U01: Research Project Cooperative Agreement
The U01 at NIDDK
The information on this page is for applicants seeking support for multi-center high-risk clinical studies.
The NIDDK supports investigator-initiated, multi-center high-risk clinical studies through a two-part process:
- Implementation planning phase (U34)
- Cooperative agreement (U01) to conduct the study
This guidance applies to all high-risk clinical studies, interventional trials as well as observational studies, conducted at more than one center. A clinical research center may encompass one or more physical locations where the clinical study is being conducted -- i.e., where study participants are recruited, and/or are intervened upon and/or have outcomes assessed under a single protocol – as long as all locations are under the overall direction of a single investigator. A data coordinating center is not considered a clinical research center.
A multi-center study is classified as “high risk” if it utilizes either a high-risk intervention and/or invasive measures or has high operational risk, or both. NOT-DK-20-051 provides more information on high-risk versus low-risk studies.
Proposed studies should be hypothesis-driven and focus on a disease relevant to the mission of NIDDK. Proposals are expected to improve understanding, diagnosis, prevention, or treatment of the disease being studied.
These FOAs will only support research within the mission of NIDDK. Research applications in areas that are primarily within the missions of other NIH Institutes and Centers are not appropriate for this FOA and will not be supported. NIDDK has many diseases within its mission, but all research related to relevant diseases may not be appropriate for NIDDK. Applicants to this FOA are strongly encouraged to contact NIDDK staff as soon as possible in the development of the application, so that NIDDK staff can help the applicant understand whether the proposed clinical study is within the goals and mission of the Institute and is appropriate for this FOA. At a minimum, prospective applicants should contact NIDDK staff no later than 12 weeks prior to a planned submission. You should contact the Program Director responsible for your area of research. If you are not certain who to contact, you should reach out to the Program Director representing the appropriate scientific division, listed at the end of PAR-21-102 and PAR-21-103, and you will be directed to the correct Program Director.
Many of the diseases or conditions within the mission of NIDDK disproportionately affect individuals from racial and ethnic minorities. NIDDK encourages research focusing on minority and underserved populations and places a high priority on clinical studies to understand and eliminate health disparities and promote health equity.
NIDDK is committed to conducting clinical studies that have been developed with active stakeholder engagement. Active stakeholder engagement entails meaningful involvement of patients, caregivers, family members, clinicians, healthcare systems, advocacy groups, and other stakeholders relevant to the study. Stakeholder engagement is expected to help shape the design of the study, as well as recruitment and retention approaches, especially for populations who are disproportionately affected by diseases in the NIDDK mission but may be underrepresented in research.
Funding for low-risk multi-center clinical studies
Low-risk observational studies or other types of human subjects research that is not a clinical trial may use the PA-20-185 or specific FOAs from NIDDK.
Only Apply for a U01 if Your Planning Phase is Complete
Most applicants will have had a U34 before applying for a U01. Planning activities are not permitted as part of the U01 application. Investigators who require a planning phase should first apply for an implementation cooperative agreement (U34). Applicants who feel they have completed all the planning elements without a U34 may apply directly for the U01.
Read the Program Announcement
Contact Program Staff At Least 12 Weeks Prior to Submission
All applicants, regardless of whether you hold a U34, are strongly encouraged to contact NIDDK program staff at least 12 weeks before submitting a U01 application. Program staff will help the investigator understand whether the proposed clinical study addresses a high priority research area and meets programmatic needs (including balance across research areas), whether it is appropriate to conduct using this mechanism, and whether funds might be available for the full clinical study.
Since this is a cooperative agreement, NIDDK will have substantive scientific involvement with the proposed project. NIDDK will need sufficient time to thoroughly consider the proposed study. It is the Institute’s experience that applications for multi-center clinical studies may be scientifically meritorious but often need further work before they are ready for submission. Allowing as much time as possible for the consultation process will allow time for revisions, should they need to be made.
Seek Pre-approval for Requests of $500,000+
Applicants are reminded that NIH requires pre-approval of applications requesting $500,000 or more in direct costs (excluding consortium facilities and administrative costs (F&A)) in any year. This preapproval process is distinct from prior consultation.
Your written request for prior consultation should be as succinct as possible. The details included in your letter may vary depending on the type of study planned (e.g., epidemiology study, drug trial, behavior intervention). Generally, the letter should include all of the following items:
- Date of proposed submission
- Study title
- Study PI, and other key investigators (attach biosketch(es))
- Primary institution
- Specific aims
- Summary of study protocol, including flow diagram depicting study
- Summary of safety/risk issues
- Proposed start date, duration, and timeline of the clinical trial or clinical study
- Proposed sample size including power calculation
- General statistical assumptions for the proposed study design and analysis
- Confirmed collaborating sites, including the demographics and availability of the study population at those sites. Include identification and a brief description of the Data Coordinating Center.
- Discussion of product/intervention to be evaluated and how it will be obtained, if applicable, including industry partners and regulatory issues that have/need to be resolved
- Detailed budget by year.
- Evidence that the U34 planning components have been completed.
Human Subjects Research
Overview of Human Subjects Research at NIDDK.
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