From the aNational Children's Health Study, NICHD, NIH, Bethesda, MD; bOffice of the Director, NIH, Bethesda, MD; and cEunice Kennedy Shriver National Institute of Child Health and Human Development; Bethesda, MD.
Editors' note: Related articles appear on pages 598 and 602.
Correspondence: Steven Hirschfeld, National Children's Health Study, NIH, NICHD, 31 Center Dr, Room 2A03, Bethesda, MD 28014. E-mail: firstname.lastname@example.org.
The commentary by David Savitz and Roberta Ness1 reflects their interest in public health research and their perspective as former investigators in the National Children's Study. However, the National Institutes of Health (NIH) has made substantive changes in the design, operations, and governance of the National Children's Study beginning in the third quarter of 2009, which represent a departure from prior practice. We therefore welcome the opportunity to outline some of the major new strategic initiatives.
The National Children's Study is an unprecedented project that will follow a cohort of children from before birth to 21 years of age to examine relationships among the environment (broadly defined), genetics, growth, development, and health. What makes the study unique is the goal of collecting numerous environmental samples and biospecimens, as well as a wide range of anthropometric, behavioral, dietary, and health data (initially from mothers and then from their children). Experience from other studies can be useful to frame the parameters of this study, but the most reliable method for designing and implementing a public project of such scope and complexity is to be as data-driven and evidence-based as possible.
Following the recommendations of a National Academy of Sciences review panel, a pilot or “Vanguard Phase” was instituted in January 2009 with 2 locations, and then expanded the pilot to 5 additional locations by April 2009. By August 2009, pilot data indicated that the original study assumptions regarding the prevalence of pregnant women (and women likely to become pregnant, based on a screening instrument) were overly optimistic. In addition, the rate of identified pregnant women who consented to participate in the study, although a respectable 60%, was less than the 75% initially projected. On the basis of these early data, the overall efficiency of recruitment would have resulted in a prolonged recruitment phase with excessive costs.
Consequently, the Vanguard Study protocol was rewritten to emphasize the operational aspects of the feasibility, acceptability, and costs of recruitment, logistics, and study visit assessments. The recruitment assumptions were re-evaluated and 3 alternate recruitment strategies were designed.
These strategies are based on experience from published studies, expert advice, consultations with other federal agencies that have programs in demographic research or public-health surveys, and input from the multiple oversight bodies of the National Children's Study. The strategies are as follows: (1) an enhanced household recruitment approach; (2) a provider-based approach; and (3) a 2-tier, high-intensity/low-intensity approach. Each recruitment strategy will be deployed in 10 locations for a total of 30 new locations, and will receive approximately equal resources to examine their potential efficiencies, limitations, logistics, and costs. The provider-based approach reflects the “point-of-care” recruitment strategy raised by Savitz and Ness.1 We agree that this recruitment strategy has potential strengths, but we feel it must be tested empirically against recruitment strategies that have been successfully used and recommended by other advisers.
After recruitment for the Vanguard Study is completed and evaluated in the summer of 2011, the Main Study will be designed and implemented based on the Vanguard Study experience. The Vanguard Study and the Main Study will run in parallel for 21 years each.
During the third quarter of 2009, the National Children's Study Program Office was reorganized to incorporate a formal planning process directed by a planning team, with strengthened interactions with other components of the Eunice Kennedy Shriver National Institute of Child Health and Development (NICHD) and NIH. The Program Office has also assumed new responsibilities to improve consistency and provide cost savings.
In addition to evaluating recruitment strategies, the National Children's Study is evaluating specimen-collection methodologies. The Vanguard Study has already collected and stored over 120,000 environmental and biospecimens from the 7 original Vanguard Study locations. Samples from the inventory will be systematically examined during the second and third quarter of 2010 for stability, effects of collection methods, thawing conditions, and analyte profile to determine which methodologies provide optimal results. On the basis of analysis of the ability to collect, store, and analyze samples, a portfolio of potential samples for the Main Study will be identified. These candidate samples will be further evaluated in the ongoing Vanguard Study for the potential to inform public health questions and costs before final selection for Main Study inclusion. Additional candidate samples will be collected during the recruitment substudies to provide a broad range of options.
The National Children's Study is also implementing a different approach to study operations from the centralized approach previously in effect. For example, the informatics procedures are transitioning from proprietary platforms to a distributed open-source strategy in which the specifications and quality-control methods are determined centrally, the details of data collection are determined locally, and all the data are transmitted using uniform standards and formats to a centralized database.
The National Children's Study governance structure has many components. The Director of NICHD is the study lead. Operations are run by a Program Office at the NICHD, and the Principal Investigator is the Director of the Program Office. Oversight is provided by the NIH Director, a federal Interagency Coordinating Committee that meets monthly, a federally chartered Advisory Committee that holds quarterly public meetings, an independent Study Monitoring and Oversight Committee that meets twice a year, a Steering Committee of National Children's Study Investigators that meets twice a year, and an Executive Committee of the National Children's Study Investigators Steering Committee that meets monthly.
The revised Vanguard Study protocol, the alternate recruitment strategies, and the National Children's Study Program Office reorganization were discussed and vetted through all the components of the study's governance structure. The scientific and operational plans for the National Children's Study were further discussed with senior officials at the Department of Health and Human Services and in a series of briefings for the Office of Management and Budget and the staffs of relevant Congressional committees and offices. The revised protocol was approved by the Institutional Review Board of record and the NICHD Institutional Review Board, and sent to the study centers.
In conclusion, the National Children's Study has reorganized with a new, transparent governance mechanism, has adopted a data-driven and evidence-based decision-making approach, and is launching initiatives to generate the evidence to make informed decisions on the design and structure of the Main Study. In addition, the National Children's Study leadership (which includes the NIH Director, the Study Investigators and the Steering Committee, the various oversight bodies, and the collaborating federal agencies) are all committed to observe, listen carefully, evaluate the evidence, engage, and incorporate the voices of the communities and people interested and involved in the study, and establish a program based on the highest scientific, ethical, and fiscally responsible standards.
ABOUT THE AUTHORS
STEVEN HIRSCHFELD is a Captain in the United State Public Health Service and serves as the Associate Director of Clinical Research for the Eunice Kennedy Shriver National Institute of Child Health and Human Development and as Acting Director of the National Children's Study. BARNETT KRAMER is Associate Director for Disease Prevention and Director of the Office of Medical Applications of Research in the Office of Disease Prevention at the National Institutes of Health and Editor-in-Chief of the Journal of the National Cancer Institute. ALAN GUTTMACHER is Acting Director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and former Deputy Director and Acting Director of the National Human Genome Research Institute.