• 1
    Bombardier C, Laine L, Reicin A, Shapiro D, Burgos-Vargas R, Davis B, et al, for the VIGOR Study Group. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. N Engl J Med 2000; 343: 15208.
  • 2
    Ray WA, Stein CM, Daugherty JR, Hall K, Arbogast PG, Griffin MR. COX-2 selective non-steroidal anti-inflammatory drugs and risk of serious coronary heart disease. Lancet 2002; 360: 10713.
  • 3
    Solomon DH, Schneeweiss S, Glynn RJ, Kiyota Y, Levin R, Mogun H, et al. Relationship between selective cyclooxygenase-2 inhibitors and acute myocardial infarction in older adults. Circulation 2004; 109: 206873.
  • 4
    Bresalier RS, Sandler RS, Quan H, Bolognese JA, Oxenius B, Horgan K, et al, for the Adenomatous Polyp Prevention on Vioxx (APPROVe) Trial Investigators. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial [published erratum appears in N Engl J Med 2006;355:221]. N Engl J Med 2005; 352: 1092102.
  • 5
    Graham DJ, Campen D, Hui R, Spence M, Cheetham C, Levy G, et al. Risk of acute myocardial infarction and sudden cardiac death in patients treated with cyclo-oxygenase 2 selective and non-selective non-steroidals anti-inflammatory drugs: nested case control study. Lancet 2005; 365: 47581.
  • 6
    Brazil M. Long-term study proposed for COX2 inhibitors. Nat Rev Drug Discov 2005; 4: 2678.
  • 7
    Food and Drug Administration. Advisory board documents. URL:
  • 8
    European Agency for the Evaluation of Medicinal Products. European Medicines Agency concludes action on COX-2 inhibi-tors. London, 27 June 2005. URL:
  • 9
    Silverstein FE, Faich G, Goldstein JL, Simon LS, Pincus T, Whelton A, et al, for the Celecoxib Long-term Arthritis Safety Study. Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: a randomized controlled trial. JAMA 2000; 284: 124755.
  • 10
    Solomon SD, McMurray JJ, Pfeffer MA, Wittes J, Fowler R, Finn P, et al, for the Adenoma Prevention with Celecoxib (APC) Study Investigators. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med 2005; 352: 107180.
  • 11
    Farkouh ME, Kirshner H, Harrington RA, Ruland S, Verheugt FW, Schnitzer TJ, et al, for the TARGET Study Group. Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), cardiovascular outcomes: randomised controlled trial. Lancet 2004; 364: 67584.
  • 12
    Food and Drug Administration. PreSAP. In Cardiovascular safety and risk-benefit assessment. URL:
  • 13
    Food and Drug Administration. AD 97-02-001. In Cardiovascular safety and risk-benefit assessment. URL:
  • 14
    Ott E, Nussmeier NA, Duke PC, Feneck RO, Alston RP, Snabes MC, et al, for the Multicenter Study of Perioperative Ischemia (McSPI) Research Group and the Ischemia Research and Education Foundation (IREF) Investigators. Efficacy and safety of the cyclooxygenase 2 inhibitors parecoxib and valdecoxib in patients undergoing coronary artery bypass surgery. J Thorac Cardiovasc Surg 2003; 125: 148192.
  • 15
    Nussmeier NA, Whelton AA, Brown MT, Langford RM, Hoeft A, Parlow JL, et al. Complications of the COX-2 inhibitors parecoxib and valdecoxib after cardiac surgery. N Engl J Med 2005; 352: 108191.
  • 16
    Solomon DH. Selective cyclooxygenase 2 inhibitors and cardiovascular events [review]. Arthritis Rheum 2005; 52: 196878.
  • 17
    Halpern SD, Ubel PA, Berlin JA, Townsend RR, Asch DA. Physicians' preferences for active-controlled versus placebo-controlled trials of new antihypertensive drugs. J Gen Intern Med 2002; 17: 68995.
  • 18
    Couzin J. Drug testing: massive trial of Celebrex seeks to settle safety concerns. Science 2005; 310: 189091.
  • 19
    Schneeweiss S, Avorn J. A review of uses of health care utilization databases for epidemiologic research on therapeutics [review]. J Clin Epidemiol 2005; 58: 32337.
  • 20
    Schneeweiss S, Glynn RJ, Tsai EH, Avorn J, Solomon DH. Adjusting for unmeasured confounders in pharmacoepidemiologic claims data using external information: the example of COX2 inhibitors and myocardial infarction. Epidemiology 2005; 16: 1724.
  • 21
    Walker AM. Confounding by indication. Epidemiology 1996; 7: 3356.
  • 22
    Bowden RJ, Turkington DA. Instrumental variables. Cambridge, UK: Cambridge University Press; 1984.
  • 23
    Angrist JD, Imbens GW, Rubin DB. Identification of causal effects using instrumental variables. J Am Stat Soc 1996; 91: 44455.
  • 24
    Angrist JD, Krueger AB. Instrumental variables and the search for identification: from supply and demand to natural experiments. J Econ Perspectives 2001; 15: 6985.
  • 25
    McClellan M, McNeil BJ, Newhouse JP. Does more intensive treatment of acute myocardial infarction in the elderly reduce mortality? Analysis using instrumental variables. JAMA 1994; 272: 85966.
  • 26
    Timpson NJ, Lawlor DA, Harbord RM, Gaunt TR, Day IN, Palmer LJ, et al. C-reactive protein and its role in metabolic syndrome: mendelian randomisation study. Lancet 2005; 366: 19549.
  • 27
    Brookhart MA, Wang PS, Solomon DH, Schneeweiss S. Evaluating short-term drug effects using physician-specific prescribing preference as an instrumental variable. Epidemiology 2006; 17: 26875.
  • 28
    Solomon DH, Schneeweiss S, Glynn RJ, Levin R, Avorn J. Determinants of selective cyclooxygenase 2 inhibitor prescribing: are patient or physician characteristics more important? Am J Med 2003; 115: 71520.
  • 29
    Schneeweiss S, Glynn RJ, Avorn J, Solomon DH. A Medicare database review found that physician preferences increasingly outweighed patient characteristics as determinants of first-time prescriptions for COX-2 inhibitors. J Clin Epidemiol 2005; 58: 98102.
  • 30
    Ray WA. Evaluating medication effects outside of clinical trials: new-user designs. Am J Epidemiol 2003; 158: 91520.
  • 31
    Moride Y, Abenhaim L. Evidence of the depletion of susceptibles effect in non-experimental pharmacoepidemiologic research [published erratum appears in J Clin Epidemiol 2004;57:111]. J Clin Epidemiol 1994; 47: 7317.
  • 32
    Raiford DS, Perez Gutthann S, Garcia Rodriguez LA. Positive predictive value of ICD-9 codes in the identification of cases of complicated peptic ulcer disease in the Saskatchewan hospital automated database. Epidemiology 1996; 7: 1014.
  • 33
    Kiyota Y, Schneeweiss S, Glynn RJ, Cannuscio CC, Avorn J, Solomon DH. Accuracy of Medicare claims-based diagnosis of acute myocardial infarction: estimating positive predictive value on the basis of review of hospital records. Am Heart J 2004; 148: 99104.
  • 34
    McKenzie DA, Semradek J, McFarland BH, Mullooly JP, McCamant LE. The validity of Medicaid pharmacy claims for estimating drug use among elderly nursing home residents: the Oregon experience. J Clin Epidemiol 2000; 53: 124857.
  • 35
    West SL, Savitz DA, Koch G, Strom BL, Guess HA, Hartzema A. Recall accuracy for prescription medications: self-report compared with database information. Am J Epidemiol 1995; 142: 110312.
  • 36
    Brookhart MA, Wang PS, Solomon DH, Schneeweiss S. Instrumental variable analysis of secondary pharmacoepidemiologic data. Epidemiology 2006; 17: 3734.
  • 37
    Greenland S. An introduction to instrumental variables for epidemiologists. Int J Epidemiol 2000; 29: 7229.
  • 38
    Greene WH. Econometric analysis. 3rd ed. Upper Saddle River (NJ): Prentice Hall; 1997. p. 7402.
  • 39
    American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. Arthritis Rheum 2000; 43: 190515.
  • 40
    Lanza FL, and the Ad Hoc Committee on Practice Parameters of the American College of Gastroenterology. A guideline for the treatment and prevention of NSAID-induced ulcers. Am J Gastroenterol 1998; 93: 203746.
    Direct Link:
  • 41
    University of British Columbia, Vancouver, Canada. Therapeutics initiative: COX-2 inhibitors update. Therapeutics Letter 43, November/December 2001 and January 2002. URL: (accessed 3/12/03).
  • 42
    Deyo RA, Cherkin DC, Ciol MA. Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J Clin Epidemiol 1992; 45: 6139.
  • 43
    Schneeweiss S, Seeger JD, Maclure M, Wang PS, Avorn J, Glynn RJ. Performance of comorbidity scores to control for confounding in epidemiologic studies using claims data. Am J Epidemiol 2001; 154: 85464.
  • 44
    Rosenbaum PR, Rubin DB. The central role of the propensity score in observational studies for causal effects. Biometrika 1983; 70: 4155.
  • 45
    Sargan J. The estimation of economic relationships using instrumental variables. Econometrica 1958; 26: 393415.
  • 46
    Shah BR, Laupacis A, Hux JE, Austin PC. Propensity score methods gave similar results to traditional regression modeling in observational studies: a systematic review [review]. J Clin Epidemiol 2005; 58: 5509.
  • 47
    Sturmer T, Schneeweiss S, Brookhart MA, Rothman KJ, Avorn J, Glynn RJ. Analytic strategies to adjust confounding using exposure propensity scores and disease risk scores: nonsteroidal antiinflammatory drugs and short-term mortality in the elderly. Am J Epidemiol 2005; 161: 8918.
  • 48
    Rothman KJ, Greenland S. Modern epidemiology. 2nd ed. London: Lippincott; 1998. p. 205.