A systematic review and meta-analysis of gene therapy in animal models of cerebral glioma: why did promise not translate to human therapy?

Background: The development of therapeutics is often characterized by promising animal research that fails to translate into clinical efficacy; this holds for the development of gene therapy in glioma. We tested the hypothesis that this is because of limitations in the internal and external validity of studies reporting the use of gene therapy in experimental glioma. Method: We systematically identified studies testing gene therapy in rodent glioma models by searching three online databases. The number of animals treated and median survival were extracted and studies graded using a quality checklist. We calculated median survival ratios and used random effects meta-analysis to estimate efficacy. We explored effects of study design and quality and searched for evidence of publication bias. Results: We identified 193 publications using gene therapy in experimental glioma, including 6,366 animals. Overall, gene therapy improved median survival by a factor of 1.60 (95% CI 1.53–1.67). Study ...

研究背景：治疗药物的研发常以颇具前景却无法转化为临床疗效的动物实验为典型特征，神经胶质瘤（glioma）的基因治疗（gene therapy）研发亦如是。本研究验证了相关假说：即报道实验性神经胶质瘤基因治疗应用的相关研究，其内部效度与外部效度均存在局限。研究方法：本研究通过检索3个在线数据库，系统筛选针对啮齿类神经胶质瘤模型开展基因治疗实验的相关研究。提取受试动物数量与中位生存期数据，并采用质量检查表对纳入研究进行质量评级。本研究计算中位生存期比值，并采用随机效应meta分析评估治疗疗效，同时探究研究设计与研究质量的影响，并检索发表偏倚的相关证据。研究结果：本研究共筛选得到193篇针对实验性神经胶质瘤开展基因治疗的文献，涉及受试动物共计6366只。整体而言，基因治疗可使受试动物的中位生存期提升1.60倍（95%置信区间：1.53~1.67）。研究...