DoD Gulf War Illness Investigator-Initiated Research Award

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The GWIRP Investigator-Initiated Research Award (IIRA) was first offered in FY06. Since then, 190 IIRA applications have been received, and 52 have been recommended for funding. New for FY14: The GWIRP IIRA includes a Case Definition Option, as described below, to encourage applications focused on developing or improving the case definition of GWI for either clinical or research purposes. The IIRA is designed to promote new ideas in GWI research and establish proof of principle for further development in future studies. Applications are not required to include preliminary data; however, preliminary data may be used to support the objectives of an application. These data are not required to have come from the GWI research field. Applications not supported by preliminary data should be based on sound scientific rationale and may reflect clinical observations or seek to evaluate discoveries made in relation to other chronic multi-symptom illnesses for their application in GWI. Regardless of the approach, the focus should be clearly on veterans with GWI. It is the responsibility of the Principal Investigator (PI) to clearly and explicitly articulate the project’s potential impact on GWI. The IIRA supports research focusing on the complex of symptoms known as GWI, improving the case definition and diagnosis of GWI, characterizing disease symptoms, and better understanding the pathobiology. The IIRA encourages basic through clinical research aimed at identification of objective measures (e.g. biomarkers) to distinguish healthy veterans from those with GWI, or improve understanding of the pathobiology underlying symptoms associated with GWI. Particular topic areas of interest include biological processes or abnormalities in GWI associated with: • Central nervous system structure and function, in particular, the role of glial cells, astrocytes, and microglia in GWI symptomatology • Central neuroinflammatory processes • Autonomic nervous system function • Neuroendocrine measures • Immune parameters/Indicators of chronic infection • Gastrointestinal complaints/symptoms • Genetic, genomic, proteomic, or metabolic characteristics • Respiratory symptoms • Sexual dysfunction • Sleep Problems • Establishing a GWI case definition Applications may also address other topic areas that are directly relevant to GWI. Studies that characterize chronic effects of neurotoxic exposures at dosages comparable to that encountered in-theatre during the Gulf War are of interest. Studies using animal models should focus on long-term and latent effects of toxic exposures to closely represent the current status of GWI patients. All studies using animal models should use an established model unless there is a compelling scientific justification for the development or use of a new model. Development of new animal models is discouraged. The IIRA can also be used for testing of GWI-targeted pharmacologic agents in Adsorption, Distribution, Metabolism, Excretion (ADME) studies, and toxicology testing, including Investigational New Drug (IND)-enabling pharmacology/ toxicology testing. Preclinical development of non-pharmacological interventions is also acceptable. Case Definition Option: The intent of this option is to support applied research aimed at producing a more robust case definition for GWI for clinical or research applications. Applications submitted under the Case Definition Option will be reviewed separately from all other IIRA applications. Projects appropriate for the Case Definition Option might include analysis of the requirements for clinical and/or research case definitions and their structures, including but not limited to establishing priorities, weighting characteristics, determining exclusionary criteria, and evaluating strategies for dealing with comorbidities. More advanced work could involve development and evaluation of methodologies to analyze clinical data to yield case definition parameters and assessment of the resulting case definitions with respect to sensitivity, selectivity, reliability, portability, identification of subgroups and validation across independent datasets. The intent of the GWIRP IIRA Case Definition Option is to meet the urgent need for a more robust consensus case definition of GWI for both clinical and research applications. In a recently released pre-publication report commissioned by the U.S. Department of Veterans Affairs (VA), an Institute of Medicine (IOM) committee noted that few of the GWI case definitions published to date include certain elements, particularly with respect to onset, duration, severity, and laboratory findings. Therefore, the IOM committee recommended further research to better characterize GWI and produce a more robust case definition. 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, also provides recommendations for a consensus case definition. Applicants to the IIRA Case Definition Option are strongly encouraged to refer to both reports released by the IOM (available online at http://www.iom.edu/Reports/2014/Chronic-Multisymptom-Illness-in-Gulf-War-Veterans-Case-Definitions-Reexamined.aspx) and the Research Advisory Committee on Gulf War Veterans’ Illnesses (available online at http://www.bu.edu/sph/files/2014/04/RAC2014.pdf). Though case definition research may make use of novel biomarkers, and biomarker validation may be necessary for the development of a case definition for GWI, this option is not intended as a vehicle for research aimed at biomarker discovery. Applications whose primary focus is biomarker discovery would not meet the intent of the IIRA Case Definition Option and should apply to the traditional IIRA mechanism. 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 (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. Applicants should consult the ARRIVE (Animal Research: Reporting In Vivo Experiments) guidelines to ensure relevant aspects of rigorous animal research are adequately planned for and, ultimately, reported. The ARRIVE guidelines can be found at http://www.nc3rs.org.uk/page.asp?id=1357.

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