DoD Gulf War Illness Clinical Trial Award
The FY14 GWIRP is offering two award mechanisms to evaluate potential interventions for GWI: the Clinical Trial Award (CTA) and the Innovative Treatment Evaluation Award (ITEA). The CTA, described in this Program Announcement/Funding Opportunity, is intended to support larger, more definitive (Phase II-III, FDA device class I-III) clinical trials. In contrast, the ITEA supports the initial evaluation of a treatment or intervention in smaller, early phase or pilot clinical trials (Phase 0, I, or I/II), and does not require preliminary data. (For information about the ITEA, see http://cdmrp.army.mil/funding/gwirp.shtml.) The CTA mechanism was first offered in FY08. Since then, 14 Clinical Trial Award applications have been received, and four have been recommended for funding. The CTA supports execution of clinical trials with the potential to have a significant impact on the health and lives of veterans with GWI. Comparative studies of GWI treatments are allowed. Health outcomes of interest should include effects of interventions on: • Global health measures (biomarkers) and/or functional status • Improvements in symptom complexes (e.g., cognitive function, musculoskeletal/pain symptoms, gastrointestinal symptoms, fatigue, respiratory problems, skin abnormalities, sleep difficulties), individually and as they may interact with each other • GWI subgroups characterized by symptom or other clinical characteristics Proposed studies may be single-center or multi-center clinical trials. Applications may be submitted by a single PI or by a team of investigators led by an Initiating Principal Investigator (PI) with up to three Partnering PIs. Multiple PI Option: The FY14 GWIRP supports collaborative projects to bring a new perspective to GWI research and/or facilitate advancement of GWI treatments through synergistic partnerships. Therefore, the FY14 GWIRP is offering a Multiple PI Option for this award mechanism. The Multiple PI Option is structured so that up to four investigators, each of whom will be designated “PI” and receive a separate award, will work synergistically on a single project. One member of the team will be identified as the Initiating PI and will be responsible for the majority of the administrative tasks associated with the application. The other member(s) will be referred to as the Partnering PI(s) (maximum of three). All the investigators must collaborate to submit a single project examining one or more treatment modalities or comparing untested or novel treatments for GWI symptoms. It should be clear that all investigators have an equal level of intellectual input and effort. The Initiating PI should have demonstrated expertise in GWI research, while the Partnering PIs may contribute expertise from a different field that can be applied to GWI. Multidisciplinary and multi-organizational projects are encouraged. If the project is multi-organizational, applications should include plans for communication between investigators at each organization. Additionally, participating organizations must be willing to resolve potential intellectual and material property issues and to remove any barriers that might interfere with achieving high levels of cooperation to ensure successful completion of the project. Application responsibilities unique to Partnering PIs will be identified in the supporting sections of this Program Announcement. Applications proposing studies whose principal focus is on the treatment of psychiatric conditions, including post-traumatic stress disorder (PTSD), will be administratively withdrawn and will not be funded under this Program Announcement/Funding Opportunity. While Gulf War veterans are affected by Amyotrophic Lateral Sclerosis (ALS, also called Lou Gehrig’s disease) at twice the rate of veterans who did not serve in the Gulf War, the GWIRP will not accept applications focusing on ALS research. However, applications that focus on GWI symptomatology may include GW veterans with ALS if the latter disorder is included in the study’s GWI case definition. [For those interested in pursuing ALS-focused studies, the office of the Congressionally Directed Medical Research Programs (CDMRP) offers a separate ALS research program (see http://cdmrp.army.mil/alsrp)]. Applications must clearly indicate how GWI cases, including any targeted illness subgroups, will be defined for purposes of the study. Applicants must provide a published case definition they intend to use to define their GWI population. Any case definition must recognize the multi-symptom nature of GWI. Note: The 2014 report of the Research Advisory Committee on Gulf War Veterans’ Illnesses, Gulf War Illness and the Health of Gulf War Veterans: Research Update and Recommendations, 2009-2013, provides information on GWI, including case definitions and research on epidemiology, etiology, pathobiology, and treatment. The 2014 report can be found online at http://www.bu.edu/sph/files/2014/04/RAC2014.pdf. In addition, the pre-publication report (available online at http://www.iom.edu/Reports/2014/Chronic-Multisymptom-Illness-in-Gulf-War-Veterans-Case-Definitions-Reexamined.aspx) released by the Institute of Medicine includes recommendations for a consensus case definition. Applications are required to include preliminary data, which does not necessarily have to come from the GWI research field. The proposed research project should also be based on sound scientific rationale that is established through logical reasoning and critical review and analysis of the literature. If there are no preliminary and/or preclinical data reflecting considerable development of a treatment, the application would not be deemed in keeping with the intent of the CTA. In this case, investigators are encouraged to apply to the GWIRP Innovative Treatment Evaluation Award (http://cdmrp.army.mil/gwirp/default.shtml). Funding from this award mechanism must support a clinical trial and may not be used for preclinical research studies. 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 exploratory information, 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 award mechanisms/funding opportunities being offered. The term “human subjects” is used in this Program Announcement/Funding Opportunity 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 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, evidence that an Investigational New Drug (IND) exemption application that meets all requirements under the Code of Federal Regulations, Title 21, Part 312 (21 CFR 312) has been submitted or will be submitted to the FDA within 60 days of award is required. 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 or will be submitted to the FDA within 60 days of award, or that the device is exempt from an IDE, is required. The Government reserves the right to withdraw funding if the IND or IDE application has not been submitted to the FDA within 60 days of the Department of Defense (DoD) award date or if the documented status of the IND or IDE has not been obtained within 6 months of the award date. 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 to be tested should offer significant potential impact for veterans with GWI. • 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). • PIs must demonstrate availability of and access to a suitable Gulf War veteran population that will support a meaningful outcome for the study. Discuss how accrual goals will be achieved and how standards of care may impact the study population. PIs are encouraged to collaborate with an investigator who has demonstrated access to a population of Gulf War veterans, particularly investigators within the U.S. Department of Veterans Affairs. • The proposed research project must be based on sound scientific rationale that is established through logical reasoning and critical review and analysis of the literature and the application must identify the pathobiological mechanism being targeted. • Inclusion of preliminary data relevant to the proposed research project is required. • 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 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). • The proposed clinical trial design should include clearly defined and appropriate endpoints, and follow Good Clinical Practice (GCP) guidelines, if applicable. • The application should include a clearly articulated statistical analysis plan, appropriate statistical expertise, 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. • 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 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 GWIRP Clinical Trial Award. • The application should clearly demonstrate strong institutional support. • The application should acknowledge the commitment to filing the study in the National Institutes of Health (NIH) clinical trials registry, www.clinicaltrials.gov.
Office: U.S. Army Medical Research Acquisition Activity
301-682-5507
