Sander Timo, Ghanawi Joly, Wilson Emma, Muhammad Sajjad, Macleod Malcolm, Kahlert Ulf Dietrich
Department of Neurosurgery, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
Independent researcher, Edinburgh, UK.
BMJ Open Sci. 2022 Jun 1;6(1):e100272. doi: 10.1136/bmjos-2021-100272. eCollection 2022.
Heterogeneity of results of exact same research experiments oppose a significant socioeconomic burden. Insufficient methodological reporting is likely to be one of the contributors to results heterogeneity; however, little knowledge on reporting habits of in vitro cancer research and their effects on results reproducibility is available. Exemplified by a commonly performed in vitro assay, we aim to fill this knowledge gap and to derive recommendations necessary for reproducible, robust and translational preclinical science.
Here, we use systematic review to describe reporting practices in in vitro glioblastoma research using the Uppsala-87 Malignant Glioma (U-87 MG) cell line and perform multilevel random-effects meta-analysis followed by meta-regression to explore sources of heterogeneity within that literature, and any associations between reporting characteristics and reported findings. Literature that includes experiments measuring the effect of temozolomide on the viability of U-87 MG cells is searched on three databases (Embase, PubMed and Web of Science).
In 137 identified articles, the methodological reporting is incomplete, for example, medium glucose level and cell density are reported in only 21.2% and 16.8% of the articles. After adjustments for different drug concentrations and treatment durations, the results heterogeneity across the studies (I=68.5%) is concerningly large. Differences in culture medium glucose level are a driver of this heterogeneity. However, infrequent reporting of most experimental parameters limits the analysis of reproducibility moderating parameters.
Our results further support the ongoing efforts of establishing consensus reporting practices to elevate durability of results. By doing so, this work can raise awareness of how stricter reporting may help to improve the frequency of successful translation of preclinical results into human application. The authors received no specific funding for this work. A preregistered protocol is available at the Open Science Framework (https://osf.io/9k3dq).
完全相同的研究实验结果的异质性带来了巨大的社会经济负担。方法学报告不足可能是导致结果异质性的原因之一；然而，关于体外癌症研究的报告习惯及其对结果可重复性的影响，我们知之甚少。以一种常用的体外试验为例，我们旨在填补这一知识空白，并得出可重复、稳健且具有转化性的临床前科学所需的建议。
在此，我们采用系统评价来描述使用乌普萨拉87型恶性胶质瘤（U - 87 MG）细胞系进行的体外胶质母细胞瘤研究中的报告实践，并进行多层次随机效应荟萃分析，随后进行荟萃回归，以探索该文献中的异质性来源，以及报告特征与报告结果之间的任何关联。在三个数据库（Embase、PubMed和Web of Science）中搜索包含测量替莫唑胺对U - 87 MG细胞活力影响的实验的文献。
在137篇已识别的文章中，方法学报告不完整，例如，仅分别有21.2%和16.8%的文章报告了培养基葡萄糖水平和细胞密度。在对不同药物浓度和治疗持续时间进行调整后，各研究间的结果异质性（I = 68.5%）大得惊人。培养基葡萄糖水平的差异是这种异质性的一个驱动因素。然而，大多数实验参数报告不频繁，限制了对可重复性调节参数的分析。
我们的结果进一步支持了正在进行的建立共识报告实践以提高结果耐久性的努力。通过这样做，这项工作可以提高人们对更严格的报告如何有助于提高临床前结果成功转化为人类应用频率的认识。作者未获得此项工作的特定资金。在开放科学框架（https://osf.io/9k3dq）上可获取预注册方案。
