NIDDK supports research on topics that encompass severe, rare, and common conditions affecting Americans today: endocrine and metabolic diseases such as diabetes and obesity, digestive diseases such as hepatitis and inflammatory bowel disease, kidney and urologic diseases such as kidney failure and prostate enlargement, and blood diseases such as the anemias. Many of the large clinical studies funded by NIDDK collect specimens from participants for analysis and future research. Specimens collected for future research from these studies serve as a valuable resource and are made available through NIDDK-CR to the research community. Use of these specimens helps to ensure that research participant contributions have an enduring impact and decreases duplicative sampling efforts.

Qualified investigators interested in submitting a request for NIDDK-CR specimens must first register with NIDDK-CR. Investigators interested in potential access to specimens must request a Volume and Impact Assessment Report, also known as an Availability Inquiry, which provides information about the availability and potential depletion impact of their planned request. Access to renewable and non-renewable specimens with highly abundant, modestly depleting resources may be granted via an internal review process if the request is considered to have a reasonable likelihood of achieving the proposed research aims. Requests for more than modestly depleting non-renewable specimens require a full grant-like application and independent scientific merit review. All qualified investigators may request access by submitting a grant-like application to the NIDDK-CR External Specimen Access Program as detailed below. These applications are accepted on a rolling basis.

NIDDK-CR has implemented various review pathways to reduce barriers to access. Eligibility for the different review access pathways is based on funding status and specimen availability, specifically the depletion risk that the study-specific specimen request will have on the remaining collection, as described in the Availability Inquiry report:

• Administrative Reviews: Investigators seeking access to “modestly depleting” specimens, those that will deplete the specific specimens by less than 10%, and have funds to complete the proposed project, may be eligible for an internal administrative review process. These reviews are generally expedited, within 30 days of submission, and require additional documentation, such as proof of funding and ethics approval documentation, before proceeding with fulfillment.
• Full Reviews: Investigators seeking access to “moderately-depleting” specimens, meaning those that will deplete any specific specimen by 10%, but no more than 25% (also known as non-depleting specimens) and “Significantly-depleting” or depleting, meaning those that will deplete the specific specimens by 25% or more, will require a full grant-like application. Details about the application and review process are provided below. Complete applications are typically reviewed within 60 days of submission, and Access Letters are generated within 90 days. These Access Letters of approval are required to submit an Access Request in NIDDK-CR Resources for Research (R4R) for specimen processing and fulfillment. Investigators planning to submit NIH or other grant applications for funding their study may undergo a shortened, secondary review after funding is secured if: (a) an Availability Inquiry report was included with the funding application, and (b) the outcome of the independent scientific review is included with the application package.

It is critical that investigators seeking access read and follow the instructions provided below. Applications that do not comply with these instructions may be delayed or returned without review.

According to NIDDK-CR policy and applicable NIH or U.S. Government policies, all qualified investigators are eligible to apply for specimens through the External Specimen Access Program. Any qualified investigators interested in taking advantage of this program must submit a complete Application package as detailed below, along with a recent (< 1 year) Availability Inquiry report to NIDDK-CRadmin@niddk.nih.gov for consideration by designated review access committees. Availability Inquiries must be submitted in advance of a formal application for access to determine whether there is sufficient quantity of specimens for the proposed project. Applications without an accompanying Availability Inquiry report will be returned without review. Additional documentation may be requested/required. In addition, Requestors are encouraged to consult NIDDK Program Staff in their research area of interest to help with any limitations of the contributing study’s design, and must consult NIDDK-CR website to pre-determine whether the proposed use of specimens and associated data is consistent with the limitations of the participants’ informed consents.

NIDDK has delegated final distribution authority to NIDDK-CR. NIDDK-CR may grant access to specimens requested in new and revised applications based on recommendations of the designated review access committees. Approvals for access depend on the alignment with the contributing study’s informed consent use limitations, scientific merit, the availability of requested specimens, and feasibility to complete the project. Successful applications will receive an Access Letter, which can be used to submit an Access Request on NIDDK-CR R4R website, and will be required to abide by the terms and conditions of access stipulated in the Data and Resources Use Agreement (DUA). The External Specimen Access Program only provides access to research resources and does not provide funding. Therefore, proof of funding to complete the proposed work is required to proceed with the request fulfillment process.

Application packages for NIDDK-CR External Specimen Access are required for the Full Review pathway. Packages should include a Research Plan, limited to three pages with the following components:

1. Background: Provide relevant information to justify the request and the Research Project being proposed.
   1. Scientific premise, including the importance of the research question and the potential impact of the project.
   2. Rationale for selection criteria, including how the specimens and data being requested will accomplish the aims of the proposed Research Project. Please note that although the new research being proposed does not need to be associated with the contributing study’s design and outcomes, it should take into consideration its limitations including the original design, how specimens were collected, prepared, analyzed, and stored, their age, outcome variables, and the accompanying data and metadata as part of their rationale for the selection of the specimens.
   3. Relevant preliminary data demonstrating the investigator(s) experience with the assay or technique that will be used.
2. Objectives and Design: Provide relevant information about the proposed research question, methods, and justification for the requested study.
   1. Include detailed and specific information about specimens, such as the number of participants, the number of vials, volumes, etc., and a clear justification for the requested amounts and sample size. In all cases, investigator(s) should only request the minimum volume and number needed for their study that will yield scientifically valid results.
   2. There should be at least one specific hypothesis that will be tested using the proposed methods and non-renewable specimens.
   3. Describe the specific procedures by which the specimens and data will be tested and analyzed. Explain any methodology limitations as applied to these specific specimens and data, and address the feasibility of accomplishing the aims.
   4. Describe the power of the project and its ability to answer the proposed question.
3. Analysis Plan: Provide a detailed plan for data analysis, the team’s expertise and experience, and project timeline.
   1. Describe how the accompanying clinical and phenotypic data, as well as the data generated from specimen analysis, will be managed. Include practices to organize, store, and archive data in a secure manner in accordance with NIH guidance for controlled-access data, and highlight team’s experience relative to new data that will be generated by the proposed project.
   2. Explicitly address how specimens will be stored, managed, and processed. Include information about the scientific environment, institutional support, and security infrastructure to support the proposed project, including all assays and data analyses to be conducted.
   3. Describe the team's roles and responsibilities, including a brief summary of their experience and expertise to perform the proposed analyses and describe plans and feasibility to accomplish the aims within the maximum project time.

      Please be reminded that access to research resources is granted for an initial period of 1 year. Access may be renewed if there is demonstrable forward progress. This should be considered in the project timeline.

4. Resource Management and Sharing Plan: Provide specifics on how new Materials generated will be stored and managed to meet the expectations of NIDDK-CR policy.
   1. The investigator(s) are expected to have a plan to return Materials directly derived from the analysis of specimens and data received from NIDDK-CR and to implement appropriate quality measures to facilitate their return to NIDDK-CR. The first generation of new Materials may be included in NIDDK-CR or another NIDDK-approved public repository at the discretion of NIDDK. The plan should acknowledge this requirement and to follow NIDDK-CR instructions at the end of the Research Project or termination of the use agreement.
   2. Materials earmarked to be deposited in NIDDK-CR must follow NIDDK-CR submission guidelines. Use of Common Data Elements (CDEs) is strongly encouraged.
5. Human Research Participant Considerations: NIDDK-CR resources are de-identified in a limited data set format, and their use does not result in a NIH-defined Human Subjects Research designation. However, resources may be subject to a Certificate of Confidentiality (COC) and/or the Genomic Data Sharing (GDS) policy. Requestors must include a statement of how the proposed Research Project fits within the authorized uses and restrictions of the informed consent. Information about informed consent use limitations can be found on the NIDDK-CR website. If the applicant has access to identifiable information from the contributing study, they must include relevant human research protections elements.

All complete applications will be reviewed by designated NIDDK Program Staff reviewers with the subject matter and scientific expertise, and by members of the NIDDK-CR resource access oversight committee and Repository Program Directors Committee, a subcommittee of the NIDDK-CR Executive Committee, in accordance with NIH and NIDDK-CR policy.

NIDDK-CR strongly recommends that Requestors consider the Overall Impact and Review Criteria delineated below while preparing their application package.

NIDDK Reviewers will consider the below in their critique:

1. Overall Impact: Reviewers will provide their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).
2. Review Criteria: Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate criterion assessment for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.
   1. Significance: How appropriate is the significance of the proposed project in relation to the impact on the number/amount of specimens that will remain in NIDDK-CR, such that projects that will substantially deplete the collection are appropriately significant?
   2. Investigator: Has the Requestor demonstrated familiarity with the contributing study that produced the resources being requested to appropriately address any limitations?
   3. Innovation: Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?
   4. Approach: How are the requested specimens uniquely suited for the proposed project? How does the proposed project take advantage of the associated data? Do the preliminary data demonstrate the accuracy and robustness of the proposed assays, and is the project feasible as applied to these specific specimens?
   5. Environment: Will the scientific environment in which the work will be done contribute to the probability of success? Is the institutional support, equipment, and other physical resources available to the Requestor adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements? Are security measures per NIH/NIDDK guidelines in place to store and analyze controlled access data?
   6. Study Timeline: Is the project feasible to be completed in the proposed time?
   7. Human Protections: Is there appropriate ethics clearance/approval? Any potential group harm to research participants who contributed (source of the requested specimens and data)?
   8. Resource Management and Sharing: Reviewers will comment on the validity and feasibility of the brief plans to implement quality measures to facilitate the return of new Materials generated as a direct result of the analyses back to NIDDK-CR or another NIH/NIDDK-approved repository. In addition, reviewers will consider the applicability and consideration of any NIH resource sharing policies, such as GDS and model organisms.

1. If the application is approved, a formal notification in the form of an Access Letter will be sent to the Requestor and Requesting Institution. The letter can then be used to submit an Access Request on the NIDDK-CR Resources for Research (R4R) website for processing and fulfillment. Any application for NIDDK-CR specimens granted access through this research resource access program will be subject to NIDDK-CR Policy, NIDDK-CR User Code of Conduct, and the terms and conditions of the DUA that the Requestor and their Requesting Institution’s legally authorized representative (AOR) will sign. The Requesting Institution must ensure that protocols are reviewed by their Institutional Review Board (IRB) or Independent Ethics Committee (IEC) to help ensure the safety and data security of participants enrolled in NIH-funded research. IRB/IEC documentation is required to gain access to NIDDK-CR Resources. Access is contingent on confirmation of funds to support analyses of NIDDK-CR specimens. Requests without Access Letters, proof of funding, and evidence of ethics review will not be processed by NIDDK-CR support staff.
2. Requestor and Requesting Institution will be responsible for submitting an annual Progress Report one year from the effective date of the signed agreement via the NIDDK-CR R4R website and every year thereafter until project closeout or termination.