Trial publication after registration in ClinicalTrials.Gov: a cross-sectional analysis.
Trial publication after registration in ClinicalTrials.Gov: a cross-sectional analysis.
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DOI：
10.1371/journal.pmed.1000144
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发表时间：
2009-09
期刊：
影响因子：
15.8
通讯作者：
Krumholz HM
中科院分区：
文献类型：
--
作者：
Ross JS;Mulvey GK;Hines EM;Nissen SE;Krumholz HM
Joseph Ross 及其同事检查了临床试验的发表率，发现即使在 ClinicalTrials.gov 注册后，发表率也很低。 ClinicalTrials.gov 是一个可公开访问、基于互联网的临床试验注册中心，由美国国家医学图书馆管理，有潜力解决选择性试验出版问题。我们的目标是检查 ClinicalTrials.gov 内注册的完整性，并确定选择性发表的范围和相关性。我们检查了 1999 年 12 月 31 日之后在 ClinicalTrials.gov 注册并更新为 2007 年 6 月 8 日完成的跨部门试验的注册信息报告，不包括 I 期试验。然后，我们在排除 2005 年 12 月 31 日之后完成的试验后，通过使用系统方案搜索 MEDLINE 来确定随机 10% 子样本的发表状态，以允许完成后至少有 2 年的发表时间。在已完成试验的完整样本中 (n = 7,515)，近 100% 报告了 ClinicalTrials.gov 规定的所有数据元素，例如干预和赞助。可选数据元素报告各不相同，其中 53% 报告试验结束日期，66% 报告主要结果，87% 报告试验开始日期。在 10% 的子样本中，只有不到一半（677 项中的 311 项，46%）的试验被发表，其中 96 项（31%）在 ClinicalTrials.gov 中引用了一份描述试验结果的出版物。与非行业/非政府资助的试验（56%，198 项中的 110 项；p<0.001）相比，主要由企业资助的试验（40%，357 项中的 144 项）发表的可能性较小，但与政府资助的试验（47%，122 项中的 57 项；p = 0.22）相比，没有显着差异。在报告结束日期的试验中，123 项试验中有 75 项 (61%) 在 2004 年之前完成，96 项试验中 50 项 (52%) 在 2004 年期间完成，149 项试验中 62 项 (42%) 在 2005 年期间完成 (p = 0.006)。可选数据元素的报告各不相同，并且在 ClinicalTrials.gov 中注册的已完成试验的发表率较低。如果不更多地关注所有数据元素的报告，ClinicalTrials.gov 解决临床试验选择性发布问题的潜力将受到限制。 请参阅本文后面的编辑摘要 人们认为，每当他们生病时，医疗保健专业人员都会确保他们得到最好的治疗。但临床医生如何知道哪种治疗最合适呢？过去，临床医生利用自己的经验来做出治疗决定。如今，他们依靠循证医学——对临床试验结果的系统审查和评估，以及调查医疗干预措施对人类的有效性和安全性的研究。然而，只有临床试验的所有结果都及时在医学期刊上发表，循证医学才能有效。不幸的是，新药的表现并不比现有药物更好或有不良副作用的试验结果通常仍未发表，或仅在美国食品和药物管理局 (FDA) 和其他政府机构批准该药物用于临床多年后才出现在公共领域。这种“选择性”出版物可能损害循证临床实践的程度尚不清楚，但被认为是实质性的。在这项研究中，研究人员通过系统地检查在 ClinicalTrials.gov（基于网络的美国和国际临床试验注册中心）注册的试验结果的发表程度来调查选择性发表的问题。 ClinicalTrials.gov 是美国国家医学图书馆根据 1997 年 FDA 现代化法案于 2000 年建立的。该法案要求对所有新药试验进行预先注册，以便向公众提供他们可能参与的试验的信息。在 ClinicalTrials.gov 中注册的强制性数据元素最初包括试验标题、试验中研究的条件、试验设计和研究的干预措施。 2007 年 9 月，FDA 修正案扩大了在 ClinicalTrials.gov 注册的强制性要求，例如，必须在试验完成后 2 年内在注册处报告试验开始日期以及主要和次要结果（干预对预定义临床测量的影响）。研究人员确定了 1999 年 12 月 31 日之后在 ClinicalTrials.gov 中注册的 7,515 项试验（不包括第一阶段安全性试验），其记录表明试验在 2007 年 6 月 8 日之前完成。大多数试验报告了 FDA 修正案法案之前 ClinicalTrials.gov 要求的所有强制性数据元素，但可选数据元素的报告不太完整。例如，只有三分之二的试验报告了其主要结果。接下来，研究人员随机选择了10%的试验，排除完成日期在2005年12月31日之后的试验（以允许至少两年的发表时间）后，通过系统地搜索MEDLINE（在选定的医学和科学期刊上发表的文章的在线数据库）来确定该子样本的发表状态。子样本中只有不到一半的试验已发表，并且这些出版物中只有三分之一的引用被输入到 ClinicalTrials.gov 中。只有 40% 的行业赞助试验已发表，而非行业/非政府赞助的试验则为 56%，这种差异不太可能是偶然发生的。最后，2004 年之前完成的试验中有 61% 已发表，但 2005 年期间完成的试验中只有 42% 已发表。这些发现表明，在研究期间，关键试验信息并未包含在 ClinicalTrials.gov 注册表中。 FDA 修正案应该弥补其中一些缺陷，但前提是仔细监控 ClinicalTrials.gov 中信息的准确性和完整性。这些发现还表明，在 ClinicalTrials.gov 上注册并不能保证试验结果会及时出现在科学文献中。然而，它们没有解决选择性发表的原因（这可能部分是因为发表阴性结果比发表阳性结果更难），并且它们可能受到用于发现试验结果是否已发表的方法的限制。尽管如此，这些发现表明 FDA、试验申办者和科学界都需要做出坚定的承诺，尽量减少选择性公布试验结果，以确保患者和临床医生能够获得做出充分知情的治疗决策所需的信息。请通过此摘要的在线版本访问这些网站：http://dx.doi.org/10.1371/journal.pmed.1000144。 PLoS Medicine 最近在 Ida Sim 及其同事和 Lisa Bero 及其同事的选定出版物上发表了两篇相关文章，以及一篇讨论 FDA 修正案的社论 ClinicalTrials.gov 提供了有关美国国立卫生研究院临床试验注册的信息，包括有关临床试验的背景信息，以及详细介绍了 2007 年 FDA 修正案对试验注册的要求的概况介绍 美国食品和药物管理局为消费者和医疗保健专业人员提供了有关美国药品审批的更多信息
Joseph Ross and colleagues examine publication rates of clinical trials and find low rates of publication even following registration in Clinicaltrials.gov. ClinicalTrials.gov is a publicly accessible, Internet-based registry of clinical trials managed by the US National Library of Medicine that has the potential to address selective trial publication. Our objectives were to examine completeness of registration within ClinicalTrials.gov and to determine the extent and correlates of selective publication. We examined reporting of registration information among a cross-section of trials that had been registered at ClinicalTrials.gov after December 31, 1999 and updated as having been completed by June 8, 2007, excluding phase I trials. We then determined publication status among a random 10% subsample by searching MEDLINE using a systematic protocol, after excluding trials completed after December 31, 2005 to allow at least 2 y for publication following completion. Among the full sample of completed trials (n = 7,515), nearly 100% reported all data elements mandated by ClinicalTrials.gov, such as intervention and sponsorship. Optional data element reporting varied, with 53% reporting trial end date, 66% reporting primary outcome, and 87% reporting trial start date. Among the 10% subsample, less than half (311 of 677, 46%) of trials were published, among which 96 (31%) provided a citation within ClinicalTrials.gov of a publication describing trial results. Trials primarily sponsored by industry (40%, 144 of 357) were less likely to be published when compared with nonindustry/nongovernment sponsored trials (56%, 110 of 198; p<0.001), but there was no significant difference when compared with government sponsored trials (47%, 57 of 122; p = 0.22). Among trials that reported an end date, 75 of 123 (61%) completed prior to 2004, 50 of 96 (52%) completed during 2004, and 62 of 149 (42%) completed during 2005 were published (p = 0.006). Reporting of optional data elements varied and publication rates among completed trials registered within ClinicalTrials.gov were low. Without greater attention to reporting of all data elements, the potential for ClinicalTrials.gov to address selective publication of clinical trials will be limited. Please see later in the article for the Editors' Summary People assume that whenever they are ill, health care professionals will make sure they get the best available treatment. But how do clinicians know which treatment is most appropriate? In the past, clinicians used their own experience to make treatment decisions. Nowadays, they rely on evidence-based medicine—the systematic review and appraisal of the results of clinical trials, studies that investigate the efficacy and safety of medical interventions in people. However, evidence-based medicine can only be effective if all the results from clinical trials are published promptly in medical journals. Unfortunately, the results of trials in which a new drug did not perform better than existing drugs or in which it had unwanted side effects often remain unpublished or only appear in the public domain many years after the drug has been approved for clinical use by the US Food and Drug Administration (FDA) and other governmental bodies. The extent of this “selective” publication, which can impair evidence-based clinical practice, remains unclear but is thought to be substantial. In this study, the researchers investigate the problem of selective publication by systematically examining the extent of publication of the results of trials registered in ClinicalTrials.gov, a Web-based registry of US and international clinical trials. ClinicalTrials.gov was established in 2000 by the US National Library of Medicine in response to the 1997 FDA Modernization Act. This act required preregistration of all trials of new drugs to provide the public with information about trials in which they might be able to participate. Mandatory data elements for registration in ClinicalTrials.gov initially included the trial's title, the condition studied in the trial, the trial design, and the intervention studied. In September 2007, the FDA Amendments Act expanded the mandatory requirements for registration in ClinicalTrials.gov by making it necessary, for example, to report the trial start date and to report primary and secondary outcomes (the effect of the intervention on predefined clinical measurements) in the registry within 2 years of trial completion. The researchers identified 7,515 trials that were registered within ClinicalTrials.gov after December 31, 1999 (excluding phase I, safety trials), and whose record indicated trial completion by June 8, 2007. Most of these trials reported all the mandatory data elements that were required by ClinicalTrials.gov before the FDA Amendments Act but reporting of optional data elements was less complete. For example, only two-thirds of the trials reported their primary outcome. Next, the researchers randomly selected 10% of the trials and, after excluding trials whose completion date was after December 31, 2005 (to allow at least two years for publication), determined the publication status of this subsample by systematically searching MEDLINE (an online database of articles published in selected medical and scientific journals). Fewer than half of the trials in the subsample had been published, and the citation for only a third of these publications had been entered into ClinicalTrials.gov. Only 40% of industry-sponsored trials had been published compared to 56% of nonindustry/nongovernment-sponsored trials, a difference that is unlikely to have occurred by chance. Finally, 61% of trials with a completion date before 2004 had been published, but only 42% of trials completed during 2005 had been published. These findings indicate that, over the period studied, critical trial information was not included in the ClinicalTrials.gov registry. The FDA Amendments Act should remedy some of these shortcomings but only if the accuracy and completeness of the information in ClinicalTrials.gov is carefully monitored. These findings also reveal that registration in ClinicalTrials.gov does not guarantee that trial results will appear in a timely manner in the scientific literature. However, they do not address the reasons for selective publication (which may be, in part, because it is harder to publish negative results than positive results), and they are potentially limited by the methods used to discover whether trial results had been published. Nevertheless, these findings suggest that the FDA, trial sponsors, and the scientific community all need to make a firm commitment to minimize the selective publication of trial results to ensure that patients and clinicians have access to the information they need to make fully informed treatment decisions. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000144. PLoS Medicine recently published two related articles on selected publication by Ida Sim and colleagues and by Lisa Bero and colleagues and an editorial discussing the FDA Amendments Act ClinicalTrials.gov provides information about the US National Institutes of Health clinical trial registry, including background information about clinical trials, and a fact sheet detailing the requirements of the FDA Amendments Act 2007 for trial registration The US Food and Drug Administration provides further information about drug approval in the US for consumers and health care professionals
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影响因子：
158.5
作者：
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发表时间：
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