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U34 Frequently Asked Questions

​Some of the most common questions about the U34 are answered below.

Introduction

What are the U34 Multi-Center Clinical Study Implementation Planning Cooperative Agreement and the U01 Multi-Center Clinical Study Cooperative Agreement?

​NIDDK will support investigator-initiated, multi-center clinical studies through a two part process: (1) an optional implementation planning cooperative agreement (U34) followed by (2) a cooperative agreement (U01) to conduct the study.
 
This policy applies to all clinical studies, interventional trials as well as observational studies, conducted at three or more sites. NIDDK will not accept applications for multi-center clinical studies that are submitted as R01s, with the exception of ancillary studies to existing cooperative agreements, which can be submitted as R01s to PAR-12-265, or applications submitted to other/future FOAs that specifically invite multi-center clinical studies.

This policy does not apply to pilot studies. Investigators who are interested in obtaining support for pilot studies may use the R21 mechanism, through the appropriate program announcement (see question #6, below).


What is the definition of a multi-center study?

A multi-center study is one which is conducted at three or more sites. A study is considered to be "multi-center" if three or more sites are involved in the actual conduct of the study. A study will not be considered to involve multiple centers if participant recruitment occurs at three or more locations in a geographic area but all interventions and/or outcomes assessments are performed by a single study team.


Why does NIDDK suggest applying for a U34 Multi-Center Clinical Study Implementation Planning Cooperative Agreement before a U01 Multi-Center Clinical Study Cooperative Agreement?

​Clinical studies require extensive administrative planning (e.g., protocol finalization, manual of operations development, case report form design, data management and study oversight, etc.) before participant recruitment may begin. These activities require significant resources and personnel; thus, the administrative planning process typically begins after the study has been peer-reviewed and funded, using valuable time that is needed for the actual conduct of the study. The U34 will provide sufficient time and funds to complete detailed clinical study activities/documents necessary to comply with NIDDK standards and regulatory requirements. This will allow participant recruitment to begin once the U01 is awarded.
 
After successfully completing the administrative implementation activities of the U34 Multi-Center Clinical Study Implementation Planning Cooperative Agreement, investigators can apply for a U01 Multi-Center Clinical Study Cooperative Agreement and request up to 5 years to conduct the clinical study.


Is the U34 Multi-Center Clinical Study Implementation Planning Cooperative Agreement limited to multi-center clinical trials?

​No. The U34 Multi-Center Clinical Study Implementation Planning Cooperative Agreement mechanism is designed to support the planning activities of all types of multi-center clinical studies including epidemiologic studies, observational studies, and interventional clinical trials. A multi-center study is one which is conducted at three or more sites (see question #2, above).


What administrative study activities are supported by the U34 Multi-Center Clinical Study Implementation Planning Cooperative Agreement?

​Study-related activities conducted during the U34 Multi-Center Clinical Study Implementation Planning Cooperative Agreement will depend on the type of clinical study (e.g., epidemiologic study, drug trial, behavior intervention). The U34 may support activities such as, but not limited to, the development/completion of the following items:

  • Final study protocol. Please note that a proposed protocol must be included in the U34 application, as an appendix. The U34 period may be used to modify and/or finalize the protocol, if necessary, based on comments received during the review process, logistical issues or new scientific progress during the U34 period
  • Informed consent form(s) and, if applicable, assent form(s)
  • Investigator’s brochure or equivalent
  • Manual of operations including details, validation, and quality control for any non-standard clinical or laboratory/mechanistic testing which will be performed
  • Data monitoring and management plan
  • A plan for the acquisition and administration of study agent(s) or device(s)
  • Required Office of Human Research Protections assurances if not already in place
  • Complete set of suitable documents for submission to the appropriate regulatory authorities
  • Safety oversight plan
  • Detailed budget for conduct and completion of the clinical trial including funding for preparation of a final study report
  • Identification of clinical study site(s)
  • Training materials and training/certification plans for study staff
  • Initial IRB approval
  • Applicable regulatory elements of the Food and Drug Administration if an IND/IDE is needed for implementation of the research plan
  • Agreements with industry, as needed, to provide drugs, devices, or other resources
  • In the event of an award, the NIDDK and the Principal Investigator will agree on a list of milestones to be completed during the U34 project period


Can the U34 Multi-Center Clinical Study Implementation Planning Cooperative Agreement be used to collect preliminary data or to conduct a pilot study in preparation for a multi-site clinical study?

​No, the U34 Multi-Center Clinical Study Implementation Planning Cooperative Agreement 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 must include the study protocol. The proposed study design and protocol will be key elements in the peer-review of all U34 Multi-Center Clinical Study Implementation Planning Cooperative Agreement applications. 
 
NIDDK supports R21 Program Announcements to support the collection of preliminary data and for conduct of pilot studies. See:


Can the U34 Multi-Center Clinical Study Implementation Planning Cooperative Agreement be used to support a group of investigators who wish to meet and plan a multi-center study?

​No. The U34 Multi-Center Clinical Study Implementation Planning Cooperative agreement is not designed for this purpose. The U34 application must include details of the proposed study design and a proposed protocol, which will be critically evaluated during the peer-review process.


Logistics

How many years of support and what level of funding will the U34 Multi-Center Clinical Study Implementation Planning Cooperative Agreement mechanism provide?

​Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. The total project period for an application submitted in response to the U34 Multi-Center Clinical Study Implementation Planning Cooperative Agreement funding opportunity may not exceed two years. Applicants may request up to $225,000 in direct costs per year (excluding consortium Facilities and Administrative [F&A] costs). The funds requested are expected to vary based on the number of clinical sites involved in the study and the complexity of the study.


Do all U34 Multi-Center Clinical Study Implementation Planning Cooperative Agreement applications have to request two years of funding to complete the administrative planning process?

​No. U34 Multi-Center Clinical Study Implementation Planning Cooperative Agreement applications are not required to request two years of funding. Applicants may request less than 2 years of funding if, in the applicant’s judgment, the planning process will require less than 2 years of funding support.


Will renewal applications be accepted for the U34 Multi-Center Clinical Study Implementation Planning Cooperative Agreement?

​No. Renewal applications will not be accepted for the U34 Multi-Center Clinical Study Implementation Planning Cooperative Agreement. The U34 mechanism will provide up to a maximum of 2 years of funding to support the planning activities required of new projects.


If a U34 Multi-Center Clinical Study Implementation Planning Cooperative Agreement is awarded, what role will NIDDK have in its implementation?

​The U34 Multi-Center Clinical Study Implementation Planning Cooperative Agreement will use a cooperative agreement award mechanism. In the cooperative agreement mechanism, the Project Director/Principal Investigator (PD/PI) retains the primary responsibility and dominant role for planning the proposed project, with NIH staff being substantially involved as a partner with the Principal Investigator, as described under Section VI. 2. Administrative Requirements, Cooperative Agreement Terms and Conditions of Award in PAR-15-068.


Application

What should I do if I want to submit a U34 Multi-Center Clinical Study Implementation Planning Cooperative Agreement?

​Applicants are strongly encouraged to contact the appropriate NIDDK Program Director to discuss their proposed application for a U34 Multi-Center Clinical Study Implementation Planning Cooperative Agreement and to do so as soon as possible, preferably at least 12 weeks before the submission date. 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. See the NIDDK Research Areas to identify the correct program director for your application. If you are not sure of the appropriate program director, you can contact one of the program directors designated as contacts for information in the PAR (PAR-15-068) and you will be directed to the appropriate individual.


How far in advance of the U34 Multi-Center Clinical Study Implementation Planning Cooperative Agreement application receipt date should I contact NIDDK?

​You should contact the appropriate Program Director at least 12 weeks before the desired receipt date. 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.


What information should be included in a letter requesting consultation about applying for a U34 Multi-Center Clinical Study Implementation Planning Cooperative Agreement?

​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 (including 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
  • 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


Who should I contact for prior consultation?

​You should contact the appropriate program director for the subject matter of the application. See the NIDDK Research Areas to identify the correct program director for your application.  If you are not sure of the appropriate program director, you can contact one of the program directors designated as contacts for information in the PAR and you will be directed to the appropriate individual (PAR-15-068).


Is a U34 Multi-Center Clinical Study Implementation Planning Cooperative Agreement always required by NIDDK before a multi-center clinical study can be funded?

​A U34 Multi-Center Clinical Study Implementation Planning Cooperative Agreement is not required by NIDDK before a multi-center clinical study is funded by a U01 mechanism. If you believe you have accomplished all the necessary planning required to conduct the clinical study, you may apply for the U01. However, the U01 application requires that you document that all necessary planning has been completed before you submit the U01 application. The recruitment of participants should be ready to begin as soon as a U01 award is made. No planning activities are allowed under the U01.


If a U34 Multi-Center Clinical Study Implementation Planning Cooperative Agreement is awarded, will NIDDK guarantee that a subsequent U01 Multi-Center Clinical Study Cooperative Agreement will also be awarded?

​No. Prospective applicants should note that obtaining a U34 Multi-Center Clinical Study Implementation Planning Cooperative Agreement award does not guarantee or imply funding for a subsequent U01 Multi-Center Clinical Study Cooperative Agreement application. If the planning phase is not successful, the NIDDK may decide not to allow a U01 Multi-Center Clinical Study Cooperative Agreement application. All U01 Multi-Center Clinical Study Cooperative Agreement applications will be peer-reviewed, and NIDDK will consider the results of the peer-review process when deciding whether to support the U01 Multi-Center Clinical Study Cooperative Agreement. Applicants should also remember that NIH requires that pre-approval be obtained for all applications requesting $500,000 or greater in direct costs (excluding consortium F&A) in any year.


Peer Review

How will a U34 Multi-Center Clinical Study Implementation Planning Cooperative Agreement application be peer-reviewed?

​U34 Multi-Center Clinical Study Implementation Planning Cooperative Agreement applications will be peer reviewed by special emphasis panels set up by the NIDDK Review Branch. Specific review criteria used to evaluate U34 applications may be found in the PAR.


When are the receipt dates for U34 Multi-Center Clinical Study Implementation Planning Cooperative Agreement applications?

  • January 20, 2015
  • June 17, 2015
  • April 18, 2016
  • January 20, 2017
  • June 19, 2017


Since the U34 only supports administrative activities to prepare to conduct the clinical study, why does the peer-review of the U34 include a review of the rationale and design of the proposed clinical study?

​NIDDK will only support the planning phase of a multi-center clinical study if the proposed clinical study is worthy of support. Therefore, the review of the U34 Multi-Center Clinical Study Implementation Planning Cooperative Agreement will include the rationale and design of the proposed clinical study, as well as a proposed protocol. If the clinical study is not significant, innovative and/or likely to answer the proposed research question, NIDDK may decide that the proposed clinical study does not meet the criteria for support of the planning phase of the study.


Since the U34 will only support administrative planning (e.g., protocol finalization, manual of operations development) required before subject recruitment can occur, how will peer-review evaluate the significance of a U34 application?

Reviewers will be asked to evaluate the innovation of the proposed study based on the rationale and design of the multi-center clinical study to be conducted after the planning phase of the U34. Reviewers may be asked to address questions such as, but not limited to, the following:

  • Is the multi-center clinical study to be conducted after the U34 planning phase original and innovative?
  • Does the project challenge existing paradigms or clinical practice?
  • Will the study address an innovative hypothesis or critical barrier to progress in the field?
  • Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area?


How will the approach of the U34 application be evaluated? Will the peer-reviewers evaluate the approach of the multi-center clinical study or the approach of the U34 planning activities proposed in the application?

​Both the approach of the U34 planning activities and of the proposed multi-center clinical study will be evaluated during peer-review of the U34 Multi-Center Clinical Study Implementation Planning Cooperative Agreement. Peer-reviewers will be asked to evaluate the following questions:

  • Will the study concept and design, methods, and analyses, including preliminary statistical analyses, successfully accomplish the aim(s) of the proposed clinical study?
  • Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well-reasoned, and appropriate to the aims of the project?
  • Are the activities proposed for the planning period adequate? Will the activities proposed be sufficient to allow for timely and successful study implementation?
  • Does the applicant acknowledge potential problem areas and consider alternative tactics?
  • Will the proposed planning activities address all major barriers that may confront the U01 clinical study, if accepted?
  • For applications designating multiple PDs/PIs, does the Leadership Plan ensure that there will be sufficient coordination and communication among the PDs/PIs?
  • Are the administrative plans for the management of the research project appropriate, including plans for resolving conflicts?


If a U34 Multi-Center Clinical Study Implementation Planning Cooperative Agreement application is not funded upon initial submission, can the application be revised and resubmitted?

​Yes. However, investigators are strongly encouraged to discuss the resubmission with their Program Director. NIDDK will consider the comments of the peer-reviewers in discussing a resubmission application with the investigator.


What are the receipt dates for revised U34 Multi-Center Clinical Study Implementation Planning Cooperative Agreement applications?

  • January 20, 2015
  • June 17, 2015
  • April 18, 2016
  • January 20, 2017
  • June 19, 2017