Beierlein Jennifer M, McNamee Laura M, Walsh Michael J, Kaitin Kenneth I, DiMasi Joseph A, Ledley Fred D
Center for Integration of Science and Industry, Department of Natural & Applied Sciences, Bentley University, Waltham, Massachusetts.
Tufts Center for the Study of Drug Development, Tufts University School of Medicine, Boston, Massachusetts.
Clin Ther. 2017 Jul;39(7):1409-1425.e20. doi: 10.1016/j.clinthera.2017.06.001. Epub 2017 Jun 23.
This study examines the complete timelines of translational science for new cardiovascular therapeutics from the initiation of basic research leading to identification of new drug targets through clinical development and US Food and Drug Administration (FDA) approval of new molecular entities (NMEs) based on this research.
This work extends previous studies by examining the association between the growth of research on drug targets and approval of NMEs associated with these targets. Drawing on research on innovation in other technology sectors, where technological maturity is an important determinant in the success or failure of new product development, an analytical model was used to characterize the growth of research related to the known targets for all 168 approved cardiovascular therapeutics.
Categorizing and mapping the technological maturity of cardiovascular therapeutics reveal that (1) there has been a distinct transition from phenotypic to targeted methods for drug discovery, (2) the durations of clinical and regulatory processes were significantly influenced by changes in FDA practice, and (3) the longest phase of the translational process was the time required for technology to advance from initiation of research to a statistically defined established point of technology maturation (mean, 30.8 years).
This work reveals a normative association between metrics of research maturation and approval of new cardiovascular therapeutics and suggests strategies for advancing translational science by accelerating basic and applied research and improving the synchrony between the maturation of this research and drug development initiatives.
本研究考察了新型心血管治疗药物转化科学的完整时间线，从基础研究启动，到确定新的药物靶点，再到临床开发以及美国食品药品监督管理局（FDA）基于该研究批准新分子实体（NME）。
本研究通过考察药物靶点研究的增长与与这些靶点相关的NME批准之间的关联，扩展了先前的研究。借鉴其他技术领域的创新研究，在这些领域中技术成熟度是新产品开发成败的重要决定因素，使用一种分析模型来描述与所有168种已批准的心血管治疗药物的已知靶点相关的研究增长情况。
对心血管治疗药物的技术成熟度进行分类和映射显示，（1）药物发现方法已从表型方法向靶向方法发生了明显转变，（2）临床和监管过程的持续时间受到FDA实践变化的显著影响，（3）转化过程中最长的阶段是技术从研究启动发展到统计学定义的既定技术成熟点所需的时间（平均30.8年）。
这项工作揭示了研究成熟度指标与新型心血管治疗药物批准之间的规范关联，并提出了通过加速基础研究和应用研究以及改善该研究的成熟度与药物开发计划之间的同步性来推进转化科学的策略。
