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Previous Volume 337:536-542 August 21, 1997 Number 8 Next

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ABSTRACT

Background Meta-analyses are now widely used to provide evidence to support clinical strategies. However, large randomized, controlled trials are considered the gold standard in evaluating the efficacy of clinical interventions.

Methods We compared the results of large randomized, controlled trials (involving 1000 patients or more) that were published in four journals (the New England Journal of Medicine, the Lancet, the Annals of Internal Medicine, and the Journal of the American Medical Association) with the results of meta-analyses published earlier on the same topics. Regarding the principal and secondary outcomes, we judged whether the findings of the randomized trials agreed with those of the corresponding meta-analyses, and we determined whether the study results were positive (indicating that treatment improved the outcome) or negative (indicating that the outcome with treatment was the same or worse than without it) at the conventional level of statistical significance (P<0.05).

Results We identified 12 large randomized, controlled trials and 19 meta-analyses addressing the same questions. For a total of 40 primary and secondary outcomes, agreement between the meta-analyses and the large clinical trials was only fair (kappa = 0.35; 95 percent confidence interval, 0.06 to 0.64). The positive predictive value of the meta-analyses was 68 percent, and the negative predictive value 67 percent. However, the difference in point estimates between the randomized trials and the meta-analyses was statistically significant for only 5 of the 40 comparisons (12 percent). Furthermore, in each case of disagreement a statistically significant effect of treatment was found by one method, whereas no statistically significant effect was found by the other.

Conclusions The outcomes of the 12 large randomized, controlled trials that we studied were not predicted accurately 35 percent of the time by the meta-analyses published previously on the same topics.

Source Information

From the Research Center, Hôtel-Dieu de Montréal Hospital, and the Department of Medicine, Faculty of Medicine, University of Montreal — both in Montreal.

Address reprint requests to Dr. LeLorier at the Research Center, Hôtel-Dieu de Montréal, 3850 St. Urbain St., Pavilion Marie de la Ferre, 2nd Fl., Montreal, QC H2W 1T8, Canada.

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