June 2003 NCSAC Meeting Summary Minutes 

The 6th Meeting of the National Children’s Study Federal Advisory Committee (NCSAC)June 5–6, 2003
Holiday Inn Select
Bethesda, MD  

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

JUNE 5, 2003

Welcome
Review Meeting Goals, Agenda, and Action Items

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

Dr. Mattison, M.D. convened the meeting of the National Children’s Study Advisory Committee (NCSAC) shortly after 8:00 a.m. Dr. Mattison welcomed the committee, noted that new members were present, and asked attendees to introduce themselves. Following introductions, Dr. Mattison made the following remarks:

• Comments, corrections, and modifications to the minutes from the March NCSAC meeting were requested. The motion to handle those via e-mail carried.

• Approximately 20 hypotheses would be reviewed during the course of the two-day meeting.

• There were signs that feedback mechanisms between the Working Groups and the NCSAC were inadequate. An Executive Committee, composed of members of the NCSAC and the Interagency Coordinating Committee (ICC), is addressing this. This group will soon issue a letter to Working Groups to update them on the status of the NCS.

• The ICC has asked the NCSAC to examine the roles of the Working Groups, some members of which cannot provide advice directly to the federal government. The ICC is concerned about turn-around of materials from the Working Groups, given the relative infrequency with which the NCSAC meets.

• Camara P. Jones, M.D., M.P.H., Ph.D., National Center for Chronic Disease Prevention and Health Promotion, CDC, DHHS will present on measures of the impact of racism on children’s health.

• The NCSAC will work on legal/ethical issues through lunch with legal counsel.

Update on Outreach, NIH, Department, and Congressional Issues

George Gaines, Chief
Office of Program and Public Liaison, NICHD, NIH, DHHS

Mr. Gaines (Office of Public Liaison, NICHD) opened his presentation by noting that his colleague, Lisa Kaeser, Senior Program Analyst, could not attend due to family responsibilities. His presentation included the following items:

• The Office of Program and Public Liaison has worked closely with the National Children’s Study Program Office to educate policymakers on the Study, including three briefings of Elias A. Zerhouni, M.D., Director of NIH. Dr. Zerhouni is said to be engaged and supportive, in part because of the response of agency heads during his discussions with them.

• The Surgeon General, Vice Admiral Richard H. Carmona, M.D., M.P.H., F.A.C.S., is also interested in supporting the Study and offered to endorse and/or assist in Study implementation. A member of the House Appropriations Committee, Rep.resentative Patrick Kennedy, received a briefing and expressed his support. Senator. Hillary Clinton’s office has requested a presentation as well.

• A Congressional staff briefing by the ad hoc group for NIH funding, and the Friends of NICHD Coalition presented the Study to an audience numbering more than 90, which included members of both parties from both houses of Congress, as well as several advocacy groups. Mr. Gaines said this was the most effective and best-attended briefing he had witnessed on Capitol Hill.

• The advocacy reception at the SAM Study Assembly (SA) in( Baltimore, MD in 2002) did not go as well as hoped, but that after a session with Nigel Paneth, M.D, M.P.H., Co-Chair of the Study Design Working Group, he hopes for a more effective liaisonship.

• The Friends of NICHD Coalition recently met with Capitol Hill appropriations staffers regarding the Study, but the response was not wholly positive in that funding may be less than optimal. Mr. Gaines suggested there might be no new dedicated funds for the Study in the fiscal year 2004 budget, which is not the same pool of funds agencies have committed to the Study.

• Those in attendance were asked to assist in the effort to obtain full funding for the Study. He noted that NCSAC members could, under certain conditions, communicate their support for the Study to policymakers. Interested members should contact Mr. Gaines’ office for further information.

Questions and Comments for Mr. Gaines

• Philip J. Landrigan, M.D., NCSAC Member, Mount Sinai School of Medicine, asked whether U.S. Department of Defense (DOD) monies could be employed on the argument that children’s health is a national security issue. Mr. Gaines remarked that it was a good argument, adding that Homeland Security funding might be a good source. Mr. Gaines said that the fiscal year 2004 allocation would need to be $26 million, a sum that is lacking by approximately half.

• Barry S. Zuckerman, M.D., NCSAC Member, Boston University School of Medicine, inquired whether preparations for chemical and biological weapons attacks could be seen as a legitimate area from which to draw funds. Mr. Gaines responded that this is an important point.

• Grace LeMasters, Ph.D., NCSAC Member, University of Cincinnati,Lem said the military has an ongoing tracking system for birth defects and that the military is a large cohort for young parents and newborns. She commented that invoking this population in the Study might engender support from the Pentagon. Mr. Gaines supported the notion. Dr. LeMasters added that many military families live on Superfund sites and therefore were a very appropriate population.

• Peter C. Scheidt, M.D., M.P.H., Study Director and ICC Co-Chair, NICHD, NIH, DHHS, stated that the ICC had planned to include military dependents in the Study. Mr. Gaines said that the rationale for using DOD funds in cancer research ran along similar lines of thinking.

• Robert T. Michael, Ph.D., NCSAC Member, University of Chicago, asked about fiscal year 2005 funding in light of the upcoming election. Mr. Gaines answered that some political visibility may arise for the Study in campaigns, but expressed the hope that it did not become a contentious issue in the presidential election. He remarked that the pitfalls included varying opinions on the validity of such spending. He added that the popularity of programs for children gave the Study considerable political appeal.

• Judith A. Graham, Ph.D., NCSAC Member, American Chemistry Council, asked whether Mr. Gaines’ office had tackled agencies for more discretionary funds for the Study. Mr. Gaines responded in the affirmative, noting that a crisis in funding had not yet arrived. He added, however, that his office is examining the options should a budget crunch arrive.

• Willa M. Doswell, R.N., Ph.D., NCSAC Member, University of Pittsburgh School of Nursing, asked which congressional committees the Study might approach. Mr. Gaines replied that the authorizing committees had a vested interest in the Study and were in a position to influence appropriators, including overlap between those in appropriations and those who crafted the Children’s Health Act of 2000.

• David C. Bellinger, Ph.D., NCSAC Member, Boston Children’s Hospital, asked if a number had been fixed to the economic benefit of the Study. Mr. Gaines stated that Dr. Zerhouni has requested such information to bolster the case for the Study. Dr. Mattison noted that he and Dr. Scheidt have agreed to assemble a summary of potential economic benefits of the Study for distribution to the NCSAC and Duane Alexander, M.D., NICHD Director. Dr. Landrigan noted two articles in recent issues of Environmental Health Perspectives that addressed the costs and benefits of abatements of various toxins/toxicants. He added that such presentations might be very persuasive.

• A member of the audience asked about a list of key legislators that individual citizens could approach to lobby for the Study. Mr. Gaines replied that those members could be identified by Congress’s Web site, and noted that constituents have "entrée and leverage" that no others have. Dr. Landrigan stated that due to security clearance procedures, letters sent via the U.S. Postal Service may be ineffective in reaching members of the U.S. Congress in a timely fashion. He recommended contacting Ccongresspersons via e-mail or fax.

Summary of the Ethics Workshop

Alan R. Fleischman, M.D., NCSAC Member
Senior Vice President, New York Academy of Medicine

Dr. Fleischman stated that on the previous day, the Ethics Working Group sponsored a workshop entitled Ethical Issues in Longitudinal Pediatric Studies: "Looking Back, Thinking Forward." The purpose of the workshop was to discuss known ethical dilemmas, including those related to recruitment, retention, and consent. Some of the discussions covered participation incentives for community involvement and undue incentives and coercive practices. Dr. Fleischman presented the following key points from the workshop:

• Dedicated staff, hired from communities, was seen as vital.

• Informed consent will need creativity and may make use of electronic means of informing and obtaining consent. Education of Study subjects may be ongoing.

• Regarding confidentiality, the workshop examined the notions of a subject’s right to know versus sharing only information that the subject can properly frame. It was noted that these will have to be reconciled. In one study, the release of information triggered stigmatization and "irrational reproductive choices."

• The longitudinal nature of the Study mandated new ways of dealing with these concerns. The Study would not be typical of community-participatory research, but that earlier experience would nonetheless be helpful. Centers will have to base their proposals on their background in community involvement and/or a means of invoking community participation.

• Some of the discussion during the workshop covered the risk status of the Study "core" and whether it should be kept at minimal risk. He noted that the discussion ran toward keeping the Study in a state of minimal risk at its core, with some sites going into more than minimal risk activities. However, some of the discussion addressed such matter from the standpoint of an interventional study, which the Study is not.

Questions and Comments for Dr. Fleischman

• Dr. LeMasters commented that there were two camps on the subject of providing subjects’ families with information obtained during the Study. One perspective is that this is an observational study, meaning feedback requirements may be minimal, and the other that the Study should inform families of various hazards in their environments and any detected genetic predispositions.

• Fernando A. Guerra, M.D., M.P.H., NCSAC Member, San Antonio Metropolitan Health District, asked what the workshop offered in the way of means of alleviating exposures as it uncovers them. Dr. LeMasters said that in some cases, the link(s) between exposures and pathologies were not obvious. She commented that families could be provided with information on reducing exposures, but some at the workshop made the case again that the Study is an observational study, and that an interventionist paradigm would have to be factored in during design.

• Dr. Fleischman commented that some thresholds should be set for intervention, should intervention be deemed desirable and practical. He added that informing families over time of the meaning of population-based data may be sensible, and that primary care physicians were another potential route of information on ameliorating hazardous conditions. He noted that information on a murky causal connection might not be ethically communicated, but that was not the case for information regarding a well-established exposure/outcome scenario.

• Dr. Doswell asked about HIPAA regulations, and Dr. Fleischman said that by the time the Study moves into the field, the legal aspects will largely have been worked out.

Discussion Regarding Letter from the Study Design Working Group

Nigel Paneth, M.D., M.P.H., Study Design Working Group Co-Chair
Michigan State University College of Medicine

Peter Gergen, M.D., M.P.H., Study Design Working Group Co-Chair
National Institute of Allergy and Infectious Diseases, NIH, DHHS

Drs. Paneth and Gergen participated in the discussion by conference call. Highlights of the discussion were as follows:

• Dr. Gergen said that the letter from the Study Design Working Group sought to address issues such as core hypothesis selection, identification of thematic areas, and development of an overarching framework.

• Dr. Bellinger asked for further information on what the Study Design Working Group needs from other Working Groups and what gaps the Study Design Working Group feels there are in the current hypothesis list. Dr. Gergen said the gaps in the Study were, in part, related to outcomes that are needed to identify measurement criteria.

• Dr. LeMasters asked if the social aspects were to be laid over the epidemiological aspects of the Study. Dr. Gergen affirmed the idea, stating that at present, the Study Design Working Group was more concerned about how etiologies will drive data collection work.

• Dr. Graham said she felt the elements missing from the Study include measures of exposures, such as dioxin. She also expressed concerns regarding absence of endpoints, such as male reproductive capacity and affective disorders. Dr. Gergen stated that the process was designed to address deficiencies on an ongoing basis.

• Daniel J. Swartz, NCSAC Member, Children’s Environmental Health Network, remarked that two issues remain from the March NCSAC meetings, namely that the hypotheses were still fairly open and that staffing was inadequate. He asked how the Study Design Working Group saw those situations. Dr. Gergen replied that the work in question did call for more dedicated staff than volunteers could hope to fill.

• Dr. Landrigan noted that some hypotheses were not well developed, and suggested an imbalance between the biological hypotheses and those for socially-induced exposures, saying that the former needed further development. Dr. Gergen did not disagree. Dr. Zuckerman made the case that the hierarchy of hypotheses was perhaps less important than the exposures to be measured, and mentioned genetics as a risk factor that should play a role in the Study.

• Dr. Michael asked about the implications for sampling of biological versus social exposures. Dr. Gergen replied that some sampling strategies would serve both needs, noting that some oversampling might be needed to develop adequate data for certain exposures.

• Dr. Doswell commented that the budget for bioterrorism may serve as a source of funding and asked about hypotheses that addressed bioterrorist activities as exposures. Dr. Gergen said that he could not discuss funding and that no specific group of chemicals and/or biological agents has been excluded from consideration for the Study.

• Dr. LeMasters commented that the Study could not reasonably be based on exposures and made a case for closure of hypotheses based on a specific set of outcomes. Dr. Gergen agreed, noting that many of the outcomes could lead to multiple exposures, and that the outcomes had as much to say about the measures as the exposures.

• George P. Daston, Ph.D., NCSAC Member, Proctor & Gamble Company, commented that the Study Design Working Group’s proposed next steps seemed reasonable, and asked whether the NCSAC should try to come to a conclusion as to how and by whom the timeline will be executed.

• Shiriki Kumanyika, Ph.D., M.P.H., NCSAC Member, University of Pennsylvania School of Medicine, remarked that the Working Group’s letter did not indicate final authority and/or responsibility, and that it cast the Study Design Working Group in the role of a passive agent. She recommended a change in the process to help the Study move along.

• M. Anne Spence, Ph.D., NCSAC Member, University of California, Irvine Medical Center, seconded Dr. Kumanyika’s comment about final authority. She asked about a difference between rates of diagnosis and the actual incidence, noting that the definitions of a disease state/diagnostic inclusion presented serious challenges to the Study, as they tended to change over time.

• Donald J. Dudley, M.D., NCSAC Member, University of Texas Health Sciences Center at San Antonio, made the case for the notion that the Study is a study of diseases and risk factors with an overlay of behavioral science. Dr. Mattison asked whether Dr. Dudley presented that as a motion, to which Dr. Dudley did not directly respond. However, another member offered it as a motion, and several members seconded the motion.

• Dr. Kumanyika again raised the question of organizational authority. Dr. Mattison said he felt that procedurally, the NCSAC was charged with the capacity to make a recommendation regarding the design and focus of the Study, but asked whether the wording of the motion needed further review. Dr. Bellinger seconded the idea, but added that the Study should also emphasize positive outcomes rather than just pathologies. Dr. Michael said that the failure of the wording to account for organism-specific factors left him unable to vote for the motion.

• Dr. Paneth remarked that a study geared toward outcomes and environmental exposures was a different study than one examining development, and noted that such a study did not require a study population of 100,000. He added that the Study should have little difficulty studying health as a concept once the set of outcomes and exposures are identified. Conversely, a study geared toward health outcomes may miss data on rare disorders. He said the Working Group feels that some of these dilemmas need to be resolved in order to proceed with the NCS.

• Mr. Swartz said that the Study can only begin when it is decided what the Study will and will not address.

• Dr. Zuckerman remarked that the Study should take an opportunity to examine phenotypic elements, and that a recent journal article indicated that identifiable genetic predisposition was a better predictor of pathology than clinical intervention. He also favored a greater emphasis on environmental factors.

• Dr. Daston suggested that the NCSAC had to come to terms with assuring the Study is designed in a way that takes advantage of its unique properties, such as size, and that the notion of building it under a new paradigm rather than a more classic construction may incur risks. He noted that leadership was also an open question.

• Dr. Graham stated that the Study might not be subject to an either/or set of choices. She made the case for the Study being "outcome-related." She recommended that if outcomes are identified, the Working Groups could meet to weave their hypotheses in ways that would lead to a more complete picture.

• Roderick Joseph Alexander Little, Ph.D., NCSAC Member, University of Michigan, said that many hypotheses lent themselves to a nested case control study that might serve as a more feasible framework than some of the alternates.

• Dr. Spence suggested a change of verbiage to the third paragraph of the Study Design Working Group letter. It would read, "The most useful study design is one that integrates insights of the social and biological sciences upon a fundamentally epidemiological design that identifies specific outcomes and specific risk factors." She felt the Study design and other issues were secondary to this.

• P. Barry Ryan, Ph.D., NCSAC Member, Emory University Rollins School of Public Health, expressed concerns about the number of hypotheses. He felt that the hypothesis descriptions indicated lack of communication within Working Groups, and recommended that the Study not cover exposures and outcomes that can be handled with smaller samples. Dr. Dudley asked whether the ICC has examined this issue. Dr. Mattison answered in the affirmative.

• Dr. Kumanyika remarked that she was unclear on the authorizing authorityability, and recommended that the letter take care to use the terms "epidemiological" and "biomedical" more carefully. Dr. Zuckerman said he is interested in how social environment can be embedded in biology, and asked what the analytical approach would be.

Action Item: Send e-mail comments and questions to Drs. Paneth and Gergen.

Drs. Paneth and Gergen ended their participation via conference call at this point.

Additional Discussion

• Dr. Scheidt informed the NCSAC that the ICC has discussed decision-making intensively, and that decisions are being made regarding hypotheses and pilot studies on an ongoing basis. Measurement decisions are also in the works.

• Pauline Mendola, Ph.D., ICC Member, Office of Research and Development, EPA, promised members that the NCSAC would hear more about the ICC’s efforts to move the Study along. She noted the existence of several ICC subcommittees that are tasked with compiling and evaluating information related to the construction of the Study. Dr. Scheidt said the ICC needs explicit advice from the NCSAC, and remarked that things not committed to in writing do not happen. Dr. Mendola added that Working Group findings must go through the NCSAC before the ICC can act on them, and that there are related time constraints.

• Dr. Mattison said communication is a problem for all group relations, and in need of the Executive Committee’s attention. Another area needing the Executive Committee’s review, with Program Office support, is the process by which information flows between the various bodies in the NCS.

• Dr. Mattison suggested that NCSAC members might volunteer to work with the Working Groups on design issues, asking Dr. Dudley to lead the ad hoc group. He asked if the NCSAC should take up the matter of a Study mission statement in relation to the Children’s Health Act.

• Dr. Graham agreed on this agenda with the proviso that the Study Design Working Group present at the next NCSAC meeting so as to facilitate action. Dr. Scheidt said the ICC had addressed a mission statement in 2001, and that they will offer it at the NCSAC’s request.

• Dr. Landrigan remarked that the NCSAC may be "spinning our wheels" assuming the ICC has developed work that the NCSAC is discussing. Dr. Mendola said that the ICC’s recommendations had been presented at both the December 2002 and March 2003 meetings. Some Working Group materials still in need of review constituted refinements of hypotheses. Dr. Landrigan asked whether there was an "overarching document" of ICC origin. Dr. Mattison characterized that document as detailing the five theme areas and their hypotheses.

• Dr. Doswell asked for the hypothesis list to be included in the Briefing Book for each meeting. Dr. Mattison suggested that the Briefing Books were getting cumbersome, and asked how members would feel about publishing the Briefing Books on a CD-ROM. One member spoke in favor, and Dr. Kumanyika asked for documents that allow tracking the evolution of hypotheses.

• Dr. Daston said the need was for documentation that made explicit the layers of organization, and noted that process and communication were problems.

• Dr. Michael said that the exhaustiveness of the measures is not reflected in any hypothesis. Dr. Mattison answered that a cataloguing of measures was part of the ICC’s work at the retreat, and suggested that the ICC provide an update on the status of hypotheses and a presentation of measures and intervals at the September NCSAC meeting.

• Dr. Graham suggested that the majority of the next meeting address hypotheses with an eye toward those that have been revised, as well as a matrix of measurements. Dr. Mendola remarked that the ICC has worked on organizing the Study and has tried to employ the Working Groups to assist in the protocol development. She said a tiered approach that lays out the changes in hypotheses may provide the needed insight Dr. Graham said she was not so interested in the history of hypotheses as in their current states.

Health Disparities and Environmental Justice Working Group Presentation

Camara Jones, M.D., M.P.H., Ph.D.
National Center for Chronic Disease Prevention and Health Promotion, CDC, DHHS

Rueben C. Warren, D.D.S., Dr.P.H., Office of Urban Affairs, CDC, DHHS, introduced the Health Disparities and Environmental Justice Working Group presentation. He noted that the Office of Minority Health was established in 1988, and in 1992, CDC hosted a symposium addressing race and morbidity/mortality. The following year, there was a symposium addressing race/ethnicity in public health surveillance. He said the issue was and is whether the disparities are the result of race or of racism.

Dr. Jones said the key message of her presentation was that it is important to examine the impact of racism, and that such elements can be scientifically examined. She commented that the Study is an appropriate forum for asking and answering these questions. Dr. Jones then presented the following items:

• Race can be described as a proxy for socio-economic status, culture, or genes, but measures social classification. The Health Disparities and Environmental Justice Working Group’s core hypothesis is that racism contributes to disparities in health outcomes between racial groups.

• Ethnicity is not identical to race because ethnicity is as much culture as biology, whereas racism is a system that structures opportunity based on phenotype, unfairly disadvantages individuals and communities,, and undermines the potential of society due to unfulfilled individual potential. There is considerable variance in the ways that ethnicity and race intersect.

• The three levels of racism were described as:

• The five strategies for racism will look at:

• These strategies were described in the proposal as specific aims, the first of which was an analytical approach that sorted SES by race to establish correlations (outcomes would include diabetes and obesity). The current constraint is that many data sets do not delineate both SES and race.

• The second aim is to establish the impact of racial climate on all children and any disparities in outcome. The measures would include a questionnaire to establish the frequency with which a subject considers his/her racial origin and control for racial origin.

• The third aim, measurement of perceived discrimination and other measures of racism, will examine the association of racial discrimination as perceived by caregivers, school-age children, and adolescents and tie those to health outcomes. Among these may be cognitive development, obesity, and school performance. This has been modeled with a six-question survey executed in several states. Other measures would matrix individual/aggregate and institutionalized/personalized.

• The fourth aim seeks to discover the rate at which physiologic markers change with age and compares those rates by race. Some of these measures may be blood pressure, bone age, age of sexual maturation, impaired glucose tolerance, and arterial atherosclerosis. A recent study demonstrated blood pressures in African American women aged 35-44 matched those for white women aged 45-54.

• In terms of birth outcomes, the best age for white women to have babies is in their twenties, while for African American women, it is in their teens. Dr. Jones said that a longitudinal follow-up like the Study offers a unique opportunity to track such things.

• The fifth item addresses structural factors, those structures, policies, practices and norms that result in racial disparities in exposures and opportunities. The Study could look at segregation in living, school curricula, and expectations of academic performance.

• Exposure measures would include race as usual classification by others and measures of perceived differential treatment by race. Outcome measures would include those that are known to vary by race, and would hopefully include age-sensitive evaluation as well as continuous measurement. Analytical approaches would have to incorporate plots of health outcomes by SES stratified by race with tracking data generating a picture of how those change over time.

• The impact on the design of the Study would require oversampling of minorities, clustering to elicit information on locale-specific exposures,, and clustering of data stratified by both race and SES.

• The pilot studies would include creation of a compendium of currently-available measures and development of measures of perceived differential treatment. Individual and aggregate measures of racism and measures of racial climate would also help round out the picture.

• The Study was a good means for developing this branch of medical science partly due to its size, but also because it is a prospective study. The longitudinal nature can shed light on how those factors impact health over time as well as how the racial climate might change. The national scope of the Study would allow assessment of regional variations and local organizational factors.

Questions and Comments for Dr. Jones

• Dr. Zuckerman asked whether there was any way to track genetic polymorphisms and how they influence outcomes exhibiting racial disparities. Dr. Jones cautioned that race does not correspond well with genetic variation and that racism expresses as stress in addition to opportunity disparities.

• Mr. Swartz said that the fourth objective lent itself to longitudinal examination more readily than the others, but that he saw great potential for all five to be incorporated into the NCS.

• Dr. Dudley recommended that the racial grouping now include one for Arab-Americans. He asked how to measure racism and elicit the intermediate measures from the data. Dr. Jones replied that a substantial body of literature exists on such concerns, and that is the reason for the compendium proposed for this hypothesis.

• Dr. Kumanyika asked about the design issues connected to within-race analyses given that genetic factors and blood pressure vary within race, and whether SES expresses itself the same way within groups. Dr. Jones replied that income does not result in the same outcomes due to structural elements of racism and that within-race evaluations might prove educational.

• Dr. Doswell commented that measures existed to address images/stereotypes, and that minorities often have similar experiences despite differences in SES. She asked about measurements of children of mixed racial parentage. Dr. Jones replied that self-identification might not be as strong an indicator of exposure to racism as how others identify the subject.

• Dr. Bellinger asked what criteria could be used to limit the number of racial groups deployed in the NCS. Dr. Jones replied that Office of Management and Budget (OMB) categories would serve as the foundation, and that ancestral origin would undergird classification and oversampling.

• Linda M. Burton, Ph.D., NCSAC Member, Pennsylvania State University, asked about studying white attitudes toward race and how whites convey attitudes about race to their children at a time of controversy over affirmative action. Dr. Jones replied that the Study could look at white parents whose children were denied enrollment due to racial set-asides or who feel they have been discriminated against for jobs. They could be cross-checked against minorities for health outcomes.

• Mr. Swartz asked if there was any evidence of differential outcomes when parents identify themselves as being of a different race than the child. He also asked whether chemical exposure measures should be controlled for race.

• Dr. Spence asked how early in life would the Study seek information from respondents on perceptions of racism. Dr. Jones said that she felt the evaluation perhaps should commence with kindergarten-aged children and that ongoing measures would be appropriate.

• Dr. Michael commented that open-ended questions may elicit better data on the racial origin, and that oversampling might not be necessary so long as the group from each racial classification is large enough to provide meaningful data. Dr. Michael commented that the Study will likely not cover subjects who were not born in the U.S. Dr. Jones replied that the oversampling strategy was aimed at including the various elements in each SES within racial groups.

• Dr. Jones stated that the interviews should begin when a child first has exposure to images of people of other racial groups rather than wait until the age of five. She also asked about how to measure self-image. Dr. Jones agreed, but said this was in need of further development.

• Dr. Guerra asked whether color and race had to be analogous, and Dr. Jones responded no, that this correlation varied among cultures/nations, and that each society employed a more- or-less unique set of indices of race. Dr. Guerra commented that measures of accomplishment might be a worthwhile pursuit, using professional athletics as a forum for minority achievement. Dr. Jones noted that this would be an interesting point to examine.

• Dr. Burton advised that the inclusion of a race hypothesis did not mean that the concept did not need to be included in the rest of the Study.

Dr. Mattison asked for a discussion of the disposition of the hypothesis:

• Dr. Daston stated that before approving hypotheses, he would like to settle some questions on the orientation of the Study.

• Dr. Zuckerman replied that data indicates that race does affect outcomes and as such, is an appropriate area of study. Dr. Duaston agreed that racism is a factor, but questioned whether it was a core hypothesis.

• Dr. Doswell suggested that the disparities constituted a call for action, and pointed out that the human experience blends biology and sociology. Dr. Graham recommended that the NCSAC not get "hung up" on the word "hypothesis," and suggested that the notion of race was somewhat integral to the NCS.

• Dr. Kumanyika urged that the racism hypothesis tie its work more closely to other hypotheses. Dr. Jones proposed that the racism hypothesis be interwoven into all hypotheses.

• Dr. Dudley said some hypotheses were overarching, and not geared toward specific outcomes, a situation in which he felt the racism hypothesis would likely function best. He added that he would like to see more pilot studies on racism.

• Dr. Landrigan said that race was inarguably an appropriate part of the Study, and that the real question was how Working Groups would incorporate instruments to elicit race information in their measurements. He added that they should exercise caution regarding the numerical needs of hypotheses.

• Dr. Burton asked how long Working Groups have to integrate meta-hypotheses into their working hypotheses. Dr. Mattison replied that the ICC and the Program Office feel they are in the best position to handle this work, but said that the Working Groups will provide substantial input on how to sew the Study together.

• Dr. Kumanyika said that some of the hypotheses proposed by the Early Origins of Adult Health Working Group dealt with the same elements as those proposed by the Health Disparities and Environmental Justice Working Group, but that none deal with racism. She described hypotheses lacking racial elements as naïve.

• Dr. Jones stated that the Study should not sacrifice relatively common diseases in favor of more unusual disease states. Dr. Mattison said that several Working Groups made the case that studies of 100,000 were helpful in drawing out some detail that might otherwise be missed in smaller studies, despite assertions that some rare disease states could be adequately studied with smaller Study sets.

• Dr. Zuckerman asked how much thought has been given to the childhood antecedents to adult disease, noting that this orientation may provide the best return on the Study dollar. Dr. Mattison said that there had been a presentation on this at the December NCSAC meeting and described it as an ongoing issue.

Dr. Mattison recapped that there is enthusiasm for the race hypothesis and for integrating it into other hypotheses, but there is a need for pilot studies.

Advocacy Group Presentation: March of Dimes

Nancy Green, M.D., Medical Director, March of Dimes

Dr. Green said her organization was pleased to support the Study, and that she would present data on gene/environment interaction. She complimented the breadth and inclusiveness of the Study. Dr. Green’s presentation included the following points:

• With regard to birth defects, low birth weight (LBW), and preterm birth, some conditions are both rare and common, depending on how one classifies each occurrence. The leading cause-specific infant mortality in 1988 was birth defects, at a rate of 208.2 per 1,000, followed by SIDS (140.1).

• The priorities of the March of Dimes are birth defects (structural/functional, 2 of 3 with no identifiable etiology) and preterm birth (LBW; one of two spontaneous preterm deliveries with no clear etiology; disparities in preterm, LBW, and defects; and multiples). Multiple births play an increasing role in preterm deliveries and LBW.

• A Venn diagram showed overlap of birth defects, LWB, and preterm birth. The study offered a unique opportunity to address these factors, and that this overlap is poorly addressed in the literature. The literature indicates that nearly half of infant deaths due to defects were in full-term infants. Morbidity data would run parallel. Preterm births are up 27 percent between 1981 and 2001 (9.4 versus 11.9 per 1,000).

• The March of Dimes prematurity awareness campaign has two prongs. One is to reduce preterm births to 10 percent and the other is to increase public awareness (seeking 60 percent versus the current 35 percent). The March of Dimes has conducted the survey yielding the awareness numbers listed,, and a broader awareness of issues of prematurity may help bolster the case for the Study among the general public.

• Preterm birthrates vary widely by racial/ethnic category (white 11 percent versus 17.5 percent for African American). Preterm births are low in the Pacific Northwest and highest in the Southeast, a distribution that correlates strongly with racial distribution.

• Once fully developed, the March of Dimes research agenda will likely consist of four areas of emphasis. One is to establish the basic mechanisms of preterm labor and premature membrane disruption. The second is to improve clinical approaches along the lines of risk identification/reduction. The third will be to improve neonatal treatment, and the last, to foster interdisciplinary approaches, especially in the area of reducing racial/ethnic disparities. While neonatal treatment was not the focus of their campaign, it is nonetheless important inasmuch as numbers have flattened since 1995, perhaps indicative of a need for a new surfactant.

• A good argument for family studies in the Study was made by a study published in the New England Journal of Medicine in 1995, which broke down outcomes by sibling and maternal birthweight. Subjects whose mother and a sibling both experienced LBW demonstrated higher rates of LBW than those with only a sibling or a mother with LBW. Subjects with neither mother nor a sibling with LBW demonstrated the lowest incidence.

• Regarding gene/environment interaction, two areas of investigation are suggested. Both cover genes responsible for regulating metabolism, with one addressing exposure to benzene and the other exposure to maternal smoking. The genes of interest are for cytochrome P450 and a gene that regulates glutathione transferase. They were selected because they are seen as highly polymorphic and are related to detoxification for organic chemicals, such as tobacco smoke ingredients.

• Material from a study in China was displayed that looked at benzene exposure as related to gestational age and haplotype. The data suggest that gestational age was sufficiently sensitive to differences between CYP1A1 and GSTT1 to cause a one-week difference. However, those genes by themselves demonstrated no differential effect if maternal tobacco use is removed. Gestational length exhibited similar propensities with regard to sensitivity to tobacco exposure, but again, none in the absence of maternal smoking.

• On the subject of multiple births, approximately 10 percent of single births in the U.S. are preterm, whereas more than half of twin births are preterm. More than 90 percent of triplet births are preterm. Overall, 3 percent of all U.S. births are multiples, a number on the rise due in part to recent increases in the average age of mothers and in part to use of reproductive technology. Questions remain as to the effect of reproductive technology on birth weight and gestational age, and urged data collection to obtain such information on multiple births.

Questions and Comments for Dr. Green

• Dr. Zuckerman said he saw four paths to prematurity, including environmental exposure, infections, and coagulopathy. He noted that questions of the influence of stress suggested a need for a gene component.

• Dr. Landrigan asked how much influence multiples and reproductive technology have on the incidence of preterm birth. Dr. Green said the data suggested that those factors accounted for between 25 percent and 30 percent. Similar numbers on the age of the mother who do not use reproductive technology are not available.

Study - Director’s Update

Duane Alexander, M.D.
Director, NICHD, NIH, DHHS

Dr. Alexander said that several presentations on the Study have been made, including one to Surgeon General Richard Carmona and NIH Director Dr. Zerhouni. Dr. Zerhouni also met with agency/institute heads to gauge their interest in the NCS, and the response was positive. This will be the first prospective study of its size that addresses the Barker hypothesis. NICHD and the Program Office will present to Congress as well. Dr. Alexander’s presentation included the following items:

• Dr. Zerhouni has agreed to support the Study and lobby for funding in the fiscal year 2005 budget, although fiscal year 2004 may provide less than the needed $26 million. Contingency plans were in development should fiscal year 2004 funding come up short. Such contingencies would include delays in recruiting and in contracting for vanguard centers. Congressional markups may occur earlier in this legislative cycle than the last.

• The NCSAC should assume the Study will indeed get off the ground, and commented that the members of the NCSAC can contribute to the success of the Study by advocating for the Study and by helping to assemble a study of such quality as to make the Study a difficult proposition to refuse. The NCSAC could also help to assure the broad appeal of the Study needed to generate the needed support. Gratitude to the March of Dimes and the American Psychological Association for their assistance was expressed.

• The next tasks include consent development, Study design, and the design of the sampling strategy, and that the Study will count heavily on the guidance of the NCSAC.

Questions and Comments for Dr. Alexander

• Dr. Graham asked if significant staff additions were en route. Dr. Alexander replied that NICHD is determined to keep the Study alive, and has set aside positions for Study staffing. The science side should be adequate, but administrative functions may be attenuated due to hiring freezes.

• Mr. Swartz queried Dr. Alexander for his "shortest pitch" for selling the Study to non-believers. Dr. Alexander replied:

  "This is a timely, needed study that can be put together only with the resources of the Ffederal government to take advantage of new advances in science and technology to gather information about environmental influences on children’s health and development in a way that we have never been able to do before. The restrictions on what we have been able to do before have resulted in many important questions going unanswered, questions not just about environmental pollution, toxicants, [and] air pollution, but also about many other influences on children’s lives and development; influences within their family, within their community, within their schools, within their churches, within their built environment, if you will.

  The fact that we have the capability now of measuring this, of collecting enormous amounts of data in larger quantities than we have ever been able to collect before and manage that data and do analyses in ways that we have never been able to do before gives us a chance to answer some questions about children’s lives and how to promote their healthy growth and development in ways that we haven’t been able to do before. It’s timely, it’s important; many of these issues have gone unaddressed because there hasn’t been methodology, or dollars or numbers to do it.

  This study provides us the opportunity to apply all those things in a way that will give us answers to questions that are extremely important. The answers that we get can make differences in their health outcomes, whether or not they develop disease, ways that we can prevent the development of disease, ways that we can make their environment safer so that as children and as adults, they are healthier, they are less likely to have adverse impacts of disease and injury on their lives, and are able to live longer [and] healthier."

• Dr. Landrigan asked if a cure for specific diseases is part of the presentation of the NCS. Dr. Alexander said that he felt that cost/benefit data was the most persuasive. He said that the numbers were such that the projected benefit of the alleviation of any one of several diseases/pathologies would cover the cost of the entire Study in one year.

• Barbara R. Foorman, Ph.D., NCSAC Member, University of Texas Houston Health Science Center, asked how the Study can be linked with other endeavors, such as bioterrorism and the No Child Left Behind program. Dr. Alexander said this is an area of great potential, commenting that the largest payoff of the Study was its impact on learning.

• Dr. LeMasters suggested that NCSAC members have a copy of the slides used to make the case for the Study. Dr. Mattison said the slides will be available in PowerPpoint format.

• Dr. Zuckerman asked if the cause would be abetted by framing the Study with a more conspicuous name. Dr. Alexander said they have worked on an alternate title, but have not come up with anything. He said an alternate title was not out of the question, and that the title arose very early in a search for names for the Study.

• Dr. Phillips said the NCSAC has struggled with a healthy development hypothesis, and Dr. Alexander said there are many things the Study could look at, including altruism and delinquency.

• Loretta Jones, M.A., NCSAC Member, Healthy African American Families, asked how to link with other campaigns, including the CDC’s VERB campaign, which promotes physical activity. Dr. Alexander noted that some time will lapse before the early cohort will be old enough to participate in VERB, but remarked that the Study is not, by nature, an interventional study. Ms. Jones clarified that she wondered how the subjects and their data could be used in partnership with various programs and other studies. Dr. Alexander approved of the idea.

• Dr. Guerra asked what the fallback position willwould be if the should financinges fall through. Dr. Alexander said that the Study has a threshold of enrollment below which it is not worth doing, but that the core of the Study can be handled independently. However, the dimensions and related costs of studying that core are not known. Current estimates run to $2.7 billion over the life of the NCS, with the greatest expense incurred in the early years. This figure is not adjusted for inflation.

• Dr. Zuckerman asked if a pilot of 1,000 subjects for two years might help work out the details of the NCS. Dr. Alexander stated that pilot studies would be undertaken, but commented that such a scenario is seen more as a fallback position rather than as an immediately-offered alternative. He wants to sell the idea on Capitol Hill and the White House based on the notion that data returns will be back in the first few years.

Status of Hypotheses, Update on Protocol Development/ICC Retreat

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

Dr. Schoendorf noted that he would present on the current status of protocol development and an outline of the ICC’s plan for further developing the Study protocol. His presentation included the following points:

• The ICC had covered considerable ground on the protocol during its recent retreat. The Study protocol is currently divided into a data collection protocol and a protocol covering non-measurement components, such as recruitment/retention, informed consent, and so on. The data collection protocol includes information such as frequency of visits, data/specimens to be taken, and demographic data to be obtained.

• The data collection process starts with priority themes and hypotheses and lays out hypothesis-specific data collection schedules that will be merged into a full protocol. Refinements and further detail will be added over time. The online database, assembled by Sarah Keim, M.A., Study Coordinator and ICC Member, NICHD, NIH, DHHS, and others at NICHD, tracks individual hypotheses but allows for additional hypotheses and facilitates tracking of hypotheses as they change over time.

• The online version of the protocol provides information on each hypothesis, including location where the sample is obtained, the sampling instrument(s), and the specimen and/or information obtained. This software will allow sorting of hypotheses by any one of a variety of categories.

• While development of the data collection protocol was properly the domain of the Program Office, the ICC opted to take up the task, rather than allow the Study to fall behind. The ICC relied on work done at the December 2002 Study AssemblyM by Inter-Working Groups, Working Groups, Working Group core hypothesis write-ups, NCSAC advice, ICC expertise, and the relevant scientific literature.

• The database is now hypothesis-specific, but must evolve so as to sort across hypotheses and to offer a more complete capacity for tracking. At that point, the database will have to incorporate more detailed information on sampling, a task for which the ICC will need input on from both the NCSAC and the Working Groups. Upon accomplishment, the ICC will forward the database to the NCSAC for review.

Questions and Comments for Dr. Schoendorf

• Dr. Michael praised the database as an index of genuine progress, and asked how the ICC intended to deal with overlap that is not duplicative enough to allow trimming of hypotheses. Dr. Schoendorf replied that the database cannot currently control for duplicative constructs, and that such work would be done by review. Some effort is going into standardization of terminology, which will help in the effort to detect duplicated elements.

• Dr. Zuckerman said much of the day’s discussion seemed to go to justifying the Study population, and asked whether some components of the study could be handled in independent studies. Dr. Scheidt said such an idea is in circulation. Dr. Phillips asked whether the exercise of such an option would entail site-specific protocols or embedded protocols. Dr. Scheidt stated that both these options would be explored.

• Mr. Swartz asked whether the ICC had considered building in the ability to pick up additional, less burdensome samples in an established sampling plan. Dr. Schoendorf replied that the ICC had worked on a list of "no-brainer" samples that should be collected, regardless of whether they are mandated by any hypotheses.

• Dr. Graham asked when the ICC anticipates sending the database to the NCSAC for review . Ms. Keim said a summary will be presented in September on the state of the database.

• Dr. Schoendorf remarked that he had the impression that the NCSAC would like to see the database as it evolves,, and Ms. Keim added that the database allowed for retrospective and prospective examination of the contents.

• Dr. Christine Bachrach asked about the roles of Working Groups in this process. Dr. Mattison replied that the current understanding of the legal picture was that Working Group members might have to work with the ICC via the NCSAC rather than directly in order to avoid endangering the ability of Working Group members and/or their institutions to pursue contracts with the NCS.

Discussion of Hypotheses

Tab 1: Roster of hHypotheses cCrafted by the Early Origins of Adult Health Working Group

Dr. Michael, Dr. Kumanyika, and Dr. Little

The group offered eight hypotheses on nine outcomes that address susceptibility to adult chronic diseases, the triggers for which can occur at any time, including prior to conception. The Working Group had to choose between focusing on either accumulation of risks or crucial-juncture exposures. They recommend the Study see itself as a lifecourse Study rather than one of just of childhood exposures. However, funding may be difficult for that term.

• Dr. Michael said he likes the hypotheses, stating that the idea of tracking insults to health could yield tremendous data and is inexpensive. However, there is not much use for some of the data in the short run. He commented further that he had received information not included in the Briefing Book that further buttresses the case for these hypotheses. This set of hypotheses should go forward.

• Dr. Little seconded Dr. Michael’s comments on the hypotheses, stating that he found the section on monozygotic and dizygotic twins interesting and the level of expertise on genes impressive.

Discussion

• Dr. Spence recommended the hypothesis on monozygotic and dizygotic twins be forwarded to the Gene-Environment Interaction Working Group, which is looking at early markers of later disease, including skin cancer.

• Dr. Kumanyika stated that the hypotheses lacked sophistication on race issues, and said that the diet hypothesis was perhaps underdeveloped.

• Mr. Swartz said the hypotheses lacked information on chemical factors and asked if the causes of retardation of fetal growth are well detailed. Dr. Dudley said the causes are numerous and difficult to isolate.

• Dr. Zuckerman commented that indices such as school performance were important and called for inclusion in the NCS. Dr. Mattison replied that the Working Group tended toward chronic adult diseases, but Dr. Zuckerman said the literature indicated that the best predictor of duration of adult disability might be educational attainment.

• Dr. Kumanyika stated that regarding osteoporosis, the critical measure should be low bone density rather than full-blown osteoporosis because peak density occurs at a point during which subjects are in the Study.

• Dr. Landrigan commented that he felt the Study should not stop at age 21, commenting on the British study. Dr. Little said that the educational outcomes were important as Dr. Zuckerman proposed. Dr. Mattison said the Early Development Origins of Adult Health Working Group could look at educational outcomes.

• Dr. Doswell expressed concern that collecting data from schools added to subject burden and to the task of the NCS . Dr. Zuckerman replied that there might be a need to determine whether academic performance was needed. Dr. Doswell suggested that other factors figured into academic performance, and Dr. Zuckerman made the case that academic performance could tell much about child health.

• Dr. Foorman remarked that hypothesis six has academic measures and that a substantial body of literature existed that addressed academic measures, including dropouts. She pointed out that the No Child Left Behind program will provide data on academic performance that perhaps could be used. Dr. Michael said there is a definite economic correlation for the life stage at which one successfully undertakes learning in a systematic fashion. Dr. Kumanyika expressed concerns about approaching academic outcomes via the means described by the Early Origins of Adult Health Working Group. Dr. Zuckerman said that some of the concerns were based on well-established science.

Recommendation: Dr. Mattison recapped that there was enthusiasm for the hypothesis, but there are reservations on the issues of race and the possibility that this hypothesis was rather large.

Tab 3: Parental Actions hHypothesis

Dr. Guerra and Dr. Daston

This hypothesis suggested parental responsibility for exposures and alternately, reducing risk. It is a timely pursuit, given modern ability to measure, and represented an opportunity to increase the level of awareness of the impact of parenting.

• Dr. Guerra stated that there is immense potential benefit, but the costs may be considerable. He recommended this as a core hypothesis, but suggested that a greater distinction should be made between parental and societal responsibilities for exposures. He said it would help to include biological agents such as emerging infectious diseases. He felt the hypothesis failed to address the ability of the parents to come up with economic means to more adequately shield their children.

• Dr. GDaston said this was useful in assessing parental understanding and use of messages on public health. He recommended sending this back to the Working Group for further development.

Discussion

• Mr. Swartz commented that this hypothesis did take parental action as a given and that the family’s SES and informational state of the parents were influences on parental action. He cautioned that this could be playing to a blame-the-victim mentality.

• Dr. LeMasters said the risk assessment questions could not be adequately responded to via mail or phone, saying that a site visit was needed. She said it needs further development to serve as a primary hypothesis.

• Dr. Graham said the question was still out as to whether this was a primary hypothesis despite the great influence on child health. She recommended they spell out the exposures, such as risk-taking behaviors. Dr. Bellinger said the quality of the data would not be good if the Study tried to apply this to all 100,000 enrollees, suggesting that a subset be the population of choice for such a hypothesis that would also ask why parents take the actions they take rather than just ask what actions they took.

• Deborah A. Phillips, Ph.D., NCSAC Member, Georgetown University, remarked that other elements could be included, such as whether a parent reads to the child,, and asked if this did not properly belong to the domain of the Social Environment Working Group. Dr. Burton said her group would focus more on outcomes than this hypothesis does. Dr. Phillips described it as a developmental hypothesis that lacked detail on how parental action changed over time.

• Dr. Little commented that this hypothesis could examine the effects of external interventions, such as those programs geared to reducing child abuse.

Recommendation: Dr. Mattison recapped that this hypothesis generated much interest, but concerns regarding specificity remained. The NCSAC could refer it to the Social Environment Working Group for help, and it could be looked at in the context of a subsample of the NCS.

Additional Comments

• Dr. LeMasters questioned whether this hypothesis could be tested in that culture had so much impact on parenting behavior. Dr. Mattison asked Drs. Burton and Phillips whether this was testable, and Dr. Phillips said that while the task was difficult, there were instruments to capture parenting data.

• Dr. Little said the hypothesis was potentially important, but not compelling.

• Ms. Jones said that she had a problem with this hypothesis because it does not address racism, and because it does not address the fact that some parents will either not know about exposures or not be in a position to do anything about exposures of which they are aware. She also mentioned that sensibilities of privacy willwould present considerable barriers.

Tab 11: Prenatal Substance Exposure and Developmental Outcomes, Youth Drug Use and Its Consequences

Dr. Fleischman, Dr. Foorman, and Ms. Jones

These were described as two essentially unrelated hypotheses. One addresses prenatal substance abuse and could generate important information, but there are legal and confidentiality issues. The second addresses initiation into drug use during adolescence

• Dr. Fleischman stated that these were less core hypotheses than just data the Study should capture.

• Dr. Foorman agreed about the status as a non-core.

• Ms. Jones cited HIPAA and reportability as potential impediments to executing these.

Discussion

• Dr. Zuckerman said he was troubled by the fact that the introduction does not present a balanced picture of drug abuse, and commented that the National Institute of Drug Abuse can offer data without running afoul of confidentiality concerns.

• Dr. Dudley asked if the Study would be ethically bound to refer a pregnant woman to drug treatment in the event the subject is found to be using. Dr. Fleischman answered that it depends on the circumstances. He said that after the fact of the abuse, one would not, but otherwise, a researcher might. He asked that the Working Group begin looking at how technology can answer some questions.

Recommendation: Dr. Mattison observed that the endpoints should be a part of the Study, but that there should be better justification for the examination of how poverty influences these exposures.

Tab 5: Family Structure and Child Well-Being

Dr. Doswell, Dr. Foorman, and Dr. Fleischman
The underlying rationale needs to be better supported for use in a study the size of the NCS, and the idea was the subject of other studies. More information was needed on analytical methods and subject burden promised to be considerable.

• Dr. Doswell added that the cost might not be high, but said she was not sure it was ready for execution.

• Dr. Foorman said this hypothesis lacked sufficient detail. Dr. Fleischman agreed.

Discussion

• Dr. Burton said this hypothesis is spelled out more clearly in section eight.

Recommendation: Dr. Mattison suggested referring this hypothesis to the Social Environment Working Group for enhancement.

Tab 4: Sleep Problems/Disorders

Dr. Zuckerman and Dr. Dudley (Dr. Suarez not present)

This hypothesis needed greater specificity for definitions, instruments and outcomes. This hypothesis could be demanding in terms of instrumentation and in correlating costs. Sleep disorders can exacerbate chronic illness and it was suggested this hypothesis examine such influence.

• Dr. Zuckerman expressed interest in how this hypothesis could also address parental sleep disorders. He described this as an important hypothesis as important and said he would like to see more information on psychometric properties and a nested cohort execution of this hypothesis.

• Dr. Dudley stated that the hypothesis was appealing, but vague. He stated that sleep disorders during pregnancy are very common and that he would like to see further development. However, he said this is not a core hypothesis.

Discussion

• Mr. Swartz said this would be more interesting if sleep problems were treated as the dependent variable than as the independent variable.

• Dr. Spence stated that self-reporting of sleep was not especially reliable, but that the question of measurement was not adequately addressed, especially for pediatric populations.

• Dr. Phillips said that data existed on adolescent sleep patterns.

Recommendation: Dr. Mattison recommended this be reported back to the originators, perhaps to be revived when the cohort reaches adolescence.

Additional Comments

• Dr. Zuckerman asked about the fate of hypotheses not cleared for inclusion as core hypotheses. Dr. Spence replied that exhaustiveness was one criterion, and another was whether the hypothesis called for a Study group of 100,000. She added that the idea was to add hypotheses slowly rather than accumulate a large number that later has to be whittled.

• Dr. Dudley asked whether the idea was to trim the number of core hypotheses to eight to 10ten. Dr. Scheidt responded that this was true to some extent, but that the NCSAC should be careful of setting hard limits. Mr. Swartz remarked that a large number of hypotheses might be politically appealing but less than scientifically optimal. Dr. Little posed the dilemma of how to establish the trade-off between a small, expensive study versus a large, more exhaustive study.

Recommendation: Dr. Mattison recapped that this hypothesis will go back to the Working Group for further development.

Tab 6: Interaction Between Environmental Exposures and Genes

Dr. Graham, Dr. Burton, and Dr. Bellinger

This was a very relevant hypothesis, given the potential association with social deviance. There is a severity and prevalence of these conditions, but developing solid data would likely be difficult, a problem that a large sample size can overcome.

• Dr. Graham was enthused about the genetic approaches, hoping that such data would be useful in the future. Chemical measures need further detail in terms of the nature and vector of exposure, as does the intersection of drug use and genetic predisposition.

• Dr. Graham said there were some omissions, including affective disorders, but noted that the genomic approach offered earlier detection of predispositions that may lead to successful interventions. The measures and analytic approaches for chemicals were said to have been inadequately detailed. She rated it as a core hypothesis that needs more integration in development hypotheses, more development of outcomes, and more attention to SES and race/ethnicity.

• Dr. Burton seconded Dr. Graham’s comments, adding that information on locations of exposures should be bolstered.

• Dr. Bellinger remarked that he liked the concept but disliked the organization, stating that it seemed to link all outcomes to all exposures. He hoped the Working Group will provide further detail, and he noted that the cost of this may be considerable. He did not rate it as a core hypothesis in its present form.

Discussion

• Dr. Landrigan stated that this could serve as the lynchpin of the Study and that this presentation was not exhaustive, saying that the cited literature leaned too much toward toxicology and not enough toward epidemiology. He stated further that functional deficits were not well developed, such as loss of cognitive capacity and behavioral sequelae that did not rise to the level of a syndrome.

• Dr. Zuckerman seconded Dr. Landrigan’s comments, and reiterated that a failure to evaluate genetic contributions to the exposure/outcome matrix represented a lost opportunity.

• Dr. LeMasters agreed genetic factors should be incorporated, but wondered if this Working Group will have time to do so.

• Dr. Spence said trying to handle genetics at this meeting would be premature.

• Dr. Graham suggested the neurobehavioral groups draft an outline of their related hypotheses.

• Dr. Guerra noted some overlap between several of the hypotheses presented, and asked how to get the Working Groups together to merge them..

Recommendation: Dr. Mattison proposed that the ICC look at incorporating this hypothesis, but that members of the relevant Working Groups address the NCSAC’s comments.

The meeting adjourned for the day at 5:25 p.m.

JUNE 6, 2003

Dr. Mattison said the day’s work would commence with discussion of sampling issues, and that the hypothesis review would continue.

Sampling Issues

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

Dr. Michael stated that sampling is the most important aspect of the Study in terms of its influence on scientific value. His presentation included the following items:

• In the past, probability sampling efforts that were deemed impossible were nonetheless executed. The British cohort study of the 1950s and the National Collaborative Perinatal Project (NCPP) were two examples. Randomness might turn out to be less important than the sheer volume of data.

• A patient orientation in the medical community meant that it would not receive the Study well if the sampling strategy were not probability-based.s A data set that does not readily lend itself to mathematical extrapolation would erode its credibility, and the credibility of the Study as a convenience study will be based principally or solely on the credibility of the hypotheses. The stakes are high and as a consequence, a non-probability sample would generate tremendous opposition.

• A non-random sample will generate information only on the Study subjects. The NCPP is a study that has contributed significantly to biometrics, but did not generate a data set of the same scientific utility as the British cohort study.

• There are four arguments against a probability sample:
  - Clinics will work harder on subjects who are also those clinicians’ patients, but
     it is doubtful that this would be a real problem.
  - It may be infeasible to do probability because of recruiting problems.
  - There is an inherent difficulty in identifying the population.
  - There is a high cost of getting subjects to a clinic.
  However, it was possible to overcome or adjust for all of these.

• Its is important to separate the case from the data. Data collection should be distinct from subject selection, and no hypothesis should drive the design away from probability sampling.

Questions and Comments for Dr. Michael

• Dr. Mattison said that two issues raised during the discussion are the purpose of the data and the subjects of the data.

• Dr. Little remarked that statistical science was divided into two camps, but endorsed Dr. Michael’s comments against a convenience sample, noting that one should start with probability sampling and move from there if a probability sample proves unwieldy.

• Dr. Kumanyika asked if anyone had experience with community involvement. She commented that negative publicity was generated by over-recruiting that led to some would-be subjects being turned away.

• Dr. Spence said that she had limited experience in dealing with parents and schools during an autism study and had to deal with how to inform parents that their child did not qualify for participation. Dr. Spence said the worst problem occurred when the school system in question subsequently withdrew services from those who were excluded from the autism study.

• Dr. Doswell added that education of the community included an explanation of probability sampling.

• Dr. Little remarked that a probability sample was not necessarily a mandate that all had an equal probability of inclusion, and that there were arguments for clustering.

• Dr. Zuckerman said that since the Study was largely a medical one, it could drive up the use of medical facilities and that those facilities should be updated on the concerns parents are likely to express.

• Dr. Landrigan said that a probability sample was perhaps inevitable. He noted that comparisons with studies in other nations and with NHANES suggested that some of the benefits of the Study would be lost with a convenience sample. He added that he saw the intended enrollment of 100,000 as arbitrary, and that a valuable study did not require that large a population, despite any loss of oversampling sub-populations.

• Mr. Swartz remarked that the best reason for probability sampling was not to establish incidence, but to enhance inferential power.

Sampling Design

Peter C. Scheidt, M.D., M.P.H.
Study Director and ICC Co-Chair, NICHD, NIH, DHHS

Dr. Scheidt led his presentation on sampling design by remarking that this has been perhaps the most intensely-debated issue the ICC has encountered. Among the issues connected to the sampling question are:

• Representativeness;
• Prepregnancy versus early pregnancy;
• Oversampling of sub-populations;
• Measures of community/neighborhood environment and characteristics;
• Stability of exposure;
• Complexity of observation; and
• Sampling units, segments, design effects.

Dr. Scheidt’s presentation included the following points:

• The range of designs includes sampling by pure probability, by concentrated clusters, by dispersed clusters, and by a center model. The Westat report analyzed the household model to screen about 500,000 households for pregnancy and used the same number to examine a physician’s office model. The models were seen as a starting point and that the design hinged on hypothesis selection.

• The ICC’s sampling design process subcommittee looked at criteria for assessing the alternate plans and recommended establishing a subcommittee to implement the process.

• During the March 2003 NCSAC meeting, NCSAC members recommended a workshop, and the ICC is assembling a committee to design the workshop. Objectives would include a thorough and balanced consideration of sampling options, assurance that the issues are all considered, and issuance of a proposal for realistic sampling options. The conference planning committee has to develop the format, the agenda, and the participants. The proposed composition of the committee is two each from the ICC and the Study Design Working Group and one from the NICHD Program Office. The planning committee would be formed by July 2003 and the conference would take place three months later.

Questions and Comments for Dr. Scheidt

• Dr. Zuckerman asked if the sampling strategy question was still on the table. Dr. Scheidt answered that it was and that the discussion needed the presence of some members of the Study Design Working Group. Dr. Zuckerman asked whether the NCSAC was of one mind on the issue of sampling.

• Dr. LeMasters asked a member of the ICC to discuss how the ICC sees this issue. Sherry G. Selevan, Ph.D., ICC Member, Office of Research and Development, EPA, responded that the ICC felt that probability sampling did not mesh well with the data collection requirements. She said she would like to see a sample that is somewhat representative, and is open to creative ways to draw a probabilistic sample.

• Mark Klebanoff, M.D., M.P.H., ICC Member, NICHD, NIH, DHHS, said that the British study is important not because it was probabilistic, but because of the follow-up. He remarked that the NCPP would have generated as much interest with such follow-up, and said the Kaiser study was potentially valuable because there is some follow-up. He said nobody on the ICC was opposed to probability sampling per se, but several members felt that non-probability sampling has generated tremendously valuable data. He said that the ICC’s sense was that it was not willing to reduce the scientific content of the protocol for the sake of probability sampling, but remarked that the question of representativeness was not necessarily the same for social science concerns.

• Dr. Zuckerman said he felt that the the Study should work out the strategies to see if a probability sample was practicable.

• James J. Quackenboss, M.S., ICC Member, Office of Research and Development, EPA, stated that he saw three issues: the representativeness of the cohort over time (changing demographic, how sample relates to cohort);, how effective adjustments for attrition can be;, and data validity expiration (avoiding selection bias).

• Mr. Swartz said that there were forces that will clamor for probabilistic sampling and would deny the validity of the Study if it does not recruit probabilistically. He asked if the ICC has looked at the political reality.

• Dr. Landrigan asked Dr. Klebanoff to summarize the achievements of the NCPP, noting that it is often derided. He said that Environmental Health Perspectives would be a good forum for such a discussion, but that the article should not mention the NCS. Dr. Landrigan said the Study should work on various cluster designs rather than continue to debate the sampling d’esign. He said that centers could serve as hubs for a clustered probabilistic model.

• Dr. Graham suggested that the organizing committee should include between one and three statisticians from the NCSAC.

• Dr. Mendola said that ICC looked at costs and benefits, and that the life-course nature of the Study meant that the internal validity of the Study cohort was perhaps the most important element. She remarked that random recruiting based on potential pregnancy was expensive and cumbersome. Dr. Little replied that a non-representative sample automatically called into question the internal validity, and that the issue of expense is divided into the sampling plan and the set of measurements, suggesting that the trade-offs were better if made on the measurements than on the sampling design.

• Dr. Spence said that someone on the planning committee, in addition to a statistician, needs to be familiar with the costs and difficulties of executing a given design. Dr. Daston noted that the political element was important and that any design would upset someone. He made the case that the NCSAC was perhaps not ready to decide on this.

• Dr. Kumanyika said she felt that the debate might not be constructive in terms of the NCSAC’s advisory function. She added that Framingham-type cohorts are not as acceptable as in times gone by. Dr. Klebanoff said that the Women’s Health Initiative tried to deploy a hybrid design, but gave up on the effort. He suggested they consult with the planners to find out what they learned.

• Dr. Michael admitted the problems with probability sampling were considerable, but did not see retention as very different across designs. He commented that bias induced by attrition could be statistically weighted for, and said the Study was a sine qua non for behavioral science. He mentioned an NIH grant he said he would not have obtained had the proposed sample not been representative, and said the NCSAC should simply offer its advice that the Study be representative.

Motion: We, the NCSAC, advise that the National Children’s Study be a probability sample of a defined population. The motion was seconded.

Discussion of the Motion

• Dr. Scheidt cautioned that the Study Design Working Group may have different opinions and that the current debate may be leavened by inclusion of Study Design Working Group feedback. He noted that the argument was not whether probability, but at what cost, especially if scientific elements would be dropped. He gave the example of placental collection, stating that previous experience suggested that obtaining placental tissue was difficult in the best of circumstances, let alone in dispersed populations. Dr. Scheidt said the ICC had initially considered including NCSAC membership on the planning committee, but felt that the urgency would preclude including members of the NCSAC due to limited availability. However, any NCSAC volunteers were welcome.

• Dr. Zuckerman made the case that a cost estimate for representative sampling should be established, and Dr. Mattison said that this did not differ substantially from Dr. Scheidt’s proposal with the exception of the NCSAC’s motion to recommend a probabilistic design.

• Tamar Lasky, Ph.D., NICHD, NIH, DHHS, asked about the terms "representative" versus "probability-based." Dr. Little discussed the importance of probability sampling for inclusion of the poor and minorities, who may not have access to major medical centers under the "medical center" model. He commented that the some tissue collections could be handled on a subset of the Study population, citing placental tissues as an example. Dr. Kumanyika stated that there should be an attempt at least to design a probability-based sample.

Final Motion: We, the NCSAC, advise that the National Children’s Study be a probability sample of a defined population. The motion was seconded. All except one voted aye, and one abstained. Drs. Landrigan, Little, Ryan, and Michael volunteered to staff the planning committee.

Report of Status of Pilots

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

Carole Kimmel, Ph.D., ICC Co-Chair
National Center for Environmental Assessment, EPA

Dr. Correa said that for the sake of the discussion, the term "pilot study" would be employed to indicate pilot studies, workshops, literature reviews, and white papers. On the subject of the rationale for the process, he noted that a number of methods and procedures will be needed, some of which are not currently available or are as yet unvalidated. His presentation included the following points:

• Among the pilots are studies of exposure studies looking at low-cost, low-burden monitoring strategies and exposures of children of California farm workers. Others will examine non-invasive means of collecting and storing tissues. Completed pilots include the Westat report on sampling strategies, a pilot that reviewed potential core hypotheses, and another for biomarkers. Workshops included those conducted to assess fetal/neonatal growth and development methods, drug/dietary supplement exposures, innovative technologies, and ethics.

• The sources of proposals for pilot studies include the NCSAC, the Working Groups, the ICC, the Program Office, the Federal Consortium, and the NCS’s lead agencies.

• The ICC’s Pilot Study subcommittee meets regularly to review proposals and make recommendations for funding. The process consists of three steps, the first of which is to review proposals. This entails selection of a primary reviewer from the subcommittee, who evaluates the relevance and urgency of the proposal. This work is presented to the subcommittee, which may modify the proposal or merge it with another, if appropriate. The second step involves further review and possible modification.. The third step is forwarding the proposal to the Program Office, which might suggest further modification and handles liaison work with the agencies for funding and execution.

Dr. Kimmel stated that the Program Office’s tracking system tracks each proposal and includes information not embodied in the original proposal. Data included in the tracking system are the source, the date of submission, the history of the proposal, and its current status. She said the December NCSAC included reviews of pilots, and the ICC subsequently ranked pilots.

• Some recommended high-priority pilots include those for lead sampling strategies, feasibility of 3D ultrasound to assess fetal development, methods for assessing newborn health, development and validation of growth and histological measurement instruments, and comparative value of fresh and frozen breast milk. The last will serve as a model for other surrogate tissue studies. Other pilots that may come through shortly include a pilot for maternal stress and pregnancy.

• Among the medium-priority pilots are those for subject retention methods, statistical methods for lifecourse studies, measurements of housing quality, and social influence on child health/development.

• Low priority items include measuring physical activity over time, rurality and child health, and a workshop on environmental exposure pending completion of a current study.

Questions and Comments for Drs. Correa and Kimmel

• Dr. Doswell asked about the status of an item that related to Dr. Camara Jones’ proposal. Dr. Kimmel stated that it was part of a set of hypotheses that was not fully tracked because of an earlier lack of a tracking instrument. She noted that the ICC seeks feedback from Working Groups on whether the ICC is in possession of the latest version of their pilots.

• Dr. Guerra asked if some hypotheses would be left out if duplicative of existing studies or those slated to come online. Dr. Kimmel said that they would. A meeting with the Center for Environmental Health Sciences (CEHS) was undertaken to avoid duplication of effort. Dr. Kumanyika asked how the list is organized. Dr. Kimmel said the document organizes items by importance rather than by thematic area.

Report from Joint ICC/FAC Executive Committee

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

Dr. Graham said the reason for assembling the Executive Committee was to handle the ICC’s need for faster feedback in procedural activity from the NCSAC than the quarterly meetings permitted. The Executive Committee roster and report was included in the Briefing Book. The document suggested interim activity to keep the NCSAC work moving, and that the purpose was to address processes rather than decisions. Dr. Graham’s presentation included the following points:

• The general communication procedure lays out a timetable for delivering materials to the NCSAC between meetings.

• There has been major improvement in the flow of information to the NCSAC due to the agenda-tracking document.

• The Draft Report on Federal Advisory Committee Processes outlines the formal review process. The document provides for, but does not mandate, attendance by Working Group members. Secret ballots are possible, and responders get a written response as to the rationale behind the vote. A simple majority is required for passage of a recommendation. When a request is tabled, the reason will be provided.

Questions and Comments for Dr. Graham

• Dr. Landrigan noted that the options listed in article nine should include one for recusalrefusal.

• Dr. Kumanyika asked about an agenda-planning committee to maintain momentum and avoid redundancy of ICC work.

• Dr. Spence said that greater detail of the ICC’s work would help avoid redundant work.

• Dr. Graham said that the roles and responsibilities discussion needed to cover the issuance of instructions to Working Groups and address publishing rights of NCSAC members. She added that a tracking device for decisions by the NCSAC is needed, and that the minutes should reflect those. Any further suggestions can be mailed to Drs. Graham, Mattison, or Scheidt.

General Discussion

• Dr. Mattison asked NCSAC members to look at the proposed letter to Working Groups regarding a NCSAC request for feedback to generate ideas to improve the conduct of the planning phase of the Study.

• Dr. Phillips asked if there was a way that Working Group members could see what materials did and did not make it into the Briefing Book. Dr. Scheidt stated that he was aware of one item that did not make the June Briefing Book because it was submitted late.

• Dr. Selevan proposed that the contents of each edition of the Briefing Book be published and archived on the portal. Whether the Briefing Book is required to be available to the public was discussed.

Motion: Dr. Graham moved that the Briefing Book be published on the Study Web site.

Discussion of the Motion

• Dr. Mattison said this should be presented as a recommendation by the NCSAC, but he did not discuss to whom the recommendation would go.

• Dr. Phillips and Dr. Kumanyika recommended publishing only the tables of contents, and Dr. Kumanyika addressed confidentiality of Working Group products. The discussion included a remark from an observer who commented that making documents available could help advocacy.

Final Motion: The motion to put the contents of the Briefing Book on the Study Web site passed.

Report of the Ad Hoc Subcommittee to Respond to the Letter from the Study Design Working Group

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

Dr. Dudley stated that the ad hoc subcommittee formed to respond to the Study Design Working Group letter included a good representation from epidemiology and sociology. He observed that Dr. Alexander’s comments generated different ideas in different individuals, and that most of the diseases were essentially biological with sociological factors. He presented a report from the ad hoc subcommittee for the NCSAC’s review. The report included the comment that the issue of biological versus sociological was "a false dichotomy," and recommended a probabilistic sample.

Discussion

• Dr. Zuckerman asked whether each exposure had two legitimate hypotheses, and stated that genetic elements could introduce additional hypothesis sets.

• Dr. Spence remarked that the Study is not a study of genes, but she reminded members that she had made the case that to fail to include some elements of genetics would omit critical information. However, the design models do not permit extensive genetic mapping. She stated that the NCSAC needs a geneticist.

• Dr. Mattison said that in the past, some Working Groups have not been as engaged as others, and that he felt that the NCSAC might more seriously engage the Gene/Environment Interactions Working Group.

• Dr. Spence said that the problem is deciding which genes to examine and how to examine them. She advocated a design that allowed for genetic evaluation rather than make genetics a driver of hypotheses.

• Dr. LeMasters recommended changing the word "biology" in the third paragraph of the subcommittee’s report to "epidemiology." She noted that the Study Design Working Group sought response to the driving theme of the Study, and Dr. Dudley agreed, but said that was not the charge of the subcommittee.

• Dr. Landrigan said the ad hoc subcommittee would have included a reference to genetics had it been charged with discussing it.

• Dr. Burton suggested revising the statement that social science was adequately represented to reflecting uncertainty as to the adequacy of such representation. She added that some scientists had experience in bridging biology and sociology and that they could be helpful.

• Dr. Phillips recommended the insertion of the term "life course" or "longitudinal" into the document, and suggested rephrasing "risk factors" as "risk and protective factors."

• Dr. Doswell said she favored inclusion of genetic factors in the NCS, and wanted to see the concerns of the public addressed at the risk of losing participants. She noted that some of their concerns would include whether they want to be informed of risk factors that medical science cannot address.

• Dr. Zuckerman said he was not sure how much genetic information would help public health, but that it would be clinically useful. He said that the central, driving theme of the Study should be at least in part, gene/environment interaction.

• Dr. Graham proposed that the September NCSAC meeting include a review of hypotheses for clearer discussions of race, gene/environment interactions, and other elements. However, she noted that some Working Groups might not be able to prepare adequately in time for the September NCSAC meeting. Those that cannot might insert a placeholder for gene/environment interactions. She further recommended dedicating three fourths of the meeting to hypotheses.

• Dr. Scheidt said that the comment about the false dichotomy between social and biological science was helpful, but that the Study Design Working Group should be more specific about what they feel is deficient. The ICC will handle the level of preconception sampling, and the Program Office will handle the final bullet point.

• Denise Dougherty, Ph.D., Agency for Healthcare Research and Quality, DHHS, said she had not heard any discussion of changes in healthcare services and their impact. Dr. Mattison said the NCSAC could propose this to a Working Group.

• Dr. Spence said some Working Groups tried to insert genetics without substantial backing of expertise and suggested again that a Working Group needs to examine this. She said there was no easy read on gene/environment interaction because the factors are not currently thoroughly mapped.

• Dr. Little asked if the words "disease" and "disorder" could be changed to "health outcomes." Dr. Spence said that the Working Groups have been looking at genetic issues, but that the committees lack genetic expertise. Dr. LeMasters recommended the NCSAC consider rewording the phrasing so as to address health systems outcomes. Dr. Correa said the Gene-Environment Interactions Working Group has expressed interest in working on hypotheses and would like a conference call on this. He noted that there are geneticists who feel the Study is too small to adequately address genetics. Dr. Spence said that some uncommon disorders need at least half a million in a genetic study.

• Dr. Mendola said that the perspective of the Study Design Working Group is that the Study should seek to link exposures to outcomes and not to evaluate healthy outcomes, because such work could be handled with a smaller study and/or with studies already in the field.

• Dr. Schoendorf said that the Working Group might have felt that they lacked information to effectively design a study. He added that the Study Design Working Group may not agree with the first two or three sentences of the ad hoc group report, but that the report imposes a framework that may facilitate work on the design, regardless of the range of opinions on how the Study should be designed.

• Dr. Burton said that the suggestions offered by several Working Groups on integrating social sciences into the Study were not intended to be prescriptive.

Action Item: Dr. Dudley will make several changes to the ad hoc committee document and circulate the amended report after lunch.

Discussion of Hypotheses

Dr. Mattison remarked that the hypotheses are sorted in order of their assigned priority status. He noted that if the two reviewers were of the same mind, their verdict would be accepted without dissent.

Tab 7: Autoimmunity Hypothesis

Dr. LeMasters, Dr. Spence, and Dr. Dudley

Dr. LeMasters said this hypothesis was relevant to the NCS, but that it needs a lot of work, which was echoed by Dr. Spence and Dr. Dudley.

Tab 8: Social Environment Working Group Hypothesis Series

Section 8.2: Family Influences on Child Health and Development

Dr. Bellinger and Ms. Jones

• Dr. Bellinger said the Working Group did a spectacular job, but saw 8.2 as too general. The hypothesis addressed familiar territory, but operational aspects were potentially innovative. He questioned whether the hypothesis rated as a core, but commented that the related measurements would serve a number of others. He noted that some of the measures may not need a cohort of 100,000 but that the additional subject burden may prove relatively low. He said this was more a structural feature of the Study than a core hypothesis.

• Ms. Jones stated her agreement with Dr. Bellinger, adding that the group should consult with the Development and Behavior Working Group regarding its hypothesis on parental actions.

Discussion

• Dr. Michael asked how to assure that this hypothesis is not lost for want of NCSAC approval. Dr. Mattison said it will be inserted in the tracking document, and that it will be reviewed further as the protocol develops.

• Dr. Doswell said that the hypothesis did not adequately include sub-populations and did not control well for SES. Dr. Mattison said that the NCSAC apparently saw a need to give each Working Group a look at all the hypotheses so as to encourage the kind of cross-pollination that will address the concerns of Dr. Doswell and others.

• Dr. Guerra said the hypothesis did not include any evaluation of the role of grandparents, who are an important presence in the lives of many children.

• Dr. Phillips said 8.2 should be a core hypothesis because of the importance of the matters addressed in the introduction.

• Dr. Ryan said some of hypothesis 8 was too finely sectioned.

• Mr. Swartz said that 8.4, which addresses social institutions, was not as strong as other sections. He noted further that the section covering religious organizations requires someone with expertise in order to avoid offending those of a religious persuasion, and that altruism should be a measure. Dr. Burton said they had looked at an overwhelming number of organizations and felt that unspecified impediments made it difficult to recruit someone with expertise in religiosity. Dr. Camara Jones made the case that churches are a vital social element in the lives of many and that the literature showed that children experience better outcomes when they demonstrate a strong affiliation with one or more of home, school, and church.

• Dr. Dudley said that environment had to do with SES, and that these should be correlated to the racism hypothesis. His biggest concern was the additional subject burden. Dr. Mattison said that the hypothesis-tracking document would give a sense of accumulatedsubject burden. Dr. Ryan said this hypothesis was intimately bound up with environmental factors and should integrate environmental and genetic factors.

• Dr. Mattison said that he saw the NCSAC’s position as that this should be a core hypothesis with added exposures to chemicals, etc.

• Dr. Graham said that this was quite a large hypothesis and could be integrated into hypotheses addressing specific health outcomes. She recommended that the Study include an examination of the influence of public health policies on outcomes, a reference to section 8.5.

• Dr. Spence said the hypothesis did not adequately address the potential change in policy. Mr. Swartz remarked that 8.5 addresses how different programs affect children at each stage, but did not account for changes in policy. He said the hypothesis should address those. Dr. Phillips said it was important that this be done well or it will result in misleading data, adding that a pilot study of administrative data might help flesh out a picture of actual use of programs.

• Dr. Camara MsJones said that the Working Group turned out a commendable piece of work and proposed that this set of hypotheses be woven in with others.

• Dr. Michael said the Study will have to be highly clustered in order to capture the data set needed for hypothesis 8, and that the size of the sample allows data partitioning that may prove instructive. Dr. Mattison said this had been a constant theme of the ICC. Mr. Swartz said that the questionnaires would be labor intensive.

• Dr. Kumanyika said the Working Groups do not seem to succeed in cross-fertilizing, and asked if the NCSAC should try to facilitate this. Dr. Mattison seconded the idea.

Dr. Mattison opened a discussion of healthcare policy as a theme.

• Dr. Phillips said this should be examined for policies that affect exposures and policies that act on those who interact with children. Dr. Guerra said this implied that the Study should look at those policies that need to be developed. Dr. Schoendorf asked whether policy has to be specified because such data are not collected from subjects. Dr. Landrigan disagreed, citing situations such as whether a subject lives in public housing.

• Dr. Michael said he would not use policy to define the Study, however important policy may be to health. Dr. Dudley recommended sending this to the Health Services Working Group.

Recommendation: Dr. Mattison recommended forming an ad hoc Working Group to make recommendations to the NCSAC in December.

• Dr. Little asked if someone from the U.S. Census Bureau could join the ICC to provide data on program participation. Dr. Scheidt remarked the idea was interesting and noted that the ICC had established criteria for membership that included agencies that provide funding. He added, however, that a number of agencies sought membership without a commitment of funds.

• Doris B. Haire, American Foundation for Maternal and Child Health, recommended adding a pediatric neurologist to the NCSAC.

Dr. Mattison closed the discussion without concluding remarks.

Tab 10: Injury Working Group Hypotheses

Dr. Mattison said these had been substantially modified from previous versions.

Section 10.1: Predictors of Child Maltreatment

Dr. Bellinger and Dr. Doswell

Dr. Bellinger said hypothesis 10.1 should be a core hypothesis, and Dr. Doswell said it should not be considered.

• Dr. Bellinger said this is not one hypothesis, but three classes of exposures, and that cost and respondent burden were high. The proposal entails observation of parent/child interaction, and Dr. Bellinger suggested that the pool of candidates for such observation be kept small. Reporting requirements costs were also said to be demanding.

• Dr. Doswell said this is an important question that may not need 100,000 subjects, and warned that when an abuse/neglect case is reported, the subject’s family will disenroll the subject. Dr. Mattison asked if the Working Group should be asked to provide an analysis of means by which retention is assured in such cases.

Discussion

• Dr. Foorman said that some research of violence at school and depression found that exposure to violence negatively correlated with academic achievement and appeared to increase the incidence of depression.

• Dr. Guerra said that SES was not addressed.

• Dr. Foorman said there was a lack of cultural frame to the hypothesis.

• Dr. Guerra added that social deprivation should be part of this hypothesis.

• Dr. Mattison said the NCSAC seemed to feel some concern about ethnic sensitivities and reporting issues that the hypothesis needs to address.

• Dr. Little commented that if injury is an outcome for the Study, the contribution of child abuse to this outcome suggests the need for including that exposure, but that ethical obligations will crop up when dealing with a child who has obviously been abused.

• Dr. Foorman said the full set of hypotheses was too fragmented and needed to be brought into a larger picture on the impacts of these settings on child health.

Recommendation: Dr. Mattison said these recommendations would be sent to the Working Group.

Section 10.2: Outcomes of Child Maltreatment

Dr. Foorman and Dr. Burton

Dr. Foorman said the hypothesis was lacking on design elements, and would like to see it framed in a broader context. Dr. Burton seconded without comment.

Recommendation: Dr. Mattison stated these comments would be sent back to the Working Group.

Section 10.3: Physical Aggression

Dr. Spence and Dr. Michael

Dr. Spence said this should be considered with "caveats." Dr. Michael stated he did not recommend it.

Recommendation : Not recommended at this time.

Section 10.4: Physical Environment and Injury Risk

Mr. Swartz and Dr. Landrigan

Mr. Swartz would not recommend this hypothesis. Dr. Landrigan agreed.

Recommendation: Hypothesis 10.4 is not recommended.

Section 10.5: Functional Outcomes of Injury: Influence of Antecedent Factors

Dr. Little and Dr. Kumanyika

• Dr. Little said this was a secondary hypothesis and asked about how this hypothesis defined injury. He said the hypothesis was interesting, but that it needs work and expressed concern regarding frequency and timing of measurements, given the unpredictable nature of the injuries addressed by this hypothesis.

• Dr. Kumanyika said the questions were interesting, but that the follow-up might need a separate protocol upon discerning an injury. She said there was almost nothing to vote on regarding this hypothesis because most of the measures are already in the protocol, and cannot make a recommendation.

Recommendation: Return to Working Group-not recommended at this time

Section 10.6: Cumulative Effects of Repeated Mild Traumatic Brain Injury

Dr. Guerra and Dr. Fleischman (not present)

• Dr. Guerra said this hypothesis addressed a legitimate area of concern, but that the work lacks specificity regarding the nature and origin of the injury, and there is tremendous difficulty in trying to gauge the force of impact. He mentioned that ERs have no consistent coding system for trauma severity and said inaccurate reporting could skew any numbers. He said there was a danger that medical providers may misinterpret routine injuries as child abuse. He did not recommend the hypothesis at present.

Discussion

• Dr. Dudley noted that this proposal looked familiar, and asked whether a pilot on mild traumatic brain injury was the subject of a pilot study. Dr. Mattison said the 10.x series included materials that had been reviewed, and confirmed that a pilot study on obtaining information from parental reports was underway.

• Dr. Scheidt said that members of NICHD’s Rehabilitative Medicine team cautioned about reporting bias, and that a lot of preliminary work would have to be done, including a workshop to see if the problems could be hurdled. He noted that a workshop to evaluate the feasibility of such work was scheduled for September 2003.

Recommendation: Return to Working Group and await results of Workshop.

Section 10.7: Psychosocial Environment and Injury Risk

Dr. Burton and Dr. Phillips

• Dr. Burton said this hypothesis is not ready; it needs work on the definitions of dependent variables and would benefit from collaboration with the Social Environment Working Group. Dr. Phillips agreed, noting that this mirrored the parental actions hypothesis.

Discussion

• Dr. Graham asked about the high rejection rate for injury hypotheses, and asked if any could be fused into others.

• Mr. Swartz said this was the second round of negative comments for injury hypotheses, and that the Working Group should consider collapsing them.

• Dr. Landrigan asked why a study of injury needs 100,000 subjects, and commented injury might not be a good fit for the NCS.

• Dr. Mattison proposed getting the co-chairs of the Injury Working Group to present their case. Dr. Spence seconded the suggestion.

• Dr. Scheidt reiterated that the area of injury is inherently problematic, and questioned whether the Study could do much with it. He said that at one point he floated a proposal to the rest of the ICC that injury should not be part of the NCS, but that the suggestion met great resistance.

• Dr. Mendola noted that injury and pediatric cancer were among the subjects of the President’s Task Force. Dr. Kumanyika asked if these were the only injury hypotheses currently under consideration, and Dr. Mendola commented that they were, with the exception of several inserted into the protocol by the ICC as placeholders. Dr. Kumanyika said that 10.5 perhaps should be developed, given that a cohort of 100,000 prospectively recruited subjects might be needed.

• Dr. Landrigan noted that injury was the subject of conflict before inclusion into the Task Force, but that at the time, no commitment was made to include it in a longitudinal effort.

• Dr. Guerra asked if the American Academy of Pediatrics had any working document looking at injury prevention. Dr. Scheidt said this was a high priority for the Academy.

Recommendation : Dr. Mattison said these comments would be reported back to the Working Group.

Tab 12: Longitudinal Assessment of Dental, Oral, and Craniofacial Disease and Conditions During Childhood and Adolescence

Dr. Zuckerman and Dr. Suarez (not present)

• Dr. Dudley said the Study needed something on dental care, but said this hypothesis was underdeveloped. He said a section on periodontal disease and preterm birth could be merged with a hypothesis on infection and preterm birth. He also recommended an evaluation of early dental caries and later periodontitis.

• Dr. Landrigan agreed and said that a clinician at the University of Rochester has been studying dental disease and could help develop this.

Recommendation: Hypothesis 12 was not recommended.

Tab 13: Eye and Vision Research and the National Children’s Study

Dr. Daston and Dr. Graham

Drs. Daston and Graham did not recommend this hypothesis, nor did Dr. Graham. This was suggested for further research and came from a group at Ohio State University.

Recommendation: Dr. Landrigan recommended a placeholder be established for vision, regardless of the fate of this hypothesis.

Report of the Ad Hoc Subcommittee to Respond to the Letter from the Study Design Working Group: Update

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

Dr. Dudley distributed a revised report and asked NCSAC members for comments within two weeks.

Program Office Presentation on the Study Timeline

Sarah Keim, M.A., Study Coordinator
NICHD, NIH, DHHS

Peter C. Scheidt, M.D., M.P.H., Study Director
NICHD, NIH, DHHS

Ms. Keim said that the Study had made its way into the startup phase, which runs to 2005 when enrollment will commence. She described the timeline as ambitious. Her presentation included the following points:

• The Study must begin implementation without sacrificing planning. Among considerations recently added are:
  - Community interests
  - Engagement of field investigators
  - Provision of startup time for sites (based on feedback from the
     Women’s Health Initiative)
  - Assurance that methods development and pilot study outcomes will be integrated
  - Integrating input from all partners.
  However, the plan is subject to change.

• Between now and 2005, the work will consist of protocol writing, reviewing, and refinement. Federal and local review and clearance will take place between November 2003 and August 2005. This will involve the Office of Management and Budget and institutional review boards.

• A coordinating function for clinical work will be developed by June 2004, as will efforts to establish a tissue repository. The NCS’s vanguard sites will be contracted by early 2005, and enrollment will commence later that year.

• Subsequent short-term steps will include fine-tuning the protocol, establishing remaining sites, bringing in further enrollees, and tabulating incoming data by 2008.

• The work in medical centers will include staff training and tweaking the Study to address local concerns.

• Ongoing concerns will be the quest for funding, the need to develop and sustain partnerships, putting tools in place to communicate evolving goals to partners, long-term pilot studies, and changes to the protocol driven by technological changes.

• Among the assumptions implicit in the timeline are that the sampling strategy is undecided, that funding in fiscal year 2004 and 2005 is adequate, that staffing is adequate, and that the peer review process keeps moving.

Dr. Scheidt said that major activities at the Program Office included frequent presentations, more than those discussed by Dr. Alexander. Communications planning is also a priority at the Program Office, and as well as the recruitment of staff at the Program Office, a task consuming a third of Dr. Scheidt’s time. Starting protocol development, the conduct of pilot studies, and technical support are also priorities at the Program Office. His remarks included the following points:

• Recruiting is most focused on the scientist for protocol development (the lead candidate already works at NICHD). A staff scientist/project officer may be available via NIEHS. The behavioral scientist position has drawn 25 viable applicants, 9 of whom have been screened; several are good candidates.

• Marion Balsam, M.D., will take the position of Director for Research Partnerships, a new position. Dr. Balsam’s background includes pediatric metabolism and extensive administrative experience with Navy healthcare.

• Term-limited staff positions include an epidemiologist (the work for which is currently handled by Dr. Schoendorf of the ICC) and environmental developmental toxicologist (handled by Dr. Kimmel, also of the ICC). The Program Office is looking into staffing for a biostatistician, an ethicist, and a geneticist (Dr. Scheidt has talked to Dr. Alan Guttmacher at the Genomics Institute, who said they could send someone to consult on genetics).

• The Program Office is in touch with a candidate, Terry Dwyer of Tasmania, for the senior epidemiologist position. Dr. Dwyer will shortly commence a one-year sabbatical from his home institution. Near future needs include a project officer for data management/clinical coordination center, several project officers for vanguard center, a contract officer for contract management, and a secretary.

• Funding uncertainty has tripped up much recruitment work and the Program Office has to dedicate resources to support the Working Groups and help Working Group members avoid conflict of interest issues. Contraction and consolidation of NIH administrative support is determined in part by a hiring freeze that cramps Human Resources and contract staff.

• Positives include:
  - The Study is the subject of increasing interest on the part of the scientific community
     and enjoys tremendous support from the leadership
     at NIH and NICHD.
  - The Study has unprecedented access to Dr. Alexander.
  - Technical support and contract support is superlative.
  - The ICC has turned in a tremendous effort and has been crucial to keeping the Study moving.

Questions and Comments for Ms. Keim and Dr. Scheidt

• Dr. Doswell asked about a partnership with the Bureau of Indian Affairs and the Center for Minority Health. Dr. Mendola said that engaging minority communities will be based largely on the results of focus groups and that the EPA’s Tribal Council is involved. Dr. Scheidt said that partnerships with other federal agencies are based on the Federal Consortium, which meets twice a year. At least 20 agencies are involved. He said more partnerships are needed for funding and to address special-needs groups.

• Dr. Graham asked about a quality assurance (QA) officer. Dr. Scheidt said that in the pProtocol planning outline, QA is prominent but not assigned a position. He said the Program Office had not concluded anything about whether such a function mandated hiring for such a position. Dr. Graham suggested Dr. Scheidt contact Nancy Wentworth at EPA.

• Dr. Landrigan asked about the impact of a change in sampling design on the vanguard centers. Dr. Scheidt said that the ICC had more or less assumed that vanguard centers would be needed in some capacity in order to avoid having to create a huge body of workers and capacity at NIH, regardless of the sampling design.

Public Comment

Dr. Mattison opened the floor to comments from the public.

• Ann Vinup, Learning Disabilities Association of America, said the materials in the folder presented at the meeting would make a great publicity item, and noted that anyone in Congress who hears from ten constituents on an issue is fairly likely to react. Dr. Mattison thanked Ms. Vinup and her organization for featuring the Study in its latest newsletter.

• Doris Haire, American Foundation for Maternal and Child Health, asked about public dissemination of reports from Working Groups. Dr. Mattison did not comment.

• Melissa Boychak, Office of Disease Prevention and Health Promotion, DHHS, asked if the title of the Study meant every state in the U.S. would be included. Dr. Mattison said this had not been determined, but that the Study will include as many states as possible.

• Dr. Landrigan asked about the status of similar studies in other nations. Dr. Scheidt said that the International Interest Working Group was active and sharing information on similar studies across national boundaries. There are roughly 25 members who will meet in Geneva, Switzerland in September 2003. The World Health Organization will underwrite the cost.

The meeting was adjourned at approximately 3:00 p.m.

NCSAC Committee Members

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

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

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

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

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

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

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

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

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

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

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

Loretta Jones, M.A.
Healthy African American Families

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

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

Grace LeMasters, Ph.D.
University of Cincinnati

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

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

Deborah A. Phillips, Ph.D.
Georgetown University

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

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

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

Daniel J. Swartz
Children’s Environmental Health Network

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

*Did not attend this meeting

Interagency Coordinating Committee Members

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

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

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

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

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

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

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

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

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

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

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

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

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

*Did not attend this meeting

Presenters/Speakers

Duane F. Alexander, M.D.
National Institute of Child Health and Human Development, NIH, DHHS

George Gaines
National Institute of Child Health and Human Development, NIH, DHHS

Peter J. Gergen, M.D., M.P.H.
National Institute of Allergy and Infectious Diseases, NIH, DHHS

Nancy S. Green, M.D.
March of Dimes

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

Camara P. Jones, M.D., M.P.H., Ph.D.
National Center for Chronic Disease Prevention and Health Promotion, CDC, DHHS

Nigel Paneth, M.D., M.P.H.
Michigan State University, College of Human Medicine

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

Observers and Other Participants

Christine Bachrach Marion Balsam Arthur Bennett Rosemary Chalk Donna Chen Stephanie Curenton Joan Cwi Elizabeth Davis Barbara DeVinney Linda Dimitropoulos Denise Dougherty Jonas Ellenberg Vivian Faden Mary Foulkes Alexa Fraser Adrienne Goslee Charles Grewe Doris Haire Leslie Hanrahan Hiroshi Hattori Joanne Hawana Raffael Jovine Jennifer Julock Jocelyn Kaiser

Susan Keane Tamar Lasky Akiva Liberman Lynn Luethke John Lutzker Victoria Moceri Judith Mopsik Ken Olden Sherri Park Jerry Rench Wendy Rueda Doug Rupert Fuki Saal Kathy Schneider Richard Sharp Angela Sharpe Christine Shreeve Patricia Smith Rebecca Sokol Karen Studwell Kristine Suozzi Ann Vinup Rueben Warren Ben Wilfond

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

 

July 28, 2003    Date

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