Abstract
BackgroundAccurate exposure estimation in environmental epidemiological studies is crucial for health risk assessment. Failure to account for uncertainties in exposure estimation could lead to biased results in exposure-response analyses. Assessment of the effects of uncertainties in exposure estimation on risk estimates received a lot of attention in radiation epidemiology and in several studies of diet and air pollution. The objective of this narrative review is to examine the commonly used statistical approaches to account for exposure estimation errors in risk analyses and to suggest how each could be applied in environmental epidemiological studies.Main textWe review two main error types in estimating exposures in epidemiological studies: shared and unshared errors and their subtypes. We describe the four main statistical approaches to adjust for exposure estimation uncertainties (regression calibration, simulation-extrapolation, Monte Carlo maximum likelihood and Bayesian model averaging) along with examples to give readers better understanding of their advantages and limitations. We also explain the advantages of using a 2-dimensional Monte-Carlo (2DMC) simulation method to quantify the effect of uncertainties in exposure estimates using full-likelihood methods. For exposures that are estimated independently between subjects and are more likely to introduce unshared errors, regression calibration and SIMEX methods are able to adequately account for exposure uncertainties in risk analyses. When an uncalibrated measuring device is used or estimation parameters with uncertain mean values are applied to a group of people, shared errors could potentially be large. In this case, Monte Carlo maximum likelihood and Bayesian model averaging methods based on estimates of exposure from the 2DMC simulations would work well. The majority of reviewed studies show relatively moderate changes (within 100%) in risk estimates after accounting for uncertainties in exposure estimates, except for the two studies which doubled/tripled naïve estimates.ConclusionsIn this paper, we demonstrate various statistical methods to account for uncertain exposure estimates in risk analyses. The differences in the results of various adjustment methods could be due to various error structures in datasets and whether or not a proper statistical method was applied. Epidemiological studies of environmental exposures should include exposure-response analyses accounting for uncertainties in exposure estimates.
Highlights
We review two main error types in estimating exposures in epidemiological studies: shared and unshared errors and their subtypes
Epidemiological studies of environmental exposures should include exposure-response analyses accounting for uncertainties in exposure estimates
A radiation epidemiological study exploring a relationship between individual colon dose from gamma radiation and solid cancer deaths [50] reported that the estimated excess relative risk per gray (ERR/Gy) increased by 38.4% after accounting for dose uncertainties by SIMEX, compared to an increase of 6.7% after adjustment by regression calibration
Summary
We review two main error types in estimating exposures in epidemiological studies: shared and unshared errors and their subtypes. When an uncalibrated measuring device is used or estimation parameters with uncertain mean values are applied to a group of people, shared errors could potentially be large In this case, Monte Carlo maximum likelihood and Bayesian model averaging methods based on estimates of exposure from the 2DMC simulations would work well. Assessment of the effects of uncertainties in exposure estimation on risk estimates received a lot of attention in radiation epidemiology and in several studies of diet and air pollution. The objective of this narrative review is to examine the commonly used statistical approaches to account for exposure estimation errors in risk analyses and to suggest how each could be applied in environmental epidemiological studies. The three main effects of performing an exposure-response analysis based on the error-prone exposure estimates are: (a) biased estimation of exposure-response parameters, (b) reduction of statistical power, and (c) hidden true exposure-response features (e.g., true exposure-response is distributed with a certain cyclic variation pattern such as sinusoidal trend, this feature may be masked if exposure is estimated with errors) [3]
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