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Shared and unshared exposure measurement error in occupational cohort studies and their effects on statistical inference in proportional hazards models.

ABSTRACT: Exposure measurement error represents one of the most important sources of uncertainty in epidemiology. When exposure uncertainty is not or only poorly accounted for, it can lead to biased risk estimates and a distortion of the shape of the exposure-response relationship. In occupational cohort studies, the time-dependent nature of exposure and changes in the method of exposure assessment may create complex error structures. When a method of group-level exposure assessment is used, individual worker practices and the imprecision of the instrument used to measure the average exposure for a group of workers may give rise to errors that are shared between workers, within workers or both. In contrast to unshared measurement error, the effects of shared errors remain largely unknown. Moreover, exposure uncertainty and magnitude of exposure are typically highest for the earliest years of exposure. We conduct a simulation study based on exposure data of the French cohort of uranium miners to compare the effects of shared and unshared exposure uncertainty on risk estimation and on the shape of the exposure-response curve in proportional hazards models. Our results indicate that uncertainty components shared within workers cause more bias in risk estimation and a more severe attenuation of the exposure-response relationship than unshared exposure uncertainty or exposure uncertainty shared between individuals. These findings underline the importance of careful characterisation and modeling of exposure uncertainty in observational studies.

SUBMITTER: Hoffmann S

PROVIDER: S-EPMC5800563 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Shared and unshared exposure measurement error in occupational cohort studies and their effects on statistical inference in proportional hazards models.

Hoffmann Sabine S Laurier Dominique D Rage Estelle E Guihenneuc Chantal C Ancelet Sophie S

PloS one 20180206 2

Exposure measurement error represents one of the most important sources of uncertainty in epidemiology. When exposure uncertainty is not or only poorly accounted for, it can lead to biased risk estimates and a distortion of the shape of the exposure-response relationship. In occupational cohort studies, the time-dependent nature of exposure and changes in the method of exposure assessment may create complex error structures. When a method of group-level exposure assessment is used, individual wo ...[more]

PMID: 29408862

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Project description:Spatiotemporal air pollution models are increasingly being used to estimate health effects in epidemiological studies. Although such exposure prediction models typically result in improved spatial and temporal resolution of air pollution predictions, they remain subject to shared measurement error, a type of measurement error common in spatiotemporal exposure models which occurs when measurement error is not independent of exposures. A fundamental challenge of exposure measurement error in air pollution assessment is the strong correlation and sometimes identical (shared) error of exposure estimates across geographic space and time. When exposure estimates with shared measurement error are used to estimate health risk in epidemiological analyses, complex errors are potentially introduced, resulting in biased epidemiological conclusions. We demonstrate the influence of using a three-stage spatiotemporal exposure prediction model and introduce formal methods of shared, multiplicative measurement error (SMME) correction of epidemiological health risk estimates. Using our three-stage, ensemble learning based nitrogen oxides (NOx) exposure prediction model, we quantified SMME. We conducted an epidemiological analysis of wheeze risk in relation to NOx exposure among school-aged children. To demonstrate the incremental influence of exposure modeling stage, we iteratively estimated the health risk using assigned exposure predictions from each stage of the NOx model. We then determined the impact of SMME on the variance of the health risk estimates under various scenarios. Depending on the stage of the spatiotemporal exposure model used, we found that wheeze odds ratio ranged from 1.16 to 1.28 for an interquartile range increase in NOx. With each additional stage of exposure modeling, the health effect estimate moved further away from the null (OR=1). When corrected for observed SMME, the health effects confidence intervals slightly lengthened, but our epidemiological conclusions were not altered. When the variance estimate was corrected for the potential "worst case scenario" of SMME, the standard error further increased, having a meaningful influence on epidemiological conclusions. Our framework can be expanded and used to understand the implications of using exposure predictions subject to shared measurement error in future health investigations.

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Project description:Several studies have compared metagenome inference performance in different human body sites; however, none specifically reported on the vaginal microbiome. Findings from other body sites cannot easily be generalized to the vaginal microbiome due to unique features of vaginal microbial ecology, and investigators seeking to use metagenome inference in vaginal microbiome research are "flying blind" with respect to potential bias these methods may introduce into analyses. We compared the performance of PICRUSt2 and Tax4Fun2 using paired 16S rRNA gene amplicon sequencing and whole-metagenome sequencing data from vaginal samples from 72 pregnant individuals enrolled in the Pregnancy, Infection, and Nutrition (PIN) cohort. Participants were selected from those with known birth outcomes and adequate 16S rRNA gene amplicon sequencing data in a case-control design. Cases experienced early preterm birth (<32 weeks of gestation), and controls experienced term birth (37 to 41 weeks of gestation). PICRUSt2 and Tax4Fun2 performed modestly overall (median Spearman correlation coefficients between observed and predicted KEGG ortholog [KO] relative abundances of 0.20 and 0.22, respectively). Both methods performed best among Lactobacillus crispatus-dominated vaginal microbiotas (median Spearman correlation coefficients of 0.24 and 0.25, respectively) and worst among Lactobacillus iners-dominated microbiotas (median Spearman correlation coefficients of 0.06 and 0.11, respectively). The same pattern was observed when evaluating correlations between univariable hypothesis test P values generated with observed and predicted metagenome data. Differential metagenome inference performance across vaginal microbiota community types can be considered differential measurement error, which often causes differential misclassification. As such, metagenome inference will introduce hard-to-predict bias (toward or away from the null) in vaginal microbiome research. IMPORTANCE Compared to taxonomic composition, the functional potential within a bacterial community is more relevant to establishing mechanistic understandings and causal relationships between the microbiome and health outcomes. Metagenome inference attempts to bridge the gap between 16S rRNA gene amplicon sequencing and whole-metagenome sequencing by predicting a microbiome's gene content based on its taxonomic composition and annotated genome sequences of its members. Metagenome inference methods have been evaluated primarily among gut samples, where they appear to perform fairly well. Here, we show that metagenome inference performance is markedly worse for the vaginal microbiome and that performance varies across common vaginal microbiome community types. Because these community types are associated with sexual and reproductive outcomes, differential metagenome inference performance will bias vaginal microbiome studies, obscuring relationships of interest. Results from such studies should be interpreted with substantial caution and the understanding that they may over- or underestimate associations with metagenome content.

Dataset Information

Shared and unshared exposure measurement error in occupational cohort studies and their effects on statistical inference in proportional hazards models.

Publications

Shared and unshared exposure measurement error in occupational cohort studies and their effects on statistical inference in proportional hazards models.

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