OpportunityTitle: Peer Reviewed Orthopaedic Clinical Translational Research Award
Description: The FY17 PRORP Clinical Translational Research Award is intended to support high-impact and/or new/emerging clinical research that may or may not be ready for a full-scale randomized controlled clinical trial. Projects should include translational research that evaluates the effectiveness of healthcare practices and/or interventions in neuromusculoskeletal injuries rehabilitation. Projects should demonstrate potential to impact the standard of care, as well as contribute to evidence-based guidelines for the evaluation and care of military or Veteran patients with orthopaedic injuries including, but not limited to, amputation and/or limb salvage. One goal is to better understand and optimize the experiences, health, functional abilities, and quality of life of individuals who receive treatment for traumatic orthopaedic injuries. Another goal is to identify the most effective diagnosis, treatment, rehabilitation, and prevention options available to support critical decision making for patients, clinicians, other caregivers, and policymakers. Proposed projects should be designed to provide information about the impact, advantages, disadvantages, and risks of specific healthcare practices and interventions. To meet the intent of the award mechanism, applications must specifically address one primary FY17 PRORP Focus Areas listed in Section II.A.1, above. Funding from this award mechanism must support clinical research studies involving human subjects. The proposed studies may be interventional and may involve some retrospective data analysis. Small pilot clinical trials with human subjects are also allowable. A clinical trial is defined as a prospective accrual of human subjects where an intervention (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. The term &#8220;human subjects&#8221; is used in this Program Announcement to refer to individuals who will be recruited for or who will participate in the proposed clinical research. For more information, a Human Subject Resource Document is provided at https://ebrap.org/eBRAP/public/Program.htm. Note that purely retrospective or database- related research is not allowed under this funding opportunity. The anticipated total costs budgeted for the entire period of performance for an FY17 PRORP Clinical Translational Research Award will not exceed $2M. Refer to Section II.D.5, Funding Restrictions, for detailed funding information. Animal research, to develop or refine new technology or research to establish the efficacy/ effectiveness of diagnostic agents, or otherwise, is not allowed under this funding opportunity. Investigators seeking support to conduct studies involving animal research should consider applying to the FY17 PRORP Applied Research Award (Funding Opportunity Number: W81XWH-17-PRORP-ARA) mechanism, which can be accessed at http://cdmrp.army.mil/funding/default.shtml. All applications are required to articulate the relevance of the proposed project to military and/or Veteran populations affected by orthopaedic injury. Studies that address how the proposed research outcomes will provide new paradigms for or novel insights into the rehabilitation of Service members and/or Veterans who have sustained orthopaedic injuries are strongly encouraged. Studies that include active duty military or Veteran participants as all or a portion of the study population are encouraged. Collaboration with military and VA researchers and/or clinicians is also encouraged. The following are important aspects of submission for the Clinical Translational Research Award: &#8226; Inclusion of preliminary data relevant to the proposed clinical research is required. &#8226; The proposed clinical research must be based on sound scientific rationale that is established through logical reasoning and critical review and analysis of the literature. &#8226; 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. &#8226; If applicable, the application should demonstrate availability of, and access to, a suitable patient population that will support a meaningful outcome for the study. The applicant should discuss how accrual goals will be achieved and how standards of care may impact the study enrollment. &#8226; If applicable, the application should demonstrate access to resources, including but not limited to, patient records, controlled study materials, and/or databases for the proposed clinical research. &#8226; 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 U.S. Food and Drug Administration (FDA) manufacturing standards applicable to the type and phase of product being developed (i.e., Quality System Regulation, Good Manufacturing Practices [GMPs]). &#8226; If applicable, the proposed intervention to be tested should offer significant potential impact for military personnel and Veterans with combat-related orthopaedic injuries or non-battle orthopaedic injuries that impact unit readiness and return to duty/work. &#8226; The application should demonstrate that the study team has experience interacting with the FDA, to include previous FDA submissions, if applicable. &#8226; The proposed study design should include clearly defined and appropriate endpoints, and follow Good Clinical Practice (GCP) guidelines. &#8226; 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. &#8226; 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. For FDA-regulated studies, compliance with Code of Federal Regulations, Title 21, Part 11 (21 CFR 11) is required. &#8226; The application should include a clearly articulated safety management plan outlining how safety and pharmacovigilance will be conducted, as applicable. &#8226; The application should include a clearly articulated clinical monitoring plan outlining how the study will be monitored for GCP compliance. &#8226; If applicable, 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 research, and coordinate participant accrual. &#8226; For studies determined to be greater than minimal risk to human subjects by the local IRB of record, the Department of Defense (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 6, for more information on study reporting authorities and responsibilities of the research monitor. &#8226; The application should include a Transition Plan (including potential funding and resources) showing how the product will progress to the next clinical phase and/or delivery to the market after the successful completion of the FY17 PRORP Clinical Translational Research Award (see Section II.D.2.b.ii, Full Application Submission Components, Attachment 10: Transition Plan). &#8226; The application should clearly demonstrate strong institutional support (refer to Section II.D.2.b.ii, Full Application Submission Components, Attachment 2: Supporting Documentation). &#8226; Funded studies that involve clinical trials 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 6, Section C, for further details. Rigor of Experimental Design: All projects should adhere to a core set of standards for rigorous study design and reporting to maximize the reproducibility and translational potential of preclinical research. The standards are described in Landis, S.C., et al. A call for transparent reporting to optimize the predictive value of preclinical research, Nature 2012, 490:187-191 (http://www.nature.com/nature/journal/v490/n7419/full/nature11556.html). While these standards are written for preclinical studies, the basic principles of randomization, blinding, sample-size estimation, and data handling derive from well-established best practices in clinical studies. 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 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. Organizations are encouraged to consider use of site personnel familiar with local/host nation regulatory review requirements. 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) &#8220;Funding Opportunities &amp; Forms&#8221; 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. If the proposed research involves the use of a drug that has not been approved by the FDA for the proposed investigational use, then an Investigational New Drug (IND) application to the FDA that meets all requirements under the 21 CFR 312 may be required and must be submitted to the FDA within 6 months of the award. 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 within 6 months of the award date, or that the device is exempt from an IDE 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 within 6 months of the award date, or if documented status of the IND or IDE has not been obtained within 12 months of the award date. 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 8: 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 or Ethics Committee (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. Use of Military and VA Populations or Resources: If the proposed research plan involves access to active duty military and/or VA patient populations or resources, the Principal Investigator (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. Use Attachment 2 to provide this documentation (see Section II.D.2.b.ii. Full Application Submission Components, Attachment 2: Supporting Documentation). Encouraged DoD or VA Collaboration and Alignment: Military relevance is a key feature of this award. Therefore, PIs are strongly encouraged to collaborate, integrate, and/or align their projects with military and/or VA research laboratories and programs. Although not a comprehensive list, the following websites may be useful in identifying information about DoD and VA areas of research interest, ongoing research, or potential opportunities for collaboration: Air Force Office of Scientific Research http://www.wpafb.af.mil/afrl/afosr/ Office of Naval Research http://www.med.navy.mil/ Air Force Research Laboratory http://www.wpafb.af.mil/afrl Armed Forces Radiobiology Research Institute http://www.usuhs.edu/afrri/ Clinical and Rehabilitative Medicine Research Program https://crmrp.amedd.army.mil Combat Casualty Care Research Program https://ccc.amedd.army.mil Congressionally Directed Medical Research Programs http://cdmrp.army.mil Defense Advanced Research Projects Agency http://www.darpa.mil/ Defense Technical Information Center http://www.dtic.mil Defense Threat Reduction Agency http://www.dtra.mil/ Military Health System Research Symposium https://mhsrs.amedd.army.mil/SitePages/Hom e.aspx Military Infectious Diseases Research Program https://midrp.amedd.army.mil Military Operational Medicine Research Program https://momrp.amedd.army.mil Naval Health Research Center http://www.med.navy.mil/sites/nhrc Navy and Marine Corps Public Health Center http://www.nmcphc.med.navy.mil/ Office of the Under Secretary of Defense for Acquisition, Technology and Logistics http://www.acq.osd.mil/ Telemedicine and Advanced Technology Research Center http://www.tatrc.org/ Uniformed Services University of the Health Sciences http://www.usuhs.edu/research U.S. Army Institute of Surgical Research http://www.usaisr.amedd.army.mil/ U.S. Army Research Institute of Environmental Medicine http://www.usariem.army.mil/ U.S. Army Medical Research Institute of Infectious Diseases http://www.usamriid.army.mil/ U.S. Army Medical Research and Materiel Command https://mrmc.amedd.army.mil U.S. Army Research Laboratory http://www.arl.army.mil U.S. Department of Defense Blast Injury Research Program https://blastinjuryresearch.amedd.army.mil/ U.S. Department of Veterans Affairs, Office of Research and Development http://www.research.va.gov U.S. Naval Research Laboratory http://www.nrl.navy.mil Walter Reed Army Institute of Research http://www.wrair.army.mil/ 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.
GrantorContactEmailDescription: CDMRP Help Desk
GrantorContactText: CDMRP Help Desk &lt;br/&gt;Phone:  301-682-5507 &lt;br/&gt;Email:  help@eBRAP.org