National Children’s Study
Federal Advisory Committee (NCSAC) Meeting
September 14–16, 2003
Holiday Inn Select
Bethesda, MD

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).

Sunday, September 14: Dinner Meeting
Review of Upcoming NCSAC Meeting

Donald R. Mattison, M.D., NCSAC Chair
National Institute of Child Health and Human Development (NICHD), NIH, DHHS

Opening Remarks
Dr. Mattison convened the Sunday dinner meeting of the National Children’s Study Advisory Committee (NCSAC) and made the following remarks:

• Important activities at the upcoming NCSAC meeting will relate to providing feedback to the Working Groups, the prioritization of exposures, and establishment of the timing of measurements.

• NCSAC liaisons were assigned to Working Groups whose tasks aligned with the expertise of the NCSAC member. NCSAC liaisons will confer with Working Groups via telephone.

• There may be gaps in hypotheses and/or thematic areas, and NCSAC members should remain alert to such possibilities while reviewing materials.

• To enhance communication between the Advisory Committee and adhere to Federal legal and ethics officials guidelines for Federal Advisory Committees, Advisory Committee members will be assigned liaison roles with individual working groups. have concluded that the Working Groups will not continue to function as they have been functioning and that the NCSAC had to interpose itself between the Working Groups and the ICC.

Committee Discussion

Following Dr. Mattison’s introductory remarks, NCSAC members raised additional issues for discussion:

• Barry Ryan, Ph.D., Emory University Rollins School of Public Health, said that he had been on several conference calls with the Working Group for which he served as liaison, and that he had encouraging feedback.

• Grace LeMasters, Ph.D., University of Cincinnati College of Medicine, asked if expectations of the NCSAC liaisons would be delineated during the general NCSAC meeting. Dr. Mattison noted that the liaisons should think through the critiques during the thematic breakout sessions and make sure that the structure of the thematic session would allow the work of the Working Group to "make sense."

• Judith Graham, Ph.D., American Chemistry Council, stated that her group had formulated an interesting hypothesis, but that it probably was more appropriate for another Working Group. Dr. Mattison responded that thematic groups of the NCSAC would reconvene in order to review work products and coordination of efforts. Jan L. Leahey, NICHD, NIH, DHHS, added that the liaisons would have to mesh their efforts so as to provide Working Groups with a clearer task. Dr. Graham asked how the ICC hypotheses interface with Working Group hypotheses. Dr. Mattison replied that such work would have to go back to Working Groups for resolution.

• Barry Zuckerman, M.D., Boston University School of Medicine, said that physical exposures tend to interact with social exposures and asked how this would be dealt with in the National Children’s Study (the Study). Dr. Mattison noted that the Working Groups and the NCSAC would consult to determine how to control for this dynamic.

• Willa Doswell, Ph.D., R.N., F.A.A.N., University of Pittsburgh School of Nursing, asked if the Study Program Office was tracking current literature to evaluate whether Study hypotheses are being duplicated by other efforts. Peter C. Scheidt, M.D., M.P.H., Study Director and ICC member, NICHD, NIH, DHHS, noted that there are no studies currently underway that duplicate the scale of the Study, despite the possibility of overlapping intent.

• Roderick Joseph A. Little, Ph.D., University of Michigan School of Public Health, asked if the NCSAC was becoming bogged down in hypotheses, stating that the more important issue may be that of the design of the Study and related measurements. Dr. Mattison replied that the December 2002 NCSAC meeting included a review of the timing of measurements, for instance. Dr. Graham expressed the hope that the following two days would lead the Study to a more concrete direction regarding Study design. Dr. Doswell was concerned about subject burden. Dr. Graham commented that until specifics are laid out, it is difficult to evaluate subject burden.

• Lucina Suarez, Ph.D., Texas Department of Health, asked if the NCSAC would establish a set of core hypotheses. Dr. Mattison commented that the Study would involve a series of measures that will have to answer questions that the public wants answered.

• Dr. Scheidt commented that work on design was underway, and associated cost estimates were being generated. He stated that as hypotheses take shape, the demands of the correlating measurements would be grafted onto the framework of the Study. Dr. Scheidt also noted that the ICC has generated a measurements database that will allow ongoing adjustments to the Study, and he stated that the economic burden of many analyses is thought to be more imposing than subject burden.

• Dr. Doswell asked if some hypotheses/measurements would be ruled out if the cost of sampling were too high. Dr. Little said the emphasis should be on core elements. Dr. Scheidt stated that managing the volume of potential hypotheses could prove very burdensome and that it may not be necessary to explicitly hypothesis if the data are already included in the Study.

• Loretta Jones, M.A., Healthy African American Families, commented that she was not confident that many communities would buy into the Study, given the perception that the Study is something that is happening to the community rather than something in which the community is an active participant. Dr. Mattison said that NCSAC members would need to think about study design and community participation/outreach. Dr. Doswell commented that it might be too late to obtain the interest of some groups. The most effective research involves the input of the population that will be recruited. Dr. Graham stated that the Study Assembly should try to draw in those from various communities at the Study Assembly so as to elicit their expertise in dealing with such considerations.

• Dr. LeMasters noted that the notion of community was rather vague and difficult to conceptualize. Yet, as Dr. Doswell pointed out, it is important for the Study to be aware of the mindset of the various communities, because they may each react differently to an element of the Study, such as a particular means of measurement.

• Dr. Suarez asked if the Working Groups should see the Study framework as it stands. Dr. Scheidt replied that this was feasible, but that the mindset was that hypotheses should drive the Study. He stated that the Program Office had to attempt to project costs, but it was important to avoid influencing hypothesis development with cost information.

• Dr. Zuckerman asked if some of the hypotheses had been included as a way to justify the Study. Dr. Scheidt replied that setting up a group of measures without correlating hypotheses was difficult to justify. Dr. Zuckerman stated that the Study would need more than merely 20 hypotheses to get funding.

• Dr. Graham stated that a study could generate data sets that will answer hypotheses that are not necessarily fully formed. Dr. Mattison noted that much of what the Study seeks to examine might not find remedy during the course of the Study. Dr. Zuckerman offered that one of the strengths of the Study is that the size of the cohort will provide substantial data on subgroups.

• In commenting on the issue of cost versus burden, Dr. Scheidt pointed out that some measures were not competitive in terms of burden (for example, sample storage over a period of decades). While these types of measures would not present any subject burden, nonetheless they would be expensive.

• Ms. Jones stated that a continued failure to bring "community" into the Study might compromise funding. Dr. Mattison commented that the Community Outreach and Communication Working Group is trying to deal with this issue. Dr. Doswell noted that in the case of dispersed communities, a series of focus groups might yield insights that would enhance the design of a study.

• Dr. Scheidt stated that the specific communities that will host the Study are not yet determined, and that prior to such determination, the protocol will have to be designed on the basis of a national set of characteristics. Ms. Jones made the case that the scientific community needs to revamp its perspective on how to interact with the population at large, because a substantial number of community-based studies are winning internal review board (IRB) approval. Dr. Scheidt stated that the center contracts would mandate community interaction.

• Certain participants expressed concern about the lack of suggestions for specific action. Donald J. Dudley, M.D., University of Texas Health Science Center at San Antonio, commented that the Community Outreach and Communication Working Group had produced papers on this issue.

• Dr. Little asked whether the Study could provide communities with a broad description of the Study to obtain feedback. Dr. Mattison noted that a researcher was examining health disparities in Michigan and that some of the structure of this project may be helpful. He also stated that the NCSAC needs an update from the Community Outreach and Communication Working Group.

Conclusions/Recommendations

• The National Children’s Study should try to engage representatives from various communities at the Study Assembly.

• In the case of dispersed communities, a series of focus groups might yield insights that could enhance the Study design.

• The NCSAC should request an update from the Community Outreach and Communications Working Group.

Monday, September 15

Welcome
Review Meeting Goals, Agenda, and Action Items

Donald R. Mattison, M.D., NCSAC Chair
NICHD, NIH, DHHS

Dr. Mattison welcomed National Children’s Study Advisory Committee (NCSAC) members to the first of the two-day session. He briefly reviewed the background of the development and evaluation of hypotheses for the Study to date, pointing out that this would be the first time that the NCSAC would be seeing all 70 hypotheses. Dr. Mattison covered several agenda items:

• Introductions.Dr. Mattison asked the NCSAC members and others present to introduce themselves.

• Review and Comments on Minutes from Last Meeting. There were no comments on the minutes of the last meeting.

• Review of Agenda and Modifications, Discussion of Meeting Objectives. Dr. Mattison briefly reviewed the meeting objectives—to review thematic areas and hypotheses so that NCSAC members could provide explicit feedback to the Working Groups for which they are liaisons.

• Review of Action Items. Dr. Mattison pointed out the action items that were identified in the previous NCSAC meeting, noting that these could be discussed later in the meeting if necessary.

Update by Program Office
Study Timelines and Protocol Development

Peter C. Scheidt, M.D., M.P.H., ICC Member, National Children’s Study Director
NICHD, NIH, DHHS

Dr. Scheidt summarized major events and activities since the last NCSAC meeting:

• Staff recruitment and introductions. Warren Galke, Ph.D., NICHD, NIH, DHHS, will work on pilot studies, and Marion Balsam, M.D., NICHD, NIH, DHHS, will focus on developing partnerships. New full-time staff to be added over the next four to six months will include a pediatric epidemiologist, who will lead the protocol development team; behavioral scientists; a scientist to lead the effort of developing and procuring the data management and clinical coordinating center; and a project officer to develop the first data collection centers for the Study.

  In addition to these full-time staff, several part-time or detailed scientists are participating in the Program Office, including:

  – Kenneth Schoendorf, M.D., Ph.D., National Center for Health Statistics (NCHS), CDC, who is working on protocol development and hypotheses
  – Carole Kimmel, Ph.D., EPA, who is working on pilot studies
  – Lester R. (Randy) Curtin, Ph.D., NCHS, CDC, a biostatistician
  – James Quackenboss, M.S., EPA.

  In February 2004, Terry Dwyer, M.P.H., M.D., University of Tasmania, a senior epidemiologist from Australia, will join the Study for a sabbatical year as a visiting scientist. Negotiations are underway to involve ethicists from two universities by IPA on a part-time basis in developing the consent and human subjects portions of the protocol and related projects. Also, there are plans to involve a part-time geneticist from the Human Genome Project.

  Additional Study staff members include Rebecca Brown, a full-time fellow with the EPA, who will work on the measures and database management; Adelaide Barnes, a research fellow; and Maryam Naser, who will assist Beth Davis in the Program Office.

• Support Contracts. A technical support contract was recently awarded to Battelle, with Warren Strauss, Sc.M., as Project Director. Battelle will assist with literature reviews, technical analyses, white papers, developing scientific reports from workshops and surveys of researchers, and similar efforts.

  Another contract mechanism is available through EPA’s contract with RTI. The Study also has ongoing contracts with Circle Solutions, Inc., for logistical support, and with the partnership of IQ Solutions and Ogilvy for communications support.

• Measures Database. Dr. Scheidt reviewed progress with the measures database developed by the ICC that Dr. Schoendorf introduced to the NCSAC at the June meeting. The records have been integrated and consolidated across the hypotheses to form a unified database. Next steps include focusing on the requirements at each interval; identifying in detail the conflicts and problems with each interval and with each measure with regard to subject burden, cost, and feasibility; filling in gaps; adding measures needed to address updated and current hypotheses; and ultimately to prepare a first draft protocol.
  
  
• Funding Status. Dr. Scheidt discussed Study funding. By the end of the current fiscal year, the Study will have committed and spent $20.7 million since the first initial planning in 2000. An estimated $26 million will be needed in 2004 to enroll the first subjects by the end of 2005. Currently, $12 million from all of the lead funding agencies is included in the president's budget. Neither appropriations bill covering the lead agencies has been signed. The figure for total implementation over 25 years (unadjusted for inflation) still remains at $2.7 billion.
  
  
• Study Assembly Meeting. Dr. Scheidt said that the Study Assembly meeting is planned for December 15–17, 2003, in Atlanta. The NCSAC is scheduled to meet December 15–16. The Working Groups may meet, depending on NCSAC deliberations and plans. The full Assembly will meet on December 17. An ICC committee is planning the meeting agenda. Study Assembly goals are to communicate the status and progress of the Study to the broad membership of the Assembly, to advance community engagement and support for the Study, and to obtain input from Assembly members regarding the hypotheses and needs of the various communities interested in the Study. Speakers for the Study Assembly will include U.S. Surgeon General Richard H. Carmona, M.D., M.P.H., F.A.C.S., and Julie L. Gerberding, M.D., M.P.H., Director, CDC. Breakout groups and poster sessions also will be included during the meeting.

Questions and Comments for Dr. Scheidt

• Dr. Graham asked about the absence of a quality assurance (QA) expert. She also commented about the measures database and asked whether it might be possible to develop a similar database for the questionnaire. Dr. Scheidt responded that the questionnaire is part of the database. Regarding a QA expert, Dr. Scheidt said that all staff are responsible for quality assurance; however, QA capability will be particularly important for the manuals and details of how to implement the protocol. Dr. Graham stressed that early involvement of QA experts is important, and she suggested that the Study get the advice of federal QA experts with regard to timing.

• Dr. LeMasters asked about the timeline for protocol development. Dr. Scheidt replied that the timeline calls for a preliminary first draft of the protocol by December, with a final protocol by summer 2004. Difficulties and delays in recruiting and hiring full-time staff might cause some slippage of that timeline. However, the hope is to be able to share with the NCSAC and others a preliminary outline or draft of a protocol as close as possible to the December timeline. Because of the necessity for openness, the draft will probably be made available on the Web page as well, for access by the interested scientific community can see what is evolving.

• David C. Bellinger, Ph.D., M.Sc., Harvard Medical School, asked about prospects for reducing the $14 million shortfall in fiscal year 2004, the impact of the shortfall on when subjects will be recruited, and whether there was a contingency plan. Dr. Scheidt replied that the Study was not optimistic about seeing additional appropriations in 2004, and the shortfall would likely delay recruitment until 2006. If funds for 2005 are sufficient to begin the implementation process, it could mean a delay of three or six months, but not necessarily an entire year.

Conclusions/Recommendations

• The Study should solicit advice from federal QA experts with regard to timing.

Report on Pilots and Workshops

Carole Kimmel, Ph.D., ICC Member, National Center for Environmental Assessment, EPA

• Dr. Kimmel presented an overview of the pilot/methods development studies, reviews, white papers, and workshops that had been completed or were being planned as of early September. She discussed sources of proposals, the review and approval process, the tracking and review process, and mechanisms for conducting pilot studies, workshops, and papers for the Study.

• Pilot and methods development studies completed to date include the Lewin report, the Westat report, a biomarkers database project, a review of new and emerging technology applicable to the Study, and a study of methods for eliciting community involvement, subject recruitment, and retention.

• Ongoing pilot studies include exposure and methods development studies, such as efforts to develop low-cost, low-burden exposure monitoring strategies and time-integrated exposure measures. A variety of health-related projects are underway, many of which are also methods development studies.

• Numerous reviews and white papers are in development, such as measures available for evaluating health status, emotional and social functioning, and mental development and cognition; successful cohort retention; measuring housing qualities and characteristics; and looking at dietary intakes and patterns in women and young children.

• Workshops that have been held have addressed community engagement, fetal and neonatal growth and development assessment methods, medications, innovative technologies for remote collection of data, ethics, and mild traumatic brain injury. Additional workshops are planned for the next few months, including workshops on placental measures, psychosocial stress and pregnancy and the infant, physical activity both during pregnancy and in children at different ages, sampling design, the effects of the media on children’s health, among others.

Questions and Comments for Dr. Kimmel

• Dr. Doswell asked about the rationale behind having a workshop on the effects of the media on children’s health. Dr. Kimmel referred the question to Christine Bachrach, Ph.D., NICHD, NIH, DHHS, who replied that this is an area that the Social Environment Working Group addressed because of the importance of media exposure in issues such as obesity, physical activity, and possibly even neurodevelopment.

• M. Anne Spence, Ph.D., University of California, Irvine, also asked Dr. Bachrach about the purpose of the media workshop. Dr. Bachrach responded that the workshop would pull together the key hypotheses in this area and recommend measures.

• There was a question from a participant concerning measures of preconception exposures. Dr. Kimmel said that was certainly an area of interest for the Study. The participant further commented that it seemed clear that the Study would be measuring prenatal and postnatal drug exposures, but not it was not clear that intrapartum exposures would be addressed. Dr. Kimmel replied that the Study was interested in such exposures.

Update of "Sampling" Strategies

James J. Quackenboss, M.S., ICC Member, Office of Research and Development, EPA

After a brief introduction by Dr. Mattison, Mr. Quackenboss summarized the activities of the Sampling Design Workshop Committee, which was formed after a proposal for the committee was approved at the June NCSAC meeting.

• The committee had its first conference calls in July and its first in-person meeting in mid-August. Committee members have been working to determine and provide information that will be needed for the workshop and to determine the workshop format.

• The committee is identifying and commissioning a number of background white papers for the workshop.

• The committee is identifying specific requirements for sampling design options to help guide the contractor, Battelle. These requirements include what is referred to as the "givens" that were discussed at the NCSAC March meeting. The "givens" are a set of key features of the Study as agreed on by Study planners.

• There are some key issues for the Study (such as recruitment and retention, measurement needs, and subject burden) that must be addressed in any design.

• The committee wants to ensure that a broad range of sampling design options are considered, from a pure household probability-type design to a more purposive-type selection of the sample, and that the pros and cons of these designs and their strengths and weaknesses relative to the Study are fully considered.

• The committee has agreed that the workshop format will be based on the NIH consensus conference model. Some key components of this model are that the science and the literature are able to help support an informed decision and that a panel of unbiased experts with relevant expertise in different areas meets to look at the evidence and reach consensus based on that evidence. The result of the workshop would be a recommendation to the Study planners (ICC, Study Program Office, and NCSAC) for the sampling designs and/or the features of designs that should be pilot tested.

• The committee is also developing criteria for selecting workshop panel members, panel chair, and speakers. The panel chair will be involved in finalizing the format, timing, location, and other details of the workshop.

• The timeframe for the workshop is most likely January or February 2004. Background papers might be completed in November.

Questions and Comments for Mr. Quackenboss

• Dr. LeMasters asked to what extent information from prior studies, reviews, and white papers is being incorporated into the workshop and whether the workshop might not be redundant. Mr. Quackenboss assured Dr. LeMasters that previous related work would be made available to contractors developing background papers and to the workshop panel.

• Dr. Little commented about clarifying the pros and cons of probability sampling. He stated that he would like to see the committee move on to addressing a feasible design that meets the measurement objectives of the Study within the framework of a probability-based sampling design. Mr. Quackenboss responded that the charge to the panel would be along those lines.

• Dr. Spence urged that there would be a complete open-mindedness about the selection of the experts to present at the consensus conference.

• Dr. Little commented that the panel would need to have information about the specific measures that are being considered and discussed in the various workshops and Working Groups.

• Dr. Scheidt responded to the above comments by saying that from his perspective as a member of the committee, that the most important aspects of this process are open and balanced deliberation and bringing as much fact as possible to the deliberation. The committee views the consensus-type conference as a means to that deliberation and has specified open-mindedness as a criterion for membership in the workshop panel. However, while the panel will make a recommendation based on a fair and balanced processing of as much information as possible, the final decision about the sampling design will be based on input from the NCSAC to the ICC and to the Institute Director.

Update by Injury Working Group

Barry Zuckerman, M.D., NCSAC Member, Boston University School of Medicine
John Lutzker, Ph.D., National Center for Injury Prevention and Control, CDC

• Dr. Mattison introduced Dr. Zuckerman, the NCSAC liaison for the Injury Working Group. Dr. Zuckerman spoke about the significance of injuries in children and said that the Study’s large cohort presents an opportunity to obtain data that can inform injury prevention interventions.

• Dr. Zuckerman introduced Dr. Lutzker, who presented statistical information about childhood injuries, including data on deaths and disability due to injuries, unintentional versus intentional injuries, child maltreatment, and youth violence and suicide. Dr. Lutzker said that injuries are considered predictable and preventable events. He described a model for analyzing the risk factors that contribute to childhood injuries and protective factors as well. He also discussed the link between child maltreatment and youth violence and suicide.

• Dr. Lutzker introduced Ruth Brenner, M.D., M.P.H., NICHD, NIH, DHHS. Dr. Brenner discussed trends in injury rates. While injury rates have declined (for several reasons), a number of challenges remain. There continue to be large racial, ethnic, and SES disparities in injury rates, and there are continued high rates of intentional injuries, both child maltreatment and interpersonal violence. Injuries continue to place a very large burden on the health care system, and injury-related disabilities place additional stress on the educational and social service system.

• Dr. Brenner highlighted a number of questions that remain to be answered, including the role of genetic and environmental factors in the development of aggressive and violent behavior; how much risk-taking behavior is learned versus genetically determined; and how a chaotic family structure/environment leads to increased rates of injury.

• Dr. Brenner stated that it is clear that future research must examine interactions among genetic, environmental, and other factors that affect injury rates. The Study, with its large sample size and long-term followup, is well suited to do this. She provided several examples of specific studies that could be done, including studies related to traumatic brain injury outcomes, youth violence, child maltreatment, and the functional outcomes of injury.

Questions and Comments for the Injury Working Group

• Dr. Dudley noted that many of the hypotheses presented by the Injury Working Group lack the rigor that the NCSAC is seeking. Dr. Lutzker said that the Working Group would be meeting over the next two days to resolve some of these issues that have been raised.

• Robert T. Michael, Ph.D., University of Chicago, asked what data the Study would need to capture to identify the kinds of behaviors children are engaging in that can lead to unintentional injuries. Dr. Brenner replied that there are two large domains—exposures (the behaviors) and measuring the injuries themselves.

• Dr. Zuckerman said that he would make a distinction between injuries that occur in the sort of activities where risk is always possible and injuries where there may be other associated factors such as risk-taking and impulsive behaviors.

• Dr. Little asked if a hypothesis related to gun control was being considered. Dr. Lutzker said that data on access to guns could be included in the Study. Dr. Zuckerman said that the Study might allow a large-scale comparison of injuries by state.

• Dr. Bachrach commented about the difficulty of handling child maltreatment issues in the context of state reporting requirements. Dr. Zuckerman responded that the obligation to report is very clear, and parents must be told this through the informed consent process.

• Dr. Spence commented about a current NICHD RFA related to the role of genetics in trauma that will lead to some interesting proposals. She discussed various concerns related to looking at the relative roles of genetics and the environment, stressed that the Study was not meant to be a genetic study, and said that for genetics questions to be answered, geneticists must have input similar to that of those who specialize in looking at environmental, social, and behavioral factors. Dr. Zuckerman replied that his impression was that a genetic component is necessary for hypotheses about injury.

• Ms. Jones commented about the need for community input and how it will be obtained. She mentioned affordability of bicycle helmets in different communities and differences in how child maltreatment is reported in different ethnic groups.

• Dr. Little said that in the child abuse and neglect area, there are serious measurement issues, and that one of the tasks of the Working Group should be to determine what is actually feasible within the context of the Study.

• Dr. Zuckerman stated that he wanted to make sure that violence in the home is studied, because he believes that there is no more significant stress on children.

Conclusions/Recommendations

• The Study should be sure to assess the impact of violence in the home.

American Psychological Association

Merry Bullock, Ph.D., American Psychological Association

• Dr. Mattison introduced Dr. Bullock, who described the American Psychological Association (APA) and its activities, saying that the APA is very interested in and supportive of the Study.

• Dr. Bullock outlined several broad areas that the APA believes are very important to include as part of the Study. She also summarized some challenges, opportunities, and cautions to be considered as decisions are made about the hypotheses and the measures. Dr. Bullock highlighted three areas of particular importance: (1) precursors and risk factors, (2) mental health outcomes, and (3) health disparities.

• Dr. Bullock stressed the importance of obtaining sufficient behavioral information to be able to identify precursors and indicators of risk for later outcomes such as childhood obesity and development of diabetes.

• Dr. Bullock discussed obtaining data on the mental health histories and status of the parents. This type of data collection involves measuring levels of maternal stress, depression, and other psychosocial factors during pregnancy, postpartum, and throughout the Study to provide critical information for understanding how families and parent-child interactions affect development. It would also be important to look at childhood mental disorders, such as autism, and positive mental health outcomes as well, such as resilience.

• Dr. Bullock noted that the pervasive influence of low socioeconomic status and race on a multitude of health and education outcomes needs further in-depth evaluation. She encouraged measurement of broad cultural and environmental factors (such as access to health care, child care, and other resources, as well as family and educational interactions) to provide a clearer picture of what leads to such disparities. The APA would recommend oversampling in minority groups from low and high socioeconomic backgrounds to gather critical information to address health disparities.

• Dr. Bullock also commented about the importance of using cutting-edge behavioral measures based on expertise from the behavioral science community; looking at positive developmental outcomes, not just disease outcomes; looking at exposures during the adolescent years; and managing and storing Study data so that future generations of scientists will be assured of meaningful access.

• Dr. Bullock concluded her remarks by saying that the APA, as an organization and through its members, can offer extensive expertise in behavioral issues, as can other behavioral science associations. She urged that the Study utilize that expertise and continue to maintain communication with the APA. She expressed appreciation on behalf of APA for being involved in the Study process.

Questions and Comments for Dr. Bullock

• Dr. Doswell agreed that exposures during adolescence were important to include and said that she thought that the idea of looking at positive outcomes, such as resilience, would make communities more willing to be involved in the Study. She also commented about the need to get at the reasons behind health disparities, not just further document that they exist.

• Dr. Michael commented that he would like to know from the APA how much data capture, in terms of duration and frequency, would be required to get a sound indicator of healthy development of the child over time.

• Dr. LeMasters asked about the precursors to resiliency and the method to measure them. Dr. Bullock replied that resiliency is a relatively new concept and that there are experts in that area who would be able to respond to these questions.

• Alan R. Fleischman, M.D., New York Academy of Medicine, suggested that the APA might also be able to advise the Study about the measuring the impact of a potential major traumatic event in the United States or elsewhere that would likely affect the mental and emotional health of children.

• Dr. Graham directed questions to Dr. Scheidt concerning the activity of the Development and Behavior Working Group and peer review of the protocols prior to bids. Dr. Scheidt responded that it would be helpful for the Working Group to be more engaged and that the NCSAC was working on that. Regarding peer review of protocols, Dr. Scheidt said that is a required part of any major research and development procurement, and the protocol will undergo intense peer review.

• Dr. Bellinger asked if there were a mechanism at APA by which someone could be detailed to the Program Office for a year (for example, through a fellowship) to provide the behavioral expertise needed by the Working Groups that are concerned with these issues. Dr. Bullock suggested that a better strategy might be to develop a mechanism for obtaining assistance from multiple experts in specific kinds of methods.

Conclusions/Recommendations

• The Study should look at childhood mental disorders, such as autism, as well as positive mental health, such as resilience.

• The APA recommends oversampling in minority groups from low- and high-socioeconomic backgrounds to gather critical information to address health disparities.

• Consider seeking APA advice about measuring the impact of a potential major traumatic event in the United States or elsewhere that would likely affect the mental and emotional health of children.

• Develop a mechanism for obtaining assistance from behavioral experts.

Update by Exposure to Chemical Agents Working Group

Haluk Ozkaynak, Ph.D., M.S., Office of Research and Development, EPA

• Dr. Ozkaynak summarized the progress of the Chemical Agents Working Group, which comprises about 15 scientists with diverse expertise in many different disciplines, including exposure sciences, environmental sciences, environmental epidemiology, risk assessment toxicology, chemistry, physics, and biology. The Working Group has been dealing with complex questions in an effort to develop strategies for implementation of exposure assessment and classification for the Study.

• Some of the questions the Working Group is addressing include who to select for exposure measurement and monitoring, when to sample, where to sample, and how to collect and archive the samples. To support Study hypotheses, data will be needed from questionnaires, time/activity diaries, and biological samples. The Working Group is looking at the feasibility of using low-cost, low-burden instruments and methods whenever possible.

• The Working Group has developed several draft hypotheses and has been collaborating with other Working Groups on exposure measurement questions, including preconception issues.

• The Working Group’s primary effort currently is preparation of a white paper on exposure measurement and evaluation considerations for the Study. To support this activity, there are two pilot studies underway—one is nearly completed and the other was just recently begun.

• Dr. Ozkaynak discussed commonly used techniques and instruments. Examples of biologic measurements include urine, saliva, and breast milk. These kinds of measurements have been used by CDC and in NHANES studies. Studies done by EPA and other agencies have dealt with indoor/outdoor sampling of air, soil, dust, water, and food, as well as personal measurements. Surveys and questionnaires are commonly used, as are ecological indices such as pesticide use and land use.

• The white paper on exposure measurement and evaluation is intended to serve as a research document to the Program Office and NCSAC in designing the exposure assessment component of the Study. It contains an evaluation of different types of exposure measures related to each of the core hypotheses and includes environmental exposure information and biomonitoring, sampling, and analysis information for different life stages of children. A series of tables and appendices will summarize potential measurements. The white paper will be about 30–50 pages in length. A draft preliminary report should be ready late this year, with a final report in April 2004.

• Dr. Ozkaynak provided additional details of the contents of the white paper and discussed some examples of exposure measures.

• The pilot study that has just been completed through EPA funding by the Battelle and Harvard School of Public Health team included a literature survey on exposure rate information and statistical methodologies suitable for a longitudinal epidemiological study; it also examined optimal design strategies. The team developed a thematic model simulating realistic exposure patterns and health outcomes to identify study design strategies that will yield adequate study power, but at the same time address bias, omission, error, and attrition. The pilot used case studies focusing on children’s IQ deficits, miscarriage, autism, and asthma. The pilot study report will be available in about one month.

• General conclusions in the white paper are that it is difficult to identify a single optimal design, as anticipated, but for each hypothesis of interest, optimally designed substudies using a fraction of the Study cohort can be conducted and should be considered.

• Dr. Ozkaynak asked the NCSAC for feedback on the contents of the white paper and on the Working Group’s efforts, how to integrate exposure-related survey instruments into the overall study instruments, and interactions with other Working Groups. He noted that Working Group members are asking when their efforts will end.

Questions and Comments for Dr. Ozkaynak

• Dr. Graham commented that she was very impressed with the amount of work that has been going on and that the Working Group’s chemical exposure expertise would be needed continually over the course of the Study. She suggested, with regard to interaction with other groups, that Working Group members could assist in getting more specificity on the chemicals, drugs, or other exposures involved as the Study hypotheses are finalized and then communicate with other Working Groups.

• Dr. Dudley echoed Dr. Graham’s comments about the work that has been done and that the Working Group’s expertise would be needed throughout the Study. He asked whether the Working Group has the necessary resources to accomplish its work and how the timeline for its products correlates with other Study timelines. Dr. Mattison responded that the coordination of timelines would be a task for the Executive Committee.

• Dr. Spence questioned whether certain measures (such as obtaining amniotic fluid) were realistic and should even be considered. She commented that genetic testing is portrayed as costly, yet the costs are rapidly decreasing. Dr. Ozkaynak replied that amniotic fluid was listed because it was part of a complete survey of tools and measures available, not because anyone was recommending that it be collected for the Study. He added that costs must be considered. If genetic testing costs have decreased, then the issue is moot. There was some additional discussion about genetic testing.

• George P. Daston, Ph.D., Procter and Gamble, commented that he thought there was a need for some sort of "exposure assessment for the complete idiot" to be developed that would outline what kinds of things can be done for what kinds of costs and show the tradeoffs between the high cost and invasive measures versus less invasive measures. He also stressed the need for coordination among the Working Groups regarding the tools for exposure assessment.

Conclusions/Recommendations

• Exposure to Chemical Agents Working Group members could assist in getting more specificity on the chemicals, drugs, or other exposures involved as the Study hypotheses are finalized and then communicate with other Working Groups.

• There is a need for coordination among the Working Groups regarding the tools for exposure assessment.

General Committee Discussion

• Dr. Mattison discussed the breakout sessions to follow, explaining that these working sessions were to focus attention on analysis of the hypotheses as they exist and the thematic areas. The goal of the sessions was to allow the liaisons an opportunity to understand the specific kinds of advice that need to be brought back to the Working Groups to engage them in this next cycle of iteration for development of hypotheses, with the focus being clarity in exposures. Each Working Group would also be asked to work toward specificity of exposures and when they should be measured.

• Dr. Mattison asked if there were questions.

Questions and Comments for the General Committee

• Dr. Daston asked for clarification about what the Working Groups should be doing and whether the charge for the breakout sessions was more an oversight charge. Dr. Mattison explained that the Working Groups were a creation of the NCSAC. They are charged and directed by the NCSAC with respect to what they do, and their products need to come back to the NCSAC for deliberation and discussion.

• Dr. Doswell also asked for clarification about the breakout sessions. Dr. Mattison replied that he would like the Working Groups to look at the hypotheses within each of the thematic areas and describe the set of questions that would go back to the Working Groups that would increase the specificity and precision or characterization of the hypotheses. Dr. Doswell asked what the Community Outreach Working Group would discuss, since there were no hypotheses for this area. Dr. Mattison suggested that the discussion could focus on outreach strategies and on developing additional questions for the Working Group.

• Dr. Spence commented that she was concerned about the use of the word "hypothesis" when many of the hypotheses listed were stated as ideas rather than as hypotheses. Dr. Mattison agreed that the hypotheses would need to be made explicit and would need to be prioritized.

• Dr. Graham raised the issue of cross-Working Group activity and discussion. Dr. Mattison said that he hoped that sort of activity would take place over the course of the afternoon and the next day’s meetings. In response to a question from Dr. Suarez, Dr. Mattison explained that the breakout sessions would primarily involve the NCSAC members and the ICC members who are liaisons to the Working Groups.
• Dr. Mattison said that one of the issues that would likely arise over the course of this meeting would be the need for a more direct, face-to-face engagement of the NCSAC member with the Working Group to produce the kind of dialogue that is needed.

• Dr. Little asked about the degree of specificity needed with regard to the hypotheses. Dr. Mattison replied that the groups should be as specific as necessary in terms of questions for the Working Groups to make it possible to evaluate the hypotheses from a subject burden, a cost, and a statistical sampling perspective.

• Ms. Leahey discussed logistical details for the breakout sessions and the lunch break.

• Dr. Scheidt commented that the Study is in a period of transition from a more active role of the ICC liaisons to a more active role of the NCSAC liaisons, based on the guidance regarding the Federal Advisory Committee Act and from NIH General Counsel. The ICC liaisons will be available to provide background support and information, but they will not be able to give any signals or take anything from this process to the Program Office without the expressed concurrence of the NCSAC.

Lunch Break/Breakout Sessions

Following the lunch break, thematic sub-group breakout sessions were held (see Appendix A–E: Thematic Sub-Group Breakout Sessions Summaries).

Afternoon Session
Review Progress of Thematic Sub-Groups

• Dr. Mattison reconvened the NCSAC following the breakout sessions. He explained that the chairs of the breakout sub-groups would be providing a report of their sub-group’s discussions and reminded the NCSAC members that, while they had been working in a collective mode, in their liaison role they would need to translate very specific directions back to the Working Groups.

Asthma Thematic Sub-Group

Barry Ryan, Ph.D., NCSAC Member, Emory University

• Dr. Ryan noted that on the whole that the group felt that these were quite good hypotheses and generally quite acceptable; however, it is now time to get more specific, such as regarding timeframes and sensitivity of instruments. The group has charges to several of the groups that will require some merging of information from a number of different Working Groups. Regarding outcomes, a series of definitions will be needed. For example, asthma is different for children at different ages. Dr. Ryan added that the group has some preliminary target dates for reporting and feedback.

Questions and Comments for the Asthma Thematic Sub-Group

• Dr. Dudley expressed concern about coordinating of information from multiple breakout thematic groups to be taken back to the Working Groups. Dr. Mattison responded that this would be worked out through the notes from the breakout sessions and through further reporting and discussion the following day.

• Dr. Graham suggested that, in the course of making asthma measurements, data on normal lung development could also be obtained.

Conclusions/Recommendations

• In the course of making asthma measurements, data on normal lung development could also be obtained.

Injury Thematic Sub-Group

Barry Zuckerman, M.D., NCSAC Member, Boston University School of Medicine

• Dr. Zuckerman commented that the injury group benefited from having two members of the Injury Working Group present, which allowed for a dialogue. The group reviewed the hypotheses and identified specifics for them, including where more definition was warranted, what instruments needed to be used, and timing of assessments. Dr. Zuckerman stated that the results of the discussion would go back to the Working Group, which will revise the hypotheses to make them more specific. Also, there might be another iteration before the revised hypotheses would be seen by the NCSAC.

• The group discussed the number of hypotheses there should be. The hypotheses fall into four areas: child maltreatment, aggression and the trajectory of aggression from childhood to adolescence or young adulthood, traumatic brain injury, and unintentional injuries. The group asked that the Working Group also prioritize the hypotheses and suggested opportunities for collaboration with other Working Groups.

Questions and Comments for the Injury Thematic Sub-Group

• Daniel J. Swartz, Children’s Environmental Health Network, commented that the last time the NCSAC had seen the injury hypotheses, questions were raised about whether the hypotheses needed such a large "N" for testing and whether injury should even remain as one of the thematic areas. He asked whether the group now felt that the inclusion of injury as a thematic area was justified. Dr. Zuckerman responded that he thought so, and that the longitudinal nature of the Study was relevant as well as the "N." In sum, Dr. Zuckerman said that he thought that the group felt comfortable that the Study is suitable for studying key hypotheses for injuries.

• Dr. LeMasters asked whether the aggression hypothesis related to parental or family aggression toward children or to aggressive behavior in the child. Dr. Zuckerman clarified that the hypothesis addresses aggressive development of children, but violence in the home would clearly be one of the factors of interest. Dr. LeMasters commented that she thought that aggression toward children (whether from family members, neighborhood or community members, or others) has an important impact on children. Dr. Zuckerman mentioned that other Working Groups have an interest in these kinds of issues as well.

• Dr. Doswell asked whether the kind of aggressive behavior such as the violence seen at Columbine High School would be a thread. Dr. Zuckerman replied that the large sample size should allow the Study to look at similar kinds of rare events.

Altered Neurobehavioral Development, Developmental Disabilities, and Psychiatric Outcomes Thematic Sub-Group

Barbara R. Foorman, Ph.D., NCSAC Member, University of Texas Health Science Center at Houston

• Dr. Foorman explained that Dr. Spence would report first. Dr. Spence described two issues that the group discussed—the role of siblings and the possibility of genetic studies. Regarding siblings, Dr. Spence said the group suggested that all Working Groups be asked whether collecting data on siblings would benefit or detract from studying their hypotheses, with the goal of getting back some input for the study design people as early as possible.

• With regard to genetic testing, Dr. Spence said that the group wanted to re-emphasize, because of interest in gene-environment interactions, that timing on what gets tested or sampled is going to be critical. Also, it will be necessary to think ahead as much as possible as to when some of these things may be important or relevant with respect to what is known about development.

• Dr. Spence mentioned four hypotheses. The asthma and folate hypotheses were well developed, but the obesity and diabetes hypotheses will require more specificity. She pointed out that the asthma hypothesis about maternal stress was an example of an area where more cross-communication among Working Groups is needed.

• Dr. Spence said that the group discussed a major issue related to measuring genotypes and gene frequencies across populations—how genotype relates to ethnicity and race. The group suggests that a critical workshop is needed to address the biology of race, the definition of race, and the handling of race within this Study, in order to sample in a way that makes sense and to have data that will be useful in relation to the U.S. population. Dr. Spence said that this should be addressed quickly to provide input to the Sampling Design group.

• Dr. Foorman reported on the discussion concerning the hypotheses from the Development and Behavior Working Group. The Working Group has not made much progress: the existing hypotheses are diffuse, and the Working Group has not really addressed developmental and behavioral outcomes in its hypotheses. Dr. Foorman’s group suggested that the Working Group be reconstituted; that the new members react to Battelle’s forthcoming white paper on outcome measures; and that this new group should interact with other Working Groups, such as the Social Environment Working Group, the Gene-Environment Interactions Working Group, and the Exposure to Chemical Agents Working Group.

Questions and Comments for the Altered Neurobehavioral Development, Developmental Disabilities, and Psychiatric Outcomes Thematic Sub-Group

• Dr. Mattison suggested that he, Dr. Foorman, and Deborah A. Phillips, Ph.D., Georgetown University (and others as appropriate) could discuss making changes to the membership of the Working Group and how to deal with inviting new members. He added that he would appreciate nominations from others as well for new members for the Working Group.

• Mr. Swartz asked whether, due the importance of this area, there might not be an indication for more full-time staff involvement to ensure that progress be made quickly. Dr. Scheidt replied that a full-time behavioral scientist is being added to the staff and will be involved in moving the process along.

• Dr. Michael recommended that the Health Services Working Group also be involved in this process because of its relevant orientation and mindset. Dr. Mattison agreed.

• Dr. Mattison if Dr. Bachrach had any comments. Dr. Bachrach said that she thought there was room for the Social Environment Working Group to provide input across the board.

Conclusions/Recommendations

• The Development and Behavior Working Group should be reconstituted. Drs. Mattison, Foorman, and Phillips will work on this issue. NCSAC members should provide Dr. Mattison with nominations for new members for the Working Group. The reconstituted Working Group should react to Battelle’s forthcoming white paper on outcome measures and interact with other Working Groups (such as the Social Environment, the Gene-Environment Interactions, and the Exposure to Chemical Agents Working Groups).

• All Working Groups should be asked whether collecting data on siblings would benefit or detract from studying their hypotheses, with the goal of getting back some input for the Study Design Working Group as early as possible.

• A workshop should be conducted to address the biology of race, the definition of race, and the handling of race within this Study, in order to sample in a way that makes sense and to have data that will be useful in relation to the U.S. population.

• The Health Services Working Group should also be involved in this process because of its relevant orientation and mindset.

• The Social Environment Working Group should provide input across the board.

Obesity and Altered Physical Development Thematic Sub-Group

Willa Doswell, Ph.D., R.N., F.A.A.N., NCSAC Member, University of Pittsburgh School of Nursing

• Dr. Doswell said that this thematic group looked at hypotheses from several Working Groups, including the Health Services Working Group; the Community Outreach and Communications Working Group; the Early Origins of Adult Health Working Group; and the Nutrition, Growth, and Pubertal Development Working Group.

• Regarding the health services hypotheses, Dr. Doswell said that although the group’s definitions of health were good, there needed to be a streamlining of the many hypotheses that the group had under different subcategories.

• There were no hypotheses in the community outreach area, so the thematic group delineated areas that the ICC had questions about to go back to the Working Group. The Working Group also will be asked whether there are any hypotheses that should be part of the Study, or whether the group saw its role primarily as facilitating the implementation of the Study.

• Regarding the Early Origins of Adult Health Working Group, the thematic group felt that it should coordinate with other groups about genomic issues.

• Mr. Swartz reported that the Nutrition, Growth, and Pubertal Development Working Group had concluded that that their hypotheses do not need 100,000 people, so the group is not submitting any core hypotheses because the questions can be answered elsewhere.

Questions and Comments for the Obesity and Altered Physical Development Thematic Sub-Group

• Dr. Mattison asked whether the Nutrition, Growth, and Pubertal Development Working Group should be reconstituted. There was some additional NCSAC discussion about this Working Group.

• Dr. LeMasters asked whether it was time to consider consolidating the Working Groups and whether it was the role of the NCSAC to address this issue. Dr. Mattison indicated that the answer to both questions was "yes." Dr. Suarez suggested discussing this matter the following day, and Dr. Mattison agreed.

Conclusions/Recommendations

• The Early Origins of Adult Health Working Group should coordinate with other groups about genomic issues.

• The NCSAC should consider consolidating the Working Groups.

Undesirable Outcomes of Pregnancy: Birth Defects and Preterm Birth Thematic Sub-Group

George P. Daston, Ph.D., NCSAC Member, Procter and Gamble

• Dr. Daston remarked that the group had reviewed the relevant core hypotheses, as well as minutes from previous NCSAC meetings where these had been discussed to see whether any progress had been made. They also discussed questions raised by the ICC.

• With regard to the Birth Defects Working Group, Dr. Daston said that a core list of potential etiological agents or contributors to good or bad outcomes needed to be compiled and evaluated uniformly throughout the Study. This would include things like folate and micronutrients. Other Working Groups, such as Fertility and Early Pregnancy, Exposure to Chemical Agents, and Medicine and Pharmaceuticals, need to identify those lists of agents or factors and outcomes that should be included in the Study as a whole. Dr. Daston identified two hypotheses in the Birth Defects area of particular interest that will require additional specificity from the Working Group.

• With regard to the Fertility and Early Pregnancy Working Group’s hypotheses, Dr. Daston said the group would be asked to identify the key exposures that need to be evaluated and encouraged to make their proposals uniform. One of the Working Group’s proposals, related to assisted reproductive technologies, would best be done elsewhere.

• Regarding the Medicine and Pharmaceuticals Working Group, Dr. Daston said that group would be charged with developing a tiered approach, including a questionnaire that would be applied uniformly across the Study to assess exposures to prescription and over-the-counter medications, as well as herbal, botanical, and other agents. This should also consider exposures in extraordinary circumstances, such as when a parent, a pregnant woman, or a child is treated aggressively in a hospital setting for a disease or condition.

• Dr. Daston noted that this group would address the final set of hypotheses the following day.

Conclusions/Recommendations

• A core list of potential etiological agents or contributors to good or bad outcomes should be compiled and evaluated uniformly throughout the Study.

• Other Working Groups, such as Fertility and Early Pregnancy, Exposure to Chemical Agents, and Medicine and Pharmaceuticals, should identify those agents or factors and outcomes that need to be included in the Study as a whole.

Report from Joint ICC/NCSAC Executive Committee

Judith A. Graham, Ph.D., NCSAC Member, Senior Scientist and Senior Director, Long-Range Research Initiative, American Chemistry Council

• Dr. Graham summarized Executive Committee activities. The Executive Committee has met four or five times by conference call since the last NCSAC meeting. Members of the Executive Committee are Dr. Mattison; Dr. Dudley; Dr. LeMasters; Philip J. Landrigan, M.D., M.Sc., Mount Sinai School of Medicine; Ms. Leahey; Dr. Scheidt; Sherry Selevan, Ph.D., EPA; Mr. Quackenboss; and the rotating co-chairs of the ICC. The Executive Committee is responsible for developing processes for presentation to the full NCSAC.

• Dr. Graham mentioned examples of activities in the past few months, including interaction with the Study Design Working Group; a letter to the editor of Science, which ultimately was not sent; and an inquiry to the Working Groups asking for ways to improve their functioning. The latter resulted in little response. Dr. Graham stated that the NCSAC liaison roles are a better way to maintain contact with the Working Groups and assist them. The Executive Committee also briefly reviewed ICC questions for the hypotheses and developed the agenda for this meeting.

• Dr. Graham said that a future emphasis would be to realistically integrate NCSAC milestones with Study milestones and develop an annual schedule. This would mean making decisions about the December meeting—what should happen at the meeting, what decisions should be made at the meeting, what instructions should be given out at the meeting, and what should be fed back to the NCSAC at its next meeting. She concluded her remarks by asking the NCSAC members to let the Executive Committee know if there are additional things that it should be doing or if there are problems with processes that should be addressed. Comments can also be directed to Dr. Mattison via e-mail.

Conclusions/Recommendations

• The NCSAC should notify the Executive Committee if there are additional activities that it should be undertaking or if there are problems with processes that should be addressed.

General Discussion and Comments

The afternoon session concluded with discussion about the next day’s schedule and several other issues:

• Revised schedule for reconvening the thematic sub-groups and plenary.

• Notetaker support, if needed.

• Dr. Mattison stated that in Tuesday’s plenary session, he wanted to make sure that each individual liaison understood what other Working Groups are going to either be referring to their Working Group hypotheses or will need input from their Working Group.

• Dr. Scheidt commented that he was puzzled about the lack of hypotheses from the Nutrition, Growth, and Pubertal Development Working Group. He suggested that the NCSAC might want to further discuss this issue further.

• Mr. Swartz remarked that the Working Group’s belief was that nutritional factors should be integrated into other hypotheses with the Working Group’s advice. He added that the NCSAC needed to determine whether or not the other sets of hypotheses asked the appropriate nutritional questions.

• Dr. Graham agreed with Mr. Swartz and said that the thematic sub-group had created a "no-brainer" list of measures that included things such as folate. She added that all the nutritional elements needed to be measured and that other Working Groups, such as the Medicine and Pharmaceuticals and the Exposure to Chemical Agents Working Groups, would need to address these measures. Dr. Spence agreed and mentioned a folate hypothesis from the Gene-Environment Interactions Working Group. Dr. Zuckerman suggested that a nutritionist be included in the other related Working Groups.

Tuesday, September 16

Dr. Mattison convened the plenary session and made opening remarks:

• The session would focus on three main items—a presentation from Doris Haire, President of the American Foundation for Maternal and Child Health; a review of the feedback that will go to each of the Working Groups; and a discussion of how to decide that it is time to close out a Working Group. Dr. Mattison cited the example of focusing on impacting health across the domains of the Study.

• Dr. Mattison noted that he also would like the NCSAC members to provide input in the message that will go to Duane Alexander, M.D., Director, NICHD, NIH, DHHS. The message will then be drafted and circulated to each of the NCSAC members for their comments.

Hypotheses Submitted by the American Foundation for Maternal and Child Health (AFMCH)

Doris Haire, President, American Foundation for Maternal and Child Health

• Ms. Haire expressed thanks for the opportunity to share her concerns with the NCSAC. She stated that she was troubled that after numerous meetings, there was no clear commitment that the Study will carefully document each child’s intrapartum exposure to drugs and procedures administered to the mother during labor and birth. The collection of that information is essential to any meaningful environmental study of human development.

• Ms. Haire stated that she had also been troubled by the fact that there appears to be no pediatric neurologist involved in the planning of the Study; however, she had been told prior to her presentation that there is such a person involved. Such expertise is essential if the Study is to make progress in determining whether or not there is a possible correlation between fetal exposure to a specific drug or regime and the subsequent development of a neurological disorder in children or early adulthood.

• Ms. Haire briefly reviewed the five hypotheses that she had previously submitted for consideration for inclusion in the Study:
  • The administration of oxytocin to parturients during labor and birth increases the incidence of jaundice in the newborn.
  • The administration of pain-relieving drugs to the mother during labor and birth increases the incidence of resuscitation of the newborn infant.
  • Drugs administered to the mother during labor and birth can adversely affect the rapidly developing nerve circuitry of the infant’s brain and central nervous system.
  • Drugs administered to parturients during labor and delivery can adversely affect the intrauterine environment, immediate newborn responses, and the future neurological development of the offspring exposed in utero to those drugs.
  • Forceps delivery, vacuum extraction, and prolonged bearing down create added trauma to the fetal head and contribute significantly to the rate of urinary and fecal incontinence in the mother.

• Ms. Haire provided some background information and mentioned references with regard to the above hypotheses. She referred the NCSAC members to the Foundation’s Web site (www.amesusa.org) for additional information on the adverse effects of obstetric drugs on the newborn, as much of this information is not readily available.

Questions and Comments for Ms. Haire

• Dr. Graham concurred with Ms. Haire that currently there is no specific hypothesis for drugs around the time of parturition. Dr. Graham noted that the Medicine and Pharmaceuticals Working Group believed very profoundly in the importance of knowing about pharmaceutical use (legal or illegal) over the entire course of a child’s life. However, the question was how to integrate drug exposure data collection into the Study. Dr. Graham stated that she thought that the next level of detail would involve adding the drugs to a list of measurements to be made without having a specific hypothesis. She added that it would be important for Ms. Haire to look at that next level of detail, which would include the timing of measurements and determine how the measurements fit with her hypotheses.

• Dr. Doswell commented on the difficulty of using patient charts to obtain data. Dr. Graham responded that the Study probably had thousands of feasibility issues. She added that she thought that there were numerous measurements that would be considered "no-brainer" measures for the Study and that collection of such data would allow additional hypotheses to be created and tested later.

Conclusions/Recommendations

• Documenting children’s intrapartum exposure to drugs and procedures administered to the mother during labor and birth is essential to any meaningful environmental study of human development.

Discussion of Agenda

• Dr. Mattison reviewed the remaining agenda items, discussed how to proceed, and asked for comments.

• Dr. Ryan asked whether it would be possible to review the information from all of the thematic sub-groups that met in breakout sessions before deciding what needs to be taken back to the Working Groups. Dr. Mattison said that he hoped that could be done verbally for the present time, but that meeting notes would be available. Ms. Leahey said she thought that could be accomplished in several weeks or a month.

• Mr. Swartz commented that he would like to receive electronic copies of meeting summaries.

• Dr. Dudley agreed with Dr. Ryan that he would rather not rely on just word of mouth among different people but would prefer to have a fairly concrete set of requests or directions for the Working Groups that resulted from all of the different thematic sub-group meetings.

• Dr. Michael asked how specific requests to the Working Groups would be funded. Dr. Mattison replied that if a Working Group needs support in any way, it should be discussed with the Program Office.

• Ms. Leahey suggested that when the NCSAC members conduct their conference calls with the Working Group chairs, it would probably be best to have the ICC liaisons on the calls as well, because they are familiar with the various types of support available to the various Working Groups.

• Dr. Doswell requested that the thematic sub-group meeting notes be circulated to the group members first. Ms. Leahey said that she could do that. She suggested that she could also pull together relevant information from previous NCSAC meetings regarding the hypotheses, if that would be helpful.

• Ms. Jones stated that she thought it would be useful to confer with other liaisons before speaking with the Working Groups. Dr. Mattison replied that this sort of interaction could be arranged via conference call and asked that anyone wishing to do this send an e-mail to him or to Ms. Leahey.

• Dr. Graham said that Dr. Selevan had raised a point about the legality of making sure that Working Group members not do anything that would make them ineligible to apply later. Dr. Mattison said that was a good point and that Ms. Leahey would work with the ethics attorneys at the NIH to obtain their help with this issue.

• Mr. Swartz suggested that each thematic sub-group report should mention any concerns and needs in their oral reports, keeping in mind that written notes would be available later. Dr. Mattison agreed.

Conclusions/Recommendations

• Include ICC liaisons when NCSAC members conduct conference calls with Working Group chairs.

• Circulate thematic sub-group meeting notes to the sub-group members first.

• Schedule conference calls among the liaisons before speaking with the Working Groups.

Action Items

• Ms. Leahey will confer with the NIH attorneys to obtain information regarding Working Group members possibly being precluded from being considered as Study centers.

• Ms. Leahey will circulate thematic sub-group meeting notes to the sub-group members first.

Summaries by Thematic Sub-Group Liaisons

• Dr. Bellinger, liaison to the Physical Environment Working Group, noted that there were no hypotheses from that Working Group as yet. He said that he would be initiating a dialogue with Working Group members. Dr. Mattison clarified that this new Working Group will be focusing on the "built environment" and the role the built environment plays in health. Dr. Mattison added that Dr. Dick Jackson at CDC has been working on this issue and has just been promoted to senior advisor to Dr. Gerberding, probably in part to manage this activity.

• Dr. Mattison said that Linda Burton, Ph.D., NCSAC Member, Pennsylvania State University, liaison to the Social Environment Working Group, was not at the meeting. However, Dr. Bachrach was present and would relay information to that Working Group. He added that there were some interactions that would have to take place.

• Dr. Daston, liaison to the Birth Defects Working Group, stated that it was clear that the Study would be recording outcomes—structural malformations—at or soon after birth. He said that first, it was important to have not only an appropriate list of outcomes from the Birth Defects Working Group, but also a list of potential etiological agents or factors, such as chemical factors, drugs, nutritional factors, and others. Second, Working Group members would be charged with using their knowledge of studies that provide some evidence of cause and effect for particular agents to help them define these lists. Dr. Daston suggested that other groups should also provide input into the identification of those potential etiological agents. In response to a question from Dr. Mattison, Dr. Daston noted that he did not feel that a new review of relevant case control studies was needed.

• Dr. Doswell said that she would be taking back to the Community Outreach and Communications Working Group the responses to ICC questions and would get their further clarification on answers to those questions. She also would again ask if there are any hypotheses coming from this Working Group and about a timetable for this group’s activities. Dr. Doswell stated that she had received a two-page document that the Working Group developed the previous day, requesting contractor support for a review of literature on successful recruitment and retention strategies in the past, such as incentive gifts.

• Dr. Dudley, liaison to the Pregnancy and the Infant Working Group, stated that the group had some fairly well developed hypotheses that the thematic sub-group had discussed earlier. Dr. Dudley indicated that he was concerned about having the Working Group revise or refine the hypotheses and how that might potentially affect the ability of Working Group members to participate later in the Study. Dr. Mattison responded that perhaps it might be most logical to indicate to the Working Group that it is now time for them to formally share their hypotheses and collaborate with other Working Groups. The Working Group should identify the questions that they want these other Working Groups to explore, in order to make sure that their expertise is incorporated into the hypothesis and requisite background material.

• Dr. Doswell asked for clarification about what the Working Groups would be asked to do and whether they would address the instruments as well as the hypotheses. Dr. Mattison replied that he thought that once the Working Groups have provided specificity around exposures and outcomes in the context of the hypotheses, the next step would be referral to the ICC and Program Office for increased specification. The hypotheses will have to be woven into the protocol, and the specific instruments and analytical methods to be used will have to be identified. Dr. Mattison said that ultimately the decisions on instruments would have to be parsed out, and that there would be public comment about these issues to consider as well.

• Dr. Michael said that he disagreed with the concept that one can separate the hypothesis from the instrumentation. Dr. Mattison agreed and said that was why the Working Groups should recommend specific instruments and methods. Dr. Michael said that he wanted the Working Groups to have ownership of their hypotheses to the extent that they would define what they want and argue for it.

• Dr. Bellinger asked for further clarification about the kind of activities that Working Group members might engage in that would disqualify them from competing. Dr. Mattison said his understanding was that if a Working Group member designs something that is incorporated into the Study, and that member’s entity or organization is the only one that can carry out that design, that would be an opportunity for disqualification. In response to a question from Mr. Swartz, Dr. Mattison explained that all Working Group members are insulated from the federal government by the NCSAC and operate under different standards.

• Dr. Graham commented further on the issue of how long Working Group members can continue to participate and pointed out that recommendations from the Working Groups must be funneled through the NCSAC and the ICC.

• In response to Dr. Bellinger’s question, Dr. Scheidt commented that it has to be answered in the context of competing for what. If competing to carry out the full protocol as a data collection center, then Working Group members are disqualified if they are involved and/or see the protocol that becomes the scope of work before being made public. If competing for a specific pilot test, they are disqualified if they are involved in the decision-making process about developing that pilot test. This would give them a competitive advantage.

• Dr. Scheidt responded to Dr. Dudley’s question about refining the hypotheses and suggested going back to the original checklist that was prepared by the Study Design Working Group and approved by the NCSAC. Dr. Scheidt added that most hypotheses were fairly well developed, at least in terms of rationale and public health significance. However, many hypotheses lack specificity, such as whether the hypothesis requires a study of this size and complexity or details about methods and measures. Dr. Mattison remarked that this issue clearly needs to be an agenda item for the December meeting.

• Dr. Foorman, liaison to the Development and Behavior Working Group, said that she would be meeting with Dr. Phillips, who would update her on what the sub-group discussed. The main issues are reconstituting the Working Group and how the new group will interface with the Battelle white paper on measures, so that there is no redundant work. Dr. Foorman added that the new Working Group would be encouraged to interact with other relevant Working Groups, such as the Exposure to Chemical Agents, Gene-Environment Interactions, Social Environment, and Health Services Working Groups.

• Dr. Graham suggested when the Development and Behavior Working Group is reconstituted, it should include a neurotoxicologist. She suggested seeking the advice of Dr. Kevin Crofton in the neurotoxicology division of EPA’s National Health and Environmental Effects Research Laboratory. Dr. Graham drew a distinction between the person who is a coauthor of the latest review article on neurotoxicology and the exposure group person who is capable of making the needed measurement.

• Dr. Graham, liaison to the Medicine and Pharmaceuticals Working Group, said that while the group has no hypotheses, members of this Working Group are anxious to participate. She will have several questions for them related to the "what, when, and how." For example: "What are the criteria for determining when a more in-depth evaluation is needed?" "How good are questionnaires?" "How should the Study use evolving technology to facilitate collection of data on pharmaceutical use?" Dr. Graham added that it was important that drugs of abuse and herbals and supplements are addressed.

• Dr. Scheidt asked Dr. Graham why there would not be any hypotheses about proposed effects for classes of pharmaceuticals administered at certain intervals, for example. Dr. Graham responded that while they were not opposed to such a hypothesis, they did not want to proliferate hypotheses. She said that the Working Group is functioning more as a support work group. Dr. Graham said that the Study could have 20 hypotheses on neurodevelopment, each one regarding a different agent, but that she did not see that as necessary. What they are saying is that the measurement has to be made, and later on, the statistical evaluation needs to be made about associations.

• There was additional discussion around the above topic by several committee members. Dr. Mattison summed up the discussion by noting that as the groups look at the hypotheses, whether or not the pharmaceuticals need to be considered as a potential etiologic agent would be clearer. Then it would be appropriate to touch base with the Medicine and Pharmaceuticals Working Group.

• Dr. Zuckerman, liaison to the Injury Working Group, said that he had no comments to add to his report from the previous day.

• Ms. Jones said that the thematic sub-group concluded that the Asthma Working Group needed to communicate with the Community Outreach and Communications Working Group. She said that the biological and the social sciences seemed to be disconnected and should be linked together. Also, the thematic group would like to send a timeline to the Working Group for consideration.

• Dr. Michael, as liaison to the Health Services Working Group, said that he needed to meet with the ICC liaison. He said that health services are intermediary to everything of interest here—the healthy development of children and all their health problems. The thematic sub-group found that many of the hypotheses discussed the previous day seemed best suited to outcomes group with a directive about what the health services aspects of that outcome should be.

• Dr. Ryan, liaison to the Exposure to Chemical Agents Working Group, said that he would like to encourage the group to complete the tables that they discussed, consider the cost of analysis of various activities that they might be suggesting, and think about more focused targets within each classification of environmental pollutant. In Dr. Ryan’s opinion, this group will need to interact with and advise many of the other groups.

• Dr. Suarez, liaison to the Fertility and Early Pregnancy Working Group, said that the thematic sub-group concluded that the Working Group should be asked to rework three hypotheses into a combined, coherent, big hypothesis that specifies exposure agents and outcomes over the life course. The hypothesis on assisted reproductive technologies is not core, but the group can specify what information needs to be collected around conception. Dr. Suarez added that this Working Group should interact with the Birth Defects Working Group and the Medicine and Pharmaceuticals Working Group.

• Dr. Spence, liaison to the Gene-Environment Working Group, commented about advances being made and how the science of genetics will be changing over the course of the Study. She identified specific tasks that she would ask the Working Group to do—develop questions related to siblings to go to all Working Groups and develop detailed responses to two specific questions: one regarding DNA samples versus cell lines on the cost factor and the other focusing on the issue of collecting family history data. Dr. Spence remarked that, in addition, there were four hypotheses related to asthma and diabetes that will require interaction with other Working Groups. Finally, there is the issue of having a workshop on race, which is extremely important from the scientific outcome perspective and is an extremely sensitive issue. The question is how it will be handled in this Study.

• Mr. Swartz, liaison to the Nutrition, Growth, and Pubertal Development Working Group, noted that there were four issues that he wanted to discuss with the group, including defining all the "whats, whens, and hows." He said that the group needed to interact with others concerning relevant hypotheses. Mr. Swartz commented that, for four of the five major health thematic areas, there is a Working Group that is the locus for that health outcome. However, obesity is an exception—there is no Obesity Working Group. Similarly, diabetes, whether related to obesity or not, does not have a separate working group.

Conclusions/Recommendations

• The Working Groups should review each hypothesis, look at potential collaboration with other Working Groups, and think about which Working Group is most appropriate to address each hypothesis.

• In refining a hypothesis, each group should refer to the original checklist that was prepared by the Study Design Working Group and approved by the NCSAC.

• The lack of specificity (for example, whether the hypothesis requires a study of this size and complexity or details about methods and measures), needs to be addressed at the December meeting.

• There should be a hypothesis on classes of chemicals.

• The Asthma Working Group needs to communicate with the Community Outreach and Communications Working Group and that the biological and the social sciences should be linked together.

• The Health Services Working Group and the thematic sub-group interacting with this Working Group should develop a module on expenditures on behalf of the whole Study, as well as a module designed for those children with special needs, because these expenditures are atypical.

• The Fertility and Early Pregnancy Working Group should rework three hypotheses into a combined, more comprehensive hypothesis that specifies exposure agents and outcomes over the life course. This Working Group should interact with the Birth Defects Working Group and the Medicine and Pharmaceuticals Working Group.

• The Gene-Environment Working Group should develop questions related to siblings; these questions should be disseminated to all Working Groups.

• NCSAC should move ahead on scheduling and conducting a workshop on race. While the Gene-Environment Working Group may take the lead, this matter will be brought to all the Working Groups for comment.

• The Nutrition, Growth, and Pubertal Development Working Group should review all references to obesity within the Study. This Working Group should collaborate with the new Physical Environment Working Group to ensure that the obesity hypotheses are adequate.

• The cultural aspects of diet and nutrition needed to be considered in the hypotheses.

Timeline for the Advisory Committee

• Dr. Mattison offered that the NCSAC needs to begin to consider how it provides comments or requests to the Working Groups, and how that meshes with other activities and timelines for Study planning, implementation, and so on. He stated that the Executive Committee had briefly discussed this issue in terms of coordinating activities. Dr. Mattison proposed that the Executive Committee continue to work on coordinating timelines. He said that Dr. Graham, who chairs the Executive Committee, would be making a report at the December meeting on this effort and what it means with respect to the Working Groups and with respect to Study implementation.

• Dr. Graham noted that, in view of the activities planned for cross-Working Group interactions and reconstituting one of the Working Groups, she thought that the revised hypotheses could be reviewed at the March NCSAC meeting. Dr. Mattison suggested a schedule for having the hypotheses due in December, reviewed in January by the Study Design Working Group, revisions made in February, and reviewed by the NCSAC at the end of March. There was additional discussion about possible timelines and the scheduled date for the March NCSAC meeting.

• Dr. Michael asked whether there was a plan for transitioning completed hypotheses into a protocol. Sarah Keim, M.A., NICHD, NIH, DHHS, responded that the measures database was the first step in that process. Other steps include eliciting the help of Battelle and the Working Groups to start pulling together instruments to go with those measures. Ms. Keim said that the Program Office was focusing on this process.

• Dr. Doswell asked who determines which hypotheses require a sample size of 100,000 and whether some might better be tested as RO1s. She also questioned the timing of interacting with the Study Design Working Group, whether children would be asked to complete questionnaires as part of the Study, and about the reading levels and cultural aspects of such instruments. Dr. Mattison said that the latter issue was important and had not been discussed. Dr. Spence also commented about how children’s perspectives differ.

• Dr. Graham commented that pieces of the Study could indeed be done as an R01, but that they should also be included in the overall Study. Dr. Mattison said that are two other components to this Study that may make it different than a traditional R01—the duration of followup and the issue of interactions, which often are not addressed by a traditional R01, which is typically more narrowly focused.

• Dr. Doswell expressed concern about subject burden, noting that people would not be willing to put in the necessary time to fully participate in the Study. Dr. Mattison said that he thought that this was a Program Office issue.

Conclusions/Recommendations

• The Executive Committee should continue to work on coordinating timelines.

• The Executive Committee should consider a schedule with hypotheses due in December, reviewed in January by the Study Design Working Group, revisions made in February, and reviewed by the NCSAC at the end of March.

Action Items

• Dr. Graham, Chair of the Executive Committee, will report at the December meeting on finalizing a timeline and what it means with respect to the Working Groups and to Study implementation.

• The process of moving hypotheses will be from each Working Group to the Study Design Working Group to the NCSAC by the end of January. However, the Study Design Working Group will be consulted as to the feasibility of this schedule.

Discussion of Changes to Working Groups

• Dr. Mattison discussed reconstitution of the Development and Behavior Working Group. It has been proposed that the group be called the "Healthy Development" or "Health" Working Group and that certain members be thanked for their participation and additional members added. There was also the suggestion of identifying a neurotoxicologist to participate. Dr. Mattison said that he, Dr. Phillips, and Ms. Leahey would consider these ideas.

• Dr. Mattison asked the NCSAC whether there was a need to review all of the Working Group membership and participation. The NCSAC liaisons to the Working Groups together with the ICC liaisons and the Working Group co-chairs could review which members have been productive and which members perhaps may need to be replaced. Dr. Mattison also said that some Working Groups really have not been vitalized yet for a range of reasons, but others should be closed out. He asked whether there were members who would like to work on that issue, or whether it depended on the timeline for the NCSAC.

• Dr. Graham responded that she thought that changes to the Working Groups depended on information not yet available. She said that an important question to answer is how far a nonfederal person can go in the study development process. Dr. Mattison said that this issue would be discussed with the attorneys.

• Ms. Jones commented that some Working Group members initially participate enthusiastically, but then tend to "burn out." Some of these participants renew their interest after a time. She suggested that rather than ask people to end their participation, perhaps they could be allowed to have the option of taking a less active role, moving into a new area as the Working Groups are revised, or ending their participation.

• Dr. Mattison responded that the Working Groups have core members who are called upon on a regular basis for writing or information or expertise and an at-large membership. Possibly participants could shift from core to at-large and back and forth as time goes on.

• Dr. Graham expressed concern that the development of the reproductive system does not appear as a theme. She said that the themes provide an intellectual and managerial construct to help with the overall Study, but they also perform a communication function in describing the Study and what it intends to achieve to other people. Dr. Graham suggested two ways this could be remedied: reproductive development could be made its own theme or the undesirable pregnancy outcomes theme could be relabeled reproductive health.

• Dr. Doswell suggested referring to the life course of the child from preconception to adulthood as a sort of unifying theme.

• Mr. Swartz commented that wordsmithing for some specific audiences, one of which clearly is the Hill, is an important issue. He also agreed with Dr. Doswell that laying out the Study in terms of life course would be useful to help people understand the Study and the need for the Study to continue for 20 years.

• Dr. Michael asked about the term "themes." Dr. Mattison clarified that themes are the domains or the broad areas of the Study focus. Hypotheses fit into these thematic areas. Dr. Michael also asked whether new themes would be added to incorporate health and focus on the healthy, whole, growing child. Dr. Mattison added that the Working Groups might be asked for input regarding any proposed changes to the themes.

Conclusions/Recommendations

• Rather than ask certain members of various Working Groups to end their participation, consider presenting the option of taking a less active role or moving into a new area as Working Groups are revised.

• Consider allowing Working Group participants to shift from core to at-large membership.

• Consider making "reproductive development" an added theme, or rename the "undesirable pregnancy outcomes" theme as reproductive health.

• Study Program Office staff should review what content is included in the undesirable pregnancy outcomes theme and refocus the theme on healthy outcomes rather than undesirable outcomes.

• Refer to the life course of the child from preconception to adulthood as a sort of unifying theme.

• Consider soliciting input from the Working Groups about recharacterizing current themes, rather than including additional themes.

Planning for the December Meeting

• Dr. Mattison asked committee members to discuss content and structure for the December meeting. He suggested inviting all Working Group co-chairs to participate, so that the ICC liaison, the NCSAC liaison, and the co-chairs would have an opportunity to confer. Dr. Spence agreed that this type of face-to-face meeting is essential in light of the timeline for finalizing the hypotheses.

• Dr. Mattison asked if Working Group members needed to attend the meeting. Dr. Dudley suggested that some time should be allowed for some "cross-pollination" across some of the Working Groups. Dr. Graham said that in some cases, it might be necessary to have additional Working Group members present in addition to the co-chairs.

• Dr. Mattison added that the Exposure to Chemical Agents Working Group likely will need to have the largest number of representatives available to meet with other Working Groups.

• Dr. Dudley pointed out that in some Working Groups, the individuals who actually wrote the hypotheses are not the co-chairs. He said that he thought it would be very important to invite those Working Group members who are actually doing the work. The co-chairs could help decide whom to invite.

• Ms. Leahey urged that the decision about whom to invite should be made as soon as possible, especially if all members of certain Working Groups will be invited. Dr. Graham said that she did not think that the entire membership of any Working Group would be needed. However, it is likely that several members (in addition to the co-chairs) of certain Working Groups might be needed.

• Ms. Leahey said that she would provide the NCSAC members rosters of all of the current Working Group members and the co-chairs within the next week to two weeks. She said that she hoped to set up conference calls with Working Group co-chairs and their NCSAC and ICC liaisons and that it would be possible to determine at that time whether additional Working Group members should be invited to the December meeting. Ms. Leahey also said that she would provide the committee with the cross-working group notes from the December 2002 meeting for reference.

• Dr. Michael said that the ICC liaisons are quite familiar with the Working Group membership and would be a good resource regarding who should be invited.

• Dr. Scheidt noted that the agenda would include the full Assembly meeting on Wednesday, plans for breakout groups, and the possibility of a poster session. He said that the planning committee for the Wednesday meeting probably would invite some Working Group members to those breakout groups. Dr. Scheidt added that it will be important to avoid confusion when informing the full Assembly about the agenda for that day. The invitation, with more specific agendas, should make clear to Working Group members that information about separate meetings will come from Dr. Mattison or the NCSAC.

• Dr. Scheidt reminded the committee of the full assembly meeting on Wednesday, the plans for breakout groups, and the possibility of a poster session. He stressed the need for clear communication with all participants about the meeting agenda.

• Marshalyn Yeargin-Allsopp, M.D., ICC Member, CDC, commented that as a member of the planning committee for the December meeting, she wanted to ensure that there is clarity about the Working Group activities, which the planning committee is assuming will be on the December 15 and 16 and separate from the Study Assembly meeting on December 17.

• Ms. Leahey said that she would plan to address the December meeting plans during the conference calls. She asked the committee members to look at two things prior to the conference calls: (1) a proposed letter that would go out to Working Group members that is a call for the revised hypotheses and (2) the letter that the NCSAC had issued to the various Working Groups that elicited responses from only three Working Group members. Dr. Graham added that the letter to the Working Groups about the hypotheses would have specific questions and instructions attached.

• Dr. Michael asked whether the Study Design Working Group had responded to the letter that was sent after the last NCSAC meeting. Dr. Mattison noted that the Study Design Working Group had not responded, but that he understood that there had been an e-mail communication the previous day that he would share. Dr. Dudley said that he had spoken with the group’s co-chairs by telephone.

Action Items

• Ms. Leahey will provide NCSAC members with rosters of all current Working Group members and the co-chairs.

• Ms. Leahey will schedule conference calls with Working Group co-chairs and their NCSAC and ICC liaisons to discuss plans for the December meeting and determine whether additional Working Group members should be invited to the meeting.

• Ms. Leahey will provide the committee with the cross-Working Group notes from the December 2002 meeting for reference.

• Before the conference call, committee members should review a proposed letter to Working Group members calling for the revised hypotheses. Committee members also should review the letter that the NCSAC had previously issued to the Working Groups.

Message to Dr. Alexander

• Dr. Mattison asked the group to consider content for the message to Dr. Alexander. He said that he thought that one of the messages would concern revising the way that themes are described, as well as interest in creating a healthy outcome theme. Another part of the message would ask that work be focused on coordinating timelines for Study implementation and work for the NCSAC. It also might be a good time to re-emphasize the issue of a representative sample across the U.S. as an NCSAC recommendation.

• Dr. Spence suggested that it might be important to discuss with Dr. Alexander the issue of having the workshop address race.

• Dr. Graham suggested providing a very short status report that the NCSAC will be giving instructions to the Working Groups, and the committee anticipates almost-final hypotheses in March. She also suggesting saying that the Development and Behavior Working Group would be reconstituted and something about the design workshop and that it will be important that the design work begin to dovetail.

• Dr. Mattison commented that Dr. Bullock of the American Psychological Association would write a letter summarizing the key recommendations made in her presentation.

• Dr. Mattison said that the letter to Dr. Alexander would be circulated to the NCSAC members for comments.

• The meeting was then adjourned.

NCSAC Committee Members

Donald R. Mattison, M.D., NCSAC Chair
National Institute of Child Health and Human Development, NIH, DHHS

Jan L. Leahey, NCSAC Executive Secretary
National Institute of Child Health and Human Development, NIH, DHHS

David C. Bellinger, Ph.D.
Boston Children’s Hospital

*Linda M. Burton, Ph.D.
Pennsylvania State University

George P. Daston, Ph.D.
Proctor & Gamble Company

Willa M. Doswell, R.N., Ph.D.
University of Pittsburgh School of Nursing

Donald J. Dudley, M.D.
University of Texas Health Sciences Center at San Antonio

Alan R. Fleischman, M.D.
The New York Academy of Medicine

Barbara R. Foorman, Ph.D.
University of Texas Health Science Center at Houston

Judith A. Graham, Ph.D.
American Chemistry Council

*Fernando A. Guerra, M.D., M.P.H.
San Antonio Metropolitan Health District

Loretta Jones, M.A.
Healthy African American Families

*Shiriki Kumanyika, Ph.D., M.P.H.
University of Pennsylvania School of Medicine

*Philip J. Landrigan, M.D.
Mount Sinai School of Medicine

Grace LeMasters, Ph.D.
University of Cincinnati

Roderick Joseph Alexander Little, Ph.D.
University of Michigan

Robert T. Michael, Ph.D.
University of Chicago

Deborah A. Phillips, Ph.D.
Georgetown University

P. Barry Ryan, Ph.D.
Emory University Rollins School of Public Health

M. Anne Spence, Ph.D.
University of California, Irvine Medical Center

Lucina Suarez, Ph.D.
Texas Department of Health

Daniel J. Swartz
Children’s Environmental Health Network

Barry S. Zuckerman, M.D.
Boston University School of Medicine

*Did not attend

Interagency Coordinating Committee Members

*Amy Branum, M.S.P.H.
National Center for Health Statistics, CDC, DHHS

Adolfo Correa, M.D., Ph.D.
National Center on Birth Defects and Developmental Disabilities, CDC, DHHS

Sarah Keim, M.A.
National Institute of Child Health and Human Development, NIH, DHHS

Woodie Kessel, M.D., M.P.H.
Office of the Secretary, DHHS

Carole A. Kimmel, Ph.D.
National Center for Environmental Assessment, EPA

Mark Klebanoff, M.D., M.P.H.
National Institute of Child Health and Human Development, NIH, DHHS

Pauline Mendola, Ph.D.
Office of Research and Development, EPA

*Sheila A. Newton, Ph.D.
National Institute of Environmental Health Sciences, NIH, DHHS

James J. Quackenboss, M.S.
Office of Research and Development, EPA

Peter C. Scheidt, M.D., M.P.H.
National Institute of Child Health and Human Development, NIH, DHHS

Kenneth Schoendorf, M.D., M.P.H.
National Center for Health Statistics, CDC, DHHS

Sherry G. Selevan, Ph.D.
Office of Research and Development, EPA

Marshalyn Yeargin-Allsopp, M.D.
National Center on Birth Defects and Developmental Disabilities, CDC, DHHS

*Did not attend

Presenters/Speakers

Ruth A. Brenner, M.D., M.P.H.
National Institute of Child Health and Human Development, NIH, DHHS

Merry Bullock, Ph.D.
American Psychological Association

Barbara R. Foorman, Ph.D.
University of Texas-Houston

Doris B. Haire
American Foundation for Maternal and Child Health

John R. Lutzker, Ph.D.
National Center for Injury Prevention and Control, CDC

Haluk Ozkaynak, Ph.D., M.S.
Office of Research and Development, EPA

Barry S. Zuckerman, M.D.
Boston University School of Medicine

Observers and Other Participants

Appendix A

Appendix B

Appendix C

Appendix D

Appendix E