BRADS Program Synopsis

All investigators must submit a proposal to gain access to data and to biospecimens. Proposals will be evaluated on scientific merit by an ad hoc technical panel overseen by the BRADS committee.

No funding is provided as part of this program nor will any be available either to support laboratory analyses or data management. Samples will only be provided to approved projects upon receipt of evidence of necessary ethical approval(s), funding and payment of repository costs and shipping. Approved projects that do not obtain funding will be canceled within one year of their approval date. A more complete description of this program follows.

DATES:

Invitation to Submit Proposal: Proposals can be submitted on an ongoing basis.
Scientific Review Dates: Technical Panels for reviews will be assembled beginning on January 1, May 1, or September 1 of the calendar year so that proposals can be evaluated well in advance of federal funding deadlines.
Anticipated Distribution of Samples: Within one month of demonstrable proof of applicant IRB approval and receipt of payment to cover repository costs and shipping.

PROPOSAL PREPARATION:

Clinical Significance: Only research projects that propose laboratory results or findings in the ancillary data that do not have immediate clinical significance to an individual will be deemed acceptable.
Applicants should address this clearly in the research proposal.

Clinical significance for laboratory studies is defined by the following criteria:
- The findings are valid and done by a CLIA-certified laboratory, and
- The findings may have significant immediate implications for the subjects’ health concerns, and
- A course of action to ameliorate, or treat the concerns is readily available.
Clinical significance for ancillary findings is defined:

The findings may have significant immediate implications for the subjects’ or their family’s health concerns, and
A course of action to ameliorate, or treat the concerns is readily available.

Proposals for Use of Biospecimens and Access to Ancillary Data: All proposals for use of Division biospecimens and access to the ancillary data will be evaluated by an ad hoc Technical Panel for scientific merit. For ethical review, the BRADSC will generally rely on the investigators’ approval of their proposal by whatever institutional review is appropriate for their specified use of the biospecimens and access. The BRADSC, however, reserves the right in questionable cases to have the NICHD institutional review board (IRB) review the proposal even if the investigators have already had an ethics review at their institution.

Technical Evaluation Criteria: To determine if the biologic specimens (a limited resource) should be used in the proposed projects or if an applicant should be given access to ancillary data, an ad hoc Technical Panel, chosen and overseen by BRADSC and comprised of two content and one statistical reviewer, will evaluate the public health significance and scientific merit of each proposed research project. Applicants may be asked to suggest outside reviewers, but the final composition of the Technical Panel will be at the discretion of the BRADSC. Scientific merit will be judged as to the scientific, technical or medical significance of the research, the appropriateness and adequacy of the experimental approach, and the methodology proposed to reach the research goals. If the project involves biologic specimens, the Technical Panel will also consider the amount of sample requested and weigh the significance of the research against the amount of sample requested and that remaining. Investigators are encouraged to request the smallest amount of sample possible consistent with best scientific practices and the aims of their study.

The proposal should outline how the results from the laboratory analysis or findings from the original forms will be used. The appropriateness of the biospecimens to address the goals of the proposal will be an important aspect of scientific merit. The Technical Panel will review the analysis plan and evaluate whether the proposal is an appropriate use of the source material and likely to be successful. The Technical Panel will also assure that the proposed project does not go beyond the specific stated goals of the proposal. The Division website will have posted for each source lists of pertinent publications on their history and methods and scientific papers with notable findings.

Ethics Review: For proposed studies where the results of new laboratory analyses on existing biospecimens from the repository will only be linked to the existing completed datasets and there will be no contact (or contact is not possible) with the original study participants, an expedited institutional review or review through some other institutional mechanism may be sufficient, as long as the rationale for the decision is clearly made and documented. However, for proposed studies that involve any re- contact of original study participants, are part of an on-going follow-up of original participants, or where new linkages are being made with administrative or other publically available databases, a full IRB review is required. Specimens will not be released from the repository without documentation of review and institutional approval.

Procedures for Proposals: All investigators (including NIH and NICHD investigators) must submit a proposal for use of biospecimens. Proposals are limited to a maximum of ten (10) single-spaced typed pages, excluding figures and tables, using 12 cpi type density. The proposal should be comprehensive and tailored to the request and not simply be sections lifted from another federal or foundation application. The cover of the proposal should include the name, address, and phone number and e-mail address of the Principal Investigator (PI) and the name of the institution where the laboratory analysis will be done if they are a component of the project. All proposals should be e-mailed to the address specified on the website. Proposals must include a cover page with the title of the proposal and the name, address, phone number and e-mail address of all investigators. The following criteria will be used for technical evaluation of proposals:

Proposals should include the following information:

(1) Specific Aims: List the broad objectives; describe concisely and realistically what the research is intended to accomplish, and state the specific hypotheses to be tested.

(2) Background and Public Health Significance: Describe the public health significance, scientific merit and practical utility of the assay or information. Briefly describe in one or two pages the background of the proposal, identifying how the project may also relate to previous (published) analyses and gaps in knowledge that the project is intended to fill. State concisely the importance of the research in terms of the broad, long-term objectives and public health relevance including a discussion of how the results will affect public health policy or further scientific knowledge. The proposer should convey how the results will be used and the relationship of the results to the already collected and/or published. The applicant should include an analysis plan. Applicants are encouraged strongly to have a statistical consultant or someone knowledgeable about statistics be part of the investigative team or, nominally, review the plan before submission. The analyses ought to be consistent broadly with the study aims and the health status variables.

(3) Research Design and Methods: Describe the research design and the procedures to be used. Data and/or biospecimen requests should specify the exact variable(s) or sample name(s) as provided in the documentation or give an expectation of findings in archival material. If there is a laboratory component, a detailed description of laboratory methods including validity and reliability must be included with references. Because the samples were collected previously, applicants should consider how aging might have affected the samples. Even if the proposal is meritorious, the BRADSC may expect, upon advice of the Technical Panel, that a pilot be completed before all specimens requested are released to the investigators.

The volume of specimen and number of samples requested must be specified. Adequate methods for handling and storage of samples must also be addressed. The laboratory must demonstrate expertise in the proposed laboratory test including the capability for handling the workload requested in the proposal. The proposal should also include a justification for determination of study sample size or a power calculation. If the researcher is requesting a regional or targeted sub-sample of specimens, a detailed description and justification must be given. The study design and analysis plan in the proposal will be evaluated to determine whether the project is feasible and can be performed using the source material.

(4) Clinical Significance or Results: Since individual results cannot be provided, the clinical significance of the proposed laboratory test should be addressed. The proposal should include a discussion of the potential clinical significance of the results and whether there is definitive evidence that results of the test would provide grounds for medical intervention even given that many years have passed since the examination of the participant and collection of the sample. Any test with results that should be reported immediately to a participant is not appropriate for testing on the stored samples.

(5) Qualifications: Provide a brief description of the Principal Investigator and other investigators’ expertise in the proposed area, including publications in this area within the last three years. A representative sample of earlier publications may be listed as long as this section does not exceed two pages.

(6) Period of performance: Specify the project period. Substantial progress must be made in the first year, and the project should be completed in two years. If additional time is needed for the research project a detailed justification with a timeline should be included. The investigators should address their ability to comply with this timeline or request and justify additional time for the project. Return of the specimens will be requested if progress is not made in the project at the end of the second year.

(7) Funding: Include the source and status of the funding to perform the requested laboratory analysis should be included. Investigators will be responsible for the cost of processing and shipping the samples. The basis for the cost structure is in the last section of this notice. Reimbursement for the samples will be collected before the samples are released.

Submission of Proposals: Proposals can be submitted in MS Word or pdf format by e-mail to the designated Chair of the BRADSC.

Summary of Evaluation Criteria:

Approved Proposals: Approved projects using data only need to have a signed Data Use Agreement (DUA) . Projects that involve specimens need to have a signed Materials Transfer Agreement (MTA). The cost of retrieving specimens from the NICHD Repository needs to be negotiated with and paid directly to the NICHD Repository. The BRADS Committee will help you complete the necessary documents. Approved projects will be provided specimens upon receipt of a check to cover the cost of accessing, preparing, and shipping the specimens. Approved projects requesting access to the ancillary material, such as microfiche archives, will be granted access once arrangements have been made with the Division. Approved and funded projects will be posted by title and abstract on the Division website once specimens have been shipped. Note that biospecimens will be distributed blinded, that is, with an identifier that will only be linked to the study identification number upon completion of laboratory analyses, unless arrangements have been made for interim analyses beforehand.

Progress Reports: Brief progress reports must be submitted annually to judge progress.

Disposition of Results and Samples: No samples provided can be used for any purpose other than those specifically requested in the proposal and approved by the Technical Panel. No sample can be shared with others, including other investigators, unless specified in the proposal and so approved. Any unused samples must be either discarded or returned to the Division Repository, according to the wishes of the BRADSC upon completion of the approved project.

Proposed Cost Schedule for Providing Biospecimens: A nominal processing fee of approximately $8.00-$16.00 per sample, plus express shipping costs is anticipated for each sample requested and received. Costs will be fully estimated at the time of proposal acceptance and will take into consideration time and materials for the collection, storage and processing of the specimens by the Division Repository along with the preparation of the accompanying data files. The material costs are for the recurring laboratory costs to dispense and prepare the samples during collection and the computer software needed for the preparation of the data files. Because size of the shipments and distance to laboratories may vary, shipping costs will be estimated at the time of proposal acceptance. Cost reimbursement structures negotiated and accepted as part of a final proposal acceptance will be honored for one year from the date of proposal acceptance.

Proposed Cost for Accessing Ancillary Materials: There is no direct cost for accessing ancillary materials, such as microfiche archives, although arrangements will have to be made for access to the building and is dependent upon the space available to accommodate a researcher.