Assessing Confounding and Effect Modification of Periodontitis–Systemic Disease Associations

  • Alexandrina L. Dumitrescu


Confounding and effect modification are of increasing importance as periodontal research addresses the putative associations between periodontal disease and systemic diseases. Unfortunately, the importance of confounding and effect modification is not always appreciated and is often overlooked. They may also appear to be similar but they are actually very different. Our goals in controlling them are also different. ‘In epidemiologic analysis one tries to eliminate confounding, but one tries to detect and estimate effect-measure modification’. We also assess effect modification first, since confounding by a variable becomes largely irrelevant if there is also interaction involving that variable.


  1. Altman DG, Bland JM. Statistics notes. Treatment allocation in controlled trials: why randomise? BMJ. 1999;318:1209.PubMedCrossRefGoogle Scholar
  2. Cleophas TJ, Zwinderman AH, Cleophas TF, Cleophas EP. Statistics applied to clinical trials. 3rd ed. New York: Springer; 2006. p. 235–44.Google Scholar
  3. Dietrich T, Hoffmann K. A comprehensive index for the modeling of smoking history in periodontal research. J Dent Res. 2004;83:859–63.PubMedCrossRefGoogle Scholar
  4. Dietrich T, Garcia RI, de Pablo P, Schulze PC, Hoffmann K. The effects of cigarette smoking on C-reactive protein concentrations in men and women and its modification by exogenous oral hormones in women. Eur J Cardiovasc Prev Rehabil. 2007;14:694–700.PubMedCrossRefGoogle Scholar
  5. Dietrich T, Jimenez M, Krall Kaye EA, Vokonas PS, Garcia RI. Age-dependent associations between chronic periodontitis/edentulism and risk of coronary heart disease. Circulation. 2008;117:1668–74.PubMedCrossRefGoogle Scholar
  6. Fitzmaurice G. Confused by confounding? Nutrition. 2003;19:189–91.PubMedCrossRefGoogle Scholar
  7. Fitzmaurice G. Adjusting for confounding. Nutrition. 2004;20:594–6.PubMedCrossRefGoogle Scholar
  8. Greenland S, Morgenstern H. Confounding in health research. Annu Rev Public Health. 2001;22:189–212.PubMedCrossRefGoogle Scholar
  9. Grimes DA, Schulz KF. Clinical research in obstetrics and gynecology: a Baedeker for busy clinicians. Obstet Gynecol Surv. 2002;57(9 Suppl 3):S35–53.PubMedCrossRefGoogle Scholar
  10. Hujoel PP, Drangsholt M, Spiekerman C, DeRouen TA. Periodontitis-systemic disease associations in the presence of smoking – causal or coincidental? Periodontol 2000. 2002;30:51–60.PubMedCrossRefGoogle Scholar
  11. Hyman J. The importance of assessing confounding and effect modification in research involving periodontal disease and systemic diseases. J Clin Periodontol. 2006;33:102–3.PubMedCrossRefGoogle Scholar
  12. Jimenez M, Krall EA, Garcia RI, Vokonas PS, Dietrich T. Periodontitis and incidence of cerebrovascular disease in men. Ann Neurol. 2009;66:505–12.PubMedCrossRefGoogle Scholar
  13. Labriola A, Needleman I, Moles DR. Systematic review of the effect of smoking on nonsurgical periodontal therapy. Periodontol 2000. 2005;37:124–37.PubMedCrossRefGoogle Scholar
  14. Leffondré K, Abrahamowicz M, Xiao Y, Siemiatycki J. Modelling smoking history using a comprehensive smoking index: application to lung cancer. Stat Med. 2006;25:4132–46.PubMedCrossRefGoogle Scholar
  15. MacKinnon DP, Krull JL, Lockwood CM. Equivalence of the mediation, confounding and suppression effect. Prev Sci. 2000;1:173–81.PubMedCrossRefGoogle Scholar
  16. Needleman I, Moles DR, Worthington H. Evidence-based periodontology, systematic reviews and research quality. Periodontol 2000. 2005;37:12–28.PubMedCrossRefGoogle Scholar
  17. Normand SL, Sykora K, Li P, Mamdani M, Rochon PA, Anderson GM. Readers guide to critical appraisal of cohort studies: 3. Analytical strategies to reduce confounding. BMJ. 2005;330(7498):1021–3.PubMedCrossRefGoogle Scholar
  18. Parodi S, Bottarelli E. Controlling for confounding in case–­control studies. Ann Fac Medic Vet Parma. 2005;25:19–46.Google Scholar
  19. Pernu HE, Pernu LM, Huttunen KR, Nieminen PA, Knuuttila ML. Gingival overgrowth among renal transplant recipients related to immunosuppressive medication and possible local background factors. J Periodontol. 1992;63:548–53.PubMedCrossRefGoogle Scholar
  20. Rothman KJ, Greenland S. Modern epidemiology. 2nd ed. Philadelphia: Lippincott, Williams & Wilkins; 1998.Google Scholar
  21. Spiekerman CF, Hujoel PP, DeRouen TA. Bias induced by self-reported smoking on periodontitis-systemic ­disease associations. J Dent Res. 2003;82:345–9.PubMedCrossRefGoogle Scholar
  22. Walter C, Kaye EK, Dietrich T. Active and passive smoking: assessment issues in periodontal research. Periodontol 2000. 2012;58:84–92.PubMedCrossRefGoogle Scholar
  23. Ylöstalo PV, Knuuttila ML. Confounding and effect modification: possible explanation for variation in the results on the association between oral and systemic diseases. J Clin Periodontol. 2006;33:104–8.PubMedCrossRefGoogle Scholar
  24. Yu B, Gastwirth JL. A method of assessing the sensitivity of the Cochran-Mantel-Haenszel test to an unobserved confounder. Philos Transact A Math Phys Eng Sci. 2008;366(1874):2377–88.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Alexandrina L. Dumitrescu
    • 1
    • 2
  1. 1.Department of PeriodontologyUniversity of Tromsø Institute of Clinical DentistryTromsøNorway
  2. 2.Private practiceBucharestRomania

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