Trade-offs of Personal Versus More Proxy Exposure Measures in Environmental Epidemiology

Abstract

The technological ability to make personal measurements of toxicant exposures is growing rapidly. While this can decrease measurement error and therefore help reduce attenuation of effect estimates, we argue that as measures of exposure or dose become more personal, threats to validity of study findings can increase in ways that more proxy measures may avoid. We use Directed Acyclic Graphs (DAGs) to describe conditions where confounding is introduced by use of more personal measures of exposure and avoided via more proxy measures of personal exposure or target tissue dose. As exposure or dose estimates are more removed from the individual, they become less susceptible to biases from confounding by personal factors that can often be hard to control, such as personal behaviors. Similarly, more proxy exposure estimates are less susceptible to reverse causation. We provide examples from the literature where adjustment for personal factors in analyses that use more proxy exposure estimates have little effect on study results. In conclusion, increased personalized exposure assessment has important advantages for measurement accuracy, but it can increase the possibility of biases from personal factors and reverse causation compared with more proxy exposure estimates. Understanding the relation between more and less proxy exposures, and variables that could introduce confounding are critical components to study design.

Profiles of Emerging and Legacy Per-/Polyfluoroalkyl Substances in Matched Serum and Semen Samples: New Implications for Human Semen Quality

“…However, it should be noted that there is greater potential for confounding by physiological conditions when PFAS exposure is assessed in semen than in serum. This is because the closer exposure and outcome are physiologically (e.g., assessed in the same organ), the greater the extraneous factors and hence potential confounders (Weisskopf and Webster 2017). For instance, if a certain condition in the prostate or testis (not influenced by PFAS) can alter both semen volume and other semen parameters, this could induce an indirect association between seminal PFASs (because an effect on semen volume may influence PFAS concentration) and other semen parameters.…”

“…As such, seminal PFAS levels are worth exploring as potential exposure markers for epidemiological studies. However, one must consider that using a more accurate measure of target organ exposure may introduce confounding that would not occur if a more remote measure of exposure was used (Weisskopf and Webster 2017).…”

Residential ambient benzene exposure in the United States and subsequent risk of hematologic malignancies

“…To the best of our knowledge, this is the first nationwide cohort examination of the association between EPA's modeled benzene estimates with individual level data and risk of hematologic malignancies in the United States. Though personal benzene measurements were not used in this study, a methodological commentary published in Epidemiology points out that proxy measures like ambient benzene levels have some advantages over personal monitors . Personal exposure measures can be subject to both confounding and reverse causation that are difficult to identify and address analytically because they are personalized to each individual.…”

“…Though personal benzene measurements were not used in this study, a methodological commentary published in Epidemiology points out that proxy measures like ambient benzene levels have some advantages over personal monitors. 28 Personal exposure measures can be subject to both confounding and reverse causation that are difficult to identify and address analytically because they are personalized to each individual. In contrast, the measurement of ambient benzene, and the distribution of ambient benzene across census tracts in the United States are unrelated to individual behaviors or characteristics of the CPS-II participants.…”

Impacts of the Mitochondrial Genome on the Relationship of Long-Term Ambient Fine Particle Exposure with Blood DNA Methylation Age

“…However, the majority of NAS participants are retired and very likely spend most of their time at home. Moreover, any resulting non-differential misclassification is likely to attenuate statistical associations rather than bias them away from the null 68–69 . Secondly, the mitochondrial genotyping technique resulted in haplogroup designations that may not encompass more recent mutations that could potentially impact the relationship of PM2.5 with DNAm-age.…”