Ahmad Tariq, Fiuzat Mona, Pencina Michael J, Geller Nancy L, Zannad Faiez, Cleland John G F, Snider James V, Blankenberg Stephan, Adams Kirkwood F, Redberg Rita F, Kim Jae B, Mascette Alice, Mentz Robert J, O'Connor Christopher M, Felker G Michael, Januzzi James L
Division of Cardiology, Duke University Medical Center, Durham, North Carolina; Duke Clinical Research Institute, Durham, North Carolina.
Division of Cardiology, Duke University Medical Center, Durham, North Carolina.
JACC Heart Fail. 2014 Oct;2(5):477-88. doi: 10.1016/j.jchf.2014.02.005. Epub 2014 Jun 11.
Heart failure is a syndrome with a pathophysiological basis that can be traced to dysfunction in several interconnected molecular pathways. Identification of biomarkers of heart failure that allow measurement of the disease on a molecular level has resulted in enthusiasm for their use in prognostication and selection of appropriate therapies. However, despite considerable amounts of information available on numerous biomarkers, inconsistent research methodologies and lack of clinical correlations have made bench-to-bedside translations rare and left the literature with countless publications of varied quality. There is a need for a systematic and collaborative approach aimed at definitively studying the clinical benefits of novel biomarkers. In this review, on the basis of input from academia, industry, and governmental agencies, we propose a systematized approach based on adherence to specific quality measures for studies looking to augment current prediction model or use biomarkers to tailor therapeutics. We suggest that study quality, rather than results, should determine publication and propose a system for grading biomarker studies. We outline the need for collaboration between clinical investigators and statisticians to introduce more advanced statistical methodologies into the field of biomarkers that would allow for data from a large number of variables to be distilled into clinically actionable information. Lastly, we propose the creation of a heart failure biomarker consortium that would allow for a comprehensive list of biomarkers to be concomitantly analyzed in a pooled sample of randomized clinical trials and hypotheses to be generated for testing in biomarker-guided trials. Such a consortium could collaborate in sharing samples to identify biomarkers, undertake meta-analyses on completed trials, and spearhead clinical trials to test the clinical utility of new biomarkers.
心力衰竭是一种具有病理生理基础的综合征,其可追溯至多个相互关联的分子途径功能障碍。能够在分子水平上对心力衰竭进行测量的生物标志物的识别,引发了人们对将其用于预后评估和选择合适治疗方法的热情。然而,尽管有大量关于众多生物标志物的信息,但研究方法不一致以及缺乏临床相关性,使得从实验室到临床的转化很少见,并且文献中充斥着大量质量参差不齐的出版物。需要一种系统且协作的方法来明确研究新型生物标志物的临床益处。在本综述中,基于学术界、产业界和政府机构的意见,我们针对旨在增强当前预测模型或使用生物标志物来定制治疗方案的研究,提出一种基于遵循特定质量标准的系统化方法。我们建议研究质量而非结果应决定论文发表,并提出一种生物标志物研究分级系统。我们概述了临床研究人员和统计学家之间开展合作的必要性,以便将更先进的统计方法引入生物标志物领域,从而能够将来自大量变量的数据提炼为具有临床可操作性的信息。最后,我们提议创建一个心力衰竭生物标志物联盟,该联盟能够在随机临床试验的汇总样本中同时分析一份全面的生物标志物清单,并生成假设以便在生物标志物引导的试验中进行检验。这样一个联盟可以在共享样本以识别生物标志物、对已完成的试验进行荟萃分析以及率先开展临床试验以测试新生物标志物的临床效用等方面开展合作。