Clinical Trial Planning and Implementation Milestones

Updated September 29, 2016

This page describes the planning, design and preparation of documentation that usually needs to be in place prior to the implementation of a U01 clinical trial. In order to accomplish this necessary planning with NIAMS support, investigators may apply for a Clinical Trial Planning Grant (R34). Completion of the agreed upon milestones of an R34 planning grant is highly recommended prior to submission of an application for a NIAMS Clinical Trial Implementation Cooperative Agreement (U01) that will support the implementation and conduct of the trial. 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 R34 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 R34 grant, the NIAMS will work with investigators to agree on a timeline for accomplishing these tasks.

Milestones that may be appropriate for a R34 include, but are not limited to:

  • Develop a clinical study protocol adhering to International Conference on Harmonization (ICH) E6 Good Clinical Practice Consolidated Guidance
  • Develop a single-site or multi-site manual of operating procedures (MOP) using the NIAMS guidelines that includes a detailed description of study procedures and process details, validation, and quality control for any non-standard clinical or laboratory/mechanistic testing which will be performed
  • Develop a preliminary data and safety monitoring plan using the NIAMS guidelines to address how risk to subjects in the clinical trial will be minimized and the process for collecting and reporting adverse events to the appropriate regulatory bodies
  • Develop an investigatorís brochure or equivalent
  • Develop a quality and data management plan
  • Initiate the IRB approval process; the NIAMS strongly encourages the use of a single IRB
  • Develop consent form(s) and, if applicable, assent form(s)
  • Develop a recruitment and retention plan which incorporates the NIH policy on the inclusion of women, minorities, and children in clinical research
  • Conduct "model recruitment" (as described in the FOA) to test recruitment feasibility
  • Develop a statistical analysis plan
  • Identify collaborators and clinical site(s), which may include negotiating sub-contracts
  • Develop training materials and training/certification plans for study staff who will carry out the study
  • Develop a plan for the acquisition and administration of study agent(s)
  • Negotiate agreements with industry or other partners, to provide drugs, devices, or other resources for trial implementation
  • Develop a complete set of suitable documents for submission to the appropriate regulatory authorities such as the FDA (i.e., Investigational New Drug (IND) application or IND exemption, or Investigational Device Exemption (IDE) application)
  • Develop a preliminary timeline and budget for conduct and completion of the future clinical trial including funding for orderly close-out of clinical sites and preparation of a final study report
  • Develop a detailed project timeline for submission of the U01 clinical trial

Clinical Trial Planning Milestone Checklist for (U01) grant application

In cases where the clinical trial planning milestones have been completed (either through a previous NIAMS R34 or U34 or other means), applicants should submit a Clinical Trial Planning Milestones Checklist to demonstrate the necessary planning accomplishments. The checklist summarizes each of the planning Milestones and provides a status and timeline of each task. Any tasks that remain incomplete before the trial can open for recruitment must be detailed and justified. Consultation with a NIAMS Program Director or Clinical Research Manager is strongly encouraged.