ATSDR’s approach to site assessment and epidemiologic considerations for multisite studies

1. ATSDR’s approach to site assessment and epidemiologic considerations for multisite studies Steve Dearwent, PhD, MPH Chief, Health Investigations Branch Division of Health Studies Agency for Toxic Substances and Disease Registry NAS - Analysis of Cancer Risks in Populations near Nuclear Facilities May 23, 2011 Agency for Toxic Substances and Disease Registry Division of Health Studies

2. ATSDR – our mandate and approach • Enabling legislation in the 1980s (CERCLA/RCRA/SARA) • Our work is a combination of: • site specific applications • public health assessments and consultations • health studies, surveillance and registries • community involvement • general information dissemination • toxicological profiles • medical education • CERCLA exclusion for facilities licensed by the NRC

3. ATSDR’s site assessment process • Initial focus of evaluations are typically exposure centric • The Public Health Assessment • a risk assessment process with associated documentation that often include site specific evaluations of: • contaminant(s) of concern • their concentrations in various environmental media • exposure pathways • potentially exposed populations • process includes a heavy reliance on the use of: • preexisting environmental sampling data • screening or comparison values to estimate risk of both malignant and nonmalignant outcomes in likely exposed populations

4. Considerations for conducting exposure and/or health effects studies • For ecologic analyses, usually a positive response to the following questions (via the public health assessment process): • completed/potential exposure pathway? • determined exposure time frame? • quantified exposed population? • sufficient exposure levels and latency? • geographic unit similar? • data available for outcomes of interest? • For analytic studies: • above considerations plus available resources, adequate statistical power and a priority data gap

5. ATSDR’s history with multisite studies • Limited experience due to a heavy focus on evaluating sites independently • Ecologic analyses (with large geographical units of aggregation) • Libby, MT daughter sites (asbestosis, lung cancer, and mesothelioma incidence/mortality within zip codes, census tracts and/or city limits) • NY landfill sites with VOC soil gas migration (cancer incidence within zip codes) • Case-control studies (constrained by significant exposure misclassification potential) • childhood brain cancers and proximity to hazardous waste sites (concentric buffering around sources) • CA birth defects to minority women proximate to waste sites (census tracts)

6. Epidemiologic considerations for a multisite study – design options • Ecologic • an update to the 1990 NCI mortality study • a study of incidence with 15+ years of data across all sites • generates hypotheses, does not test hypotheses • Cohort • likely too resource intensive for these circumstances (i.e. very low doses, rare outcomes, geographically disparate populations) • Case/control • more efficient • adequate number of incident cases when combining 100+ sites over the last 15+ years • must focus on controlling exposure misclassification

7. Epidemiologic considerations for a multisite study – case/control design • Assessing outcomes is relatively easy due to broad cancer registry coverage and quality of this data • Two of the biggest concerns are selection of controls and exposure assessment for all participants • Many exposure misclassification concerns • low levels (i.e. typically within regulatory standards) • residential migration combined with lengthy latency for cancer outcomes (i.e. are you studying cases that were exposed?) • other anthropogenic and natural sources for exposure (e.g. radon)

8. Epidemiologic considerations for a multisite study – case/control design • Municipal parcel data and associated tax records • Strengths • available in most urban (and some rural) locations • identify and select controls • impose residential requirement criteria for all participants (control for exposure misclassification) • locate residences accurately if using proximity to source(s) as part of a participant’s exposure assessment • Limitations • “renters bias” - exclusion of lower SES residents (is there exposure differential when compared to long term home owners?) • initially enumerating households not individuals as controls - requires limited follow-up for actual control selection