Iorio Emma G, Khanteymoori Alireza, Fond Kenneth A, Keller Anastasia V, Davis Lex Maliga, Schwab Jan M, Ferguson Adam R, Torres-Espin Abel, Watzlawick Ralf
Department of Neurological Surgery, University of California, San Francisco, California, USA.
Department of Neurosurgery, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Neurotrauma Rep. 2024 Jul 16;5(1):686-698. doi: 10.1089/neur.2024.0038. eCollection 2024.
Translation of spinal cord injury (SCI) therapeutics from pre-clinical animal studies into human studies is challenged by effect size variability, irreproducibility, and misalignment of evidence used by pre-clinical versus clinical literature. Clinical literature values reproducibility, with the highest grade evidence (class 1) consisting of meta-analysis demonstrating large therapeutic efficacy replicating across multiple studies. Conversely, pre-clinical literature values novelty over replication and lacks rigorous meta-analyses to assess reproducibility of effect sizes across multiple articles. Here, we applied modified clinical meta-analysis methods to pre-clinical studies, comparing effect sizes extracted from published literature to raw data on individual animals from these same studies. Literature-extracted data (LED) from numerical and graphical outcomes reported in publications were compared with individual animal data (IAD) deposited in a federally supported repository of SCI data. The animal groups from the IAD were matched with the same cohorts in the LED for a direct comparison. We applied random-effects meta-analysis to evaluate predictors of neuroconversion in LED versus IAD. We included publications with common injury models (contusive injuries) and standardized end-points (open field assessments). The extraction of data from 25 published articles yielded = 1841 subjects, whereas IAD from these same articles included = 2441 subjects. We observed differences in the number of experimental groups and animals per group, insufficient reporting of dropout animals, and missing information on experimental details. Meta-analysis revealed differences in effect sizes across LED versus IAD stratifications, for instance, severe injuries had the largest effect size in LED (standardized mean difference [SMD = 4.92]), but mild injuries had the largest effect size in IAD (SMD = 6.06). Publications with smaller sample sizes yielded larger effect sizes, while studies with larger sample sizes had smaller effects. The results demonstrate the feasibility of combining IAD analysis with traditional LED meta-analysis to assess effect size reproducibility in SCI.
将脊髓损伤（SCI）治疗方法从临床前动物研究转化为人体研究面临着效应大小变异性、不可重复性以及临床前与临床文献所使用证据不一致等挑战。临床文献重视可重复性，最高等级的证据（1类）由荟萃分析组成，这些荟萃分析表明在多项研究中都能重复出现较大的治疗效果。相反，临床前文献更看重新颖性而非重复性，并且缺乏严格的荟萃分析来评估多篇文章中效应大小的可重复性。在此，我们将改良的临床荟萃分析方法应用于临床前研究，将从已发表文献中提取的效应大小与来自这些相同研究的个体动物原始数据进行比较。将出版物中报告的数值和图形结果的文献提取数据（LED）与存放在联邦支持的SCI数据存储库中的个体动物数据（IAD）进行比较。将IAD中的动物组与LED中的相同队列进行匹配以进行直接比较。我们应用随机效应荟萃分析来评估LED与IAD中神经转化的预测因素。我们纳入了具有常见损伤模型（挫伤性损伤）和标准化终点（旷场评估）的出版物。从25篇已发表文章中提取的数据产生了n = 1841个研究对象，而来自这些相同文章的IAD包括n = 2441个研究对象。我们观察到实验组数量和每组动物数量存在差异，对失访动物的报告不足，以及实验细节信息缺失。荟萃分析揭示了LED与IAD分层之间效应大小的差异，例如，严重损伤在LED中的效应大小最大（标准化平均差[SMD = 4.92]），但轻度损伤在IAD中的效应大小最大（SMD = 6.06）。样本量较小的出版物产生的效应大小较大，而样本量较大的研究效应较小。结果表明，将IAD分析与传统的LED荟萃分析相结合以评估SCI中效应大小的可重复性是可行的。
