DoD Peer Reviewed Orthopaedic, Clinical Trial Award

Orthopaedic injuries have a profound impact on military readiness and return to work/activity/duty. In the military, extremity battle wounds comprise approximately 50% of injuries reported in the Joint Theatre Trauma Registry. Additionally, orthopaedic injuries and conditions that occur outside of combat (e.g., during training, leisure activities, resultant from old injuries, etc.) present one of the greatest threats to the readiness of our Service Members and military. Early stabilization, treatment, and rehabilitation of orthopaedic injuries in both civilian and military populations have led to better outcomes, particularly in the prevention of secondary complications and in minimizing morbidity. Availability of orthopaedic care and treatment as early as possible, or as close to the point of injury as possible, also minimizes limb loss and affects military readiness. The PRORP is interested in supporting research that will have an impact on the lives of all individuals that have sustained a major musculoskeletal injury.The PRORP Clinical Trial Award supports the rapid implementation of clinical trials with the potential to have a significant impact on the treatment or management of military combat-related orthopaedic injuries or non-battle injuries that significantly impact unit readiness and return to duty/work rates. Applicants are encouraged to address how the proposed research will support patient care closer to the point of injury and/or allow patients to more quickly return to duty/work. Clinical trials may be designed to evaluate promising new products, pharmacologic agents (drugs or biologics), devices, clinical guidance, and/or emerging approaches and technologies. Proposed projects may range from small proof-of-concept trials (e.g., pilot, first in human, phase 0), to demonstrate feasibility or inform the design of more advanced trials, through large-scale trials to determine efficacy in relevant patient populations.Applications to the FY22 PRORP Clinical Trial Award mechanism must support a clinical trial and may not be used for animal or preclinical studies.The FY22 PRORP CTA differs from the FY22 PRORP Clinical Translational Research Award (CTRA) in that the CTRA allows for clinical research projects, whereas the CTA is restricted to clinical trials only.A clinical trial is defined as a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of the interventions on biomedical or behavioral health-related outcomes. For more information, a Human Subject Resource Document is provided at https://cdmrp.army.mil/pubs/pdf/Human%20Subjects%20Resource%20Document.pdf. Principal Investigators (PIs) seeking funding for a preclinical research project should consider one of the other FY22 PRORP program announcements being offered.All applications submitted to this program announcement, regardless of the selected Focus Area, are eligible for Research Level 1.Collaborative Care Option (Research Level 2): Applications submitted to the FY22 PRORP CTA Translation of Early Findings – Soft Tissue Trauma Focus Area are eligible for a Collaborative Care Option (Research Level 2; refer to Section II.D.5, Funding Restrictions). The Collaborative Care Option provides additional support to encourage collaborative interdisciplinary research among physical therapists, occupational therapists, prosthetists, surgeons, and other orthopaedic are providers. The proposed research should include both surgical and rehabilitation strategies that create a cohesive project. Surgical strategies are reconstruction and repair and/or application of biologics, pharmaceuticals, and devices for the purpose of restoration of native architecture, composition, and function of traumatically injured tissues. Rehabilitative strategies are those that restore function following injury or illness, with the goal of optimal health and independence. Projects should integrate principles and approaches from surgical and rehabilitative strategies, beyond what each approach would provide by itself, with the goal of optimizing form, function, and independence for those who have sustained traumatic orthopaedic injuries. The rehabilitation strategy and the standard of care must be specified. Projects that follow patients across the continuum of care are highly encouraged. To encourage meaningful and productive multidisciplinary collaborations, projects submitted for this option must include at least one investigator with orthopaedic rehabilitation expertise and at least one clinician who specializes in orthopaedic or trauma care. A Letter(s) of Collaboration from both specialists (rehabilitation expert and surgeon) is required for this option. A clinician is defined as an individual who is credentialed (possesses the necessary degrees, licenses, and other certifications) and practicing as a care provider in a relevant capacity.If the proposed clinical trial involves the use of a drug that has not been approved by the Food and Drug Administration (FDA) for the proposed investigational use, then an Investigational New Drug (IND) application to the FDA that meets all requirements under 21 CFR 312 may be required. It is the responsibility of the applicant to provide evidence from the IRB of record or the FDA if an IND is not required. If an IND is required, the IND application must be submitted to the FDA within 6 months of the award date. The IND should be specific for the product (i.e., the product should not represent a derivative or alternate version of the investigational agent described in the IND application) and indication to be tested in the proposed clinical trial. For more information on IND applications, the FDA has provided guidance at https://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/ap provalapplications/investigationalnewdrugindapplication/default.htm.If the investigational product is a device, then an Investigational Device Exemption (IDE) application to the FDA that meets all requirements under 21 CFR 812 may be required. It is the responsibility of the applicant to provide evidence if an IDE is not required or the device qualifies for an abbreviated IDE. If an IDE is required, the IDE application must be submitted to the FDA within 6 months of the award date. The IDE should be specific for the device (i.e., should not represent a derivative or modified version of the device described in the IDE application) and indication to be tested in the proposed clinical trial.If the proposed research includes a clinical trial of an investigational product to be conducted at international sites, an application to the relevant national regulatory agency of each host country must be submitted within 6 months of the award date.The government reserves the right to withdraw funding if an IND or IDE application and/or international regulatory application is necessary but has not been submitted within 6 months of the award date.Key aspects of the PRORP Clinical Trial Award Mechanism:• Clinical Trial Start Date: The proposed clinical trial is expected to begin no later than 12 months after the award date or 18 months after the award date for FDA-regulated studies.• Preliminary data are required: Inclusion of preliminary data relevant to the proposed clinical trial is required.• Study Population: The application should demonstrate the availability of and access to a suitable patient population that will support a meaningful outcome for the study. The application should include a discussion of how accrual goals will be achieved, as well as the strategy for inclusion of women and minorities in the clinical trial appropriate to the objectives of the study.• Intervention Availability: The application should demonstrate the documented availability of and access to the drug/compound, device, and/or other materials needed, as appropriate, for the proposed duration of the study.• Personnel and Environment: The application should demonstrate the study team’s expertise and experience in all aspects of conducting clinical trials, including appropriate statistical analysis, knowledge of FDA processes (if applicable), and data management. The application should include a study coordinator(s) who will guide the clinical protocol through the local Institutional Review Board (IRB) of record and other federal agency regulatory approval processes, coordinate activities from all sites participating in the trial, and coordinate participant accrual. The application should show strong institutional support and, if applicable, a commitment to serve as the FDA regulatory sponsor, ensuring all sponsor responsibilities described in the 21 CFR 312, Subpart D, are fulfilled.• Statistical Analysis and Data Management Plans: The application should include a clearly articulated statistical analysis plan, a power analysis reflecting sample size projections that will answer the objectives of the study and a data management plan and use of an appropriate database to safeguard and maintain the integrity of the data. If FDA-regulated, the trial must use a 21 CFR 11-compliant database and appropriate data standards. For more on data standards, see https://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/ElectronicSubmissions/UCM511237.pdf.Funded trials are required to post a copy of the informed consent form used to enroll subjects on a publicly available federal website in accordance with federal requirements described in the Code of Federal Regulations, Title 32, Part 219 (32 CFR 219). Funded studies are required to register the study in the National Institutes of Health (NIH) clinical trials registry, www.clinicaltrials.gov, prior to initiation of the study. Refer to the General Application Instructions, Appendix 1, Section B, for further details.The types of awards made under the program announcement will be assistance agreements. An assistance agreement is appropriate when the federal government transfers a “thing of value” to a “state, local government,” or “other recipient” to carry out a public purpose of support or stimulation authorized by a law of the United States instead of acquiring property or service for the direct benefit and use of the U.S. government. An assistance agreement can take the form of a grant or cooperative agreement. The level of involvement on the part of the Department of Defense (DOD) during project performance is the key factor in determining whether to award a grant or cooperative agreement. If “no substantial involvement” on the part of the funding agency is anticipated, a grant award will be made (31 USC 6304). Conversely, if substantial involvement on the part of the funding agency is anticipated, a cooperative agreement will be made (31 USC 6305), and the award will identify the specific substantial involvement. Substantial involvement may include, but is not limited to, collaboration, participation, or intervention in the research to be performed under the award. The award type, along with the will be determined during the negotiation process.The anticipated total costs budgeted for the entire period of performance for an FY22 PRORP Clinical Trial Award will not exceed $2.5M (Research Level 1) or $3.0M (Research Level 2). Refer to Section II.D.5, Funding Restrictions, for detailed funding information.Awards will be made no later than September 30, 2023. For additional information, refer to Section II.F.1, Federal Award Notices.The CDMRP expects to allot approximately $10.0M to fund approximately four Research Level 1 Clinical Trial Award applications and approximately $6.0M to fund two Research Level 2 Clinical Trial Award applications. Funding of applications received is contingent upon the availability of federal funds for this program as well as the number of applications received, the quality and merit of the applications as evaluated by scientific and programmatic review, and the requirements of the government. Funds to be obligated on any award resulting from this funding opportunity will be available for use for a limited time period based on the fiscal year of the funds. It is anticipated that awards made from this FY22 funding opportunity will be funded with FY22 funds, which will expire for use on September 30, 2028.
Categories: Science and Technology and other Research and Development.