Adjunct Studies 

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, involving individually or in combination, any of the following: the Study participants, bio-specimens, and/or environmental samples. Adjunct studies can take place at one or more Study locations, involving all or a portion of the location participants but not all participants at all locations. 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), by intramural federal resources, by public private partnerships, or from other sources.

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 and the Working Teams, not through the adjunct studies process.

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 participants
• and/or analysis of stored, current, or future biologic specimens
• and/or analysis of stored, current, or future environmental samples

Requests for existing data only are not considered adjunct studies. 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 requests for intervention research with the prospect of direct benefit (as in an embedded case control study) may be considered, but with more stringent review requirements and implementation oversight.

Human Subjects Considerations

All adjunct studies that involve additional interaction with human subjects will require separate (adjunct study specific) informed consent which must clearly state that participation in an adjunct study is voluntary. The adjunct study proposal must reflect the plan for informed consent. Local IRB approval(s) 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 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.

The review must assure the quality and integrity of the proposed adjunct study and 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) 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, Centers, and locations;(5) do not unduly complicate or compromise the core Study; and (6) require the unique characteristics of the Study cohort such that there is mutual benefit.

The Adjunct Studies Review Group will assess the proposals in general, including the science, fit, and burden. In addition, for those studies that propose to use biological specimens or environmental samples, the Sample Oversight Group will review the proposal primarily from the perspectives of prioritizing best use of scarce resources and also whether that use is in accordance with the “spirit” with which these materials were initially provided and for which consent was given. Membership on these groups will include Program Office, Interagency Coordinating Committee, Study Center, and Study location members, as well as other scientists, community representatives, and ad hoc members.

Funding details will be required only after the Full Application is approved. Upon approval of the Full Application, documentation of National Children’s Study approval will be provided to assist proposers in seeking funding. Final approval to implement the adjunct study will be contingent upon documented assurance of funding and completion/approval of required reviews (e.g., IRB, peer review) as indicated. Adjunct Study proposals must include funding for Coordinating Center and other support and administrative functions as necessary to carry out the project, such as for specimen retrieval from the repository, data retrieval, data analysis, etc. Guidance will be provided to assist in these estimates.

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 Co-Investigator.” This is distinct from co-investigators who are proposing the adjunct study. The National Children’s Study Co-Investigator’s role is essentially to facilitate the application process and assure accountability to the Study for that adjunct study’s use of participants, bio-specimens, environmental samples, and related data. Potential National Children’s Study Co-Investigators include Study Center/location Principal Investigators or designated (named in contract) members of their National Children’s Study team, or alternatively Program Office or Interagency Coordinating Committee (ICC) members. This National Children’s Study Co-Investigator will be a named co-investigator of the adjunct study. When an adjunct study is based at a particular Study location(s), the location PI (or named designee) will generally serve as the National Children’s Study Co-Investigator for that adjunct study. If an adjunct study takes place at more than one location, then each additional location will have a named “Facilitator” to work with the National Children’s Study Co-Investigator to facilitate aspects of the specific adjunct study at each location.

At the time of application submission, some applicants may not know which Study location(s) or National Children’s Study Co-Investigators are most appropriate as collaborators for that proposal. Identifying or contacting a specific Study location(s) and/or a potential National Children’s Study Co-Investigator is not required prior to application submission; however, if proposers have a specific Study location(s) and/or National Children’s Study Co-Investigator in mind, they are encouraged to contact that location early in the process of developing the proposal. This would be advantageous in facilitating the review process. If not selected in advance, a National Children’s Study Co-Investigator and location Facilitator(s) will need to be mutually agreed upon as part of the review and approval process. The Study location(s) for carrying out the proposal and the National Children’s Study Co-Investigator/Facilitator(s) 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 confidentiality as well as publication procedures. Requests for just data are not considered adjunct studies and should be submitted to the Data Access Committee rather than the Adjunct Studies Team. Adjunct Study investigators who require access to data (in addition to participants, specimens, or samples) will need to apply to the Data Access Committee for a “license” for restricted use data as part of the adjunct studies application process. 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 National Children’s Study Publications Subcommittee.

Timing

Ideally, investigators should review the core protocol for the applicable time period and review data access and confidentiality, publication, and laboratory related policies prior to submitting an adjunct study application. Check the National Children’s Study Web site for updated information about the timeline. Adjunct studies will pertain only for the full Study; not for the preceding Vanguard pilot phase. Thus, at this time it may be reasonable to consider adjunct studies within the timeframe of the developed protocol: pre-conception, pregnancy, newborn, and early infancy. Ideally, investigators should submit only those proposals with approximate study and/or sample onset within the approximate timeframe of the developed protocol. This will enable better prioritization of competing projects and more insightful judgment about core content and needs. Upon approval, the National Children’s Study resource commitment (“reservation”) will be one year from the time of National Children’s Study approval to the acquisition of funding and other required approvals (e.g., IRB, etc.) after which a request for extension must be submitted.

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 completing 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.