The NIAMS has determined that investigator-initiated, interventional clinical trials requesting NIAMS support should undergo a rigorous planning, design, and documentation phase before a decision is made to implement a study with a substantial fiscal and human resource investment.

The NIAMS has determined that investigator-initiated, interventional clinical trials requesting NIAMS support should undergo a rigorous planning, design, and documentation phase before a decision is made to implement a study with a substantial fiscal and human resource investment. The implementation of a clinical trial requires extensive administrative planning (e.g., protocol finalization, manual of operations development, establishing collaborations and estimating recruitment potential) before participant enrollment can occur. The R34 planning grants will give investigators the time and funds necessary to complete detailed clinical trials planning to meet NIAMS and NIH standards and regulatory requirements. A structured planning process will allow studies to determine the optimal design strategy and to complete the administrative activities as expeditiously as possible so that time is not spent during the implementation phase (U01) completing such activities. Read the full PAR-20-090 funding opportunity announcement. 

Purpose

The R34 planning grant process is designed to:

• Permit early peer review of the rationale and feasibility of the proposed clinical trial.
• Permit optimization of the design of the proposed trial (see below).
• Provide support for the development of a complete study protocol and associated documents and of other essential elements of a clinical trial.

Rationale

Clinical research is a significant NIAMS investment aimed at answering critical questions about a particular disease or disease process. The NIAMS will support trials to test promising new interventions with the potential to improve health practices and clinical care.

The activities required in the R34 planning grant will depend on the type and complexity of the study (e.g., drug trial, surgical, behavioral intervention, or multi-site or single-site). Please refer to the Program Announcement PAR-20-090 for examples of research activities that are appropriate for a Clinical Trial Planning Grant.

The R34 application is designed to provide the investigators an early review of the rationale for the proposed clinical trial and to provide support for the applicant to establish the research team, develop tools for data management and oversight of the research, define recruitment strategies, develop and finalize the clinical protocol and all essential elements of the study required for the clinical trial including all the appropriate documents.

The R34 application should identify clear milestones to be achieved during the planning process. Before an award is made, the NIAMS and the Principal Investigator will agree on the milestones to be completed during the R34 project period, and these milestones will be incorporated into the notice of grant award (NoA). Completion of certain milestones will be required prior to submission of an application for a U01 to implement the trial and will vary with the nature of the trial being planned. The NIAMS is committed to minimizing any delay in implementing the trial, and will work with the investigator to tailor the milestones and duration of the trial preparation phase, supported by the planning grant, so as to proceed quickly to trial implementation, supported by a U01. This flexibility will allow for a range of durations of grants, from short—when many milestones have already been met—to the full two years—when many elements of trial preparation would benefit from a more extensive planning phase. In addition, as discussed above, the NIAMS may accept an application for a U01 implementation grant without a prior R34 planning grant if all elements of trial preparation are complete.

The NIAMS R34 is intended to support necessary administrative study activities before recruitment of subjects into the future clinical trial begins. The R34 cannot be used to recruit human subjects. In addition, it cannot be used to collect data on research participants unless those data are only for the purpose of testing recruitment strategies on a potential pool of interested and eligible subjects (e.g., through conducting “model recruitment” using focus groups, surveys, questionnaires, etc.). In cases where additional data is needed on dosing or other aspects of a trial that would require human subjects, investigators should consider submitting an Exploratory Clinical Trial Grant (R21) application or a Clinical Observational (CO) Studies in Musculoskeletal, Rheumatic, and Skin Diseases (R01) grant to generate that additional data. If substantial preliminary data are needed to support the Clinical Trial Implementation grant (U01), it is suggested the R21 or CO R01 grant be submitted prior to the R34 submission.

Milestones for R34 Applications

The R34 application should identify clear milestones to be achieved during the planning process. Before an award is made, the NIAMS and the Principal Investigator will agree on the milestones to be completed during the R34 project period, and these milestones will be incorporated into the notice of grant award (NoA). Completion of certain milestones will be required prior to submission of an application for a U01 to implement the trial and will vary with the nature of the trial being planned. The NIAMS is committed to minimizing any delay in implementing the trial, and will work with the investigator to tailor the milestones and duration of the trial preparation phase, supported by the planning grant, so as to proceed quickly to trial implementation, supported by a U01. This flexibility will allow for a range of durations of grants, from short—when many milestones have already been met—to the full two years—when many elements of trial preparation would benefit from a more extensive planning phase. In addition, as discussed above, the NIAMS may accept an application for a U01 implementation grant without a prior R34 planning grant if all elements of trial preparation are complete (see milestones).

Allowable Research Activity Examples

The NIAMS R34 is intended to support necessary administrative study activities before recruitment of subjects into the future clinical trial begins. Some examples include, but are not limited to:  

• Develop a clinical study protocol adhering to International Conference on Harmonisation (ICH) E6 Good Clinical Practice Consolidated Guidance.
• Develop a manual of operating procedures (MOP) using the NIAMS guidelines which include 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 of adverse events to the appropriate regulatory bodies.
• Develop an investigator’s brochure or equivalent.
• Develop a quality and data management plan.
• Initiate the IRB approval process; the NIAMS strongly encourages the use of a central 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 and 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.

Prohibited R34 Research Activities

The NIAMS R34 cannot be used for the following:

• To recruit subjects.
• To collect data on research participants unless those data are only for the purpose of testing recruitment strategies on a potential pool of interested and eligible subjects (e.g., through conducting “model recruitment” using focus groups, questionnaires, etc.).

In cases where additional data is needed on dosing or other aspects of a trial that would require human subjects, investigators should consider submitting an Exploratory Clinical Trial Grant (R21) application or a Clinical Observational (CO) Studies in Musculoskeletal, Rheumatic, and Skin Diseases (R01) grant to generate that additional data.

If substantial preliminary data are needed to support the Clinical Trial Implementation Grant (U01), it is suggested the R21 or CO R01 grant be submitted prior to the R34 submission.