Agricultural Health Study Follow-up

Pesticides are a common environmental exposure due to their widespread use for agricultural,
residential, and public health purposes. Farmers and their families represent a unique
population for studying the chronic health effects of pesticides because farmers know what
chemicals they use, furthermore, farmers tend to remain at the same location over most of
their adult life. The Agricultural Health Study (AHS), a cohort of approximately 89,000
pesticide applicators and spouses from Iowa and North Carolina, is the largest US cohort
study of individuals working with pesticides. The AHS cohort was enrolled in 1993 to 1997 to
assess human health effects associated with well-characterized exposures to pesticides and
other agricultural factors. Detailed exposure data were collected at enrollment and in two
five-year follow-up interviews. As a result, the AHS has a wealth of information on pesticide
use by both farmers and their spouses, as well as the ability to account for changes in
pesticide use over time. Information on medical history and important covariates was also
collected at enrollment and in the follow-up interviews, and will continue to be collected
over time.Only mortality and cancer incidence are updated annually through linkage to vital
statistics and cancer registries; all other health outcomes are based on self-reported
information from participants.The accuracy of self-reported health outcome information can
vary from quite good (e.g., asthma) to poor (e.g., rheumatoid arthritis). In order to ensure
high quality epidemiologic analyses, validation of self-reported disease is necessary prior
to statistical analysis. To date, several health endpoints have been validated through
follow-up with AHS participants and their physicians. The purpose of the current protocol is
three-fold: 1) update information on medical history and other important covariates through
ongoing follow-up interviews of the cohort; 2) validate self-reported diseases among cohort
participants over the duration of cohort follow-up (at least through 2020); and 3) complete
initial contact of potential participants to inform them of other health outcome studies
being conducted within the cohort by an outside institution.

We will contact AHS cohort members to complete a follow-up interview allowing one of three
modes of response: self-administered paper questionnaire, self-administered web survey
(CAWI), and interviewer-administered telephone interview (CATI). We will contact proxy
respondents if the participant is unable to provide information.

We will validate a variety of diseases of interest as they are ascertained in the cohort.
While the characteristics of the diseases may vary, the strategy for disease validation is
similar to the cohort wide follow-up. Validation efforts may also include a request for
permission to contact the participant s physician, and contacting the physician s office to
obtain the relevant medical information. We will contact proxy respondents if the participant
is unable to provide information.

- INCLUSION AND EXCLUSION CRITERIA:

All members of the AHS cohort who were eligible for the Phase 3 interview were eligible for
the Phase 4 health follow-up. We will apply the same eligibility criteria for future
cohort-wide follow-ups. Individuals who only completed the enrollment questionnaire were
excluded from Phase 3 eligibility. Depending upon the disease outcome of interest, we may
conduct the disease confirmation and validation efforts under this protocol among all
participants in the AHS who provided self-reported diagnoses at any interview (e.g.
Baseline, or Phases 2-4). For individuals who are unable to participate, we will allow a
proxy to provide the information.

For the validation efforts, individuals who do not confirm their diagnosis of interest (via
self or proxy report) will not be asked to provide physician contact for medical records.
For specimen collection, we will ask the proxy respondent about whether the individual
would be able to provide a sample. In order to obtain MRR we will allow the participant or
their medical proxy to sign the form. For cases who are cognitively impaired or deceased, a
medical proxy will be identified.

Determination of cognitive impairment will be made by report of proxy or by interviewer
during conversation with participant. Because the AHS enrolled husband - wife pairs, we
should be able to identify an appropriate proxy for most participants.