W81XWH-17-PRMRP-CTA.pdf

This Program Announcement must be read in conjunction with the General Application Instructions, version 20170516. The General Applications 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 FY17 Peer Reviewed Medical 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 Medical Research Program

Clinical Trial Award

Announcement Type: Initial

Funding Opportunity Number: W81XWH-17-PRMRP-CTA

Catalog of Federal Domestic Assistance 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), July 20, 2017

• Invitation to Submit an Application: August 2017

• Application Submission Deadline: 11:59 p.m. ET, October 26, 2017

• End of Application Verification Period: 5:00 p.m. ET, October 31, 2017

• Peer Review: December 2017

• Programmatic Review: February 2018

DoD FY17 Peer Reviewed Medical 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. FY17 PRMRP Topic Areas

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. Address to Request Application Package

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

II.D.3. Dun and Bradstreet Universal Numbering System (DUNS) Number 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. CDMRP 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

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APPENDIX 1 ACRONYM LIST

APPENDIX 2 AREAS OF ENCOURAGEMENT

APPENDIX 3 DOD AND VA WEBSITES

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II. DETAILED INFORMATION ABOUT THE FUNDING

OPPORTUNITY

II.A. Program Description

Applications to the Fiscal Year 2017 (FY17) Peer Reviewed Medical Research Program (PRMRP) are being solicited for the Defense Health Agency (DHA) J9, Research and Development Directorate, 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). As directed by the Office of the Assistant Secretary of Defense for Health Affairs (OASD[HA]), the DHA manages the Defense Health Program (DHP) Research, Development, Test, and Evaluation (RDT&E) appropriation. The execution management agent for this Program Announcement is the Congressionally Directed Medical Research Programs (CDMRP). The PRMRP was initiated in 1999 to provide support for military health-related research of exceptional scientific merit. Appropriations for the PRMRP from FY99 through FY16 totaled $1.371 billion. The FY17 appropriation is $300 million (M).

The vision of the FY17 PRMRP is to improve the health and well-being of all military Service members, Veterans, and beneficiaries. The PRMRP challenges the scientific and clinical communities to address at least one of the FY17 Topic Areas with original ideas that foster new directions along the entire spectrum of research and clinical care. The program seeks applications in laboratory, clinical, behavioral, epidemiologic, and other areas of research to advance knowledge in disease etiology, improve prevention, detection, diagnosis, treatment, and quality of life for those affected by a relevant disease or condition, and to develop and validate clinical care or public health guidelines.

II.A.1. FY17 PRMRP Topic Areas

All applications for PRMRP funding must specifically address at least one of the Topic Areas as directed by Congress and must be directly relevant to the healthcare needs of military Service members, Veterans, and/or beneficiaries. If the proposed research does not specifically address at least one of the FY17 PRMRP Topic Areas, the Government will administratively withdraw the application. The Government reserves the right to reassign the application’s Topic Area if submitted under an inappropriate Topic Area. The FY17 PRMRP Topic Areas are listed below.

• Acute Lung Injury

• Antimicrobial Resistance

• Arthritis

• Burn Pit Exposure

• Chronic Migraine and Post-Traumatic Headache

• Congenital Heart Disease

• Constrictive Bronchiolitis

• Diabetes

• Diarrheal Diseases

• Dystonia

• Early Trauma Thermal Regulation

• Eating Disorders

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• Emerging Infectious Diseases

• Epidermolysis Bullosa

• Focal Segmental Glomerulosclerosis

• Fragile X

• Guillain-Barré Syndrome

• Hepatitis B and C

• Hereditary Angioedema

• Hydrocephalus

• Immunomonitoring of Intestinal Transplants

• Inflammatory Bowel Diseases

• Influenza

• Integrative Medicine

• Interstitial Cystitis

• Malaria

• Metals Toxicology

• Mitochondrial Disease

• Musculoskeletal Disorders

• Nanomaterials for Bone Regeneration

• Non-Opioid Pain Management

• Pancreatitis

• Pathogen-Inactivated Dried Cryoprecipitate

• Polycystic Kidney Disease

• Post-Traumatic Osteoarthritis

• Pulmonary Fibrosis

• Respiratory Health

• Rett Syndrome

• Rheumatoid Arthritis

• Scleroderma

• Sleep Disorders

• Spinal Muscular Atrophy

• Sustained-Release Drug Delivery

• Tinnitus

• Tuberculosis

• Vaccine Development for Infectious Disease

• Vascular Malformations

• Women’s Heart Disease

Research relevant to one or more FY17 PRMRP Topic Areas may be considered for funding.

Applicants should select the FY17 PRMRP Program Announcement most appropriate to the stage of the proposed research. Areas of Encouragement related to the FY17 PRMRP Topic Areas have been identified by the Department of Defense (DoD), the Department of Veterans Affairs (VA), and other relevant stakeholders (Appendix 2). Applicants are urged to read and consider these Areas of Encouragement before preparing their applications. The information provided is not exhaustive, and applicants are not restricted to submitting applications that address an Area of Encouragement in this list.

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II.B. Award Information

The PRMRP Clinical Trial Award supports the rapid implementation of clinical trials with the potential to have a significant impact on a disease or condition addressed in at least one of the Congressionally directed FY17 PRMRP Topic Areas. 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. All studies must be responsive to the healthcare needs of the military Service members, Veterans, and/or beneficiaries; however, the use of military or Veteran populations is not required.

Funding from this award mechanism must support a clinical trial. A clinical trial is defined as a prospective accrual of human subjects where one or more intervention(s) (e.g., device, drug, biologic, surgical procedure, rehabilitative modality, behavioral intervention, or other) is tested on a human subject for a measurable outcome with respect to safety, effectiveness, and/or efficacy. This outcome represents a direct effect on the human subject of that intervention or interaction. Principal Investigators (PIs) seeking funding for a preclinical research project should consider one of the other FY17 PRMRP Program Announcements being offered. The term “human subjects” is used in this Program Announcement to refer to individuals who will be recruited for or who will participate in the proposed clinical trial. For more information, a Human Subject Resource Document is provided at https://ebrap.org/eBRAP/public/Program.htm.

If the proposed clinical trial involves the use of a drug that has not been approved by the U.S.

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 the Code of Federal Regulations, Title 21, Part 312 (21 CFR 312) may be required and must be submitted to the FDA by the application submission deadline. If the investigational product is a device, evidence that an Investigational Device Exemption (IDE) application that meets all requirements under 21 CFR 812 has been submitted to the FDA by the application submission deadline, or that the device is exempt or qualifies for an abbreviated IDE, is required. The Government reserves the right to withdraw funding if an IND or IDE is necessary but has not been submitted to the FDA prior to the grant submission deadline, or if documented status of the IND or IDE has not been obtained within 6 months of the award date.

Applications are not restricted to a predetermined cost limit. The requested budget must be justified and appropriate to the scope of the clinical trial proposed. Refer to Section II.D.5, Funding Restrictions, for detailed funding information.

The following are important aspects of submission for the Clinical Trial Award:

• The proposed clinical trial is expected to begin no later than 12 months after the award date, or 18 months for FDA-regulated studies.

• The proposed intervention(s) to be tested should offer significant potential impact for individuals affected by the specified disease(s)/condition(s).

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

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• Inclusion of preliminary data relevant to the proposed clinical trial is required.

• The proposed clinical trial must be based on sound scientific rationale that is established through logical reasoning and critical review and analysis of the literature.

• The application should describe the planned indication for the product label, if appropriate, and include an outline of the development plan required to support that indication.

• The application should demonstrate availability of, and access to, a suitable patient population that will support a meaningful outcome for the study. The PI should discuss how accrual goals will be achieved and how standards of care may impact the study population.

• The application should demonstrate documented availability of and access to the drug/ compound, device, and/or other materials needed, as appropriate. The quality of the product should be commensurate with FDA manufacturing standards applicable to the type and phase of product being developed (i.e., Quality System Regulation, Good Manufacturing Practices

[GMP]).

• The application should demonstrate the study team has experience interacting with the FDA to include previous FDA submissions, if applicable.

• The proposed clinical trial design should include clearly defined and appropriate endpoints, and follow Good Clinical Practice (GCP) guidelines.

• The application should include a clearly articulated statistical analysis plan, appropriate statistical expertise on the research team, and a power analysis reflecting sample size projections that will clearly answer the objectives of the study.

• The application should include a clearly articulated data management plan and use of an appropriate database to safeguard and maintain the integrity of the data.

• The application should include a clearly articulated safety management plan outlining how safety pharmacovigilance will be conducted, as applicable.

• The application should include a clearly articulated clinical monitoring plan outlining how the study will be monitored for GCP compliance.

• 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 include a Transition Plan (including potential funding and resources) showing how the product will progress to the next clinical trial phase and/or delivery to the market after the successful completion of the FY17 PRMRP Clinical Trial Award.

• The application should clearly demonstrate strong institutional support.

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• Funded studies are required to file the study in the National Institutes of Health (NIH) clinical trials registry, www.clinicaltrials.gov. Refer to the General Application Instructions, Appendix 1, Section C, for further details.

Military Relevance: Relevance to the healthcare needs of military Service members, Veterans, and beneficiaries is a key feature of this award. Investigators are encouraged to consider the following characteristics as examples of how a project may demonstrate military relevance:

• Explanation of how the project addresses an aspect of the target disease/condition/ technology that has direct relevance to military Service members, Veterans, and/or other military health system beneficiaries

• Description of how the knowledge, information, products, or technologies gained from the proposed research could be implemented in a dual-use capacity to benefit the civilian population and also address a military need

• Use of military or Veteran populations or datasets in the proposed research, if appropriate to the proposed research project

• Collaboration with DoD or VA investigators

• Involvement of military consultants (Army, Air Force) or specialty leaders (Navy, Marine Corps) to the Surgeons General in a relevant specialty area

PIs are encouraged to integrate and/or align their research projects with DoD and/or VA research laboratories and programs. Collaboration with the DoD or VA is also encouraged. A list of websites that may be useful in identifying additional information about ongoing DoD and VA areas of research interest or potential opportunities for collaboration within the FY17 PRMRP Topic Areas can be found in Appendix 3.

Use of Active Duty Military and VA Populations: If the proposed research plan involves access to active duty military and/or VA patient populations or resources, the PI is responsible for establishing such access. If possible, access to target active duty military and/or VA patient populations/resources should be confirmed at the time of application submission by inclusion of a letter of support, signed by the lowest ranking person with approval authority, for studies involving active duty military Service members, Veterans, military- and/or VA-controlled study materials, and military and/or VA databases. If access cannot be confirmed at the time of application submission, the Government reserves the right to withhold or revoke funding until the PI has demonstrated support for and access to the relevant population(s) and/or resources.

Note that access to a Veteran population for clinical studies may only be obtained by either collaboration with a VA investigator where the VA investigator has a substantial role in the research or by advertising to the general public.

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 U.S. Army Medical Research and Materiel Command (USAMRMC) Office of Research Protections (ORP), Human Research Protection Office (HRPO) prior to research http://www.clinicaltrials.gov/

DoD FY17 Peer Reviewed Medical Clinical Trial Award 9 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. The HRPO is mandated to comply with specific laws and requirements governing all research involving human anatomical substances, human subjects, or human cadavers that is supported by the DoD. These laws and requirements will necessitate information in addition to that supplied to the IRB/EC. Allow a minimum of 2 to 3 months for HRPO regulatory review and approval processes. Additional time for regulatory reviews may be needed for clinical studies taking place in international settings. When possible, protocols should be written for research with human subjects and/or human anatomical substances that are specific to the DoD-supported effort outlined in the submitted application. Submission to HRPO of protocols covering more than the scope of work in the DoD-funded award will require HRPO review of the entire protocol as DoD-supported research and may include extensive modifications to meet DoD human subjects protection requirements. Refer to the General Application Instructions, Appendix 1, and the Human Subject Resource 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 IRB determines that a trial presents greater than minimal risk to human subjects, the DoD requires an independent research monitor with expertise consistent with the nature of risk(s) identified within the research protocol. If applicable, refer to the General Application Instructions, Appendix 1, for more information on study reporting authorities and responsibilities of the research monitor.

Multi-Institutional Clinical Trials: If the proposed clinical trial is multi-institutional, plans for the multi-institutional structure governing the research protocol(s) should be outlined in the Attachment 9: Study Personnel and Organization. The lead organization 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. A single IRB/EC pathway is strongly recommended whenever possible. The master protocol and consent form must be reviewed by HRPO prior to distribution to the additional sites for IRB/EC review.

Communication and data transfer 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 upon by all participating institutions is also required for multi-institutional clinical trials.

The CDMRP intends that information, data, and research resources generated under awards funded by this Program Announcement be made available to the research community (which includes both scientific and consumer advocacy communities) and to the public at large. For additional guidance, refer to the General Application Instructions, Appendix 2, Section K.

Awards will be made no later than September 30, 2018. For additional information refer to Section II.F.1, Federal Award Notices.

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II.C. Eligibility Information

II.C.1. Eligible Applicants

II.C.1.a. Organization: All organizations, including 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 academia, biotechnology companies, foundations, Government, and research institutes. Extramural Submission: Application submitted by a non-DoD organization to Grants.gov.

Intramural DoD Organization: A DoD laboratory, DoD military treatment facility, and/or DoD activity embedded within a civilian medical center. Intramural Submission: Application submitted by a DoD organization for an intramural investigator who is a DoD military or civilian employee working within a DoD laboratory or military treatment facility or in a DoD activity embedded within a civilian medical center.

Note: Applications from an intramural organization or from an extramural non-DoD Federal organization may be submitted through a research foundation.

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

II.C.1.b. Principal Investigator:

PIs at or above the level of Assistant Professor (or equivalent) are eligible to submit applications.

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

The CDMRP 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 http://orcid.org/.

II.C.2. Cost Sharing

Cost sharing/matching is not an eligibility requirement.

http://orcid.org/

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II.C.3. Other

Extramural 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.

There are no limitations on the number of applications for which an investigator may be named as a PI.

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). As an exception, applicants may submit the research project described in their Clinical Trial Award application as part of an application to the FY17 PRMRP Focused Program Award (Funding Opportunity Number: W81XWH-17-PRMRP-FPA); however, accepting multiple awards to support the same project will not be allowed.

Extramural Submission is defined as an application submitted by a non-DoD organization to Grants.gov.

Intramural Submission is defined as an application submission by a DoD organization for an intramural investigator, who is a DoD military or civilian employee working within a DoD laboratory or military treatment facility, or working in a DoD activity embedded within a civilian medical center.

II.D.1. Address to Request Application Package

Submitting Extramural and Intramural Organizations: Pre-application content and forms can be accessed at eBRAP (https://eBRAP.org).

Submitting Extramural Organizations: Full application packages can be accessed at Grants.gov.

Submitting Intramural DoD Organizations: Full application packages can be accessed at eBRAP.org.

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

https://ebrap.org/

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

Submission is a two-step process requiring both pre-application and full application as indicated below. The submission process should be started early to avoid missing deadlines. There are no grace periods.

Pre-application Submission: All pre-applications for both extramural and intramural organizations must be submitted through eBRAP (https://eBRAP.org/).

eBRAP is a multifunctional web-based system that allows PIs to submit their pre-applications electronically through a secure connection, to view and edit the content of their pre-applications and full applications, to receive communications from the CDMRP, and to submit documentation during award negotiations and period of performance.

Full Application Submission: Full applications must be submitted through the online portals as described below.

Submitting Extramural Organizations: Full applications from extramural organizations must be submitted through Grants.gov. Applications submitted by extramural organizations (e.g., research foundations) on behalf of intramural DoD or other Federal organizations or investigators will be considered extramural submissions.

Submitting Intramural DoD Organizations: Intramural DoD organizations may submit full applications to either eBRAP or Grants.gov. Intramural DoD organizations that are unable to submit to Grants.gov should submit through eBRAP. Intramural DoD organizations with the capability to submit through Grants.gov may submit following the instructions for extramural submissions through Grants.Gov or may submit to eBRAP. Applications from extramural organizations, including non-DoD Federal organizations, received through eBRAP will be withdrawn. See definitions in Section II.C.1, Eligible Applicants.

eBRAP allows intramural organizations to submit full applications following pre-application submission.

For both Extramural and Intramural applicants: A key feature of eBRAP is the ability of an organization’s representatives and PIs to view and modify the full application submissions associated with them. eBRAP will validate full application files against the specific Program Announcement requirements and discrepancies will be noted in an email to the PI and in the Full Application Files tab in eBRAP. It is the applicant’s responsibility to review all application components for accuracy as well as ensure proper ordering as specified in this Program Announcement.

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 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 CDMRP Help Desk at help@eBRAP.org or 301-682-5507 prior to the application deadline.

mailto:help@eBRAP.org

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

During the pre-application process, each submission is assigned a unique log number by eBRAP. This unique eBRAP log number will be needed 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 may result in delays in 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 CDMRP Help Desk at help@eBRAP.org or 301-682-5507.

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.

PIs and organizations 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 PI must contact the CDMRP Help Desk at help@eBRAP.org or 301-682-5507.

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):

• Tab 1 – Application Information

Select the FY17 PRMRP Topic Area addressed by the proposed research. If the proposed research project is aligned with more than one FY17 PRMRP Topic Area, select the topic area of highest relevance as the required first choice.

• 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 (R&R) 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 (R&R) 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.

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

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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.

FY17 PRMRP 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 CDMRP Help Desk at help@eBRAP.org or 301-682-5507.

To preserve the integrity of its peer and programmatic review processes, the CDMRP discourages inclusion of any employee of its review contractors having any role in pre-application or application preparation, research, or other duties for submitted pre-applications or applications. For FY17, the identities of the peer review contractor and the programmatic review contractor may be found at the CDMRP website (http://cdmrp.army.mil/about/ 2tierRevProcess). Pre-applications or applications that include names of personnel from either of these companies will be administratively withdrawn unless plans to manage conflicts of interest (COIs) are provided and deemed appropriate by the Grants Officer.

Refer to the General Application Instructions, Appendix 3, for detailed information.

• Tab 4 – Conflicts of Interest

List all individuals other than collaborators and key personnel who may have a COI in the review of the application (including those with whom the PI has a personal or professional relationship). Refer to the General Application Instructions, Appendix 3, Section C, for further information regarding COIs.

• 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 (four-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 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:

– Topic Area: Describe how the proposed project relates to at least one FY17 PRMRP Topic Area. If applicable, describe how the proposed research project addresses an FY17 PRMRP Area of Encouragement (Appendix 2).

http://cdmrp.army.mil/prmrp/panels/panels17 mailto:help@eBRAP.org http://cdmrp.army.mil/about/2tierRevProcess http://cdmrp.army.mil/about/2tierRevProcess

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– Research Idea: Describe the ideas and reasoning on which the proposed clinical trial is based; include relevant literature citations. Briefly describe the level of scientific evidence that supports the progression of this research to a clinical trial. Clearly specify which type (e.g., drug, device, behavioral) of clinical trial is being proposed and indicate the phase of trial and/or class of device and regulatory status, as appropriate.

– Research Strategy: Concisely state the project’s hypothesis and/or objectives, and specific aims. Briefly describe the patient population(s) to be recruited for the clinical trial and the experimental approach.

– Personnel: Briefly state the qualifications of the PI and key personnel to perform the clinical trial. Note any DoD- or VA-relevant collaborations.

– Impact and Military Relevance: Describe how the proposed work will have an impact on accelerating the movement of a promising treatment into clinical application. Explain how the project is relevant to the healthcare needs of military Service members, Veterans, and/or beneficiaries.

○ 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 (five-page limit per individual). All biographical sketches should be uploaded as a single combined file. Biographical 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 DHP and the PRMRP, pre-applications will be screened based on the following criteria:

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• Research Idea: The degree to which the proposed clinical trial addresses an important question in one or more of the FY17 PRMRP Topic Areas. How well the rationale is supported, and how well the background provided indicates the research is ready to move into the phase of clinical trial proposed.

• Research Strategy: How well the specific aims, patient population, and proposed methodology will address the hypothesis and/or reach the desired objectives.

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

• Impact and Military Relevance: The degree to which the proposed clinical trial, if successful, will improve patient care in the FY17 PRMRP Topic Area(s) addressed. How well the research will address a healthcare issue relevant to military Service members, Veterans, and/or beneficiaries.

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 time frame 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 the PI has received notification of invitation.

All contributors and administrators to the application must use matching compatible versions of Adobe software when editing and preparing application components. The use of different software versions will result in corruption of the submitted file. Refer to the General Application Instructions, Section III, for details on compatible Adobe software.

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 (http://www.grants.gov/) for extramural organizations or through eBRAP (https://ebrap.org/) for intramural organizations. See Table 1 below for more specific guidelines.

http://www.grants.gov/

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

Extramural organizations, including non-DoD Federal agencies, must submit full applications through Grants.gov. Submissions of extramural applications through eBRAP may be withdrawn.

Table 1. Full Application Submission Guidelines

Extramural Submissions Intramural DoD Submissions

Application Package Location Download application package components for W81XWH-17-PRMRP-CTA from Grants.gov (http://www.grants.gov).

Download application package components for W81XWH-17-PRMRP-CTA from eBRAP (https://ebrap.org).

Full Application Package Components SF424 (R&R) 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.

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

• Attachments

• Research & Related Senior/Key Person

Profile (Expanded)

• Research & Related Budget

• Project/Performance Site Location(s) Form

• R&R Subaward Budget Attachment(s) Form

(if applicable)

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 Submit package components to Grants.gov (http://www.grants.gov).

If either the Project Narrative or the budget fails eBRAP validation or if the Project Narrative or the budget need 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.

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 “Enter Your Password Here” and press the “Submit Full Application” button. eBRAP will notify your Resource Manager/Comptroller or equivalent Business Official by email to log into eBRAP to review and to approve prior to the application submission deadline.

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

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Extramural Submissions Intramural DoD Submissions

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 verification period, the full application package, with the exception of the Project Narrative and Budget Form, may be modified.

After eBRAP has processed the full application, the organizational Resource Manager/ Comptroller or equivalent Business Official and PI will receive an email 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, with the exception of the Project Narrative and Budget Form, may be modified.

Further Information 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 organization’s Business Official or Authorized Organization Representative (or Resource Manager/Comptroller) should approve/verify the full application submission prior to the application verification deadline.

Application viewing, modification, and verification in eBRAP are strongly recommended, but not required. The Project Narrative and Budget cannot be changed after the application submission deadline. Prior to the full application deadline, a corrected or modified full application package may be submitted. Other application components may be changed until the end of the application verification period. After the end of the application verification period, the full application cannot be modified.

Material submitted after the end of the application verification period, unless specifically requested by the Government, will not be forwarded for processing.

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 (R&R) Application for Federal Assistance Form: Refer to the General Application Instructions, Section III.A.1, for detailed information.

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• 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 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.

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

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 6-8 described below.

Failure to submit these attachments as part of the application package will result in rejection of the entire application.

○ 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 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.

Describe the proposed project in detail using the outline below.

– Background: Describe in detail the rationale for the study. Provide a literature review and 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. 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 findings to the relevant FY17 PRMRP Topic Area(s).

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.

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– Objectives/Specific Aims/Hypotheses: Provide a description of the purpose and objectives of the study with detailed specific aims and/or study questions/ hypotheses. The aims should agree with the primary aims and associated tasks described in the Statement of Work.

– Study Design: Describe the type of study to be performed (e.g., prospective, randomized, controlled) and outline the proposed methodology in sufficient detail to show a clear course of action. Describe potential challenges and alternative strategies where appropriate.

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

Define the study variables, outline why they were chosen, and describe how they will be measured. Include a description of appropriate controls and the endpoints to be tested.

Describe the study population and inclusion and exclusion criteria that will be used.

Describe the methods that will be used to recruit a sample of human subjects from the accessible population (e.g., convenience, simple random, stratified random).

Describe the human subject-to-group assignment process (e.g., randomization, block randomization, stratified randomization, age-matched controls, alternating group, or other procedures), if applicable. Explain the specific actions to accomplish the group assignment (e.g., computer assignment, use of table of random numbers).

If using psychometric measures, describe their reliability and validity.

– Statistical Plan and Data Analysis: Describe the statistical model and data analysis plan with respect to the study objectives. Specify the approximate number of human subjects to be enrolled. If multiple study sites are involved, state the approximate number to be enrolled at each site. Include a complete power analysis to demonstrate that the sample size is appropriate to meet the objectives of the study. If a subpopulation of a recruited sample population will be used for analysis, complete a statistical analysis to ensure appropriate power can be achieved within the subpopulation study.

○ Attachment 2: Supporting Documentation: Combine and upload as a single file named “Support.pdf.” Start each document on a new page. If documents are scanned to PDF, the lowest resolution (100 to 150 dpi) should be used. The Supporting Documentation attachment should not include additional information such as figures, tables, graphs, photographs, diagrams, chemical structures, or drawings. These items should be included in the Project Narrative. Any additional material viewed as an extension of the Project Narrative will be removed or may result in administrative withdrawal of the application.

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There are no page limits for any of these components unless otherwise noted. Include only those components described below; inclusion of items not requested will result in the removal of those items or may result in administrative withdrawal of the application.

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

– List of Abbreviations, Acronyms, and Symbols: Provide a list of abbreviations, acronyms, and symbols.

Facilities, Existing Equipment, and Other Resources: Describe the facilities and – equipment available for performance of the proposed project and any additional facilities or equipment proposed for acquisition at no cost to the award. Indicate whether or not Government-furnished facilities or equipment are proposed for use. If so, reference should be made to the original or present Government award under which the facilities or equipment items are now accountable. There is no form for this information.

Publications and/or Patents: Include a list of relevant publication URLs and/or patent – abstracts. If publications are not publicly available, then copies of up to five published manuscripts may be included in Attachment 2. Extra items will not be reviewed.

Letters of Organizational Support: Provide a letter (or letters, if applicable), signed – by the Department Chair or appropriate organization official, confirming the laboratory space, equipment, and other resources available for the project.