Towards regulatory endorsement of drug development tools to promote the application of model-informed drug development in Duchenne muscular dystrophy
Towards regulatory endorsement of drug development tools to promote the application of model-informed drug development in Duchenne muscular dystrophy
复制标题
DOI：
10.1007/s10928-019-09642-7
复制
发表时间：
2019-10-01
影响因子：
2.5
通讯作者：
Romero, Klaus
中科院分区：
文献类型：
--
作者：
Conrado, Daniela J.;Larkindale, Jane;Romero, Klaus
罕见病的药物开发受到人口少和数据有限的挑战。这使得临床试验方案的开发变得困难，并导致潜在疗法是否有效的不确定性。使用数据标准来汇总来自多个来源的数据，并使用此类集成数据库来开发统计模型，可以为方案开发提供信息，并降低开发新疗法的风险。通过美国食品药品监督管理局和欧洲药品管理局规定的途径实现对此类模型的监管认可，允许药物开发界将此类工具用于规定的使用环境，而无需进一步讨论基础模型。Duchenne监管科学联盟（D-RSC）汇集了多个利益相关者，使用这种方法开发了Duchenne肌营养不良症的临床试验模拟工具。在这里，我们描述了D-RSC的工作，作为这种方法如何有效减少罕见疾病药物开发的不确定性的一个例子，从而更快地为患者提供有效的治疗。
Drug development for rare diseases is challenged by small populations and limited data. This makes development of clinical trial protocols difficult and contributes to the uncertainty around whether or not a potential therapy is efficacious. The use of data standards to aggregate data from multiple sources, and the use of such integrated databases to develop statistical models can inform protocol development and reduce the risks in developing new therapies. Achieving regulatory endorsement of such models through defined pathways at the US Food and Drug Administration and European Medicines Authority allows such tools to be used by the drug development community for defined contexts of use without further need for discussion of the underlying model(s). The Duchenne Regulatory Science Consortium (D-RSC) has brought together multiple stakeholders to develop a clinical trial simulation tool for Duchenne muscular dystrophy using such an approach. Here we describe the work of D-RSC as an example of how such an approach may be effective at reducing uncertainty in drug development for rare diseases, and thus bringing effective therapies to patients faster.