未发表的新型神经药物临床试验结果：系统评价。
Nonpublication of trial results for new neurological drugs: A systematic review.
机构信息
Studies of Translation, Ethics, and Medicine (STREAM), Biomedical Ethics Unit, McGill University, Montreal, Quebec, Canada.
Centre for Practice Changing Research, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
出版信息
Ann Neurol. 2017 Jun;81(6):782-789. doi: 10.1002/ana.24952. Epub 2017 Jun 5.
OBJECTIVE
To evaluate nonpublication rates among trials of new successful and unsuccessful neurological drugs.
METHODS
"Licensed" drugs consisted of all novel agents receiving US Food and Drug Administration (FDA) licensure 2005-2012 inclusive in seven neurological disorders. "Stalled" drugs included all experimental agents tested in the same domains that had at least one completed phase III trial in the same time frame, but failed to receive FDA approval. Trials of these drugs were included in our sample if their primary outcome collection occurred before October 1, 2010. We determined the publication status of eligible trials using searches of clinicaltrials.gov, Google Scholar, PubMed, Embase, sponsor websites, and direct electronic query of trial contacts and sponsors. The primary outcome was time to journal publication (or results reporting in other media) after study completion.
RESULTS
The adjusted hazard ratio for publication was 1.79 (95% confidence interval, 1.20-2.67) in favor of licensed drugs. Based on the criteria for nonpublication in this report, 14,092 and 33,882 volunteers participated in unpublished trials of licensed and stalled neurological drugs, respectively. Result data were not publicly available in any form for 10% (16 of 163) and 46% (94 of 203) of trials of licensed and stalled drugs, respectively.
INTERPRETATION
Results of trials for stalled drugs are heavily under-reported. This deprives research and care communities of evidence about pathophysiology, drug class effects, and the value of surrogate endpoints in trials. Ann Neurol 2017;81:782-789.
目的
评估新成功和不成功的神经药物试验的未发表率。
方法
“许可”药物包括在 2005 年至 2012 年期间获得美国食品和药物管理局（FDA）许可的所有新型药物，涵盖七种神经疾病。“停滞”药物包括在同一领域测试的所有实验药物，这些药物至少进行了一项在同一时间框架内的 III 期临床试验，但未能获得 FDA 批准。如果这些药物的主要结果收集发生在 2010 年 10 月 1 日之前，则将其临床试验纳入我们的样本中。我们使用 clinicaltrials.gov、Google Scholar、PubMed、Embase、赞助商网站以及直接向试验联系人或赞助商电子查询来确定合格试验的发表状态。主要结局是研究完成后向期刊发表（或在其他媒体上报告结果）的时间。
结果
发表的调整后风险比为 1.79（95%置信区间，1.20-2.67），有利于许可药物。根据本报告中未发表的标准，分别有 14092 名和 33882 名志愿者参加了许可和停滞的神经药物的未发表试验。许可药物和停滞药物的试验中，分别有 10%（16 项）和 46%（94 项）的结果数据未以任何形式公开。
解释
停滞药物试验的结果严重未报告。这使研究和护理社区无法获得关于病理生理学、药物类别效应以及替代终点在试验中的价值的证据。神经病学 2017；81：782-789。
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