, Volume 27, Issue 8, pp 627–634 | Cite as

Case-Control Studies in Pharmacoeconomic Research

An Overview
  • J. Jaime CaroEmail author
  • Krista F. Huybrechts
Leading Article


The case-control approach has been a mainstay of epidemiological studies, particularly those investigating aetiology. Many articles addressing pharmacoeconomic topics have reported studies purported to be of the case-control type. However, on examination, these were actually standard cohort studies that were misnamed because they compared cases of a particular illness to ‘controls’ without the illness. The actual case-control design involves a series of cases with the outcome of interest. In pharmacoeconomic applications, the outcome of interest would typically be high cost, or hospitalization, or return to full quality of life. The illness does not define cases, but rather is actually the ‘exposure’. The ‘controls’ must be a sample of the study base, not subjects without the illness. In this article, we review the features of a proper case-control study and contrast them with those of the more common cohort study. Confusing the control series of a cohort study with the ‘controls’ in a case-control study leads to serious problems with understanding the research, its strengths and drawbacks (e.g. confounding concerns), and interpretation of the findings. Although the case-control design has so far been used little to address pharmacoeconomic questions, it can be very efficient in certain situations, particularly when obtaining data on all subjects is burdensome or when conditions provide a ready case series but not the rest of the subjects.


Study Base Control Series Reference Series Pharmacoeconomic Study Exposure Distribution 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



No sources of funding were used to assist in the preparation of this article. The authors have no conflicts of interest that are directly relevant to the content of this article.


  1. 1.
    Cornfield J. A method of estimating comparative rates from clinical data: application to cancer of the lung, breast and cervix. J Natl Cancer Inst 1951; 11: 1269–75PubMedGoogle Scholar
  2. 2.
    Miettinen OS. Variance and dissent: the “case-control” study. Valid selection of subjects. J Chron Dis 1985; 38: 543–8PubMedCrossRefGoogle Scholar
  3. 3.
    Ibrahim MA. Case-control study: consensus and controversy. J Chron Dis 1979; 32: l-90CrossRefGoogle Scholar
  4. 4.
    Schlesselman JJ. Case-control studies: design, conduct, analysis. New York: Oxford University Press, 1982: 354Google Scholar
  5. 5.
    Feinstein AR. Clinical biostatistics XX: the epidemiologic trohoc, the ablative risk ratio, and ‘retrospective’ research. Clin Pharm Ther 1973; 14: 291–307Google Scholar
  6. 6.
    Miettinen OS. Epidemiology: quo vadis? Euro J Epidemiol 2004; 19: 713–8CrossRefGoogle Scholar
  7. 7.
    Miettinen OS. Estimability and estimation in case-referent studies. Am J Epidemiol 1976; 102: 226–35Google Scholar
  8. 8.
    Cole PT, Monson RR, Haning H, et al. Smoking and cancer of the lower urinary tract. N Engl J Med 1971; 284: 129–34PubMedCrossRefGoogle Scholar
  9. 9.
    Oliveira A, Barros H, Lopes C. Gender heterogeneity in the association between lifestyles and non-fatal acute myocardial infarction. Public Health Nutr 2009; 23: 1–8Google Scholar
  10. 10.
    Jick H, Vessey MP. Case-control studies in the evaluation of drug-induced illness. Am J Epidemiol 1978; 107: 1–7PubMedGoogle Scholar
  11. 11.
    Scélo G, Metayer C, Zhang L, et al. Household exposure to paint and petroleum solvents, chromosomal translocations, and the risk of childhood leukemia. Environ Health Perspect 2009; 117: 133–9PubMedGoogle Scholar
  12. 12.
    de Medeiros AP, Gouveia N, Machado RP, et al. Traffic-related air pollution and perinatal mortality: a case-control study. Environ Health Perspect 2009; 117: 127–32PubMedGoogle Scholar
  13. 13.
    Witschi H. A short history of lung cancer. Tox Sci 2001; 64: 4–6CrossRefGoogle Scholar
  14. 14.
    Wang XR, Yu IT, Chiu YL, et al. Previous pulmonary disease and family cancer history increase the risk of lung cancer among Hong Kong women. Cancer Causes Control. Epub 2009 Jan 25Google Scholar
  15. 15.
    Miettinen OS. Etiologic research: needed revisions of concepts and principles. Scand J Work Environ Health 1999; 25: 484–90PubMedCrossRefGoogle Scholar
  16. 16.
    Jedrychowski W, Maugeri U, Pac A, et al. Protective effect of fish consumption on colorectal cancer risk: hospital-based case-control study in Eastern Europe. Ann Nutr Metab 2009; 53: 295–302CrossRefGoogle Scholar
  17. 17.
    Rutherford ME, Dockerty JD, Jasseh M, et al. Preventive measures in infancy to reduce under-five mortality: a case-control study in the Gambia. Trop Med Int Health. Epub 2009 Jan 20Google Scholar
  18. 18.
    Yan Yuen S, Krizova A, Ouimet JM, et al. Pregnancy outcome in systemic lupus erythematosus (SLE) is improving: results from a case control study and literature review. Open Rheumatol J 2008; 2: 89–98PubMedCrossRefGoogle Scholar
  19. 19.
    Baer HJ, Collins LC, Connolly JL, et al. Lobule type and subsequent breast cancer risk: results from the Nurses’ Health Studies. Cancer. Epub 2009 Jan 23Google Scholar
  20. 20.
    DAS A, Manickam P, Hutin Y, et al. Two sequential outbreaks in two villages illustrate the various modes of transmission of cholera. Epidemiol Infect 2009 Jan; 27: 1–7Google Scholar
  21. 21.
    Cotté FE, Mercier F, De Pouvourville G. Relationship between compliance and persistence with osteoporosis medications and fracture risk in primary health care in France: a retrospective case-control analysis. Clin Ther 2008; 30: 2410–22PubMedCrossRefGoogle Scholar
  22. 22.
    Goldman M, Xi G, Yi QL, et al. Reassessment of deferrals for tattooing and piercing. Transfusion. Epub 2009 Jan 2Google Scholar
  23. 23.
    Strömbeck B, Jacobsson LT, Bremander A, et al. Patients with ankylosing spondylitis have increased sick leave: a registry-based case-control study over 7 yrs. Rheumatology. Epub 2009 Jan 22Google Scholar
  24. 24.
    Medin J, Ekberg K, Nordlund A, et al. Organisational change, job strain and increased risk of stroke? A pilot study. Work 2008; 31: 443–9PubMedGoogle Scholar
  25. 25.
    Vila-Corcoles A, Salsench E, Rodriguez-Blanco T, et al. Clinical effectiveness of 23-valent pneumococcal polysaccharide vaccine against pneumonia in middle-aged and older adults: a matched case-control study. Vaccine. Epub 2009 Jan 23Google Scholar
  26. 26.
    Izadi S, Salehi M. Evaluation of the efficacy of ribavirin therapy on survival of crimean-congo hemorrhagic fever patients: a case-control study. Jpn J Infect Dis 2009; 62: 11–5PubMedGoogle Scholar
  27. 27.
    Fosgate GT, Cohent ND. Epidemiological study design and the advancement of equine health. Equine Vet J 2008; 40: 693–700PubMedCrossRefGoogle Scholar
  28. 28.
    Chaix C, Durand-Zaleski I, Alberti C, et al. Control of endemic methicillin-resistant Staphylococcus aureus: a cost-benefit analysis in an intensive care unit. JAMA 1999; 282: 1745–51PubMedCrossRefGoogle Scholar
  29. 29.
    Kaushal R, Bates DW, Franz C, et al. Costs of adverse events in intensive care units. Crit Care Med 2007; 35: 2479–83PubMedCrossRefGoogle Scholar
  30. 30.
    Frost FJ, Hurley JS, Petersen HV, et al. A comparison of two methods for estimating the health care costs of epilepsy. Epilepsia 2000; 41: 1020–6PubMedCrossRefGoogle Scholar
  31. 31.
    Smith PB, Morgan J, Benjamin JD, et al. Excess costs of hospital care associated with neonatal candidemia. Pediatr Infect Dis J 2007; 26: 197–200PubMedCrossRefGoogle Scholar
  32. 32.
    Volkova N, Klapper E, Pepkowitz SH, et al. A case-control study of the impact of WBC reduction on the cost of hospital care for patients undergoing coronary artery bypass graft surgery. Transfusion 2002; 42: 1123–6PubMedCrossRefGoogle Scholar
  33. 33.
    Gournay J, Tchuenbou J, Richou C, et al. Percutaneous ethanol injection vs resection in patients with small single hepatocellular carcinoma: a retrospective case-control study with cost analysis. Aliment Pharmacol Ther 2002; 16: 1529–38PubMedCrossRefGoogle Scholar
  34. 34.
    Gutterman EM, Markowitz JS, Lewis B, et al. Cost of Alzheimer’s disease and related dementia in managed-Medicare. J Am Geriatr Soc 1999; 47: 1065–71PubMedGoogle Scholar
  35. 35.
    Barnett A, Birnbaum H, Cremieux PY, et al. The costs of cancer to a major employer in the United States: a case-control analysis. Am J Manag Care 2000; 6: 1243–51PubMedGoogle Scholar
  36. 36.
    Fader DJ, Wise CG, Normolle DP, et al. The multidisciplinary melanoma clinic: a cost outcomes analysis of specialty care. J Am Acad Dermatol 1998; 38: 742–51PubMedCrossRefGoogle Scholar
  37. 37.
    Scheffler RM, Feuchtbaum LB, Phibbs CS. Prevention: the cost-effectiveness of the California Diabetes and Pregnancy Program. Am J Public Health 1992; 82: 168–75PubMedCrossRefGoogle Scholar
  38. 38.
    Halder SLS, Locke III GR, Talley NJ, et al. Impact of functional gastrointestinal disorders on health-related quality of life: a population-based case-control study. Alimen Pharmacol Ther 2004; 19: 233–42CrossRefGoogle Scholar
  39. 39.
    Lipton RB, Liberman JN, Kolodner KB, et al. Migraine headache disability and health-related quality-of-life: a population-based case-control study from England. Cephalalgia 2003; 23: 441–50PubMedCrossRefGoogle Scholar
  40. 40.
    Tarasiuk A, Greenberg-Dotan S, Brin YS, et al. Determinants affecting health-care utilization in obstructive sleep apnea syndrome patients. Chest 2005; 128: 1310–4PubMedCrossRefGoogle Scholar
  41. 41.
    Ramaiah KD, Guyatt H, Ramu K, et al. Treatment costs and loss of work time to individuals with chronic lymphatic filariasis in rural communities in south India. Trop Med Int Health 1999; 4: 19–25PubMedCrossRefGoogle Scholar
  42. 42.
    Hazinski MF, Chahine AA, Holcomb GW, et al. Outcome of cardiovascular collapse in pediatric blunt trauma. Ann Emerg Med 1994; 23: 1229–35PubMedCrossRefGoogle Scholar
  43. 43.
    Benito-León J, Louis ED, Bermejo-Pareja F; on behalf of the Neurological Disorders in Central Spain (NEDICES) Study Group. Population-based case-control study of morale in Parkinson’s disease. Eur J Neurol 2009; 16 (3): 330–6PubMedCrossRefGoogle Scholar
  44. 44.
    Trakakis E, Balanika A, Baltas C, et al. Hemodynamic alterations and wall properties in large arteries of young, normotensive, and non-obese women with polycystic ovary syndrome. J Endocrinol Invest 2008; 31: 1001–7PubMedGoogle Scholar
  45. 45.
    Theodore RF, Thompson JM, Waldie KE, et al. Determinants of cognitive ability at 7 years: a longitudinal case-control study of children born small-for-gestational age at term. Eur J Pediatr. Epub 2009 Jan 23Google Scholar
  46. 46.
    Rocha E, Soares M, Valente C, et al. Outcomes of critically ill patients with acute kidney injury and end-stage renal disease requiring renal replacement therapy: a case-control study. Nephrol Dial Transplant. Epub 2009 Jan 22Google Scholar
  47. 47.
    Rothman KJ, Greenland S, Lash TL. Case-control studies. In: Rothman KJ, Greenland S, Lash TL, editors. Modern epidemiology. 3rd ed. Philadelphia (PA): Lippincott Williams & Wilkins, 2008; 111–27Google Scholar
  48. 48.
    Nurminen M. To use or not to use the odds ratio in epidemiologic analyses? Euro J Epidemiol 1995; 11: 365–71CrossRefGoogle Scholar
  49. 49.
    King G, Zeng L. Estimating risk and rate levels, ratios and differences in case-control studies. Stat Med 2002; 21: 1409–27PubMedCrossRefGoogle Scholar
  50. 50.
    Miettinen OS, Cook EF. Confounding: essence and detection. Am J Epidemiol 1981; 114: 593–603PubMedGoogle Scholar
  51. 51.
    Wacholder S, Silverman DT, McLaughlin JK, et al. Selection of controls in case-control Studies: III. Design options. Am J Epidemiol 1992; 135: 1042–50PubMedGoogle Scholar
  52. 52.
    Wacholder S, McLaughlin JK, Silverman DT, et al. Selection of controls in case-control Studies: I. Principles. Am J Epidemiol 1992; 135: 1019–28Google Scholar
  53. 53.
    Wacholder S. Practical considerations in choosing between the case-cohort and nested case-control designs. Epidemiology 1991; 2: 155–8PubMedCrossRefGoogle Scholar
  54. 54.
    Sartwell PE, Masi AT, Arthes FG, et al. Thromboembolism and oral contraceptives: an epidemiologic case-control study. Am J Epidemiol 1969; 90: 365–80PubMedGoogle Scholar
  55. 55.
    Ernster VL. Nested case-control studies. Prev Med 1994; 23: 587–90PubMedCrossRefGoogle Scholar
  56. 56.
    Essebag V, Platt RW, Abrahamowicz M, et al. Comparison of nested case-control and survival analysis methodologies for analysis of time-dependent exposure. BMC Med Res Methodol 2005; 5: 5PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2009

Authors and Affiliations

  1. 1.Department of Epidemiology, Biostatistics and Occupational Health, and Division of General Internal MedicineMcGill UniversityMontrealCanada
  2. 2.UnitedBiosource CorporationLexingtonUSA

Personalised recommendations