Planning and Implementation Milestones

Updated July 16, 2014

This page describes administrative aspects that usually need to be in place before initiating a clinical trial application. They represent milestones that must be reached for successful completion of a NIAMS U34 Clinical Trial Planning Grant and before proceeding to opening for participant enrollment in a funded study.

The NIAMS recognizes that planning and administrative activities for starting a trial can vary based on the type of study being conducted. For example, regulatory approvals for a Phase III multi-site study of a new therapeutic agent will differ from a trial of a behavioral intervention or a device. 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 on a timeline for accomplishing these tasks.

Milestones that may be appropriate for a U34 may include, but are not limited to:

  • Identify study collaborators and convene meetings to finalize protocol development
  • Complete clinical protocol (allowing for subsequent changes by regulatory bodies)
  • Budget plan. If requesting funding through the NIAMS, details in the requested budget should include major budget categories (key/senior and other personnel, equipment, travel, trainee support, other direct costs), indirect costs, and total costs for each year of the requested application.* PLEASE NOTE: Applicants with budgets with direct costs greater than $500,000 in any year must request permission to submit the application. See Letters of Request.
  • Identification and qualification of clinical trial enrollment site (s), data coordinating center (DCC), Clinical Research Organization (CRO), pharmacies and laboratories*
  • Clinical Trial Agreement (CTA) and/or Cooperative Research and Development Agreement (CRADA), when applicable
  • Investigator’s Brochure or equivalent for study intervention
  • Manual of Operations* (see Single Site MOOP Guidelines or multisite MOOP Guidelines)
  • Data management/collection system for primary and remote sites
  • Plans and materials for training and site initiation
  • Consent/assent forms
  • Plans and timeline for submission to Institutional Review Boards (IRBs) and receiving approvals*
  • Plans and timelines for meetings and submission of documents to appropriate regulatory bodies (e.g., the Food and Drug Administration)*
  • Finalize plans to obtain intervention related products (e.g., drugs, placebo, device)*
  • If drug or biologic, 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 U01 application

(*) Milestones that typically should be accomplished prior to submission of a U01 clinical trial implementation cooperative agreement

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. 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 the NIAMS in consultation with the investigators before funding of a U34. Please note, once these milestones are met, it may be appropriate to submit the application for the U01 even if it is 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 U01 Clinical Trial Implementation Grant. However, when the planning process has already been completed through another means, for example by a previously funded R34 grant, an investigator may wish to apply directly for a U01 without a preceding NIAMS U34. In these cases a U34 waiver request must be submitted. The U34 planning grant requirement may be waived, and direct submission of the U01 may be permitted if it can be demonstrated that the planning tasks have been or will be accomplished prior to implementation of the clinical trial. Applicants should consult with the NIAMS to determine if the NIAMS will consider a U34 waiver request.