OBJECTIVE To examine the design characteristics, risk of bias, and reporting adequacy of pivotal randomised controlled trials of cancer drugs approved by the European Medicines Agency (EMA). DESIGN Cross sectional analysis. SETTING European regulatory documents, clinical trial registry records, protocols, journal publications, and supplementary appendices. ELIGIBILITY CRITERIA Pivotal randomised controlled trials of new cancer drugs approved by the EMA between 2014 and 2016. MAIN OUTCOME MEASURES Study design characteristics (randomisation, comparators, and endpoints); risk of bias using the revised Cochrane tool (bias arising from the randomisation process, deviations from intended interventions, missing outcome data, measurement of the outcome, and selection of the reported result); and reporting adequacy (completeness and consistency of information in trial protocols, publications, supplementary appendices, clinical trial registry records, and regulatory documents). RESULTS Between 2014 and 2016, the EMA approved 32 new cancer drugs on the basis of 54 pivotal studies. Of these, 41 (76%) were randomised controlled trials and 13 (24%) were either non-randomised studies or single arm studies. 39/41 randomised controlled trials had available publications and were included in our study. Only 10 randomised controlled trials (26%) measured overall survival as either a primary or coprimary endpoint, with the remaining trials evaluating surrogate measures such as progression free survival and response rates. Overall, 19 randomised controlled trials (49%) were judged to be at high risk of bias for their primary outcome. Concerns about missing outcome data (n=10) and measurement of the outcome (n=7) were the most common domains leading to high risk of bias judgments. Fewer randomised controlled trials that evaluated overall survival as the primary endpoint were at high risk of bias than those that evaluated surrogate efficacy endpoints (2/10 (20%) v 16/29 (55%), respectively). When information available in regulatory documents and the scientific literature was considered separately, overall risk of bias judgments differed for eight randomised controlled trials (21%), which reflects reporting inadequacies in both sources of information. Regulators identified additional deficits beyond the domains captured in risk of bias assessments for 10 drugs (31%). These deficits included magnitude of clinical benefit, inappropriate comparators, and non-preferred study endpoints, which were not disclosed as limitations in scientific publications. CONCLUSIONS Most pivotal studies forming the basis of EMA approval of new cancer drugs between 2014 and 2016 were randomised controlled trials. However, almost half of these were judged to be at high risk of bias based on their design, conduct, or analysis, some of which might be unavoidable because of the complexity of cancer trials. Regulatory documents and the scientific literature had gaps in their reporting. Journal publications did not acknowledge the key limitations of the available evidence identified in regulatory documents.

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设计特征，偏倚风险以及支持癌症药物获得欧洲药品管理局批准的随机对照试验的报告，2014-16年：横截面分析。

目的研究由欧洲药品管理局（EMA）批准的癌症药物的关键随机对照试验的设计特征，偏倚风险和报告的充分性。设计横截面分析。设置欧洲法规文件，临床试验注册记录，方案，期刊出版物和补充附录。合格标准EMA在2014年至2016年间批准的新的癌症药物的关键随机对照试验。主要观察指标研究设计特征（随机，比较和终点）；使用修订的Cochrane工具产生偏见的风险（由随机化过程引起的偏见，与预期干预措施的偏差，缺少结果数据，结果的测量以及报告结果的选择）；和报告的充分性（试验方案，出版物，补充附录，临床试验注册记录和法规文件中信息的完整性和一致性）。结果2014年至2016年，EMA在54项关键性研究的基础上批准了32种新的抗癌药物。其中41例（76％）为随机对照试验，13例（24％）为非随机研究或单组研究。39/41随机对照试验已有可用出版物，并纳入了我们的研究。只有10项随机对照试验（26％）将总体生存率作为主要或共同主要终点指标进行了评估，其余试验则评估了替代指标，例如无进展生存期和缓解率。总体而言，有19项随机对照试验（占49％）被认为在其主要结局中存在偏倚的高风险。对于缺少结果数据（n = 10）和测量结果（n = 7）的担忧是导致偏见判断高风险的最常见领域。评估整体生存率作为主要终点的随机对照试验比那些评价替代功效终点的试验（分别为2/10（20％）v 16/29（55％））有较高的偏倚风险。当分别考虑监管文件和科学文献中的信息时，八项随机对照试验（21％）的偏倚判断的总体风险有所不同，这反映了两种信息来源的报告不足。监管机构确定了超出10种药物的偏倚评估风险所涵盖范围之外的其他缺陷（31％）。这些缺陷包括临床获益的幅度，不适当的比较者，以及非首选的研究终点，在科学出版物中没有作为限制公开。结论2014年至2016年间，构成EMA批准新癌症药物的基础的大多数关键研究均为随机对照试验。然而，根据他们的设计，行为或分析，几乎有一半被判断为有偏见的高风险，由于癌症试验的复杂性，其中某些可能是不可避免的。监管文件和科学文献的报告存在差距。期刊出版物不承认监管文件中确定的可用证据的主要局限性。然而，根据他们的设计，行为或分析，几乎有一半被判断为有偏见的高风险，由于癌症试验的复杂性，其中某些可能是不可避免的。监管文件和科学文献的报告存在差距。期刊出版物不承认监管文件中确定的可用证据的主要局限性。然而，根据他们的设计，行为或分析，几乎有一半被判断为有偏见的高风险，由于癌症试验的复杂性，其中某些可能是不可避免的。监管文件和科学文献的报告存在差距。期刊出版物不承认监管文件中确定的可用证据的主要局限性。