Eligible Applicants: Unrestricted (i.e., open to any type of entity above), subject to any clarification in text field entitled "Additional Information on Eligibility"

Agency Name: Jennifer Shankle Grantor

Description:

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 Department of Defense Trauma Registry. Additionally, orthopaedic injuries and conditions that occur outside of combat (e.g., during training, leisure activities, resultant from old injuries) 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.

Although the PRORP is interested in supporting military-focused research, research supported by the PRORP is expected to also apply to all individuals who have sustained a major orthopaedic injury.

With the initiation of the Arthritis Research Program, the FY24 PRORP may not fund arthritis research; however, research that addresses conditions or health abnormalities related to arthritis is permitted provided the proposed research addresses the selected Focus Area.

The PRORP CTRA is intended to support high-impact and/or emerging clinical research that may not be ready for a full-scale randomized controlled clinical trial. Projects should demonstrate potential to impact the standard of care, both immediate and long-term, as well as contribute to evidence-based guidelines for the evaluation and care of military, Veterans, and all patients with orthopaedic injuries.

• One goal of the FY24 PRORP CTRA is to translate current and emerging techniques and interventions into the clinical space to better serve military and non-military patients. A holistic approach that takes into account the health, functional abilities, and quality of life of individuals who have sustained an orthopaedic injury should be considered.

• Another goal is to identify the most effective diagnosis, treatment, rehabilitation, and prevention options available to support critical decision-making for patients, clinicians, other caregivers, and policymakers.

The FY24 PRORP CTRA differs from the FY24 PRORP Clinical Trial Award (CTA) in that the CTRA allows for clinical research projects that may or may not include a clinical trial, whereas the CTA is restricted to clinical trials only.

Funding from this award mechanism must support clinical research and may not be used for animal research.

Clinical research encompasses research with patient samples, data, and interaction with patients that may or may not be considered a clinical trial. Clinical research is observational in nature and includes: (1) Research that does not seek to evaluate the effects of interventions. Research conducted with human subjects (or on material of human origin such as data, tissues, specimens, and cognitive phenomena) for which an investigator (or colleague) directly interacts with human subjects but does not seek to assess the effects of an intervention, qualifies as clinical research. Patient-oriented research may include but is not limited to: (a) mechanisms of human disease, (b) diagnostic or detection studies (e.g., biomarker or imaging), (c) health disparity studies, and (d) development of new technologies. (2) Epidemiologic and behavioral studies that do not seek to study the safety, effectiveness, and/or efficacy outcomes of an intervention. (3) Outcomes research and health services research that do not fit under the definition of clinical trial. Excluded from the definition of clinical research are in vitro studies that utilize human tissues that cannot be linked to a living individual. Note: Studies that meet the requirements for exemption under §46.104(d)(4) of the Common Rule are not considered clinical research as defined by the CDMRP. Exemption category 4 refers to secondary research for which consent is not required.

A clinical trial is defined in the Code of Federal Regulations, Title 45, Part 46.102 (45 CFR 46.102) as a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include a placebo or another control) to evaluate the effects of the interventions on biomedical or behavioral health-related outcomes.

Studies that do not seek to measure safety, effectiveness, and/or efficacy outcome(s) of an intervention are not considered clinical trials.

For more information, a Human Subject Resource Document is provided at https://cdmrp.health.mil/pubs/pdf/Human%20Subjects%20Resource%20Document_DEC2022.pdf.

Proposed studies submitted to the CTRA may be interventional and may involve some retrospective data analysis. Note that purely retrospective or database-related research is not allowed under this funding opportunity. Small pilot clinical trials with human subjects are allowable.

Key aspects of the PRORP CTRA mechanism:

• Preliminary Data Are Required: Inclusion of preliminary data relevant to the proposed clinical research 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 research appropriate to the objectives of the study. Studies utilizing human biospecimens or datasets that cannot be linked to a specific individual, gender, ethnicity, or race (typically classified as exempt from Institutional Review Board [IRB] review) are exempt from this requirement.

• 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.

• 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 that includes use of an appropriate database to safeguard and maintain the integrity of the data. If proposing a clinical trial that requires oversight by a Regulatory Agency, the trial must use a 21 CFR 11-compliant database and appropriate data standards.

For the purposes of this funding opportunity, Regulatory Agency refers to the U.S. Food and Drug Administration (FDA) or any relevant international regulatory agency unless otherwise noted.

If the proposed clinical research involves the use of a drug that has not been approved by the relevant Regulatory Agency for the country where the research will be conducted, then submission of an Investigational New Drug (IND) application, or equivalent, 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 relevant Regulatory Agency if an IND, or equivalent, is not required. If an IND, or equivalent, is required, the regulatory application must be submitted to the relevant Regulatory Agency within 12 months of the CTRA award start date. The IND, or equivalent, should be specific for the product and indication to be tested in the proposed clinical trial. For more information on IND applications specifically, the FDA has provided guidance at https://www.fda.gov/drugs/types-applications/investigational-new-drug-ind-application.

If the investigational product is a device, then submission of an Investigational Device Exemption (IDE), or equivalent, application that meets all requirements under 21 CFR 812 may be required. It is the responsibility of the applicant to provide evidence if an IDE, or equivalent, is not required. If an IDE, or equivalent, is required, the IDE application, or equivalent, must be submitted to the relevant Regulatory Agency within 12 months of the CTRA award start date. The IDE, or equivalent, should be specific for the device and indication to be tested in the proposed clinical trial.

Women’s Health: The CDMRP encourages research on health areas and conditions that affect women uniquely, disproportionately, or differently from men, including studies analyzing sex as a biological variable. Such research should relate anticipated project findings to improvements in women's health outcomes and/or advancing knowledge for women's health. Applications proposing research that solely address women’s health may also consider the FY24 PRORP WHRA mechanism, Funding Opportunity Number HT942524PRORPWHRA.

Use of Department of Defense (DOD) or VA Resources: If the proposed research involves access to DOD or VA resources or databases, the application must describe the access at the time of submission and include a plan for maintaining access as needed throughout the proposed research. Refer to Section II.D.2.b.ii, Full Application Submission Components, for detailed information.

The funding instrument for awards made under the program announcement will be grants (31 USC 6304).

The anticipated total costs budgeted for the entire period of performance for an FY24 PRORP CTRA should not exceed $1.5M. Refer to Section II.D.5, Funding Restrictions, for detailed funding information.

Awards supported with FY24 funds will be made no later than September 30, 2025.

The CDMRP expects to allot approximately $6.0M to fund approximately four CTRA applications. Funding of applications received is contingent upon the availability of federal funds for this program, the number of applications received, the quality and merit of the applications as evaluated by peer 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 FY24 funding opportunity will be funded with FY24 funds, which will expire for use on September 30, 2030.

Grantor Contact Information: CDMRP Help Desk Phone: 301-682-5507 Email: help@eBRAP.org