Frequently Asked Questions About NIDDK Central Repository

Who can submit data and specimens to the NIDDK Central Repository?

In general, NIDDK supported clinical studies, including but not limited to clinical trials, prevention and control trials, and epidemiological studies, with significant programmatic involvement will have within the terms and conditions of their funding award a requirement to share and make available to the public the study data, and if applicable, a representative archival set of specimens for future research use. These studies may be eligible to deposit the data generated and a portion of the associated specimens into the NIDDK-CR when conditions for submission are met. Other NIDDK-funded and non-NIDDK funded studies may also be eligible to deposit data and a representative archival set of specimens for future research use depending on the relevance of the collections to NIDDK’s mission, and the benefit to the broader scientific community. Studies may deposit data only, or data and specimens. More information can be found in the NIDDK-CR policy in Section 2.1. Researchers can also reach out to NIDDK-CR’s Support staff for additional information about eligibility and submission requirements.

Are completed or currently ongoing NIDDK-funded multi-site studies required to submit data and specimens to the NIDDK Central Repository?

NIH policy is that scientific data (resources) generated through NIH funding are to be shared with the research community, to the extent that sharing of data and materials is practical. Therefore, all current and complete multi-site NIDDK-funded studies should have a plan or should develop a plan for sharing data and specimens with the broader scientific community that complies with current NIH and NIDDK policies. Wherever appropriate, the NIDDK-CR or an NIDDK-approved repository should be used to facilitate sharing.

Are requestors of renewable or non-renewable specimens required to submit new data or specimens generated into the NIDDK Central Repository?

In accordance with the signed user agreements, requestors seeking access to NIDDK-CR held resources may be required to submit materials generated or produced in the conduct of their Research Project to the NIDDK-CR. All requestors are expected to manage the data as if the analyses were going to be eventually deposited back to the repository for sharing (i.e., with the necessary level of quality), although acceptance to deposit is not guaranteed and is at the discretion of NIDDK. At a minimum, requestors should provide an accompanying codebook/data dictionary and any documentation on procedures/analyses performed so future users will meaningfully understand and be able to use the resulting data.

I am an investigator with an NIDDK sponsored R01, is my grant eligible to deposit my data or specimens into the NIDDK Central Repository?

Investigators funded by an R01 are encouraged to deposit and make resources available to the community via data type specific or generalist repositories adhering to NIH Data Management and Sharing (DMS) Policy and NIDDK DMS Guidance for selecting an appropriate repository. In general, investigators funded through individual R01s will not be eligible or expected to submit resources into NIDDK-CR. There are instances when an R01 grant that transitions to or from a larger multi-site study funded via a cooperative agreement, or is an ancillary study to a cooperative agreement, may be eligible to deposit resources into NIDDK-CR, if the resources generated via the cooperative agreement will be submitted to or are under the guardianship of NIDDK-CR. A list of possible repositories can be found on the External Links page.

Are there any costs associated with depositing resources in the NIDDK Central Repository?

Studies eligible to deposit resources, may do so at no additional cost to the contributing study, meaning, NIDDK-CR does not normally charge for the transfer and curation of data, or for the transfer and accessioning of specimens. Moreover, NIDDK-CR will cover the incoming shipping costs of the specimens (shipping boxes and waybill). NIDDK-CR does not cover costs associated with reconciling and prepackaging data for deposit, nor the costs associated with collection, processing, local storage, retrieval, sorting, and packaging specimens for transfer.

What is the proprietary period for stored data and specimens?

NIDDK Central Repository Resource Archival and Sharing Policy seeks to balance the interests of the contributing study investigators and those of the larger scientific community by setting defined proprietary periods. The proprietary period for each study will be mutually agreed upon by the study leadership and NIDDK-CR in writing. NIDDK-CR policy requires a written protocol-level Resource Archival and Sharing Request before participants are enrolled that establishes submission and public sharing timeframes and proprietary periods per NIH Data Management and Sharing Policy.

In alignment with NIH DMS policy, NIDDK-CR policies and procedures support initial and continuing access by the contributing study investigators, but not of prolonged and exclusive access, thus encouraging timely release and sharing of study generated resources. This should include both data and a corresponding set of specimens to be submitted and made available for access by the scientific community.

What data should be sent to the NIDDK Central Repository?

Contributing studies should submit, with appropriate participant consent, all data collected, associated metadata, data attributes, and analysis datasets. Data are to be submitted as defined in 45 CFR 164.514(e)(2) for limited data set format (LDS). The NIDDK-CR has opted to receive data in LDS format because data are devoid of direct identifiers, although retain other elements permitted by HIPAA that allow NIDDK-CR to manage and share the data and associated specimens more responsibly over time. More information about data and documentation submission guidelines can be found under the Data Submission Guidance page.

What is a linking or linkage file? When should the linkage file be provided?

A linkage file is a list that associates (walks-through) the specimens with the relevant clinical data, and/or metabolomics, proteomics, sequencing, or genomics data, by matching the IDs that were used for the specimens to those that were used for the clinical data for all of the study participants. The linkage file and the key to decode information on the specimen labels is not normally shared with outside requestors and is held privately for internal NIDDK-CR use only. The linkage file should be provided by the contributing study at the time the clinical data are submitted to NIDDK-CR.

What interaction will the study have with the NIDDK Central Repository to prepare data for archiving?

The Data Repository component will work with the contributing study team to prepare the dataset for archiving, and to develop appropriate documentation that is comprehensive and will allow investigators not familiar with the study data to use it.

Which specimens should be sent to the NIDDK Central Repository and when should those specimens be sent?

The Biorepository component accepts a wide variety of specimens with some of the most common being serum, plasma, urine, tissue, DNA, and stool. Eligible studies approved to submit specimens to the NIDDK Biorepository should submit a representative archival set of specimens from all consented participants for future research use along with the specimen metadata and biological attributes. A representative archival set is defined as a set of specimens that includes a portion of every material type collected at every timepoint from every consented participant. Contributing studies are encouraged to submit the archival set at regular intervals during the active study period, determined by participant and specimen accrual rates, rather than at the end of the study. In general, the Biorepository should not be used to store specimens that are being used for the active conduct of the study to meet main study, sub-study, or ancillary study aims. The Biorepository does not serve as the primary repository to support the day-to-day needs of active or ongoing studies, with few exceptions. In rare instances, and as determined by NIDDK Program and Repository personnel, specimens stored at the Biorepository as part of the archival set may be made available to the contributing study if needed to meet study-related aims.

Who has oversight and decision-making authority of the specimens at the NIDDK Central Repository?

For specimens held at the Biorepository that are under the guardianship of NIDDK-CR, decisions related to access and release are governed by established NIDDK-CR policy, processes, and procedures, with NIDDK-CR and Program staff participating jointly in the review of requests for access to resources and, when appropriate, collaborate with external subject matter experts.

Can the NIDDK Central Repository do aliquoting?

Yes, the Biorepository component can aliquot specimens as needed to preserve the collection. The Biorepository does not perform aliquoting for convenience, such as aliquoting specimens into multiple vials for shipment. If you are submitting specimens from an approved contributing study, we recommend that specimens be submitted in the lowest volume for future downstream analyses specified for the material type, to preserve specimen integrity by avoiding freeze-thaw cycles. If you are a requestor, there may be additional cost recovery charges associated with aliquoting and custom requests.

Can the NIDDK Central Repository serve as the primary receipt point for specimens, processing, aliquoting, and shipping specimens to various analysis laboratories?

No. In general, each contributing study should have its own plan for specimen processing and storage during study conduct. This can involve a central receiving laboratory that processes, analyzes, or stores the specimens needed for the planned analyses. Alternatively, studies may have the specimens processed at the collection site and then batch shipped to the central receiving laboratory.

Can the NIDDK Central Repository carry out specimen processing or routine clinical analyses?

The Biorepository component is not intended to serve as a clinical laboratory; however, it may be able to perform some routine quality and quantitative assays for specified material types and, when approved, other specialized services. Please contact the NIDDK Biorepository Support staff for additional information.

What types of data and specimens are available for request?

A comprehensive list of studies available for request can be found on the Studies page of the NIDDK-CR R4R. You may also search by specimen material types.

If my only goal is to use a dataset to demonstrate the statistical methodology and I do not plan to draw any scientific conclusions using the dataset, do I need to go through the IRB process?

NIDDK-CR is a controlled access repository. Unless otherwise indicated on the study page, for any level of access to the data, you must have your institution's IRB approval (or waiver), or ethics committee approval for international institutions. In addition, all requests must be accompanied by a description of the research that justifies the use of the resources, a research objective and design that describes your hypothesis and approach, an analysis plan that includes security safeguards for the data, and a research use statement to be made publicly available.

Do you have genotype data available? For which studies?

NIDDK-CR does not hold raw genomic data. Genomic data generated from NIDDK-supported studies are made available through other repositories such as dbGaP and Gene Expression Omnibus (GEO). Phenotypic and clinical data associated with those studies may be available via dbGaP and NIDDK-CR. Datasets that are available from both dbGaP and NIDDK-CR may vary from each other. NIDDK-CR works with dbGaP to provide access to approved requestors of NIDDK studies in dbGaP without having to go through additional scientific review. However, they will be required to submit an application, upload their approved dbGaP Data Access Request (DAR), and sign a NIDDK-CR Data and Resources Use Agreement. Requestors may also need to submit additional documentation before data are released. A search via the NIDDK-CR R4R Studies page can be used to generate a list of studies with available genomic data in dbGaP.

What are renewable and non-renewable resources?

Renewable and non-renewable resources refer to the likelihood of regenerating the resource versus having a finite quantity. Generally, data resources are considered renewable, as are specimens generated from cell lines such as DNA. Non-renewable resources are those that cannot be regenerated including serum, plasma, urine, tissue, DNA (not from cell lines), and others that may eventually be depleted. Non-renewable resources may have a higher threshold for release.

What types of data are available in the NIDDK-CR?

There are many different types of data available in the NIDDK-CR such as clinical phenotype data, clinical lab tests/results, genotype/genetic data (e.g., allele data), survey data, specimen inventory data, qualitative data (e.g., interview transcripts), and images (e.g., MRI, CT scan, retinal photos). Users can find studies through faceted or keyword searches on the Studies page and learn more about the available data on the study overview pages.

Who can access stored resources?

Resources under the guardianship of NIDDK-CR are available to qualified researchers including community scientists via the R4R system independent of their institutional affiliation or geographical location, only limited by informed consent or applicable NIH or U.S. Government policy use restrictions. All interested researchers must submit a request for access, provide all required documentation, and receive approval before resources are released. Researchers must have an authorized institutional signatory official to execute a legally binding agreement with NIDDK, or if unaffiliated, shall have a legal signatory authority to enter into valid binding agreements to legally bind themselves.

Can the study group that collected the specimens retrieve some of the specimens stored in the NIDDK Central Repository?

Contributing studies may be granted access to the specimens they submitted. For example, during the study period, NIDDK-CR may make an exception and allow the contributing study access to the archival set if those specimens are needed to meet study aims (aims that could not be accomplished otherwise). The use of the archival set of specimens from a contributing study should be minimized in order to preserve the integrity of the collection for future use. After the study is complete and the proprietary period has ended, contributing study investigators will go through the same request process as any other requestor.

Can non-U.S. researchers apply for access to data and specimens via the NIDDK-CR R4R?

The data and specimen request process is open to all qualified investigators interested in using data or specimens for research. However, use of some resources may be restricted to U.S. researchers by the terms of the study’s informed consent, or applicable NIH or U.S. Government policy use restrictions.

Can commercial organizations apply for access to data and specimens via the NIDDK-CR R4R?

The data and specimen request process is open to all organizations interested in using data or specimens for research. However, use of some resources may be restricted to non-commercial entities or for non-commercial purposes by the terms of the study’s informed consent.

I am a student planning on using the NIDDK-CR data for my thesis. Would I list myself as the Principal Investigator?

While students may submit requests for resources, students may not be listed as the Principal Investigator (PI). The PI must be an employee of the requesting institution, as they will need to sign the Data and Resources Use Agreement. We recommend listing your mentor or advisor as the PI. PhD students may be able to be the PI for the request if they are an employee or have an appointment at their institution. We recommend asking your institutional official or the grants management office and they can provide guidance on what your institution allows.

Are there costs associated with requests for resources?

In general, resources are available at no or modest costs. NIDDK-CR may charge modest cost recovery fees associated with preparing and sending resources to requestors. More details on cost recovery practices are included under the question, ‘Is there a cost to obtain specimens?’

How do I obtain data via the NIDDK-CR R4R?

For all data requests, interested researchers are encouraged to become familiar with the study collection by visiting the specific study page and browsing the study documents before submitting the request. This may facilitate the review process and reduce the number of iterations during the request process. Once requestors have decided whether the resources available can help answer their research question, the next step is to submit a Data Request.

The NIDDK-CR R4R data request application will require a Research Project summary, which requestors will be able to complete by copying and pasting the relevant information from their protocol into the appropriate fields of the electronic application. They will also need to have IRB documentation ready in order to complete and submit the application. For additional information on the application process, please see the How to Request NIDDK-CR Resources video.

I still need access to the requested NIDDK-CR provided resources, how do I extend my access?

NIDDK-CR R4R has revamped and streamlined the request extension process into a simple online form, the Progress Report tab. Each year, requestors are asked to complete the online progress report, and indicate whether they would like continued access to the requested resources. Failure to submit an annual progress report will result in termination of the Research Project and resource access discontinuation per the terms and conditions of the signed agreement.

On the Data and Resources Use Agreement (DUA) form, who should provide the Authorized Signature for my institution?

The Authorized Organization Representative (AOR) as defined by NIH is the individual, named by the applicant organization, who is authorized to act for the applicant and to assume the obligations imposed by the Federal laws, regulations, requirements, and conditions that apply to grant applications or grant awards. The AOR is also referred to as the authorized signatory or Signing Official (SO). Please see the NIH Grants Glossary page for additional details. The authorized person fulfilling this role may have any number of titles in your organization (e.g., a Manager, Officer, Director, Vice President, or Chief of contracts, grants, licensing, research administration, or sponsored programs for the institution). The AOR should not be the same individual as the Principal Investigator. If you are a part of a startup, small business, or citizen scientist, or your PI and AOR are the same person, please contact the NIDDK-CR Support staff for assistance. Note: If registered with eRA Commons (not required), requestors should use the same authorized person (e.g., Grants Management Specialist) as listed in eRA Commons.

Who makes the decision about granting access to specimens?

NIDDK has final decision authority for granting access to specimens under the guardianship of NIDDK-CR. For active studies, study leadership in collaboration with NIDDK will make a determination for granting access.

Is there a difference in consideration of requests for renewable (infinite supply) and non-renewable specimens?

Yes. Requests for renewable specimens, such as DNA from immortalized cell lines or DNA that has been 'whole-genome-amplified', may be granted access if the project for which they are being requested is approved via the appropriate review process.

Requests for non-renewable specimens, such as plasma or urine, may be granted through different pathways. Requests for highly abundant and modestly depleting renewable and non-renewable resources may be granted access through 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 resources require independent peer-review. NIDDK-CR provides the X01 mechanism, a full grant-like application that provides an independent scientific merit review.

If we were working together with a contributing study investigator, would this affect our situation and chances of accessing the data?

Working with a contributing study team has no impact on NIDDK’s decision to approve a request. Each request is reviewed independently, and all information is considered. However, please note that working with a contributing study investigator may pose additional requirements. For instance, any original investigator requesting resources has to submit an IRB approval or exemption letter and cannot use a Not Human Subjects Research determination letter because the original investigator has the potential to access identifiable information in the original study.

During the proprietary period, while a study is ongoing, how do researchers gain access to specimens stored in the NIDDK Central Repository?

During the proprietary period, researchers may be able to apply directly to the study group to carry out an ancillary study. Ancillary studies that are approved by the study leadership for access to specimens stored in the NIDDK-CR may then use the R4R system to submit an ancillary specimen request. Requestors must be R4R registered users in order to complete and submit a request.

I would like to receive more of the specimens that I have requested or additional specimens. What process should I follow?

To request additional specimens or volumes for an ongoing Research Project, requestors should submit a new request. Requestors should enter the original request number in the “Originating Request” field to ensure the subsequent requests are linked and should provide a justification for requesting additional resources. For an ancillary study, contact the study team directly to request access to additional specimens or volumes. NIDDK reviewers will make a final determination for the release of additional specimens or volumes.

How do you interpret the following section in NIDDK Central Repository Non-renewable Sample Access Notice of Funding Opportunity: "Applicants must include in this section a statement of how the proposed research fits within the limitations (if any) of the subjects' informed consent. Information about the informed consents for each study can be obtained from the NIDDK Central Repository."?

This refers to the ‘Human Subjects Considerations’ portion of the Research Plan for a Notice of Funding Opportunity (NOFO), including NIDDK-CR X01 PAR-22-171. In general, resources made available through NIDDK-CR are considered Not Human Subjects Research and this section does not apply. However, you are being asked to consider any restrictions for use before you submit your application. NIDDK has verified that all resources made available to the scientific community through NIDDK-CR have been consented for secondary and future research use, and carefully considers all requests against any informed consent restrictions for use prior to release.

How are specimen requests reviewed?

All requests are reviewed by study-specific staff member(s) and administrative staff. There are several review pathways for specimen requests as described below.

• Administrative Review Path: This pathway is available to researchers requesting renewable specimens or non-renewable specimens with a less than 10% specimen loss (meaning that no specific specimen from a specific participant visit would be depleted by 10% or more). This pathway does not require the full peer review process.
• X01 Grant Application Path: This pathway is available to researchers requesting non-renewable specimens with a specimen loss of 10% or more and without a prior peer reviewed project. This pathway will provide a full peer review process.
  
  Note: If you are planning to submit an X01 or other NIH funding application (e.g., R01), you must submit an Availability Inquiry request to request a volume and impact assessment report that estimates quantity available and verify any research use limitations per the contributing study’s informed consent, before submitting the X01 (or other funding) application. A volume and impact assessment report is required to be submitted with your X01 grant application. Applications without this report are administratively withdrawn without review.
• Secondary Review Path of NIH/Non-NIH Awards (R01 or other): This pathway is available to researchers requesting non-renewable specimens with a specimen loss of 10% or more, who have a prior peer review with a fundable score, or who are planning to submit a peer review grant application. This pathway will provide secondary review of the summary findings of the peer review.
  
  Note: For secondary review, a volume and impact assessment report for the impact on the specimen collection must be obtained from NIDDK-CR by submitting an Availability Inquiry request, prior to grant submission and included with the grant application.

Under what conditions are specimens distributed?

Requests for renewable and non-renewable specimens are distributed under a number of conditions. Non-renewable specimen requests with moderate to high impact thresholds (≥ 10%) require a peer review process. Applicants may submit an X01 grant application which provides access to non-renewable specimens, but no funds. It is possible to gain access by submitting to some other grant mechanism that will provide independent scientific review to assess the merit of the proposed research. NIDDK and other NIH Institutes often have NOFOs specifically aimed at encouraging use of reposited specimens.

Non-renewable specimen requests with modest impact to the collection (< 10%) and renewable specimen requests (mainly, DNA from cell lines and whole genome amplified DNA) are reviewed through an internal administrative review process by NIDDK staff.

How do I obtain specimens?

• To request access to NIDDK-CR held specimens, all interested requestors must complete a two-phase request process. During the first phase, requestors submit an Availability Inquiry. Requestors interested in specimens will receive a volume and impact assessment report, usually with the intent to include the report in a grant application, either R01, X01, or other funding mechanism. Grants do not need to be NIDDK-specific. NIDDK-CR Support staff will follow up with you after you submit your Availability Inquiry.
• Once the impact report is accepted, and you have secured funding, you may move into the second phase known as an Access Request. Here, you will be asked to provide proof of funding, IRB approval, your research plan, and additional points of contact for NIDDK review and approval prior to accessing NIDDK-CR resources.
• Requestor may also be able to obtain access to specimens from active and ongoing studies held at NIDDK-CR in accordance with the contributing study’s ancillary sharing policies for specimens not otherwise available through the study’s biobank. To request access to specimens for an approved ancillary study, you must work with the parent study to submit an Ancillary request. NIDDK-CR Support staff will follow up with you after you submit your request.

Is there a cost to obtain specimens?

Per Section 301.h of the PHS Act (42 USC241(h)) and NIH Policy, NIDDK-CR charges modest amounts to requestors for cost recovery. Cost recovery efforts assist with reimbursement of costs incurred while making specimens available to the scientific community.

Requestors will be invoiced for specimens according to the prices outlined on the NIDDK-CR Specimen Service Cost Recovery and Processing Times page; shipping is not included in the cost. This page also contains the policies for submitting payment, including a requirement that all requests over $5000, custom DNA requests, or international shipments pre-pay prior to the repository beginning preparation of the shipment.

How much does shipping cost?

Shipping costs are determined by multiple factors such as institution-negotiated courier rates, shipper types, and box dimensions and weight. Since these factors differ between institutions and requests, it is difficult to provide estimates. However, the NIDDK-CR Specimen Service Cost Recovery and Processing Times page outlines two common shipper types that requestors can use to obtain a shipping cost estimate from their courier (e.g., FedEx).

Once my request for specimens is approved, how long will it take for me to receive the specimens?

Depending upon availability, a specimen request can take anywhere from 3 business days to over 3 months to fulfill. More information is found on the NIDDK-CR Specimen Service Cost Recovery and Processing Times page. The clock begins once the fully completed request is approved by NIDDK and an agreement is executed. Specimen turnaround time depends on many factors, including:

• Does the request require relabeling of vials?
• How many specimens are being requested?
• Do they need to be aliquoted?
• Are the specimens stored in one freezer or scattered in several freezers?
• Are specimens being pulled from -80C freezers or liquid nitrogen freezers?
• Where will the specimens be shipped?
• Does the request require payment by the recipient before the request may be processed?

I am unable to open a file (or data set) I received from the NIDDK Central Repository with my approved request, what do I do next?

If you are having issues opening a file or data set you received via NIDDK-CR R4R, please contact us through the ‘Comments’ tab of your request for assistance. You may also email us at NIDDK-CRsupport@niddk.nih.gov regarding any questions or issues with the resources received from NIDDK-CR.

Is IRB clearance required for internal analysis in an organization, or is IRB clearance required only if the analysis will be published?

For any level of access to the data, you must have your institution’s IRB clearance or waiver. If you do not have an IRB, you must use an external IRB. Some institutions use ethics committee review boards, in which NIDDK will accept an approval or waiver. This IRB step is required whether or not you publish your findings. Since the data we offer is provided in Limited Datasets, devoid of direct identifiers, and there is no direct human-subject interaction, sometimes your IRB will make a determination of Not Human Subjects Research (NHSR) rather than provide IRB approval. If your IRB documentation is not in English, you must provide an official English language translation, self-translations via Google Translate will not be accepted.

I will have co-investigators working with me on the resources I am requesting. Does NIDDK need IRB approval from each co-investigator or their institution separately, or do you just need the IRB approval from the Principal Requestor's institution?

The principal requestor is responsible for obtaining IRB approval or a determination of NHSR from their institution’s IRB or an external IRB. Information submitted to the IRB should clearly describe the involvement and role of any co-investigators from the same or a different institution. When submitting the request for resources to NIDDK-CR, any co-investigators should be identified. Collaborators from other institutions who play a significant role in the research project and will have access to NIDDK-CR resources should be included under the “Independent Collaborators” section of the request form. Independent Collaborators must sign their own agreement (a secondary agreement) for use of the resources. NIDDK-CR Support staff will initiate the primary and any secondary Data and Resources Use Agreements as appropriate.

If I produce a manuscript using NIDDK data and/or specimens, am I required to acknowledge this?

Researchers producing manuscripts and other works (abstracts, presentations) using NIDDK-CR provided data and/or specimens are required to acknowledge the use of the repository and the contributing study resources. NIDDK-CR recommends use of data availability statements and Digital Object Identifiers (DOIs) when acknowledging use of resources. Study-specific acknowledgements may be required with some of the data/specimen sources.

Why should I use a Digital Object Identifier (DOI) when citing a study?

A DOI is unique and persistent making it ideal for citing resources. URLs are not permanent and can hinder future research reproducibility when links are inactive or route to unknown pages. NIDDK-CR uses DataCite to register DOIs, increasing NIDDK-CR resource discoverability, accessibility, and reusability. The study DOI and citation guidance can be found on each study’s overview page.

What information should I provide if a journal submission requires a data availability statement?

NIDDK-CR provides specific language for requestors to use as data availability statements. Study specific language can be found on a study’s overview page, below the dataset citation information.