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 March 2004 NCSAC Meeting Summary Minutes

The 9th Meeting of the National Children’s Study Federal Advisory Committee (NCSAC)

March 4-5, 2004
Holiday Inn Select
Bethesda, MD

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

Welcome: Review Agenda, Meeting Goals and Objectives

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

Dr. Mattison welcomed National Children’s Study Advisory Committee (NCSAC) members and other participants to the ninth meeting of the NCSAC. The stated goals of this meeting were to:

  • Focus on the transition from National Children’s Study (Study) planning to implementation
  • Establish a specific set of goals and objectives for the June 2004 NCSAC meeting
  • Determine the status of work products submitted to date by the Working Groups, including current proposed hypotheses, measures of exposures and outcomes pilot studies, and workshop reports
  • Determine the activities required to finalize these products
  • Consider measurements of healthy development
  • Discuss timelines for phasing out or reconfiguring various Working Groups
  • Discuss an appropriate response to the President’s Council on Bioethics’ request to include an assessment of artificial reproductive techniques as part of the Study.

Jan L. Leahey, NCSAC Executive Secretary, NICHD, NIH, DHHS, provided an overview of NCSAC administrative issues. Ms. Leahey said that the NCSAC’s 10th meeting will be held June 28-29, 2004, in the Washington, DC, area. The minutes for the NCSAC eighth meeting have been posted to the Study’s Web site. To date, there have been no comments on these minutes. Ms. Leahey asked participants to forward briefing materials and other information to the Program Office to keep the Study Web site current. Ms. Leahey listed the following action items for the meeting:

  • Recommendations on Working Group work products
  • Determine where individual Working Groups stand
  • Determine what additional products are needed
  • Determine what the NCSAC can do to facilitate getting those products
  • Discuss future schedule and activities of the NCSAC and Working Groups.

Program Office Update: Study Timelines, Institute Updates

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

Dr. Scheidt summarized the major events and activities since the last NCSAC meeting in December 2003:

  • Program Office Staffing.  Dr. Scheidt listed the following full-time staff members who joined in the fall of 2003:
    • Ruth A. Brenner, M.D., M.P.H., protocol development leader
    • Sarah S. Knox, Ph.D., behavioral scientist
    • Warren Galke, Ph.D., data management/clinical coordinating center project officer
    • Marion J. Balsam, M.D., partnerships/project officer.
    Current part-time/detailed scientists in the Program Office include:
    • Kenneth Schoendorf, M.D., M.P.H.
    • Carole A. Kimmel, Ph.D.
    • James J. Quackenboss, M.S.
    • Rebecca Brown, M.P.H., M.E.M.
    • Lester R. Curtin, Ph.D.
    Three new part-time/detailed scientists have joined the staff since December 2003:
    • Terry Cox, M.D., Ph.D., epidemiologist, neuro-opthalmologist, biostatistician
    • Terry Dwyer, M.D., M.P.H., protocol development, cohort and epidemiological studies specialist
    • Tracey Thomas, P.H.D., biomarker specialist.
  • Contracts.  Battelle, technical support contractor for the Study Program Office, is currently assigned the following tasks:
    • Provide background information for the Study sampling strategy
    • Identify developmental measures in four domains for the Study
    • Develop a sample protocol for the Practice Based Research Network (PBRN) feasibility study
    • Perform power analyses for social environment hypothesis
    • Review extant databases for the Study
    • Review literature and write a white paper on measurement of housing quality.
    The information technology (IT) system for the Study is being developed by a consortium of Booz Allen Hamilton Inc. (project lead); RTI; Battelle; and Levine, Fricke, and Sanz. These contractors are involved in the following tasks:
    • Defining the IT requirements for recruitment and enrollment
    • Identifying mechanisms for questionnaire data collection
    • Identifying mechanisms for electronic capture of clinical data.
    Dr. Scheidt explained that the electronic capture of clinical data is important for the success of the Study. However, because of the diversity of information sources and disparities in medical records systems, electronic data capture will be challenging. The Program Office anticipates contractual procurements for the following:
    • Clinical/data coordinating center (concept clearance approved and currently under development)
    • Repository (sources-sought announcement made and responses received)
    • Vanguard centers.
  • Pilot Studies.  Dr. Scheidt noted that there about 30 pilot studies that are currently ongoing for the Study. He listed the following recent and upcoming workshops and dates:
    • Rurality Workshop, March 2, 2004
    • Sampling Design Workshop, March 21-22, 2004
    • Possible Roles for Inclusion of the Study of Cancer Workshop, tentatively April 2004
    • Questionnaire and Diary-Based Methods for the Early Assessment of Asthma-Related Health Outcomes Workshop, tentatively May 27, 2004
    • Assessing Dietary Intakes and Patterns in Women and Children, tentatively spring 2004
    • Day-Specific Probabilities of Conception and Prospective Pregnancy Studies Workshop, tentatively May 2004
    • Measurement of Maternal and Fetal Infection and Inflammatory Responses Workshop, date to be determined
    • Gene Expression and Behavior Workshop, date to be determined
    • Social Environment Measures Workshop, date to be determined.
  • Protocol Development.  Dr. Scheidt explained that as the Program Office engages in protocol development, the Study is entering a new phase. Elements of the protocol will become part of the scope of work for procurements. Because of this, there are potential problems with possible contractors or competitors regarding possible conflicts of interest, "inside track" information, and procurement integrity. Dr. Scheidt listed the following implications for the protocol phase of the Study:
    • Findings and proposals about Study design and measures (that is, protocol elements) can be shared with Working Groups and NCSAC.
    • Conversely, protocol elements cannot be shared with Working Groups and NCSAC ahead of other potential contractors.
    • To protect Working Groups and NCSAC, communication about the evolving protocol must be in the public domain.
    • Therefore, the Working Groups and NCSAC will have limited interaction with the Interagency Coordinating Committee (ICC) and the Program Office.
    • There will be reduced intensity of Working Group and NCSAC activities.
  • Partnership Development.  Dr. Scheidt briefly discussed partnership development with the Foundation for the National Institutes of Health:
    • A memorandum of understanding is being prepared.
    • Implementation of specific partnerships will depend on funding for the full Study.
    • The Program Office is exploring cosponsorship of congressional briefings with the American Chemical Council, the Children’s Environmental Health Network, and other organizations.
  • Proposed Expansion of the Study.  Dr. Scheidt explained that the proposal to expand the adult component of the study is still under consideration and will continue to be explored. While decisions about funding with Congress and the current administration are in progress, the Study will continue as it has. The National Human Genome Research Institute and other institutes engaged with the adult component will continue to address conceptual questions and relationships with other adult genetic studies. When funding for the Study is clarified, the proposed three-generational study will be given more detailed consideration.
  • Funding Status Update.  Dr. Scheidt briefly discussed the status of funding for the Study. For fiscal year 2004, the total funding required is approximately $26 million. However, to date, only $12 million has been allocated for fiscal year 2004. According to Dr. Scheidt, the Study is ready for launching. With funding, the Study will start collecting data beginning with participant enrollment in 2006. The funding needs for fiscal year 2005 are $27 million. The President’s budget request for fiscal year 2005 of the Study contains approximately $12 million. Dr. Scheidt noted that the total projected costs for the Study-$2.7 billion spread over 25 years-have not changed.

In a question-and-answer session, Dr. Scheidt addressed the following issues and concerns:

  • Calculation of Economic Benefits of the Study.  Although no formal calculation of the economic benefits has been performed, many experts familiar with the Study believe that the overall economic benefits will be enormous. The costs benefits from a single year could possibly pay for the entire study.
  • Quality Assurance.  Although there is not a specific quality assurance component stipulated for the vanguard centers, quality assurance is part of the procurement process, and activities of the vanguard centers are heavily laced with quality assurance requirements.
  • Enrollment of Vanguard Centers.  Vanguard centers will be enrolled through competitive procurements. However, caveats to the competitive process are sampling needs and geographic requirements. Participant enrollment may require stratification, and there may be requirements for certain types of data collection. Vanguard centers may not be exclusively academic centers. Centers may be private hospital systems, state health entities, or federal entities (for example, Native American areas). Optimum linkages with communities will be highly encouraged as part of the requirements for selection. Although the study protocol may have certain rigid elements, flexibility will be included to incorporate input from communities.
  • Study Advocates.  Because Study consortium partners are federal agencies, they cannot lobby Congress directly for Study funding. Study partners and allies such as the Foundation for the National Institutes of Health and the American Chemistry Council can, however, keep Congress informed on the Study efforts. There is no current need to lobby Congress for increased funding. Those involved in the Study will continue to cultivate advocates for the Study. Fiscal year 2005 is the first year for which appropriations will be required to implement the Study.
  • Procurement Processes.  Some of the pros and cons of various funding mechanisms such as requests for applications, requests for proposals, and P30 grants were mentioned. Other issues and concerns in the procurement process include ethics, the use of human research subjects, advice from the Office of Management and Budget, consent issues, internal review boards, data ownership, and publishing.
  • Budget Allocation.  Because of the amount of funding allocated to the Study, health science researchers have expressed concern about potential impact on budget allocations for investigator-initiated research. Although additional funding is required to begin the Study, this should not affect funding for other research. The Study will create a large database for potential use to researchers and will eventually create more opportunities for a vast program of research.

Update on Protocol Development

Ruth Brenner, M.D., National Children’s Study Program Office, NICHD, NIH, DHHS

Dr. Brenner described the Program Office’s role in protocol development; defined the Study protocol; described the processes, issues, and challenges in this effort; and presented a timeline for continued protocol development. At this time, the Program Office is:

  • Drafting the text of the Study protocol
  • Overseeing and coordinating development of operational manuals
  • Working with the contracting office to develop relevant procurement documents.

According to Dr. Brenner, the background, goals, and objectives of the Study protocol will outline the science in a precise manner. The Study design and methods will describe:

  • Who the Study will be enrolling (that is, sampling) as participants
  • When and where participant contacts will occur
  • What will occur when participants are contacted
  • Limited information on how data will be collected (details on data collection will appear in the operational manuals).

Dr. Brenner explained that the Study protocol is not a detailed operational manual, which will be developed at a later date. The protocol will address the appropriate issues of human subjects in research, including descriptions of:

  • The benefits and risks of Study participation
  • Confidentiality policies and regulations
  • Consent and assent policies and regulations.

The protocol will also address appropriate issues regarding the handling and processing of data, including data analyses and data sharing and dissemination.

Dr. Brenner listed the following "givens" about what the Study protocol will involve:

  • Environmental influences on child health and development
  • Environment broadly defined
  • Enrollment of approximately 100,000 children
  • Enrollment during or before pregnancy
  • Follow-up for 21 years
  • National in scope.

Dr. Brenner commented that the protocol is driven by the focus of the Study-the infant/child, not the mother or family. She briefly described the guidelines for protocol development. The Program Office and protocol development team are developing a unified Study protocol that is:

  • Hypothesis-driven
  • Focused enough to be a cohesive document
  • Broad enough to cover all relevant exposures and outcomes.

The process of protocol development is derived from a complex collaboration among hypotheses, workshops, pilot studies, and other reports and documents. The draft protocol will then be submitted for federal input and comments. The draft protocol will be modified, revised, or refined in response to the feedback from federal entities. The next step in the process is to submit the protocol as a public document and to invite additional input and comments.

The current major issues for protocol development, and the resources for addressing them, include the following:

  • Sampling strategy
    • Westat document
    • Battelle document
    • Sampling design workshop (March 21-22, 2004)
  • Timing of enrollment
    • Same materials as cited for sampling strategy
    • Publications
    • Other documents
  • Participant burden (for example, the number of blood draws)
    • Focus groups
    • Pilot studies (PBRN)
  • Ethical issues (for example, will there be a central internal review board or multiple internal review boards?)
    • Workshop (June 2003)
    • Working Group recommendations.

The current challenges for protocol development include reviewing, synthesizing, and integrating all of the materials prepared to date for the Study. The solution to this challenge, Dr. Brenner said, is to organize these materials into manageable "bites." Program Office staff members are dividing up the workload, with different members focusing on different areas. Another challenge for protocol development is the limitations on who can provide input to the process. The Program Office is prohibited from seeking input from outside the federal government. The solution to this challenge is to rely heavily on expertise with the federal government.

The current strengths for protocol development include:

  • Voluminous study documents
  • Expertise within the Program Office
  • Full-time senior scientific staff and their areas of expertise:
    • Marion J. Balsam, M.D., pediatrics, health care management
    • Ruth A. Brenner, M.D., M.P.H., pediatrics, epidemiology
    • Warren Galke, Ph.D., environmental epidemiology
    • Sarah S. Knox, Ph.D., behavioral sciences
    • Peter C. Scheidt, M.D., M.P.H., general pediatrics
  • Part-time senior scientific staff and their areas of expertise:
    • Terry Cox, M.D., Ph.D., neuro-opthalmology, biostatistics
    • Carole A. Kimmel, Ph.D., development toxicology
    • James J. Quackenboss, M.S., environmental exposures
    • Kenneth Schoendorf, M.D., M.P.H., pediatric epidemiology
  • Temporary senior scientific staff and their areas of expertise:
    • Terry Dwyer, M.D., M.P.H., pediatric epidemiology.

The projected timeline for protocol development is as follows:

  • 2004           Circulate draft protocol to federal experts
  • 2004-2006   Ongoing public comment and revision
  • 2004-2005   Release initial requests for proposals
  • 2005-2006   Selection of vanguard study sites
  • 2006           Initial phase of vanguard sites
  • 2007+         Additional sites added.

In concluding her presentation, Dr. Brenner reminded meeting participants that children are the focus of the Study. In a question-and-answer session, Dr. Brenner addressed the following issues:

  • NCSAC Assistance to the Program Office.  Dr. Brenner reiterated that one of the challenges for the Program Office is the extent to which it can ask for help, assistance, and input from various groups and organizations, particularly those outside the federal government. The NCSAC can best assist the Program Office by making sure that the Working Groups have answered all questions posed to them, that they submit all work products in a timely manner, and that they define and submit their lists of exposure and outcome measurements.
  • Composition of Expertise.  A participant recognized that the Study design is an integral part of the science and that it is important to have scientific expertise among the protocol development team. However, the participant suggested that the team might be lacking in the area of social sciences. In response to this comment, Dr. Scheidt acknowledged that the current protocol development team is a "skeleton crew" that depends on input from many sources. There are plans to recruit social scientists to the team, and the Program Office expects its staff to increase in numbers when current hiring restrictions are lifted.

Report from Joint ICC/NCSAC Executive Committee

Judith A. Graham, Ph.D., NCSAC Member and Chair of the Executive Committee, American Chemistry Council

Dr. Graham reported that the Joint ICC/NCSAC Executive Committee met three times since the NCSAC’s eighth meeting in December 2003. During those meetings, the Executive Committee focused on the agenda for the current meeting and drafted a schedule for receiving and reviewing the Study strategic plan, which includes all activities and actions for 2004. The draft schedule lists the goals and expected outputs of the upcoming meetings; it also specifies the responsibilities of the NCSAC in this process. Dr. Graham explained that the NCSAC needs to "look downstream" at these future meetings in an effort to make the schedule more realistic. The NCSAC also needs to coordinate its efforts with the Working Groups and synchronize with other Study entities. Dr. Graham asked NCSAC and ICC members to provide input on the draft schedule, particularly the feasibility of the dates.

According to Dr. Graham, the strategic plan is basically a management plan that describes the "who, what, when, and where" of Study activities. The process of moving from Study planning to implementation is complex, and therefore, the strategic plan is complex. Dr. Graham discussed her outline of the draft strategic plan, which was provided to meeting participants. She provided an overview of upcoming events and activities of the NCSAC and other Study entities, including the ICC, Working Groups, and Program Office. Dr. Graham reiterated the goals of the current meeting and described her vision of goals and objectives of the NCSAC’s June 2004 meeting.

During a brief open discussion of the strategic plan, a participant commented on the sequence of Study events, suggesting that the development of the protocol and study design needs to "mesh" and that other activities listed in the strategic plan also need to "mesh."

Exposure to Chemical Agents Working Group

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

Dr. Ryan reported on the activities of the Exposure to Chemical Agents Working Group. He introduced the co-chairs and members of this Working Group and noted that the Working Group has been very active over the past 18 months. Dr. Ryan became NCSAC liaison to this Working Group in August 2003. To date, the Exposure to Chemical Agents Working Group has proposed four hypotheses, refined hypotheses during meetings in 2002 and 2003, participated in workshops in 2003 and 2004, prepared background information for a pilot investigation, responded to all ICC questions and comments, and identified relevant measures of exposures and outcomes.

Over the last 6 months, the Working Group has been actively working to complete draft sections of its white paper. Working Group members held a working meeting in October 2003 to draft sections of the white paper, and they have been having routine conference calls to provide updates on progress. A review draft of their white paper was recently provided to Dr. Ryan, and he recommend that it be forwarded to the ICC and Program Office for review and comment. The Working Group has discussed having a contractor work with the draft white paper to develop a consolidated outline and revise the paper and tables. Dr. Ryan discussed the possibility of using the RTI contract for this with Carole A. Kimmel, Ph.D., National Center for Environmental Assessment, EPA, and Pauline Mendola, Ph.D., Office of Research and Development, EPA. Drs. Ryan, Kimmel, and Mendola are currently drafting a work assignment and government cost estimate before seeking approval from the Pilot Study Committee and the ICC.

The primary focus of this white paper is the measurement and analysis of exposures to environmental pollutants and biological agents for the Study. The completed document will be approximately 200 pages and will contain the following sections:

  • Introduction
  • Relevant chemical and biological agents for different study hypotheses, with listings of specific hypotheses and exposure measurements needed to assess them
  • Methods for measurement of exposures and candidate environmental chemicals and aeroallergens, with discussion of measurement methods strengths and weaknesses by pollutant class
  • Methods for measurement of chemicals in biological media, including a comprehensive overview and review of biological monitoring state of the art
  • Survey collection instruments for use in the Study and evaluation of exposure-related questionnaire instruments
  • Study design issues related to exposure measurements for the Study, including an assessment of where exposure fits into the Study.

Drs. Ryan and Graham have reviewed the draft white paper, and the Working Group is currently seeking direction from the NCSAC via feedback through their liaison. Specifically, the Working Group requests input, through hypotheses and thematic Working Groups, on the specific pollutants and time periods of exposures. The Exposure to Chemical Agents Working Group will then be able to provide a more focused response in the white paper. Although the document is still in the review process, the Working Group expects to complete the white paper by the end of March 2004.

In a question-and-answer session, Dr. Ryan addressed the following issues:

  • Important Chemical Exposures.  A participant expressed concern that the Working Group’s hypotheses seemed to be missing important chemical exposures, particularly chemicals that might affect reproduction and testicular function. The participant mentioned metal compounds, volatile organic compounds, and chlorinated compounds. Dr. Ryan explained that there is a historical account of the chemical exposures that the Working Group considered; chemicals that were not listed in Dr. Ryan’s presentation may have discussed and considered.
  • Exposure Assessments.  Dr. Graham expressed her concern about chemical exposures that may have been left out because of lack of expertise in health toxicology. George P. Daston, Ph.D., Proctor and Gamble Company, emphasized the importance of performing cumulative exposure assessments. Dr. Ryan commented that the Working Group is attempting to identify and address all appropriate chemical exposure assessments.
  • Publication Review.  Dr. Mattison asked whether groups outside the Study would review the Working Group’s white paper. Dr. Ryan briefly discussed peer-reviewed publications. Other Working Groups could certainly serve as part of the review process, which would enhance cross-Working Group activities.
  • Multiple Chemical Exposures.  Several participants suggested that the clustering of chemical exposures, the correlations of certain exposures such as lead, and the interactions of these exposures should somehow be incorporated into the Study measures. Dr. Ryan replied that there might be a need to expand on this idea and to seek advice from other Study entities.

Repository Working Group

Mark Cosentino, D.P.M., Ph.D., Repository Working Group Co-Chair, Science Applications International Corporation

Dr. Cosentino explained that the meeting goal is to complete the transition from Study planning to implementation. To accomplish this goal, the Study design logistics need to be:

  • Discussed
  • Flexible/expandable
  • Decided on
  • Communicated to Working Groups
  • Factored into contract applications
  • Continuously upgraded as needed.

Dr. Cosentino said that the Study must begin to address logistical design issues, including communication, data sharing, and the handling and processing of samples and specimens. The following logistical design issues need to be discussed and decided:

  • Study database design
    • A single unified system?
    • Several stand-alone systems?
    • Several stand-alone systems but federated?
  • Information that needs to be tracked in real time
    • Subject-relevant
    • Sample collection
    • All sample shipments
    • Vial location at the repository and testing sites
    • Test results
  • Specimen identification format and label design
  • The type, quantity, and storage configuration of specimens needed to answer the hypotheses
  • Determine specimen sharing between hypotheses
  • Regional/satellite repositories
  • Specimen processing at repositories or regional laboratories
  • Quality assurance/quality control-centralized or regional?
  • Need stable contractors that will plan for the future.

Dr. Cosentino emphasized the importance of minimizing contractor turnover during the Study. He said that specific contractual terms can help protect the Study against contractor turnover. He suggested that contracts include specific terms about source code ownership. Because some repositories may also be performing tests, testing labs and vanguard centers will need to coordinate their efforts and integrate their information systems. Other issues regarding specimens include shipping, tracking, processing, and storage configurations. Dr. Cosentino warned that managing the database may be one of the more challenging aspects of the Study. He emphasized that the logistical design needs to be flexible and expandable, yet have built-in safeguards to ensure contractor stability.

Recommendation

Dr. Costentino recommended that the Study establish a Logistical Working Group to address the logistical design issues.

In a question-and-answer session, Dr. Cosentino addressed the following issues:

  • Specimens.  Given the anticipated large number of specimens for the Study (speculated to be on the order of 2-20 billion), the anticipated costs of freezers simply to store the large number of specimens are great (speculated to be on the order of $40 billion over the 21-year Study).
  • Procurement.  Procurement issues for the logistical design were briefly discussed.

Assisted Reproductive Technologies

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

Dr. Dudley explained that the President’s Council on Bioethics had approached several individuals involved in the Study to discuss an assessment of assisted reproductive technologies (ART) as a possible component of the Study. As a result of these discussions, O. Carter Snead, General Counsel of the President’s Council on Bioethics, presented an overview of the Council’s preliminary findings on ART in the United States. This presentation was given at the NCSAC’s December 2003 meeting in Atlanta, Georgia. At that time, the NCSAC recommended that the Council contact the Reproductive Medicine Network to discuss a possible longitudinal study of the health and developmental impacts of ART on children born with their aid. In addition, the NCSAC Executive Committee agreed to seek input from the Fertility and Early Pregnancy, Birth Defects, and Health Services Working Groups. Subsequently, the Executive Committee formally requested the Fertility and Early Pregnancy Working Group to:

  • Identify the need for further studies of ART on child health
  • Explore implications of several alternatives to examine ART within the Study and as a parallel adjunct to the Study.

Dr. Dudley said that the response to the Executive Committee’s request began with a review of a hypothesis submitted by the Fertility and Early Pregnancy Working Group. A recent meta-analysis on ART was reviewed, and discussions were held with the following subject matter experts:

  • Phyllis Leppert, M.D., Ph.D.
  • Dorrie Lamb, Ph.D.
  • Jim Segars, M.D.
  • Robert Brzyski, M.D., Ph.D.
  • Germaine M. Buck, Ph.D.

Dr. Dudley characterized the Fertility and Early Pregnancy Working Group’s hypothesis on ART as follows:

  • Primary outcomes: intrauterine growth retardation, birth defects
  • Other outcomes: preterm birth, mortality, cost/financial burden, quality of life
  • Strong rationale for this hypothesis
    • Justification for large sample size
    • Scientific merit
  • No sample size calculation
  • No consideration of potential oversampling needs
  • Some consideration of control groups.

Dr. Dudley described the findings from a recent meta-analyses titled Perinatal Outcomes of Singletons and Twins After Assisted Conception: A Systematic Review of Controlled Studies (Helmerhorst et al., British Medical Journal, 2004 Jan 31;328(7434):261):

  • 25 studies reviewed; 17 controlled; studies published 1985-2002
  • Of the singletons, 5,361 conceived via ART, compared with 7,038 spontaneous births
    • Very preterm(<32 weeks), relative risk = 3.27 (ART)
    • Preterm (<37 weeks), relative risk = 2.04 (ART)
  • Of the twins, 3,427 conceived by ART, compared with 3,429 spontaneous births
    • Very preterm(<32 weeks), relative risk = 0.95
    • Preterm (<37 weeks), relative risk = 1.07
  • Birth weight of singletons
    • <1,500 grams, relative risk = 3.00 (ART)
  • Birth weight of twins
    • <1,500 grams, relative risk = 0.89
    • <2,500 grams, relative risk = 1.03
  • SGA in singletons: relative risk = 1.40-1.46
  • SGA in twins: no difference
  • Perinatal mortality:
    • Singletons: 1.68 ART (skewed by one study)
    • Twins: 0.58

Dr. Dudley noted that this recent meta-analysis had problems with matched cohort studies (one study dominated and three had different control groups) and that matching for GA was questionable. Dr. Dudley listed the following meta-analysis conclusions:

  • Shift emphasis from achieving pregnancy to normal outcomes
  • Consider any multiple pregnancy as a failure of ART technology
  • Narrow the gap in perinatal outcomes from assisted pregnancies.

The consensus opinion from the subject matter experts who were consulted is as follows:

  • No study on ART ongoing in the United States
  • Not all ART is the same
  • Unclear whether the Study is the best design
    • 1 percent of pregnancies are by ART (2 percent in the future)
  • Indications for ART are varied
  • Adjust for cause of infertility (data are difficult to acquire)
  • Necessity for oversampling?

Dr. Dudley briefly discussed a comparison of the elements of epidemiological methods of the Study and those required for studying the effect of ART on child health. Based on this comparison, Dr. Dudley suggested that the Study might not necessarily offer the best circumstances to best address the concerns of the President’s Council on Bioethics. However, Dr. Dudley offered three possible courses of action:

  • Decline consideration
  • Accept as hypothesis and develop
  • Reconsider: Fertility and Early Pregnancy and Study Design Working Groups determine
    • Power calculation
    • Need for oversampling
    • Effect on Study overall.

In a question-and-answer session, Dr. Dudley addressed the following issues and concerns:

  • Risk of Prematurity.  There is a greater risk of prematurity among twins, and there is a greater chance of twins with ART.
  • Study Design.  Given that the Study seeks to examine a representative sampling of the U.S. population, the current study design may not be able to answer the questions that the President’s Council on Bioethics is asking. Dr. Daston commented that incorporating the ART hypothesis would require a marked alteration of the study design. To this end, Study entities could provide the necessary statistical background in order to make a wiser recommendation.
  • Additional Resources.  At this time, it is not clear whether inclusion of the ART hypothesis would bring additional resources to the Study.
  • Conception Data.  Although the Study will attempt to collect data on the circumstances of conception (to the extent possible), it is very difficult to collect information on the indications for ART, which often involve very private issues. Participants acknowledged that there is an interest in the long-term effects of ART but emphasized that the Study does not offer an ideal design to collect data on ART outcomes and is not conducive to investigating ART. The Study will attempt to capture data on ART, if possible. A participant noted that the Study cannot adequately or scientifically address rare outcomes.
  • Preconception Study Enrollment.  Enrolling a preconception subgroup is still being considered. The Sampling Design Workshop will examine this issue, and the NCSAC will make a recommendation on the preconception subgroup during their June 2004 meeting.
  • Pending Legislation.  Dr. Dudley commented that the discussion on ART might be moot because of legislation sponsored by Senator Lamar Alexander to study preterm births. According to Dr. Dudley, an amendment to Senator Alexander’s bill directs the Study to examine the effects of ART on child health. The bill’s current status was not known, nor was it known whether funding will be provided for the ART mandate.

Recommendation

The NCSAC recommends that a full study of ART not be included as a component of the National Children’s Study. However, the lack of a full study does not preclude the collection of data on ART or the ability to explore questions that can be answered by those data, as they exist. The NCSAC recommends that Study entities seek a dialogue with the President’s Council on Bioethics to further discuss the scientific issues of studying the effects on ART on child health. This discussion would identify the challenges of implementing a full study of ART within the Study and explain the types of outcomes that are achievable with the Study’s anticipated sample size.

Defining Positive Health

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

Dr. Phillips reminded the participants that the consensus from the last NCSAC meeting was to include measures and definitions of positive health as a component of the Study. In the present meeting, she suggested that participants focus their discussions on the status of measures of exposures and outcomes, particularly identifying what may be missing. Dr. Phillips noted, as an example, that neurodevelopment was one of the thematic areas that had "fallen through the cracks." Although neurodevelopmental outcomes have now been included, they need to be expanded and refined. Dr. Phillips urged participants to assess the work done to date and to determine where Study activities are headed. She briefly discussed some of the upcoming Study workshops and proposed that the Study form an ad hoc working group to advise on issues concerning positive health. The NCSAC seeks additional input to help craft the hypotheses on positive health outcomes regarding neurodevelopment for the next NCSAC meeting in June 2004.

Dr. Phillips presented an overview of a proposed conceptual approach and hypotheses that were developed by Neal Halfon, M.D., Ph.D., University of California, Los Angeles, and Paul Wise, M.D., M.P.H., Boston University. The approach and hypotheses were summarized in an 8-page document that was distributed to participants. Drs. Halfon and Wise explained that their focus was not to resolve ongoing tensions between different analytical frameworks and potential etiologic pathways, but rather to develop proposed hypotheses that reflect an approach while making use of the best science available, in a manner that responds purposefully to the specific, practical requirements of the Study.

Historically, health has been defined within three evolving contexts:

  • Negative
  • Normative
  • Positive.

Positive health was initially defined as simply a lack of negative health; then it was viewed in light of what was considered normative. In 1948, the World Health Organization defined positive health as "a state of physical, mental, and social well-being, not merely the absence of disease or infirmity." Dr. Phillips provided a composite of recent definitions of positive health:

Health is the extent to which an individual or group is able, on the one hand, to develop and realize aspirations and satisfy needs, and on the other hand, to develop the capacities that allow them to change and cope with the environment.

Some of the proposed components of positive health include:

  • Character
  • Spirituality
  • Virtues
  • Hope
  • Satisfaction
  • Social engagement
  • Sense of purpose.

Dr. Phillips said that the primary goal of a positive health outcomes hypothesis is to reframe the central elements of this complex field to meet the specific, practical requirements of the Study. The specific objectives are to:

  • Develop an analytic approach to identify the critical determinants of optimal health in children who do not have known health problems
  • Assess whether approaches to address positive health could be helpful in elucidating the critical determinants of optimal health outcomes in children with known, serious health conditions.

Special considerations for the positive health outcomes hypothesis include:

  • The impact of developmental modulation
  • The requirement for predictive capacity in the context of development.

According to Drs. Halfon and Wise, the first challenge to creating analytical strategies is a direct reflection of the developmental cadence of childhood. Factors that influence child health at 1 year of age may take on a very different form than those that affect a 4-year-old child. The second challenge reflects the inherent quality of positive health measures in children that they are often fundamentally referenced to later outcomes. Most positive health measures are "tilted forward" and convey a predictive or speculative element to any effort to assess positive health in a longitudinal cohort.

In response to these considerations, Dr. Halfon and Wise propose that the development hypothesis not depend on the adoption of any particular definition of positive health. Moreover, they propose that the effort to generate hypotheses not be directed at identifying a comprehensive list of factors determining positive child health. Their proposed approach focuses on the designation of a highly focused set of capabilities that generally reflect a broad array of child capabilities. Identification of selected "sentinel capabilities" would help ground the hypothesis generation and facilitate the search for appropriate measurement instruments.

The characteristics of the sentinel capabilities would conform to the following requirements:

  • Capacity to transform potential into functioning
  • Reflect generic pathways of effect
  • A strong consensus that they relate directly to essential elements of positive health
  • Relate to critical transition points in childhood
  • Evidence exists to suggest important genetic and environmental determinants
  • Relevant measurement tools available.

Drs. Halfon and Wise proposed two sentinel capabilities and two corresponding hypotheses.

Capability 1

School readiness is a measure of a child’s capacity to respond to challenges and opportunities presented by entering the formal education process.

School readiness includes:

  • Physical/motor development
  • Cognitive development
  • Social and emotional development
  • Language development
  • Approach to learning.

School readiness hypothesis

School readiness will be influenced by the character of family work patterns.

Several school readiness subhypotheses were also proposed:

  • Genetic and biological variations will influence the impact of parental work on school readiness.
  • Preschool childcare will mediate and modify the role of parental work in altering school readiness trajectories.
  • Exposure to media will influence school readiness and will be related to parental work patterns.

Capability 2

Antecedents of positive and negative health behaviors appear in adolescence; positive health behaviors include patterns of avoidance of tobacco, alcohol, and illicit drugs.

Positive health behaviors in adolescence hypothesis

Positive health behaviors will be influenced by the level and content of exposure to media.

Several positive health behavior subhypotheses were also proposed:

  • Biological and genetic differences alter susceptibilities to the influence of media on the development of positive behaviors.
  • Family relationships, routines, and practices mediate the influence of media on the development of positive health behaviors.
  • Schools and peer-group relationships modify media effects on positive health behaviors.

In a question-and-answer session, Dr. Phillips addressed the following issues and concerns:

  • Self-Regulation.  A participant noted that adolescent self-regulation appears to be defined by the absence of negative behaviors. Dr. Phillips explained that interest is in how self-regulation affects outcomes, not necessarily behaviors.
  • Media Effects.  Positive health can be considered in the context of "freedom," that is, transforming opportunity into positive outcomes. Media effects can have both positive and negative outcomes. The purpose of including media effects was to simplify, not trivialize, the assessment of this exposure and allow the Study to assess media effects across fields and disciplines.
  • Racism.  Because positive outcomes tend to be mostly political and economic in nature, a participant asked how racism could be assessed in the context of positive health. Dr. Phillips acknowledged that mechanisms to assess racism are currently unknown. She suggested that the Study could perform characterizations of media exposure, including violence and portrayals of values and racism. Christine A. Bachrach, Ph.D., NICHD, NIH, DHHS, emphasized the importance of assessing the content of media exposure. To this end, media data could be collected, archived, and content analyzed at a later time.
  • Adverse Events.  The collection of data on adverse events such as law enforcement encounters and violent or aggressive encounters with peers will overlap with activities of other Working Groups. Dr. Wise stressed that activities on positive health will coordinate with other Working Groups to assess functional outcomes and to implement data collection efficiently.
  • Measurement Issues.  Capturing infant and early childhood positive outcomes may prove challenging. Issues such as attachment are heavily tilted forward to older ages. Outcomes such as attachment, attentional issues, and language development will be considered under the concept of school readiness. Dr. Wise noted that measures of negative outcomes in infancy and early childhood need to be examined, and he asked for input from all Working Groups. He also asked for input on proximal measures of exposures that contribute to sentinel capabilities. Barry S. Zuckerman, M.D., Boston University School of Medicine, commented that although there are more concrete measures for older children, there are some measures in early childhood that may carry through life, such as mutually satisfying parent-child relationships. Among the more practical measures of positive health for infants and toddlers are physical measures such as finger pointing by age 12 months. Barbara R. Foorman, Ph.D., University of Texas Health Science Center at Houston, explained that measurements have to start early in infancy and should cover all of the important domains; the Study must collect the right measures at the right ages. Assessments of newborns might be performed, but the measures for this assessment have not yet been determined.
  • Cultural Sensitivity.  Positive health approaches need to retain a culturally sensitive component to capture differences in measuring success. Dr. Wise said that he and Dr. Halfon recognized the need to reflect cultural diversity when assessing positive health outcomes. Although there may be many arenas to reflect the cultural diversity of success, there seems to be a consensus across cultures that school readiness and the avoidance of addictive behaviors are important positive health outcomes.

Reports from the Working Group Liaisons

NCSAC liaisons provided presentations to the full NCSAC on the status of various Working Group products-what is needed to complete their work, whether the Program Office can provide assistance, and when the outstanding work products will be completed. For Working Groups that have completed their assignments and tasks, the NCSAC liaison indicated when the Working Group should be thanked and disbanded. These Working Groups were asked to provide general recommendations concerning their findings to Duane Alexander, M.D., Director, NICHD, NIH, DHHS; the Program Office; and the ICC.

  • Asthma Working Group.  Stephanie J. London, M.D., Dr.P.H., NIEHS, NIH, DHHS, reported that the Working Group is sponsoring a workshop in May 2004. The workshop will address questionnaire and diary-based methods for the early assessment of asthma and will consider outcome measurements and biomarkers. The workshop results will be reported at the September 2004 NCSAC meeting. The Working Group is coordinating with the Exposure to Chemical Agents Working Group, but has not yet developed specific hypotheses to address multiple interactions such as chemical exposures, diet, and genetic variables.
  • Birth Defects Working Group.  Dr. Daston, NCSAC liaison to the Birth Defects Working Group, reported that, since December 2003, this Working Group had completed several conference calls; he said that the Working Group would convene one more face-to-face meeting. The Working Group is:
    • Refining and attending to the final details for its hypothesis
    • Addressing the ICC’s questions
    • Examining lists of potential exposures developed by other Working Groups
    • Developing its own list of potential exposures.
    Dr. Daston concluded that the Working Group has basically accomplished its tasks and assignments and fulfilled its responsibilities.
  • Community Outreach and Communication Working Group.  Willa M. Doswell, R.N., Ph.D., University of Pittsburgh School of Nursing, stated that the guidance document would be completed in approximately 2 to 3 weeks. Dr. Doswell listed the following request-for-proposal criteria:
    • Community listening sessions
    • Outreach strategies
    • Community profiles to recruit
    • Community leaders
    • Community outreach advisory board.
    Dr. Doswell said that the Working Group would continue to formalize outreach and communication strategies. She explained that the Working Group’s recommendations would be incorporated into the guidance document and that specific strategies would follow.
  • Development and Behavior Working Group.  Dr. Foorman stated that this Working Group would participate in the Gene Expression and Behavior Workshop to be held in June 2004. The goal of this workshop is to discuss the environment and windows of vulnerability. There is the possibility of another related workshop sometime in the near future. The Working Group will be working closely with contractor Battelle in an effort to list measures of key outcome domains. A main focus of exposures will be chemicals. Participants briefly discussed the idea that this Working Group might evolve into two Working Groups, one involved with positive health and the other involved in neurodevelopment. There was a brief discussion of whether to consider reproductive outcomes of chemical exposures. A participant suggested developing a matrix relating various exposures to brain outcomes. Through such a matrix, researchers could systematically pose a series of questions to develop a comprehensive list of tests. Dr. Mattison explained that the Fertility and Early Pregnancy Working Group would address exposures and outcomes related to reproduction and endocrine function. However, he agreed that the matrix might prove worthwhile, and he highly encouraged collaboration across Working Groups.
  • Fertility and Early Pregnancy Working Group.  Lucina Suarez, Ph.D., Texas Department of Health, reported that the Working Group had completed its assigned tasks and achieved its goals, to date. This successful Working Group will complete its responsibilities by the end of June 2003. Answers to the ICC’s questions will appear in the Working Group’s white paper.
  • Gene-Environment Interactions Working Group.  M. Anne Spence, Ph.D., University of California, Irvine Medical Center, explained that the Working Group is drafting responses to two questions from the ICC. The first question involves critical influences in disease development. Critical influences are those with biologically important outcomes such as diabetes and obesity. The Working Group will continue to identify which genes need to be assessed and will develop a list of candidate genes for the Study. The ICC’s second question concerns the possible gathering of data on siblings, particularly twins. The Working Group will analyze the pros and cons of including siblings and report its findings in the near future. Dr. Spence said that the Working Group would be ready for "sunsetting" when the Study sampling design is finalized. Dr. Gaston commented that the level of knowledge about human genetics is increasing and that more genes will be identified as factors in disease. Dr. Spence noted that because of this issue, the Working Group would periodically reexamine topics in gene-environment interactions; it will update hypotheses and make recommendations as necessary.
  • Health Disparities and Environmental Justice Working Group.  Loretta Jones, M.A., Healthy African American Families, reported that the Working Group would explore measures of racism in an upcoming workshop, develop a list of concrete measures, and report its findings at the June NCSAC meeting. This Working Group may possibly be incorporated into the Social Environment Working Group.
  • Health Services Working Group.  Although there are modified hypotheses for five domains, more specificity is needed. The Sampling Design Workshop will help identify the measures that will serve as covariants. The measures identified will be described and discussed in a subsequent white paper.
  • Immunity, Infections, and Vaccines Working Group.  William J. Rodriguez, M.D., Ph.D., Center for Drug Evaluation and Research, U.S. Food and Drug Administration, DHHS, reported that the Working Group has drafted nine hypotheses and is currently planning a workshop on fetal infection and inflammatory responses. Outcomes under consideration include obsessive-compulsive and bipolar disorders. The Working Group would like to integrate its hypotheses with the activities of other Working Groups. The Working Group will wait until its workshop in spring 2004 is completed before considering a timetable for "sunsetting."
  • Injury Working Group.  Dr. Zuckerman explained that the Working Group’s submitted hypothesis was not accepted by the NCSAC and that the Working Group was perplexed as to why it was not accepted. The Working Group asked for specific guidance from Dr. Zuckerman and the NCSAC. In its efforts to draft an acceptable hypothesis, the Working Group developed, and Dr. Zuckerman presented, the following aims, hypotheses, and subhypotheses concerning injury:
    • Aim 1:  Identify the predictors of physical abuse of children in the first 3 years of life.
    • Hypothesis 1:  Marital/relationship violence during pregnancy or in the first year of a child’s life will lead to increased incidence of physical abuse of the child by age 3.
      • Parent psychopathology (for example, depression, anxiety, post-traumatic stress disorder) and neighborhood factors (higher crime index, increased joblessness, increased poverty, and high family mobility) will further increase the likelihood of physical abuse.
    • Aim 2:  Identify the consequences of physical and sexual abuse.
    • Hypothesis 2a:  Chronic physical abuse will result in altered cortisol levels, increased likelihood of post-traumatic stress disorder, chronic depression, and oppositional defiant disorder, and impaired developmental functioning (including cognitive, social, and emotional development).
    • Subhypotheses on physical abuse:
      • Chronic physical abuse will result in more severe outcomes (listed above) than will single incidents of physical abuse.
      • The relationships between physical abuse and its adverse consequences are exacerbated by environmental (for example, household lead, pesticides) and community (high rates of poverty, exposure to or witnessing of violence, unemployment, family mobility, and childcare burden) factors.
      • Exposure to media violence increases the likelihood of adverse outcomes in the presence of environmental and community factors.
      • Of those children who experience physical abuse, those with the genetic disposition will develop chronic depression or oppositional defiant disorder.
      • The quality and duration of intervention programs will decrease the likelihood of the above adverse outcomes.
    • Hypothesis 2b:  Chronic sexual abuse will result in altered cortisol levels, increased likelihood of post-traumatic stress disorder, and impaired developmental functioning (including cognitive, social, and emotional development).
    • Subhypotheses on sexual abuse:
      • Outcomes of sexual abuse will be modified by the developmental age of the child at the start of the abuse and the duration of the abuse.
      • The relationship between sexual abuse and its adverse consequences will be exacerbated by community factors including high rates of poverty, exposure to or witnessing of violence, and the childcare burden in the home.
      • The quality and duration of intervention programs will decrease the likelihood of the just-mentioned adverse outcomes.

    Dr. Zuckerman said the Working Group requests specific feedback on these aims, hypotheses, and subhypotheses. In a subsequent discussion, a participant questioned whether these were testable hypotheses. Dr. Scheidt reiterated the criteria for Study hypotheses. He explained that the more narrow and specific a hypothesis becomes, the less interesting and compelling it is. Hypotheses need to be sufficiently broad and within the context of the Study’s 100,000-subject sample size. A participant asked how physical abuse will be defined and how it will be measured. Dr. Daston commented that because injury is one of the most concrete outcomes, the Study must be able to adequately and appropriately further the understanding of injury. Legal and ethical issues concerning abuse, neglect, and intervention may prove to be particularly challenging within the context of the Study. Most states have strict reporting requirements for suspected physical abuse. Another challenge will be determining cognitive and behavioral outcomes as related to severity of traumatic head and brain injury. Dr. Zuckerman noted that the Working Group is focusing on three areas: aggression, physical abuse, and physical injury. Dr. Dudley questioned whether families that are susceptible to abuse are likely to be enrolled in the Study, and if they are, the probability that such families will be lost to follow-up. Participants agreed that high-risk families must be included in the Study. Participants also discussed the following topics:

    • Impact of contact sports
    • Power calculations
    • Continuous effects versus threshold effects
    • Data collection issues
    • Cultural norms for physical abuse and violence.
  • Medicine and Pharmaceuticals Working Group.  Dr. Graham said that the Working Group had identified best practices and compiled answers to the ICC’s questions. The Working Group proposed a pilot study on drug coding and is planning a workshop on this topic to finalize the details. The Working Group has essentially completed its activities and will gladly serve as future consultants.
  • Nutrition, Growth, and Pubertal Development Working Group.  This Working Group was formed after most of the other Working Groups were formed, and it will have a role in the Study as the protocol is further developed. To date, the Working Group has completed activities that it was asked to perform. The Working Group has planned or completed workshops on the following topics:
    • Physical activity
    • Dietary intake methods
    • Body composition
    • Early markers of puberty.
    The Working Group is assessing several promising new technologies as they are developing the framework for body composition measures. Because of the rapidly evolving research on candidate genes related to delayed sexual development, early markers of pubertal development will be reevaluated in several years, perhaps in 2010. Priorities in measuring exposures and outcomes will be reassessed as the protocol continues to evolve. The Working Group is planning an upcoming workshop on body composition.
  • Pregnancy and the Infant Working Group.  Dr. Dudley reported that Working Group issued the request for proposal for the pilot study on three-dimensional ultrasound analysis. Remaining issues include data transmission, storage, and retrieval. RTI will help address these issues. The Working Group completed its hypotheses and developed a list of exposure and outcome measures. The stress hypothesis needs some refining. Subhypotheses may be developed, and there are questions concerning sample size and instruments to measure stress. Dr. Dudley said that the Working Group is close to completing its activities.
  • Repository Working Group.  Dr. Cosentino stated that the Working Group has fulfilled its responsibilities and is ready for "sunsetting." Dr. Cosentino expressed his desire to have this Working Group evolve into a new Working Group on logistics to help address contract issues.
  • Social Environment Working Group.  Linda M. Burton, Ph.D., Pennsylvania State University, reported that the Working Group developed its hypothesis and has responded to the ICC’s questions. The Working Group is concerned about how it will integrate its activities with those of other working groups. The Working Group participated in both Media Effects and Rural Children Workshops. Upcoming endeavors include addressing emerging themes developed from the Sampling Design Workshop, including an assessment of home-scale diary methods. Dr. Burton stated that the Working Group has delivered its work products. However, the Working Group will continue to help develop appropriate measures of social environment issues for other Working Groups. Dr. Burton recommended that the Working Group remain empanelled to review data and make recommendations concerning future social issues. Because investigators cannot predict what social environment issues will be important and relevant to the Study 20 years from now, new hypotheses may be developed as data on developmental phases is produced.

Overview of the Department of Health and Human Services Initiative on Electronic Medical Records

Carolyn M. Clancy, M.D., Chair, Council on Applications of Health Information Technology (CAHIT), and Director, Agency for Healthcare Research and Quality (AHRQ), began her presentation by saluting all of the people who are involved with the planning and implementation of the Study, which she described as a large and ambitious endeavor. The purpose of Dr. Clancy’s presentation was to describe CAHIT and explore how AHRQ could collaborate with the Study for mutual benefit. Personnel from the two organizations had been sharing information, and these discussions led to the question: How might AHRQ relate to the Study?

CAHIT was formed in June 2003, under the direction of DHHS Secretary Tommy G. Thompson. CAHIT is an internal DHHS deliberative body whose purpose is to:

  • Create synergy within DHHS
  • Coordinate activities across DHHS agencies
  • Improve quality and safety for a variety of research activities
  • Provide an efficient and accurate method for gathering information
  • Promote timely exchange of information about DHHS activities and opportunities
  • Serve as primary forum for identifying and evaluating activities and investments that complement private sector initiatives
  • Make recommendations to the Secretary to create strategic opportunities to enhance applications of health information technology in U.S. health care.

Dr. Clancy described health information technology as a network to connect and allow communication across health care entities. A national health information infrastructure would serve as a paperless, electronic health care and medical system. Such health information technology applications can:

  • Support clinical care and its coordination, as well as research activities
  • Improve health care quality and patient safety measurement
  • Improve data accuracy and reliability (no more handwritten charts, units and conversions, weight-based dosing for children).

Dr. Clancy cautioned that health information technology systems require local health information infrastructures such as the Indianapolis hospitals system and the Santa Barbara health care data exchange. These systems require unified standards to facilitate networking and information sharing.

Because of the low penetration of information technology in U.S. medical systems, health information technology has an opportunity to improve several areas, including:

  • Electronic health and medical records
  • Computerized decision support systems (guideline-based prompts)
  • Patient-physician communication (e-mail, patient portals)
  • Smart cards
  • Community-level data sharing and integration
  • Computerized prescription order entry
  • Web-facilitated research.

In the future, health information technology may create wearable data collection technologies to reduce patient burden.

According to Dr. Clancy, health information technology issues focus on increasing the use and effectiveness of electronic medical records. Information technology experts will have to become involved to develop appropriate health care and medical systems. Dr. Clancy noted that an electronic research infrastructure could be one of the Study’s legacies. Other issues include:

  • Privacy and confidentiality
    • Health Insurance Portability and Accountability Act regulations
    • Beyond-identity theft
  • A thousand flowers blooming-need interconnectivity
  • Standards and platforms
    • HL7 (a standard for information exchange between medical applications; an abbreviation of "Health Level Seven," seventh OSI layer protocol for the health environment)
    • SNOMED (Systematized Nomenclature of Medicine, the universal health care terminology that makes health care knowledge usable and accessible wherever and whenever it is needed)
  • Cost
    • Short-term capital investment
    • Long-term savings/efficiencies?
  • Research-practice connection.

Dr. Clancy listed two topics for discussion:

  • The Study is a strategic opportunity for CAHIT.
  • CAHIT is a strategic opportunity for the Study.
Dr. Clancy offered the following as "some initial ideas":
  • Paperless records
  • Link different data collection efforts
    • A laptop or personal digital assistant (PDA) for every child
  • Dynamic and quick access to data
    • Research papers
    • Identify needs for more rigorous studies
    • Identify opportunities for improvement
      • Toxic exposures
      • Disparities in health care
      • Quality improvements
  • Leave systems behind for participating
    • Communities (coordination within and across sites)
    • Research participants (smart cards)
  • Quick future study expansions and adaptations.

In a question-and-answer session, Dr. Clancy addressed the following issues and concerns:

  • Information Technology Vendors.  Vendors that use Web-based applications on HL7 platforms are able to communicate between systems through open architecture. Study vendors will need to build local systems that interact with each other. The Study will provide opportunities for a consortium of vendors, but long-term commitments will be necessary. The magnitude of the Study will help identify and promote a unified health information system.
  • Use of Technology.  A participant noted that most commercial information technology products are geared toward adults and may have limited adaptation to children and pediatric medicine. Physicians and medical researchers will use electronic medical records if the electronic systems are effective and efficient. Veterans Affairs systems and Medicare demonstrations have proven the effectiveness of electronic systems. Data sharing, registries, and network-to-network communication systems (for example, from hospital to hospital) will validate the use of electronic medical records.
  • Legal Issues.  A key underpinning for electronic data exchange is a series of legal agreements between entities. These agreements help to ensure that no data are shared without permission. Other legal issues concern consent, confidentiality, privacy, and misuse of data.
  • Data Abstraction.  Because of the great amount of data that will be generated by the 40 Study centers, much information will have to be abstracted to facilitate information exchange and sharing. An information system will have to be planned and implemented and will require input from technical experts. The data will vary in complexity and will need to include not only medical records but also information on social environment and other exposures.
  • Systems Development.  The Study’s information system will have two domains: the research infrastructure and the medical/health care infrastructure. Issues for this system include capturing data in electronic medical records and gathering information during subject enrollment. The Study provides an opportunity to develop an important information system, which may, in itself, be a major contribution to continuing research.

Update on Sampling Design Workshop

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

Mr. Quackenboss began his presentation by listing the members of the Sampling Design Workshop Planning Committee:

  • Lester R. Curtin, Ph.D., National Center for Health Statistics, CDC, DHHS (Study Program Office)
  • Jonas H. Ellenberg, Ph.D., Westat (Study Design Working Group)
  • Robert T. Michael, Ph.D., University of Chicago (NCSAC)
  • James J. Quackenboss, M.S., Office of Research and Development, EPA (ICC)
  • P. Barry Ryan, Ph.D., Emory University Rollins School of Public Health (NCSAC)
  • Peter C. Scheidt, M.D., M.P.H., NICHD, NIH, DHHS (National Children’s Study Director and ICC)
  • Sherry G. Selevan, Ph.D., Office of Research and Development, EPA (ICC)
  • Frank E. Speizer, M.D., Harvard School of Public Health (Study Design Working Group).

To plan and prepare for the Sampling Design Workshop, the planning committee identified documents needed to inform sampling decisions, including background white papers and design options. White papers were developed by Battelle under a contract with the Study Program Office. The design options paper was reviewed and revised by the planning committee and sent to the workshop panel. The workshop panel was selected in collaboration with panel chair David Savitz, Ph.D., University of North Carolina, Chapel Hill. Workshop participants were identified and invited.

To inform the sampling design deliberations during the workshop, Battelle wrote a white paper titled "Initial Sampling Design Options for the National Children’s Study and Criteria for Evaluation." This white paper (published in September 2003) addresses the definitions, design elements, and range of design options for the Study. It identified the following questions and issues for developing the sampling design:

  • Advantages and limitations of alternative sampling methods for the Study
    • Internal and external validity: level of detail and generalization
  • Recruitment and retention for the Study
    • Rates and their impact on design selection
  • Measures for Study core hypotheses
    • Design requirements and burden.

A second white paper titled "Family of Designs (Hybrids) for the Study," which was produced by Battelle and Westat, addressed the following issues:

  • Multiple sampling frames to provide coverage of target populations, possibly including
    • National probability-based sample
    • Center-based (patients and MSA sample)
  • Organizational structure(s) and their existing relationships with potential participants
  • Selection methods/criteria for:
    • Groupings (for example, geographic areas, clinics, centers)
    • Individuals.

Battelle’s sampling design options report suggested the following tasks:

  • Identify critical measures for Study priority outcomes and current hypotheses
  • Assess design options for:
    • Recruitment and long-term retention rates
    • Estimated costs for the Study
    • Power to test selected hypotheses
      • Exposure-outcome relationships
      • Different life stages
      • Given estimated retention rates.

The criteria to evaluate Study sampling design options include:

  • Ability to satisfy "givens"
    • Engage communities
    • Specialized measures
    • Prenatal recruitment (with some preconception)
  • Scientific merit
    • External validity (probability basis)
    • Population diversity; range of exposures
    • Internal validity (measures, confounders, covariates)
    • Power (in unweighted and weighted analyses)
    • Resource for future (standardization, data access)
  • Costs (relative to sample sizes, power, and measures).

Mr. Quackenboss explained that the Study Sampling Design Workshop format will be similar to the format of a National Institutes of Health Consensus Development Conference. The format will include:

  • An impartial panel of experts to discuss issues and trade-offs
  • Debate informed by documents and presentations from different viewpoints.

The 2-day workshop will be held March 21-22, 2004. On the first day, participants will discuss the Battelle designs and white papers, and additional speakers may be included. On the second day, the workshop panel will deliberate and report its findings.

The Study Sampling Design Workshop expert panel consists of the following people:

  • David Savitz, Ph.D., University of North Carolina, Chapel Hill (Chair)
  • Scott Zeger, Ph.D., Johns Hopkins Bloomberg School of Public Health (Co-Chair)
  • Jean Golding, Ph.D., University of Bristol
  • Barry Graubard, Ph.D., National Cancer Institute, NIH, DHHS
  • Graham Kalton, Westat
  • Michael Kramer, McGill University
  • Anne R. Pebley, Ph.D., University of California, Los Angeles
  • John Spengler, Ph.D., Harvard University
  • Clarice R. Weinberg, Ph.D., NIEHS, NIH, DHHS.

The tentative speakers for the Sampling Design Workshop include the following people:

  • Battelle design team
    • Warren Strauss, John Menkedick, and Jeff Lehman (Battelle employees)
    • Louise Ryan, Harvard University
    • Colm O’Muircheartaigh, University of Chicago and National Opinion Research Center
    • Alan Zaslavsky, Harvard University
  • Alternative perspectives on Study sampling needs
    • Mark Klebanoff, M.D., M.P.H., NICHD, NIH, DHHS (ICC)
    • Robert T. Michael, Ph.D., University of Chicago (NCSAC)
    • Christine A. Bachrach, Ph.D., NICHD, NIH, DHHS (Social Environment Working Group)
    • Germaine M. Buck, Ph.D., NICHD, NIH, DHHS (Fertility and Early Pregnancy Working Group)
    • Nigel Paneth, M.D., M.P.H., Michigan State University (Study Design Working Group).

The proposed next steps and timetable for the Sampling Design Workshop include:

  • Workshop reports to the ICC, NCSAC, Sampling Design Working Group, and other interested Working Groups by the end of April 2004
  • NCSAC receives the findings from the Working Groups; NCSAC members are assigned to review and discuss key questions and issues by the end of May 2004
  • NCSAC prepares written advice for the ICC and NICHD Director by the end of June 2004
  • The ICC and NICHD Director make decisions on sampling design and pilot studies by the end of July 2004
  • Study Program Office implements feasibility/pilot studies by the end of August 2004.

In a question-and-answer session, Mr. Quackenboss addressed the following issues and concerns:

  • Community Involvement.  Community leaders and community researchers are essential to the success of the Study. Mr. Quackenboss acknowledged the importance of community involvement and noted that community experts will participate in the Sampling Design Workshop.
  • Consensus Process.  A participant asked whether the Sampling Design Workshop would generate a single decision or recommendation through a formal consensus. Dr. Scheidt explained that the Federal Advisory Committee Act prohibits advisory committees from implementing a formal consensus process; that is, an advisory committee cannot, by vote, give advice to the federal government. The expert panel of the Sampling Design Workshop will present its findings-including pros and cons, costs and benefits, and any trade-offs-to the NCSAC. The ICC will also assess the workshop’s findings.
  • Information Sharing.  Because of its size and complexity (approximately 200 pages of detailed findings), the Battelle report will not be distributed to the NCSAC prior to the Sampling Design Workshop. Workshop participants will assess the accuracy and validity of the report and make the appropriate interpretations of the facts presented by Battelle. The purpose of the workshop is to determine those elements that are relevant and important and to address the high-level issues and concerns. After the workshop findings are presented to the NCSAC, there will be sufficient time to digest and interpret the information before the NCSAC ultimately advises the federal government on the appropriate sampling design.

Update of the Health Disparities and Environmental Justice Working Group Workshop

Rueben Warren, D.D.S., Dr.P.H., Working Group Co-Chair, CDC, DHHS

Dr. Warren began his presentation by naming the Working Group’s other co-chairs: Charles Lee, EPA, and Kristine O. Suozzi, Ph.D., Bernalillo County Environmental Health Department. Dr. Warren explained the Working Group’s intent to balance the voice and influence of non-federal group members with those of federal members. At this time, a major charge for the Working Group is to not let the racism hypothesis overcome all of the Working Group’s other responsibilities. The intent of the upcoming workshop is to specifically focus on measures and outcomes of racism.

Dr. Warren explained that public health experts have only recently considered the concept of racism as a factor in health disparities. He described the literature that brought this issue into the domain of public health. Researchers and public health experts are still struggling to explain the gaps in morbidity and mortality data for different racial and social groups in the United States (that is, is it race or racism?).

The Working Group’s workshop on racism will bring together experts in the field to examine the issues surrounding the measurement and outcomes of racism. The Working Group will distill the findings of the workshop, develop a hypothesis on racism, and integrate their findings into other Working Groups’ activities. The Working Group will develop a list of core measures and draft a preliminary list of presenters and other participants prior to the workshop. The Working Group will deliberate on the measures and present the findings at the NCSAC’s June 2004 meeting. Names of potential participants-both individuals and organizations-should be submitted to Dr. Warren.

NCSAC Open Forum

Donald Mattison, M.D., NCSAC Chair, NICHD, NIH, DHHS (Moderator)

Dr. Mattison reminded the NCSAC that their role during the transition from Study planning to implementation is clearly outlined in advisory committee meeting materials that were distributed prior to the meeting. He drew particular attention to the goals and responsibilities for the NCSAC June meeting (listed in Tab 5, page 3, of the meeting binder). A primary focus during the June meeting will be to discuss the findings of the Sampling Design Workshop. Dr. Mattison emphasized that the NCSAC needs to finalize its recommendations on Study themes, hypotheses, and measures during the June meeting.

Dr. Michael proposed that, in preparation for the June meeting, NCSAC members list and prioritize their visions of, aspirations for, and objectives of the Study. Dr. Michael offered the following questions:

  • What are people hoping that the Study will accomplish, achieve, or produce?
  • What are the expectations for the Study?
  • Which children are the main focus of the Study?
  • What are the Study priorities?
  • Which hypotheses are most important?
  • What do Study investigators want to know?
  • What outcomes are most important?

Answering these questions will provide the proper perspective for the Study’s focus, and within this context, the NCSAC will be able to assess and interpret the finding of the Sampling Design Workshop and make its recommendation on sampling design.

Action Item

NCSAC members will send their lists of answers to Dr. Michael, who will compile them and report the findings to the NCSAC at the June meeting.

In an open discussion, participants recognized the possibility of additional hypotheses emerging in the future as the Study gathers and analyzes data. However, they acknowledged that a set of measure must be proposed at this stage of the Study to frame discussions on sampling design strategies. Establishing the measures will help guide both hypotheses and protocol development. Dr. Mattison suggested that each NCSAC member prepare a matrix of exposures and outcomes. Weighting the priorities of exposures and outcomes will enhance the discussions of sampling design. Dr. Scheidt explained that the matrix should help determine whether measures of exposures and outcomes are sufficient to address the Study hypotheses.

Action Item

NCSAC members will develop a matrix of Study exposures and outcomes, with weighted priorities, and present them at the NCSAC June meeting.

Participants acknowledged the importance of the Study hypotheses and their role in generating scientific credibility for Study findings. The hypotheses provide a scientific method to define Study boundaries and create a tool to allocate resources. Because important exposure and outcome measures will help develop future hypotheses, the Study design will need to remain flexible.

Action Item

Prior to the June meeting, NCSAC members need to provide written comments on:

  • Revised theme description and core hypotheses (from the ICC)
  • Sampling Design Workshop report
  • Study strategic plan
  • Any additional input from Working Groups on measures.

Action Item

Prior to the June meeting, Working Group liaisons need to provide the following from their respective Working Groups:

  • Critiques and comments on the ICC’s hypotheses
  • Sets of measures of exposures and outcomes
  • Answers to the ICC’s and NCSAC’s questions.

NCSAC Members

Donald R. Mattison, M.D., NCSAC Chair, NICHD, NIH, DHHS
Jan L. Leahey, NCSAC Executive Secretary, NICHD, NIH, DHHS
David C. Bellinger, Ph.D., Boston Children’s Hospital
Linda M. Burton, Ph.D., Pennsylvania State University
George P. Daston, Ph.D., Proctor and Gamble
Willa M. Doswell, R.N., Ph.D., University of Pittsburgh School of Nursing
Donald J. Dudley, M.D., University of Texas Health Sciences Center at San Antonio
Alan R. Fleischman, M.D., New York Academy of Medicine
Barbara R. Foorman, Ph.D., University of Texas Health Science Center at Houston
Judith A. Graham, Ph.D., American Chemistry Council
*Fernando A. Guerra, M.D., M.P.H., San Antonio Metropolitan Health District
Loretta Jones, M.A., Healthy African American Families
*Shiriki Kumanyika, Ph.D., M.P.H., University of Pennsylvania School of Medicine
Philip J. Landrigan, M.D., Mount Sinai School of Medicine
*Grace LeMasters, Ph.D., University of Cincinnati
Roderick Joseph A. Little, Ph.D., University of Michigan
Robert T. Michael, Ph.D., University of Chicago
Deborah A. Phillips, Ph.D., Georgetown University
P. Barry Ryan, Ph.D., Emory University Rollins School of Public Health
M. Anne Spence, Ph.D., University of California, Irvine Medical Center
Lucina Suarez, Ph.D., Texas Department of Health
*Daniel J. Swartz, Children’s Environmental Health Network
Barry S. Zuckerman, M.D., Boston University School of Medicine

*Did not attend.

ICC Members

Amy Branum, M.S.P.H., National Center for Health Statistics, CDC, DHHS
*Adolfo Correa, M.D., Ph.D., National Center on Birth Defects and Developmental Disabilities, CDC, DHHS
Sarah A. Keim, M.A., NICHD, NIH, DHHS
Woodie Kessel, M.D., M.P.H., Office of the Secretary, DHHS
Carole A. Kimmel, Ph.D., National Center for Environmental Assessment, EPA
Mark Klebanoff, M.D., M.P.H., NICHD, NIH, DHHS
Pauline Mendola, Ph.D., Office of Research and Development, EPA
*Sheila A. Newton, Ph.D., NIEHS, NIH, DHHS
James J. Quackenboss, M.S., Office of Research and Development, EPA
Peter C. Scheidt, M.D., M.P.H., NICHD, NIH, DHHS
Kenneth C. Schoendorf, M.D., M.P.H., National Center for Health Statistics, CDC, DHHS
Sherry G. Selevan, Ph.D., Office of Research and Development, EPA
*Marshalyn Yeargin-Allsopp, M.D., National Center on Birth Defects and Developmental Disabilities, CDC, DHHS

*Did not attend.

Observers and Other Participants

Gerry G. Akland, M.S.
Teneshia G. Alston, NICHD, NIH, DHHS
Tye E. Arbuckle, Ph.D., Environmental Health Science Bureau, Health Canada
Christine A. Bachrach, Ph.D., NICHD, NIH, DHHS
Tina Bahadori, Sc.D., American Chemistry Council
Marion J. Balsam, M.D., NICHD, NIH, DHHS
Adelaide Barnes, M.A., NICHD, NIH, DHHS
Arthur M. Bennett, M.E.A., B.E.E., NICHD, NIH, DHHS
Ruth A. Brenner, M.D., M.P.H., NICHD, NIH, DHHS
Davis Bu, Ph.D., Booz Allen Hamilton Inc.
Leni Buff, NICHD, NIH, DHHS
Audrey Burwell, Office of the Secretary, DHHS
Carolyn Clancy, M.D., Agency for Healthcare Research and Quality, DHHS
Mark Cosentino, D.P.M., Ph.D., Science Applications International Corporation
Ben P. Daughtry, R.Ph., M.B.A., FACHE, Dynport Vaccine Company
Elizabeth A. Davis, NICHD, NIH, DHHS
Diane Dennis-Flagler, M.P.H., CDC, DHHS
Virginia DeSeau, NICHD, NIH, DHHS
Leslie J. DiFonzo, Booz Allen Hamilton Inc.
Denise Daugherty, Ph.D., Agency for Healthcare Research and Quality, DHHS
Pam Smeder Douglas, Booz Allen Hamilton Inc.
Terence Dwyer, M.D., Ph.D., NICHD, NIH, DHHS
Jonas H. Ellenberg, Ph.D., Westat
Alexa Fraser, Ph.D., Westat
Warren Galke, Ph.D., NICHD, NIH, DHHS
Anoop Ghuman
Lynn R. Goldman, M.D., M.P.H., Johns Hopkins University
William D. Grubbs, Ph.D., Science Application International Corporation
Doris B. Haire, American Foundation for Maternal and Child Health
Melissa Hardt, Oracle Corporation
Mary L. Hediger, Ph.D., NICHD, NIH, DHHS
John H. Himes, Ph.D., M.P.H., University of Minnesota
Jamie Hui, Booz Allen Hamilton Inc.
Anne E. Imrie, Science Application International Corporation
Raffael Jovine, Ph.D., Booz Allen Hamilton Inc.
Sarah S. Knox, Ph.D., NICHD, NIH, DHHS
Danuta Krotoski, Ph.D., NICHD, NIH, DHHS
William F. Lawrence, M.D., M.S., Agency for Healthcare Research and Quality, DHHS
Rebecca T. Leeb, Ph.D., CDC, DHHS
Stephanie J. London, M.D., Dr.P.H., NIEHS, NIH, DHHS
William Lyman, Ph.D., Wayne State University
Stephen Marcus, Ph.D., National Cancer Institute, NIH, DHHS
Ellen L. Marks, RTI International
John R. Menkedick, M.S., Battelle Memorial Institute
Luke P. Naeher, Ph.D., University of Georgia
Maryam Naserghodsi, NICHD, NIH, DHHS
Haluk Ozkaynak, Ph.D., M.S., EPA
Susan Pagliaro, NICHD, NIH, DHHS
Nigel Paneth, M.D., M.P.H., Michigan State University
Sherri L. Park, NICHD, NIH, DHHS
Layna McConkey Peltier, Capitol Health Group
Bobbie Peterson, M.S., McKesson BioServices
Pat Phibbs, Daily Environment Report
Barbara J. Porter, B.S., National Institutes of Standards and Technology, U.S. Department of Commerce
Nancy Potischman, Ph.D., National Cancer Institute, NIH, DHHS
Jonathan Radow, The Blue Sheet
Jerry D. Rench, Ph.D., RTI International
William J. Rodriguez, M.D., Ph.D., Center for Drug Evaluation and Research, U.S. Food and Drug Administration, DHHS
Marquette Roher, NICHD, NIH, DHHS
Beth D. Roy, Social and Scientific Systems, Inc.
Lee Salamore, American Chemistry Council
Gary D. Sandefur, Ph.D., University of Wisconsin, Madison
Kathy Schneider, Ph.D., Iowa Foundation for Medical Care
Julie A. Schoenborn, M.B.A., Brady Corporation
Paul J. Seligman, M.D., M.P.H., Center for Drug Evaluation and Research, U.S. Food and Drug Administration, DHHS
Christine Shreeve, Ogilvy Public Relations Worldwide
Anita Singh, Ph.D., Food and Nutrition Service, U.S. Department of Agriculture
David C. Songco, NICHD, NIH, DHHS
Paul D. Sorlie, Ph.D., National Heart, Lung, and Blood Institute, NIH, DHHS
Catherine Y. Spong, M.D., NICHD, NIH, DHHS
Paul Swidersky, B.Sc., Quality Associates, Inc.
Mary Jane Teta, Dr.P.H., Exponent, Inc.
Hale Vandermer, Ph.D., Native American Management Services, Inc.
Ann M. Vinup, Learning Disabilities Association of American
Diane K. Wagener, Ph.D., RTI International
Rueben C. Warren, D.D.S., Dr.P.H., M.P.H., CDC, DHHS
Robin M. Whyatt, Ph.D., Columbia University
Cathy Spatz Widom, Ph.D., University of Medicine and Dentistry of New Jersey
Marian Willinger, Ph.D., NICHD, NIH, DHHS
Paul Wise, M.D., M.P.H., Boston University
Edward Tin Wong, Science Applications International Corporation
Robert H. Yolken, M.D., Johns Hopkins University Medical Institutions

 

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

 

   May 4, 2004   
       Date
Dr. Mattison's Signature
Donald Mattison, M.D.
Chairperson
National Children’s Study
Federal Advisory Committee
  6/1/2008
  11/28/2005