Letters of Request for Permission to Submit an Application for a Clinical Trial Implementation Cooperative Agreement (UM1/U01)

Updated July 17, 2012

The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) is committed to improving the health of patients with rheumatic, musculoskeletal, and skin diseases by supporting investigator-initiated clinical trials that lead to better clinical outcomes. The NIAMS' goal is to identify and support trials that are as timely and informative as possible, and which will lead to improvements in clinical practices for disease prevention, diagnosis, and treatment. To this end, the NIAMS has enhanced its clinical trials program.

As announced in NOT-AR-11-014, the NIAMS will support investigator-initiated, clinical interventional trials through a two-part process: (1) a Clinical Trial Planning Grant (U34) followed by (2) a Clinical Trial Implementation Cooperative Agreement (UM1 for multi-site trials or U01for single-site trials) to fully implement and conduct the study. For investigators considering applying for either a U34 or a UM1/U01, speaking with an NIAMS Program Director prior to submission of an application is strongly recommended.

Furthermore, investigators who are considering applying for a Clinical Trial Implementation Agreement with a budget that exceeds $500,000 in direct costs in any year are required to seek the NIAMS' prior agreement to accept an application, as per NIH policy (NOT-OD-02-004). Potential applicants must submit a Letter of Request (LOR) to the NIAMS that addresses each of the items below.

Note that the NIAMS may require up to ten weeks after submission of the LOR to make a decision as to whether to accept a large UM1/U01 application. Please consider this when constructing the grant application submission timeline. If the NIAMS agrees to accept an application, the NIAMS will provide a letter of approval that should be included with the application package.

Letter of Request (LOR) for a UM1/U01

Investigators who wish to propose a clinical trial should apply for funding through a NIAMS Clinical Trial Implementation Cooperative Agreement (UM1/U01), particularly if the proposed trial is complex or involves large numbers of subjects. It is expected that most trials, particularly larger and more complex trials, will require substantial planning and preparation prior to opening for recruitment, and investigators will be required to apply for a NIAMS Clinical Trial Planning Cooperative Agreement (U34) prior to applying for the UM1/U01 to implement the trial unless an exemption is allowed by the NIAMS. Submission of a LOR for a UM1/U01 will be a milestone in awarded U34 grants, which will be tailored to the specific planning activities required before implementation of the proposed trial.

Applicants with a prior NIAMS Clinical Trial Planning Grant (U34) must submit an LOR for UM1/U01applications with budgets of $500,000 or more in direct costs in any year and must include:

  • Name, address, and telephone number of the PD(s)/PI(s)
  • Names of other key personnel
  • Participating institutions
  • Number and title of this funding opportunity
  • The proposed date of submission of the UM1/U01 application
  • Documentation that the milestones designated in the U34 award agreement have been met
  • Any refinements or changes in the Principal Investigator(s), rationale, objectives, protocol, study sites, and industry partners for the proposed trial, from that outlined in the U34 application
  • Any tasks that remain to be completed before a trial can open for recruitment
  • The anticipated budget for the proposed trial
  • A one page synopsis of the likely impact of the proposed study on disease prevention, diagnosis, or treatment

To apply for a UM1/U01 without a preceding Clinical Trial Planning Grant (U34), investigators must demonstrate they have c ompleted all of the documentation which would have been prepared during the planning grant. If an investigator has completed all planning tasks (see Milestones web page) and is ready to begin implementation, written justification that outlines the completed milestones with completed documents must be provided prior to the submission of an LOR for the UM1/U01. Once the waiver of the U34 has been granted by the NIAMS, the LOR may be submitted. Since t he NIAMS may require up to ten weeks after submission of the LOR to make a decision as to whether to accept a large UM1/U01 application, applicants are encouraged to submit the U34 waiver request early to allow adequate time for review. If the completed materials will not be available at the time the waiver is requested, the investigator should submit an application for the U34 planning grant. Similarly, t he LOR should document that a planning grant is not necessary and that the necessary steps required prior to opening for recruitment are largely complete as discussed above.

Applicants without a prior NIAMS Clinical Trial Planning Grant (U34) must submit an LOR for UM1/U01 applications with budgets of $500,000 or more in direct costs in any year and must include:

  • Name, address, and telephone number of the PD(s)/PI(s)
  • Names of other key personnel
  • Participating institutions
  • Number and title of this funding opportunity
  • Documentation that the planning milestones have been met and the NIAMS' decision to grant a U34 planning grant waiver
  • A complete clinical protocol (allowing for subsequent changes by regulatory bodies)
  • Identification and qualifications of clinical trial sites, pharmacies, and laboratories
  • The Investigator's Brochure or equivalent for study products
  • A Manual of Operations, including:
    • Data management plan
    • Site quality management plan
    • Statistical analysis plan and power calculation
    • Safety plan
    • Recruitment plan
    • Consent forms
  • A plan for submission of regulatory documents to appropriate authorities, including IND and IRB documents (if applicable)
  • Drug availability, acquisition and formulation, including placebo, where applicable
  • Documentation of adequate co-funding, if applicable and necessary for completion of the trial
  • The proposed date of submission of the UM1/U01 application
  • Any tasks that remain to be completed before a trial can open for recruitment
  • The anticipated budget for the proposed trial
  • A one page synopsis of the likely impact of the proposed study on disease prevention, diagnosis, or treatment

Contact information to submit an LOR for a UM1/U01:

Anna Nicholson
Division of Extramural Research Activities
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Democracy One, Room 808
6701 Democracy Blvd.
Bethesda, MD 20892
Telephone: (301) 594-2463
Fax: (301) 480-4543
Email: nicholsona@mail.nih.gov