Planning and Implementation Milestones

Reviewed October 18, 2011

The following are administrative aspects that usually need to be in place before initiating a clinical trial. They represent milestones that must be reached for successful completion of a U34 Clinical Trial Planning Grant, before proceeding to opening for participant enrollment. The NIAMS recognizes that circumstances differ between different types of trials. For example, the regulatory requirements for a trial of a behavioral intervention or a device will differ from those for a Phase III study of a new therapeutic agent. An application for a U34 should provide a list of the milestones that must be met before the implementation of the proposed trial can begin, and a plan for reaching these milestones. Prior to awarding a U34 grant, the NIAMS will work with investigators to agree upon a timeline for accomplishing these tasks. Milestones that may be appropriate for a U34 include:

  • Complete clinical protocol (allowing for subsequent changes by regulatory bodies)*
  • Budget plan*
  • Identification and qualifications of clinical trial sites, pharmacies and laboratories*
  • Investigator’s Brochure or equivalent for study products
  • Manual of Operations, including:
    • Data management plan*
    • Site quality management plan*
    • Statistical analysis plan and power calculation*
    • Safety plan*
    • Recruitment plan*
    • Consent forms
  • 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 *

One of the goals of the NIAMS clinical trials programs is to fund timely trials. Thus, NIAMS will strive to minimize any delay between the planning and implementation phases of a trial. To this end, certain milestones will be identified for each U34 which, when reached, would be sufficient to permit the investigator to submit an application for a U01 (single site) or UM1 (multi-site) to fund implementation of the trial. Milestones that typically should be accomplished prior to submission of an application for funding for implementation of a trial are indicated above with (*). Which of these milestones are appropriate for a given trial would be determined by NIAMS in consultation with the investigators before funding of a U34. Note that, once these milestones are met, it may be appropriate to submit the application for theU01 or UM1 before the end of the planning grant, with an agreement that certain tasks would be completed in the remaining period of U34 grant funding. Consultation with the appropriate Program Officer is strongly encouraged, as described here .

NIAMS policy is that a U34 Clinical Trial Planning Grant be obtained before proceeding to a UM1/U01 Clinical Trial Implementation Grant. However, when the planning process has already been completed, for example by current R34 awardees, an investigator may wish to apply for a UM1/U01 without a preceding U34. The investigator must be able to document that the planning and administrative tasks are already completed or provide a justification as to why they are not needed. In general, these are the same elements indicated above with (*), the principle being that these are the elements that need to be in place before a complete UM1/U01 application could be submitted, although allowing for different circumstances for different types of trials. Submission of a Letter of Request is required for applications with a budget of $500,000 or more in direct costs.

Prior consultation with the NIAMS is strongly encouraged for submission of the NIAMS Clinical Trial Implementation (UM1/U01) Grant application, including new and resubmission applications. NIAMS staff will consider whether the proposed clinical trial meets the goals and mission of the Institute and whether it is appropriate to conduct it as an investigator-initiated clinical trial, but will not evaluate the technical and scientific merit of the proposed trial. Technical and scientific merit will be determined during peer review. In the presubmission consultation phase, if the proposed trial does not meet the goals and mission of the NIAMS, applicants will be so informed. If the NIAMS ascertains that substantial additional planning may be necessary, submission of the application may be considered under the Clinical Trial Planning Grant (U34) Cooperative Agreement FOA. The NIAMS reserves the right to determine that support for clinical trials may be directed through other available mechanisms supported by the NIAMS.