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

Timo Sander; Joly Ghanawi; Emma Wilson; Sajjad Muhammad; Malcolm Macleod; Ulf Dietrich Kahlert

doi:10.1136/bmjos-2021-100272

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

BMJ Open Sci. 2022 Jun 1;6(1):e100272. doi: 10.1136/bmjos-2021-100272. eCollection 2022.

Authors

Timo Sander¹, Joly Ghanawi², Emma Wilson³, Sajjad Muhammad¹, Malcolm Macleod³, Ulf Dietrich Kahlert⁴

Affiliations

¹ Department of Neurosurgery, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
² Independent researcher, Edinburgh, UK.
³ Centre for Clinical Brain Sciences, The University of Edinburgh Medical School, Edinburgh, UK.
⁴ Department of Molecular and Experimental Surgery, Clinic for General, Visceral, Vascular and Transplant Surgery, Otto von Guericke Universität Magdeburg, Magdeburg, Germany.

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).

Keywords: Biomedical Research; Cell Proliferation; Translational Medical Research.