Comparison of Evidence of Treatment Effects in Randomized and Nonrandomized Studies

JAMA. 2001 Aug 15;286(7):821-30. doi: 10.1001/jama.286.7.821.

Abstract

Context: There is substantial debate about whether the results of nonrandomized studies are consistent with the results of randomized controlled trials on the same topic.

Objectives: To compare results of randomized and nonrandomized studies that evaluated medical interventions and to examine characteristics that may explain discrepancies between randomized and nonrandomized studies.

Data sources: MEDLINE (1966-March 2000), the Cochrane Library (Issue 3, 2000), and major journals were searched.

Study selection: Forty-five diverse topics were identified for which both randomized trials (n = 240) and nonrandomized studies (n = 168) had been performed and had been considered in meta-analyses of binary outcomes.

Data extraction: Data on events per patient in each study arm and design and characteristics of each study considered in each meta-analysis were extracted and synthesized separately for randomized and nonrandomized studies.

Data synthesis: Very good correlation was observed between the summary odds ratios of randomized and nonrandomized studies (r = 0.75; P<.001); however, nonrandomized studies tended to show larger treatment effects (28 vs 11; P =.009). Between-study heterogeneity was frequent among randomized trials alone (23%) and very frequent among nonrandomized studies alone (41%). The summary results of the 2 types of designs differed beyond chance in 7 cases (16%). Discrepancies beyond chance were less common when only prospective studies were considered (8%). Occasional differences in sample size and timing of publication were also noted between discrepant randomized and nonrandomized studies. In 28 cases (62%), the natural logarithm of the odds ratio differed by at least 50%, and in 15 cases (33%), the odds ratio varied at least 2-fold between nonrandomized studies and randomized trials.

Conclusions: Despite good correlation between randomized trials and nonrandomized studies-in particular, prospective studies-discrepancies beyond chance do occur and differences in estimated magnitude of treatment effect are very common.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Clinical Trials as Topic*
  • Data Interpretation, Statistical
  • Evidence-Based Medicine*
  • Humans
  • Meta-Analysis as Topic*
  • Randomized Controlled Trials as Topic*