Yao Yanhong, Liu Zhentao, Zhang Hua, Li Jian, Peng Zhi, Yu Jinyu, Cao Baoshan, Shen Lin
Department of Medical Oncology and Radiation Sickness, Peking University Third Hospital, Beijing, China.
Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing, China.
Front Pharmacol. 2021 Nov 18;12:754858. doi: 10.3389/fphar.2021.754858. eCollection 2021.
The occurrence, development, and prognosis of serious adverse events (SAEs) associated with anticancer drugs in clinical trials have important guiding significance for real-world clinical applications. However, to date, there have been no studies investigating SAEs reporting in randomized clinical trials of colorectal cancer treatments. This article systematically reviewed the SAEs reporting of phase III randomized clinical trials of colorectal cancer treatments and analyzed the influencing factors. We reviewed all articles about phase III randomized clinical trials of colorectal cancer treatments published in the PubMed, Embase, Medline, and New England Journal of Medicine databases from January 1, 1993, to December 31, 2018, and searched the registration information of clinical trials the internet sites such as "clinicaltrials.gov". We analyzed the correlation between the reported proportion (RP) of SAEs in the literature and nine elements, including the clinical trial sponsor and the publication time. Chi-square tests and binary logistic regression were used to identify the factors associated with improved SAEs reports. This study was registered on PROSPERO. Of 1560 articles identified, 160 were eligible, with an RP of SAEs of 25.5% (41/160). In forty-one publications reporting SAEs, only 14.6% (6/41) described the pattern of SAEs in detail. In clinical trials sponsored by pharmaceutical companies, the RP of SAEs was significantly higher than that in those sponsored by investigators (57.6 versus 20.7%, < 0.001). From 1993 to 2018, the RP of SAEs gradually increased (none (0/6) before 2000, 17.1% (12/70) from 2000 to 2009, and 34.5% (29/84) after 2009). The average RP of SAEs published in the New England Journal of Medicine (N Engl J Med), the Lancet, the Journal of the American Medical Association (JAMA), the Lancet Oncology (Lancet Oncol), and the Journal of Clinical Oncology (J Clin Oncol) was significantly higher than that published in other journals (31.9 versus 16.7%, 0.030). In the clinical trials referenced by clinical guidelines, the RP of SAEs was higher than that in non-referenced clinical trials (32.0 versus 15.9%, 0.023). Binary logistic regression analysis showed that pharmaceutical company sponsorship, new drug research, and sample size greater than 1000 were positive influencing factors for SAEs reporting. Although the RP of SAEs increased over time, SAEs reporting in clinical trials needs to be further improved. The performance, outcomes and prognosis of SAEs should be reported in detail to guide clinical practice in the real world.
临床试验中与抗癌药物相关的严重不良事件（SAEs）的发生、发展及预后情况，对实际临床应用具有重要指导意义。然而，迄今为止，尚无研究调查结直肠癌治疗随机临床试验中的SAEs报告情况。本文系统回顾了结直肠癌治疗Ⅲ期随机临床试验的SAEs报告情况，并分析了影响因素。我们检索了1993年1月1日至2018年12月31日期间发表在PubMed、Embase、Medline及《新英格兰医学杂志》数据库中关于结直肠癌治疗Ⅲ期随机临床试验的所有文章，并在“clinicaltrials.gov”等互联网网站上搜索临床试验注册信息。我们分析了文献中SAEs报告比例（RP）与九个因素之间的相关性，包括临床试验申办者和发表时间。采用卡方检验和二元逻辑回归来确定与SAEs报告改善相关的因素。本研究已在PROSPERO注册。在检索到的1560篇文章中，160篇符合纳入标准，SAEs的RP为25.5%（41/160）。在41篇报告SAEs的出版物中，只有14.6%（6/41）详细描述了SAEs的模式。在制药公司赞助的临床试验中，SAEs的RP显著高于研究者赞助的试验（57.6%对20.7%，<0.001）。从1993年到2018年，SAEs的RP逐渐升高（2000年前无（0/6），2000年至2009年为17.1%（12/70），2009年后为34.5%（29/84））。发表在《新英格兰医学杂志》（N Engl J Med）、《柳叶刀》、《美国医学会杂志》（JAMA）、《柳叶刀肿瘤学》（Lancet Oncol）及《临床肿瘤学杂志》（J Clin Oncol）上的SAEs平均RP显著高于发表在其他杂志上的（31.9%对16.7%，P = 0.030）。在临床指南引用的临床试验中，SAEs的RP高于未被引用的临床试验（32.0%对15.9%，P = 0.023）。二元逻辑回归分析显示，制药公司赞助、新药研究以及样本量大于1000是SAEs报告的积极影响因素。尽管SAEs的RP随时间增加，但临床试验中的SAEs报告仍需进一步改进。应详细报告SAEs的表现、结局及预后情况，以指导实际临床实践。
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