| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 1984 Oxford University Press
research-article |
The Design of Case-Control Studies: The Influence of Confounding and Interaction Effects
*Department of Medical Statistics and Epidemiology, London School of Hygiene and Tropical Medicine London WC1E 7HT, UK.
**Unit of Biostatistics, International Agency for Research on Cancer 69372 Lyon Cedex 08, France
This paper considers quantitatively the extent to which the interaction or confounding effects of covariates may influence the design of case-control studies with particular reference to sample size requirements and the role of matching. For the most part, attention is confined to a dichotomous exposure variable, and a single dichotomous covariate. Adjustment for confounding variables appears to have little effect on the power of a study unless they are strongly (odds ratio of 5 or more) related to both the disease and the exposure of interest, and only in similar circumstances will matching be of appreciable value. Matching also makes only a small improvement in the power to detect interaction effects, except under fairly extreme conditions. Both to control confounding and to detect interaction, the effect of matching may sometimes be to reduce the power of a study. The difference in power between matched and unmatched studies diminishes rapidly as the control-to-case ratio is increased. The implications of interaction effects for sample size requirements are more important. If one aim of a study is to detect interactions, the size of the study will have to be at least four times larger than if attention were confined to detecting main effects of the same magnitude. These conclusions are based on a quantitative evaluation of a wide range of possible situations.
Received 1 October 1983
![]()
CiteULike
Connotea
Del.icio.us What's this?
This article has been cited by other articles:
![]() |
P. F. Pinsky Claims of Sex-Gene Interactions JAMA, December 19, 2007; 298(23): 2741 - 2742. [Full Text] [PDF] |
||||
![]() |
A. M Elliott, M. Kizza, M. A Quigley, J. Ndibazza, M. Nampijja, L. Muhangi, L. Morison, P. B Namujju, M. Muwanga, N. Kabatereine, et al. The impact of helminths on the response to immunization and on the incidence of infection and disease in childhood in Uganda: design of a randomized, double-blind, placebo-controlled, factorial trial of deworming interventions delivered in pregnancy and early childhood [ISRCTN32849447] Clinical Trials, February 1, 2007; 4(1): 42 - 57. [Abstract] [PDF] |
||||
![]() |
J. A. Hanley, I. Csizmadi, and J.-P. Collet Two-Stage Case-Control Studies: Precision of Parameter Estimates and Considerations in Selecting Sample Size Am. J. Epidemiol., December 15, 2005; 162(12): 1225 - 1234. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. F. Masson, L. Sharp, S. C. Cotton, and J. Little Cytochrome P-450 1A1 Gene Polymorphisms and Risk of Breast Cancer: A HuGE Review Am. J. Epidemiol., May 15, 2005; 161(10): 901 - 915. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. L. N. Wood, J. R. Newton, N. Chanter, and J. A. Mumford Association between Respiratory Disease and Bacterial and Viral Infections in British Racehorses J. Clin. Microbiol., January 1, 2005; 43(1): 120 - 126. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. B Cologne, G. B Sharp, K. Neriishi, P. K Verkasalo, C. E Land, and K. Nakachi Improving the efficiency of nested case-control studies of interaction by selecting controls using counter matching on exposure Int. J. Epidemiol., June 1, 2004; 33(3): 485 - 492. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. L. Saunders and J. H. Barrett Flexible Matching in Case-Control Studies of Gene-Environment Interactions Am. J. Epidemiol., January 1, 2004; 159(1): 17 - 22. [Abstract] [Full Text] [PDF] |
||||
![]() |
A C. Janssens, P A van Doorn, J B de Boer, N F Kalkers, F G. van der Meche, J Passchier, and R Q Hintzen A nxiety and depression influence the relation between disability status and quality of life in multiple sclerosis Multiple Sclerosis, August 1, 2003; 9(4): 397 - 403. [Abstract] [PDF] |
||||
![]() |
S. Rollinson, A. P. Levene, F. K. Mensah, P. L. Roddam, J. M. Allan, T. C. Diss, E. Roman, A. Jack, K. MacLennan, M. F. Dixon, et al. Gastric marginal zone lymphoma is associated with polymorphisms in genes involved in inflammatory response and antioxidative capacity Blood, August 1, 2003; 102(3): 1007 - 1011. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. R. Merikangas and N. Risch Will the Genomics Revolution Revolutionize Psychiatry? Am J Psychiatry, April 1, 2003; 160(4): 625 - 635. [Full Text] [PDF] |
||||
![]() |
K. T. Zondervan, L. R. Cardon, and S. H. Kennedy What makes a good case-control study?: Design issues for complex traits such as endometriosis Hum. Reprod., June 1, 2002; 17(6): 1415 - 1423. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Bennett, C. Lienhardt, O. Bah-Sow, P. Gustafson, K. Manneh, G. Del Prete, V. Gomes, M. Newport, K. McAdam, and A. Hill Investigation of Environmental and Host-related Risk Factors for Tuberculosis in Africa. II. Investigation of Host Genetic Factors Am. J. Epidemiol., June 1, 2002; 155(11): 1074 - 1079. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. A. Nelson and J. S. Witte Androgen Receptor CAG Repeats and Prostate Cancer Am. J. Epidemiol., May 15, 2002; 155(10): 883 - 890. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. M. Psaty, N. L. Smith, S. R. Heckbert, H. L. Vos, R. N. Lemaitre, A. P. Reiner, D. S. Siscovick, J. Bis, T. Lumley, W. T. Longstreth Jr, et al. Diuretic Therapy, the {alpha}-Adducin Gene Variant, and the Risk of Myocardial Infarction or Stroke in Persons With Treated Hypertension JAMA, April 3, 2002; 287(13): 1680 - 1689. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Sturmer and H. Brenner Flexible Matching Strategies to Increase Power and Efficiency to Detect and Estimate Gene-Environment Interactions in Case-Control Studies Am. J. Epidemiol., April 1, 2002; 155(7): 593 - 602. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. T. Goodman, K. McDuffie, B. Hernandez, L. R. Wilkens, C. C. Bertram, J. Killeen, L. Le Marchand, J. Selhub, S. Murphy, and T. A. Donlon Association of Methylenetetrahydrofolate Reductase Polymorphism C677T and Dietary Folate with the Risk of Cervical Dysplasia Cancer Epidemiol. Biomarkers Prev., December 1, 2001; 10(12): 1275 - 1280. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Luan, M. Wong, N. Day, and N. Wareham Sample size determination for studies of gene-environment interaction Int. J. Epidemiol., October 1, 2001; 30(5): 1035 - 1040. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. M. Psaty, N. L. Smith, R. N. Lemaitre, H. L. Vos, S. R. Heckbert, A. Z. LaCroix, and F. R. Rosendaal Hormone Replacement Therapy, Prothrombotic Mutations, and the Risk of Incident Nonfatal Myocardial Infarction in Postmenopausal Women JAMA, February 21, 2001; 285(7): 906 - 913. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Andrieu, A. M. Goldstein, D. C. Thomas, and B. Langholz Counter-Matching in Studies of Gene-Environment Interaction: Efficiency and Feasibility Am. J. Epidemiol., February 1, 2001; 153(3): 265 - 274. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. R. Weinberg and D. M. Umbach Choosing a Retrospective Design to Assess Joint Genetic and Environmental Contributions to Risk Am. J. Epidemiol., August 1, 2000; 152(3): 197 - 203. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Millikan, G. Pittman, C.-K. Tse, D. A. Savitz, B. Newman, and D. Bell Glutathione S-Transferases M1, T1, and P1 and Breast Cancer Cancer Epidemiol. Biomarkers Prev., June 1, 2000; 9(6): 567 - 573. [Abstract] [Full Text] |
||||
![]() |
N Andrieu, T Prevost, T. Rohan, E Luporsi, M. Le, M Gerber, D. Zaridze, Y Lifanova, R Renaud, H. Lee, et al. Variation in the interaction between familial and reproductive factors on the risk of breast cancer according to age, menopausal status, and degree of familiality Int. J. Epidemiol., April 1, 2000; 29(2): 214 - 223. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. C. Millikan NAT1*10 and NAT1*11 Polymorphisms and Breast Cancer Risk Cancer Epidemiol. Biomarkers Prev., February 1, 2000; 9(2): 217 - 219. [Abstract] [Full Text] |
||||
![]() |
M. Garcia-Closas, N. Rothman, and J. Lubin Misclassification in Case-Control Studies of Gene-Environment Interactions: Assessment of Bias and Sample Size Cancer Epidemiol. Biomarkers Prev., December 1, 1999; 8(12): 1043 - 1050. [Abstract] [Full Text] |
||||
![]() |
A. M. Goldstein and N. Andrieu Detection of Interaction Involving Identified Genes: Available Study Designs J Natl Cancer Inst Monographs, December 1, 1999; 1999(26): 49 - 54. [Abstract] [Full Text] |
||||
![]() |
Y. Liao, R. S. Cooper, G. A. Mensah, and D. L. McGee Left Ventricular Hypertrophy Has a Greater Impact on Survival in Women Than in Men Circulation, August 15, 1995; 92(4): 805 - 810. [Abstract] [Full Text] |
||||











