Smoothing in occupational cohort studies: an illustration based on penalised splines

Occupational and Environmental Medicine
E A EisenH Checkoway

Abstract

To illustrate the contribution of smoothing methods to modelling exposure-response data, Cox models with penalised splines were used to reanalyse lung cancer risk in a cohort of workers exposed to silica in California's diatomaceous earth industry. To encourage application of this approach, computer code is provided. Relying on graphic plots of hazard ratios as smooth functions of exposure, the sensitivity of the curve to amount of smoothing, length of the exposure lag, and the influence of the highest exposures was evaluated. Trimming and data transformations were used to down-weight influential observations. The estimated hazard ratio increased steeply with cumulative silica exposure before flattening and then declining over the sparser regions of exposure. The curve was sensitive to changes in degrees of freedom, but insensitive to the number or location of knots. As the length of lag increased, so did the maximum hazard ratio, but the shape was similar. Deleting the two highest exposed subjects eliminated the top half of the range and allowed the hazard ratio to continue to rise. The shape of the splines suggested a parametric model with log hazard as a linear function of log transformed exposure would fit well. This flexib...Continue Reading

References

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Citations

Jan 20, 2007·Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA·A Díez-PérezUNKNOWN Ecografía Osea en Atención Primaria study investigators
Mar 24, 2012·World Journal of Urology·Chang Wook JeongSang Eun Lee
May 9, 2012·Cancer Causes & Control : CCC·Melissa C FriesenEllen A Eisen
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Jun 18, 2005·Occupational and Environmental Medicine·R McNamee
Apr 24, 2007·Occupational and Environmental Medicine·Katie M ApplebaumEllen A Eisen
Mar 3, 2007·Occupational and Environmental Medicine·Kanta SircarMichael Attfield
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Jan 12, 2013·Environmental Health Perspectives·Giulia CesaroniFrancesco Forastiere
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