ClinicalTrials.gov与美国食品药品监督管理局药品数据库：新药批准试验结果报告的比较
ClinicalTrials.gov and Drugs@FDA: A Comparison of Results Reporting for New Drug Approval Trials.
作者信息
Schwartz Lisa M, Woloshin Steven, Zheng Eugene, Tse Tony, Zarin Deborah A
机构信息
From The Dartmouth Institute for Health Policy and Clinical Practice, Dartmouth Hitchcock, and Informulary, Lebanon, New Hampshire, and the National Library of Medicine, Bethesda, Maryland.
出版信息
Ann Intern Med. 2016 Sep 20;165(6):421-30. doi: 10.7326/M15-2658. Epub 2016 Jun 14.
BACKGROUND
Pharmaceutical companies and other trial sponsors must submit certain trial results to ClinicalTrials.gov. The validity of these results is unclear.
PURPOSE
To validate results posted on ClinicalTrials.gov against publicly available U.S. Food and Drug Administration (FDA) reviews on Drugs@FDA.
DATA SOURCES
ClinicalTrials.gov (registry and results database) and Drugs@FDA (medical and statistical reviews).
STUDY SELECTION
100 parallel-group, randomized trials for new drug approvals (January 2013 to July 2014) with results posted on ClinicalTrials.gov (15 March 2015).
DATA EXTRACTION
2 assessors extracted, and another verified, the trial design, primary and secondary outcomes, adverse events, and deaths.
RESULTS
Most trials were phase 3 (90%), double-blind (92%), and placebo-controlled (73%) and involved 32 drugs from 24 companies. Of 137 primary outcomes identified from ClinicalTrials.gov, 134 (98%) had corresponding data at Drugs@FDA, 130 (95%) had concordant definitions, and 107 (78%) had concordant results. Most differences were nominal (that is, relative difference <10%). Primary outcome results in 14 trials could not be validated. Of 1927 secondary outcomes from ClinicalTrials.gov, Drugs@FDA mentioned 1061 (55%) and included results data for 367 (19%). Of 96 trials with 1 or more serious adverse events in either source, 14 could be compared and 7 had discordant numbers of persons experiencing the adverse events. Of 62 trials with 1 or more deaths in either source, 25 could be compared and 17 were discordant.
LIMITATION
Unknown generalizability to uncontrolled or crossover trial results.
CONCLUSION
Primary outcome definitions and results were largely concordant between ClinicalTrials.gov and Drugs@FDA. Half the secondary outcomes, as well as serious events and deaths, could not be validated because Drugs@FDA includes only "key outcomes" for regulatory decision making and frequently includes only adverse event results aggregated across multiple trials.
PRIMARY FUNDING SOURCE
National Library of Medicine.
背景
制药公司和其他试验申办者必须向ClinicalTrials.gov提交某些试验结果。这些结果的有效性尚不清楚。
目的
对照美国食品药品监督管理局（FDA）在Drugs@FDA上公开的审评内容，验证ClinicalTrials.gov上公布的结果。
数据来源
ClinicalTrials.gov（注册库和结果数据库）以及Drugs@FDA（医学和统计审评）。
研究选择
2013年1月至2014年7月期间用于新药批准的100项平行组随机试验，其结果于2015年3月15日在ClinicalTrials.gov上公布。
数据提取
2名评估人员提取，另一名人员核实试验设计、主要和次要结局、不良事件及死亡情况。
结果
大多数试验为3期试验（90%）、双盲试验（92%）且采用安慰剂对照（73%），涉及24家公司的32种药物。从ClinicalTrials.gov确定的137项主要结局中，134项（98%）在Drugs@FDA有相应数据，130项（95%）定义一致，107项（78%）结果一致。大多数差异不显著（即相对差异<10%）。14项试验的主要结局结果无法验证。在ClinicalTrials.gov的1927项次要结局中，Drugs@FDA提及了1061项（55%），并包含367项（19%）的结果数据。在任一来源中有1项或更多严重不良事件报告的96项试验中，14项可进行比较，7项不良事件发生人数不一致。在任一来源中有1项或更多死亡报告的62项试验中，25项可进行比较，17项不一致。
局限性
对非对照试验或交叉试验结果的普遍适用性未知。
结论
ClinicalTrials.gov与Drugs@FDA之间，主要结局的定义和结果基本一致。一半的次要结局以及严重事件和死亡情况无法验证，因为Drugs@FDA仅包括用于监管决策的“关键结局”，且通常仅包括多个试验汇总的不良事件结果。
主要资金来源
国立医学图书馆。
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