Variable selection and Bayesian model averaging in case-control studies

Covariate and confounder selection in case‐control studies is often carried out using a statistical variable selection method, such as a two‐step method or a stepwise method in logistic regression. Inference is then carried out conditionally on the selected model, but this ignores the model uncertai...

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Published inStatistics in medicine Vol. 20; no. 21; pp. 3215 - 3230
Main Authors Viallefont, Valerie, Raftery, Adrian E., Richardson, Sylvia
Format Journal Article
LanguageEnglish
Published Chichester, UK John Wiley & Sons, Ltd 15.11.2001
Wiley
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ISSN0277-6715
1097-0258
DOI10.1002/sim.976

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Abstract Covariate and confounder selection in case‐control studies is often carried out using a statistical variable selection method, such as a two‐step method or a stepwise method in logistic regression. Inference is then carried out conditionally on the selected model, but this ignores the model uncertainty implicit in the variable selection process, and so may underestimate uncertainty about relative risks. We report on a simulation study designed to be similar to actual case‐control studies. This shows that p‐values computed after variable selection can greatly overstate the strength of conclusions. For example, for our simulated case‐control studies with 1000 subjects, of variables declared to be ‘significant’ with p‐values between 0.01 and 0.05, only 49 per cent actually were risk factors when stepwise variable selection was used. We propose Bayesian model averaging as a formal way of taking account of model uncertainty in case‐control studies. This yields an easily interpreted summary, the posterior probability that a variable is a risk factor, and our simulation study indicates this to be reasonably well calibrated in the situations simulated. The methods are applied and compared in the context of a case‐control study of cervical cancer. Copyright © 2001 John Wiley & Sons, Ltd.
AbstractList Covariate and confounder selection in case-control studies is often carried out using a statistical variable selection method, such as a two-step method or a stepwise method in logistic regression. Inference is then carried out conditionally on the selected model, but this ignores the model uncertainty implicit in the variable selection process, and so may underestimate uncertainty about relative risks. We report on a simulation study designed to be similar to actual case-control studies. This shows that p-values computed after variable selection can greatly overstate the strength of conclusions. For example, for our simulated case-control studies with 1000 subjects, of variables declared to be 'significant' with p-values between 0.01 and 0.05, only 49 per cent actually were risk factors when stepwise variable selection was used. We propose Bayesian model averaging as a formal way of taking account of model uncertainty in case-control studies. This yields an easily interpreted summary, the posterior probability that a variable is a risk factor, and our simulation study indicates this to be reasonably well calibrated in the situations simulated. The methods are applied and compared in the context of a case-control study of cervical cancer.Covariate and confounder selection in case-control studies is often carried out using a statistical variable selection method, such as a two-step method or a stepwise method in logistic regression. Inference is then carried out conditionally on the selected model, but this ignores the model uncertainty implicit in the variable selection process, and so may underestimate uncertainty about relative risks. We report on a simulation study designed to be similar to actual case-control studies. This shows that p-values computed after variable selection can greatly overstate the strength of conclusions. For example, for our simulated case-control studies with 1000 subjects, of variables declared to be 'significant' with p-values between 0.01 and 0.05, only 49 per cent actually were risk factors when stepwise variable selection was used. We propose Bayesian model averaging as a formal way of taking account of model uncertainty in case-control studies. This yields an easily interpreted summary, the posterior probability that a variable is a risk factor, and our simulation study indicates this to be reasonably well calibrated in the situations simulated. The methods are applied and compared in the context of a case-control study of cervical cancer.
Covariate and confounder selection in case‐control studies is often carried out using a statistical variable selection method, such as a two‐step method or a stepwise method in logistic regression. Inference is then carried out conditionally on the selected model, but this ignores the model uncertainty implicit in the variable selection process, and so may underestimate uncertainty about relative risks. We report on a simulation study designed to be similar to actual case‐control studies. This shows that p ‐values computed after variable selection can greatly overstate the strength of conclusions. For example, for our simulated case‐control studies with 1000 subjects, of variables declared to be ‘significant’ with p ‐values between 0.01 and 0.05, only 49 per cent actually were risk factors when stepwise variable selection was used. We propose Bayesian model averaging as a formal way of taking account of model uncertainty in case‐control studies. This yields an easily interpreted summary, the posterior probability that a variable is a risk factor, and our simulation study indicates this to be reasonably well calibrated in the situations simulated. The methods are applied and compared in the context of a case‐control study of cervical cancer. Copyright © 2001 John Wiley & Sons, Ltd.
Covariate and confounder selection in case‐control studies is often carried out using a statistical variable selection method, such as a two‐step method or a stepwise method in logistic regression. Inference is then carried out conditionally on the selected model, but this ignores the model uncertainty implicit in the variable selection process, and so may underestimate uncertainty about relative risks. We report on a simulation study designed to be similar to actual case‐control studies. This shows that p‐values computed after variable selection can greatly overstate the strength of conclusions. For example, for our simulated case‐control studies with 1000 subjects, of variables declared to be ‘significant’ with p‐values between 0.01 and 0.05, only 49 per cent actually were risk factors when stepwise variable selection was used. We propose Bayesian model averaging as a formal way of taking account of model uncertainty in case‐control studies. This yields an easily interpreted summary, the posterior probability that a variable is a risk factor, and our simulation study indicates this to be reasonably well calibrated in the situations simulated. The methods are applied and compared in the context of a case‐control study of cervical cancer. Copyright © 2001 John Wiley & Sons, Ltd.
Covariate and confounder selection in case-control studies is often carried out using a statistical variable selection method, such as a two-step method or a stepwise method in logistic regression. Inference is then carried out conditionally on the selected model, but this ignores the model uncertainty implicit in the variable selection process, and so may underestimate uncertainty about relative risks. We report on a simulation study designed to be similar to actual case-control studies. This shows that p-values computed after variable selection can greatly overstate the strength of conclusions. For example, for our simulated case-control studies with 1000 subjects, of variables declared to be 'significant' with p-values between 0.01 and 0.05, only 49 per cent actually were risk factors when stepwise variable selection was used. We propose Bayesian model averaging as a formal way of taking account of model uncertainty in case-control studies. This yields an easily interpreted summary, the posterior probability that a variable is a risk factor, and our simulation study indicates this to be reasonably well calibrated in the situations simulated. The methods are applied and compared in the context of a case-control study of cervical cancer.
Author Richardson, Sylvia
Viallefont, Valerie
Raftery, Adrian E.
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  surname: Richardson
  fullname: Richardson, Sylvia
  organization: INSERM-U. 170, 16 av P. Vaillant-Couturier, 94 807 Villejuif Cedex, France
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Issue 21
Keywords Bayes estimation
Human
Statistical analysis
Average
Uterine cervix
Case control study
Malignant tumor
Epidemiology
Female genital diseases
Statistical method
Risk factor
Female
Uterine cervix diseases
Language English
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CC BY 4.0
Copyright 2001 John Wiley & Sons, Ltd.
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References Racine A, Grieve AP, Fluhler H, Smith AFM. Bayesian methods in practice: experiences in the pharmaceutical industry (with discussion). Applied Statistics 1986; 35:93-150.
Madigan D, Raftery AE. Model selection and accounting for model uncertainty in graphical models using Occam's window. Journal of the American Statistical Association 1994; 89:1535-1546.
Armitage P. Statistical Methods in Medical Research. Blackwell Scientific Publications: Oxford, UK, 1971.
Berger JO, Delampady M. Testing precise hypotheses (with discussion). Statistical Science 1987; 3:317-352.
Richardson S, Gerber M, Cénée S. The role of fat, animal protein and some vitamin consumption in breast cancer: a case-control study in southern France. International Journal of Cancer 1991; 48:1-9.
Bernardo JM, Smith AFM. Bayesian Theory. Wiley: New York, 1994.
Miller AJ. Subset Selection in Regression. Chapman and Hall: London, UK, 1990.
Chatfield CC. Model uncertainty, data mining and statistical inference (with discussion). Journal of the Royal Statistical Society, Series A 1995; 158:419-466.
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Breslow NE. Statistics in epidemiology: the case-control study. Journal of the American Statistical Association 1996; 91:14-28.
Raftery AE. Approximate Bayes factors and accounting for model uncertainty in generalized linear models. Biometrika 1996; 83:251-266.
Draper D. Assessment and propagation of model uncertainty (with discussion). Journal of the Royal Statistical Society, Series B 1995; 57:45-98.
Lee PM. Bayesian Statistics: An Introduction. Oxford University Press: Oxford, U.K., 1989.
Volinsky CT, Madigan D, Raftery AE, Kronmal RA. Bayesian model averaging in proportional hazard models: predicting the risk of a stroke. Applied Statistics 1997; 46:443-448.
Jeffreys H. Theory of Probability. 3rd edn. Oxford University Press: Oxford, U.K., 1961.
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Hosmer DW, Lemeshow S. Applied Logistic Regression. Wiley: New York, 1989.
Leamer EE. Specification Searches: Ad Hoc Inference With Nonexperimental Data. Wiley: New York, 1978.
Hoeting JA, Raftery AE, Madigan D. A method for simultaneous variable selection and outlier identification in linear regression. Journal of Computational Statistics 1995; 22:251-271.
Gelman A, Carlin JB, Stern HS, Rubin DB. Bayesian Data Analysis. Chapman and Hall: London, 1995.
Mickey RM, Greenland S. The impact of confounder selection criteria on effect estimation. American Journal of Epidemiology 1989; 129(1):125-137.
Rubin DB, Schenker N. Efficiently simulating the coverage properties of interval estimates. Applied Statistics 1986; 35:159-167.
Raftery AE, Madigan D, Hoeting JA. Model selection and accounting for model uncertainty in linear regression models. Journal of the American Statistical Association 1997; 92:179-191.
Kass RE, Raftery AE. Bayes factors. Journal of the American Statistical Association 1995; 90:773-795.
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Peters RK (e_1_2_1_9_2) 1986; 77
Armitage P (e_1_2_1_31_2) 1971
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– reference: Lee PM. Bayesian Statistics: An Introduction. Oxford University Press: Oxford, U.K., 1989.
– reference: Volinsky CT, Madigan D, Raftery AE, Kronmal RA. Bayesian model averaging in proportional hazard models: predicting the risk of a stroke. Applied Statistics 1997; 46:443-448.
– reference: Miller AJ. Subset Selection in Regression. Chapman and Hall: London, UK, 1990.
– reference: Mickey RM, Greenland S. The impact of confounder selection criteria on effect estimation. American Journal of Epidemiology 1989; 129(1):125-137.
– reference: Raftery AE. Approximate Bayes factors and accounting for model uncertainty in generalized linear models. Biometrika 1996; 83:251-266.
– reference: Richardson S, Gerber M, Cénée S. The role of fat, animal protein and some vitamin consumption in breast cancer: a case-control study in southern France. International Journal of Cancer 1991; 48:1-9.
– reference: Leamer EE. Specification Searches: Ad Hoc Inference With Nonexperimental Data. Wiley: New York, 1978.
– reference: Hoeting JA, Raftery AE, Madigan D. A method for simultaneous variable selection and outlier identification in linear regression. Journal of Computational Statistics 1995; 22:251-271.
– reference: Berger JO, Delampady M. Testing precise hypotheses (with discussion). Statistical Science 1987; 3:317-352.
– reference: Freedman DA. A note on screening regression equations. American Statistician 1983; 37:152-155.
– reference: Gelman A, Carlin JB, Stern HS, Rubin DB. Bayesian Data Analysis. Chapman and Hall: London, 1995.
– reference: Raftery AE, Madigan D, Hoeting JA. Model selection and accounting for model uncertainty in linear regression models. Journal of the American Statistical Association 1997; 92:179-191.
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– reference: Bernardo JM, Smith AFM. Bayesian Theory. Wiley: New York, 1994.
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– reference: Jeffreys H. Theory of Probability. 3rd edn. Oxford University Press: Oxford, U.K., 1961.
– reference: Hosmer DW, Lemeshow S. Applied Logistic Regression. Wiley: New York, 1989.
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– reference: Savitz DA, Tolo K-A, Poole C. Statistical significance testing in the American Journal of Epidemiology, 1970 -1990. American Journal of Epidemiology 1994; 139(10):1047-1052.
– reference: Rothman KJ, Greenland S. Modern Epidemiology. 2nd edn. Lippincott, Williams & Wilkins: Philadelphia, 1998.
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Snippet Covariate and confounder selection in case‐control studies is often carried out using a statistical variable selection method, such as a two‐step method or a...
Covariate and confounder selection in case-control studies is often carried out using a statistical variable selection method, such as a two-step method or a...
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SubjectTerms Analysis of Variance
Bayes Theorem
Biological and medical sciences
Biometry
Case-Control Studies
Female
Female genital diseases
Gynecology. Andrology. Obstetrics
Humans
Medical sciences
Odds Ratio
Risk Factors
Tumors
Uterine Cervical Neoplasms - epidemiology
Title Variable selection and Bayesian model averaging in case-control studies
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