Since veterans returning from the Persian Gulf first started to report symptoms and illnesses in late 1991, a significant number of clinical evaluation and research activities have been undertaken. The magnitude of the current research effort requires implementation of a comprehensive plan. This working plan for research maps out the course by which the following goals can be pursued:

The working plan for research is coordinated by the VA, and the research conducted under the aegis of this plan is executed by various departments and agencies, including VA, DoD, HHS and EPA. The Research Working Group, through the Persian Gulf Veterans Coordinating Board, is the primary research coordinating body and is charged with assessing the state and direction of research; identifying gaps in factual knowledge and conceptual understanding; identifying testable hypotheses; recommending research directions for participating agencies; reviewing research concepts as they are developed; and collecting and disseminating scientifically peer-reviewed research information.

Establishment of the prevalence of symptoms and illnesses in comparison with appropriate control populations is an essential basis upon which additional research depends. If Persian Gulf veterans are experiencing symptoms and illnesses that are in excess of expectations for such a population, further research into the risk factors can then be approached by separating the overall investigation into two categories: analysis of exposures, and analysis of health outcomes. These analyses need to be conducted in a manner that defines the association between exposures and outcomes.

Based on the findings of three scientific panels -- the Defense Science Board Task Force (DSB,1994); the NIH Technology Assessment Workshop (NIH, 1994); and the Institute of Medicine (IOM, 1995) -- and other current information, exposures to psychophysiological war stressors, Leishmania tropica (L. tropica), petroleum products, insecticides and insect repellents (possibly in combination with pyridostigmine bromide), are important to consider if any excess illnesses are found. Vaccines, chemical agents resistant coating (CARC) paint, depleted uranium and smoke from oil well fires are considered by the scientific panels as unlikely sources of unexplained illnesses. Confirmation of exposure to chemical or biological agents is also lacking. However, if reports of such exposures should be confirmed, additional investigations should be undertaken. With respect to health outcomes, research on psychological and cognitive outcomes, leishmaniasis, reproductive outcomes, genitourinary disorders, pulmonary function abnormality, immunological outcomes, cancer outcomes, and short and long-term mortality may need to be considered in greater depth as population-based studies begin to yield information.

VA, DoD, and HHS have initiated important epidemiologic studies that will provide information about the prevalence of symptoms and illnesses, adverse reproductive events, and self-reported exposures among Persian Gulf veterans and their families. In conjunction with these epidemiologic studies, several laboratory-based clinical and toxicological research projects have already begun which are testing specific plausible hypotheses in advance of epidemiological findings. The conduct of these studies in advance of epidemiological study findings will avoid unnecessary start-up delays as findings from the epidemiologic studies begin to appear. These studies will also provide important scientific knowledge that is generalizable beyond the current needs of Persian Gulf veterans and has benefit for veterans of future conflicts.

Important specific areas of inquiry for which significant gaps in knowledge exist include:

As new information becomes available, the need for targeted research projects addressing new, emerging hypotheses will continue to arise. The appropriateness and relevance of these studies will be the subject of programmatic review by the Research Working Group for the purpose of developing requests for proposals (RFP). After proposals that are responsive to the RFPs have been reviewed and ranked for scientific merit by outside peer-review panels, the Research Working Group, through the Persian Gulf Veterans Coordinating Board, will be asked to provide programmatic guidance to individual funding agencies.

Because of the changing nature of scientific research, this plan is meant to be flexible and changeable. Periodically, this document will undergo revision that will reflect the current scientific thinking at the time of revision.