Key Dates

Related Announcements

PAR-21-101 - NIDDK High Risk Multi-Center Clinical Study Implementation Planning Cooperative Agreements (U34 Clinical Trial Optional)

PAR-21-102 - NIDDK High Risk Multi-Center Clinical Study Cooperative Agreement (U01 Clinical Trial Required)

PAR-21-103 - NIDDK High Risk Multi-Center Clinical Study Cooperative Agreement (U01 Clinical Trial Not Allowed)

PA-20-183 - Research Project Grant (Parent R01 Clinical Trial Required)

PA-20-184 - Research Project Grant (Parent R01 Basic Experimental Studies with Humans Required)

PA-20-185 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)

PAS-20-160 - Small R01s for Clinical Trials Targeting Diseases within the Mission of NIDDK (R01 Clinical Trial Required)

Issued by

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Purpose

This Notice is to update NIDDK guidance and procedures for the acceptance of grant applications from institutions proposing investigator-initiated, multi-center clinical studies, described in  NOT-DK-14-025 "Clarification of NIDDK Policy: Investigator-Initiated Multi-Center Clinical Studies."

NIDDK has previously supported multi-center clinical studies involving three or more centers exclusively through cooperative agreements, regardless of the nature of the clinical study. The NIDDK is changing this requirement from one based solely on the number of centers involved in a clinical study to a risk-based approach. Under the new NIDDK guidance, investigators proposing to conduct low-risk (see below) multi-center clinical studies (including observational studies as well as clinical trials) may now submit their applications as R01s under PA-20-183, PA-20-184, PA-20-185, PAS-20-160 or other appropriate FOAs.

Multi-center clinical studies (i.e., more than one center) that are considered high-risk (see below) will still be required to use the two-part, cooperative agreement process described below. The risk level of a study may be related to interventional and/or operational risk. The examples below provide general guidelines for risk assessment and are not exhaustive. Potential applicants are strongly encouraged to contact NIDDK staff to discuss their proposed study and determine the most appropriate mechanism for submitting their application.

Examples of high-risk interventions include:

• An intervention that has an unknown safety profile or has substantial side effects (including all studies requiring an IND/IDE application). This would include studies of a drug in a new population, or study of a licensed product for an unapproved indication;
• A complex or invasive intervention, including diagnostic procedures;
• A study involving complex assessment of multiple outcomes, including the ascertainment of outcomes using invasive research procedures;
• Pragmatic trials proposing significant changes to standard of care practices, or significant coordination with multiple care providers and healthcare data systems;
• A multi-center study involving more than minimal risk in vulnerable study populations (as defined in 45 CFR 46)

Studies that do not meet the above criteria will generally be considered to involve low-risk interventions. Low-risk multicenter studies usually include the administration/use of a licensed product for an approved indication, or the provision of a routine intervention that could be used in the setting in which it is being studied (e.g., a lifestyle intervention to promote weight loss).

Examples of multicenter studies with high operational risk include:

• An inexperienced investigator, defined by lack of experience in conducting clinical trials, coordinating research across multiple centers, or recruiting the population to be studied;
• A complex study design that involves standardization of research measures and outcomes collection and research data capture over multiple centers;
• A study that involves the establishment of agreements with third parties that intend to utilize research study data to support regulatory filings with the FDA

Multicenter studies that do not meet the above criteria will generally be considered to have low operational risk.

A multicenter study is classified as “high risk” if it utilizes either a high-risk intervention or has high operational risk, or both.

NIDDK will support high-risk, multi-center clinical studies typically through a two-part process that usually requires use of a U34 planning grant followed by a separate application for the clinical trial or study (U01). NIDDK will not accept applications for high-risk, multi-center clinical studies that are submitted as R01s, except for applications submitted in response to other/future FOAs that specifically invite multi-center applications.

Rationale

When a complex and/or high-risk multi-center clinical study application is funded, extensive administrative planning (e.g., protocol finalization, manual of operations development) is generally required before participant recruitment can occur. These planning activities may consume valuable time and resources. NIDDK believes that a two-part cooperative agreement process that separates administrative implementation from participant recruitment and study conduct will remedy these issues. Therefore, NIDDK will support implementation planning (U34) cooperative agreements for high-risk, multi-center clinical studies. The U34 is a cooperative agreement award mechanism, with the NIH staff being substantially involved as a partner with the Program Director/Principal Investigator (PD/PI). The U34 is designed to provide early peer review of the rationale and design of the proposed clinical study and to support all administrative study group planning activities that are required in order to begin recruitment of participants. These planning 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 and 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 and the protocol. U34 applications will be peer reviewed by special emphasis panels set up by the NIDDK Review Branch.

Successful completion of an awarded U34 will result in an application (U01) to conduct the clinical study. It is expected that receipt of a U34 grant will lead to the timely submission of an application for support of the full-scale study, incorporating the elements developed under the planning grant. Prospective applicants should note that funding of a U34 does not guarantee or imply funding for a subsequent U01 application. Applicants who feel they have completed all the planning activities without a U34 may apply directly for the U01. Applicants are strongly encouraged to contact NIDDK Scientific/Research staff at least 12 weeks before submitting a U34 or U01 application. This pre-application consultation does not take the place of the NIH requirement for prior-approval for large budget applications. Applicants seeking $500,000 or more in direct costs in any year (excluding consortium F&A) must contact Scientific/Research staff at least 6 weeks before the receipt date to obtain approval to submit.

Clinical studies proposed should be hypothesis-driven and address diseases relevant to the mission of NIDDK.

More detailed instructions regarding the multi-center clinical study application process are contained in three FOAs, one for the Multi-Center Clinical Study Implementation Planning Cooperative Agreement (U34) (PAR-21-101)and two for the Multi-Center Clinical Study Cooperative Agreement (U01) (TEMP9972 for clinical trials and TEMP9973 for observational studies), as well as on the NIDDK website.

Inquiries

Please direct all inquiries to:

Barbara Linder, M.D. Ph.D
Division of Diabetes, Endocrinology and Metabolic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-0021
Email: linderb@mail.nih.gov

Tracy L. Rankin, M.P.H, Ph.D.
Division of Kidney, Urologic and Hematologic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-4748
Email: rankint@mail.nih.gov
 

Aynur Unalp-Arida, M.D., Ph.D.
Division of Digestive Diseases and Nutrition
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-8879
Email: aynur.unalp-arida@nih.gov