Skip Navigation

Skip sharing on social media links

 December 2003 NCSAC Meeting Summary Minutes

The 8th Meeting of the National Children’s Study Federal Advisory Committee (NCSAC)

December 15–16, 2003
Sheraton Atlanta Hotel
Atlanta, GA

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).

Monday, December 15: Plenary Session

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

Welcome

Review Agenda, Modifications, and Goals

Dr. Mattison welcomed National Children’s Study Advisory Committee (NCSAC) members to the eighth meeting of the NCSAC. He said an updated agenda was available in participants’ white folders, and he added that he would discuss some additional late-breaking items later. Dr. Mattison covered:

  • Discussion of Meeting Objectives. Dr. Mattison stated that this would be a highly focused, working meeting to develop a work plan so that at the end of the March meeting the NCSAC can deliver finalized hypotheses and themes to Duane Alexander, M.D., NICHD, NIH, DHHS. Additional goals of the NCSAC meeting were to assure the completeness of or identify any missing elements in the 70 hypotheses from the Working Groups and to develop descriptions and measures of exposures and outcomes.

    Dr. Mattison explained that both themes and hypotheses are important because they help reach two different audiences. The themes provide a way to quickly explain aspects of the Study to parents or legislators. Hypotheses, in contrast, explain the scientific aspects of the Study to colleagues and scientists.

  • Health Theme. A theme that emerged at the September 2003 NCSAC meeting was health. The Executive Committee of the NCSAC and the ICC asked Working Groups and the thematic breakout groups to evaluate how health should be defined in the National Children’s Study. Dr. Mattison explained that later in the day, Neal Halfon, M.D., M.P.H., University of California, Los Angeles, would give a presentation on a work plan for incorporating health into the Study.

  • Role of Liaisons. Jan Leahey, NICHD, NIH, DHHS, Sarah Keim, M.A., NICHD, NHI, DHHS, Peter Scheidt, M.D., M.P.H., NICHD, NIH, DHHS, and Dr. Mattison have been discussing how to improve and support NCSAC members in their role as liaisons. They requested that NCSAC and Working Group members consider how to enhance the liaison role.
     
  • Comments on Minutes from Last Meeting. Dr. Mattison said that NCSAC members have a summary of recommendations and minutes from the September meeting plenary and breakout sessions, and he asked that any editorial or substantive issues be brought to his or Ms. Leahey’s attention.
  • Breakout Session Attendance. Before moving on to the morning’s presentations, Dr. Mattison mentioned that some Working Groups had several members at the meeting, and he encouraged them not to all attend the same thematic breakout session.

Update from Program Office

Study Timelines, Institute Updates, 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:

  • Director’s Response to the NCSAC. Dr. Alexander appreciated the specific and formal recommendations he received from the NCSAC at the September 2003 meeting, and he requests that he receive similar formal recommendations in the future.

    Dr. Alexander realizes that the liaison role for the members of theNCSAC is important and recognizes that the alignment of timelines of the NCSAC and ICC are critical. He agrees with the recommendation for a probability-based sample as much as feasible and welcomes exploring that in considerable detail. Dr. Alexander looks forward to seeing:

    • Revised and updated hypotheses where needed
    • Inclusion of healthy development, social factors, and race/ethnicity
    • A re-energized Development and Behavior Working Group.

    Dr. Alexander recognizes that the NCSAC will need to examine and re-evaluate the structure and functions of itself and the Working Groups as the Study evolves.

  • Program Office Staffing. The Program Office has added three staff members since the last NCSAC meeting, including:
    • Ruth Brenner, M.D., M.P.H., a pediatric epidemiologist who is the protocol development leader
    • Sarah Knox, Ph.D., an experienced behavioral psychologist who will be leading the health behavior and development pilot study efforts and the behavioral and social science components of protocol development
    • Warren Galke, Ph.D., an environmental epidemiologist who will work at the Program Office on data management and as the Clinical Coordinating Center Project Officer.

    In addition to these full-time staff, several part-time or detailed scientists from CDC and EPA continue to work in the Program Office. In addition, Terry Dwyer, M.D., M.P.H., a distinguished senior epidemiologist from Australia, will spend his sabbatical (six to nine months) as a visiting scientist.

  • Contracts. Hiring Battelle as the technical support contractor has given the Program Office the capacity to undertake specific pilot studies, complex reviews, scientific papers, white papers, and other projects. Work assignments underway on that contract include:
    • Advantages and limitations of probability-based sampling for the National Children’s Study
    • Critical data collection requirements (data collection efforts for hypotheses)
    • Recruitment and response rates, including what has been achieved in other relevant studies, projections for the Study, and impact on sampling strategies
    • Sample design options, particularly hybrid options.

    Battelle has begun work quickly and the Program Office already has initial drafts of three of four papers. Work has also begun on an extensive literature review, critical analysis, and proposed candidate developmental measures.

    The Program Office needs to identify and procure a clinical coordinating and data management center. That process will take approximately one year, and the Program Office cannot wait for that to have been done before identifying and planning the information technology (IT) system for the Study. Therefore, a contract was developed with the following objectives:

    • Information management system planning
    • Database development
    • Data collections systems
    • Operations systems.

    This contract has been awarded, for a period of up to five years, to a team of Booz Allen (lead), RTI International, Battelle, Levine Frickie, and Sanz. Dr. Scheidt added that this is a blue ribbon team, and the Program Office is glad to have them on board.

  • Protocol Status. The original projection was that there would be a first draft protocol by December 2003. That is not in place due to the tremendous delays in staffing for the National Children’s Study because of the personnel freezes at the NIH and the difficulty in recruiting in the face of uncertain funding. Now that staff is in place, the process is underway and moving quickly, starting with:
    • The 2001 draft protocol by ICC
    • Core hypotheses and Study areas document written a year ago and updated for this meeting
    • Measures database that the ICC developed last spring.

    A protocol team is in place at the Program Office, led by Dr. Brenner. The protocol draft outline has been laid out and the writing has already started. This protocol is not as detailed as an operations manual in which every single measure might be specified by how it is collected. It will, however, contain enough detail to define potential risks, timing of measures, and the potential burden on participants. It also must be thorough enough to obtain Institutional Review Board (IRB) and Office of Management and Budget (OMB) review and approval. The first rough draft will be available by March 2004.

  • Partnership Development. In the last three months, Marion J. Balsam, M.D., NICHD, NIH, DHHS, has held discussions with the Foundation for NIH, which is set up to establish public/private partnerships with various entities at the NIH. A proposal of the National Children’s Study was presented to the board of the Foundation for NIH, and it was officially approved. The Foundation for NIH will reach out, identify, and broker partnerships for the Study. These partnerships might:
    • Fund adjunct and sub-studies
    • Identify additional financial support for elements or the Study itself
    • Provide incentives and contributions for the Study.

    The National Children’s Study and the Foundation for NIH are preparing a memorandum of understanding.

  • Proposed Expansion of the National Children’s Study. A very large adult cohort is required to translate the enormous progress that has been made in identifying the human genome into how major adult diseases might be further understood and perhaps prevented. The leaders of the National Human Genome Research Institute (NHGRI) have been considering ways to initiate these large cohort studies.

    In December, the NHGRI and several other Institutes held a meeting of scientific experts in adult epidemiology and genetic diseases to consider the necessity and advisability of a large adult cohort and whether merging with the National Children’s Study would be the best way to do that. Several members of the ICC attended the meeting. This consultation affirmed that it is scientifically sound and advisable to merge an adult cohort with the National Children’s Study. They proposed the possibility of combining a longitudinal followup of all the parents and available grandparents of children enrolled in the Study to achieve the kinds of numbers needed to answer questions about common adult diseases.

    The ICC, Program Office, and the NCSAC are beginning to consider the implications of this proposal. Dr. Scheidt said that Alan Guttmacher, M.D., Deputy Director of the NHGRI, would make a presentation to the NCSAC on Tuesday morning and would meet with the ICC Tuesday afternoon.

  • Timeline and Coordination. Dr. Scheidt said that the plan is to begin Study enrollment at initial sites in early to mid 2006. Previous timelines said 2005, but that date was pushed back because there have been no funding increases in 2004. Dr. Scheidt presented the current Study timelines:
    • Pilot studies. The NCSAC continues to review and advise on pilot study proposals.
    • Partnership development and community engagement. The NCSAC and ICC welcome input, ideas, and contacts for this ongoing endeavor.
    • Preliminary protocol development. A reasonable draft protocol should be complete by June 2004. Currently, the NCSAC is proposing refinements, additional hypotheses, and specific measures.
    • Information management system design and development. Work has begun and the Program Office will seek NCSAC advice on specific aspects as needed.
    • Protocol refinement, OMB clearance, and selection of measurement techniques. This will occur in the latter half of 2004 and 2005, but IRB approvals must be obtained by the end of 2005 in order to begin enrollment on time. NCSAC will advise later in 2004 about tradeoffs of including and/or excluding major components of the protocol.
    • Contracting for coordinating center, pilot protocol, vanguard centers, and repository. These activities will occur in 2004 and 2005.
    • Enroll participants at initial sites. Enrollment should begin in 2006.

    Dr. Scheidt said that the above timeline shows that 2004 will be an intense year for the NCSAC and its Working Groups. He added that a great deal of expertise is needed to plan the Study, and the NCSAC gives an essential broad overview of Study planning, integrates findings, and provides advice and wisdom. Working Groups are particularly important for giving advice on focused scientific areas. The Working Groups have been relatively inactive in 2003, and Dr. Scheidt cautioned the NCSAC that the pace must pick up. The information that the ICC and Program Office receive from the NCSAC and the Working Groups are critical to the process ahead.

Questions and Comments for Dr. Scheidt

  • Dr. Mattison mentioned that one issue that has been discussed in the past is how the Study is going to be carried out. For instance, will it be contracted out? Will only academic health centers participate? How can the Study best develop a probability-based sample? How will the Study issue an RFA and to whom will it be issued? Dr. Scheidt responded that they anticipate a central coordinating data management center and multiple sites (probably 35 to 40) around the nation. The sites will most likely be primarily, but not exclusively, major academic centers. Site selection will depend on geographic area and ability to do the work. The Program Office expects to develop a contractual mechanism with considerable input from investigators at individual sites.
  • Dr. Guttmacher made a brief comment about the NHGRI and the exciting prospect of broadening the Study. He thought it might be helpful to brainstorm with the NCSAC at this meeting because they would not meet again for several months. Dr. Scheidt said that the ICC and NCSAC have not had time to deal with any specifics. Dr. Mattison invited Dr. Guttmacher to the dinner that evening, and he asked Judith A. Graham, Ph.D., American Chemistry Council, if she could track the issues that arise and assign them to NCSAC members after the meeting. Dr. Graham agreed.
  • Dr. Graham congratulated Dr. Scheidt on the excellent people hired by the Program Office. She asked how they planned to ensure comparability of outcome measures and exposure measures at different sites. For instance, did they plan to have a central lab run all pesticide tests? Dr. Scheidt said they would do whatever was necessary, and he added that quality assurance needs to be central to that process. The requirements to train, monitor, and test will be part of the responsibilities of the clinical coordinating center.
  • Dr. Graham then asked how the Working Groups and external peer reviewers would be involved in evaluating the draft protocol. Dr. Scheidt responded that when the draft protocol is ready for review, it would become a public process. At that point, the NCSAC, the Working Groups, the public, and institutions and entities that will carry out the protocol can all provide input. The Program Office has already asked for guidance on specific elements from the Working Groups through the NCSAC. The Program Office needs that advice to develop the protocol. The set of questions sent to the NCSAC two meetings ago was an attempt to obtain expert advice from the Working Groups.
  • Fernando Guerra, M.D., M.P.H., San Antonio Metropolitan Health District, asked whether an announcement for information technology (IT) systems development would include connections to large data management systems already in place, for example, chronic disease surveillance systems, disease registries, or newborn screening programs. Ms. Keim responded that the Program Office recognized that need and has already started discussions with federal and nonfederal systems that have databases in place, so that they can link rather than reinvent. Dr. Scheidt said that the Battelle group was commissioned to examine many of the databases available that might be candidates for possible links and mergers.
  • Mark Cosentino, D.P.M., Ph.D., Science Applications International Corporation, said that he hoped in developing the Study IT system they had not forgotten about the repository because once the material is in, it is sometimes difficult to link the epidemiological information and results with a particular specimen. If this is factored in during the planning stages, it can prevent expensive retrofitting of the system later. Dr. Scheidt asked Dr. Galke to respond. Dr. Galke said that they are very aware of the need to be able to track each individual sample to its origin and that the system is being designed with that capability.
  • Dr. Guerra asked whether the Study would attempt to enroll parents and grandparents of enrolled children that live in other parts of the world. Some current longitudinal studies compare the health of near relatives who stay in their native lands with family members who live in this country. Dr. Scheidt said that the details of accessing grandparents have not yet been considered, but one approach might be similar to plans for people who move. One advantage of a national study is that participants who move can be passed from one center to another. However, this is very challenging when people live in different countries. He said the concept is intriguing and perhaps a way can be found to address that.
  • Robert T. Michael, Ph.D., University of Chicago, asked Dr. Scheidt who would make decisions about the protocol after the NCSAC, Working Groups, and the public provided input. Dr. Scheidt replied that the ICC and Institute Director would make final decisions on the protocol. However, they need input from the NCSAC and Working Groups as the protocol evolves.

    Dr. Michael’s second question concerned the role of academic centers. He asked for more information on the difference between data capturing, which investigators at institutions will do, versus data analysis, which they may or may not do. Dr. Scheidt explained that investigators at data collection sites would be involved in data analysis of data collected at their centers. However, the ICC was committed to making sure that there will be early and accessible public use of data sets; data sets will not be owned and occupied by investigators at centers. The Program Office is more concerned that the data be maximally and optimally used, and cost projections for the budget include costs for answering specific hypotheses as well as successive uses of the data sets. The details on how to balance these two interests have not yet been worked out.

  • Deborah A. Phillips, Ph.D., Georgetown University, wondered how data collection sites would have input into protocol development. Refining a protocol based on institutional input can take a year, and she noted that this process is not built into the timeline. Dr. Scheidt answered that part of the RFA will require that applying sites display competence to carry out the work. National scope is critical, as is having support from individual sites and their communities. He added that the protocol would need to reserve some flexibility in order to adapt to local input and needs. He estimated that 75 to 80 percent of the protocol would be a highly rigorous national plan, and the rest could allow for flexibility and input from individual sites.

    Dr. Phillips then asked that Dr. Scheidt be brutally honest about funding strategy, because she is concerned that support has been ambivalent due to financial uncertainly. She added that some colleagues are concerned that funding for the Study will decrease available monies for investigator initiated studies. In terms of funding, Dr. Scheidt said that the Study would have to learn to continue living with financial uncertainty, despite a feeling that momentum is increasing. He also was encouraged by the enthusiastic support from Dr. Zerhouni, Director of the NIH, and by the possible addition of an adult component, which may make this effort easier to fund.

  • Loretta Jones, M.A., Healthy African American Families, congratulated Dr. Scheidt and his colleagues for considering expanding the Study to include parents and grandparents. She said that looking at the whole rather than just the parts could provide enormous amounts of information and more support from communities. She recommended that Study planners start talking to communities earlier rather than later to maximize community buy-in and to obtain community input. Dr. Scheidt said that theme of the Assembly on Wednesday is to start that process with communities across the nation.
  • Carol Hogue, Ph.D, M.P.H., Emory University, congratulated Dr. Scheidt on the progress made to date. She said that when she was at CDC, they contracted with the University of North Carolina Biostatistics Department and found that it was virtually impossible to enroll pregnant women before they obtained prenatal care unless the researchers did community based sampling. She also suggested that the Study work with the full spectrum of groups interested in abortion and try to evaluate abortion’s effect on women. She recommended that the Study prospectively follow a sample of 9- to 10-year-old boys and girls prior to sexual activity and pregnancy. Dr. Scheidt said that it was an interesting proposal, but that the Study was already designed to enroll women who plan to become pregnant in the next three years or who are already pregnant. Dr. Hogue than asked what proportion of pregnancies occurred in 16 to 19 year olds, and Dr. Scheidt said that he did not know. Dr. Hogue said more than one out of four.
  • Doris B. Haire, American Foundation for Maternal and Child Health, asked if a pediatric neurologist had been assigned to the NCSAC. Ms. Keim answered that there would be one available on the Battelle team to provide input on the white papers concerning developmental issues. Dr. Mattison added that the Behavior and Development Working Groups was dealing with those issues as well.

Conclusions/Recommendations

  • The NCSAC and Working Groups should forward refinements, additional hypotheses, and specific measures to the ICC for inclusion into the first draft protocol, which will be available in March 2004.
  • The ICC, Program Office, and the NCSAC will consider the implications of the proposed adult cohort proposal.
  • The Study will begin to reach out to the community for input.

Status of Themes and Hypotheses, ICC Document

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

Dr. Schoendorf thanked Dr. Mattison and the NCSAC for the opportunity to talk to them.

  • Purpose of Presentation. Dr. Schoendorf said that the purpose of the presentation was to update the NCSAC on core hypotheses, introduce priority outcomes and exposures, and refocus efforts on development of Study measures.
  • Reasons for a Hypothesis-Driven Study. He stated that the National Children’s Study is a hypothesis-driven study designed to answer specific research questions and it would not be another general survey of children’s health. NCSAC Working Groups, the ICC, and others developed the original core hypotheses. The original set of core hypotheses were presented by Dr. Alexander at the December 2002 assembly meeting.

    The reasons for having core hypotheses were to:

    • Establish a framework for Study design
    • Draft the protocol (sampling strategy, periodicity of followup, and collection of data)
    • Prioritize pilot studies
    • Provide public identity for the Study
    • Help stakeholders understand what the Study would do.

    The set of hypotheses was also intended to:

    • Be considered a set
    • Move the discussion to the next level
    • Identify specific measurement issues.

    The set of hypotheses was not intended to represent the entirety of the Study or to exclude all other areas of study. Dr. Schoendorf explained that protocol development was an evolutionary process that focused on the development and inclusion of individual hypotheses. He explained that this set of individual hypotheses does not successfully convey the scope of the Study. The hypotheses can possibly draw attention from important areas that do not have specific, separate hypotheses.

    Dr. Schoendorf pointed out an internal contradiction that has resulted in some confusion. One of the reasons for having hypotheses was to provide a public identity, but at the same time they were never meant to represent the entire scope of the Study. The ICC thought it was important to refocus at this time, because the goal is not to have the perfect set of hypotheses, but rather to develop measures, create a Study protocol, and actually have a Study.

  • Outcomes and Exposures. Dr. Schoendorf outlined the current priority Study areas—outcomes and exposures. Outcomes were previously codified in the original set of core hypotheses, and they represent key components of child health and development. Priority outcomes are:
    • Pregnancy outcomes
    • Neurodevelopment and behavior
    • Injury
    • Asthma
    • Obesity and physical development.

    Exposures were mentioned in the authorizing legislation, included in original core hypotheses documents, and are now explicitly enumerated. They are:

    • Physical environment (housing)
    • Chemical exposures (air pollution, water pollution)
    • Biologic environment (infections, allergens, diet, nutrition)
    • Genetics
    • Psychosocial milieu (family, school, community).
  • Next Steps. Dr. Schoendorf concluded his presentation by discussing the next steps for the Study. He said that it is necessary to acknowledge that the set of core hypotheses is necessary but not sufficient for explaining the entire Study. As planning proceeds, it will be necessary to move beyond core hypotheses and specifically define outcome and exposure measurements.

Questions and Comments for Dr. Schoendorf

  • Dr. Graham said that there is an opportunity for using the ICC document to market the Study. She added that air pollution, drugs of abuse, and pharmaceuticals are exposures in the Study, and they should probably be mentioned in this document as well. Dr. Schoendorf said that marketing is not the Study organizers’ forte, and he added that a communications specialist would tailor the information for specific audiences. He explained that drugs of abuse and pharmaceuticals are in the Study but did not make it into this document.
  • Lucina Suarez, Ph.D., Texas Department of Health, commended the group on refocusing attention on outcomes and exposures.
  • Robert Michael, Ph.D., University of Chicago, asked that in the section discussing outcomes and exposures and how they impact an organism, a bullet be added that said "and the process by which they interact."
  • Alan R. Fleischman, M.D., New York Academy of Medicine, stated that this is an extremely helpful document but the hypotheses are very biologized. Psychosocial milieu is defined under exposures, but in the hypotheses, the complexity of how the psychosocial milieu will impact each and every one of the exposures is not included. Dr. Schoendorf said that the planners intend to measure the interactions. He added that it is not easy to express in English, and it is even harder to make it happen in a study because measurements are discrete measures in disparate areas. It is complicated, and when the Study planning process evolves it will become clearer what the Study has captured and what it lacks.

    Dr. Scheidt said that following the last round of hypotheses review, the Program Office realized exactly what Dr. Fleischman was saying with regard to the Social Environment hypothesis. They challenged the Social Environment Working Group to explain how these interactions can be analyzed in this large a study. The Working Group replied that it is a multi-factorial process that requires complex multi-level modeling. Last week, the Program Office sent Battelle a work assignment to connect a group of statisticians with the Social Environment Working Group to develop the complex models necessary to answer these questions.
  • Daniel J. Swartz, Children’s Environmental Health Network, wanted to add his voice to the chorus that this document is definitely a step in the right direction. He suggested that three graphics might be helpful to clarify complicated interactions. The first is a simple matrix with outcomes across the top, divided into sub outcomes, and exposures down the other axis. This can show the possible interplay of the factors. The second would be to take a couple of the boxes from the matrix and look at how these are not separate physical, social, and biological environments, but instead all interact with each other. The third graph, which might be especially helpful for legislators, would show outcomes over time. One could then see what the Study hopes to learn over the course of a real human life. These would be helpful not only for creating selling points, but to help people truly understand what the Study is.
  • Deborah A. Phillips, Ph.D., Georgetown University, said that this is a big step forward and it is exciting to see the Study get to the verge of where it is supposed to be. One missing piece is the need to stress that it is a longitudinal, not a static, study. The Study will enable researchers to look at how health and non-health processes unfold over time. This is the beauty of the Study and should be emphasized. She added that she continues to hope to see a bullet that says "healthy development." Dr. Schoendorf thanked Dr. Phillips for stressing the longitudinal aspect of the Study and agreed that it needs to be emphasized. In terms of healthy development, he said that he thought they had incorporated the concept, but need to think more about how to measure health. Dr. Mattison reminded members of the committee that later in the morning Dr. Halfon will present a conceptual framework for incorporating healthy development into the Study.
  • Philip J. Landrigan, M.D., Mount Sinai School of Medicine, said that he remains concerned that the section dealing with chemical and environmental influences on development and behavior is still sparse in comparison to the asthma or obesity sections. For instance, it does not include a specific hypothesis about the impact of metals on brain development. He stated that he understands from the minutes that the Working Group is lagging behind the others, but right now it is a rather serious omission and the Study has to get it right. Dr. Schoendorf acknowledged that there are omissions in what is essentially a communications document. But measures are now being developed and if mention of important exposures and outcomes are missing from that list, then it will be time to become concerned.
  • Kristine Suozzi, Ph.D., Bernalillo County Environmental Health Department, a member of the Health Disparities and Environmental Justice Working Group, acknowledged that her Working Group is late in sending their cumulative risk hypothesis, which looks at multiple exposures particularly in communities of color, to the ICC. It. She asked about the status of the measures of racism hypothesis. Dr. Mattison said he would talk with Dr. Suozzi about this later because there had been some miscommunication.
  • Denise Dougherty, Ph.D., Agency for Healthcare Research and Quality, DHHS, introduced herself as one of the two federal co-chairs of the Health Services Working Group. She said that the health services hypothesis draft is an improvement because it addresses inappropriate health services for treating asthma, but it could contain similar broadly-stated hypotheses for the four other outcome areas as well. Dr. Schoendorf said that the health guide measurements should be considered as a set. Dr. Mattison commented that Dr. Halfon has moved into a role as an advisor on health development, and he said that Dr. Dougherty, William F. Lawrence, M.D., M.S., Agency for Healthcare Research and Quality, DHHS, and Lisa Simpson, M.B., B.Ch., M.P.H., Institute for Child Health Policy, University of Florida, have agreed to take leadership roles in the Health Services Working Group. The hope is that this will generate more activity in that Working Group.
  • Dr. Graham added that some of the issues raised during this session could be discussed in the thematic breakout sessions in the afternoon. Participants could discuss what needs to be added and subtracted from the core hypotheses.
  • Ms. Haire said that hypothesis two on page four of the ICC document contains no mention of antenatal exposure to drugs or effects of procedures caused by the use of drugs used during childbirth. Only 12 drugs have ever been approved by the FDA for obstetric care. She has abstracted important information about risks from the packet inserts, and she asked permission to send copies of these to each member of the NCSAC. Dr. Mattison said that if Ms. Haire sent it in, he would include it in the meeting packet.
  • Dr. Scheidt explained that the ICC document does not denigrate the importance of hypotheses, but it does elevate the importance of the broad databases needed for exposures and outcomes. Although that was needed, hypotheses are still critically important. The questions raised here about gaps in hypotheses are very important. The ICC needs well-developed, complete hypotheses that justify their health importance, justify that they require a study of this size and complexity, and demonstrate that the Study can answer them. He stated that if the Working Groups provide satisfactory hypotheses, they would be included in the Study.

Conclusions/Recommendations

  • The set of hypotheses does not represent the entire Study.
  • The Study will refocus on developing outcome and exposure measures and writing a protocol.
  • Statisticians from Battelle will work with the Social Environment Working Group to develop models to analyze complex interactions between exposures and psychosocial milieu.
  • Dr. Dougherty, Dr. Lawrence, and Ms. Simpson will assume leadership roles in the Health Services Working Group.

Report from Joint ICC/NCSAC Executive Committee

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

Dr. Graham reported on several conference calls of the Executive Committee. Items discussed included developing the agenda for this meeting and how to incorporate the continuum of health into the Study to prevent a focus solely on disease. In addition, the Executive Committee discussed the future of the Working Groups and the NCSAC and how the roles will change as the Study evolves. They also reviewed some previous work they had done on communications guidelines. They want to make sure that at the end of this meeting they have developed clear recommendations for communications rather than a long list of opinions. This effort is consistent with the advice from Dr. Alexander.

Future activities include developing schedules and interfaces among Study planners. They also need to appoint subcommittees to consider emerging issues such as the proposal from the NHGRI. The work of the subcommittee dealing with design issues should continue as needed. She asked that anyone with additional items for the Executive Committee send an e-mail to Dr. Mattison.

Questions and Comments for Dr. Graham

  • Donald Dudley, M.D., University of Texas Health Sciences Center at San Antonio, noted that one of the issues that had been discussed by the Executive Committee was ways to engage the Working Groups through the liaison process. The plan was for each liaison to work with his or her Working Group prior to this meeting so that each Working Group would provide initial input on developing measures of exposures and outcomes. He noted that the Pregnancy and Infancy Working Group had responded. He asked Dr. Graham what he should do with this information. Dr. Graham said that the Executive Committee did not receive responses from all of the Working Groups, so that part of the process did not work out. But those with information from the Working Groups should bring a summary to the afternoon thematic breakout sessions. She said that a way must be found to develop a process for filtering this information and forwarding it to the ICC for consideration.
  • Dr. Dudley then asked if the entire NCSAC needed to consider the information from the Working Groups, or should individual liaisons present findings to the ICC. Dr. Graham responded that that process had not been decided, but her opinion was that the entire committee should review the material. She added that summaries from each thematic group would be presented tomorrow. The NCSAC could then accept or modify the summaries and then send them on to the ICC.
  • Dr. Scheidt commented that if one considers the amount of work that needs to be done in the next year, sending this information through the NCSAC as a whole might slow the process down. He asked that the process be streamlined by telling the liaisons what needs to go to the whole committee and what can be forwarded directly to the ICC. Posting it on the Web site would ensure that information sent directly to the ICC was publicly available.
  • Dr. Dudley said that the volume of information he has is extensive, and he urged the committee to keep in mind that a huge volume of material was coming from Working Groups and it is unrealistic to expect it to be reviewed in the amount of time available at the meeting. Dr. Graham responded that the Working Groups exist because they have a tremendous amount of expertise and the committee would not be second-guessing them; rather, the committee would determine if members agree conceptually or not.
  • Ms. Leahey commented that over the last few months, she and Dr. Mattison had been trying to develop a hypotheses-tracking system. Such a system will allow them to take information from individual Working Groups and send it to individual members of the Working Group, all members of the Working Group, or NCSAC members for comments. She hoped that this will help speed up the process. She also wanted to remind members that she had arranged two working lunches. One will be today to follow up on Dr. Fleischman’s recommendation to discuss some of the issues raised by Dr. Scheidt, and the Executive Committee will meet tomorrow at lunch.
  • Dr. Graham said they did not want to strip the level of detail from information supplied by Working Groups or turn the NCSAC into a barrier. They need to make sure that the richness of the Working Group results are forwarded to the ICC, not just summaries. Dr. Scheidt suggested that workshop and pilot study information did not need to go through the NCSAC before going to the ICC; only findings from the Working Groups need to go through the NCSAC.
  • Dr. Fleischman asked for the names of the members of the Executive Committee. Dr. Graham listed the following: Dr. Mattison, Dr. LeMasters, Dr. Dudley, Dr. Phillips, Dr. Landrigan, Dr. Scheidt, Ms. Leahey, and the co-chairs of ICC. The co-chairs rotate, so whoever is currently a co-chair is a member of the Executive Committee. Mr. Quackenboss is the standing member from the ICC.

Action Item

The Executive Committee will develop a streamlined process for forwarding information from the Working Groups to the ICC.

Update of Pilot Studies

Carole Kimmel, Ph.D., ICC Member, Office of Research and Development, EPA

Dr. Kimmel began by saying that many of the pilot studies focus on methods development and specification of measures for the Study. A few pilot studies focus on design issues. The briefing book and folders for the meeting contain summaries of the ongoing pilot studies. She urged people to attend the pilot study poster session Wednesday afternoon.

  • Studies Currently Being Developed. Some of the studies not included in the summaries, updates, or posters are those in development. These include:
    • Burden of data collection on Study participants
    • Methods for newborn assessment
    • Utility of frozen breast milk in accurate assessment of environmental toxicants or their metabolites, metabolic, nutritional, and genomic endpoints (compares frozen breast milk to fresh breast milk and blood)
    • Feasibility of using 3D ultrasound for fetal assessment
    • Comparison and independent assessment of the abilities and functionality of two nomenclature systems for prescription drugs, over-the-counter drugs, herbals, and supplements
    • Followup of initial focus groups for the Study
    • A review exploring the measures available for evaluating health status, emotional and social functioning, mental development, and cognition
    • Methods for successful cohort retention in a longitudinal followup of children and families
    • Measuring housing quality and characteristics
    • Assessing dietary intakes and patterns in women and young children
    • Statistical methods for the life course approach to the development of disease: causal inference, collinearity, interactions, and sample size.
  • Completed Workshops. Many workshops have been completed and most of them have explanatory posters at the Study Assembly meeting on Wednesday. They include:
    • Community Engagement (December 3, 2002)
    • Fetal and Neonatal Growth and Development Assessment Methods (December 15–16, 2002)
    • Medicines Exposure: Collection, Coding, and Classification (December 16, 2002)
    • International Consultation in Longitudinal Cohort Studies (December 16, 2002)
    • Innovative Technologies for Remote Collection of Data for the National Children’s Study (May 12–13, 2003)
    • Ethical Issues in Longitudinal Pediatric Studies: "Looking Back, Thinking Forward" (June 4, 2003)
    • Assessing the Incidence and Outcomes of Mild Traumatic Brain Injury (September 11–12, 2003)
    • Placental Measurements (November 3–4, 2003)
    • Psychosocial Stress and Pregnancy and the Infant (November 12–13, 2003)
    • Physical Activity (November 17–18, 2003).
  • Workshops Scheduled/Planned. Several workshops are planned, including:
    • Use of Herbal Products in Pregnancy, Breastfeeding, and Childhood Workshop
      (December 16, 2003)
    • Sampling Design (TBD)
    • Effects of Media (January 22–23, 2004)
    • Measures of Social Environment (TBD)
    • Impact of Rurality (TBD)
    • Day-Specific Probabilities of Pregnancy (TBD)
    • Questionnaire and Dairy-Based Methods for the Early Assessment of Asthma-Related Health Outcomes (May 27, 2004)
  • Proposed Workshops. Dr. Kimmel said that a workshop on health services measures has been approved, and several additional proposals are in review. She said that the Program Office tries to expedite review of pilot studies and workshops as much as possible to allow rapid implementation.
  • Workshop Oversight. In November 2003, the ICC met with researchers running the various pilot studies to do in-depth reviews. This is done on an annual basis to track pilot study progress and to make sure they are addressing issues specific to the National Children’s Study. Dr. Kimmel reported that reviews have been a fruitful process and the posters are a result of the annual reviews.

Questions and Comments for Dr. Kimmel

  • Dr. Landrigan made a comment concerning the workshop on recruitment and retention. He said that at least 3 of the 12 children’s centers (Mount Sinai, Columbia, and Berkeley) have been running prospective cohort studies for the past five years. In the aggregate, he estimated that at least 1,500 children are enrolled in the three studies. The Mount Sinai and Columbia studies are looking at neurodevelopment in inner-city children, and the Berkeley study is evaluating the impacts of pesticides on rural children. All of them use a design similar to that proposed for the National Children’s Study—recruiting while the babies are in utero and then following them forward. He suggested the Program Office develop a mechanism to consult with the people running those three studies. Dr. Kimmel said they already have begun to encourage children’s centers to develop papers on lessons learned about recruitment and retention and pesticide exposure measurement. She hopes that Dr. Landrigan will help develop those papers. Dr. Scheidt said that a series of focus groups had gathered information, but they did not address empirical experiences at children’s centers. Proposals for pilot studies can come from any of the entities of the National Children’s Study, not just the Program Office or the Working Groups. If the NCSAC or any of its members want to propose pilot studies, Dr. Scheidt encourages them to do so.
  • Dr. Graham said that she is concerned about the adequacy of the budget for pilot studies. She wondered if it would be useful for the NCSAC to express the importance of pilot studies and to state that they are an investment in the quality of the large Study. She added that an appropriate number of pilot studies need to be conducted and done properly. Dr. Kimmel thought such a recommendation would be very helpful. Dr. Graham asked how the NCSAC should formally send a recommendation. Dr. Mattison said that someone on the NCSAC should draft a letter and then the entire committee should discuss it. Dr. Landrigan asked whether it should include a dollar amount or should ask for adequate funds to support the work. Dr. Graham suggested that the drafter should decide, and the group asked Dr. Dudley, Dr. Graham, and Dr. Landrigan to draft a letter. Dr. Scheidt said that the planning budget was currently stable, at approximately $12 million. Dr. Kimmel said that there are many other things beyond pilot studies that need funding to plan for a study of this magnitude. She said encouragement would be helpful because of continued budget pressures and uncertainty about funding for the entire Study.
  • Dr. Suozzi said that she had a proposal for a measures of racism workshop that they were hoping to hold in March. She had not yet turned in the proposal. Dr. Kimmel said that there is an online proposal form and the turnaround is very quick for workshops. She asked that perhaps one of the NCSAC members could provide feedback during this meeting, and Dr. Mattison offered to do that.
  • Nancy Potischman, Ph.D., National Cancer Institute, NIH, DHHS, and a member of the Early Origins of Adult Health Working Group, expressed appreciation that some of the pilot studies they proposed were being planned. She asked how the Program Office would contact the writers of the proposals to include them in the pilot planning process. Dr. Kimmel said that the proposers are contacted when pilot projects are approved, and if that had not happened to let her know.

Conclusions/Recommendations

  • The Study will encourage children’s centers engaged in longitudinal research to develop papers on lessons learned about recruitment, retention, and measures.

Action Items

  • The NCSAC will draft a letter encouraging full funding for pilot studies.

Update of Sampling Design Workshop

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

Mr. Quackenboss said that his presentation is an update of the one given at the September 2003 NCSAC meeting. He explained the status of the joint committee composed of members of the NCSAC, Study Design Working Group, the ICC, and the Program Office. A new member is Lester R. (Randy) Curtin, Ph.D., National Center for Health Statistics, CDC, a sampling biostatistician. Mr. Quackenboss described the process to select a chairman for the panel. The reviewed a list of 20 names from a variety of disciplines, and narrowed that list to five specialists including experts in epidemiology, sampling design, and biostatistics. The committee chose David Savitz, Ph.D., Chair, Department of Epidemiology, University of North Carolina, to serve as chairman of the committee.

  • Sampling Design Workshop Planning Committee Update. The first role of the committee was to identify the panel members and the chair. They are:
    • NCSAC: Dr. Michael and P. Barry Ryan, Ph.D., Emory University Rollins School of Public Health
    • Study Design Working Group: Dr. Ellenberg, Dr. Speizer
    • ICC: Mr. Quackenboss and Sherry G. Selevan, Ph.D., EPA
    • Program Office: Dr. Scheidt and Dr. Curtin
    • Workshop Chair: Dr. Savitz.
  • Role of the Sampling Design Workshop Committee. Additional roles of the committee are:
    • Identify documents needed to inform sampling decisions (background white papers and design options) and hand them off to Battelle.
    • Develop papers (Battelle and consultants Colm O’Muircheartaigh, Ph.D., University of Chicago, a sampling statistician and expert in large study design; Alan Zaslavsky, Ph.D., Harvard Medical School; and Louise Ryan, Ph.D., biostatistics department at the Harvard School of Public Health)
    • Plan, organize, and conduct workshop (develop format and agenda, and identify participants).
  • White Papers to Inform Sampling Deliberations. White papers have been commissioned on the following topics:
    • Recruitment and retention rates and their impact on design selection
    • Advantages and limitations of probability-based sampling (specify assumptions needed from generalization)
    • Overview of critical data collection requirements for the Study (what needs to be collected, what infrastructure is necessary to collect it, what the burden is on participants, and how these limit design options)
    • Initial sampling design options and criteria for evaluation (definitions, design elements, and range of design options to form the basis for discussions with consultants).
  • Sampling Design Options for the Study. Mr. Quackenboss explained that creating the sampling design for the Study is very complex. He compared it to the complexity of looking at all of the different hypotheses and deciding how to develop measures related to those hypotheses. Rather than having a "one size fits all" approach, the consultants recommended that the Program Office consider a family of designs:
    • Identify target populations and geographic areas
    • Develop multiple sampling frames to provide coverage of target populations
    • Have well-defined selection methods and criteria for groups (geographic areas, clinics, centers) and individuals
    • Consider organizational structure(s) and their existing relationships with potential Study participants.
  • Next Steps for Battelle and Consultants. Mr. Quackenboss said that discussions were held in October 2003 with Battelle and their consultants about further investigation of statistical properties (power, design effects, implications for analysis) of "hybrid" designs (multiple frames, probability, and purpose of sampling). They also discussed how to assess the feasibility, strengths, and limitations of hypotheses "givens" and criteria.
  • Sampling Design Workshop. Panel membership is being developed in conjunction with Dr. Savitz. Mr. Quackenboss said that the membership panel should reflect a very broad range of expertise. There is an ongoing effort to identify potential panel members, rank them, and decide whom to invite. They expect panels to have approximately eight members including a perinatal epidemiologist, a general epidemiologist with expertise in both medical and social epidemiology, a biostatistician, an expert in mechanics of sampling design, an expert in the analytic implications of design, a population researcher (sociologist or demographer), and an environmental or exposure scientist. Logistics of the two-day workshop include:
    • Day 1: Presentation by Battelle of designs and white papers; additional presentations; discussion
    • Day 2: Panel deliberations and developing recommendations for designs and features of designs. Results from the meeting will also include areas in which information is not adequate and a determination of what needs to be pilot tested before decisions can be made.

    Proposed dates for the meeting are February 16–17 or February 23–25. The meeting will probably be held in the southern or southeastern U.S. near a major airport. Next steps for the workshop committee are:

    • Develop the agenda, arrange for speakers, and invite participants
    • Develop charge and questions for the panel.
  • Timeline for Sampling Workshop and Decisions. Battelle has prepared internal drafts of white papers and preliminary design documents. At this point, these are being circulated to their consultants and the Program Office for review and comment. Draft versions of these documents will be available in January. Mr. Quackenboss said that timing is becoming tight, and he outlined the current timeline:
    • Papers due (January 2004)
    • Workshop (February 2004)
    • Report to ICC and NCSAC (March 2004)
    • NCSAC and ICC proposal to NICHD Director (May 2004)
    • Feasibility and pilot testing sampling design (July to December 2004).

    Mr. Quackenboss said his presentation was a brief overview of a great deal of effort by members of the committee, people at Battelle, and their consultants.

Questions And Comments for Mr. Quackenboss

Dr. Halfon said that there have been several longitudinal studies in other domains, for example, the Health Care Utilization Study for AIDS and the Chicago and Los Angles studies. The people who developed those could possibly help with planning for this Study. He also suggested that the planners should not just consult with biostatisticians used to looking at odds ratios and relative risks. Other techniques such as longitudinal growth modeling and latent variable analysis are also important for measuring trajectories of disease and health over time. He also suggested that they get Jeannie Brook Scott involved in planning, because she has considerable expertise planning longitudinal studies involving children.

Conclusions/Recommendations

  • A chairman and panel members have been selected.
  • Plans for a sampling design workshop, to be held in February 2004, are underway.
  • Battelle and their consultants are developing white papers on four topics to inform sampling decisions.

Presentation and Discussion of Positive Health Framework

Neal Halfon, M.D., M.P.H. Co-Chair, Health Services Working Group, Professor of Pediatrics and Public Health, University of California, Los Angeles

Dr. Halfon thanked the NCSAC for asking him to speak and said he had been serving as the co-chair of the Health Services Working Group for the last two years. His presentation, on positive health and its measurement, was prepared with a colleague, Paul Wise.

  • Introduction. Dr. Halfon stated that members of the NCSAC and Dr. Alexander have expressed interest in the various influences on positive health and are concerned with the lack of current hypotheses focusing on measuring how health develops in children. Dr. Halfon stressed that it is very important to measure health, not just disease, and to develop hypotheses that examine the relationship of various influences on health and development. He said that this is a valuable research topic, especially for the goals of the Study. While there has been a lack of consensus in the field on how to conceptualize positive health for children and adults, as well as how to measure it, there are several recent and forthcoming reports that have demonstrated a converging set of notions and potential methods to accomplish this task.
  • Proposal. Given the interest by the NCSAC in positive health and development, the potential importance as a theme or integrating construct for the Study, and the lack of specific hypotheses that address the determinants of positive health, he and his colleagues propose a targeted set of activities over the next six months to formulate a conceptual approach. Their recommendations are:
    • Formulating a conceptual framework for considering the influences on positive health and development.
    • Examining the current status of measurement approaches and specific measures of positive health and development. This would build upon the Institute of Medicine’s recent report on children, youth, and families, and several other longitudinal studies, including the one currently being developed in Australia.
    • Considering and proposing a series of hypotheses that could be tested on what influences positive health and development.
    • Proposing a set of options for the NCSAC to consider how to most effectively integrate these findings within the Study.

    He said that this proposal was specifically for the Study and was not an attempt to solve the issues of positive health and development for the entire field. Given what the Study needs to do, this proposal sets a conceptual framework within those needs and priorities. He also suggested asking each of the Working Groups which aspects of healthy development are relevant to their specific interests.

  • Methods. Dr. Halfon proposed convening an ad hoc work group of approximately 8 to 10 people, including representatives from the NCSAC and the Development and Behavior, Health Services, Social Environment, and Study Design Working Groups. He expected that three to four people would perform the initial work, and the others would review and comment. He suggested in-person meetings in January, March, and May, supplemented by additional phone meetings. The NCSAC would receive a progress report at the March 2004 meeting and a final report and presentation in June 2004.
  • Final Report. Dr. Halfon expects the final report to contain:
    • The importance of understanding the influences on measuring positive health and development.
    • Challenges and opportunities presented by the Study to measure positive health.
    • Proposed conceptual framework for considering health and development and how it would influence design and measurement issues.
    • Proposed conceptual definitions that could be operationalized, measures that could be implemented, and specific variables that should be considered.
    • Proposed set of overarching, thematic, and main effect hypotheses on positive health that could be tested. These would evaluate how positive health development might act as a mediator on the expression, onset, duration, and impact of specific diseases or pathological processes.
    • Measurement issues and options to consider in order to develop a measurement strategy and a set of valid and reliable variables.
    • A suggested approach on how to move forward to test the hypotheses and measure key variables.
    • Other considerations for the NCSAC.

    Dr. Halfon passed out photocopies of 16 slides that provided additional information on the proposal.

Questions and Comments for Dr. Halfon

  • Dr. Graham stated that health has to be included in the Study, and her questions would be on how best to accomplish this. She began by saying that some people have lost sight of the notion that when a child is tested for birth defects and is found to have none—that is normal. When the Study tests children for asthma, a pattern of normal lung development will emerge. Her first concern is the mention of overarching hypotheses. She would like the hypothesis about birth outcomes to include the entire range of outcomes. She said that the ICC hopes to have a draft protocol in place by June and the final report from Dr. Halfon’s group is scheduled for June. She would like healthy development to be in the protocol in June. She suggested that Dr. Halfon and colleagues talk with the ICC to ensure that their hypotheses are included in the protocol.
  • Dr. Halfon responded that the question is whether health development becomes a core hypothesis for the Study. He agrees that this work ideally should have started two years ago, but given its importance they will work as quickly as they can. Dr. Mattison asked Dr. Graham if she was suggesting that the NCSAC look at the existing hypotheses and determine where they can be modified to include healthy development as an outcome. He added that they have asked that people discuss this during the afternoon breakout sessions.

    Dr. Foorman said that there currently is a list of early exposures and a list of negative and depressing outcomes. She said that opportunity moderators are access to health care, caring adults, quality childcare, and good schooling. She asked every Working Group to think about and list the opportunities for positive outcomes and send their ideas to Dr. Halfon.
  • Dr. Landrigan said that when one looks at an obituary, it lists accomplishments, not “he was not sick and had no birth defects.” It is good to have a Working Group that emphasizes the positive. However, he wanted to echo what Dr. Graham said. He would like to see good cross talk between the positive factors group and the people concerned with specific exposures (for example, lead) that can physically undermine a child. Dr. Halfon agreed that that link is essential. He added that one of the problems is that many current measures for health in children, especially emerging health-related quality of life measures, are really based on abnormalities. They tend to look at what is good enough, but fail when they try to measure optimum functioning.
  • Dr. Fleischman said that he thought the effort was terrific and he appreciates the speed with which they intend to do it. He appreciates looking at mediators and moderators with the same exposures and different outcomes. One of the questions that the Ethics Working Group has considered is the notion of the Study as intervener. He said many things that enhance the health and well being of children are known (health insurance, access to care), and Study researchers might know how children could obtain those things in their communities. Dr. Halfon said that this is an issue addressed by the Health Services Working Group and he needs to defer the question because it is both complicated and essential. There is a big gap between how children are raised optimally and how they fail. In this Study, researchers will see situations in which they know an intervention might boost the child to a higher level of functioning. He asked how does one intervene to prevent children from falling further behind and also how could one intervene to boost them up. These are important ethical questions, but he said his group would not be able to solve them.
  • Dr. Michael said that he was pleased to see the good health issues put on the table. He commented that the integrative potential across the Working Groups and providing the ability to make essential links is terrific. He would advocate that “good health” be put on the list of outcomes. Dr. Halfon said that the concept would not be how to operationalize good health across the hypotheses, but how to measure it and include a hypothesis on healthy development.
  • Adolfo Correa, M.D., Ph.D., National Center on Birth Defects and Developmental Disabilities, CDC, DHHS, stated that he considered healthy development as part of well being. He said that trying to define it and measure it is difficult and that it would be most helpful if Dr. Halfon’s group came up with concrete measures. Dr. Halfon said they hope to do that.
  • Robert Bradley, Ph.D., University of Arkansas, Little Rock, Co-Chair of the Development and Behavior Working Group, expressed support for the efforts of Dr. Halfon and his colleagues. He said that his group had sent in a draft hypothesis dealing with some of the same issues and themes. When they sent in the hypothesis, they had three issues in mind: measuring healthy outcomes is critical to this Study, knowing healthy outcomes is critical for understanding management and response to exposures, and evaluating synergistic systems. He said that he is looking forward to working with Dr. Halfon.
  • Mr. Swartz suggested that Dr. Halfon consult with the Health Disparities and Environmental Justice Working Group for some important perspectives. He also said that there has been writing in the religion/ethics field on the topic of wellness and health. It might not be useful for determining operational definitions, but he would be glad to provide some references.
  • Dr. Dudley said that the Health Services Working Group had submitted a very well developed and overarching hypothesis and it might be helpful to review that hypothesis. The other issue he mentioned was that by the end of the March meeting, a fairly well developed set of hypotheses would be complete. He asked if Dr. Halfon’s group should review that and look at the hypotheses from a positive, rather than a negative, perspective. He realized that it would be a lot of work and time is short. Dr. Halfon said they would consider all the comments, prioritize them, and then develop a work plan.
  • Dr. Phillips asked the Working Groups to consider whether, for a particular exposure, there are other developmental or behavioral outcomes that the Study needs to evaluate in order to truly capture the broad array of potential effects of that exposure. She said her second point concerned mediating variables. Between a given exposure and a given health/medical outcome, she asked what the protective factors and vulnerabilities within children were that determine why some children succumb and some do not.
  • Dr. Landrigan said that in the previous administration, he was privileged to be invited to a conference on influences on child development. The entire focus was on positive influences. He reminded the group that they have to consider both sides in the Study, not just the positive one.
  • Dr. Scheidt thanked Dr. Halfon for taking on a difficult challenge. He asked to what extent they planned to get into the biology of successful development. He reminded them not to forget the importance of sampling requirements and he asked if it could be done with a sample of 5,000 or 10,000 rather than the entire cohort. He added that the concept of healthy development has been subsumed in some of the other hypotheses already. Dr. Halfon responded that certain pathways in certain populations have begun to be understood in terms of how biological, economic, and social exposures affect outcomes. This Study will examine those pathways in individual children. They are hoping to do a three-level pathway analysis including population, individual, and biological levels. From an analytic standpoint, the ethical, social, and scientific issues need to be considered as they move forward.
  • Dr. Guerra asked how they plan to include individuals with pre-existing problems such as disabilities. Dr. Halfon referred to a slide of a child with a pre-existing neurological impairment who had high cognitive and emotional functioning that helped to compensate for decreased physical functioning. Another slide showed a child with an identical lesion, but whose overall functioning was much lower. It could be that one child has a stress reactivity response that is genetically determined, and he lives in a chaotic environment. Part of what Dr. Halfon and his colleagues want to do is perform measures to enable understanding of the dimensions of health and their interactions over time, not just measure what disease or biological category children occupy or when they fail.

Conclusions/Recommendations

  • Dr. Halfon and a work group will develop a conceptual framework for considering the influences on positive health and development for the Study.

Monday, December 15: Thematic Group Breakout Sessions

Following the lunch break, thematic group breakout sessions were held on the following topics:

I.    Pregnancy Outcome

II.   Neurodevelopment and Behavior

III.  Asthma

IV.  Injury

V.  Obesity and Physical Development

See Appendices I–V: Thematic Group Breakout Session Summaries.

Monday, December 15: Dinner Meeting

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

Dr. Mattison welcomed attendees to the dinner meeting and reviewed the three meeting goals:

  • Develop good relationships between Working Groups and liaisons
  • Review themes and hypotheses in order to develop a work plan for the March meeting
  • Provide final recommendations to Duane Alexander, M.D., NICHD, NIH, DHHS, by the end of the March meeting.

Dr. Mattison then introduced Dr. Scheidt, who discussed the recent interest from the National Human Genome Research Institute (NHGRI) in building an adult cohort on the framework of the National Children’s Study. Dr Scheidt stated that Alan Guttmacher, M.D., NHGRI, NIH, DHHS, was present at the meeting to discuss the potential for a joint effort and to answer any questions from members of the National Children’s Study Advisory Committee (NCSAC) and the Interagency Coordinating Committee (ICC). Dr. Scheidt explained that Dr. Guttmacher planned to give a presentation on the proposal the next morning, but he would be happy to answer a few questions at the dinner meeting.

Dr. Guttmacher thanked participants for inviting him to the meeting. He said that NHGRI was one of several agencies interested in gene-environment interactions that cause or contribute to adult disorders and diseases. He explained that NHGRI was in the very preliminary stages of considering the development of a longitudinal cohort study of adults. Dr. Guttmacher was at the meeting to see if it made sense to consider a marriage of the two endeavors: the National Children’s Study and a large cohort study of adults. He stressed that the Institute wanted to help make the National Children’s Study more powerful and more successful and to discuss if it even made sense to propose a joint venture. He then opened the discussion for comments and questions.

Comment: It is exciting to think of a large study that studies families and not just children. It is important to learn from what the National Children’s Study has done.

Answer: Dr. Guttmacher said that the Study planners had done an enormous amount of good work and that the NHGRI certainly do not want to recreate the wheel or make the same mistakes. He remarked that some issues are different in an adult study, but many will be the same. NHGRI has many of the same concerns and devotion to the same issues, for example, long-term health disparities. The Institute would like to make sure that minority populations are overrepresented rather than underrepresented.

Question: What kind of new information would you expect to get from this study that is different from other adult cohort studies?

Answer: Dr. Guttmacher said that the Institute would expect the cohort size to be larger than that of any other U.S. adult cohort study. Although there are large studies in other countries trying to do similar kinds of things, they would not serve as models for the U.S. For example, some environmental exposures in the U.S. are different in quantity, if not quality, from those of other countries. In addition, the populations are different in the U.S. than in other countries. Some populations in the U.S. might not be represented at all in studies in other countries.

Question: What kinds of environmental exposures or gene-environment interactions are you interested in evaluating?

Answer: Dr. Guttmacher replied that Institute members were in such a preliminary stage of thinking about an adult cohort study that they had only considered broad issues. He could not provide any detailed information about what exposures they would look at because they were not yet at that point in the planning process. He added that if NHGRI joins forces with the National Children’s Study, it would be possible to obtain household and cultural information about the entire family. Obviously many of the diseases in adults are different—for instance, cardiovascular diseases of aging and Alzheimer’s disease are not issues for the National Children’s Study. However, much can be learned about children by studying several generations of the same family.

Dr. Mattison thanked Dr. Guttmacher for his comments and restated that Dr. Guttmacher would give a formal presentation in the morning. Participants would have an opportunity at that time to ask other questions or express concerns. Dr. Mattison then asked if there were any comments, questions, or concerns that arose in the sessions earlier in the day.

Question: Have you had any meetings with lawyers about ethics? How can the Working Group members engage in the Study in a way most appropriate for their expertise and still be protected from potential conflicts of interest?

Answer: Dr. Mattison replied that this is an important question that has been a concern of his and the Program Office. The Study has been trying to further separate the Working Group members from federal staff by using liaisons. Each of the NSCAC members should try to appropriately insulate their Working Group members from potential conflicts of interest.

Question: Could we see a statement of work for the Booz Allen Hamilton Inc. technology support contract?

Answer: Dr. Mattison asked Dr. Scheidt to answer this question. Dr. Scheidt said that if that was a need, then a session should be scheduled at the next NCSAC meeting to share that information. He stated that part of the selection process included a presentation from Booz Allen Hamilton Inc. He added that the statement of work was very broad and that the contractor had enormous flexibility to get what was needed to define the job. Dr. Mattison reminded Working Group members that they should have no direct interaction with the contractors to protect against charges of conflict of interest.

Question: What is the current role of the Working Groups?

Answer: Dr. Mattison said that the NCSAC had begun to discuss the natural lifespan of the various Working Groups. Individuals need to take cues from liaisons because some of the groups have been effective and productive and are close to being thanked for completing their jobs. Other Working Groups still have a fair amount of work to do. Dr. Scheidt commented that the Working Groups should contact the ICC to demand that specific hypotheses and pilot studies be included in the study. He said the ICC needed a lot of input from the Working Groups and it has been a quiet year.

Comment: It is not clear to some of us what exactly we should be doing at this point.

Answer: Dr. Scheidt said that there is still time to send the ICC information about any compelling hypotheses or gaps that need to be filled. At this point, the ICC cannot deal with 300 new hypotheses, but if there are still significant gaps that need to be filled, they should be identified and developed. Dr. Mattison said that the various parties are trying to align the timelines of the Working Groups and the federal staff. As the Study grows from planning to pilots to initial sites, roles of the NCSAC and the Working Groups will evolve. Right now there is still a fair amount of work to be done, but it is important to plan for the future.

Dr. Mattison then ended the session and thanked participants for their questions and comments.

Tuesday, December 16: Plenary Session

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

Welcome: Review Agenda and Modifications

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

  • Two Presentations. Dr. Mattison said that the session would start with two presentations. Mr. O. Carter Snead, the President’s Council on Bioethics, would make a presentation and a proposal concerning the role that assisted reproductive technologies play in pregnancy and child health. Next, Alan Guttmacher, M.D., NHGRI, NIH, DHHS, would talk about a proposal for an adult cohort of the National Children’s Study.
  • Thematic Breakout Summaries. Dr. Mattison said that following those presentations, chairs of Monday’s thematic breakout sessions would provide summaries.
  • Upcoming Work. Dr. Mattison noted that the committee would then discuss work that needs to be done over the next several months. Specific instructions for Working Groups will come from the NCSAC liaison to that group. A plan is being developed for the March meeting, which will focus on finalizing recommendations from the NCSAC to the ICC on themes, hypotheses, measures, and healthy outcomes. He said that the plan should be completed within a week and forwarded to members of the NCSAC.
  • Working Groups. Dr. Mattison hoped that the Program Office would provide feedback to the NCSAC on the input from Working Groups that are far along in their work. Working Groups that have not completed their discussions by the end of the March meeting will continue to provide input at the June meeting. Specific timelines for each Working Group will come from the liaisons.
  • Steering Committee Meetings. Dr. Mattison said that the NCSAC Steering Committee met that morning and planned to meet again after this plenary session to determine next steps and timeframes.

Overview of the President’s Council on Bioethics

Mr. O. Carter Snead, General Counsel, The President’s Council on Bioethics

Mr. Snead thanked Dr. Mattison and the NCSAC for inviting him to speak about a project that has special relevance to the National Children’s Study and he hopes that there will be an opportunity for collaboration. He said that the President’s Council on Bioethics is a advisory commission constituted in 2002 to advise the President on all bioethical and public policy questions that arise from advances in biomedical sciences and biomedical technology.

The Council is very enthusiastic about the work done to develop the Study, and Mr. Snead commended the NCSAC and ICC for embarking on this massive and important project. Mr. Snead said that one question of particular interest to the commission is the regulation of biotechnologies. During discussion, the Council learned that not much is known about public and private regulation and governance of the intersection of human reproduction and genetics. They performed a critical assessment of this issue, including input from scientists, clinical practitioners, and patient advocates. Commission discussions were transcribed and working papers developed by staff are available at www.bioethics.gov. The committee arrived at several preliminary conclusions, described in the document entitled “U.S. Public Policy and Biotechnologies That Touch the Beginnings of Human Life: Findings” that was handed out to NCSAC members.

Mr. Snead briefly outlined the preliminary findings of the Council. Members determined that the fields of assisted reproduction, genetics, and human embryo research are increasingly converging. Since 1985, 170,000 children have been born in the U.S. with the aid of assisted reproductive technology (ART), and in 2000, patients took almost 100,000 cycles of ART. The committee concluded that there is no uniform, comprehensive, enforceable system of data collection, monitoring, or oversight for the biotechnologies that touch the beginnings of human life. Regulatory oversight is currently provided by a patchwork of public and private regulations. He outlined the following areas of concern:

  • Well-being of children, egg donors, and gestational mothers
  • Access to services
  • Movement of techniques and practices from experimental to clinical use
  • Public discussion and deliberation regarding ethical significance of new technologies and practices.

Mr. Snead said that ART procedures have been an enormous benefit to women suffering from infertility and have provided much happiness to families. However, despite the enormous amount of time since the advent of these procedures and the speed with which they enter clinical practice, council members were concerned to learn that there is no definitive understanding of how ART affects the health and well being of children born with its aid. Efforts are underway to review existing literature on this issue, and the American Infertility Association has begun to create a voluntary registry to track development and health of children through three years of age. Mr. Snead stated that there are no longitudinal studies on the long-term effects of these procedures, particularly the ones that intervene at the genetic level.

In September 2003, the Council developed a draft recommendations document entitled “U.S. Public Policy and the Biotechnologies That Touch the Beginnings of Human Life: Draft Recommendations.” Mr. Snead provided copies to NCSAC members and read aloud the first recommendation in the document: “Undertake a federally funded longitudinal study on the health and development impacts of ARTs on children born with their aid. A most important unanswered question before the Council concerns the precise effects of ART and adjunct technologies on the health and normal development of children born with their aid. There have been a few studies, mostly undertaken abroad, reaching variable and sometimes contrary results. The Council strongly believes that what is needed now is a prospective longitudinal study that is national, comprehensive, and federally funded, and which looks at both the short-term and long-term effects of these technologies and practices on the health of children produced with their assistance, including any cognitive, developmental, or physical impairments. An ideal vehicle for this study is the National Children’s Study now being planned by a consortium of federal agencies led by the National Institute of Child Health and Human Development (NICHD), which, beginning in 2005, will track the health and development of 100,000 children across the United States from birth until age 21.”

Mr. Snead explained that the Commission sees the Study as the opportunity of a lifetime to really take a thorough look at this particular area and an endeavor that has enormous potential. Mr. Snead then offered to take questions.

Questions and Comments for Mr. Snead

  • Dr. Landrigan asked for the current number of babies born in this country through ART. Mr. Snead replied that 100,000 cycles of ART were done in 2000 and the rate of success is about 25 percent. Therefore, approximately 25,000 children were born in the U.S. in 2000 through the use of ART. He added that if one includes multiple births, the number might be closer to 30,000. Dr. Landrigan then asked why Mr. Snead thinks the Study is the proper vehicle for investigating this question, rather than a prospective epidemiological study that would build a cohort of these children and follow them specifically. Dr. Landrigan added that he sees some divergence between the questions the National Children’s Study is asking and the questions the Council would like to see addressed. Mr. Snead said that the opportunity to build a prospective study from the ground up has not presented itself. He added that he did not know how much flexibility the Study would have and he wondered if it might be possible to increase the number of children enrolled in certain areas. He said that he met with Dr. Mattison, Dr. Scheidt, and Dr. Alexander several months ago and discussed this important question.
  • Dr. Mattison said that when they met with Mr. Snead and his colleagues, they explained several aspects of the Study to them, including that there had been a hypothesis concerning ART and concerns were raised about how it would fit into the Study. Dr. Mattison thought an appropriate response from the NCSAC would be to assign this request to the appropriate Working Groups. He asked if it would make sense to incorporate children born through ART or to use the Study as a control for a parallel study. Dr. Dudley added that the Fertility and Early Pregnancy Working Group had a very nice hypothesis on this, but it did not meet the criteria for a core hypothesis, primarily because the power calculation suggested that they did not need 100,000 children to answer that question. He said it might be worthwhile to have the Working Group readdress the issue. He stated that ART as a method of conception would be recorded as an exposure and duly followed. He suggested that the Reproductive Medicine Network might be interested in developing a study in this population, and they might have access to the requisite number of ART pregnancies in a year needed to look at this.
  • Dr. Fleischman said that this is a very important topic and added that the New York State Task Force on Life and the Law issued a report on this issue five years ago. The greatest risk to children is preterm birth, due to the likelihood of multiple births. He said that a longitudinal study on this issue would require far more than a random sample of children in the U. S. to sort out the problems of prematurity, which are quite substantial, as well as any effects from the technologies themselves. He commented that many of the Council’s suggestions on health policy are excellent.
  • Dr. Guerra agreed that it is an important question with many dimensions that need to be addressed. One that concerns him is that the Study would not include a representative sample of families because ART is available to few people. The ability to pay for it and the level of education needed for informed consent limit availability of ART.
  • Dr. Landrigan said that all forms of ART are probably not equal in terms of effects on children. He suggested that a study might need more than 1,000 pregnancies to answer that question, because once one starts subdividing, one runs into issues of statistical power.
  • Daniel J. Swartz, Children’s Environmental Network, said that the NCSAC has been struggling to increase political support for the Study. He asked whether adding something like this would make the Study more attractive to Congress or more controversial. Mr. Snead said that regardless of the response to their request, the Council is very enthusiastic about the Study and wants to promote it. As a political matter, that regardless of where one is on the left/right spectrum, most people agree on the importance of the health and safety of children.
  • Dr. Little said if there were 1,000 children in the Study born through ART, several hypotheses could address specific ART issues, using other children in the Study as controls. He said if this is an important issue, then it should be included in the Study. As the Study goes in different directions and has multiple aims, it becomes easier to do an equal probability sample rather than a probability sample that over weights in a particular direction. He added that an overarching issue that needs to be addressed is whether the Study is going to oversample underprivileged children who are at higher risk for certain disorders or whether it is going to sample everyone equally.
  • Dr. LeMasters said that she was concerned with Roman numeral I versus Roman numeral II in the Council’s draft recommendations report. Roman numeral I has to do with research interests in general. Roman numeral II addresses issues such as monitoring physicians. Mr. Snead said that the second portion is simply advice to professional societies on ways to increase their self-oversight. It is not a call for increased governmental regulation of clinicians. Dr. LeMasters said that these should be treated as two separate issues.
  • Lucinda Suarez, Ph.D., Texas Department of Health, said that they had asked the Fertility and Early Pregnancy Working Group to develop data items on this issue.
  • Dr. Scheidt said that ART is a significant event for pregnancy and it will be recorded and included in the Study. However, it was examined as a possible focal point for the Study, and it was found that the numbers did not support its inclusion. Given the frequency of the exposure, a study of this size was not sufficient to address it. The question is, given the current interest, should it be reexamined? He asked whether the NCSAC wanted to ask the Pregnancy and the Infant Working Group or the Fertility and Early Pregnancy Working Group to reexamine what would be necessary to address the concerns of the commission.
  • Dr. Mattison said that three Working Groups should be asked to respond: Fertility and Early Pregnancy, Birth Defects, and Health Services. He proposed that this be a discussion item for the Steering Committee at noon. Dr. LeMasters suggested collecting responses from the Working Groups and making a decision based upon their expert input.
  • Dr. Dudley said the Fertility and Early Pregnancy Working Group could resurrect their hypothesis, but he recommended that Mr. Snead contact the Reproductive Medicine Network about that organization conducting a prospective study.
  • Mr. Swartz asked that the NCSAC keep in mind how representative the sample would be, what socioeconomic levels would be included, and how many times one can oversample. He said that if the Study had to choose between oversampling low socioeconomic groups versus the ART group, his preference is the former.

Recommendation

  • A recommendation was made that Mr. Snead contact the Reproductive Medicine Network.

Action Items

  • The Executive Committee will ask the Fertility and Early Pregnancy Working Group, Birth Defects Working Group, and Health Services Working Group for input on the proposal from the President’s Council on Bioethics.
  • The Executive Committee will work out a process so that the entire NCSAC will determine a recommendation.

Adult Health Study and Potential Linkages

Alan Guttmacher, M.D., National Human Genome Research Institute (NHGRI), NIH, DHHS

Dr. Guttmacher thanked the NCSAC for inviting him to speak at the meeting. He said that NHGRI was one of several agencies interested in gene-environment interactions that cause or contribute to adult disorders and diseases. He explained that NHGRI was in the very preliminary stages of considering the development of a longitudinal cohort study of adults. In December, they convened a group of 50 people, half from inside NIH and half from outside, to think about scientific questions, including:

  • Did a large U.S. based study make sense?
  • What would such a study look like?
  • Would it make sense to link it with the National Children’s Study?

A resounding consensus was that it was time to push for an adult longitudinal study. After extensive discussion of the possible pros and cons of linking with the National Children’s Study, it was decided that the concept should be explored. The next step was to discuss at this meeting whether it made sense to consider a marriage of the two endeavors: the National Children’s Study and a large cohort study of adults.

Preliminary thoughts include getting more comprehensive phenotypic, genotypic, and exposure data about the available parents and grandparents of the 100,000 subjects. This would create a three-generation study of health in the U.S. Some ways that this might help the Study are:

  • The study would have more detailed information about parents and grandparents and more information about cultural and environmental influences.
  • Enrolling several generations might help maintain individuals in the study.
  • A joint study might bring in more scientific resources.
  • A joint study might add more financial support than either study would have independently.

Some concerns that might arise from linked studies are:

  • Might lose the focus on children.
  • Logistic issues might delay the National Children’s Study. For instance, recruitment might be more complicated for a joint study.
  • The planning for the adult portion of a joint study would need to develop quickly. One advantage, however, is that the National Children’s Study framework is already partially built.

Dr. Guttmacher said that figuring out the funding part would need to occur over the next few months in order to not delay the National Children’s Study. Dr. Guttmacher emphasized that children should be front and center and that this effort should only move forward if it helps the National Children’s Study. He concluded that a joint project would require a lot of work and cooperation among a lot of different people.

Questions and Concerns for Dr. Guttmacher

  • Dr. Little said that this is a very exciting prospect. He asked how much of a limitation on a family study would it be to not include siblings. Dr. Guttmacher replied that in terms of adult illnesses, data from siblings would not be as meaningful as that from parents and grandparents. If a merger occurs, the Study could revisit whether it made sense to also enroll siblings in the Study.
  • Dr. Landrigan asked whether Dr. Guttmacher was proposing to obtain detailed histories and physical examinations of parents and grandparents or just material for genetic analysis. Dr. Guttmacher said that they did intend to get histories and perform physical exams. He added that even though the NHGRI is trying to move this discussion forward, they are not proposing a genomic study. Instead, they are interested in getting good environmental data, good health data, and good genetic data.
  • Dr. Landrigan asked if they planned to develop a series of hypotheses for the adult cohort. Dr. Guttmacher said that it would be a hypotheses-informed enterprise. They thought that they would develop representational hypotheses that they would want their data to answer initially, but the intention so far is not to have specific hypotheses that the study would be designed to answer. They want to create a resource that would be as widely available as confidentiality allows in order to enable researchers now and in the future to answer questions that cannot even be imagined today. The hypotheses should help determine what data to collect, not limit how the data are used.
  • Dr. Landrigan said that three years ago, Dr. William Castle, designer of the Framingham study, spoke about developing longitudinal studies. Dr. Castle said that the data were used to answer questions that arose years after the data were collected. For example, people did not know about high-density lipoproteins in 1948 when the study was launched. Dr. Castle said that it is essential to have hypotheses help form the core architecture of a study when it is planned. Dr. Guttmacher said he agreed with everything Dr. Landrigan said.
  • Dr. Phillips said that the National Children’s Study places significant participant burden on the parents. The Study plans to collect data from them about their role as providers of the social, physical, and economic environments of their children. The Study also plans to ask them to play a role as informants about their children. Adding a third role might tip the scale. Dr. Guttmacher said adding an adult component clearly will add complications, and pilots should be done on parental burden.
  • Dr. Phillips asked if they planned to include nonparents in the adult cohort. Dr. Guttmacher said they would, with two caveats. The family does not necessarily mean biological parents. Including nonbiological parents means a loss of genetic impact, but not of the other data. Another question the study could address is whether adults who do not have biological children have different sources of diseases than those who do. He added that the current thinking is to include an arm of adults that do not have offspring.
  • Dr. Halfon raised several for issues for consideration:
    • From a policy standpoint, children are considered a special interest group. Pitching the combined study raises different policy issues than a stand-alone children’s study does.
    • The nature of the epidemiology of children’s diseases is different from that of adults. Adults suffer from common, end organ diseases, but children have a large number of low-incidence diseases. The epidemiology of the studies would be different, because a children’s longitudinal prospective study looks at endpoints of various exposures. An adult cohort would be a retrospective look, and the nature of the hypotheses and the measurement issues would be very different.
    • Conceptualization of developmental issues.
    • The addition of an adult cohort and inclusion of several other Institutes might swamp the planned longitudinal Study.
  • Dr. Michael said that one issue not yet raised is economy of scale. He pointed out that one of the costliest aspects of running a study is identifying participants, so running a study of this size with two cohorts is financially advantageous. Many of the home environments and some of the community environments would be the same, also allowing for savings. Some of the information about families will be complimentary, and learning more about the families is to the Study’s advantage. He added that managing the existing 22 committees is difficult, and the prospect of making the Study bigger is frightening. Managing the size, politics, and focus would be cumbersome. He agreed with Dr. Phillips that the burdens on the mother could be overwhelming. An additional point made was that over 21 years, some of the babies would grow up and have babies, allowing data collection on another generation. Dr. Guttmacher responded that in terms of adult studies, this would incorporate the best of both worlds. The first data cut would be a combination of retrospective and prospective data. But in 20 years, a combined study would have good prospective data on participating children who have become adults. He added that joint enrollment is a huge economy versus running two separate studies. He pointed out that a possible political economy of scale could result from combining support for the need to build better health in the United States.
  • Dr. Swartz mentioned two thematic economies of scale and one dissonance. Three underlying themes of the National Children’s Study are:
    • Gene-environment interaction. Including adults would help explore this area.
    • Developmental windows of vulnerabilities. Although some are different for children, adults, and seniors, clearly these exist across the age spectrum.
    • Small perturbations early in life can have big effects later on. This theme would not be replicated in the adult study, and the unique importance of it should not be overlooked.

    Dr. Guttmacher said that in a merged study, the developmental perspective could not be lost. He agreed that adults are not large children, so there will be areas of overlap and areas of differences for each population.

  • Ms. Jones shared concerns from her perspective as a member of the community:
    • Educating the community about the Study is a handful, and combining it with educating the community about a longitudinal adult cohort study would be hard to do.
    • This effort will require early involvement and support from the community.
    • The adult portion will require time to develop community outreach, and the process will be different.

    Dr. Guttmacher said that they are really talking about the health of American families. This is an issue that many communities can understand and support. Planners want early and strong community involvement in shaping a joint study. He added that the NHGRI used part of the funding for the genome project to look at the ethical, legal, and social implications of their work and they would bring that perspective to this project.

  • Dr. Foorman said that the gene-environment emphasis and including adults would help market the study to the broad population. Rather than calling it the “National Family Study” she’d prefer to call it the National Children’s Study and in small letters “and their families.” This would keep the focus on children, and would take the family as it exists, even if the parents are not biological parents. She agreed that the burden on the mother is extensive, but mothers might be motivated if the Study helps their families.
  • Dr. Landrigan said that although the proposal was intellectually compelling, he was concerned that the logistics of governing a joint study might be overwhelming. Dr. Guttmacher agreed and said that Francis Collins, M.D., NHGRI, NIH, DHHS, had stated that this project would be much harder to conduct than the Human Genome Project was. They are well aware of the difficulties.
  • Dr. Mattison said that the NCSAC had two choices:
    • Acknowledge the presentation and encourage the Program Office to engage in further discussions.
    • Appoint a subcommittee to consider the proposal and provide feedback.
  • Dr. Michael said that the NCSAC is an advisory committee for Dr. Duane Alexander. What is Dr. Alexander’s question to the NCSAC in regard to this issue? Dr. Scheidt said that Dr. Alexander has consulted with the Director of the NIH and Dr. Collins and has made the decision to proceed with consideration of this proposal. He needs advice on how to proceed.
  • Dr. Fleischman said that he did not want the last comment from Dr. Landrigan to be the committee’s last comment on the proposal. He said that the NCSAC is comfortable that Dr. Alexander would not lose the focus on children and that he recognizes that the leaders of the NHGRI are knowledgeable about children. As long as the focus on children is not lost, the potential for success is greatly enhanced by this merger, even though it increases the complexity. He summarized by saying that if the focus is not lost and if a merger increases the likelihood of funding, he recommends moving aggressively forward.
  • Dr. Little echoed what Dr. Fleischman said. He said that separate studies sometimes use a common frame, and he suggests that input on this project is needed at the design meeting in the spring.
  • Dr. Mattison remarked that he was hearing enthusiasm with the following caveats:
    • Attention to children
    • Attention to funding
    • Attention to logistics.
  • Dr. LeMasters asked if it would be possible by the March meeting to know how this new initiative could be integrated into the National Children’s Study and whether that would change the proposed timeline for the children’s component. Dr. Guttmacher said that he hoped by the March meeting to know enough about the funding to say whether the proposal should move forward or not.
  • Dr. Mattison thanked Dr. Guttmacher for his presentation.

Recommendation

  • The NCSAC supports further discussion on the proposal to add an adult component to the National Children’s Study

Update of Hypothesis Tracking Software

Jai Evans, Center for Information Technology, NIH, DHHS

Ms. Leahey said that they have been fortunate to work with Jai Evans to manage the logistics of Study planning. Software was developed to send information to Working Group members and NCSAC committee members and track incoming comments. She then introduced Mr. Evans.

Mr. Evans said he would present a technical overview of the new hypothesis-tracking database. He provided handouts and said that a computer was available for members to explore the capabilities of the software.

  • Features of database. Mr. Evans provided a quick overview of some of the features of the hypotheses database. These include:
    • Contains text and original files of all hypothesis proposals submitted to the National Children’s Study
    • Provides password protection on the portal
    • Allows capability for full-text search
    • Traces hypothesis proposals throughout the review process
    • Tracks reviews of hypothesis proposals
    • Tracks versions with validation and release
    • Allows e-mail messaging for questions and responses and allows for links in e-mails
    • Eliminates downloading files because material is translated into HTML and can be read on the Web.
  • List of Proposed Hypotheses Page.  Mr. Evans showed a slide of the proposed hypotheses page with core hypotheses on the left and all hypotheses on the right. The hypothesis tab on the portal allows the user to sort by Working Group or by thematic area.
  • Detail Page.  Users can track submissions, contacts, and text of hypotheses on the detail page.
  • Questions to Working Groups Page.  E-mails for the co-chairs of each Working Group are available on this page. E-mails received by Working Groups and responses are also available.
  • Conclusion Rollup.  The Web site contains all questions and responses for review.
  • Editing Hypotheses.  The Web site allows authors to update hypotheses on the Web.
  • Future.  The system is extensible, so as new requirements emerge, they can be added. In the current version, reviews are not available for at-large members.

Mr. Evans encouraged members to explore and use the new hypotheses database.

Questions and Comments for Mr. Evans

  • Dr. Fleischman asked if the NCSAC is in that loop, because they want to enhance relationships between liaisons from the NCSAC and the Working Group Chairs. Mr. Evans said that they plan to add that in the next week or two.
  • Christine Bachrach, Ph.D., NICHD, NIH, DHHS, asked whom to contact if any errors are found. Mr. Evans said to contact ncshelp@mail.nih.gov, and that will provide an e-mail link for reporting errors. He added that there should not be any technical errors, but there might be content problems.
  • Dr. LeMasters said it would help if members’ e-mails allowed access to the portal, rather than requiring members to remember passwords. She asked if it was possible to make the portal address sensitive. Mr. Evans said that the verification of identity is best done with passwords, but the system could be set up to respond to e-mails by requiring a return e-mail to establish identity. He verified that she only wanted access to the rollups and then said he would look into it more.
  • Dr. Scheidt asked how to provide information about the new software to the Working Group chairs, which are some of the primary users of this system. Dr. Mattison said that Mr. Evans and Ms. Leahey have discussed sending out e-mail descriptions of the system. He also said that the system was set up on a computer for people to explore after the plenary session. Mr. Evans said that he would be at the meeting until Wednesday afternoon and would be happy to answer any questions. Dr. Mattison explained that this was the first presentation of the new system, but the next step would be to let all Working Group members and co-chairs know about it and how to use it.

Action Items

  • Mr. Evans will explore the possibility of using e-mails addresses in lieu of passwords.
  • Mr. Evans and Ms. Leahey will send out information on the new system to members of the Working Groups.

Letter to Dr. Alexander

Dr. Mattison said that the next NCSAC meeting is March 4–5 at the Holiday Inn Select in Bethesda. He then handed out copies of a letter drafted by Drs. Graham, Dudley, and Landrigan. The draft covers issues related to staffing, planning, Study implementation, and funding. Dr. Mattison asked for any comments and there were none. He said that the letter would be included in the set of recommendations forwarded to Dr. Alexander.

Action Item

  • Dr. Mattison will include the letter in the set of recommendations for Dr. Alexander.

Summaries of Thematic Breakout Sessions

Dr. Mattison said that the chairs of the thematic breakouts would each give a short summary of their discussions.

Injury Breakout Session Summary

Alan Fleischman, MD, the New York Academy of Medicine

Dr. Fleischman noted that in the ICC subcommittee draft document, the hypotheses concerning injury were inadequate, and more work needs to be done to develop hypotheses that the ICC would accept.

He said that the group determined that injury is not only an outcome or endpoint, but also an exposure that has the potential to affect function and future disability. The Study needs to look at the response to injury and the potential for rehabilitation. It also needs to evaluate pre-injury biologic and social factors that have the potential to impact development of injury and the response to injury.

The group suggested that the Social Environment Working Group and the Development and Behavior Working Group work with the Injury Working Group to define measurements of exposures and serial measurements of brain function. The hypotheses should not only be concerned with cognitive and motor skills, but also impulsivity, attention, and hyperactivity. Those measurements will be needed in order to identify antecedents to injury.

Participants noted that good instruments are needed to measure exposures, and these might not yet be in existence. Physical and environmental exposures include:

  • The home and surrounding area
  • Multiple child-care settings
  • School environments (preschool through college)
  • Recreational settings (land and water)
  • Work environment for teens and young adults
  • Availability of cars, guns, knives and other things that injure children.

The group discussed whether parental report is an acceptable method of both ascertainment and description of the injury or whether the Study will need to evaluate medical records. Dr. Fleischman also asked if parental reporting of outcomes is sufficient. A poster session will be presented about a Puget Sound experience that evaluated whether parents remember and accurately report what occurred. The group also discussed whether data should be collected only on injuries that result in medical intervention. That eliminates capturing data from children without access to health care.

Chemical exposures should include both acute and chronic neurotoxins, alcohol use by subject or subject’s caretakers, licit and illicit drugs, alternative and complementary medicines, and nutritional supplements.

In the biologic and genetic domain, the group discussed known polymorphisms that impact response to injury, inflammatory mediators and neuromediators, and the ability to detoxify substances, which may affect effects of exogenous substances.

Dr. Fleischman described the discussion on psychosocial environment, family conflict, violence, child maltreatment, and family disruption. This included reporting maltreatment and observing or hearing about potentially dangerous environmental issues. What will be the obligations of the Study to report or intervene after obtaining that information? Perhaps it would be advisable to give broad-based health information to all participants in the Study, including places families might go with concerns about things that might injure their children. Participants talked about having a Study operations manual that describes parameters for dealing with findings of concern. This could provide data gatherers with a mechanism for discussing with health professionals whether a child is in danger of imminent harm and whether the situation requires any intervention. This topic will need more discussion as the Study is developed.

Questions and Comments for Dr. Fleischman

  • Dr. Guerra asked Dr. Fleischmann whether the group discussed discipline and corporal punishment. Dr. Fleischman said they did not specifically discuss that.
  • Dr. Phillips said that the Consumer Product Safety Commission four or five years ago developed a methodology for assessing health and safety problems in childcare settings. She suggested that the Study should evaluate that tool. Dr. Mattison reminded members that one way to track a hypothesis is to use the portal and the hypotheses tab. This will enable suggestions and information, such as what Dr. Phillips mentioned, available to everyone.

Recommendations

  • The NCSAC should try to revitalize the Injury Working Group and reassure them that the Study does care about their hypotheses and their interaction with other Working Groups.
  • The Social Environment Working Group and the Development and Behavior Working Group should consult with the Injury Working Group to define measurements of exposures.
  • The Study should begin to develop policies regarding reporting and interventions for children at risk of injury.

Pregnancy Outcomes Breakout Session Summary

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

Dr. Dudley said that the pregnancy outcomes thematic breakout group had a spirited discussion. He asked the Working Group co-chairs about the communication they had had with their liaisons. The Birth Defects Working Group had a conference call with Dr. George Daston and hoped to have a response by the March meeting. The Fertility and Early Pregnancy Working Group expected to have a response by the March meeting. The Pregnancy and the Infant Working Group has received a response and submitted a response, and the Working Group has developed a detailed document on exposures and outcomes. The Medicine and Pharmaceuticals Working Group was waiting for someone to tell them where they could be of service.

Dr. Dudley said that the group discussed whether there were any gaps in the hypotheses. They noted that nothing in the pregnancy outcomes group addresses exposures from chemicals and physical environment. This might not be part of a core hypothesis but certainly needs to be addressed in the Study. There was broad agreement that maternal stress needed to be evaluated. The hypothesis on this topic would involve pregnancy, asthma, development and behavior, birth defects, injury, and social environment.

The group discussed the Psychosocial Stress and Pregnancy and Infancy Workshop, which had not yet released a final document for NCSAC to review. That should be available by the March meeting and it will contain very detailed exposure and outcome measures. The Workshop determined that:

  • Stress can be defined.
  • Stress can be measured.
  • Measures are relatively straightforward and not too burdensome to subjects.
  • The Study should include preconception and postpartum measures.

Core exposures and outcomes that might not be addressed by specific hypotheses were discussed. Dr. Dudley said that the Study should not forget obvious things, such as birth weight, stillbirth, method of conception (for example, in vitro fertilization), or if the mother had a spontaneous or induced abortion.

The group discussed preconceptional sampling and paternal exposures, which have not been discussed in any great detail. The ICC subcommittee draft contains the hypothesis dealing with the risk of birth defects in women with impaired glucose tolerance. Drs. Erickson and Jones of the Birth Defects Working Group advanced this hypothesis. Exposures and outcomes for this hypothesis were discussed in detail, including:

  • Glucose testing
  • Hemoglobin testing preconceptionally, and at 6, 12, and 18 weeks.

Outcomes included birth defects that will be evaluated by growth measures and dysmorphology. The group agreed that the Study needs a standardized protocol for neonatal evaluation, including photos of head, face, and hands and renal and cardiac ultrasounds.

The group identified interactions with other Working Groups including Development and Behavior, Nutrition, Exposure to Chemical Agents, Medicine and Pharmaceuticals, Gene-Environment, and Birth Defects (which has a tie-in with one of the hypotheses in the Obesity Thematic Group).

Dr. Dudley said that the Birth Defects Working Group needs another face-to-face meeting to identify some standardized exposures and outcomes and also to refine their hypothesis.

The group discussed the well-developed hypothesis on intrauterine infections and preterm birth. They reviewed the exposures and outcomes, including the most appropriate times to sample. Dr. Dudley pointed out that this hypothesis is directly related to two from the Development and Behavior Working Group (infection/cerebral palsy and infection/schizophrenia). Because this is a life course Study, these three hypotheses are all related to what happens during pregnancy. This highlights the need for a standardized neurodevelopment protocol that looks at cerebral palsy. It was noted that this would not be easy to do at 40 different sites.

Other issues discussed were:

  • Core exposures, including prenatal data
  • The form that data records will be in—all computerized? Records that the clinician uses or exclusive of that?
  • Exposures across gestation including cumulative, peak, intermittent exposures
  • Postpartum measures that need to be collected (lactation, incontinence).

A discussion was then held on healthy outcomes. Dr. Dudley said that both of the hypotheses discussed could be turned around and considered from a health perspective. For example, why do women with impaired glucose tolerance have normal children? Why do women with intrauterine infections not deliver preterm or have babies with cerebral palsy? The group discussed different effect modifiers such as gene-environment interactions, nutrition, folate, and antioxidants. They decided to defer to Dr. Halfon on this issue.

The adequacy of the thematic areas was discussed. They pointed out that there is no thematic area that looks at reproductive development, but one participant commented that this is included in obesity and physical development. They thought that this thematic area should consider a name change to Obesity, Growth, and Pubertal Development or something more descriptive of the range of issues they are looking at.

They discussed work plans and times, and Dr. Dudley said the Executive Committee would help determine those. They encourage the Working Groups to collaborate and support one another.

Questions and Comments for Dr. Dudley

  • Dr. Guerra asked how the Working Groups would cover differences in pregnancy outcomes from foreign-born women compared to those who are U.S. born. Some early observations of populations in transition or assimilation show that the pregnancy outcomes for the first generation is quite good compared to later generations. Dr. Dudley said that this issue was not directly addressed, but it would most likely fall under the maternal stress hypothesis. He suggested that that Working Group be asked to incorporate those measures in the stress hypothesis.
  • Dr. Landrigan asked about measurement exposures during pregnancy, for example, of lead, pesticides, PCBs, or phthalates. He asked what is the right time to take those measurements and how they planned to separate prenatal from postnatal exposures. Dr. Dudley asked Dr. Graham to answer that question.
  • Dr. Graham said that she has concerns at two levels. The first is the quality of the science of the Study that will be determined by the measurements of exposures and outcomes and the robustness of the statistical analysis. That is the reality. The second concern is how the Study portrays that reality. Dr. Graham said that she is confident that these chemicals will be measured in children across time, but it appears from the core hypotheses that they will not be measured. So, there is a collision of reality and appearance. She hopes that when she sees the draft protocol, it will contain a compete set of measurements. Dr. Dudley added that Larry L. Needham, Ph.D., National Center for Environmental Health, CDC, DHHS, sat in on the breakout session, and Dr. Needham said, “Tell me what you want measured and when you want it measured, and I’ll measure it,” but they do not feel comfortable telling people when specific measurements should be done.
  • Dr. Graham said that gestational age and susceptibility to chemicals can determine pregnancy outcome. That information needs to be incorporated into the chemical exposure design. Dr. Landrigan pointed out that many of the chemicals do not have a long half-life in the body, so if samples are not taken on several occasions during pregnancy, critical exposures can be missed. Dr. Dudley agreed and said that periods of vulnerability constantly change during pregnancy and that a determination needs to be made on which chemicals to look for and when to look for them. Dr. Graham said that she has not observed that debate for many of the exposures and outcomes. Dr. Landrigan suggested testing at least once every trimester. Dr. Dudley said that right now the plan is to obtain the following samples:
    • If possible, preconceptional
    • First prenatal visit
    • 15–18 week sample
    • 24–28 week sample
    • 36–week sample
    • Delivery sample.
  • Dr. Little agreed that this has to be a hypothesis-driven study but stated that it is important to realize that the hypotheses are not the Study. The Study is what actually gets measured.
  • Mr. Swartz said that the Working Groups developed the hypotheses, but now they should review the outcomes and exposures across the hypotheses in a systematic way. Dr. Mattison said that part of the role of the liaisons is to capture cross-group discussions. He added that cross Working Group liaisons will need to be set up to facilitate this process, and the hypothesis portal area can also support these discussions.
  • Dr. Landrigan said if the Working Groups had a list of the analyses that the Study contemplates, it would help them sharpen up the hypotheses. Dr. Graham said the Working Groups have been asked to provide specific exposures and outcomes. They have been instructed to “name those chemicals.” Some have done that, and some have not. When those are in, they will go through the NCSAC to the Program Office to help develop the protocol. Dr. Landrigan asked if the chemicals tested would be limited to the 20 or 30 listed in specific hypotheses. He said that the CDC lab has the capacity to look at many chemicals whose health effects are not known, and it seems wasteful to have the samples and not run the tests.
  • P. Barry Ryan, Ph.D., Emory University Rollins School of Public Health, commented that much would come out of analytical runs that may not be directly related to the questions the hypotheses are asking. Part of the Study is to gather the information so that later other hypotheses can use that data to answer different questions.
  • Dr. Little suggested that the Study have a core and modular (subsample) structure. He said that it could not be looked at just from the hypothesis side. The evaluation has to include measurements, costs in terms of time, and expense of measurements. He said he has not heard that type of discussion yet.

Recommendations

  • The Study should develop a standardized protocol for neonatal evaluation including photos of head, face, and hands and renal and cardiac ultrasounds.
  • The Study should develop a standardized neurodevelopmental protocol.
  • The Birth Defects Working Group should have another face-to-face meeting to identify some standardized exposures and outcomes and also to refine their hypothesis.
  • The obesity thematic area should consider a name change to Obesity, Growth, and Pubertal Development.
  • The Working Groups that have not already done so should provide a list of specific exposures and outcomes to the NCSAC.

Asthma Breakout Session Summary

Grace LeMasters, Ph.D., University of Cincinnati

Dr. LeMasters said that her session was fortunate to include members from other Working Groups including the Community Outreach and Communications, Exposure to Chemical Agents, and other outcome groups. They made a lot of progress in terms of exposures and outcomes:
They recommend that the thematic area be expanded to include airway reactive disease, allergies, and asthma. They were glad to see the data tracking of hypotheses, because they wanted to see how they were written prior to being condensed into their present form. For instance, there are six hypotheses, and the third one was on maternal stress during pregnancy. They wanted to extend maternal stress beyond pregnancy and also look at childhood, family, and community stressors.

They approached the task by first defining outcomes at every stage to be measured, including during pregnancy and every year up to five years of age. They then discussed what exposures they wanted to measure in relation to time and outcomes for hypotheses including indoor/outdoor air pollution, respiratory/viral infections, and bacterial/microbial products. They evaluated these in terms of both adverse and possible positive exposures (the hygiene hypothesis).

They requested that the notes for the breakout session be sent to each participant of the meeting for review. She added that they had filled up 16 large sheets covering everything the group wanted to see happen. After review, they would like to ask the Program Office to take the minutes and set up a matrix of outcome by exposure.

The group did not address methodology or how to measure the exposures.

They went through five of six hypotheses in terms of positive health. Most of the measures identified had a continuum of health to poor health.

They would like the Nutrition, Growth, and Pubertal Development Working Group to delve deeper into obesity and antioxidants and their relation to asthma and what should be measured in a nutritional diary. The group also discussed measures of biological, psychological, and social stress in infants and children. They hope that the workshop will deal with childhood, family, social, and maternal stresses.

Overarching the discussion were the genetic aspects of outcomes of asthma. They listed measures, but did not prioritize them. She added that this should come after all measures from various Working Groups are merged. They hope that by March, with the minutes and the matrix from the Program Office, they can bring the group to closure.

Questions and Comments for Dr. LeMasters

  • Dr. Guerra said the group also talked about the burden on participants, and he stressed the importance of this issue.
  • Dr. Dudley said that the Stress Workshop discussed infant stress, but not stressors of childhood. He said they did not think it was part of their charge, but the expertise is there, so asking them to extend that is perfectly reasonable.
  • Dr. Phillips asked if the group discussed links between asthma and academic performance. Dr. LeMasters said that they stopped at age five, so it was not addressed.

Recommendations

  • Expand the thematic area to include airway reactive disease, allergies, and asthma.

Neurodevelopment and Behavior Breakout Session Summary

Deborah A. Phillips, Ph.D., Georgetown University

Dr. Phillips said that her group brought together the Development and Behavior, Gene-Environment Interactions, and Social Environment Working Groups. She said the room was packed, and they had a remarkable constructive discussion. They had the benefit of a document that had been prepared by the Social Environment Working Group containing suggestions on how to improve the existing core hypotheses and a list of measures of the social environment relevant to this domain.

The group tackled four issues:

  • Adequacy of the theme
  • Three hypotheses
  • Gaps in hypotheses
  • Positive health outcomes.

Discussion of the theme centered on the awkwardness of the architecture, with one box for exposures and one for outcomes. There are aspects of child behavior and development that increase the odds of exposures. In addition, many issues related to child functioning belong between the two boxes and some things go in the outcome box. She asked if positive development is an overarching theme and where it should be positioned in the visual aids. She pointed out that the ICC document is organized around exposures and outcomes.

The group concluded that it would make sense to remove the “neuro” from the “Neurodevelopment and Behavior” theme. Calling it “Development and Behavior” would allow consideration of domains other than “neuro.” Any given developmental outcome is a continuum from the adaptive to the maladaptive.

In the three core hypotheses, there were four overarching issues. Dr. Phillips stressed that these four issues applied to all hypotheses in the Study:

  • Explicit consideration of synergistic/cumulative effects of exposures rather than considering exposures one at a time. With a sample size of 100,000, the Study can look at constellations of exposures rather than isolated exposures.
  • Expand the hypotheses to address the interactions among social, familial, and genetic environments.
  • Expand to address a broader range of adaptive as well as problematic outcomes, as well as co-morbidities.
  • Anticipate the adult outcomes of concern and then think back to consider the influence of early exposures on later health and disease. What will be measured up to age 21, and beyond if the Study is extended?

The group then considered the first three core hypotheses and applied those themes to them. They wrote down the recommended changes to the hypotheses and will hand those out. They also said that the second and third hypotheses are really the same. Dr. Phillips suggested adding seizure disorders and schizophrenia outcomes to the list of outcomes for the first hypothesis.

The group went through a long list of possible additional core hypotheses, and information about this is in the minutes. They evaluated a long list of social and environmental variables to measure, and these are also in the minutes. They then added a list of development and behavior variables that they felt are crucial to measure, including:

  • Executive functions (impulsivity, attention, planning)
  • Emotional and behavioral control (self regulation capacity)
  • Stress reactivity
  • Temperament
  • Cognitive and language development
  • Academic success
  • Productive engagement outside of school
  • Social competence
  • Risk-taking behaviors.

Questions and Comments for Dr. Phillips

  • Dr. Graham said that she liked the proposed thematic area title change, because development of the reproductive system is not visible but development of the nervous system is visible. She said that she saw a hypothesis for schizophrenia, but not for bipolar, depression or other mental health disorders. She asked if the proposed measures would capture other mental health issues. Dr. Phillips said that they have to. The exercise of going through the existing hypotheses and checking what is in there on both the negative and positive ends is extremely important.
  • Dr. Guerra said that there is a general descriptive category for children that are not doing well but do not fit into a particular category, for example, failure to thrive. He asked whether that was addressed. Dr. Phillips said it was an important point, but it was not addressed in the breakout session.
  • Dr. Landrigan said that environmental factors were usually looked at in isolation, and a sample size of 100,000 can be justified when one looks at multiple exposures and interactive effects.
  • Rick Rader, The President’s Committee for People with Intellectual Disabilities, wanted to underscore the need to address the developmental milestones of children with special health needs such as Fragile X or Down syndrome. Dr. Phillips said that that issue was on the list, thanks to Mr. Rader’s contribution.
  • Dr. Michael asked whether, if the thematic title were changed, the Development and Behavior theme would become the positive health outcomes theme. Dr. Graham said that it was an important question. She does not see this as the only health theme. Dr. Phillips said that both positive and negative elements of development would be covered by the theme, rather than trying to break up the continuum among the themes. Dr. Mattison asked Dr. Michael if he was proposing that all healthy outcomes (pulmonary, renal) be included in this theme. Dr. Phillips said that this needs to be clarified; the breakout session focus was on child development and behavior, but reproductive development would be in another theme. Dr. Graham said this is a very important issue. She asked whether development of the lung would go under the development and behavior theme or the asthma theme.
  • Fernando D. Martinez, M.D., University of Arizona, Tucson, from the Asthma Working Group, said that they defined asthma in children as a developmental disease that affects the lungs and the immune system. Ultimately, that is the way researchers will understand many chronic diseases. He said he was sure the intention was not to isolate development in one theme, but it would be a dangerous direction to go.

Recommendations

  • Change the “Neurodevelopment and Behavior” theme to the “Development and Behavior” theme.
  • Provide explicit consideration of synergistic/cumulative effects of exposures rather than considering exposures one at a time.

Obesity Breakout Session Summary

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

Dr. Michael said that the group reviewed the hypotheses in the ICC subcommittee draft and attempted to accomplish two things:

  • Identify areas that were not there but that should be. He mentioned obesity, physical development, and pubertal development.
  • Identify measures and timing of capturing the data. He added that what you get, when you get it, and how often you get it are important.

Dr. Michael stressed that timing of obtaining data is important for making linkages. He said that domains that require augmentation in the document are:

  • Gene-environment interaction
  • Access to food
  • Location of grocery stores
  • Level of physical activity
  • Amount of television watching
  • Linkage between puberty and obesity.

The group felt that the above domains were not adequately covered by the hypotheses, so they wrote three additional hypotheses. They view these as placeholders for information and measurements that need to be included in the hypotheses.

Dr. Michael added that there was a tremendous amount of expertise in the breakout session, especially on the properties of breast milk and the relationship of endocrine function and obesity. One member of the group had printed out documents from the portal that outlined what measurements were necessary to take and at what time intervals. These documents were helpful.

Dr. Michael added that, in his opinion, the Study is not the hypotheses. Hypotheses are important for motivating, justifying, prioritizing, guiding, and providing an intellectual agenda for the Study, but the data are the Study. He is not yet comfortable that the architecture for adequately crafting a protocol is in place. He said that a lot of good things are going on, but he is troubled by the current vulnerability of the process.

General Questions and Comments

  • Dr. Graham asked whether a specific recommendation should be made before the end of the meeting on whether healthy outcomes should be included in every theme area or one theme area. She added that a recommendation could be made on whether the NCSAC thinks that the five theme areas are the right themes. Dr. Landrigan said that he thought the Study should capture the full range of outcomes in every area. Dr. Mattison said his sense from the meeting was that health had been discussed and added to every theme area as a component.
  • Dr. Little said that the obesity theme provides a good example of an unnecessary theme. He did not know what results could be learned about the topic that were not already known. The mechanism for becoming obese is clear, and it is well known that obesity is a health problem. But, he said, it is not clear to him what the Study is going to accomplish on this topic and why it is a core theme. He added that getting 100,000 people to fill out questionnaires might not be a good use of time and money.
  • Mr. Swartz asked for a timeline for the document containing lists of measures, exposures and outcomes and a process for review by Working Groups. Dr. Mattison asked for opinions from the NCSAC. Dr. Dudley suggested that the protocol would contain that information. Dr. Graham said that a draft protocol should be available in June. Dr. Landrigan asked whether there would then be an opportunity to modify it. Dr. Graham said that it would be a draft available for both NCASC and public review.

Summary

Dr. Mattison summarized the meeting:

  • The meeting provided an opportunity to develop stronger relations between liaisons and their groups.
  • The Executive Committee will meet at lunch to create a detailed schedule through the fall of 2004 on deliverables from Working Groups.
  • The NCSAC will work with the Program Office to provide the kind of support the liaisons need to facilitate interactions with Working Groups.
  • The Executive Committee will develop explicit deadlines for Working Group products that include feedback from Dr. Alexander, the ICC, and the Program Office.

Dr. Mattison thanked NCSAC members, the ICC, the Program Office staff, and the Working Group members for their participation. He encouraged members to participate in a series of Working Group sessions in the afternoon. 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.
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

Presenters/Speakers

Jai Evans
Center for Information Technology, NIH, DHHS

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

Alan E. Guttmacher, M.D.
National Human Genome Research Institute, NIH, DHHS

Neal Halfon, M.D., M.P.H.
University of California, Los Angeles

Carole A. Kimmel, Ph.D.
Office of Research and Development, EPA

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

O. Carter Snead
President’s Council on Bioethics

Observers and Other Participants

Gerry G. Akland, M.S.


Amoke Alakoye, M.H.S.
RTI International

Norma J. Allred, Ph.D., M.S.N.
CDC, DHHS

Tye E. Arbuckle, Ph.D.
Health Canada

Christine A. Bachrach, Ph.D.
National Institute of Child Health and
Human Development, NIH, DHHS

Nancy M. Betts, Ph.D., R.D.
University of Nebraska

Jeffrey R. Botkin, M.D., M.P.H.
University of Utah

Cheryl A. Boyce, Ph.D
Division of Mental Disorders, Behavioral
Research, and AIDS, NIH, DHHS

Robert H. Bradley, Ph.D.
University of Arkansas, Little Rock

Rebecca Brown, M.P.H., M.E.M.
Office of Research and Development, EPA

Leni Buff
National Institute of Child Health and
Human Development, NIH, DHHS

Audrey Burwell
Office of Minority Health, DHHS

Christina Chambers, Ph.D., M.P.H.
University of California, San Diego

Robert E. Chapin, Ph.D.
Pfizer Inc.

Luenda E. Charles, Ph.D., M.P.H.
National Institute for Occupational Safety
and Health, CDC, DHHS

Michelle Chiezah, M.P.H.
Hennepin County Community Health
Department

Mark Cosentino, D.P.M., Ph.D.
Science Applications International
Corporation

Carry W. Croghan, M.S.
Office of Research and Development, EPA

Gala B. Hambrick, M.P.A.
State of Georgia Department of Human
Resources

Gary D. V. Hankins, M.D.
University of Texas Medical Branch,
Galveston

John H. Himes, Ph.D., M.P.H.
University of Minnesota

Carol Hogue, Ph.D., M.P.H.
Emory University

Carl E. Hunt, M.D.
NHLBI, NIH, DHHS

Anne E. Imrie
Science Applications International
Corporation

Fleda Mask Jackson, M.S., Ph.D.
Emory University

George S. Jesien, Ph.D.
Association of University Centers on
Disabilities

Chet Johnson, M.D.
American Academy of Pediatrics

Jeannette Johnson, Ph.D.
Center for Substance Abuse Prevention

Carol Jones, M.A.
Psychotherapist

Kenneth Lyons Jones, M.D.
University of California, San Diego

Raffael Jovine, Ph.D.
Booz Allen Hamilton Inc.

Deborah E. King, Ph.D.
DEBLAR & Associates

Larry L. Needham, Ph.D.
National Center for Environmental Health,
CDC, DHHS

Maurice Owens, Ph.D.
Science Applications International
Corporation

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

Shuma R. Panse, M.P.H.
Office of Genomics and Disease Prevention,
CDC, DHHS

Edith Ann Parker, Dr.PH
University of Michigan School of Public
Health

Joseph B. Perrone, Sc.D.
Science Applications International
Corporation

Barbara J. Porter, B.S.
U.S. Department of Commerce

Nancy Potischman, Ph.D.
National Cancer Institute, NIH, DHHS

Rebecca Prevots, Ph.D., M.P.H.
National Institute of Allergy and Infectious
Diseases, NIH, DHHS

Rick A. Rader, M.D.
Exceptional Parent Magazine

Mark Raizenne, Sc.D.
Health Canada

Jerry D. Rench, Ph.D.
RTI International

Gladys H. Reynolds, Ph.D.
CDC, DHHS

Richard Y. Wang, D.O.
National Center for Environmental Health,
CDC, DHHS

Rueben C. Warren, D.D.S., Dr.P.H., M.P.H.
National Center for Environmental Health,
CDC, DHHS

Ann Marie White, Ed.D.
Office of Behavioral and Social Sciences
Research, NIH, DHHS

Marion J. Balsam, M.D.
National Institute of Child Health and
Human Development, NIH, DHHS

Adelaide Barnes
National Institute of Child Health and
Human Development, NIH, DHHS

Stephen J. Bedosky, B.A., M.S.
LFR Levine Fricke

Arthur M. Bennett, M.E.A., B.E.E.
National Institute of Child Health and
Human Development, NIH, DHHS

Fletcher S. Crowe, Ph.D.
Science Applications International
Corporation

Andrew Dannenberg, M.D., M.P.H.
National Center for Environmental Health,
CDC, DHHS

Elizabeth A. Davis
National Institute of Child Health and
Human Development, NIH, DHHS

Diane Dennis-Flagler, M.P.H
Agency for Toxic Substances and Disease
Registry, CDC, DHHS

Linda L. Dimitropoulos, Ph.D.
RTI International

Denise Dougherty, Ph.D.
Agency for Healthcare Research and Quality

William E Ebomoyi, Ph.D.
University of Northern Colorado

Dave Erickson, D.D.S., Ph.D., M.P.
National Center on Birth Defects and
Developmental Disabilities, CDC, DHHS

Warren Galke, Ph.D.
National Institute of Child Health and
Human Development, NIH, DHHS

Rachel Grindstaff
U.S. Environmental Protection Agency

Doris B. Haire
American Foundation for Maternal and
Child Health

Sarah S. Knox, Ph.D.
National Institute of Child Health and
Human Development, NIH, DHHS

William F. Lawrence, M.D., M.S.
Agency for Healthcare Research and
Quality, DHHS

Stephanie J. London, M.D., Dr.PH
National Institute of Environmental Health
Sciences, NIH, DHHS

Jeffrey L. Longacre, M.D.
Uniformed Services University of the Health
Sciences

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

William Lyman, Ph.D.
Wayne State University

Jesse Marquez
Coalition for a Safe Environment

Fernando D. Martinez, M.D.
University of Arizona, Tucson

Toyojiro Matsuishi
Kurume University School of Medicine

Suzanne B. McMaster, Ph.D.
Office of Research and Development, EPA

Fatima Donia Mili, M.D., Ph.D.
RTI International

Allen A. Mitchell, M.D.
Slone Epidemiology Center at Boston
University

John P. Murray, Ph.D.
Kansas State University

Donna L. Rickert, Dr.P.H., M.P.H., M.A.
National Immunization Program, CDC,
DHHS

William J. Rodriguez, M.D., Ph.D.
U.S. Food and Drug Administration

Beth D. Roy
Social and Scientific Systems, Inc.

Gary D. Sandefur, Ph.D.
University of Wisconsin, Madison

Christopher Santos
CIT, NIH, DHHS

Kathy Schneider, Ph.D.
Iowa Foundation for Medical Care

Kathy S. Sebuck
Sun Microsystems

Paul J. Seligman, M.D., M.P.H.
U.S. Food and Drug Administration

M. Nicole Shumpert, M.P.H.
National Center on Birth Defects and
Developmental Disabilities, CDC, DHHS

David C. Songco
National Institute of Child Health and
Human Development, NIH, DHHS

Kristine O. Suozzi, Ph.D.
Bernalillo County Environmental Health
Department

Tracey W. Thomas, Ph.D.
National Center for Environmental
Assessment, EPA

Scyatta A. Wallace, Ph.D.
Department of Epidemilogy, CDC, DHHS

Robert H. Yolken, M.D.
Johns Hopkins University Medical
Institutions

Paula W. Yoon, Sc.D., M.P.H.
National Center for Environmental Health,
CDC, DHHS

Dea Zullo
RTI International

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

 

   January 30, 2004   
          Date
Dr. Mattison's Signature
Donald Mattison, M.D.
Chairperson
National Children’s Study
Federal Advisory Committee
  6/26/2008
  6/26/2008