Trusheim M R, Shrier A A, Antonijevic Z, Beckman R A, Campbell R K, Chen C, Flaherty K T, Loewy J, Lacombe D, Madhavan S, Selker H P, Esserman L J
MIT, Center for Biomedical Innovation, Cambridge, Massachusetts, USA.
Riptide Management, Cambridge, Massachusetts, USA.
Clin Pharmacol Ther. 2016 Dec;100(6):713-729. doi: 10.1002/cpt.514. Epub 2016 Oct 19.
Adaptive, seamless, multisponsor, multitherapy clinical trial designs executed as large scale platforms, could create superior evidence more efficiently than single-sponsor, single-drug trials. These trial PIPELINEs also could diminish barriers to trial participation, increase the representation of real-world populations, and create systematic evidence development for learning throughout a therapeutic life cycle, to continually refine its use. Comparable evidence could arise from multiarm design, shared comparator arms, and standardized endpoints-aiding sponsors in demonstrating the distinct value of their innovative medicines; facilitating providers and patients in selecting the most appropriate treatments; assisting regulators in efficacy and safety determinations; helping payers make coverage and reimbursement decisions; and spurring scientists with translational insights. Reduced trial times and costs could enable more indications, reduced development cycle times, and improved system financial sustainability. Challenges to overcome range from statistical to operational to collaborative governance and data exchange.
作为大规模平台执行的适应性、无缝、多申办方、多疗法临床试验设计,可能比单申办方、单药物试验更有效地产生更优质的证据。这些试验流程还可以减少试验参与的障碍,增加真实世界人群的代表性,并在整个治疗生命周期中创建系统性的证据开发,以不断完善其应用。多臂设计、共享对照臂和标准化终点可能产生可比的证据,有助于申办方证明其创新药物的独特价值;帮助医疗服务提供者和患者选择最合适的治疗方法;协助监管机构进行疗效和安全性判定;帮助支付方做出覆盖范围和报销决定;并激发科学家获得转化见解。缩短试验时间和成本可以带来更多适应症、缩短开发周期,并提高系统的财务可持续性。需要克服的挑战涵盖从统计到运营,再到协作治理和数据交换等各个方面。