Studies of Translation, Ethics, and Medicine (STREAM), Biomedical Ethics Unit, Department of Social Studies of Medicine, McGill University, H3A 1X1, Montreal, Canada.
Studies of Translation, Ethics, and Medicine (STREAM), Biomedical Ethics Unit, Department of Social Studies of Medicine, McGill University, H3A 1X1, Montreal, Canada
BMJ. 2015 Mar 9;350:h1116. doi: 10.1136/bmj.h1116.
To quantify the proportion of trials for unsuccessfully licensed drugs that are not published.
A systematic assessment of the availability of published research reports for publicly registered trials testing drugs stalling in clinical development ("stalled drugs") and drugs receiving regulatory licensure in the same time period ("licensed drugs").
Searches of clinicaltrials.gov, Google Scholar, PubMed, Embase, and electronic query of contacts in registries to identify trials and assess publication status.
The cohort of licensed drugs consisted of all disease modifying drugs in cancer, cardiovascular disease, or neurological disorders that received Food and Drug Administration licensure during 2005 to 2009 inclusive. The cohort of stalled drugs included unlicensed drugs in the same disease areas that had at least one completed phase III trial before 2009 and no evidence of any clinical trial activity after 31 December 2009. Inclusion criteria for registered trials advanced into publication searching were an intervention tested in a disease modifying, phase II, III, or IV trial registered on clinicaltrials.gov, with enrolment of at least one patient, that reported primary outcome collection end date between 1 January 2006 and 31 December 2008.
The unadjusted publication proportion for registered trials of licensed drugs was 75% (72/96) versus 37% (30/81) for stalled drugs. The adjusted hazard ratio for publication was 2.7 (95% confidence interval 1.7 to 4.3) in favour of licensed drug trials. Higher publication rates for licensed drug trials were observed regardless of disease type, sponsorship, trial phase, and geography. The rate of non-publication of stalled drug trials was significantly higher for studies that did not complete enrolment compared with licensed drug trials. A total of 20,135 patients participated in trials of stalled drugs that were never published.
Much of the information collected in unsuccessful drug trials is inaccessible to the broader research and practice communities. These findings provide an evidence base and rationale for policy reforms aimed at promoting transparency, ethics, and accountability in clinical research.
量化未获得许可的药物试验中未发表的比例。
对公开注册的临床试验报告进行系统评估，这些试验测试了临床开发中失败的药物（“停滞药物”）和同期获得监管许可的药物（“许可药物”）。
在 clinicaltrials.gov、Google Scholar、PubMed、Embase 中进行检索，并查询注册处的联系人，以确定试验并评估其发表状态。
许可药物组包括 2005 年至 2009 年期间获得美国食品和药物管理局许可的癌症、心血管疾病或神经紊乱疾病的所有改良药物。停滞药物组包括在同一疾病领域未获得许可的药物，这些药物在 2009 年前至少有一项完成的 III 期试验，并且在 2009 年 12 月 31 日之后没有任何临床试验活动的证据。纳入注册试验进行出版搜索的标准是在 clinicaltrials.gov 上注册的、针对改良疾病的 II、III 或 IV 期试验中测试的干预措施，至少有一名患者入组，报告的主要结局采集结束日期在 2006 年 1 月 1 日至 2008 年 12 月 31 日之间。
未经调整的许可药物注册试验的发表比例为 75%（72/96），而停滞药物的发表比例为 37%（30/81）。发表的调整后的风险比为 2.7（95%置信区间 1.7 至 4.3），有利于许可药物试验。在疾病类型、赞助、试验阶段和地理位置方面，许可药物试验的发表率都较高。与许可药物试验相比，未完成入组的停滞药物试验的未发表率明显更高。共有 20,135 名患者参加了从未发表过的停滞药物试验。
许多不成功的药物试验所收集的信息无法为更广泛的研究和实践社区所获得。这些发现为旨在促进临床研究透明度、伦理和问责制的政策改革提供了证据基础和理由。
