibility of preconceptional enrollment. Dr. Buck countered that vulnerable populations were not more difficult to engage “a point that would be demonstrated in one of the group’s white papers” and added that Caucasian, middle-class women were typically overrepresented in studies, while little was known about women of other cultural backgrounds. Dr. Scheidt stated that the issue of preconceptional enrollment was still open for consideration. Dr. Buck noted that the group was looking at direct marketing strategies to potential subjects, rather than obtaining access to subjects via physicians.
• One member requested more discussion as to whether the entire cohort should be enrolled preconceptionally, or if this group could be a subset.
• One member suggested the potential for another study on non-pregnant women and why they fail to conceive, which would also present an opportunity to compare exposures between women who are, or are not trying to conceive.
• The NCSAC proposed including vitamins, the biochemical environment, soy products, and others in the broad definition of exposures and asked if the group had considered the potential exposures associated with assisted reproductive technologies. Dr. Buck indicated that there may be very subtle exposures associated with these technologies, but that there had never been the power available to answer such questions.
• It was noted that at least part of the cohort should be enrolled preconceptionally, and that there may be more than 1,200 twins in the cohort, which also presented a valuable research opportunity. The NCSAC suggested that there may also be an opportunity to conduct some analyses related to women’s health.
• One member expressed concern about the expanding units of observation in the Study and the potential cost associated with preconceptional enrollment. Dr. Buck stated that the study planners had a responsibility to answer questions that, to date, had not been answered, and that preconceptional enrollment offered the greatest opportunity to answer questions about what was harmful, what was harmless, and what was helpful. The member cautioned the group regarding the enormous cost of tracking women who may or may not conceive. Dr. Chapin responded that the only way to assess exposure windows that were critical to fertility was to enroll women preconceptionally.

G. Development and Behavior

Jay H. Giedd, M.D., of the National Institute of Mental Health indicated that the Working Group was attempting to tackle a range of issues, including what is meant by the terms “development" and "behavior,” the levels to target for outcome measures, the potential for generalizability later in the study, and the feasibility of examining these issues. Dr. Giedd noted that existing instruments were not useful because they we unable to predict outcomes. He added that the group hoped to focus on the very early years of development, with the first round of assessments possibly linked to well-baby checks.

Dr. Giedd stated that the group was considering looking at behavioral disorders such as attention deficit/hyperactivity disorder (ADHD) and autism, and that the proposed sample size was particularly conducive to studying autism. Another potential area of study was schizophrenia and how the brain develops and prunes itself. The group was struggling with the challenge of what to measure, how to measure it, and how often to measure it.

The following questions and comments were noted:

• One member noted the ongoing controversy surrounding ADHD and the validity of the diagnosis. Dr. Giedd stated that no laboratory test exists that can diagnose ADHD, and that the validity of current questionnaires was questionable. He added that the NCS might shed new light on ADHD and more accurate procedures for diagnosis.
• When asked about other psychiatric disorders, such as bipolar disorder and schizophrenia, Dr. Giedd stated that the Study presented an opportunity to examine the full range of childhood psychiatric disorders. He added that the group needed more guidance, perhaps via a pilot study, on assessment measures in very young children.
• It was noted that there were some well-validated screening constructs that may aid the group in its deliberations. When asked how much time would be needed with each child, Dr. Giedd replied that the group felt 1.5 to 2 hours during a well-baby check would probably be sufficient.
• One member stated that many people would expect to see the Study address the impact of maternal thyroid and chemical interaction on brain development. Other areas of potential study could include cerebral palsy, and possible protective factors and benefits associated with ADHD that could help young people with the disorder succeed. The NCSAC also encouraged the group to examine the potential use of scanning technologies for assessment purposes.
• It was suggested that the group examine measures in the home instead of in clinical settings to assess development and behavior, and to examine cross-cultural validity (e.g., do kids get different signals depending on the location of the interview), as well as how urban youngsters were constantly aroused by noise and compare the findings to rural youth.

H. Birth Defects

Dave Erickson, D.D.S., Ph.D., M.P.H., of CDC explained that the Working Group, which was focused on birth defects and congenital malformations, also wanted to recruit subjects prior to conception. Dr. Erickson summarized a current study in China that was recruiting more than 50,000 women prior to conception and following them over time.

He added that the group was working on three hypotheses related to:1) Impaired glucose metabolism; 2) Alcohol consumption during pregnancy; and 3) Relationship between environmental exposures, endocrine disrupters, and abnormal sexual development, especially in males. The group proposed convening a workshop to develop a standardized instrument for assessment of newborns during the neonatal period.

The following questions and comments were noted:

• One member expressed concern that there were no measures for endocrine function in humans, asked which birth defects would be studied, and inquired whether the sample size would be large enough.
• When asked how alcohol consumption could be measured before a woman knows she is pregnant, Dr. Erickson replied that the group had not yet gotten to that point, but that damage could occur throughout pregnancy, and that there were signs that consumption in early pregnancy affected cognitive development.

I. Repository

Barbara J. Potter of the U.S. Department of Commerce described they key issues related to establishing a repository of the magnitude required for the Study, including developing standard operating procedures for the repository and data systems management; long-term storage of specimens; and the physical requirements of the repository. The group distributed a questionnaire to the other groups to assess their sample and storage requirement, but had received no responses.

The group anticipated that anywhere from 1-to-10 billion samples would be stored in the repository. The cost associated with storing these samples in about 24,000 freezers would be approximately $432 million (not including tubes, jars, nitrogen, or other supplies for sample collection).

Ms. Potter described the challenges associated with long-term and short-term specimen archival and noted that decisions would have to be made regarding standard operating procedures for collecting samples, adding preservatives to samples, strategies to reduce costs, and other key issues. The group sought guidance from the NCSAC regarding future directions.

The following questions and comments were noted.

• When asked if it would make more sense to buy a permanent facility or building that already had much of the necessary equipment, the group stated that there were private sector resources to help address those issues.
• It was suggested that the Study fund a pilot study to get input from the private sector on how to design such a science construction project.
• When asked if the maintenance of non-physical data fell under the jurisdiction of this group, Ms. Potter stated the repository would only store physical samples, but that there would be a high-level of data integration.

J. Nutrition, Growth, and Pubertal Development

It was reported that a federal co-chair had only recently been named to the Nutrition, Growth, and Pubertal Development Working Group, and that the individual was working on assembling the group’s membership. No one from the Working Group was present at the meeting.

K. Medicine and Pharmaceuticals

Sandra Kweder, M.D., of FDA stated that the role of the group was to identify measures for hypotheses, to anticipate new hypotheses, and to examine the role of medicine and pharmaceuticals (including over-the-counter medications) that may influence growth and development. Dr. Kweder noted that the Study presented an opportunity to determine the safety of certain medications, such as the currently unregulated St. John’s Wort.

Other issues to be addressed by this group included determining the role of the maternal medical history in the outcome (e.g., antiepileptic drugs), determining the most beneficial people to conduct interviews with women, and developing methods for ascertaining exposures to alcohol and substances of abuse. Another important issue was whether drugs in foods to which children were exposed in utero (e.g., caffeine) would be included in the Study and how.

The following questions and comments were noted:

• Dr. Scheidt stated that the issue of illicit drug and alcohol exposure would be addressed by the Behavior and Development Working Group.
• One member asked about the work of the Office of Nutritional Products, Labeling, and Dietary Supplements at FDA, and whether there was new information coming that may inform the Study design. Dr. Keweder explained that the Office was working on voluntary standards, but that official regulations were years away.
• It was noted that questioning women about alcohol or drug use, or potential situations of abuse, raised serious ethical concerns. Another concern was that very little is known about drug exposure during pregnancy, and that the Study could fill knowledge gaps regarding which drugs were safe and which were not.
• Members asked what the Study’s role should be in informing subjects when certain substances were found to put women or children at risk, suggested that metabolism changes during pregnancy be included, and added that the group should develop measures to assess dosing and how it varies.
• It was suggested that the group include methodologists in its proposed workshop.
• It was also suggested that the group suggest how often pharmaceutical use should be measured.

L. Injury

Ruth Brenner, M.D., M.P.H., of NICHD explained that injuries were the leading cause of death in the first year of life, and that for each death, there were 50 injuries serious enough to require hospitalization. She added that many injuries result in life-long physical and cognitive impairments. She noted that the group had expanded its expertise to include child abuse and neglect.

The Working Group had developed five hypotheses that could only be examined longitudinally, and that required a sample size of 100,000 subjects. It also worked to identify exposures during the first five years of life and planned to develop adolescent-focused hypotheses at a later time. Dr. Brenner noted that the group needed guidance regarding next steps in hypothesis refinement and submission. The group also proposed a number of pilot studies.

The following questions and comments were noted:

• When asked if the group had considered the potential impact of falls and injuries during pregnancy, Dr. Brenner stated that another group had agreed to develop that hypothesis.
• Members were pleased that the group was addressing child abuse and neglect issues, noted that the Study would be required to report incidents of abuse and neglect to the proper authorities, and added that it would be necessary to determine how that would affect the data. It was also suggested that the group address the persistent public health challenge of teen suicide.
• Members noted that it would have to be determined what constituted child abuse and neglect, and that there was a role for the group in helping the NCSAC better understand this issue and its impact on Study implementation. Another issue for exploration was parental behaviors, how they affect child behavior and growth, and how to measure those behaviors.
• Regarding known predictors for injury, it was suggested that the Study intervene whenever possible, to keep children as healthy as possible, and to observe the outcomes, as this approach would represent an added value to participants. Dr. Brenner added that it might also be possible to do some randomizing to see if behaviors change after an intervention (e.g., giving participants a helmet and observing future use).
• One member indicated that the ICC proposed a pilot study on parental reporting, while the Injury Working Group proposed pilot studies on other issues, such as neighborhood characteristics. Dr. Brenner stated that having a better definition of injuries would be a valuable asset to the injury field.
• When asked if the NCSAC was in favor of funding the pilot study on parental reporting of injuries, members indicated they were comfortable with moving forward with that pilot study.
• The meeting chair noted that the NICHD was trying to locate resources for staff support for the Working Groups and the NCSAC.

M. Physical Environment

Dr. Scheidt stated that this Working Group had not yet been formed because of the range of activities underway, and because the group simply did not materialize as quickly as others did. He noted that the group was to examine issues including sun exposure, electromagnetic radiation, ultrasound in utero, heat, and the built environment. Dr. Scheidt stated that NICHD and the ICC both felt these issues were important to include in the Study, but asked for the NCSAC’s advice on inclusion. Several NCSAC members stated that the group was critical to the study and identified several experts to serve on its membership, while others expressed concern about creating another Working Group. Dr. Scheidt agreed to continue to try to establish the Working Group.

III. The NCSAC Meeting Schedule

Dr. Mattison presented the NCSAC meeting schedule through 2004:

• September 12-13, 2002 (Study Assembly, with Working Group chairs attending)
• March 6-7, 2003 (with Working Group chairs attending)
• June 5-6, 2003
• September 15-17, 2003 (Study Assembly, with Working Group chairs attending)
• December 11-12, 2003
• March 4-5, 2004 (with Working Group chairs attending)
• June 28-29, 2004
• September 27-29, 2004 (Study Assembly, with Working Group chairs)
• December 9-10, 2004

He added that each meeting would be approximately 1.5 days in length and agreed to send the upcoming meeting schedule to the NCSAC members via e-mail.

IV.Closing Discussion

Dr. Mattison noted that the meeting no longer had the quorum needed for decision-making. The remaining NCSAC members offered final comments:

• The need for more interaction between and among the Working Groups was underscored. One member suggested creating core hypotheses groups that would attract the appropriate membership from the Working Groups for the purpose of creating more robust hypotheses, noting that the Study did not want to lose the intellectual power represented in the Working Groups, but that it was not wise to proceed with five uncoordinated hypotheses on asthma. It was suggested that the next step was to focus on particular issues such as asthma, mental health, diabetes, the impact of maternal and child stress, and other key issues, and to refine hypotheses associated with those outcomes.
• The issue of preconceptional recruitment was raised, and NCSAC members were asked to comment on the matter. The NCSAC members stated that the approach offered benefits, but that there were persistent questions about the feasibility of the approach, whether or not it would answer critically important questions, and whether or not it could demonstrate scientific worth. One member suggested that a tentative list of core hypotheses be assembled as soon as possible so that groups could conduct feasibility analyses. It was noted that a great deal of overlap across hypothesis proposals existed, and that the groups needed to realize the degree of overlap.
• It was noted that, while some core hypotheses might require a sample size of 100,000, other core hypotheses may not require such a large sample. It was also noted that the Study data would be a valuable resource for future investigators.
• Members expressed concern that there was no process in place for providing the feedback that the Working Groups were requesting. The meeting chair noted that all NCSAC meetings were held in a public forum or in open conference calls, but that the NCSAC was free to deliberate in small groups to develop materials and information for presentation at a public NCSAC meeting.
• The NCSAC reviewed the small groups established to work on specific issues until the next meeting.
• Several members expressed the urgent need for the Study to move forward in reviewing hypotheses and pilot studies, and in providing feedback to the Working Groups within the next few weeks. It was suggested that the ICC could carry out much of the work, and then ask the NCSAC to make formal recommendations during the next meeting.
• It was decided that the NCSAC would thank Working Group chairs for their presentations via letters. It was also suggested that a letter of appreciation be drafted and distributed to the Working Group members.

V. Adjournment

Dr. Mattison thanked the NCSAC members for their work, persistence, and contribution to the Study. He adjourned the meeting at 3:16 p.m.

I hereby certify that, to the best of my knowledge, the foregoing minutes are accurate and complete.

August 15, 2002   Date

Donald Mattison, M.D. Chairperson National Children’s Study Federal Advisory Committee

Appendix A

NCSAC Members Present

Donald R. Mattison, M.D., Chair Peter Scheidt, M.D., Executive Secretary David C. Bellinger, Ph.D. Willa M. Doswell, R.N., Ph.D. Alan R. Fleischman, M.D. Lynn Goldman, M.D. Judith A. Graham, Ph.D.,

Shiriki Kumanyika, Ph.D., M.P.H. Grace LeMasters, Ph.D. Roderick J. Little, Ph.D. Robert T. Michael, Ph.D. Lucina Suarez, Ph.D. Daniel J. Swartz

Interagency Coordinating Committee Members Present

Amy Branum, M.S.P.H. Adolfo Correa, M.D., Ph.D., M.P.H. Sarah A. Keim, M.A. Woodie Kessel, M.D., M.P.H. Carole Kimmel, Ph.D.

Mark Klebanoff, M.D., M.P.H. Pauline, Mendola, Ph.D. Kenneth C. Schoendorf, M.D., M.P.H. Sherry G. Selevan, Ph.D. Marshalyn Yeargin-Allsopp, M.D.

 

Working Group Chairs Present

Christine Bachrach, Ph.D., Social Environment Working Group
Jeffrey R. Botkin, M.D., M.P.H., Ethics Working Group
Ruth Brenner, M.D., M.P.H., Injury Working Group
Germaine M. Buck, Ph.D., M.S., Fertility and Early Pregnancy Working Group
Robert Chapin, Ph.D., Fertility and Early Pregnancy Working Group
Diane Dennis-Flagler, M.P.H., Community Outreach and Communications Working Group
David Erickson, D.D.S., Ph.D., Birth Defects Working Group
Jay N. Giedd, M.D., Development and Behavior Working Group
Matthew Gillman, M.D., S.M., Early Origins of Adult Health Working Group
Neal Halfon, M.D., M.P.H., Health Services Working Group
Gary Hankins, M.D., Pregnancy and the Infant Working Group
Sandra Kweder, M.D., Medicine and Pharmaceuticals Working Group
William F. Lawrence, M.D., M.S., Health Services Working Group
Charles Lee, Health Disparities and Environmental Justice Working Group
Larry Needham, Ph.D., Exposures to Chemical Agents Working Group
Haluk Ozkaynak, Ph.D., M.S., Exposures to Chemical Agents Working Group
Nigel Paneth, M.D., M.P.H., Study Design Working Group
Barbara J. Porter, Repository Working Group
William Rodriguez, M.D., Ph.D., Immunity, Infections and Vaccines Working Group
Catherine Spong, M.D., Pregnancy and the Infant Working Group
Diane Wagener, Ph.D., Ethics Working Group
Rueben Warren, D.D.S., Dr.P.H., M.P.H., Health Disparities and Environmental Justice Working Group
Mary White, Sc.D., Asthma Working Group
Marian Willinger, Ph.D., Pregnancy and the Infant Working Group
Robert Yolken, M.D., Immunity, Infections, and Vaccines Working Group
Paula Yoon, Sc.D., M.P.H., Gene-Environment Interaction Working Group

Others Present

Elizabeth Adam Arthor Bennett Jon Courtney Denise Dougherty George Gaines Lisa Kaeser Jeanellen Kallevang Fred Ledley Pamela Moore

Sherri L. Park Emeralda Pereira Christina Poirier Mary Plummer Lucina Suarez Eleanor Smith-Khuri Charles WellAl Wigmore