dard diagnostic classifications, registries were not designed to probe for novel diagnoses6 or to search for biological correlates. Thus, because of their methodological limitations, registry studies cannot stand alone as a basis for conclusions or for the conduct of research.
Registry programs are, however, a valuable resource for information and for generating hypotheses. These hypotheses can be tested in more rigorous epidemiologic studies with control groups in order to estimate the population prevalence of symptoms among Gulf War veterans and to compare these to rates among otherwise similar troops who were not deployed to the Gulf War.
A number of epidemiologic studies have been conducted on the health status of Gulf War veterans. The driving issues behind many of these studies are to determine (1) the nature of symptoms and symptom clusters; (2) whether symptom clusters constitute a new, unique syndrome; and/or (3) what types of exposures may have produced the symptoms.
The second issue highlighted above—the quest to define a new syndrome—requires some explanation. The question is whether or not these unexplained symptoms constitute a syndrome(s) and, if so, are they best studied and treated as a unique new syndrome(s) or a variant form(s) of an existing syndrome (see Appendix D). The finding of any new set of unexplained symptoms in a group of patients does not automatically qualify as a new syndrome.7 It represents the beginning of a process involving many types of studies to demonstrate that the patients are affected by a unique clinical entity distinct from all other established clinical diagnoses.
The process of defining a new syndrome usually begins with a case definition that lists classification criteria to distinguish the potentially new patient population from patients with existing clinical diagnoses. Development of the first case definition is a vital milestone designed to spur research and surveillance. More like a hypothesis than a conclusion, the first case definition is an early step in the process and is often revised as more evidence comes to light. Case definitions usually are a mix of clinical, demographic, and/or laboratory criteria. Clinical criteria refer to signs (physical examination findings) and symptoms (subjective experiences or reports of patients). Demographic criteria refer to age, gender, ethnicity, or other individual characteristics or exposure-related variables. Laboratory criteria are biological measures of either pathology or etiology (e.g., x-ray, blood test).