“Comparison of Evidence of Treatment Effects in Randomized and Nonrandomized Studies”, 2001-08-01 (; backlinks; similar):
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 < 0.001); however, nonrandomized studies tended to show larger treatment effects (28 vs 11; p = 0.009). 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.
Conclusion: 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.