Meta-analysis on reporting practices as a source of heterogeneity in in vitro cancer research.

Q1 Medicine BMJ Open Science Pub Date : 2022-06-01 eCollection Date: 2022-01-01 DOI:10.1136/bmjos-2021-100272
Timo Sander, Joly Ghanawi, Emma Wilson, Sajjad Muhammad, Malcolm Macleod, Ulf Dietrich Kahlert
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Abstract

Objectives: 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.

Methods: 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).

Results: 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 (I2=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.

Conclusions: 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).

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对作为体外癌症研究异质性来源的报告方法进行元分析。
目的:完全相同的研究实验结果的异质性会造成巨大的社会经济负担。方法学报告不足很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,目前却知之甚少。方法:在此,我们利用系统综述描述了使用乌普萨拉-87 恶性胶质瘤(U-87 MG)细胞系进行体外胶质母细胞瘤研究的报告习惯,并进行了多层次随机效应荟萃分析(multi-level random-effects meta-analysis),随后进行了元回归(meta-regression),以探索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。我们在三个数据库(Embase、PubMed 和 Web of Science)中检索了包含替莫唑胺对 U-87 MG 细胞活力影响实验的文献:结果:在已发现的 137 篇文章中,报告方法不完整,例如,仅有 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,各研究结果的异质性(I2=68.5%)之大令人担忧。培养基葡萄糖水平的差异是造成这种异质性的原因之一。然而,由于大多数实验参数的报告不频繁,限制了对可重复性调节参数的分析:我们的研究结果进一步支持了目前正在进行的建立共识报告实践的努力,以提高结果的持久性。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的频率的认识。作者在这项工作中没有获得任何特定资助。预注册协议可在开放科学框架 (https://osf.io/9k3dq) 上查阅。
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来源期刊
BMJ Open Science
BMJ Open Science Medicine-General Medicine
CiteScore
10.00
自引率
0.00%
发文量
9
审稿时长
31 weeks
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