荟萃分析与随后的大型随机对照试验之间的差异。

Discrepancies between meta-analyses and subsequent large randomized, controlled trials.

作者信息

LeLorier J, Grégoire G, Benhaddad A, Lapierre J, Derderian F

机构信息

Research Center, Hôtel-Dieu de Montréal Hospital, Department of Medicine, University of Montreal, QC, Canada.

出版信息

N Engl J Med. 1997 Aug 21;337(8):536-42. doi: 10.1056/NEJM199708213370806.

DOI:10.1056/NEJM199708213370806

PMID:9262498

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.

摘要

背景

荟萃分析目前被广泛用于提供证据以支持临床策略。然而，大型随机对照试验被认为是评估临床干预疗效的金标准。

方法

我们将发表在四种期刊（《新英格兰医学杂志》《柳叶刀》《内科学年鉴》和《美国医学会杂志》）上的大型随机对照试验（涉及1000名或更多患者）的结果与先前发表的关于相同主题的荟萃分析结果进行了比较。对于主要和次要结局，我们判断随机试验的结果是否与相应荟萃分析的结果一致，并在传统统计学显著性水平（P<0.05）下确定研究结果是阳性（表明治疗改善了结局）还是阴性（表明治疗后的结局与未治疗时相同或更差）。

结果

我们确定了12项大型随机对照试验和19项针对相同问题的荟萃分析。对于总共40个主要和次要结局，荟萃分析与大型临床试验之间的一致性仅为中等（kappa = 0.35；95%置信区间，0.06至0.64）。荟萃分析的阳性预测值为68%，阴性预测值为67%。然而，在40项比较中，随机试验与荟萃分析之间的点估计差异仅有5项（12%）具有统计学显著性。此外，在每例不一致的情况中，一种方法发现治疗有统计学显著性效果，而另一种方法未发现统计学显著性效果。