OBJECTIVE
In response to the discussions and input from Council last fall and at the January meeting, the Division of Population and Health Promotion Sciences staff members have developed a policy announcement, several revisions to existing program announcements, and a new program announcement. In total, these describe a method for concept clearance of trials prior to submission of a formal application, define a path for investigators for development of clinical trials, and announce an area of program priority for clinical trials. These items are brought to the attention of Council members for their information.
Creation of a Defined Path at NIDCR for Clinical Trial Development
A defined path for clinical trial grant applications submitted in any topic area has been developed. It entails a new management policy for clinical trial grant applications concept clearance and a revision of the two existing planning and pilot clinical trials program announcements. This path is designed to assist investigators in the creation of initial clinical testing studies arising from basic and translational science findings, i.e. phase 1/2 trials. It also is designed to help both investigators and institute staff in planning and managing the clinical trial program. It proposes that all investigator-initiated clinical trial grant applications receive concept clearance prior to submission, although the planning and pilot grant path is not required for investigators who are prepared for phase 3 clinical trials. For these latter grant applications, it is assumed that they already have proceeded through the planning and pilot stages and met the criteria described in the policy announcement. It also should be recognized that to assure broad applicability of findings to the population in general, most NIDCR phase 3 clinical trials will necessarily have a multicenter design involving representative groups of subjects.
Clinical Trials Policy Announcement
The need for a concept clearance process, before submission of a formal clinical trial grant application, was proposed at the last Council meeting. A policy announcement will be issued instructing investigators to submit a short (2-3 page) proposal to program staff outlining the topic, population, methods, and anticipated outcomes of a proposed clinical trial prior to preparation of an initial application. This initial concept clearance would be required of all investigators contemplating clinical trials, including those that fall below a 500K budget. These short submissions will be reviewed by senior program staff using the criteria for clinical trial significance discussed at the previous Council meeting and as part of program strategic plans. The criteria identified by Council members in January include: relevance to NIDCR's mission; ability to address gap in current portfolio; potential to reduce health disparities and/or impact on the public's health; focus on prevention versus treatment; potential for success (short- and long-term); and evidence of partnerships. The goals of this review will be to work with investigators at the earliest part of the planning process, inform them of current areas of high program priority, describe the NIDCR clinical trial pathway and review the required elements for a complete clinical trial application. This approach will help both investigators and the NIDCR staff in planning and managing the clinical trial program.
Revised Clinical Trial Planning Grant Program Announcement
It is recognized that clinical trial development is becoming increasingly complex, with more complicated protocols and many regulatory considerations. The planning process should be distinct from the conduct of the trial. This will result in more complete and higher quality clinical trial applications and more efficient use of institute funds. The existing program announcement for clinical trial planning grants, issued in August 1999, will be modified. The duration of these planning grants now will be for no longer than 2 years (they may be for a shorter period), and for a maximum of $100K. The anticipated goals and outcomes of the planning grant will be refined, as well. These will be: to write and refine a clinical trial protocol, including clear definition of research objectives and outcome measures; to develop an investigative group (ideally multiple sites); to identify plans for an overall coordinating center that will include a data coordinating center; to identify the patient population and recruitment strategies; to perform sample size estimates and develop an analytic plan; to write a manual of operating procedures; to begin regulatory approval processes; to develop a data quality assurance plan and appropriate forms; and to develop a data and safety monitoring plan. Staff will work closely with the investigators during this phase, providing advice and assistance, as appropriate and as requested.
Revised Clinical Trial Pilot Grant Program Announcements
The pilot grant would prepare an investigator to move forward to an application for a planning grant or a definitive Phase 3 clinical trial. The revision of the existing pilot grant, also issued in August 1999, will specify that these applications should be for a maximum of 2 years, with costs not exceeding $100K. By definition, these are not definitive trials and this should be reflected in the size and budget of the trial. Data from these studies might serve as justification for larger, longer, and more expensive NIH-defined phase 3 trails of safety and efficacy. As the clinical trial development path is envisioned, a protocol developed with the planning grant could be implemented with the feasibility/pilot grant, generating meaningful clinical data that would support an application for a full NIH-defined Phase 3 clinical trial. We are considering using the cooperative agreement mechanism for clinical trial planning and pilot grants. Regardless of the mechanism used, staff will work closely with the investigators at all stages of the proposal. One important goal will be to assure that proposals on the same theme from different investigative groups have endpoints and procedures that will be comparable.