Likelihood of Null Effects of Large NHLBI Clinical Trials Has Increased over Time
Likelihood of Null Effects of Large NHLBI Clinical Trials Has Increased over Time
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DOI：
10.1371/journal.pone.0132382
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发表时间：
2015-08-05
期刊：
影响因子：
3.7
通讯作者：
Irvin, Veronica L.
中科院分区：
文献类型：
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作者：
Kaplan, Robert M.;Irvin, Veronica L.
背景我们探索国家心肺和血液研究所(NHLBI)资助的大型试验中无效结果的数量是否随着时间的推移而增加。方法我们确定了1970年至2012年期间所有由NHLBI支持的大型随机对照试验，评估用于治疗或预防心血管疾病的药物或膳食补充剂。如果直接费用为500,000美元/年，参与者是成年人，并且主要结果是心血管风险、疾病或死亡，则试验包括在内。符合这些标准的55项试验的编码依据是它们是在2000年之前还是之后发表的，是否在发表前在临床试验网站上注册，是否使用了有效的或安慰剂比较器，以及试验是否得到了行业的共同赞助。结果在2000年之前发表的30项研究中，有17项(57%)显示干预对主要结果有显著益处，而在2000年之后发表的25项试验中，只有2项(8%)显示干预对主要结果有显著益处(chi(2)=12.2df=1，p=0.0005)。将治疗与安慰剂和活性比较剂进行比较的试验比例没有变化。行业联合赞助与报告显著收益的可能性无关。在临床试验中预先注册。gov与无效发现的趋势密切相关。结论2000年以后，NHLBI试验报告阳性结果的数量下降。临床试验所要求的随机对照试验结果的预期宣布，以及采用透明的报告标准。政府，可能是导致零发现的趋势的原因之一。
BackgroundWe explore whether the number of null results in large National Heart Lung, and Blood Institute (NHLBI) funded trials has increased over time.MethodsWe identified all large NHLBI supported RCTs between 1970 and 2012 evaluating drugs or dietary supplements for the treatment or prevention of cardiovascular disease. Trials were included if direct costs >$500,000/year, participants were adult humans, and the primary outcome was cardiovascular risk, disease or death. The 55 trials meeting these criteria were coded for whether they were published prior to or after the year 2000, whether they registered in clinicaltrials.gov prior to publication, used active or placebo comparator, and whether or not the trial had industry co-sponsorship. We tabulated whether the study reported a positive, negative, or null result on the primary outcome variable and for total mortality.Results17 of 30 studies (57%) published prior to 2000 showed a significant benefit of intervention on the primary outcome in comparison to only 2 among the 25 (8%) trials published after 2000 (chi(2)=12.2, df= 1, p=0.0005). There has been no change in the proportion of trials that compared treatment to placebo versus active comparator. Industry co-sponsorship was unrelated to the probability of reporting a significant benefit. Pre-registration in clinical trials.gov was strongly associated with the trend toward null findings.ConclusionsThe number NHLBI trials reporting positive results declined after the year 2000. Prospective declaration of outcomes in RCTs, and the adoption of transparent reporting standards, as required by clinicaltrials. gov, may have contributed to the trend toward null findings.