抗抑郁药物试验的选择性发表及其对表面疗效的影响。

Selective publication of antidepressant trials and its influence on apparent efficacy.

作者信息

Turner Erick H, Matthews Annette M, Linardatos Eftihia, Tell Robert A, Rosenthal Robert

机构信息

Department of Psychiatry, Oregon Health and Science University, Portland, OR, USA.

出版信息

N Engl J Med. 2008 Jan 17;358(3):252-60. doi: 10.1056/NEJMsa065779.

DOI:10.1056/NEJMsa065779

PMID:18199864

Abstract

BACKGROUND

Evidence-based medicine is valuable to the extent that the evidence base is complete and unbiased. Selective publication of clinical trials--and the outcomes within those trials--can lead to unrealistic estimates of drug effectiveness and alter the apparent risk-benefit ratio.

METHODS

We obtained reviews from the Food and Drug Administration (FDA) for studies of 12 antidepressant agents involving 12,564 patients. We conducted a systematic literature search to identify matching publications. For trials that were reported in the literature, we compared the published outcomes with the FDA outcomes. We also compared the effect size derived from the published reports with the effect size derived from the entire FDA data set.

RESULTS

Among 74 FDA-registered studies, 31%, accounting for 3449 study participants, were not published. Whether and how the studies were published were associated with the study outcome. A total of 37 studies viewed by the FDA as having positive results were published; 1 study viewed as positive was not published. Studies viewed by the FDA as having negative or questionable results were, with 3 exceptions, either not published (22 studies) or published in a way that, in our opinion, conveyed a positive outcome (11 studies). According to the published literature, it appeared that 94% of the trials conducted were positive. By contrast, the FDA analysis showed that 51% were positive. Separate meta-analyses of the FDA and journal data sets showed that the increase in effect size ranged from 11 to 69% for individual drugs and was 32% overall.

CONCLUSIONS

We cannot determine whether the bias observed resulted from a failure to submit manuscripts on the part of authors and sponsors, from decisions by journal editors and reviewers not to publish, or both. Selective reporting of clinical trial results may have adverse consequences for researchers, study participants, health care professionals, and patients.

摘要

背景

循证医学的价值取决于证据库是否完整且无偏倚。临床试验的选择性发表——以及这些试验中的结果——可能导致对药物疗效的不切实际估计，并改变明显的风险效益比。

方法

我们获取了美国食品药品监督管理局（FDA）对12种抗抑郁药的研究综述，这些研究涉及12564名患者。我们进行了系统的文献检索以识别匹配的出版物。对于文献中报道的试验，我们将已发表的结果与FDA的结果进行比较。我们还将已发表报告得出的效应量与整个FDA数据集得出的效应量进行比较。

结果

在74项FDA注册的研究中，31%（涉及3449名研究参与者）未发表。这些研究是否发表以及如何发表与研究结果相关。FDA认为有阳性结果的37项研究已发表；1项被视为阳性的研究未发表。FDA认为有阴性或可疑结果的研究，除3项例外，要么未发表（22项研究），要么以我们认为传达了阳性结果的方式发表（11项研究）。根据已发表的文献，似乎所进行的试验中有94%是阳性的。相比之下，FDA的分析表明51%是阳性的。对FDA和期刊数据集的单独荟萃分析表明，个别药物的效应量增加幅度在11%至69%之间，总体为32%。