U34: Implementation Planning Cooperative Agreement

Most recent NIDDK funding announcement: PAR-24-094

The U34 at NIDDK

The NIDDK supports investigator-initiated, high-risk multi-center clinical (more than one center) studies through a two-part process:

1. Implementation planning phase (U34)
2. 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 provided more information on high-risk versus low-risk studies.

The U34 is intended to support all administrative study group activities that are required to begin recruitment of subjects. These activities include, but are not limited to:

• establishing the research team
• developing the tools for data management and oversight of the research
• defining the recruitment strategies
• finalizing the protocol and investigators brochure
• writing the Manual of Operations
• establishing a data and safety monitoring plan
• initiating the IRB approval process

The U34 is not designed for the collection of preliminary data, for the conduct of pilot studies to support the rationale for a clinical study, or for the design of the study. The U34 application will include the proposed study design, a full protocol, and a budget for the clinical study to be conducted under the U01.

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.

This NOFO 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 NOFO 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 NOFO 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 NOFO. At a minimum, prospective applicants should contact NIDDK staff 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-24-094, 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

The U34 will provide up to two years of support.  It is expected that receipt of a U34 will lead to the timely submission of an application for support of the full-scale study (U01), incorporating the elements developed during the planning phase. Prospective applicants should note that funding of a U34 does not guarantee or imply funding for a subsequent application.

Applying

Read the Program Announcement

More detailed instructions regarding the U34 application process are contained in PAR-24-094.

Contact Program Staff At Least 12 Weeks Prior to Submission

All applicants are strongly encouraged to contact NIDDK program staff at least 12 weeks before submitting a U34 application. Program staff will help the investigator understand whether the proposed full 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 subsequent, full clinical study.

Since this is a cooperative agreement, NIDDK will ultimately 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.

Required Documents

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 the following items:

• Date of Proposed Submission
• Study title
• Study PI (attach biosketch)
• Primary institution
• Specific Aims
• Significance
• 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
• Estimated sample size including brief power calculation
• General statistical assumptions for the proposed study design and analysis
• Potential 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 partner(s) and regulatory issues that have/need to be resolved
• Total cost for the U34 phase
• Total cost estimate of the clinical study, not the planning grant, by year
• Milestones to be accomplished during the U34

Human Subjects Research

Overview of Human Subjects Research at the NIDDK

Review

U34 applications will be peer reviewed by special emphasis panels set up by the NIDDK Review Branch.

FAQs

U34 Frequently Asked Questions

Staff Contact

Division of Diabetes, Endocrinology and Metabolic Diseases
Barbara Linder, M.D., Ph.D.

Division of Digestive Diseases and Nutrition
Aynur Unalp-Arida, MD, Ph.D.

Division of Kidney, Urologic and Hematologic Diseases
Tracy Rankin, Ph.D., M.P.H.