Data from: 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 quality was low and the type of gene therapy did not account for differences in outcome. Study design characteristics accounted for a significant proportion of between-study heterogeneity. We observed similar findings in a data subset limited to the most common gene therapy. Conclusion: As the dysregulation of key molecular pathways is characteristic of gliomas, gene therapy remains a promising treatment for glioma. Nevertheless, we have identified areas for improvement in conduct and reporting of studies, and we provide a basis for sample size calculations. Further work should focus on genes of interest in paradigms recapitulating human disease. This might improve the translation of such therapies into the clinic.

背景：治疗疗法的研发通常以"颇具前景的动物实验结果却无法转化为临床疗效"为典型特征，胶质瘤（glioma）基因治疗（gene therapy）的研发亦属此列。我们提出如下假说：该现象的成因，在于报告实验性胶质瘤基因治疗应用的相关研究，其内部效度（internal validity）与外部效度（external validity）均存在局限。
方法：我们通过检索3个在线数据库，系统筛选了在啮齿类动物胶质瘤模型（rodent glioma models）中测试基因治疗效果的研究。提取受试动物数量与中位生存期（median survival）数据，并采用质量检查表（quality checklist）对纳入研究进行质量评分。我们计算了中位生存期比值（median survival ratios），并使用随机效应荟萃分析（random effects meta-analysis）评估治疗疗效。随后探讨了研究设计与研究质量对结果的影响，并检索了发表偏倚（publication bias）的相关证据。
结果：我们共纳入193项实验性胶质瘤基因治疗相关研究，涉及受试动物6366只。整体而言，基因治疗可使受试动物的中位生存期提升至1.60倍（95%置信区间（Confidence Interval，CI）：1.53~1.67）。纳入研究的整体质量偏低，且不同类型的基因治疗并未导致疗效结果出现显著差异。研究设计特征可解释研究间异质性的显著比例。在限定于最常见基因治疗类型的子数据集分析中，我们得到了一致的研究结果。
结论：鉴于关键分子通路失调是胶质瘤的典型病理特征，基因治疗仍是颇具前景的胶质瘤治疗手段。不过，我们也发现当前研究在实施与报告环节存在诸多可改进之处，并为样本量计算（sample size calculations）提供了参考依据。未来研究应聚焦于可重现人类疾病特征的实验范式中所关注的基因靶点，这或将有效推动此类疗法向临床应用的转化。