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Dose-response Analyses Using Restricted Cubic Spline Functions In Public Health Research.
L. Desquilbet, F. Mariotti
Published 2010 · Mathematics, Medicine
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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).
This paper references
Dichotomizing continuous predictors in multiple regression: a bad idea.
P. Royston (2006)
A set of SAS macros for calculating and displaying adjusted odds ratios (with confidence intervals) for continuous covariates in logistic B-spline regression models
M. Gregory (2008)
The effect of folic acid fortification on plasma folate and total homocysteine concentrations.
P. Jacques (1999)
The cost of dichotomising continuous variables
D. Altman (2006)
A Practical Guide to Dose-Response Analyses and Risk Assessment in Occupational Epidemiology
K. Steenland (2004)
Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report.
S. Grundy (2002)
Use of spline regression in an analysis of maternal prepregnancy body mass index and adverse birth outcomes: does it tell us more than we already know?
S. Gilboa (2008)
Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III).
S. Grundy (2001)
Association of lipids and lipoprotein level with total mortality and mortality caused by cardiovascular and cancer diseases (Poland and United States collaborative study on cardiovascular epidemiology).
S. Rywik (1999)
Regression models and life tables (with discussion
D. Cox (1972)
No evidence of a change in HIV-1 virulence since 1996 in France
P. Troude (2009)
Folate and vitamin B6 intake and risk of colon cancer in relation to p53 expression.
E. Schernhammer (2008)
Selection of important variables and determination of functional form for continuous predictors in multivariable model building.
W. Sauerbrei (2007)
Quantile regression and restricted cubic splines are useful for exploring relationships between continuous variables.
R. Marrie (2009)
Comparing smoothing techniques in Cox models for exposure-response relationships.
Usha S Govindarajulu (2007)
Regression Models and Life-Tables
D. Cox (1972)
Updated Data on Proximal Femur Bone Mineral Levels of US Adults
A. Looker (1998)
Total and Percent Free Prostate-Specific Antigen Levels among U.S. Men, 2001-2002
M. Saraiya (2005)
The role of epidemiology in determining when evidence is sufficient to support nutrition recommendations. Summary statement.
T. Byers (1999)
Regression models in clinical studies: determining relationships between predictors and response.
F. Harrell (1988)
Akaike's information criterion in generalized estimating equations.
W. Pan (2001)
Generalized Additive Models
T. Hastie (1990)
Causal criteria in nutritional epidemiology.
N. Potischman (1999)
Serum total homocysteine concentrations in adolescent and adult Americans: results from the third National Health and Nutrition Examination Survey.
P. Jacques (1999)
The concept of residual confounding in regression models and some applications.
H. Becher (1992)
Multivariable regression model building by using fractional polynomials: Description of SAS, STATA and R programs
W. Sauerbrei (2006)
Dose‐Response and Trend Analysis in Epidemiology: Alternatives to Categorical Analysis
S. Greenland (1995)
A new look at the statistical model identification
H. Akaike (1974)
The relationship between nontraditional risk factors and outcomes in individuals with stage 3 to 4 CKD.
D. Weiner (2008)
Depression and increased myocardial ischemic activity in patients with ischemic heart disease.
W. Jiang (2003)
Energy adjustment methods for nutritional epidemiology: the effect of categorization.
C. Brown (1994)
Efficiency loss from categorizing quantitative exposures into qualitative exposures in case-control studies.
L. Zhao (1992)
Is serum ferritin within the reference range a risk predictor of cardiovascular disease? A population-based, long-term study comprising 2874 subjects.
N. Friedrich (2009)
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Detection, Evaluation, and Treatment of High Blood Cholesterol Education Program (NCEP) Expert Panel on Executive Summary of the Third Report of the National
W. Taylor (2009)
Ten-year mortality from cardiovascular disease in relation to cholesterol level among men with and without preexisting cardiovascular disease.
J. Pekkanen (1990)
Fractional polynomials and model selection in generalized estimating equations analysis, with an application to a longitudinal epidemiologic study in Australia.
J. Cui (2009)
Tests for trend and dose response: misinterpretations and alternatives.
M. Maclure (1992)
Regression using fractional polynomials of continuous covariates: parsimonious parametric modelling.
P. Royston (1994)
Controlling for Continuous Confounders in Epidemiologic Research
H. Brenner (1997)
Splines as a Useful and Convenient Statistical Tool
P. Smith (1979)
Avoiding power loss associated with categorization and ordinal scores in dose-response and trend analysis.
S. Greenland (1995)
Flexible regression models with cubic splines.
S. Durrleman (1989)
Gaining more flexibility in Cox proportional hazards regression models with cubic spline functions.
H. Heinzl (1997)
Longitudinal data analysis for discrete and continuous outcomes.
S. Zeger (1986)
The use of fractional polynomials to model continuous risk variables in epidemiology.
P. Royston (1999)
A meta-analysis of the effect of calcium intake on bone mass in young and middle aged females and males
D. Welten (1995)
This paper is referenced by
Serum Perfluorinated Compound Concentration and Attention Deficit/Hyperactivity Disorder in Children 5–18 Years of Age
C. Stein (2011)
Potassium measurements and risk of type 2 diabetes: a dose-response meta-analysis of prospective cohort studies
Y. Peng (2017)
Outcome Relationship for Robotic-Assisted Radical Prostatectomy : Implications for Centralization of Care
B. Gershman (2017)
ASPIRIN AND THE RISK OF NON-DIGESTIVE TRACT CANCERS: AN UPDATED META-ANALYSIS TO 2019.
C. Santucci (2020)
Identification of novel modifiable risk factors of gastric adenocarcinoma
Zhensheng Wang (2017)
Mammographic density, parity and age at first birth, and risk of breast cancer: an analysis of four case–control studies
C. Woolcott (2011)
Analysis of Continuous Covariates and Dose-Effect Analysis
H. Becher (2014)
Impact of Early-Life Weight Status on Cognitive Abilities in Children
N. Li (2018)
Longitudinal patterns of cancer patient reported outcomes in end of life care predict survival
G. Stukenborg (2015)
Non-linear associations between sleep duration and the risks of mild cognitive impairment/dementia and cognitive decline: a dose–response meta-analysis of observational studies
Y. Liang (2018)
Urinary metabolites of polycyclic aromatic hydrocarbons, sperm DNA damage and spermatozoa apoptosis.
P. Yang (2017)
Prenatal exposure to chlordecone, gestational weight gain, and birth weight in a Guadeloupean birth cohort.
David Hervé (2016)
Genetic association of telomere length with hepatocellular carcinoma risk: A Mendelian randomization analysis.
Y. Cheng (2017)
Association Between Maximal Activated Clotting Time and Major Bleeding Complications During Transradial and Transfemoral Percutaneous Coronary Intervention.
David W. Louis (2018)
Mortality study of civilian employees exposed to contaminated drinking water at USMC Base Camp Lejeune: a retrospective cohort study
F. J. Bové (2014)
Low-carbohydrate diets and prevalence, incidence and progression of coronary artery calcium in the Multi-Ethnic Study of Atherosclerosis (MESA).
T. Hu (2019)
What is the hospital volume threshold to optimize inpatient complication rate after partial nephrectomy?
S. Arora (2018)
Cognitive impairment, all-cause and cause-specific mortality among non-demented older adults.
L. Perna (2015)
Tobacco Use Cessation Among Quitline Callers Who Implemented Complete Home Smoking Bans During the Quitting Process
A. Jung (2017)
Blood lead level association with lower body weight in NHANES 1999-2006.
F. Scinicariello (2013)
Association between adherence to the French dietary guidelines and the risk of type 2 diabetes.
E. Kesse-guyot (2020)
Extreme heat and occupational heat illnesses in South Australia, 2001–2010
J. Xiang (2015)
Coffee consumption and mortality from all causes, cardiovascular disease, and cancer: a dose-response meta-analysis.
A. Crippa (2014)
Long-term population effects of pneumococcal vaccines on carriage of pneumococcal serotypes and subsequent disease in Kenya
John Ojal (2018)
Preoperative cardiac function parameters as valuable predictors for nurses to recognise delirium after cardiac surgery: A prospective cohort study
S. Cai (2019)
Circulating angiopoietin‐2, its soluble receptor Tie‐2, and mortality in the general population
R. Lorbeer (2013)
Statins and risk of treated incident diabetes in a primary care population.
N. Zaharan (2013)
Respirable indium exposures, plasma indium, and respiratory health among indium-tin oxide (ITO) workers.
K. Cummings (2016)
Temporal trends in HIV-1 incidence and risk behaviours in men who have sex with men in Bangkok, Thailand, 2006-13: an observational study.
F. van Griensven (2015)
Maternal and cord blood 25(OH)-vitamin D concentrations in relation to child development and behaviour.
S. Keim (2014)
Relation of Mitral Valve Surgery Volume to Repair Rate, Durability, and Survival.
Joanna Chikwe (2017)
Predictive markers of clinical outcome in the GRMD dog model of Duchenne muscular dystrophy
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