A comparison of observational studies and randomized, controlled trials

N Engl J Med. 2000 Jun 22;342(25):1878-86. doi: 10.1056/NEJM200006223422506.


Background: For many years it has been claimed that observational studies find stronger treatment effects than randomized, controlled trials. We compared the results of observational studies with those of randomized, controlled trials.

Methods: We searched the Abridged Index Medicus and Cochrane data bases to identify observational studies reported between 1985 and 1998 that compared two or more treatments or interventions for the same condition. We then searched the Medline and Cochrane data bases to identify all the randomized, controlled trials and observational studies comparing the same treatments for these conditions. For each treatment, the magnitudes of the effects in the various observational studies were combined by the Mantel-Haenszel or weighted analysis-of-variance procedure and then compared with the combined magnitude of the effects in the randomized, controlled trials that evaluated the same treatment.

Results: There were 136 reports about 19 diverse treatments, such as calcium-channel-blocker therapy for coronary artery disease, appendectomy, and interventions for subfertility. In most cases, the estimates of the treatment effects from observational studies and randomized, controlled trials were similar. In only 2 of the 19 analyses of treatment effects did the combined magnitude of the effect in observational studies lie outside the 95 percent confidence interval for the combined magnitude in the randomized, controlled trials.

Conclusions: We found little evidence that estimates of treatment effects in observational studies reported after 1984 are either consistently larger than or qualitatively different from those obtained in randomized, controlled trials.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Bone Density / drug effects
  • Cohort Studies*
  • Cross-Sectional Studies
  • Female
  • Heart Diseases / therapy
  • Hormone Replacement Therapy
  • Humans
  • Odds Ratio
  • Randomized Controlled Trials as Topic*
  • Research Design*
  • Retrospective Studies
  • Therapeutics*
  • Treatment Outcome