W81XWH-22-PRORP_CTA_GG.pdf

This program announcement must be read in conjunction with the General Application

Instructions, version 702. The General Application Instructions document is available for downloading from the Grants.gov funding opportunity announcement by selecting the

“Package” tab, clicking “Preview,” and then selecting “Download Instructions.”

DOD FY22 Peer Reviewed Orthopaedic Clinical Trial Award 1

I. OVERVIEW OF THE FUNDING OPPORTUNITY

Program Announcement for the Department of Defense

Defense Health Program

Congressionally Directed Medical Research Programs

Peer Reviewed Orthopaedic Research Program

Clinical Trial Award

Announcement Type: Initial

Funding Opportunity Number: W81XWH-22-PRORP-CTA

Assistance Listing Number: 12.420 Military Medical

Research and Development

SUBMISSION AND REVIEW DATES AND TIMES

Pre-Application Submission Deadline: 5:00 p.m. Eastern time (ET), June 16, 2022

Invitation to Submit an Application: July 20, 2022

Application Submission Deadline: 11:59 p.m. ET, September 13, 2022

End of Application Verification Period: 5:00 p.m. ET, September 16, 2022

Peer Review: November 2022

Programmatic Review: January 2023

DOD FY22 Peer Reviewed Orthopaedic Clinical Trial Award 2

TABLE OF CONTENTS

I. OVERVIEW OF THE FUNDING OPPORTUNITY

II. DETAILED INFORMATION ABOUT THE FUNDING OPPORTUNITY

II.A. Program Description

II.A.1. FY22 PRORP Clinical Trial Award (CTA) Focus Areas

II.A.2. Award History

II.B. Award Information

II.C. Eligibility Information

II.C.1. Eligible Applicants

II.C.2. Cost Sharing

II.C.3. Other

II.D. Application and Submission Information

II.D.1. eBRAP and Grants.gov

II.D.2. Content and Form of the Application Submission

II.D.3. Unique Entity Identifier (UEI) and System for Award Management (SAM)

II.D.4. Submission Dates and Times

II.D.5. Funding Restrictions

II.D.6. Other Submission Requirements

II.E. Application Review Information

II.E.1. Criteria

II.E.2. Application Review and Selection Process

II.E.3. Integrity and Performance Information

II.E.4. Anticipated Announcement and Federal Award Dates

II.F. Federal Award Administration Information

II.F.1. Federal Award Notices

II.F.2. Administrative and National Policy Requirements

II.F.3. Reporting

II.G. Federal Awarding Agency Contacts

II.G.1. eBRAP Help Desk

II.G.2. Grants.gov Contact Center

II.H. Other Information

II.H.1. Program Announcement and General Application Instructions Versions

II.H.2. Administrative Actions

II.H.3. Application Submission Checklist

APPENDIX 1: ACRONYM LIST

APPENDIX 2: DOD AND VA WEBSITES

DOD FY22 Peer Reviewed Orthopaedic Clinical Trial Award 3

II. DETAILED INFORMATION ABOUT THE FUNDING

OPPORTUNITY

II.A. Program Description

Applications to the Fiscal Year 2022 (FY22) Peer Reviewed Orthotics Research Program

(PRORP) are being solicited by the U.S. Army Medical Research Acquisition Activity

(USAMRAA) using delegated authority provided by United States Code, Title 10, Section 2358

(10 USC 2358). The execution management agent for this program announcement is the

Congressionally Directed Medical Research Programs (CDMRP) at the U.S. Army Medical

Research and Development Command (USAMRDC). The PRORP was initiated in 2009 to provide support for research of exceptional scientific merit focused on optimizing recovery and restoration of function for military personnel with orthopaedic injuries sustained in combat or combat-related duties. Appropriations for the PRORP from FY09 through FY21 totaled $458.5 million (M). The FY22 appropriation is $30M.

The FY22 PRORP challenges the scientific community to address the most significant gaps in care for the leading burden of injury and for facilitating return to duty. The program intends to support high-impact and clinically relevant research to advance the optimal treatment and rehabilitation from musculoskeletal injuries (excluding spinal cord injuries) sustained during combat, combat-related activities, and non-battle injuries that impact unit readiness and the ability to return to duty/work. It is expected that research findings would also benefit the general population. Applications involving multidisciplinary collaborations among academia, industry, the military Services, the U.S. Department of Veterans Affairs (VA), and/or other federal agencies are highly encouraged.

The proposed research must be relevant to active-duty Service Members, Veterans, military beneficiaries, and/or the American public.

II.A.1. FY22 PRORP Clinical Trial Award (CTA) Focus Areas

In September 2021, the PRORP hosted a stakeholders meeting to identify critical knowledge and capability gaps in orthopaedic research and care. Representatives from non-profit organizations, academia, industry, government institutions, and the public shared broad perspectives on potential barriers in research and patient outcomes, key knowledge and scientific gaps, and potential approaches for addressing orthopaedic needs. Resources shared during the meeting and outcomes of the effort can be found on the CDMRP website (https://cdmrp.army.mil/ prorp/default). The FY22 PRORP Focus Areas incorporate several of the stakeholder-identified gaps.

Applications submitted to this program announcement must address one of the following

FY22 PRORP Applied Research Award Focus Areas. Selection of the appropriate Focus Area is the responsibility of the applicant.

https://cdmrp.army.mil/prorp/default https://cdmrp.army.mil/prorp/default

DOD FY22 Peer Reviewed Orthopaedic Clinical Trial Award 4

1. Limb Stabilization and Protection: Clinical evaluation of rapid limb stabilization and novel wound protectants for severely or critically wounded limbs to enable prolonged care and eventual transport to the point of definitive treatment.

2. Retention Strategies: Optimization and/or validation of battlefield-feasible diagnostic capabilities, decision support tools, interventions, and/or rehabilitation strategies that can facilitate retention on duty or avoid reinjury for common combat-related musculoskeletal injuries. Biomarker studies are excluded. The current standard of care must be noted. The rehabilitation strategy to be used in the proposed study must be specified, as applicable.

2a. Battlefield Care: Strategies that can be utilized at or near the point of injury to allow an injured Service Member to remain on the battlefield or on mission without the need for evacuation. Treatment strategies that allow return to mission effectiveness within 30 days will be considered.

2b. Return to Duty: Treatment strategies that can be utilized along the continuum of care and enable return to duty of the Service Member within 1 year of injury.

3. Translation of Early Findings: Translation of early research findings in the orthopaedic surgical care Topic Areas listed below to move the research toward clinical practice.

3a. Soft Tissue Trauma: Strategies for musculoskeletal extremity soft tissue trauma treatments for shoulder, knee, or chronic ankle instability and sequela only, to optimize return to duty, work, or reintegration.

3b. Fracture-Related Infection: Strategies to decrease the burden of fracture-related infections (may include prevention, early detection, or improved eradication). Alternatives to systemic antibiotic delivery are encouraged. Novel approaches that improve the current standard of treatment to prevent fracture-related infections are encouraged.

II.A.2. Award History

The PRORP Clinical Trial Award mechanism was first offered in FY09. Since then, 194

Clinical Trial Award applications have been received, and 42 (21.6%) have been recommended for funding.

II.B. Award Information

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

DOD FY22 Peer Reviewed Orthopaedic Clinical Trial Award 5 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 care 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 https://cdmrp.army.mil/pubs/pdf/Human%20Subjects%20Resource%20Document.pdf

DOD FY22 Peer Reviewed Orthopaedic Clinical Trial Award 6 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 https://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/investigationalnewdrugindapplication/default.htm https://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/investigationalnewdrugindapplication/default.htm

DOD FY22 Peer Reviewed Orthopaedic Clinical Trial Award 7 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 start date, will be determined during the negotiation process.

https://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/ElectronicSubmissions/UCM511237.pdf https://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/ElectronicSubmissions/UCM511237.pdf http://www.clinicaltrials.gov/

DOD FY22 Peer Reviewed Orthopaedic Clinical Trial Award 8

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.

Research Involving Human Anatomical Substances, Human Subjects, or Human

Cadavers: All DOD-funded research involving new and ongoing research with human anatomical substances, human subjects, or human cadavers must be reviewed and approved by the USAMRDC Office of Research Protections (ORP), Human Research Protection Office

(HRPO), prior to research implementation. This administrative review requirement is in addition to the local IRB or Ethics Committee (EC) review. Local IRB/EC approval at the time of submission is not required. Allow up to 3 months to complete the HRPO regulatory review and approval process following submission of all required and complete documents to the HRPO.

Refer to the General Application Instructions, Appendix 1, and the Human Research Protections

Office Resources and Overview document available on the electronic Biomedical Research

Application Portal (eBRAP) “Funding Opportunities & Forms” web page

(https://ebrap.org/eBRAP/public/Program.htm) for additional information.

If the proposed research involves more than one institution, plans for the multi-institutional structure governing the research protocol(s) should be outlined in Attachment 10: Study

Personnel and Organization. In addition, a written plan for single IRB review arrangements must be provided for research conducted in the United States involving more than one institution. The lead institution responsible for developing the master protocol and master consent form should be identified and should be the single point of contact for regulatory submissions and requirements. Communication and data transfer between or among the collaborating institutions, as well as how specimens and/or imaging products obtained during the study will be handled, should be included in the appropriate sections of the application. A separate intellectual and material property plan agreed on by all participating institutions is also required for multi-institutional clinical trials.

Encouraged DOD and/or VA Collaboration: Military relevance is a key feature of this award.

PIs are encouraged, but not required, to collaborate with DOD or VA researchers and clinicians

(Appendix 2).

https://ebrap.org/eBRAP/public/Program.htm

DOD FY22 Peer Reviewed Orthopaedic Clinical Trial Award 9

Use of DOD or VA Resources: If the proposed research involves access to active-duty military or VA patient populations and/or 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. Refer to the General Application Instructions, Appendix

1, for additional information.

II.C. Eligibility Information

II.C.1. Eligible Applicants

II.C.1.a. Organization: All organizations, including foreign organizations, foreign public entities, and international organizations, are eligible to apply.

Government Agencies Within the United States: Local, state, and federal government agencies are eligible to the extent that applications do not overlap with their fully funded internal programs. Such agencies are required to explain how their applications do not overlap with their internal programs.

As applications for this program announcement may be submitted by extramural and intramural organizations, these terms are defined below.

Extramural Organization: An eligible non-DOD organization. Examples of extramural organizations include academic institutions, biotechnology companies, foundations, federal government organizations other than the DOD, and research institutes.

Intramural DOD Organization: A DOD laboratory, DOD military treatment facility, and/or

DOD activity embedded within a civilian medical center. Intramural Submission: An application submitted by a DOD organization for an intramural investigator working within a

DOD laboratory or military treatment facility or in a DOD activity embedded within a civilian medical center.

The USAMRAA makes awards to eligible organizations, not to individuals.

II.C.1.b. Principal Investigator

Independent investigators at all academic levels (or equivalent) may be named by organizations as the PI on the application.

There is no limitation on the number of applications for which an investigator may be named as a

PI.

An eligible PI, regardless of ethnicity, nationality, or citizenship status, must be employed by, or affiliated with, an eligible organization.

The CDMRP strongly encourages all PIs to participate in a digital identifier initiative through

Open Researcher and Contributor ID, Inc. (ORCID). Registration for a unique ORCID identifier can be done online at https://orcid.org/.

https://orcid.org/

DOD FY22 Peer Reviewed Orthopaedic Clinical Trial Award 10

II.C.2. Cost Sharing

Cost sharing/matching is not an eligibility requirement.

II.C.3. Other

Organizations must be able to access .gov and .mil websites in order to fulfill the financial and technical deliverable requirements of the award and submit invoices for payment.

For general information on required qualifications for award recipients, refer to the General

Application Instructions, Appendix 3.

Refer to Section II.H.2, Administrative Actions, for a list of administrative actions that may be taken if a pre-application or application does not meet the administrative, eligibility, or ethical requirements defined in this program announcement.

II.D. Application and Submission Information

Submission of applications that are essentially identical or propose essentially the same research project to different funding opportunities within the same program and fiscal year is prohibited and will result in administrative withdrawal of the duplicative application(s).

II.D.1. eBRAP and Grants.gov eBRAP (https://ebrap.org) is a secure web-based system that allows PIs to submit their pre-applications, view and verify extramural full applications submitted to Grants.gov

(https://grants.gov), receive communications from the CDMRP, and submit documentation during award negotiations and throughout the period of performance. eBRAP also allows intramural organizations to submit full applications following pre-application submission.

Grants.gov is a federal system required to be utilized by agencies to receive and process extramural grant applications. Full applications may only be submitted to Grants.gov after submission of a pre-application through eBRAP.

Contact information for the eBRAP Help Desk and the Grants.gov Contact Center can be found in Section II.G, Federal Awarding Agency Contacts.

Extramural Submission:

Pre-application content and forms must be accessed and submitted at eBRAP.org.

Full application packages must be accessed and submitted at Grants.gov.

Intramural DOD Submission:

Pre-application content and forms must be accessed and submitted at eBRAP.org.

Full application packages must be accessed and submitted at eBRAP.org.

https://ebrap.org/ https://grants.gov/

DOD FY22 Peer Reviewed Orthopaedic Clinical Trial Award 11

Note: Applications from an intramural DOD organization or from an extramural federal government organization may be submitted to Grants.gov through a research foundation.

II.D.2. Content and Form of the Application Submission

Submission is a two-step process requiring both pre-application (eBRAP.org) and full application (eBRAP.org or Grants.gov) as indicated below. The submission process should be started early to avoid missing deadlines. There are no grace periods. Full application submission guidelines differ for extramural (Grants.gov) and intramural (eBRAP.org) organizations (refer to Table 1, Full Application Guidelines).

The application title, eBRAP log number, and all information for the PI, Business Official(s), performing organization, and contracting organization must be consistent throughout the entire pre-application and full application submission process. Inconsistencies may delay application processing and limit or negate the ability to view, modify, and verify the application in eBRAP. If any changes need to be made, the applicant should contact the eBRAP Help Desk at help@eBRAP.org or 301-682-5507 prior to the application submission deadline.

II.D.2.a. Step 1: Pre-Application Submission Content

During the pre-application process, eBRAP assigns each submission a unique log number.

This unique eBRAP log number is required during the full application submission process.

To begin the pre-application process, first select whether the submitting organization is extramural or intramural, then confirm your selection or cancel. Incorrect selection of extramural or intramural submission type will delay processing.

If an error has been made in the selection of extramural versus intramural and the pre-application submission deadline has passed, the PI or Business Official must contact the eBRAP Help Desk at help@eBRAP.org or 301-682-5507 to request a change in designation.

All pre-application components must be submitted by the PI through eBRAP

(https://eBRAP.org/). Because the invitation to submit an application is based on the contents of the pre-application, investigators should not change the title or research objectives after the pre-application is submitted.

The applicant organization and associated PI(s) (and mentors) identified in the pre-application should be the same as those intended for the subsequent application submission. If any changes are necessary after submission of the pre-application, the applicant must contact the eBRAP Help

Desk at help@eBRAP.org or 301-682-5507.

PIs with an ORCID identifier should enter that information in the appropriate field in the “My

Profile” tab in the “Account Information” section of eBRAP.

The pre-application consists of the following components, which are organized in eBRAP by separate tabs (refer to the General Application Instructions, Section II.B, for additional information on pre-application submission):

mailto:help@eBRAP.org mailto:help@eBRAP.org mailto:help@eBRAP.org

DOD FY22 Peer Reviewed Orthopaedic Clinical Trial Award 12

Tab 1 – Application Information

Submission of application information includes assignment of primary and secondary research classification codes, which may be found at https://ebrap.org/eBRAP/public/

Program.htm. Applicants are strongly encouraged to review and confirm the codes prior to making their selection.

Tab 2 – Application Contacts

Enter contact information for the PI. Enter the organization’s Business Official responsible for sponsored program administration (the “person to be contacted on matters involving this application” in Block 5 of the Grants.gov SF424 Research & Related Form). The Business

Official must be either selected from the eBRAP list or invited in order for the pre-application to be submitted.

Select the performing organization (site at which the PI will perform the proposed work) and the contracting organization (organization submitting on behalf of the PI, which corresponds to Block 5 on the Grants.gov SF424 Research & Related Form), and click on “Add

Organizations to this Pre-application.” The organization(s) must be either selected from the eBRAP drop-down list or invited in order for the pre-application to be submitted.

It is recommended that PIs identify an Alternate Submitter in the event that assistance with pre-application submission is needed.

Tab 3 – Collaborators and Key Personnel

Enter the name, organization, and role of all collaborators and key personnel associated with the application.

FY22 PRORP Programmatic Panel members should not be involved in any pre-application or application. For questions related to panel members and pre-applications or applications, refer to Section II.H.2.c, Withdrawal, or contact the eBRAP Help Desk at help@eBRAP.org or 301-682-5507.

Tab 4 – Conflicts of Interest

List all individuals other than collaborators and key personnel who may have a conflict of interest in the review of the application (including those with whom the PI has a personal or professional relationship).

Tab 5 – Pre-Application Files

Note: Upload documents as individual PDF files unless otherwise noted. eBRAP will not allow a file to be uploaded if the number of pages exceeds the limit specified below.

○ Preproposal Narrative (three-page limit): The Preproposal Narrative page limit applies to text and non-text elements (e.g., figures, tables, graphs, photographs, diagrams, chemical structures, drawings) used to describe the project. Inclusion of URLs that https://ebrap.org/eBRAP/public/Program.htm https://ebrap.org/eBRAP/public/Program.htm http://cdmrp.army.mil/prorp/panels/panels22 mailto:help@eBRAP.org

DOD FY22 Peer Reviewed Orthopaedic Clinical Trial Award 13 provide additional information to expand the Preproposal Narrative and could confer an unfair competitive advantage is prohibited and may result in administrative withdrawal of the pre-application.

The Preproposal Narrative should include the following:

– Research Idea: State the ideas and reasoning on which the proposed work is based, and further indicate whether the research is ready to move into a clinical trial. State the hypothesis to be tested or the objective to be reached. State the intervention to be tested and indicate the phase of clinical trial and/or class of device. State how this project addresses an important problem relevant to combat-related or traumatic orthopaedic injuries.

– Research Strategy: Clearly describe the research strategy for the proposed project.

Concisely state the specific aims and proposed methods. Identify the patient population to be engaged during the study.

– Impact and Alignment with Focus Area: State explicitly how the proposed work may have a short- and/or long-term impact on patient care and/or restoration of function for those who have sustained orthopaedic injuries. Explain how the proposed work addresses an FY22 PRORP CTA Focus Area.

– Military Benefit: Describe how the proposed work would impact point of injury care and/or the healthcare needs of Service Members and/or Veterans who have sustained combat-related orthopaedic injuries, as well as the treatment of non-battle injuries that significantly impact unit readiness and return to duty/work rates.

– Personnel: Briefly state the qualifications of the PI and key personnel to perform the clinical trial (detailed key personnel biographical sketches [six pages per individual] are allowed as part of pre-application supporting documentation, as described below).

For the Collaborative Care Option, indicate how the expertise of the clinician(s) and rehabilitation specialist(s) are complementary and cover orthopaedic rehabilitation as well as orthopaedic or trauma care.

○ Pre-Application Supporting Documentation: The items to be included as supporting documentation for the pre-application must be uploaded as individual files and are limited to the following:

– References Cited (one-page limit): List the references cited (including URLs if available) in the Preproposal Narrative using a standard reference format that includes the full citation (i.e., author[s], year published, reference title, and reference source, including volume, chapter, page numbers, and publisher, as appropriate).

– List of Abbreviations, Acronyms, and Symbols: Provide a list of abbreviations, acronyms, and symbols used in the Preproposal Narrative.

– Key Personnel Biographical Sketches (six-page limit per individual): All biographical sketches should be uploaded as a single combined file. Biographical

DOD FY22 Peer Reviewed Orthopaedic Clinical Trial Award 14 sketches should be used to demonstrate background and expertise through education, positions, publications, and previous work accomplished.

Tab 6 – Submit Pre-Application

This tab must be completed for the pre-application to be accepted and processed.

Pre-Application Screening

Pre-Application Screening Criteria

To determine the technical merits of the pre-application and the relevance to the mission of the Defense Health Program (DHP) and the PRORP, pre-applications will be screened based on the following criteria:

○ Research Idea: How well the ideas and reasoning for the proposed work is supported, and how well the background provided indicates the research is ready to move into a clinical trial.

○ Research Strategy: How well the specific aims, patient population, and proposed methodology will achieve the desired outcomes.

○ Impact and Alignment with Focus Area: The extent to which the study will make important short- and/or long-term contributions to patient care and/or restoration of function for those who have sustained orthopaedic injuries. How well the proposed research addresses the selected FY22 PRORP CTA Focus Area.

○ Military Benefit: The degree to which the proposed clinical trial will impact point of injury care and/or the healthcare needs of military Service Members and Veterans who have sustained combat-related orthopaedic injuries or non-battle orthopaedic injuries that impact unit readiness and return to duty/work.

○ Personnel: Whether the background and experience of the PI and other key personnel are appropriate to successfully complete the clinical trial.

Notification of Pre-Application Screening Results

Following the pre-application screening, PIs will be notified as to whether or not they are invited to submit applications; however, they will not receive feedback (e.g., a critique of strengths and weaknesses) on their pre-application. The estimated timeframe for notification of invitation to submit an application is indicated in Section I, Overview of the Funding Opportunity. Invitations to submit a full application are based on the Pre-Application Screening Criteria listed above.

II.D.2.b. Step 2: Full Application Submission Content

Applications will not be accepted unless notification of invitation has been received.

DOD FY22 Peer Reviewed Orthopaedic Clinical Trial Award 15

The CDMRP cannot make allowances/exceptions to its policies for submission problems encountered by the applicant organization using system-to-system interfaces with Grants.gov.

Each application submission must include the completed full application package for this program announcement. The full application package is submitted by the Authorized Organizational Representative through Grants.gov (https://grants.gov/) for extramural organizations or through eBRAP (https://ebrap.org/) for intramural organizations. See Table 1 below for more specific guidelines.

II.D.2.b.i. Full Application Guidelines

Extramural organizations must submit full applications through Grants.gov. Applicants must create a Grants.gov Workspace for submission, which allows the application components to be completed online and routed through the applicant organization for review prior to submission.

Applicants may choose to download and save individual PDF forms rather than filling out webforms in Workspace. A compatible version of Adobe Reader must be used to view, complete, and submit an application package consisting of PDF forms. If more than one person is entering text into an application package, the same version of Adobe Reader software should be used by each person. Check the version number of the Adobe software on each user’s computer to make sure the versions match. Using different versions of Adobe Reader may cause submission and/or save errors – even if each version is individually compatible with Grants.gov.

Refer to the General Application Instructions, Section III, and the “Apply For Grants” page of Grants.gov (https://www.grants.gov/web/grants/applicants/apply-for-grants.html) for further information about the Grants.gov Workspace submission process. Submissions of extramural applications through eBRAP may be withdrawn.

Do not password protect any files of the application package, including the Project Narrative.

Table 1. Full Application Submission Guidelines

Extramural Submissions Intramural DOD Submissions

Application Package Location

Download application package components for W81XWH-22-PRORP-CTA from Grants.gov (https://grants.gov/) and create a Grants.gov Workspace. Workspace allows online completion of the application components and routing of the application package through the applicant organization for review prior to submission.

Download application package components for W81XWH-22-PRORP-CTA from eBRAP (https://ebrap.org).

Full Application Package Components

SF424 Research & Related Application for Federal Assistance Form: Refer to the General Application Instructions, Section III.A.1, for detailed information.

Tab 1 – Summary: Provide a summary of the application information.

Tab 2 – Application Contacts: This tab will be pre-populated by eBRAP; add Authorized Organizational Representative.

https://grants.gov/ https://ebrap.org/ https://www.grants.gov/web/grants/applicants/apply-for-grants.html https://grants.gov/

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Extramural Submissions Intramural DOD Submissions

Descriptions of each required file can be found under Full Application Submission Components:

Attachments

Research & Related Personal Data

Research & Related Senior/Key Person

Profile (Expanded)

Research & Related Budget

Project/Performance Site Location(s) Form

Research & Related Subaward Budget

Attachment(s) Form

Tab 3 – Full Application Files: Upload files under each Application Component in eBRAP.

Descriptions of each required file can be found under Full Application Submission

Components:

Attachments

Key Personnel

Budget

Performance Sites

Tab 4 – Application and Budget Data:

Review and edit proposed project start date, proposed end date, and budget data pre-populated from the Budget Form.

Application Package Submission

Create a Grants.gov Workspace.

Add participants (investigators and Business

Officials) to Workspace, complete all required forms, and check for errors before submission.

Submit a Grants.gov Workspace Package.

An application may be submitted through

Workspace by clicking the “Sign and Submit” button on the “Manage Workspace” page, under the “Forms” tab. Grants.gov recommends submission of the application package at least

24-48 hours prior to the close date to allow time to correct any potential technical issues that may disrupt the application submission.

Note: If either the Project Narrative or the budget fails eBRAP validation or needs to be modified, an updated Grants.gov application package must be submitted via Grants.gov as a

“Changed/Corrected Application” with the previous Grants.gov Tracking ID prior to the application submission deadline. Do not password protect any files of the application package, including the Project Narrative.

Submit package components to eBRAP

(https://ebrap.org).

Tab 5 – Submit/Request Approval Full

Application: After all components are uploaded and prior to the full application submission deadline, enter your password in the space provided next to “Enter Your Password

Here” and press the “Submit Full Application” button. eBRAP will notify your Resource

Manager/Comptroller/Task Area Manager or equivalent Business Official by email. Do not password protect any files of the application package, including the Project Narrative.

Application Verification Period

The full application package submitted to

Grants.gov may be viewed and modified in eBRAP until the end of the application verification period. During the application

After eBRAP has processed the full application, the organizational Resource Manager/

Comptroller/Task Area Manager or equivalent

Business Official and PI will receive email

DOD FY22 Peer Reviewed Orthopaedic Clinical Trial Award 17

Extramural Submissions Intramural DOD Submissions verification period, the full application package may be modified with the exception of the

Project Narrative and Research & Related

Budget Form.

notification of this status and will be able to view and modify application components in eBRAP. During the application verification period, the full application package may be modified with the exception of the Project

Narrative and Research & Related Budget

Form. Your Resource Manager/

Comptroller/Task Area Manager or equivalent

Business Official should log into eBRAP to review and to approve prior to the application verification deadline.

Further Information

Tracking a Grants.gov Workspace Package.

After successfully submitting a Workspace package, a Grants.gov Tracking Number is automatically assigned to the package. The number will be listed on the “Confirmation” page that is generated after submission.

Refer to the General Application Instructions, Section III, for further information regarding

Grants.gov requirements.

Refer to the General Application Instructions, Section IV, for further information regarding eBRAP requirements.

The full application package must be submitted using the unique eBRAP log number to avoid delays in application processing.

II.D.2.b.ii. Full Application Submission Components

Extramural Applications Only

SF424 Research & Related Application for Federal Assistance Form: Refer to the

General Application Instructions, Section III.A.1, for detailed information.

Extramural and Intramural Applications

Attachments:

Each attachment to the full application components must be uploaded as an individual file in the format specified and in accordance with the formatting guidelines listed in the

General Application Instructions, Appendix 4.

For all attachments, ensure that the file names are consistent with the guidance. Attachments will be rejected if the file names are longer than 50 characters or have incorrect file names that contain characters other than the following: A-Z, a-z, 0-9, underscore, hyphen, space, and period. In addition, there are file size limits that may apply in some circumstances.

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Individual attachments may not exceed 20 megabytes (MB), and the file size for the entire full application package may not exceed 200 MB.

○ Attachment 1: Project Narrative (20-page limit): Upload as

“ProjectNarrative.pdf”. The page limit of the Project Narrative applies to text and non-text elements (e.g., figures, tables, graphs, photographs, diagrams, chemical structures, drawings) used to describe the project. Inclusion of URLs (uniform resource locators) that provide additional information to expand the Project Narrative and could confer an unfair competitive advantage is prohibited and may result in administrative withdrawal of the application.

The Project Narrative is NOT the formal clinical trial protocol. Instead, all essential elements of the proposed clinical trial necessary for scientific review must be included as directed in Attachment 1 (the Project Narrative) and Attachments 6–9 described below. Failure to submit these attachments as part of the application package will result in rejection of the entire application.

Describe the proposed project in detail using the outline below.

– Background: Describe in detail the scientific rationale for the study. Provide a literature review and analysis. Describe the preliminary studies and/or preclinical data that led to the development of the proposed clinical trial. Provide a summary of other relevant ongoing, planned, or completed clinical trials and describe how the proposed study differs. Describe how the proposed intervention, if applicable, compares/improves on standard of care or other available interventions. Include a discussion of any current clinical use of the intervention under investigation, and/or details of its study in clinical trials for other indications (as applicable). The background section should clearly support the choice of study variables and should explain the basis for the study questions and/or study hypotheses. This section should establish the relevance of the study and explain the applicability of the proposed research outcomes to the relevant FY22 PRORP CTA Focus Area.

If the proposed clinical trial was initiated using other funding prior to this application, explain the history and background of the clinical trial and declare the source of prior funding. Specifically identify the portions of the study that will be supported with funds from this award. For applications submitted to Research Level 2

(Collaborative Care Option), explain how the surgical and rehabilitative strategies are integrated beyond what each approach would result in alone regarding the goal of optimizing form, function, and independence for those who have sustained traumatic orthopaedic injuries.

– Objectives/Specific Aims/Hypotheses: Provide a description of the purpose and objectives of the study with detailed specific aims and/or study questions/hypotheses.

– Study Design: Describe the type of study to be performed (e.g., treatment, prevention, diagnostic), the study phase or class (if applicable), and the study model

DOD FY22 Peer Reviewed Orthopaedic Clinical Trial Award 19

(e.g., single group, parallel, crossover). Outline the proposed methodology in sufficient detail to show a clear course of action.

Identify the intervention to be tested and describe the projected results.

Define the primary and any secondary or interim endpoints/outcome measures, outline why they were chosen, and describe how and when they will be measured.

Include a description of appropriate controls.