Abstract
Observational studies are important tools for providing information on the safety and benefit of approved medications; they provide data on real-life use, rare outcomes and long-term effects that were undetectable in randomized controlled trials. We review various administrative databases in the US and Canada, in addition to European medical records databases, which have been used extensively to assess drug safety. We present their advantages, which include their large size and the availability of systematic and accurate medication data from pharmacies and extensive outcome data from hospital records, and limitations, including the questionable validity of diagnostic information and absence of information on confounders (e.g. disease severity) and over-the-counter drugs. We illustrate these challenges in the investigation of the cardiovascular risks of the cyclo-oxygenase 2 inhibitor rofecoxib and highlight important methodological issues, beyond the limitations of the databases, which could explain the contradictory findings from three observational studies that used these databases. We show that issues relating to the duration of drug use, immortal time, depletion of susceptibles and overadjustment were problematic sources of bias in these studies and discuss remedies to avoid these pitfalls. With careful attention to their design and analysis, observational database studies are powerful and modern tools for providing crucial data on drug effects.
Key Points
-
Observational studies provide important information on the safety and benefit of medications that complements data from randomized controlled trials
-
Administrative health databases offer large sources of rapidly accessible data for these studies, with accurate medication records from pharmacies and extensive outcome information from hospital records
-
These databases can contain invalidated diagnostic information, sometimes lack information on important confounders and have no data on over-the-counter drugs
-
Improper methodological aspects of observational studies, beyond the limitations of the databases, can lead to contradictory findings—for example, the cardiovascular risks of cyclo-oxygenase 2 inhibitors
-
With careful attention to design and analysis, observational database studies can be powerful and modern tools for providing crucial data on drug effects
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Levy M (1974) Aspirin use in patients with major upper gastrointestinal bleeding and peptic-ulcer disease. A report from the Boston Collaborative Drug Surveillance Program, Boston University Medical Center. N Engl J Med 290: 1158–1162
Carson JL et al. (1987) The association of nonsteroidal anti-inflammatory drugs with upper gastrointestinal tract bleeding. Arch Intern Med 147: 85–88
Strom BL (2005) Pharmacoepidemiology, edn 4. Chichester: John Wiley & Sons Ltd
Strom BL et al. (1991) Using a claims database to investigate drug-induced Stevens-Johnson syndrome. Stat Med 10: 565–576
Spitzer WO et al. (1992) The use of beta-agonists and the risk of death and near death from asthma. N Engl J Med 326: 501–506
Suissa S et al. (1994) Patterns of increasing beta-agonist use and the risk of fatal or near-fatal asthma. Eur Respir J 7: 1602–1609
Strom BL and Carson JL (1990) Use of automated databases for pharmacoepidemiology research. Epidemiol Rev 12: 87–107
Ray WA and Griffin MR (1989) Use of medicaid data for pharmacoepidemiology. Am J Epidemiol 129: 837–849
Downey W et al. (2005) Health databases in Saskatchewan. In Pharmacoepidemiology, edn 4 295–310 (Ed Strom BL) Chicester: John Wiley & Sons Ltd
Selby JV et al. (2005) Kaiser Permanente Medical Care Program. In Pharmacoepidemiology, edn 4 261–270 (Ed Strom BL) Chichester: John Wiley & Sons Ltd
Saunders KW et al. (2005) Group Health Cooperative. In Pharmacoepidemiology, edn 4 223–240 (Ed Strom BL) Chichester: John Wiley & Sons Ltd
Solomon SD et al. (2005) Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med 352: 1071–1080
Bombardier C et al. (2000) Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N Engl J Med 343: 1520–1528
Ray WA et al. (2002) COX-2 selective non-steroidal anti-inflammatory drugs and risk of serious coronary heart disease. Lancet 360: 1071–1073
Mamdani M et al. (2003) Effect of selective cyclooxygenase 2 inhibitors and naproxen on short-term risk of acute myocardial infarction in the elderly. Arch Intern Med 163: 481–486
Solomon DH et al. (2004) Relationship between selective cyclooxygenase-2 inhibitors and acute myocardial infarction in older adults. Circulation 109: 2068–2073
FDA Advisory Committee, U.S. Food and Drug Administration (online 9 December 2004) Cardiovascular safety review of rofecoxib [http://www.fda.gov/ohrms/dockets/ac/01/briefing/3677b1_11_thrombo.doc] (accessed 20 September 2007)
Suissa S (2007) Immortal time bias in observational studies of drug effects. Pharmacoepidemiol Drug Saf 16: 241–249
Mamdani M et al. (2002) Observational study of upper gastrointestinal haemorrhage in elderly patients given selective cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs. BMJ 325: 624
Ray WA (2003) Evaluating medication effects outside of clinical trials: new-user designs. Am J Epidemiol 158: 915–920
McGettigan P and Henry D (2006) Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of the observational studies of selective and nonselective inhibitors of cyclooxygenase 2. JAMA 296: 1633–1644
Andersohn F et al. (2006) Use of first- and second-generation cyclooxygenase-2-selective nonsteroidal anti-inflammatory drugs and risk of acute myocardial infarction. Circulation 113: 1950–1957
Suissa S et al. (2004) Newer disease modifying anti-rheumatic drugs (DMARDS) and the risk of serious hepatic adverse events in rheumatoid arthritis. Am J Med 117: 87–92
Brassard P et al. (2006) Antirheumatic drugs and the risk of tuberculosis. Clin Infect Dis 43: 717–722
Bernatsky S et al. (2005) Anti-rheumatic drug use and risk of hospitalization for congestive heart failure in rheumatoid arthritis. Rheumatology (Oxford) 44: 677–680
Suissa S et al. (2006) Antirheumatic drug use and the risk of acute myocardial infarction. Arthritis Rheum 55: 531–536
Acknowledgements
S Suissa's research is funded by the Canadian Institute of Health Research (CIHR).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
S Suissa has acted as a consultant for Bristol-Myers Squibb, Merck, Pfizer and Sanofi-Aventis, and has received grants or research support from Sanofi-Aventis and Wyeth. E Garbe has declared no competing interests
Rights and permissions
About this article
Cite this article
Suissa, S., Garbe, E. Primer: administrative health databases in observational studies of drug effects—advantages and disadvantages. Nat Rev Rheumatol 3, 725–732 (2007). https://doi.org/10.1038/ncprheum0652
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/ncprheum0652
This article is cited by
-
Cross-validation of comorbidity items in two national databases in a sample of patients with end-stage kidney disease
BMC Health Services Research (2023)
-
Clinical competence, communication ability and adherence to choosing wisely recommendations for lipid reducing drug use in older adults
BMC Geriatrics (2023)
-
Scalable Infrastructure Supporting Reproducible Nationwide Healthcare Data Analysis toward FAIR Stewardship
Scientific Data (2023)
-
Systemic quinolones and risk of retinal detachment III: a nested case–control study using a US electronic health records database
European Journal of Clinical Pharmacology (2022)
-
Hospitalizations and deaths related to adverse drug events worldwide: Systematic review of studies with national coverage
European Journal of Clinical Pharmacology (2022)