DOD Gulf War Illness Clinical Trial Award

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The FY12 GWIRP is offering two award mechanisms to evaluate potential interventions for Gulf War Illness: the Clinical Trial Award (CTA) and the Innovative Treatment Evaluation Award (ITEA). The Clinical Trial Award, 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 II or I/II), and does not require preliminary data. (For information about the ITEA, see http://cdmrp.army.mil/funding/gwirp.shtml.) The Clinical Trial Award mechanism was first offered in FY08. Since then, 9 Clinical Trial Award applications have been received, and 3 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. 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 Studies whose principal focus is on treatment of psychiatric conditions, including Post-Traumatic Stress Disorder (PTSD), will not be funded under this Program Announcement/Funding Opportunity. While Gulf War veterans are affected by Amyotrophic Lateral Sclerosis (ALS, or 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. The office of the Congressionally Directed Medical Research Programs (CDMRP) is offering a separate ALS Research Program in FY12 (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. Principal Investigators (PIs) 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 2008 report of the Research Advisory Committee on Gulf War Veterans’ Illnesses, Gulf War Illness and the Health of Gulf War Veterans, provides information on GWI case definitions (pp. 29-30, p. 57), previous treatment research in Gulf War veterans (pp. 36-39), and treatment research related to other multi-symptom conditions (pp. 285-287). The report can be found online at: http://www1.va.gov/RAC-GWVI. 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 ITEA, which supports small pilot Phase II or Phase I/II combined clinical trials (http://cdmrp.army.mil/funding/gwirp). 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. PIs interested in funding for a preclinical research project should consider the GWIRP Investigator- Initiated Research Award (http://cdmrp.army.mil/funding/gwirp.shtml). 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 on clinical research, see the Human Subject Resource Document at https://cdmrp.org/Program_Announcements_and_Forms/. If the proposed study involves the use of a drug that has not been approved by the U.S. Food and Drug Administration (FDA) for its clinical investigational use, an Investigational New Drug (IND) application must be submitted to the FDA within 60 days of award. If the proposed study involves an Investigational Device that has not been approved or cleared by FDA for its clinical investigational use, the study may be required to comply with FDA Investigational Device Exemption (IDE) regulations. If applicable, the IDE application must be submitted within 60 days of award. The Government reserves the right to withdraw funding if the status of the submitted IND or IDE application has not been determined 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. • It is expected that the drug, device or other intervention to be used in the proposed trial will be available in sufficient quantities and ready for clinical trials at the time the award is made. • 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 ill and healthy 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. Preliminary data supporting the rationale must also be provided. • The proposed clinical trial should include clearly defined and appropriate endpoints. • 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 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 ill Gulf War veteran population after successful completion of the GWIRP Clinical Trial Award. • The application should demonstrate evidence of institutional support.

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