Fergusson Dean A, Wesch Neil L, Leung Garvin J, MacNeil Jenna L, Conic Isidora, Presseau Justin, Cobey Kelly D, Diallo Jean-Simon, Auer Rebecca, Kimmelman Jonathan, Kekre Natasha, El-Sayes Nader, Krishnan Ramya, Keller Brian A, Ilkow Carolina, Lalu Manoj M
Clinical Epidemiology Program, BLUEPRINT Translational Research Group, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.
Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Mol Ther Oncolytics. 2019 May 21;14:179-187. doi: 10.1016/j.omto.2019.05.004. eCollection 2019 Sep 27.
Irreproducibility of preclinical findings could be a significant barrier to the "bench-to-bedside" development of oncolytic viruses (OVs). A contributing factor is the incomplete and non-transparent reporting of study methodology and design. Using the NIH Principles and Guidelines for Reporting Preclinical Research, a core set of seven recommendations, we evaluated the completeness of reporting of preclinical OV studies. We also developed an evidence map identifying the current trends in OV research. A systematic search of MEDLINE and Embase identified all relevant articles published over an 18 month period. We screened 1,554 articles, and 236 met our -defined inclusion criteria. Adenovirus (43%) was the most commonly used viral platform. Frequently investigated cancers included colorectal (14%), skin (12%), and breast (11%). Xenograft implantation (61%) in mice (96%) was the most common animal model. The use of preclinical reporting guidelines was listed in 0.4% of articles. Biological and technical replicates were completely reported in 1% of studies, statistics in 49%, randomization in 1%, blinding in 2%, sample size estimation in 0%, and inclusion/exclusion criteria in 0%. Overall, completeness of reporting in the preclinical OV therapy literature is poor. This may hinder efforts to interpret, replicate, and ultimately translate promising preclinical OV findings.
临床前研究结果的不可重复性可能是溶瘤病毒(OVs)“从 bench 到 bedside”发展的重大障碍。一个促成因素是研究方法和设计的报告不完整且不透明。我们依据美国国立卫生研究院(NIH)的临床前研究报告原则和指南(一套包含七项建议的核心内容),评估了临床前 OV 研究报告的完整性。我们还绘制了一张证据图谱,以确定 OV 研究的当前趋势。通过对 MEDLINE 和 Embase 进行系统检索,找出了在 18 个月期间发表的所有相关文章。我们筛选了 1554 篇文章,其中 236 篇符合我们定义的纳入标准。腺病毒(43%)是最常用的病毒载体。经常研究的癌症包括结直肠癌(14%)、皮肤癌(12%)和乳腺癌(11%)。小鼠异种移植植入(61%)(96%的研究使用小鼠)是最常见的动物模型。仅 0.4%的文章列出了使用临床前报告指南的情况。1%的研究完整报告了生物学和技术重复,49%报告了统计学内容,1%报告了随机分组,2%报告了盲法,0%报告了样本量估计,0%报告了纳入/排除标准。总体而言,临床前 OV 治疗文献的报告完整性较差。这可能会阻碍对有前景的临床前 OV 研究结果进行解读、重复以及最终转化应用的努力。