the United Kingdom and other European countries) should also be considered.
Cohort studies of sufficient size and length of follow-up in which information on military service was collected for all subjects, or can be collected retrospectively in a valid manner from records or from the subjects themselves, may prove useful in examining the relationship between ALS and military service. In some studies, it may be convenient to design a case-control study nested within the cohort to reduce the cost of additional data collection about military exposures. The advantage of traditional cohort studies or nested case-control studies is that they provide a well-defined base population (although not necessarily representative of the general population), and information for a number of potential confounding variables has been collected prior to disease occurrence, thus avoiding recall bias. A cohort would be especially valuable if subjects had provided extensive details about their military experience. Ideally, “exposure” information should include
Whether a person served in the military.
Location of military service.
Years of military service.
Jobs and duties during military service.
The opportunity to validate military service using historical documents would further add to the methodologic rigor of such a study. Linkage with death certificates or other mechanisms for monitoring the occurrence of ALS would be necessary. Prospective monitoring of the cohort for ALS incidence that allows for application of the modified El Escorial diagnostic criteria would be ideal because it would reduce underascertainment and misclassification of disease. However, that may not be feasible. Alternatively, if death certificates are the only source of information on ALS, the investigators should consider validating a subset of diagnoses to estimate the frequency of false positives and false negatives.
High quality case-control studies could also be used to assess the relationship between ALS and military service.