Center for Biomarker Discovery, Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
Cancer Epidemiol Biomarkers Prev. 2010 Dec;19(12):2995-9. doi: 10.1158/1055-9965.EPI-10-0580. Epub 2010 Oct 20.
After more than a decade of biomarker discovery research using advanced genomic and proteomic technologies, very few biomarkers have been translated into clinical diagnostics for patient care. This has become an urgent issue to be addressed because the continuing funding from both the public and private sources are called into question.
We use as an example, OVA1, the first in vitro diagnostic multivariate index assay (IVDMIA) of proteomic biomarkers recently cleared by the US FDA (Food and Drug Administration) to describe our experience through the long road from biomarker discovery, to validation, and finally to multi-institutional trial for regulatory approval by the FDA.
We discuss 3 issues that are key bridges in the path of biomarker development to actual clinical diagnostics: 1) to generate sufficient and "portable" evidence in preliminary validation studies to support investment for large-scale validation trials; 2) to carefully and clearly define clinical utility that balances desire for broad applicability and feasibility for completing clinical trials for regulatory approval; and 3) to select/develop assays with analytical performance suitable for clinical deployment.
We learned that the road from biomarker discovery, validation, to clinical diagnostics could be long and winding, and often frustrating. However, we also know that, with the right approaches, at the end of the road, there is a rainbow waiting for us.
Provide insights and recommendations for the translation of proteomic biomarkers into clinical diagnostics.
经过十多年使用先进基因组学和蛋白质组学技术的生物标志物发现研究，只有极少数生物标志物被转化为用于患者护理的临床诊断。这已经成为一个亟待解决的问题，因为公共和私人资金的持续投入受到质疑。
我们以 OVA1 为例，这是最近获得美国食品和药物管理局（FDA）批准的首个体外诊断多变量指数分析（IVDMIA）蛋白质组生物标志物，描述了我们从生物标志物发现到验证，最终到 FDA 监管批准的多机构试验的漫长道路上的经验。
我们讨论了在生物标志物开发到实际临床诊断的路径中的 3 个关键桥梁问题：1）在初步验证研究中生成足够和“可移植”的证据，以支持大规模验证试验的投资；2）仔细和明确定义临床效用，平衡广泛适用性的愿望和完成监管批准临床试验的可行性；3）选择/开发具有适合临床部署的分析性能的测定法。
我们了解到，从生物标志物发现、验证到临床诊断的道路可能漫长而曲折，常常令人沮丧。然而，我们也知道，只要采取正确的方法，在道路的尽头，就会有彩虹在等待着我们。
为蛋白质组生物标志物转化为临床诊断提供见解和建议。
