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Dose‐response analyses using restricted cubic spline functions in public health research
Author(s) -
Desquilbet Loic,
Mariotti François
Publication year - 2010
Publication title -
statistics in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.996
H-Index - 183
eISSN - 1097-0258
pISSN - 0277-6715
DOI - 10.1002/sim.3841
Subject(s) - confounding , logistic regression , statistics , linear regression , confidence interval , mathematics , covariate , medicine , national health and nutrition examination survey , linear model , econometrics , environmental health , population
Taking into account a continuous exposure in regression models by using categorization, when non‐linear dose‐response associations are expected, have been widely criticized. As one alternative, restricted cubic spline (RCS) functions are powerful tools (i) to characterize a dose‐response association between a continuous exposure and an outcome, (ii) to visually and/or statistically check the assumption of linearity of the association, and (iii) to minimize residual confounding when adjusting for a continuous exposure. Because their implementation with SAS® software is limited, we developed and present here an SAS macro that (i) creates an RCS function of continuous exposures, (ii) displays graphs showing the dose‐response association with 95 per cent confidence interval between one main continuous exposure and an outcome when performing linear, logistic, or Cox models, as well as linear and logistic‐generalized estimating equations, and (iii) provides statistical tests for overall and non‐linear associations. We illustrate the SAS macro using the third National Health and Nutrition Examination Survey data to investigate adjusted dose‐response associations (with different models) between calcium intake and bone mineral density (linear regression), folate intake and hyperhomocysteinemia (logistic regression), and serum high‐density lipoprotein cholesterol and cardiovascular mortality (Cox model). Copyright © 2010 John Wiley & Sons, Ltd.