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14 EXPOSURE OF VETERANS TO AGENT ORANGE AND OTHER HERBICIDES
units maintain detailed histories of their Vietnam experience and active
contact with their former members, and they may also present opportuni-
ties for epidemiologic research.
The E4 EOI does not measure dose or actual exposure of individuals
to herbicides. It is instead a systematic means of classifying potential
exposure. Individual dose or exposure measures are the most desirable
inputs to epidemiologic studies, but it is often impossible or impractical
to obtain them, so researchers routinely assign exposure estimates that
are based on indirect or aggregate indexes. That strategy is the norm, for
example, in occupational-cohort studies: because individual exposure
data are seldom available, workers' exposures are typically assigned from
estimates of the average exposure of groups defined by job or work area.
Because of individual variations in behavior, biology, and exposure con-
ditions, individuals with identical exposure indexes may have different
actual exposures. That is a form of exposure-measurement error. Such
errors are typically random with respect to disease status, and in that
situation they are likely to cause epidemiologic studies to underestimate
the magnitude of any association between exposure and outcome. That
potential for bias does not invalidate the use of indexes but instead means
that care must be exercised in constructing studies based on such mea-
sures and interpreting their results.
It is also important to recognize that an exposure index like the E4
EOI cannot be directly validated or invalidated through an epidemiologic
study. Studies based on well-formed hypotheses about outcomes associ-
ated with exposure would provide the strongest evidence regarding the
validity of exposure estimates. A positive association with an end point
strongly believed to be related to herbicides or dioxin in particular would
tend to confirm that the E4 EOI measures relevant exposures. However,
given the uncertainties inherent in all epidemiologic studies, it is unlikely
that any single study could constitute a strong test of validity. Rather,
evaluation of the patterns of results from multiple studies would provide
guidance as to the performance of the E4 EOI as an indicator of any
particular exposure.
CONCLUSIONS AND RECOMMENDATIONS
On the basis of the findings discussed above, the committee con-
cludes that a valid exposure reconstruction model for wartime herbicide
exposures of US veterans of Vietnam is feasible.
The committee therefore recommends that the Department of Veter-
ans Affairs and other government agencies facilitate additional epidemio-
logic studies of veterans by nongovernment organizations and indepen-
dent researchers. The committee responsible for the 1994 report, in making
Representative terms from entire chapter:
exposure estimates
