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Published Online: 1 August 2012

Designing Case-Control Studies: Decisions About the Controls

Abstract

The authors quantified, first, the effect of misclassified controls (i.e., individuals who are affected with the disease under study but who are classified as controls) on the ability of a case-control study to detect an association between a disease and a genetic marker, and second, the effect of leaving misclassified controls in the study, as opposed to removing them (thus decreasing sample size). The authors developed an informativeness measure of a study's ability to identify real differences between cases and controls. They then examined this measure's behavior when there are no misclassified controls, when there are misclassified controls, and when there were misclassified controls but they have been removed from the study. The results show that if, for example, 10% of controls are misclassified, the study's informativeness is reduced to approximately 81% of what it would have been in a sample with no misclassified controls, whereas if these misclassified controls are removed from the study, the informativeness is only reduced to about 90%, despite the reduced sample size. If 25% are misclassified, those figures become approximately 56% and 75%, respectively. Thus, leaving the misclassified controls in the control sample is worse than removing them altogether. Finally, the authors illustrate how insufficient power is not necessarily circumvented by having an unlimited number of controls. The formulas provided by the authors enable investigators to make rational decisions about removing misclassified controls or leaving them in.

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Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Pages: 785 - 789
PubMed: 22854929

History

Received: 14 November 2011
Revision received: 30 January 2012
Revision received: 15 March 2012
Accepted: 15 March 2012
Published online: 1 August 2012
Published in print: August 2012

Authors

Details

Susan E. Hodge, D.Sc.
From the Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York; the Department of Epidemiology and the Division of Statistical Genetics, Department of Biostatistics, Mailman School of Public Health, Columbia University; and the Division of Epidemiology and the Division of Clinical Therapeutics, New York State Psychiatric Institute, New York.
Ryan L. Subaran, Ph.D.
From the Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York; the Department of Epidemiology and the Division of Statistical Genetics, Department of Biostatistics, Mailman School of Public Health, Columbia University; and the Division of Epidemiology and the Division of Clinical Therapeutics, New York State Psychiatric Institute, New York.
Myrna M. Weissman, Ph.D.
From the Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York; the Department of Epidemiology and the Division of Statistical Genetics, Department of Biostatistics, Mailman School of Public Health, Columbia University; and the Division of Epidemiology and the Division of Clinical Therapeutics, New York State Psychiatric Institute, New York.
Abby J. Fyer, M.D.
From the Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York; the Department of Epidemiology and the Division of Statistical Genetics, Department of Biostatistics, Mailman School of Public Health, Columbia University; and the Division of Epidemiology and the Division of Clinical Therapeutics, New York State Psychiatric Institute, New York.

Notes

Address correspondence to Dr. Hodge ([email protected]).

Funding Information

Dr. Weissman has received research support from NIMH, the National Institute on Drug Abuse, NARSAD, the Sackler Foundation, the Templeton Foundation, and the Interstitial Cystitis Association and receives royalties from Perseus Books, American Psychiatric Press, Oxford University Press, and Multi-Health Systems. The other authors report no financial relationships with commercial interests.Supported by NIMH grants MH60912 (to Dr. Weissman), MH37592 (to Dr. Donald F. Klein and Dr. Fyer), MH65213 (to Drs. Subaran and Hodge), MH48858 (to Dr. Hodge), and MH090966 (to Drs. Jay Gingrich, Weissman, and Hodge).

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