Overview

As the National Children’s Study proceeds, scientific knowledge will evolve and the Study will serve as an appropriate platform upon which to build additional scientific studies. Investigators from various sectors (such as academia, government, and industry) will propose adjunct studies. To assure the quality and integrity of the Study, such proposals will be reviewed and approved by a defined, rigorous process. Adjunct studies will enhance the breadth, depth, and value of the National Children’s Study and will assure continued interest of a diverse group of investigators, which is critical to the overall success of the Study. Adjunct studies will generally require outside (non-Study) funding.

Definitions

Adjunct Studies: An adjunct study involves a portion of the National Children’s Study cohort, utilizing individually or in combination, any of the following: the Study participants, their bio-specimens, their environmental samples. Adjunct studies can take place at one or more Study Centers, on all or a portion of their Center participants. Generally, adjunct studies will be initiated and planned outside of the Study protocol planning process and funded with non-Study funds; that is, by such mechanisms as government grants (e.g., NIH or other federal agency) applied for by the initiator, by intramural federal resources, through public private partnerships, or from other sources.

Requests for just data are not considered Adjunct Studies and should not be submitted to the Adjunct Studies Team, but rather to the Data Access Committee.

Outside-Initiated Additions to the Core Protocol: Formal proposals initiated from outside the National Children’s Study protocol planning process that pertain to the entire cohort are considered modifications of or additions to the core protocol and are therefore not adjunct studies. They are addressed within the Program Office protocol planning process. These additions or changes, once approved, will be incorporated into the core protocol through the core protocol planning process. If such proposals add cost to the Study, they will likely require outside funding.

Internal Adjunct Studies: In specific circumstances, the National Children’s Study may require, authorize, and fund specific adjunct studies to be planned outside the core protocol planning process, yet funded with Study funds. These are referred to as “Internal Adjunct Studies” to reflect internal (Study) direction, initiation, and funding despite external development.

Categories of Adjunct Studies

• direct interaction with National Children’s Study participants
• and/or analysis of  archived or current biologic specimens
• and/or analysis of archived or current environmental samples

or any combination of the above.                                                                                                                                

The core National Children’s Study is “minimal risk” research. Proposals for specific adjunct studies which represent “more than minimal risk” research with no prospect of direct benefit or intervention research with prospect of direct benefit (as in an embedded case control study) may be considered, but with more stringent review requirements and implementation oversight.–

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Requests for just data are not considered Adjunct Studies.

Human Subjects Considerations

National Children’s Study policies and procedures provide guidance on the requirements for separate (adjunct study specific) informed consent from National Children’s Study participants. All adjunct studies that involve additional interaction with human subjects will require separate informed consent. The adjunct study proposal must reflect the plan for informed consent for that project. When informed consent is required, the document will clearly inform that participation in an adjunct study is separate from the core Study and will clearly state the voluntary nature of deciding whether to participate. IRB approval will be required as appropriate.

Review of Adjunct Study Proposals

The National Children’s Study Program Office/Research Partnerships Program Director leads the formal process for review and approval of all adjunct studies. This is a two-tier approach with evaluation first of a brief Preliminary Application which, if it appears to be an appropriate adjunct study proposal, is then followed by a more in-depth Full Application. Several aspects of review will occur simultaneously to the extent possible in order to facilitate timeliness of review. (Requests for just data do not fall within the Adjunct Studies purview.)

To assure the quality and integrity of the proposed adjunct study and to assess its impact on the core Study and on the participants, specific areas of review include but are not limited to: scientific value, relevance and “fit” with the Study; burden to participants and to the Study infrastructure; appropriate use of precious biospecimens and environmental samples; risk, and other human subjects issues. Highest priority shall be given to studies that (1) relate to and enhance the core Study objectives; (2) have strong scientific and public health merit; (3) have potential for positive impact on healthcare practice or policy; (4) produce minimal burden on Study participants and Study Centers and do not unduly complicate or compromise the core Study; and (5) require the unique characteristics of the Study cohort such that there is mutual benefit.

There will be two main reviews to assess proposals for adjunct studies. The Adjunct Studies Review Group will assess the proposals in general, including the science, fit, and burden. The Sample Oversight Group’s focus will be specifically on the use of biospecimens and environmental samples, primarily from the perspectives of prioritizing best use of scarce resources and also whether that use is in accordance with the ”spirit” with which the specimens and samples were initially provided and consent given. Membership on these teams will include Program Office, Interagency Coordinating Committee and Study Center members, as well as other scientists, community representatives, and ad hoc members.

Upon National Children’s Study approval of the Full Application, documentation of that approval will be provided to assist proposers in seeking funding. Final approval to initiate the adjunct study will be contingent upon assurance of funding and completion of required reviews (e.g., IRB, peer review) as indicated. Adjunct Study proposals must include funding for Coordinating Center and Study Center support and administrative functions as necessary to carry out the project, such as retrieval of specimens from the repository, data retrieval, data analysis, etc.

The areas of review on the National Children’s Study Adjunct Study Application largely mirror the major areas in NIH Research Grant applications. The adjunct study application allows for ”cutting and pasting” relevant portions of those grant applications in order to minimize work. Funding details will be requested only after the proposal application is approved.

The National Children’s Study (Program Office) Adjunct Studies Team will work with investigators proposing adjunct studies to enhance opportunity for success of proposals. The Adjunct Studies Team will monitor the status of adjunct study applications, completion of appropriate reviews and documentation, receipt of funding, and initiation of the project. Progress reports will be required periodically from each adjunct study Principal Investigator (PI).

Participation of National Children’s Study Investigators as “National Children’s Study Co-Investigators”

Every adjunct study requires the participation of a National Children’s Study investigator as a “National Children’s Study (Adjunct Study) Co-Investigator.” This person’s essential role is to ensure accountability to the Study for that adjunct study’s use of Study participants, bio-specimens, and/or environmental samples and the related data. Potential Study Co-Investigators include Study Center Principal Investigators or designated (named in Study Center contract) senior members of their National Children’s Study team, and Program Office and Interagency Coordinating Committee (ICC) members. This Study Co-Investigator must be a named co-investigator of the adjunct study. When an adjunct study is based at a particular Study Center or Centers, the Center PI (or a named senior investigator on the Study Center’s National Children’s Study team, as designee) will generally serve as the Study Co-Investigator for that adjunct study.

At the time of application submission, some applicants may not know which Study Center(s) or Study Co-Investigators are most appropriate as collaborators for that proposal. Identifying or contacting a specific Study Center(s) and/or a potential Study Co-Investigator is not required prior to application submission; however, if proposers have a specific Study Center(s) and/or Study Co-Investigator in mind, they are encouraged to contact that Center or individual early in the process of developing the proposal. This would be advantageous in facilitating the review process. If not selected in advance, a Center(s) and Study Co-Investigator will need to be mutually agreed upon as part of the review and approval process. The Study Center(s), locations for carrying out the proposal, and the Study Co-Investigator must be approved prior to final approval of an adjunct study.

Data Access and Publications

As part of the full application, the proposer must agree to comply with National Children’s Study policies and procedures regarding data access and disclosure control (or confidentiality protection) as well as publication procedures. Access to adjunct study participants, relevant data, biospecimens, and/or environmental samples will be limited to that which is specifically pertinent to and authorized for the approved adjunct study. All publications will require approval by the Publications Subcommittee.

Timing

The current National Children’s Study timeline calls for Vanguard Centers to enroll participants for the Vanguard pilot phase from September of 2008 to January 2010. There will not be adjunct studies during the Vanguard pilot phase. Enrollment for the full Study is expected to begin in January 2010. Adjunct studies will pertain to the full Study. Thus, at this time it may be reasonable to consider adjunct studies for the pre-conception, pregnancy, newborn and early infancy time frames, for those participants enrolling as early as January 2010.

Applications for adjunct studies are available on this National Children’s Study Web site. The Tech Support Team is available to answer technical questions about filling out and submitting the electronic application, at NCSADJtechteam@mail.nih.gov or 301-402-1978. Questions about the Adjunct Studies Program should be addressed to the Adjunct Studies Team at NCSAdjunctStudies@mail.nih.gov.

These guidelines updated March 26, 2008.