What is the purpose of having a centralized repository?
A centralized repository enhances the value of study generated resources by simplifying access to these resources for secondary use. It provides organized, well integrated resources using common standards to promote sharing to address new research questions, reproducibility studies, or pooling of resources across different collections. and biospecimens are stored under uniform conditions in a cost effective and scalable manner.
What is NIDDK Central Repository - Resources for Research (R4R)?
NIDDK Central Repository (NIDDK-CR) is a contract supported centralized repository managed by two, separate, yet integrated components, the Data Repository, and the Biorepository. These components work together to acquire, store, and distribute resources generated from large multicenter studies supported by NIDDK or that are within the research areas and mission of NIDDK. The mission of NIDDK-CR is to facilitate sharing of resources for secondary uses, thus encouraging work by junior or established investigators, investigators with novel approaches, and others not included in current collaborations. Secondary research use helps to maximize research participants contributions and decreases duplicative sampling efforts, increasing the scientific value and impact of the originating study.
Established in 2003, NIDDK-CR has continually expanded its portfolio over the years, creating a valuable data resource with which researchers can rapidly validate clinical hypotheses and algorithms for clinical decision-making, and matched biospecimen collections, which are also advancing the development of prognostic variables, biomarkers, and therapeutics for diseases related to the mission of NIDDK. In 2022, NIDDK- CR restructured and relaunched its website, Resources for Research (R4R), featuring a streamlined approach to the request process continuing to support accessibility and findability of NIDDK resources.
Who can submit data and specimens to 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 a portion of the specimens and associated data generated into NIDDK- CR when additional conditions for submission are met. Other NIDDK-funded and non-NIDDK funded studies may also be eligible to deposit representative archival sets 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. Please reach out to NIDDK-CR’s Administrative 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 NIDDK Central Repository?
NIH policy is that the unique resources developed through NIH funding are to be shared with the research community, to the extent that sharing of clinical 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, NIDDK-CR or an NIDDK-approved repository should be used to facilitate sharing.
Are requestors of renewable or non-renewable specimens required to submit data and specimens into NIDDK Central Repository?
In accordance with the signed user agreements, requestors seeking access to specimen resources may be required to submit materials generated or produced in the conduct of their Research Project to NIDDK-CR. Terms and conditions for submission of any materials back into NIDDK-CR or an NIDDK approved repository will be discussed and agreed between the requestor and NIDDK prior to release of resources.
I am an investigator with an NIDDK sponsored R01, is my grant eligible to deposit my data or specimens into NIDDK Central Repository?
Investigators funded by an R01 are encouraged to deposit and make resources available to the community via targeted or generalist repositories. 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 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 Central Repository?
Studies eligible to deposit resources, may do so at no additional cost to the contributing study, meaning, NIDDK-CR does not 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 retrieval, sorting, and packaging specimens for transfer.
What is the proprietary period for stored data and specimens?
NIDDK 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's materials will be mutually agreed upon by the study leadership and NIDDK. leadership and NIDDK.
In alignment with NIH 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 NIDDK Data 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). NIDDK-CR Data Repository component 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 overtime.
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 biological specimens with the relevant clinical 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 use only. The linkage file should be provided by the study at the time the clinical data are delivered to the Data Repository.
What interaction will the study have with the Data Repository to prepare data for archiving?
The repository will work with the study to prepare the data set for archiving. Repository personnel will consult with the study team to develop appropriate documentation that is comprehensive and will allow investigators not familiar with the study data to use it. In addition, the repository personnel will interact with the study team to familiarize themselves with the data, metadata, and supporting documents in preparation for archiving.
Which specimens should be sent to NIDDK Biorepository and when should those specimens be sent?
NIDDK Biorepository component accepts a wide variety of biological materials 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 their archival set that are designated for future research use 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 repository 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. NIDDK 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 NIDDK Biorepository as part of the archival set may be made available to the study if needed to meet study-related aims.
Who has oversight and decision-making authority of the specimens at NIDDK Biorepository?
For specimens held at NIDDK Biorepository that are under the guardianship of NIDDK- CR, decisions related to access and release are governed by established NIDDK policy and procedures, with NIDDK Repository and Program staff participating jointly in the review of requests for access to resources.
Can NIDDK Biorepository do aliquoting?
Yes, the repository can aliquot specimens. If you are a submitting study, we recommend that specimens be submitted in the lowest volume for future downstream analyses specified for the material type, to preserve sample 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 NIDDK Biorepository serve as the primary receipt point for specimens, processing, aliquoting and shipping samples out to various analysis laboratories?
No. In general, each study should have its own plan for specimen processing. 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.
Can NIDDK Biorepository carry out specimens processing or routine clinical analyses?
No. The Biorepository 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. 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 at the Studies page. You may also search by 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 R4R makes controlled access data available to qualified researchers. For any level of access to the data, you must have your institution's IRB approval. 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 R4R does not hold genomic data. Genomic data generated from NIDDK-supported studies is made available through dbGaP. Phenotypic and clinical data associated with those studies may be available via dbGaP and NIDDK-CR R4R. Datasets that are available from both dbGaP and NIDDK-CR R4R may vary from each other. NIDDK-CR R4R works with dbGaP to provide access to approved users of NIDDK studies in dbGaP without having to go through additional review. However, they will be required to submit an application, upload their approved dbGaP DAR, and sign a DUA. Requestors may also need to submit additional documentation before data are released. The Study Search page can be searched for 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 like DNA. Non-renewable resources are those that can’t be regenerated including serum, plasma, urine, tissue, DNA (not from cell lines), and others that may eventually be depleted resulting in a higher threshold for release.
Do you have a Type 1 Diabetes dataset in NIDDK-CR R4R? If so, what is the procedure to gain access to it?
NIDDK-CR R4R has several T1D studies. The list of studies available by conditions and other key terms can be searched at the Study Search page.
Who can access stored materials?
Resources under the guardianship of NIDDK are available to qualified researchers including community scientist via the R4R system. All interested researchers must submit an application for access, must provide all required documentation, and receive approval before resources are released.
Can the study group that collected the specimens retrieve some of the specimens stored in NIDDK Biorepository?
Yes, although the use of archival set of specimens from a large study should be minimized in order to preserve the integrity of the collection for future use. However, studies will always have access to the specimens needed to carry out assays that are part of the approved study protocol.
Can non-U.S. researchers apply to use data and specimens from NIDDK-CR R4R?
Yes. In general, all applications will be judged without regard to the geographical location of the applicant, although it is conceivable that there will be certain non-renewable samples collected in specific studies that are restricted to U.S. researchers by the terms of the study or of the consent.
Can commercial organizations apply to use data and specimens from NIDDK-CR R4R?
The data and specimens 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.
Are there costs associated with requests for resources?
There are no costs to the requestor for data requests. There are cost recovery fees associated with ancillary and external requests for specimens. More details on cost recovery practices are included under question ‘Is there a cost to obtain specimens’.
How do I obtain data from 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 browse the readme file and the study documents before submitting the request. This will speed up the review process and reduce the number of iterations during the submission process. Once researchers have decided whether the resources available can help answer their research question, the next step is to submit a Data Request.
The R4R data request application will require a Research Project summary, which researchers 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 reach out to NIDDK-CRsupport@niddk.nih.gov.
If I have several datasets, may I use one extension letter to cover all of them?
Extension letters are associated with an individual signed agreement. You must submit one extension request letter for each signed agreement. In general, you may be able to request several datasets under one single project, and under one single agreement and therefore, one single extension request. Extension requests are only considered for Research Projects compliant with the terms and conditions of the signed agreement.
On the Data and Resources Use Agreement forms, 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). 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 samples, 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 judged to have a reasonable likelihood of achieving its stated aims. Requests for non-renewable samples, such as plasma or urine, may be granted access only if judged to have high scientific merit and therefore require a complete scientific justification.
If we were working together with a contributing Study investigator, would this affect our situation and chances of accessing the data?
No. Each request is reviewed independently, and all information is considered. If you want to include information that you are working with a Study investigator, the reviewers would consider that in the request. Ultimately, that information alone should not be a deciding factor for access to data
During the proprietary period, while a study is ongoing, how do researchers gain access to specimens stored in NIDDK Biorepository?
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 NIDDK Biorepository may then use the R4R system to submit an ancillary study request. Requestors must be R4R registered users in order to complete and submit an application.
I would like to receive more of the specimens that I have requested or additional specimens. What process should I follow?
Any modifications, including additional specimens require submission of a modification to the Research Project for review and approval. For an ancillary study, contact the study team directly to request access to additional specimens or volumes. If modification for additional specimens is approved by the study leadership, NIDDK-CR R4R will work with you to get the modification processed. For external renewable and non-renewable specimen request, you must initiate the process for modification by entering a note in the Comments section of your active request and provide the amount of additional material desired with a justification. NIDDK reviewers will make a final determination for the release of additional numbers or volumes.
How do you interpret the following section in Funding Opportunity Announcements: "Applicants must include in this section a statement of how the proposed research fits within the limitations of the subjects' informed consent Information about the informed consents for each study can be obtained from NIDDK Repository."?
This refers to the ‘Human Subjects Considerations’ portion of the Research Plan for many Funding Opportunity Announcements (FOA), including NIDDK-CR X01 PAR-22-171. In general, resources made available through NIDDK-CR R4R 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. If you are planning to submit an X01 application, you must reach out to NIDDK-CR R4R support staff to request an availability report that estimates quantity available and verify any research use limitations per the contributing study’s informed consent, before submitting the X01 application.
NIDDK-CR has verified that all resources made available to the scientific community through the R4R system have been consented for secondary and future research use, and carefully considers all requests against any informed consent restrictions for use prior to release.
Under what conditions are specimens distributed?
Requests for renewable and non-renewable specimens are distributed under a number of conditions. Non-renewable specimen request with moderate to high impact thresholds (≥10%) require 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 FOAs specifically aimed at encouraging use of reposited samples.
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?
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.
Ancillary requestors and those not affiliated with the original study will be invoiced for specimens according to the prices outlined on the Biospecimen Service Cost Recovery 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 being shipped internationally 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 Biospecimen Service Cost Recovery 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, before pulling the samples, will I be contacted regarding retrieval and shipment methods?
If necessary, special processing requests may be taken into consideration.
Once my request for specimens is approved, how long will it take for me to receive the specimens?
Depending upon availability, a sample request can take anywhere from 3 days to 2 months to fulfill. It may take longer if the specimens are from a legacy study and have not yet been delivered to the Biorepository. The clock begins once the fully completed request is approved by NIDDK. Specimen turnaround time depends on many factors, including:
I am unable to open a data set I received from the Repository, what do I do next?
If you are having issues opening a data set you received from 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 R4R.
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 institutions IRB clearance or waiver. If you do not have an IRB, you must use an external IRB. This IRB step is required whether or not you publish your findings. Since the data we offer is provided in Limited Datasets and, 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.
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 institutions 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. NIDDK-CR team will initiate the appropriate 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 data and/or specimens are required to acknowledge the use of the repository and the originating study resources. NIDDK-CR recommends use of data availability statements and Digital Object Identifiers (DOI) when acknowledging use of resources. Study-specific acknowledgements may be required with some of the data/sample 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 R4R 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.
What provisions should be included about future research use in the informed consent for participants?
NIDDK has developed model language for use in informed consents that describes the repository and explains what will happen to the specimens and data that are collected. The most important point is that the repository will not accept any personal identifiers on specimens or in the data. The model language is available on the NIDDK-CR R4R website.
What participant identification or specimen identification code will NIDDK Biorepository use?
NIDDK Biorepository can use the study's assigned identification (ID) for each participant. In situations where this would be inappropriate, because the ID contains potential direct personal identifiers, the study should assign a different, masked, identifier. There may be relabeling and linking file needs if masked identifiers are needed. Please contact NIDDK-CR support team for detailed information.
Does NIDDK Repository maintain a Certificate of Confidentiality?
No. NIDDK-CR does not play a role in confidentiality agreements or Certificate of Confidentiality or plays a role in confidentiality agreements or certificates of confidentiality. It is the contributing study’s responsibility to establish these and for maintaining participant’s information protected to the extent possible. Nevertheless. the Repository takes measures to protect the privacy and security of study participants’ information it holds.
Who owns the data and specimens submitted to the repository? Does the Institution or contributing study submitting the data and specimens maintain ownership, or are they owned by NIDDK once they have been submitted?
NIDDK-CR does not address its holdings in terms of "ownership", it is more a matter of control of the resources. NIDDK-CR is the guardian of data and specimens from designated studies. The study group submitting the resources control their distribution while studies are ongoing and during an agreed-upon proprietary period. Once the proprietary period ends, NIDDK-CR and the appropriate oversight committee(s) assume responsibility for distributing the resources in accordance with applicable NIH/NIDDK policies and procedures.
Will I have to share my data and how do I plan for it?
As of January 25, 2023, the NIH Policy for Data Management and Sharing (DMS) is in effect. All research that is funded in whole or in part by NIH, regardless of funding amount, is required to submit a DMS plan outlining how scientific data and accompanying metadata will be managed and shared. NIH DMS plans should address the elements described in the Supplemental Information to NIH DMS Policy. NIH has provided a DMS plan format on the Writing a Data Management and Sharing Plan page on the NIH Scientific Data Sharing website. NIDDK has Institute-specific guidance for Writing a DMS Plan and provides NIDDK DMS Tools and Examples.