Background: The process of creating a cohort or cohort substudy may induce misleading exposure–health effect associations through collider stratification bias (i.e., selection bias) or bias due to conditioning on an intermediate. Studies of environmental risk factors may be at particular risk.
Objectives: We aimed to demonstrate how such biases of the exposure–health effect association arise and how one may mitigate them.
Methods: We used directed acyclic graphs and the example of bone lead and mortality (all-cause, cardiovascular, and ischemic heart disease) among 835 white men in the Normative Aging Study (NAS) to illustrate potential bias related to recruitment into the NAS and the bone lead substudy. We then applied methods (adjustment, restriction, and inverse probability of attrition weighting) to mitigate these biases in analyses using Cox proportional hazards models to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).
Results: Analyses adjusted for age at bone lead measurement, smoking, and education among all men found HRs (95% CI) for the highest versus lowest tertile of patella lead of 1.34 (0.90, 2.00), 1.46 (0.86, 2.48), and 2.01 (0.86, 4.68) for all-cause, cardiovascular, and ischemic heart disease mortality, respectively. After applying methods to mitigate the biases, the HR (95% CI) among the 637 men analyzed were 1.86 (1.12, 3.09), 2.47 (1.23, 4.96), and 5.20 (1.61, 16.8), respectively.
Conclusions: Careful attention to the underlying structure of the observed data is critical to identifying potential biases and methods to mitigate them. Understanding factors that influence initial study participation and study loss to follow-up is critical. Recruitment of population-based samples and enrolling participants at a younger age, before the potential onset of exposure-related health effects, can help reduce these potential pitfalls.
1Department of Epidemiology, and 2Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA; 3Veterans Affairs Normative Aging Study, Veterans Affairs Boston Healthcare System, and Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA; 4Division of Epidemiology, 5Division of Global Health, and 6Division of Occupational and Environmental Health, Department of Medicine, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada; 7Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
Recommended Citation:
Marc G. Weisskopf,1,2 David Sparrow,et al. Biased Exposure–Health Effect Estimates from Selection in Cohort Studies: Are Environmental Studies at Particular Risk?[J]. Environmental Health Perspectives,2015-01-01,Volume 123(Issue 11):1113