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 March 2003 NCSAC Meeting Summary Minutes

The 5th Meeting of the National Children’s Study Federal Advisory Committee (NCSAC)

March 6–7, 2003
NIH/NICHD, 6100 Executive Boulevard
Rockville, MD

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

March 6, 2003

Welcome: Review Meeting Goals, Agenda, and Action Items

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

Dr. Mattison thanked attendees for their attendance. He noted that the agenda for the two-day meeting was extensive and welcomed Dr. Yvonne Maddox, Deputy Director of the National Institute of Child Health and Human Development (NICHD).

Dr. Maddox welcomed attendees on behalf of the various NIH Institutes. She stated that she was looking forward to launching the NCS. She commented that one of her recent roles was Deputy Director of NIH, and that her work experience had afforded her some familiarity with attendees.

Dr. Maddox noted that the NCS had the endorsement of Dr. Zerhouni and that she was aware of the effort put into the study by members of the ICC, the NCSAC, and Working Groups (WGs). She recommended that participants see themselves as part of NICHD and expressed confidence that the study "is going to move ahead." However, she asserted that other potential partners existed that were as yet unidentified.

Dr. Mattison discussed that NCSAC members will be rotating on and off, which he stated was fairly standard for advisory committees. Departures included Drs. Lynn Goldman, Ken Sexton, and Johnathan Samet. Dr. Mattison offered Drs. Samet and Goldman each a token of appreciation (Dr. Sexton was absent).

New ad hoc members included Dr. Loretta Jones, Dr. Deborah Phillips, Dr. Barry Ryan, and Dr. Fernando Guerra.

Orientation of New Members

Mary Plummer, Committee Management, NICHD

Mary Plummer stated that the Federal Advisory Committee Act (FACA), which became law in 1972, was written to govern advisory committees in the executive branch of the federal government. She stated that NIH uses more of these than any other branch of the government.

Ms. Plummer commented that program advisory committees can be discretionary or non-discretionary and that the NCSAC is a discretionary committee.

Some of the governing regulations include requirements that notices of all meetings be posted in Federal Register at least 30 days in advance and that the meetings must be open to the public. However, some meetings covering study design, for instance, may be closed with the approval of the Office of General Counsel.

All transcripts of advisory committee meetings are in the public domain and they must each have a clear purpose described in its charter. Advisory committees must also demonstrate a balance in points of view, ethnicity, geographic distribution, and sex.

Expenses must be documented, to be included in annual report to Congress and the White House. Service on advisory committees is intermittent and the NIH payroll system compensates members for attendance. Financial disclosure forms are required at membership and just prior to each meeting.

More Comments from Dr. Mattison

Dr. Mattison noted the addition of Ms. Jan Leahey to the staff of the NCS. Ms. Leahey is on detail from the NICHD contracts office, where she was charged with supervision of contracts related to the NCS.

He noted that each member had a booklet of orientation materials for advisory committee membership. During a closed working lunch meeting, the NCSAC will consult with legal counsel on a range of subjects.

Future NCSAC meeting dates include June, September, and December 2003, and March, June, September, and December 2004.

Action Items

Four action items presented to the NCSAC from WGs and the ICC include:

  • Preconception recruitment discussion: Dr. Germaine Buck will provide information
  • Community involvement/participatory research: Drs. Edith Parker and Diane Dennis-Flagler will provide information
  • Measurement strategies for characterizing fetal growth
  • Interaction between the NCSAC and the ICC.

On Thursday afternoon, the NCSAC will focus on coordination with the ICC. Tracking documents will be examined as well as white papers and workshops by the various WGs. Themes and hypotheses will be discussed as well.

At the December 2002 Study Assembly, WGs were tasked with cross-disciplinary efforts to develop measures and timings of measurements. Earlier NCSAC recommendations will be reviewed further as well. Dr. Mattison asked that any concerns regarding minutes from the previous meeting be e-mailed to him or to Ms. Leahey.

Action Item: E-mail any comments on previous NCSAC meeting minutes to Dr. Mattison or Ms. Leahey.

December 2002 Meeting Minutes

Dr. Mattison stated that an NCSAC review of the minutes from the last meeting will be handled by Dr. Tamar Lasky and Mr. Frank Holloman. This will allow another discussion of any issues.

Mr. Holloman read from the recommendation table and said that four or five WGs would rotate through each meeting of the NCSAC. The types of information needed from WGs included summaries of existing hypotheses, justifications/scientific merits of each hypothesis, unresolved issues, and recommendations for pilot studies.

Dr. Mattison stated that WG updates perhaps should be based on interactions between the ICC and NCSAC, depending on what WGs need to move forward. He stated that there was a need to more vigorously link these two groups.

Mr. Quackenboss stated that some WGs did not feel "invested" in the study at this time while other groups were making progress. He commented that an effort to improve communications might include establishment of a liaison between the NCSAC and each WG.

Dr. Dudley questioned the need for a liaison, stating that there was no restraint on the ability of WGs to communicate with the NCSAC. Dr. Graham asked what sort of information needs to be communicated. She said that some may be unclear on the NCSAC’s perspective on a particular issue, and that a liaison may be stuck for something to convey. Dr. Suarez echoed Dr. Graham’s comment. Dr. Doswell commented that some WGs may feel disenfranchised because their hypotheses are not represented.

Dr. Goldman questioned whether WGs were clear on the nature of the roles of the NCSAC and the ICC and what the WGs should convey to each. She seconded Dr. Doswell’s comment as to why WGs might feel disenfranchised. Dr. Yeargin-Allsopp felt that the ICC and NCSAC might need to delve into this issue at greater length.

Dr. Swartz remarked that WGs should be apprised of the fact that their concerns are welcome in forms other than formal submissions. Dr. Graham stated that cross-disciplinary efforts will be crucial to the design and implementation of the study. She also stated that flexibility of WG configuration was important.

Dr. Mattison stated that a merge of the NCSAC and ICC was an interesting proposition and informed attendees that this would not exceed the chartered threshold for total membership on the NCSAC.

Dr. Scheidt mentioned that this could hamper the advisory function of the NCSAC, but Dr. Landrigan held that the notion made "a certain amount of sense." He observed that the complexity induced by having two groups was a burden. However, he admitted that Dr. Scheidt’s comments regarding potential conflicts of interest had some merit.

Dr. Michael expressed reservations about the effect of the size of such a group on the ability to accomplish work. Dr. Fleischman stated he saw the NCSAC’s role as similar to that of a board of trustees of a non-profit organization in that they advise, but do not handle executive/management functions. He added that the NCSAC and the ICC should interact regularly, but did not favor the notion that they merge.

Dr. Goldman stated that the difficulty of the situation was that WGs functioned largely as appendages of the NCSAC, which gave the NCSAC some management responsibilities, a situation at odds with the lack of available time for members of the NCSAC. She added that the situation might not lend itself to full resolution. Dr. Fleischman made the case that any organizational concerns regarding the WGs were the domain of the NCSAC.

Dr. Dudley recommended that the responsibilities for communication between groups be committed to paper. Dr. Yeargin-Allsopp stated that the ICC had reviewed the roles and responsibilities of each group, which she concurred can seem confusing.

Dr. Mattison stated that some of the afternoon agenda included a review of NCSAC/ICC roles work. Dr. Landrigan stated that "the absence of a command structure could be a fatal flaw," and that a system of checks and balances was a necessary part of the structure of the NCS. Dr. Mattison noted a suggestion by Dr. Yeargin-Allsopp that these two groups engage in a retreat to go over these issues.

Dr. Bellinger noted that only four WGs were presenting at this meeting and observed that this pace would not cover all WGs in the course of a year. He recommended as a standing agenda item a chance to review each WG twice a year.

There were no further questions from the remaining minutes from the April 2002 meeting.

June 2002 Meeting Minutes

Regarding the June 2002 minutes, Dr. Little stated that volunteers would not suffice to staff the study. Dr. Goldman commented that a sample size determination might not be a function of WGs or the NCSAC.

Dr. Landrigan asked how many full-time professional staff were assigned to the study. Dr. Scheidt stated that at present, the Program Office had 1.4 full-time equivalents for scientific staff. Recruitment efforts are underway for three additional full-time staff, but that a six-to-eight month delay was incurred in those efforts. Dr. Scheidt noted that the expertise of the WGs, the NCSAC, and the ICC were assets both in the development of the study and in the recruiting effort. He also stated that Dr. Alan Guttmacher of the National Human Genome Research Institute, NIH, volunteered to send a geneticist to assist in developing this branch of science for the study.

Dr. Yeargin-Allsopp stated that the ICC’s Plan B for understaffing entailed more work done by the ICC. Dr. Michael commented that the design of the study was too murky to allow a clear definition of the needed size for specific hypotheses/themes. He added that attrition figured to influence the initial sample size.

Dr. Little remarked that in a study of similar size, a staff of 50 was assembled and commented that "500 volunteers working five percent of the time" was not a good approach. Dr. Landrigan affirmed that a dedicated staff was crucial.

Dr. Mendola stated that the ICC needed to submit quarterly material to the NCSAC, and that ICC members were undertaking tremendous efforts in support of the NCS. She added that the roles of these two groups were distinct and that some of the discussions were on subjects the ICC was addressing.

Dr. Fleischman asked whether the NCSAC could come to a consensus on how to deal with personnel issues. Dr. Goldman replied that staffing would have to be added in order to move further in deploying the NCS. She remarked that item 8 from the June meeting had been started despite the note that said otherwise.

Dr. Bellinger asked whether the ICC felt the resources available to the NCS were sufficient to push the study forward. Dr. Mendola replied that the difficulty was in recruiting committed scientists who will get a time-limited appointment, although Dr. Alexander was open to lengthening terms to five years. Dr. Scheidt stated that the ICC had discussed staffing as early as 15 months ago and that the funding uncertainty made commitments to staffing a difficult proposition.

Dr. Yeargin-Allsopp assured the NCSAC that the ICC had worked diligently on this issue for a long time. Dr. Little claimed that newly graduated scientists might not be especially concerned about long-term employment.

Dr. Dudley asked how the NCS would deal with problems arising later in the study if personnel issues persisted. He stated he met researchers who were reluctant to get involved in the NCS because of uncertainty over the fate of the study.

Dr. Graham stated that "an agency’s management can do what it wants," adding that the agencies should examine the option of hiring for a position not wholly dedicated to the NCS. She confessed she was worried about the fate of the study because of the staffing difficulties.

Dr. Mattison stated he had heard three issues. One was the structure of relations between the WGs, the NCSAC, and the ICC. The second was assuring feedback between the WGs on one hand and the ICC and the NCSAC on the other. The third was the "substantial concerns" regarding staffing. Dr. Mattison added that he would like to see a formal response regarding any contributions toward NCS staff from all the relevant agencies.

Action Item: Agencies should forward ideas about contributing staff for the NCS to Dr. Mattison.

Preconception Recruitment

Germaine Buck, Ph.D., Division of Epidemiology, Statistics, and Prevention Research, NICHD

Dr. Buck stated that several groups had worked on preconception recruitment, including Early Origins of Adult Health. She commented that failure to include preconception enrollment would deprive the study of critical data.

Dr. Graham complimented the quality of the preconception enrollment proposal, adding that obtaining data from the first trimester was critical. Dr. Mattison stated that he felt there was assent that this was important, but that questions remained on sampling frequency, cost, and generalizability.

Dr. Bellinger was unclear on how many would be enrolled preconceptionally. Dr. Buck stated this was deliberately vague and that differences of opinion existed even within groups. The lower end of the range of expressed preferred percentages was 30 percent and the upper end of the range was full preconception enrollment. She added that some groups assumed full preconception enrollment and that she felt that a good number would be about one third.

Dr. Suarez asked about the likely ratio of the number enrolled to the number recruited. Dr. Buck replied that it might be around 55 to 60 percent enrolled. She added that exposure profiles for women without previous successful pregnancies may vary widely from those without previous reproductive success.

Dr. Samet stated that, with regard to pilot studies, sampling/modeling can help reduce costs and may be preferable to full preconceptional recruitment. Dr. Buck seconded the notion, adding that the Kaiser Family Foundation had some experience showing that there was interest among the U.S. population in environmental risk and that this could be employed in setting up the study.

Dr. Michael stated that the passion for and lack of evidence in support of preconception enrollment were both impressive and that he had doubts about the undertaking. He commented that unplanned pregnancy was not random in nature, and that such a sample would not be representative. Dr. Buck’s response was that she was aware of the differences, but that the data suggested that planned versus unplanned led to "divergent results," leading open the possibility that deriving such information may prove valuable.

Dr. Swartz commented that there was a near-universal desire to see preconceptional enrollment for at least part of the study cohort. He added that he was aware of other bodies of experience in this area, one of which was the EPA/NIEHS Children’s Environmental Health Research Centers, which focus on sampling and reaching hard-to-reach populations.

Dr. Buck stated that one of the co-principal investigators for one of the centers is on her WG, and has some notions on preconception enrollment and data collection.

Dr. Bachrach stated that there were good reasons for preconception enrollments, but was concerned about attempts to dismiss the differences between planned and unplanned pregnancies, recommending a broadening of expertise from social and behavioral sciences before any decision is made. Dr. Buck stated that her WG was pursuing exposures first and foremost and commented that while it can be difficult to establish a precise meaning for planned and unplanned pregnancy, there was nonetheless some literature on how to pose the question to study subjects that will avoid the pitfall of stock responses to those queries.

Dr. Goldman stated that the statistics on successful planned pregnancy suggested a recruitment of at least a factor of ten of the target enrollment, with an additional multiplier dictated by a rate of participation. She added that obtaining the numbers needed might require an effort to contact virtually every woman in the U.S. who is planning to get pregnant.

Dr. Landrigan stated that preconception recruitment did not control well for potentially episodic exposures. Dr. Buck replied that the design would help establish acute, non-chronic exposures and that day-specific exposure probabilities might be elucidated.

Dr. Selevan stated that exposures may exhibit seasonal or other periodic characteristics and that some exposures were for materials that the body metabolized too quickly to be detected after conception. She added that preconceptional sampling of only a small cohort may yield valuable data and that preconceptional sampling of the entire 100,000 was indeed a daunting proposition.

Dr. Mattison summarized the discussion by stating that there was a clear interest in a preconceptional cohort, but that some outstanding issues could not be handled only by the Fertility and Early Pregnancy WG. He declared that the FEP WG would have to collaborate with the environment groups and the Study Design WG to get after some of the issues.

Ms. Jones stated that the community element was critical and that pregnancy location was affected by transience, which could dictate exposures. Dr. Chapin stated that some of the questions were based on different experiences and that the more specific the NCSAC can be about the questions to be answered by the WGs, the more quickly WGs could complete their tasks and avoid generating useless data.

Community Outreach and Communications WG

Diane Dennis-Flagler, M.P.H., Agency for Toxic Substances and Disease Registry
Edith Parker, Dr. Ph., University of Michigan School of Public Health

Dr. Dennis-Flagler stated the they had an expert panel workshop in December looking at roles and expectations in engaging communities in research as well as communication, intervention, and sustainability. The group sent out a report on the expert panel workshop and wanted to develop some draft recommendations for site criteria for the RFP. The first draft is completed and will undergo peer review before submission to the NCSAC.

She stated that the workshop concluded that participatory approaches were crucial to the success of a study and that community involvement was necessary to build the trust needed to sustain the NCS.

The workshop participants recommend that her WG establish a definition for the word "community," and that each site be required to demonstrate "true evidence of community partnerships." She added the NCS might need to develop community profile models to identify community leaders and establish parallel community advisory panels to work with the NCSAC.

They feel that selecting centers with existing partnerships will save time and effort and that the NCSAC should encourage centers to hire community members to take on various tasks. Another recommendation is that the study hold regular "communication events" (health fairs, workshops, etc.) to keep the communities updated.

Dr. Dennis-Flagler stated that some of the concerns include whether there is a mechanism to assure such efforts are coordinated and implemented across the study. The group felt there was a need to determine how, when, and whether to intervene. She added that there might not be a very realistic view of the willingness of subjects to go along with the type and frequency of proposed sampling.

This group has a first draft of RFP criteria and wants to assemble models for community profiles with other WGs to apply to the entire study.

Dr. Doswell asked if the NCS should provide some education to each community on the purpose of the NCS, to which Dr. Dennis-Flagler responded in the affirmative. Dr. Doswell stated that communities responded negatively to assumptions of a deficit condition and that evaluating community strengths should be a publicized part of the NCS. Dr. Doswell asked if the community could not be used as a resource to address transportation issues for study subjects.

Dr. Swartz stated that there were tensions between community concerns and study design imperatives. He asked about how the community model would affect randomness and representativeness. Dr. Swartz stated that communities might bristle at the notion of not having any input into the design of a study. He asked whether some flexibility in local implementation was needed.

Dr. Fleischman asked if the meaning of the word "community" entailed a geographic construct. He added that there were subsections of the community that would require specific address and that the various ethnic and other demographically-unique subcommunities would have to be accounted for early in the design of the study. Dr. Mattison stated that the NCSAC looked to this WG to provide this kind of input.

Dr. Little stated that a community model could be designed around a probability-based selection process, but commented that he saw little coordination between the Study Design WG and this group on this subject. The reply was that the Community Outreach and Communications WG was concerned about how this would all be pulled together across groups. Dr. Dennis-Flagler stated further that there was no mechanism in place to assure that all concerned parties were there at the meetings.

Dr. Mattison stated that there was an obvious range of issues to be dealt with and that the staff from all agencies would have to weigh in on this.

Dr. Guerra stated that transitional communities, such as those populated by many recent immigrants, and the relevant assimilation patterns may be worthwhile inputs and asked if this was addressed. The answer was that it had been discussed, but not extensively. Dr. Guerra referred to a National Academy of Science study and more recent health department data that suggested some "worrisome trends" he characterized as invisible.

Measures of Exposures and Outcomes: Work Done Since the December Meeting

Tamar Lasky, Ph.D., National Children’s Study, NICHD

Dr. Lasky stated that inter-WG groups were tasked with developing lists of variables for exposures and outcomes as well as timing of data collections. She added that the variables were classified by biological (up to five), chemical (up to 50), physical (up to 10), and psychosocial (40 to 50) variables. Outcome variables were grouped into those for birth, neurodevelopmental behavior, injury, obesity, growth and puberty, asthma/respiratory, and diabetes and metabolic. She stated the list needs much work and that the list demonstrates lack of time to develop them, but that it does serve as a starting point.

On the subject of the timing of visits, Dr. Lasky stated that some groups suggested no particular point during pregnancy while others were fairly specific. Most favored a fairly intense regime in infancy and childhood, with a slackening of pace over time.

Dr. Lasky stated that a measurement of lead was not specified by any group, but that it would surely be identified in later study development.

Dr. Graham asked if the interdisciplinary teams had met since December. The answer was no, and Dr. Graham asked what the barriers might exist. Dr. Yearing-Allsopp commented that the permanence of specific WGs was discussed by the ICC, but that responsibility for the final decision lay with the NCSAC. Some concerns in this area included time and disciplinary competence.

Dr. Graham stated she had reservations on the termination of WGs and asked how the NCS might get to a point at which the work was moving forward.

Dr. Mendola commented that the NCSAC had given some WGs a charge to follow up on specific tasks. Dr. Swartz stated that members working on cost estimates should be present during such discussion. Dr. Fleischman commented that he would like to review "the dirty data," and Dr. Lasky pointed out that some liked raw data whereas others preferred finished products.

Dr. Michael stated that he was concerned about data collection not assigned to specific groups. He added that it was "amazing how much is being done."

Mr. Quackenboss suggested that a next step might be that groups review the question of subject burden for sample collection. The second item he suggested was that they attach the measurements to hypotheses and that this would assist protocol development.

Dr. Lasky stated that only measurements related to the hypotheses should have been suggested and that the WGs might not have had time to exhaust all the possible exposures of their respective hypotheses. She added that a spreadsheet file would allow tracking the origin of the hypotheses.

Dr. Doswell asked whether focus groups would be a good way to vet some issues and that the sample collection work should be discussed in focus groups. Dr. Mendola replied that the results of this kind of work would notion surface sometime in the next month.

Dr. Phillips asked how to insert notions of non-pathological outcomes into the study. Dr. Mendola informed her that the ICC had begun looking at study elements that require 100,000 subjects. She added that subjects such as optimal health outcomes and adjustment are not specified in any documents because it was likely that there would be justified criticism that examination of such questions called for a more precisely-aimed study.

NCSAC-ICC Procedures for Interaction

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

Dr. Mattison introduced Dr. Ken Schoendorf, who presented a discussion on the communication protocol between the NCSAC and the ICC. He stated that the point is to assure that Dr. Duane Alexander, Director, NICHD, will obtain the information and advice he needs to supervise the study.

The ICC agreed on an ad hoc process for vetting information before forwarding that information to Dr. Alexander. However, some notions developed during this period were found to be somewhat impractical. The two-week turnaround proved unrealistic partly because it did not allow the NCSAC enough time to examine the material and partly because of the need for public deliberation.

Dr. Schoendorf proposed that any materials needing NCSAC review would be presented two weeks prior to the quarterly meeting, to be included in the Briefing Book. The ICC would ask for return on the submission six weeks after the meeting, giving the ICC five weeks to react to that feedback and return it to the NCSAC two weeks prior to the next NCSAC meeting.

Dr. Graham commented that it might be more appropriate for the NCSAC to come to some agreement on the issue during each meeting. Dr. Schoendorf stated that the six-week window for feedback was simply an outside timeframe to assure the ICC will have time to respond. Dr. Selevan remarked that the six weeks gave the NCSAC time to confer with WGs before replying to the ICC.

Dr. Fleischman stated that the proposal gives the NCSAC an opportunity to develop a communication process with the WGs. Dr. Mattison agreed to this, asking for suggestions for synchronizing the NCSAC effort with that of the WGs.

Action Item: Forward suggestions for synchronizing the NCSAC effort with that of the WGs to Dr. Mattison or Ms. Leahey.

Draft Criteria for Selection of Sampling Design

Sherry G. Selevan, Ph.D., National Center for Environmental Assessment, EPA

Dr. Selevan asked members to comment on the draft criteria for selection of a sampling design. She stated that the aspects most in need of discussion included feasibility, generalizability and statistical representativeness, retention, and appropriateness for the core hypotheses and themes.

Dr. Swartz commented that a discussion of community involvement and outreach should not be restricted to the category of recruitment response and retention. He stated that this effort be listed under categories other than recruitment.

Dr. Mattison asked which WGs should be included or excluded in this effort. Dr. Fleischman urged avoidance of creating a process that requires that each question presented to the NCSAC be forwarded to WGs.

Dr. Selevan responded that the criteria were intended to serve as a filter for the designs described in the Westat report as well as the subsequently-proposed hybrid designs. The ICC and/or WGs would further develop the designs that survive this first-round clearance, which they would again run through the criteria to establish which design best served the needs of the NCS.

Dr. Fleischman asked whether there were any controversies over that process, and Dr. Selevan responded that there were, most of which were based on the degree of representativeness and/or randomness, as well as the limitations each design imposed on various measurement and recruitment efforts.

Dr. Yeargin-Allsopp asked if the criteria were controversial. Dr. Selevan replied that she felt they were not especially so because the ICC spent a great effort to obtain input from a wide range of sources. Dr. Mattison stated that the document constituted a set of criteria for exploration in greater detail in pilot studies. These criteria will be vetted further after the pilots have wound down. He added that the five major elements were not an issue, but that the numbered items under each were issues, especially the question of community involvement. He asked if the NCSAC could accept the criteria with those provisos. The only expressed opinions assented.

Dr. Graham stated that the document did not clearly describe a connection between outcomes and hypotheses and that the relative importance of the hypotheses was not adequately addressed.

One member asked if a point system would assist the sorting process. Dr. Selevan stated that the ICC had discussed a point system, but concluded that to do so might not be helpful. Dr. Little remarked that the selected model was important enough to hold a conference to sort through the sampling models.

Dr. Michaels requested that the sampling design not be selected until there was a more sound sense of how the data would be coded and used. He added that he saw a potential problem with the generalizability of the overall study versus that of a specific hypothesis or measurement.

Dr. Landrigan stated that the Framingham Study captured mostly white males, but that the resulting data was nonetheless enormously valuable to other populations. Dr. Klebanoff commented that the trade-off might run between generalizability and acquisition of sufficient sample size to collect a useful body of data.

Dr. Little asked if an individual was charged with primary responsibility for selecting the sampling design. He professed to being troubled by the fact that a committee was handling this task. Dr. Mattison stated that the Program Office had responsibility for this, pending input from the NCSAC, the ICC, and the WGs.

Dr. Phillips stated that the Framingham Study looked at only part of the population and was not strongly representative of the U.S. population, but that it disclosed a lot about risk factors that nonetheless applied to other demographic groups. Dr. Suarez commented that a representative sample might not yield good data to evaluate varying rates of exposure. Dr. Selevan made the case that the purpose was not to determine prevalence, but to establish etiology.

Dr. Michaels stated that one criterion for etiology should perhaps include whether behavior can change outcomes, which he said suggested that the method of recruitment could make a difference in the quality of the data. He added that causation was modified by behavior in many instances, using the example of lead in housepaint that a child might not be exposed to if the wall is covered.

Dr. Mendola asked if the NCSAC had a strong recommendation about the criteria, asking whether the ICC should proceed to the next step in this area or examine the criteria further.

Dr. Graham commented that the hypotheses and the ability to collect samples were of some influence on the sampling plan and that a plan had to account for these. Dr. Landrigan commented that several EPA/NIEHS Children’s Environmental Health Centers have been running pilot studies for more than three years.

Dr. Landrigan asked when the design would be completed. Dr. Scheidt stated that the Program Office was working on bringing the process along, but had no definite date for design completion. He added that the NCS would have to upgrade the Westat report and settle on the core hypotheses first. Sampling analysis will consume another round, to be followed by the vetting of the sampling design plans.

Dr. Selevan stated that she felt the reaction of the NCSAC indicated a need to work on generalizability and sample size, and asked if she could send out amendments via e-mail. Dr. Mattison said those changes would have to be discussed in the meeting rather than via e-mail.

Pilot Studies Update

Carole A. Kimmel, Ph.D., National Center for Environmental Assessment, EPA
Frank Holloman, M.P.A., National Children’s Study

Mr. Holloman stated that events demonstrated a need for a tracking instrument for proposals as they are passed around between the NCSAC, the ICC, and the Program Office. Mr. Holloman described the spreadsheet used to track those proposals.

Dr. Kimmel remarked that her ICC subcommittee had further work to do to review ongoing pilot studies. She stated that the ICC had just completed the first round of pilot study reviews employing this process and had no feedback yet as to the efficacy of the process. Dr. Kimmel commented further that the ICC would attempt to send all such proposals to the NCSAC prior to making a decision, but that urgent needs may involve a bypass of the normal procedure. She stated that the first priority for pilot study review were those needed early in the NCS, such as those looking at pregnancy, neonatal health, and sampling.

Dr. Mattison stated that the goal would be to establish a similar tracking process for each hypothesis/project, allowing the public and members of the ICC and WGs to visit a pilot study site to review the accomplishments. Dr. Kimmel thanked Mr. Holloman for his work on the process, noting that it will help the ICC and the NCSAC mesh their efforts more effectively.

Dr. Michaels asked if this information would be sent back to WGs, to which Dr. Mattison responded in the affirmative, albeit in a "very uneven way." He reiterated Dr. Kimmel’s assertion that the process was designed to ease communication with WGs. Dr. Michaels commented that it is important for members of the WGs to hear why a proposal was not deemed a high priority.

Discussion of Scientific Themes and Hypotheses Proposed by the ICC
Discussion led by Donald R. Mattison, M.D., Division of Epidemiology, Statistics, and Prevention Research, NICHD

Dr. Mattison stated that the NCSAC looked at many hypotheses in September 2002 and drew up recommendations summarized in the Briefing Book. He added that the ICC created five thematic areas to help condense hypotheses with overlapping purposes. He stated that the NCSAC would now have an opportunity to review and discuss hypotheses and the five thematic areas identified by the ICC.

Introducing the topic, Dr. Klebanoff stated that the ICC saw the study as etiological in nature rather than as a snapshot of pediatric health in the U.S. He noted that some hypotheses needed further development and that the ICC left those in place as markers for review at a later date. He stated that the criteria developed by the Study Design WG were used to evaluate hypotheses, but that a point system was not used. Some were dropped because they simply did not fit within financial and/or functional parameters. He stated that the subcommittee also examined whether a hypothesis could be tied in with others, given the samples and data that accepted hypotheses would generate.

Dr. Mattison reminded attendees that the number of proposed hypotheses totaled more than 50. He added that the NCSAC should examine how comfortable it was with those hypotheses that were included, and whether anything important had been left out. Dr. Little asked that the sampling criteria be submitted to the Study Design WG before finalizing them and the group agreed.

Dr. Doswell said she was concerned about overemphasis on childhood and earlier periods and a lack of emphasis on later life stages. She commented that racial and ethnic considerations were not explicitly addressed, as well as the concerns expressed by Dr. Bachrach.

Dr. Schoendorf stated that some of the emphasis on early life stage work was driven by a need to maintain the study’s momentum. He noted that the elements of altered neurobehavioral development ran through the proposed span of the subject’s involvement in the study, including schizophrenia, obesity, and other outcomes expressed later in life. On the questions of race/ethnicity and other social contexts, he assured that while such concerns would not be explicitly addressed in specific hypotheses, the routine collection of data would nonetheless generate relevant data that would allow researchers to examine such ideas.

Dr. Landrigan proposed that obesity and altered physical development be divided into two categories. These would be obesity and somatic growth and puberty/sexual maturation, which would assure that the study would provide data on reproductive outcomes. Dr. Landrigan commented that race/ethnicity would probably be treated as a co-variate rather than as a driver of specific outcomes.

Dr. Graham stated that she saw little inclusion of new material in the themes list, including the reproductive systems of male enrollees. She stated that some of the hypotheses seemed to reflect a tendency toward areas of existing expertise, noting that there was no examination of attention-deficit disorder, nor a review of some persistent pesticides. She also was concerned that cognitive development was not explicitly addressed.

Dr. Mendola stated that some of those items are not listed as core hypotheses because a review of such matters does not require a cohort of 100,000 study subjects, such as reproductive development and ADHD (attention-deficit/hyperactivity disorder). She added that the first step of the process was to generate a "big picture" of the NCS and that other areas of interest that are not initially explicated may nonetheless work their ways into the study at a later date.

Dr. Scheidt seconded Dr. Mendola’s comment that the process was iterative and open to additions. Dr. Michaels observed that the investment in human capital was not made explicit in the themes list. He commented that the return of children to a productive life should be made clear as a benefit of the study, an outcome, or a theme area.

Dr. Little observed that the list of themes seemed to link single factors to single outcomes, but that there might be multi-factorial interactions. He said he saw nothing on genetics in the document. Dr. Klebanoff stated that the ICC liked both those ideas; they are underlying all of the themes in the document, but may need to be more explicit. Dr. Mendola added that ethnic concerns would be addressed later as a screening review of acquired data.

Dr. Landrigan stated that neurobehavioral development as affected by some chemicals such as lead, PCBs, and so on, might be a good place to look at the effects of these interactions. Dr. Phillips stated that a placeholder could be made for a category called "health and growth" or "health and adjustment." She said the study was not laid out developmentally and that some exposures/outcomes, such as injury, implied different things at different life stages.

Ms. Jones commented she wanted to know how communities’ hypotheses fit into the picture. She observed that there was no space designated for this in the hypothesis document and that generalizability was not addressed within the context of community-specific elements of the study. Dr. Mattison stated that the community outreach WG was working to address this.

Dr. Graham stated that expectations had to be matched by presentations of study hypotheses and that some of the hypotheses should be further integrated, especially in the asthma hypotheses. She stated that one of the asthma hypotheses left NCS researchers with the dilemma of whether to treat under-treated or untreated diagnosed cases, and that the inclusion of schizophrenia and the exclusion of depression may strike some as incongruous.

Dr. Yeargin-Allsopp stated that several years ago, ICC members underwent an exercise to develop the "straw man" hypothesis and that this could be applied to developmental perspectives. She said that the exercise suggested a complex interweave of exposures and outcomes and that graphically depicting this complexity may be of some use.

Dr. Guerra stated there was nothing on infectious diseases, that CDC had data on prevention that could be useful, and that depression should be listed in the study.

Dr. Swartz commented that puberty was described as though it was a disease and that he had heard questions as to whether the NCS was a good vehicle to study to asthma. He indicated that he felt that some of the hypotheses were not very generalizable and that many researchers informed him that the NCS was attempting to research too many conditions. However, Dr. Swartz admitted that the multiple purposes enhanced the ability to build support among the various publics and communities for the NCS. He asked if the Study Design WG and the ICC could more explicitly address not only what the NCS would do well, but also what it cannot do well in order to address the interests of the various publics with which it has to deal.

Dr. Klebanoff stated that hypotheses could be designed around either exposures or outcomes, but that reconciling the two became difficult when some hypotheses were oriented to exposures and others to outcomes. He added that the ICC was warned early on to be hypothesis-driven as opposed to repeating the National Health and Nutrition Examination Survey (NHANES) model. Dr. Graham replied that her comments were aimed more at the logic of the hypotheses rather than their proliferation.

Dr. Schoendorf stated that depression had been mentioned several times, but that the ICC saw schizophrenia as a hypothesis because it is more measurable whereas depression is not so readily gauged. Dr. Graham asked if the ICC arrived at this conclusion because of the presence of someone with a background in schizophrenia and ICC members replied this was not the case. Dr. Klebanoff replied that the Development and Behavior WG would generate hypotheses related to some of these conditions, but that this group had not progressed as far as some others.

Dr. Mattison noted that disparities in WG productivity should be addressed by the NCSAC and that a formal review activity may help fill in some gaps for hypothesis development.

Dr. Landrigan commented that selling the study to some stakeholders might require a document that more explicitly discusses disease states and healthy outcomes. He added that the document needed filling out in neurocognitive diseases and developmental conditions. Dr. Mendola stated that the ICC first sought to present answerable questions with scientific rigor and that perhaps documents were not explicit enough regarding exposures to endocrine disruptors.

Dr. Doswell asked about focus groups, and Dr. Mendola discussed a series of 18 focus groups of expectant mothers and parents to gain a better feel for their interests. They held similar groups for physicians and nurses. Ms. Jones asked if community-based agencies were included. Dr. Mendola stated that they were and that the moderator’s guide for these workshops had received favorable reviews from WGs focused on community issues.

Dr. Mendola stated that while no specific racial/ethnic criteria currently exist, representation will be from across the country. There are currently no inclusion/exclusion criteria for enrollment.

Dr. Bachrach commented that many hypotheses did not list environment as an exposure, stating that the hypotheses suggested an "inside the body" bias. She also asked if the ICC was comfortable with leaving race/ethnicity in the background. Ms. Jones commented that failure to investigate those points will omit much valuable data.

Dr. Mattison stated that NIEHS/EPA was looking at such questions, adding that should the ICC model the NCS in a developmental way, each stage of the study would have to include an environmental exposure-related outcome. Dr. Mendola stated that a developmental description made it difficult to sell the fully-budgeted NCS and that a menu of benefits was crucial to obtaining funding.

Dr. Scheidt stated that the Injury WG agreed to reframe/redraft its hypotheses, but is not done with this work as yet. They want to develop hypotheses for violence/aggression, child abuse, unintentional injury, and the consequences of blunt trauma. The unintentional injury is receiving less attention over time because the notion is not well-suited to the NCS.

Dr. Michaels asked if the epidemiological orientation of the ICC could be leavened with other expertises and Dr. Klebanoff replied that the ICC recognized the importance of "out of body" factors. He asserted that the NCS might have to decide between being a medical/epidemiological study that tries to incorporate other elements or a study of environmental factors that manages to include epidemiology.

Dr. Mattison said the discussion needed to go deeper in terms of examining which issues are most influential on human health "across development," but which will nonetheless exclude some exposures/outcomes. He stated that the study would have to examine a variety of influences, including those of a sociological nature.

Dr. Landrigan asked whether the second injury hypothesis and the last asthma hypothesis could be dropped because they do not require 100,000 subjects. Dr. Mendola answered that the hypotheses as presented did not represent a perfect set for any observer, but that the current list of hypotheses was perhaps the best that could be had.

Dr. Bellinger asked if it was possible to recast the hypotheses, but noted that they may be bound by discipline. However, he felt the rationale document should discuss the developmental model to be applied throughout the study.

Dr. Doswell asked if the WG members expected that all WGs would contribute to the hypotheses. Dr. Mattison responded in the affirmative, but the ICC members disagreed. Dr. Yeargin-Allsopp stated that the WGs were told that their input was needed, but there was no promise that all hypotheses would find a place in the study.

Mr. Quackenboss stated that in regard to "external exposures," some will be biological or environmental, but that the available tools for measurement and classification would shape some measurements.

Dr. Little stated that the ICC was doing much of the work of designing the study and that if the ICC’s expertise was seen as too narrow, its membership should be expanded to include expertises in other areas.

Dr. Swartz offered the notion that the ICC and the NCSAC could present a plea of "humility" as a means of limiting the number of hypotheses. He admitted that the list of measures could become infinite, but stated that the list of measures be allowed to expand.

Dr. Scheidt stated that the question of the composition of the ICC was not a product of intent, but more of availability and institutional resource. He added that the ICC demonstrated an interest in a diversity of inputs, but that the NCS could not become a fishing expedition. He also noted that the NCS would not be able to address some questions, but that it could pull data that may be applied to those questions.

Dr. Doswell stated that race plays a role in an individual’s perspective on what it means to be an American and that such factors influence behavior which in turn influence outcomes. Dr. Phillips proposed that an exposure to discrimination should become a study hypothesis if the race was a factor to be understood.

Alexa Fraser of Westat, who was in the audience, stated that while any data collection had to be linked to a core hypothesis, the ICC could nonetheless ask for additional indicators, referring to racism as an exposure.

A woman from a parent group for learning disabilities expressed her hope that such concerns will be included. Doris Haire of the American Foundation for Maternal and Child Health stated that permitting consumption of food and beverages during delivery led to improved outcomes and expressed the hope that midwifery hospitals would be included in the NCS.

The meeting was adjourned for the day.

March 7, 2003

Dr. Mattison reconvened the NCSAC meeting at approximately 8:15 a.m.

Children’s Exposure to Chemical Agents

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

Dr. Needham expressed his gratitude to several individuals and groups, including the Exposure to Chemical Agents WG and Jim Quackenboss. His discussion covered biomonitoring of pediatric exposures.

He defined an environmental chemical as a chemical compound present in air, water, food, soil, dust, or other environmental media. He defined biomonitoring as assessment of human exposure to chemicals, chemical metabolites, or reaction products.

He stated that human exposure starts with a source that goes into either an environmental matrix (air, food, water, or dust) or a biological matrix, and that this source may proceed directly to human exposure or to a vehicle for delivery to an exposure.

He described the effect paradigm as proceeding from exposure to internal dose, then target organ dose, followed by the biologically effective dose. Subsequent steps in the process are early biological effect, altered structure/function, and disease induction, which result in neurodevelopmental alterations or asthma, for instance.

The lifecycle presented by Dr. Needham demonstrated the difficulty of assessing exposure during various life stages. He stated that biomonitoring did not permit researchers to answer all questions on exposure, but that it must be deployed along with environmental monitoring and the use of questionnaires.

He described the National Health and Nutrition Examination Survey (NHANES) at some length. Administered by the National Center for Health Statistics at CDC, NHANES I commenced in 1971 and ran for four years. This first iteration did not look at environmental chemicals. NHANES II, 1976 to 1980, measured lead as well as persistent and non-persistent pesticides.

Hispanic NHANES ran from 1982 to 1984 and evaluated exposures for Hispanic populations for the elements included in NHANES II, as well as organochlorine pesticides.

NHANES III was a two-stage study of 30,000 spanning the years 1988 to 1994. This study examined the prevalence of lead, cadmium, selenium, and cotinine. This included a priority toxic reference range study that looked at 32 volatile organic chemicals and 12 non-persistent pesticides.

NHANES 99+ is a continuous survey of a representative population that started with roughly 5,000 participants for 116 environmental chemicals and includes home interviews and oversamples minorities, the elderly, and pregnant women. In 2000, low-income whites were included for further review.

For subjects aged 12 and under, NHANES 99+ looks at tetrachlorodibenzo-p-dioxins (TCDDs), dibenzofurans (PCDF)s, polychlorinated biphenyls (PCBs), and organic compounds (OCs) via serum. For children aged six and above, NHANES 99+ examined urine for phthalates, phytoestrogens, and polyaromatic hydrocarbons. Non-persistent pesticides were the subjects of tests for those aged six to 59. This iteration of NHANES tested for metals such as lead and cadmium in subjects older than one, and mercury for subjects between the ages of one and five and women of childbearing age (16 to 49).

One member asked about the age span for women of childbearing years. The consensus was that the standard range was 15 to 49. Dr. Needham replied that he was not certain as to the rationale for the span used in NHANES.

The National Report on Human Exposure to Environmental Chemicals is a biennial assessment measuring the presence of a range of chemicals in urine, blood, and blood components (whole blood stores poorly). Spot urine samples were said to be possibly problematic due to coffee consumption and the question of whether creatinine compensates for caffeine. The reported data includes geometric means, and is divided into percentiles (10th, 25th, 50th, 75th, 90 th, and 95th). The report was published in March.

Dr. Needham stated that this report:

  • Identifies environmental chemicals in the U.S. population
  • Provides a reference range for selected chemicals
  • Identifies exposure status in individuals
  • Identifies the prevalence of those with elevated levels
  • Identifies groups with elevated levels
  • Monitors changes in exposure over time
  • Assesses the effectiveness of efforts aimed at reducing exposures
  • Provides exposure data for risk assessment
  • Helps set priorities for health/epidemiological research.

Three chemicals most implicated as neurotoxicants are lead, mercury, and PCBs. Dr. Needham stated that the case for the impact of various pesticides was less clear. Analytical chemistry methods employed include high-resolution mass spectrometry and gas chromatography for organic compounds.

Lead content in gasoline paralleled a drop in mean blood lead levels and exceeded the decreases widely predicted when the effort to reduce gasoline lead content first commenced. However, the perceived tolerance for blood lead levels also dropped over the years. In 2000, the geometric mean for blood lead averages in the U.S. was less than 2 micrograms per deciliter, down from 16 when lead levels in gasoline were unregulated.

In NHANES III, phase II, the 4.4 percent of the population that had blood lead equal to or more than ten micrograms per decileter was made up of principally the socio-economically disadvantaged of minority or refugee extraction living in urban settings. However, Dr. Landrigan stated that 10 to 15 percent of children of more affluent homes in the U.S. Northeast registered more than ten micrograms per deciliter when home remodeling work is underway. He commented that this fact might help market the study.

Mercury. Dr. Needham stated that women of childbearing age demonstrated greater exposure to mercury than "young children" and that the levels corresponded to fish consumption. More than 95 percent of women of childbearing age demonstrated measurable levels of mercury (mostly organic mercury), but mostly less than six micrograms per liter (15 micrograms per liter is the threshold at which neurocognitive sequelae are thought to set in).

Dioxin/PCBs. Measures of dioxins in NHANES are hampered by insufficient serum. Dr. Needham stated that measures of PCBs are currently based on 20-25 milliliters of serum, but NHANES attempted to measure PCBs using only four milliliters from each subject. He stated that the effort might involve pooling blood samples, which will provide only a mean level of exposure for those samples rather than percentiles. He stated that the data obtained in the latest iteration of NHANES indicated that the levels of these two compounds were "decreasing rapidly in the U.S. population." In the mid-1980s, the average U.S. rate of 2,3,7,8 TCDD measured at seven parts per trillion on a lipid basis whereas the current level is one part per trillion. He added that the survey suggested a similar drop for other PCBs.

Pesticides. In addition to chlorpyrophos, the NHANES tested for metabolites for malathion, diazinon, and parathion. For the most part, the first two occurred in undetectable quantities. He stated that the data for parathion was ambiguous because the metabolite in question is not specific to parathion. However, the data suggested that Mexican-Americans experience higher levels, and among children, those between the ages of six and 11 years tested at the highest levels.

Phthalates. Phthalates are metabolized first by cleavage of an ester, the measure employed by NHANES. Levels of the monoethyl metabolite were highest, suggesting exposure to diethyl hexyl phthalate, which is used primarily to bind scent compounds to perfumes and colognes. Dibutyl is used in nail polish and auto refinishing compounds, whereas the butyl benzyl is used in adhesives. Dr. Needham stated that levels of diethyl hexyl were higher in adults than immature subjects, higher in women than in men, and higher in non-Hispanic African Americans. However, children demonstrate higher levels of most phthalates.

Others. Dr. Needham stated that children registered higher levels of cotinine, a tobacco-smoke metabolite, than adults. This metabolite correlated positively with low birthweight. Dr. Needham stated that NHANES had little data from birth to six years for endocrine disruptors.

He stated that the effort to collect data for time periods not covered in the NHANES consisted of collaboration with other entities looking at exposure in utero, in infants and toddlers, and those conducting case-control studies. Among the collaborators are the National Children’s Centers, Columbia University, the University of California at Berkeley, the University of Washington, Mt. Sinai, and several other university research centers as well as medical clinics inside and outside the continental U.S.

Dr. Needham stated that NHANES researchers were examining other tissues for sampling, including placenta, milk, hair, and fingernails and toenails. They are working on means of deriving more exposure information from small quantities of blood as well.

Dr. Doswell asked if phthalates were present in hair care products, to which he responded in the affirmative. Dr. Bellinger asked if the exposure report presented anything that was unexpected and should be looked at in the NCS. Dr. Needham stated that no new chemicals were examined and that he was disappointed that he could not measure levels of one type of dioxin. However, the reports on cotinine and lead were very encouraging. He added that the numbers on mercury generated some controversy.

NHANES employs a blood analysis for chlorphyrifos that will distinguish between this chemical and its methylated conjugate. He added that these methyls will soon be on the list.

Dr. Guerra asked about DDT levels. Dr. Needham stated that while levels are lower across all groups, Mexican-Americans still exhibit higher levels. As for whether demographic data distinguish between U.S.-born Mexican Americans and those born in Mexico, Dr. Needham stated that did not know whether the questionnaire made this distinction.

Dr. Little asked what the cost is for the NHANES measurements and whether this lab is the only one capable of making such measurements. Dr. Needham stated the cost was about $6.5 million, and that his lab was not the only lab capable of doing so. However, he commented that this was perhaps the only lab that could turn out that much work in the interval required by the NCS.

Dr. Ryan asked if pyrethroids would be the "pesticide of the future" and whether this boded for increased exposures in the future. Dr. Needham noted that the biennial nature of the NHANES made it likely that such numbers would not show up for a couple of years.

Dr. Landrigan commented that the expense of such work made the information a great value for the taxpayer. He noted that many manufacturers were moving overseas, and asked whether there were plans to collaborate with other nations or the World Health Organization (WHO) to evaluate exposures. Dr. Needham stated he could not recall any contact with WHO, but that there was some contact with Canadian and Mexican authorities to this end.

Ms. Jones commented that residents of Los Angeles, CA exhibited high levels of toxic exposures, especially in low-income areas, and asked if any of the tests deployed in the metro Los Angeles area were "different." Dr. Needham replied that there were studies in the Del Lamo area "a few years back." He remarked that NHANES was a national survey and that the agency had deployed only 15 stands, the precise locations of which he could not list.

Dr. Scheidt asked how the experience of NHANES might aid the NCS. Dr. Needham replied that NHANES data could help the study target specific populations. He added that the collaboration between NHANES and the EPA/NIEHS Children’s Environmental Health Centers could provide the study with a tremendous resource.

Pregnancy and the Infant-Testing Feasibility of 3-D Ultrasound

Cathy Spong, M.D. and Marian Willinger, Ph.D., Center for Research for Mothers and Children, NICHD

Dr. Spong stated that she would discuss a pilot study to test the feasibility of 3-D ultrasound in the reliable storage and retrieval of fetal images. She stated that the fetal growth workshop at the December 2002 Study Assembly inspired this pilot study proposal. She added that the study would need ways to evaluate fetal and placental growth and integrity.

Dr. Spong reminded the group that the size and growth rate of the fetus dependent partly on placental integrity. Fetal organ volumes may correlate to outcomes, and volumetric assessment of the fetus and organs will be part of the pilot. Still, she remarked, the effort must avoid interfering with the pregnancy.

She noted that 3-D ultrasound allows measurement of the volumes of fetal organs and placenta without requiring the subject to remain still during the scan, as is the case with magnetic resonance imaging. She reiterated that volume measurements are one of the benefits of 3-D ultrasound, as is the ability to obtain morphological information on the fetus.

Dr. Graham asked if the described characteristics of 3-D ultrasound were unique to that technology. Dr. Spong stated that in broad terms, most two-dimensional scanning technologies provided a more limited set of measurements, such as bone length, without enough data to determine volume. This technology allows a viewer to manipulate the stored images to view the organ or fetus from various perspectives and minimizes patient burden. The scans can be performed in as little as five to 10 minutes.

3-D allows multiplanar information and curved structures in one image, which two-dimensional data sources cannot provide. Data storage allows retrieval and manipulation, and the technology reduces observer-induced variability.

The Doppler feature of this scanning allows evaluation of bloodflow, which is important because vascularity has a substantial impact on the placenta and, in turn, the pregnancy. Images can be reconstructed from any angle.

Dr. Spong stated that a pilot study for 3-D ultrasound is called for because of the novelty of the technology, but also because this technology may offer minimal patient burden and superior image retrieval. The pilot will address feasibility of obtaining reliable images from multiple centers, the degree of burden on the patient, and the reliability of retrieval of archived image data. The goal is to take images during each trimester, test the transmission and retrieval of those images, and obtain a realistic cost estimate of image acquisition, storage, and retrieval.

Dr. Spong stated that the pilot would entail selection of three sites with 20 subjects from each. The pilot proposal calls for both 2-D and 3-D scans of each subject. She stated that this pilot ties into several hypotheses.

An attendee asked about image size and storage requirements. Current estimates are that the images will consume approximately 160 megabytes per patient.

Dr. Doswell asked about locations of pilot sites. Dr. Spong replied that major universities most likely have the equipment needed and that the Pacific Northwest will likely host one site. Dr. Spong stated that not all machines will be identical and the current cost of this pilot would be $70,000-$80,000. The total cost per scan may run between $100 and $400, and the machines can run as high half a million dollars. Dr. Klebanoff remarked that those who were familiar with this technology informed him that the raw cost of scanning was about $75 without figuring in storage, retrieval, and review.

Dr. Fleischman asked whether any conflict of interest existed in this discussion. Dr. Mattison stated that the Ethics team discussed this with the Office of General Counsel at NIH and that while there are few locations in a position to implement such technology, by the time the NCS is deployed, the installed base will have expanded considerably, which would render the current discussion insufficiently specific to present a conflict of interest. The exception would come in the case of NCSAC members who might participate in the pilot study under discussion. The presenters were employed by NIH, and so long as WG members were only guiding the use in broad terms, no conflict existed. Institutions would compete for contracts for the pilot.

Dr. Landrigan asked if 3-D ultrasound would pick up "potentially correctible" anatomical anomalies that would present ethical dilemmas. Dr. Spong replied that the 3-D images would only be stored, not analyzed. Dr. Landrigan asked whether the archive without review was itself ethically questionable. Dr. Spong replied that 2-D ultrasound was not widely seen as called for "in every pregnancy," let alone 3-D ultrasound.

Dr. Swartz asked whether the WG expected that 3-D ultrasound would be used three times on every enrollee, should the pilot be included in the NCS. She responded that it depended on the hypotheses chosen for the NCS. Dr. Swartz remarked that while the per-subject scan cost was low, the aggregate cost of scanning the entire NCS cohort might be prohibitive. She agreed and reiterated that the number of subjects recruited for scanning would hinge on the selected hypotheses. When asked about validation studies for 3-D ultrasound in connection with low birth weight, Dr. Spong replied that the question of the correlation between low fetal mass of normal and pathological implication was an issue of interest, but the pilot would examine the question of fetal weight in contrast with 2-D without directly addressing the question of the correlation between fetal mass and pathology.

One participant stated that the time of exposure to ultrasound should be recorded and Dr. Scheidt asked if 3-D ultrasound exerted more pressure than the 2-D version. Dr. Spong stated that the pilot will look at exposure times needed to obtain scans. Dr. Willinger said that some studies showed that 3-D scans tended to be shorter because practitioners tended to mull over the images during the scan. Dr. Lasky stated that the June Ethics workshop would include a discussion of 3-D ultrasound.

Dr. Little questioned the fiscal feasibility of including this in the NCS due to the large numbers to be enrolled and commented that this study could include controls. Dr. Spong replied that 2-D ultrasound might be less costly, but that 3-D scans will be much more common and less expensive in the future. She added that archived data is much richer with 3-D, such as retrieving specific organ volumes, which is not possible with 2-D.

Dr. Doswell commented that there were serious legal and ethical dangers involved in not making diagnoses with 3-D that could result in termination of a pregnancy. Dr. Spong replied that in the past, such interventions have triggered iatrogenic outcomes. This study is to evaluate the utility of the tool and patients would be informed of the purpose of the ultrasound. She added that other studies deleted subject identifiers in the records.

Dr. Willinger stated that studies of birth defects using 2-D ultrasound involved a review of scans by the physician, who had the option of recommending intervention. She added that an ethical review of this issue is called for, assuming the pilot study wins approval. She commented further that the "quick and dirty" paradigm for studying 3-D ultrasound was already done, and that the data from 2-D work was not conclusive regarding birth defects.

Dr. Goldman commented that she backed the pilot, but that the technology will evolve and that such developments may negate some of the value of this pilot.

Dr. Samet asked about standardization of measurements. Dr. Spong stated that 2-D measurements included algorithms for ensuring measurement accuracy and that the 3-D pilot would establish whether such algorithms applied to 3-D ultrasound. Dr. Willinger added that the study could provide new algorithms.

Dr. Klebanoff stated that the mindset had arisen that storage of the raw scan data was perhaps the most important thing to accomplish with this pilot, given that algorithms would improve in the future. Dr. Willinger added that the pilot might include regular updates from manufacturers to stay abreast of technological changes.

Alexa Fraser of Westat asked when in the third trimester researchers would obtain the third scan. Dr. Spong stated that this was not yet determined and that the pilot would not likely result in such a determination. Regarding the question of how the machines would be configured and designed, Dr. Spong replied that this would depend on availability.

Dr. Doswell asked about the location of the clinic in which the scans would take place and how this would affect patient burden, and Dr. Spong agreed that this was a concern, but noted that the sites would compete for participation and that the pilot would look at patient burden.

One member stated that there may be an important difference between raw and processed data volumes, and Dr. Spong replied that this question was not addressed as yet, but that the pilot would be able to answer.

Dr. Mattison commented he saw this as something in which the NCSAC saw some potential and that conflict of interest would likely be handled by the competitive process for site selection. However, he noted that conflict of interest would be looked at further.

Draft Criteria for Selection of Sampling Design

Sherry G. Selevan, Ph.D., National Center for Environmental Assessment, EPA

Dr. Selevan presented the amended language for the sample design criteria. She commented that the community involvement and participation section was removed from the recruitment heading and placed under the heading for feasibility. The section covering generalizability and statistical representativeness reflected amended language.

Dr. Landrigan questioned the sequence of elements listed under generalizability, commenting that the NCS was not intended to determine prevalence. Dr. Selevan replied that the list did not reflect priorities. Dr. Michael stated that Dr. Landrigan may be misreading the intent of the first item, that the section discusses the parameters of outcomes rather than the prevalence, a distinction he stated was important because it described how the link between exposures and outcomes affected the selection of hypotheses.

Dr. Goldman expressed her concern that the question of measures of exposures and outcomes might conflict with representativeness. Dr. Little seconded this concern, noting that representativeness did not necessarily equate with equality of probability, an issue he said was key because a given design might miss high-end exposure populations.

Dr. Selevan commented that NHANES reviewed special case situations, but that those numbers did not fall into their national distribution calculations. Dr. Scheidt added that targeting some specific exposures left the possibility that the study would miss other exposures.

Dr. Little stated that this predicament could be compensated for by developing an index of exposures and selection of study subjects with higher probabilities of exposure according to the index. Exposure variables could be accounted for by stratifying the sample.

Dr. Goldman asked about explicating cultural and racial groups in the document, adding that such considerations could shape sampling, geographically or otherwise. Mr. Quackenboss stated that he was under the impression that the primary purpose was not to establish distributions, but to provide valuable data on estimating exposures in the U.S. population and in some communities. He added that on the subject of stratification, exposures can vary over time and this fact made the NCS a study of exposures of "person-years."

Dr. Swartz observed that the comments raised the question of how the NCS would be presented to the public. He remarked that it was important to emphasize what the NCS can do that other studies cannot. Dr. Correa commented that while the exercise was geared toward helping to evaluate competing sampling designs, he sensed an interest in a hybrid design on the part of the NCSAC. He asked whether this was the case.

Dr. Goldman mentioned that it was difficult to know how a hybrid design would work. Dr. Landrigan pointed out that some healthcare settings would defy categorization, possibly calling for a "hybrid-hybrid" design. Dr. Little complained that the document lacked sufficient specificity to address concerns such as oversampling. Dr. Selevan asked if a reordering of criteria was still indicated. Dr. Little responded in the negative.

NCS Program Office Update

Peter Scheidt, M.D., National Children’s Study Director, NICHD

Dr. Scheidt discussed the function of the Program Office, noting its support of all organizational components and its reporting responsibility. Those entities and their respective roles and responsibilities are:

Agency Director (Dr. Alexander)
Working Groups
Program Office
Strategic Decisions
Operational Decisions
Operations, Infrastructure

He added that Dr. Alexander has made himself available to Drs. Scheidt and Mattison frequently, to the point of offering almost "unparalleled accessibility" for an agency head. Dr. Scheidt stated that before "signing checks" for the study, Dr. Alexander will ask about NCSAC recommendations and will delegate many executive functions to the ICC.

Dr. Scheidt stated that the WGs were essentially consultative in function and described the Program Office’s roles as including:

  • Pilot study management and oversight
  • Protocol development
  • Reports
  • Presentations
  • Communication
  • Infrastructure
  • Planning and finance.

Dr. Scheidt discussed the staffing situation at the Program Office, including management interns, but noted that the Program Office has only one staff scientist despite that the plan calls for several more positions. He described the staff as lean despite the dedication of time of several members of the ICC and WGs. Dr. Scheidt stated that the study’s progress has been greatly abetted by the use of support contracts.

Ms. Keim discussed several contract resources aimed at getting the NCS off the ground. For logistical support, the NCS has retained the services of Circle Solutions, Inc. of Vienna, VA, who arrange meetings and conference calls, set up workshops and symposia, and handle information management. Circle also works on reports, directories, and provides information technology support.

IQ Solutions and Ogilvy Public Relations are working on a five-year communication plan to address the various stakeholders such as policy makers, scientists, and community leaders. An e-newsletter will be part of the regular communication that will help participants stay abreast of the NCS.

The planning document is complete for information management capability, but the Program Office is assessing needs for data and clinical coordination functions. To complete this plan, the functional groups must be determined.

Dr. Scheidt stated that the Program Office was working with contractors to conduct literature reviews, white papers, workshops, and general planning support tasks, including analysis of organizational structure and costs. Potential contractors are submitting capability statements, which the Program Office will examine.

Regarding the conduct of pilot studies for developing clinical measures, Dr. Scheidt stated that the list of pilot studies has been winnowed and will be assigned to each agency per the capabilities of each. He stated that the NCS will test the feasibility of sampling strategies.

Protocol development activities consist of a process for protocol development, which called for Program Office staffing that has not been provided. The ICC and one of the WGs have assumed responsibility for this task. The schedule consists of submission of drafts covering the frequency of visits and acquisition of measures in draft form in July and drafts covering further development in December 2003 and March 2004.

The WGs will serve as consultants to the protocol development effort and the Program Office is aggressively pursuing further staffing.

Funding currently allocated to the NCS consists of $10 million for FY 2003 and, at present, $12 million is targeted for FY 2004. The projected need for FY 2004 is $26 million if the NCS is to commence with subject enrollment toward the end of FY 2005. The outlook beyond FY 2004 is uncertain. However, Dr. Zerhouni’s office is supporting discussions with the Office of Management and Budget (OMB) and the White House for these subsequent years.

Dr. Landrigan asked if the Program Office had adjusted its cost estimates for the disproportionate share needed in the early years of enrollment. Dr. Scheidt confirmed that the Program Office had done so and noted that funding needs peaked at approximately $220 million in FY 2007 and decreased to $80 million unadjusted in subsequent years.

Dr. Doswell asked how the uncertain figures would affect funding. Dr. Scheidt replied that Congress asked them to cost the study out and that those on Capitol Hill were aware of the pitfalls in such a process.

Dr. Graham commented that the enrollment date of 2005 suggested potential problems with the OMB clearance process, asking Dr. Scheidt about the realism of the proposed start date. Dr. Scheidt replied that in a center-based strategy, the NCS could recruit initial centers, which would, in turn, involve communities that would allow sampling strategy testing. The clinical investigators in those centers would provide input that would allow enrollment. Dr. Scheidt admitted that this was an ambitious agenda. Dr. Graham replied that in the event that all the pre-protocol work was completed and the protocol was ready for OMB, a year each would be called for with OMB and contractors. Dr. Scheidt replied that the NCS had already covered much of this ground with OMB and that OMB had committed to conducting its review in parallel with protocol development.

Ms. Jones asked about costs for community engagement and the long-term effects of getting into communities by 2005 with something resembling permanence. Dr. Scheidt answered that community involvement does not show up as a line item, but that the costs were included in several activities. He added that the plan called for funding the centers "well ahead" of study enrollment. Ms. Jones replied that cost estimates for many studies "gets stuck in the institution," which leaves communities with insufficient resources to maintain engagement. She added that communities end up with no control over studies and are in a subservient role. Dr. Fleischman commented that the $80 million a year might not suffice to maintain the community engagement effort. He asked if part of the community engagement process included "creative thinking about the informed consent process."

Dr. Scheidt replied that the ICC hoped that the Ethics WG or other sources would generate some ideas regarding the informed consent process. Dr. Fleischman commented that the Ethics WG could create content, but might not have the resources to create a mechanism for developing a communication plan to keep communities abreast of study activities. Dr. Scheidt stated that the ICC was open to suggestions.

Dr. Doswell asked if the study would include English as a Second Language (ESL) populations. Dr. Scheidt responded in the affirmative. Dr. Guerra asked when the communication effort would commence. Dr. Scheidt replied that the Program Office received a number of invitations to discuss the NCS, but that media curiosity about the NCS had not reached a substantial level at the time of this meeting. Ms. Keim noted that a communication plan will include such things, but that the excitement will follow the allocation of substantial funding. However, the sampling design will greatly influence the communication plan.

Chris Shreeve of Ogilvy Public Relations stated that the media will be more interested when there is a protocol in hand. When recruitment begins, the communication plan will have to include ground-level communication work.

A representative of the American Psychological Association asked how Study Assembly members participated in the study. Dr. Scheidt answered that public meetings constituted the "major face-to-face opportunities" to communicate bi-directionally with the NCS, and that the current listserv totaled more than 2,000 recipients. He stated that the sheer numbers on the listserv limited how deeply the NCS could engage the audience via this vehicle, but that the electronic newsletter would abet this effort.

Ms. Keim added that there was no reason that the NCS could not take in new ideas for pilot studies and hypotheses, and Dr. Scheidt commented that the Program Office triaged information and assured the members that the information is routed to its proper destination.

Dr. Bachrach asked if protocol development would include a collection of substantial data that did not fall under an existing hypothesis. Dr. Scheidt answered that this would be the case, but that such elements would comprise about 30 to 40 percent of the "ultimate value" of the NCS.

He added that expensive design elements would have to be backed by well-justified rationales and that a hypothesis was the standard for such justification. Dr. Bachrach stated that she was under the impression that the hypotheses seemed to drive protocol development and that she saw no provision for inexpensive data collection measures, such as media exposure.

Dr. Scheidt testified that he always expected a range of items to make the study. However, he noted that any media study would have to be relatively inexpensive unless backed by a working hypothesis.

Dr. Schoendorf stated that some efforts to capture media effect were incorporated into a hypothesis for obesity and declared that the protocol development document specifies a number of non-hypothesis data collection efforts, including social context indices.

Dr. Doswell asked what the status was of WG hypotheses. Dr. Mattison stated that the NCSAC had not heard from all WGs, but noted that the NCSAC had looked at a request to fund some case studies for integration of hypotheses. He added that some WGs might be disbanded if their work is no longer needed.

Dr. Landrigan asked if any of the WGs were working on the onset of puberty, commenting that he felt that such hypotheses were lacking in numbers. Dr. Mattison responded in the affirmative, and Dr. Graham commented that she had seen "four or five" such hypotheses, but that the NCSAC had asked the relevant WGs to merge them. She remarked that she was surprised that these were not described in the Briefing Book.

The Fertility and Early Pregnancy WG had a meeting at the end of August, from which several proposals arose that were not reviewed at the September 2002 NCSAC meeting. Dr. Mattison added that because the December meeting included no hypothesis work, much of that work had not been reviewed, but that he hoped to see this work in the June NCSAC meeting.

One member of the public asked if some components of women’s health not currently on the list will be included. Dr. Mattison noted that some such topics will make the NCS, perhaps including one addressing the function and structure of the pelvic floor.

Ms. Jones remarked that the importance of community involvement and empowerment was based on the tendency of universities to be biased toward other priorities. She added that communities lacking influence over the uses of funding tended not to be honest in disclosing opinions of studies because such honesty can result in termination of funding of related community projects. Ms. Jones stated that if the community becomes a partner early on, research protocols can disclose more about the intent of the study. She encouraged the NCSAC and the ICC to set aside funds for communities to give them a stake in the study and encourage frank discussion.

Dr. Landrigan commented that the RFP for the EPA/NIEHS Children’s Environmental Health Centers was a good example of how to incorporate the community into such projects. The proposal requires that each center set up a community-based prevention research project and one of the criteria for judging a proposal is the extent of community involvement.

Dr. Scheidt remarked that some communities are experienced in such processes and asked whether a competitive process might not eliminate communities without experience in hosting research studies. Ms. Jones replied that universities and other entities often had existing partnerships with their respective communities and that the institutions often tended to veer away from community boards that presented unwanted dilemmas.

Discussion Regarding Proposals for a Workshop and White Paper on the Injury Pilot Study

Lucina Suarez, Ph.D., Texas Department of Health

Dr. Suarez stated that the intent of this workshop was to assess the cumulative effects of repeated injuries. A panel of experts would use this time to develop a more complete core hypothesis and some definitions, including for mild traumatic brain injury (MTBI). The workshop would also review neuroimaging, neuropsychiatric outcomes, and biomarkers.

The group hoped to get this underway this fiscal year. Dr. Fleischman commented that the absence of a workshop suggested the need for more expert opinion, but asked that MTBI be defined and what the relevant examination/imaging modalities would be. He asked for confirmation that the relevant imaging work, which may require sedation, was permissible under federal guidelines. Dr. Suarez agreed, adding that the risks of sedation would have to be examined. No objections were raised in sending this project to the ICC for prioritization.

Developmental Measures Pilot Study

David C. Bellinger, Ph.D., Children’s Hospital, Harvard University

Dr. Bellinger stated that this is a proposal to review literature on available measures to assess key domains in development and behavior. The measures of interest address physical development, health status, emotional/social function, and language and cognition. The review would look at key milestones in each area, measures available to assess each domain, describe known developmental problems and vulnerabilities in each domain, and describe interactions between each domain and the other three. He added that this could aid planning for the NCS.

He proposed the review focus on the first two goals, namely identification of major milestones within each domain and identification of tools available to assess each domain. The reviewers would then focus on the measures to identify how they would apply to the NCS. Other concerns include:

  • Degree of standardization of measures
  • Psychometric properties
  • Reliability and validity of different measures
  • Sensitivity and specificity to the outcomes of interest
  • Degree to which the measures are appropriate for the populations under study.

He commented that some tests may never have been applied to those for whom English is a second language.

Administration issues to be addressed include cost, the time needed to draw a sample for measurement, training of clinical staff, and any special equipment and space. He stated that the result would be encyclopedic.

Dr. Doswell remarked that the definition of development and should be more precise for a literature review. Dr. Dudley commented that the WG might need to reduce the scope to a more manageable set of objectives.

Dr. Michael recommended this pilot and literature review focus on the five best objectives by domain and by life stage. Dr. Bachrach commented that there was recent work on shortening measures for longitudinal studies and that NICHD had recently sponsored three workshops to examine the notion. Dr. Little seconded Dr. Bachrach’s observation about the measures for longitudinal studies, adding that there was some trade-off between the "relativeness" and content.

Dr. Mattison asked if there was any disagreement with moving this forward with the proviso that this WG reduce the list of objectives. No objections were voiced.

Creation of Standardized NCSAC Meeting Agenda and Briefing Book for Future NCSAC Meetings

Jan Leahey, National Children’s Study, NICHD

Ms. Leahey informed members that she saw her role as that of facilitating communication to WGs, assisting in standardizing processes, and standardizing administrative areas such as the agenda for NCSAC meetings. She hoped to standardize communications between this meeting and the June meeting.

Ms. Leahey asked NCSAC members how she might more effectively convey information on the progress of the NCS. She stated that she had spent some time with ethics lawyers to provide guidance to NCSAC members and that she hoped to craft a process for reviewing ethical dilemmas. The agenda for future meetings will be more detailed, but she stated that she would like feedback on needs for future meetings.

Dr. Landrigan asked if the standard meeting site had been selected. She stated that the site had not been determined and that she needed feedback via an evaluation form from NCSAC members. Dr. Landrigan weighed in on behalf of a site in downtown DC because of ease of access from National Airport. Dr. Dudley commented that the hotel in Bethesda in which he was staying was a good hotel in a poor location in terms of nearby amenities.

Integrated Framework

Dr. Mattison asked members to discuss the strengths and weaknesses of the "integrated framework." After the December 2002 Study Assembly, several WGs began working on three case studies to evaluate the utility of a framework for gene/environment interaction as related to asthma, autism, and positive health. They will present their work at the June NCSAC meeting.

The Health Disparities and Environmental Justice WG is examining measurements of racism, also to be presented in June. Dr. Mattison commented that the proposal in which WGs should report to the NCSAC twice a year would be incorporated into agendas.

Dr. Graham stated she would like to see the "next generation of hypotheses." Regarding the integrated framework, she commented that while she finds the notion appealing, she also finds it ambiguous.

Dr. Little asked if anyone had proposed a pilot for the entire study. Dr. Mendola responded in the affirmative, but that it was not fully developed. Dr. Klebanoff stated the ICC would not be ready to present this at the June meeting.

Dr. Michael commented that it might help the NCSAC if it had a review of the effect of instrument on subject response, a notion seconded by Dr. Fleischman.

Dr. Doswell was concerned about the site of the focus groups, commenting that the composition of groups perhaps should be wholly one racial/ethnic group to allow discussions that would otherwise never take place.

Dr. Dudley wanted to see more substance on sampling design. Dr. Guerra stated that racism should be expanded to look at color, culture, and language, and that at times the issue was not race, but culture. He also stated that migrant workers be included in the NCS.

Dr. Suarez complimented the Program Office on the Briefing Book and other materials. She asked that unfinished core hypothesis business be put on the agenda for June.

Dr. Graham invited the ICC to the June meeting. Dr. Schoendorf stated that the ICC would benefit by more specific recommendations from the NCSAC regarding further development of the study.

Dr. Mendola took Dr. Schoendorf’s comments further, recommending that the NCSAC decide how it wants to go about reviewing materials related to the study, an important question given that the volume of material is "overwhelming." Dr. Landrigan replied that it might be simpler if the ICC informed the NCSAC of new developments, possibly including a hyperlink to materials stored on the Portal.

Dr. Klebanoff remarked that ICC members also found the Portal unwieldy and that the contractor will examine ways of making it more accessible.

Dr. Mattison informed members that the February issue of the American Journal of Public Health had material on measurements of racism on health.

Dr. Landrigan commented that the investment meant that those involved in the NCS would have to work diligently to sell the NCS inasmuch as the budget would consume about one fifth of that of NICHD. He felt that if the personnel working on the NCS did not ramp up some such effort, the study may either be attenuated or never get off the ground at all.

Dr. Dudley stated that he recently received a call to give a talk on the NCS and that he did so without prepared materials. He suggested that a standard slide show presentation might be helpful.

Dr. Bellinger proposed that the NCSAC consider "making a strong statement" on the lack of resources committed to the Program Office. No dissenter spoke.

Dr. Dudley asked that NCSAC decisions be made by secret ballot to weed out concerns about potential personal affronts. Ms. Leahey commented that the FACA might influence the permissibility of the idea.

Dr. Mattison thanked all attendees for their participation and proposed closing the meeting. There were no dissenters. The meeting was adjourned at 1:53 p.m.

NCSAC Committee Members

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

Peter Scheidt, M.D., NCSAC Executive Secretary
National Institute of Child Health and Human Development, NIH

David C. Bellinger, Ph.D.
Children’s Hospital, Harvard University

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

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

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

Lynn R. Goldman, M.D.
Johns Hopkins University Bloomberg School of Public Health

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

*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 Chicago School of Medicine

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

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

Jonathan M. Samet, M.D.
Johns Hopkins University Bloomberg School of Public Health

*Ken Sexton, Sc.D.
University of Minnesota School of Public Health

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

*Stephen P. Spielberg, Ph.D., M.D.
Johnson & Johnson Pharmaceutical

Lucina Suarez, Ph.D.
Texas Department of Health

Daniel J. Swartz
Children’s Environmental Health Network

*Did not attend this meeting

Ad Hoc NCSAC Committee Members

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

Loretta Jones
Healthy African American Families

Deborah Phillips, Ph.D.
Georgetown University

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

Interagency Coordinating Committee Members

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

*Gwen W. Collman, Ph.D.
National Institute of Environmental Health Sciences, NIH

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

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

*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

Tamar Lasky, Ph.D.
National Institute of Child Health and Human Development, NIH

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

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

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

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

*Did not attend this meeting


Germaine Buck, Ph.D.
National Institute of Child Health and Human Development, NIH

Robert Chapin, Ph.D.
Pfizer, Inc.

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

Frank L. Holloman, M.P.A.
Presidential Management Intern, NCS

Holli Beckerman Jaffe, J.D.
Office of General Counsel, DHHS

Jan Leahey
Executive Secretary, NCSAC

Yvonne Maddox, Ph.D.
National Institute of Child Health and Human Development, NIH

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

Edith Parker, Dr. P.H.
University of Michigan School of Public Health

Mary Plummer
National Institute of Child Health and Human Development Committee Management, NIH

Catherine Spong, M.D.
National Institute of Child Health and Human Development, NIH

Gretchen Weaver, J.D.
Office of General Counsel, DHHS

Marian Willinger, Ph.D.
National Institute of Child Health and Human Development, NIH

Observers and Other Participants

Christine Bachrach
Arthur M. Bennett
Leni Buff
Linda Burton
Jessica J. Campbell
Chris Chavis
Elizabeth Davis
Alexa Fraser
Rebecca Goodman
Doris B. Haire
Raffael Jovine
Donna Lloyd-Kolkin
Judith Mopsik
Daniel Raiten
Jerry Rench
Mike Sacca
Kathy Schneider
Angela Sharpe
Christine Shreeve
Karen Studwell
Audrey Thurm
Kevin Vigilante
Ann Vinup
Diane Wagener

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

   May 15, 2003   
Dr. Mattison's Signature
Donald Mattison, M.D.
National Children’s Study
Federal Advisory Committee