Clinical Epidemiology Program, Blueprint Translational Research Group, Ottawa Hospital Research Institute, Ottawa, Canada.
Telfer School of Management, University of Ottawa, Ottawa, Canada.
Elife. 2023 Mar 9;12:e76300. doi: 10.7554/eLife.76300.
Multicentric approaches are widely used in clinical trials to assess the generalizability of findings, however, they are novel in laboratory-based experimentation. It is unclear how multilaboratory studies may differ in conduct and results from single lab studies. Here, we synthesized the characteristics of these studies and quantitatively compared their outcomes to those generated by single laboratory studies.
MEDLINE and Embase were systematically searched. Screening and data extractions were completed in duplicate by independent reviewers. Multilaboratory studies investigating interventions using in vivo animal models were included. Study characteristics were extracted. Systematic searches were then performed to identify single lab studies matched by intervention and disease. Difference in standardized mean differences (DSMD) was then calculated across studies to assess differences in effect estimates based on study design (>0 indicates larger effects in single lab studies).
Sixteen multilaboratory studies met inclusion criteria and were matched to 100 single lab studies. The multicenter study design was applied across a diverse range of diseases, including stroke, traumatic brain injury, myocardial infarction, and diabetes. The median number of centers was four (range 2-6) and the median sample size was 111 (range 23-384) with rodents most frequently used. Multilaboratory studies adhered to practices that reduce the risk of bias significantly more often than single lab studies. Multilaboratory studies also demonstrated significantly smaller effect sizes than single lab studies (DSMD 0.72 [95% confidence interval 0.43-1]).
Multilaboratory studies demonstrate trends that have been well recognized in clinical research (i.e. smaller treatment effects with multicentric evaluation and greater rigor in study design). This approach may provide a method to robustly assess interventions and the generalizability of findings between laboratories.
uOttawa Junior Clinical Research Chair; The Ottawa Hospital Anesthesia Alternate Funds Association; Canadian Anesthesia Research Foundation; Government of Ontario Queen Elizabeth II Graduate Scholarship in Science and Technology.
多中心方法广泛应用于临床试验,以评估研究结果的普遍性,然而,它们在基于实验室的实验中是新颖的。目前尚不清楚多实验室研究在实施和结果方面与单一实验室研究有何不同。在这里,我们综合了这些研究的特点,并定量比较了它们的结果与单一实验室研究的结果。
系统地检索了 MEDLINE 和 Embase。由两名独立审查员进行筛选和数据提取。纳入了使用体内动物模型进行干预的多中心研究。提取了研究特征。然后进行了系统搜索,以确定通过干预和疾病相匹配的单一实验室研究。然后计算标准化均数差(DSMD)在研究之间的差异,以评估基于研究设计的效应估计值的差异(>0 表示单一实验室研究中的效应较大)。
16 项多中心研究符合纳入标准,并与 100 项单一实验室研究相匹配。该多中心研究设计应用于多种疾病,包括中风、创伤性脑损伤、心肌梗死和糖尿病。中心数量中位数为 4(范围 2-6),样本量中位数为 111(范围 23-384),最常使用啮齿动物。多中心研究遵循的实践显著降低了偏倚风险的频率高于单一实验室研究。多中心研究还显示出比单一实验室研究小得多的效应量(DSMD 0.72 [95%置信区间 0.43-1])。
多中心研究显示出了在临床研究中已经得到很好认识的趋势(即多中心评估的治疗效果较小,研究设计更严谨)。这种方法可能为评估实验室之间的干预措施和研究结果的普遍性提供一种方法。
渥太华大学初级临床研究主席;渥太华医院麻醉替代基金协会;加拿大麻醉研究基金会;安大略省政府伊丽莎白二世研究生科学和技术奖学金。