Peripheral nerve stimulation for amputee pain

摘要：目前提出的商业化准备试点(CRP)项目的目标是 为可植入系统(在第二阶段开发)的商业化做准备，该系统能够提供 新的周围神经刺激(PNS)疗法在治疗顽固性疼痛方面显示出高效的疗效。 大多数截肢者在以前的研究中(包括第一阶段)。在美国，大约有180万人。 每年约有18.5万人接受截肢。邮寄- 截肢疼痛的发生率很高(95%)，并经常导致进一步的残疾、抑郁和 生活质量的下降。现有的长期疼痛疗法长期效果不佳，而且价格昂贵。 (在美国，每年总计高达27亿至130亿美元)。 之前的第一阶段项目成功地证明了缓解截肢后疼痛的可行性 88%的受试者在临床测试期间使用周围神经刺激(PNS)的方法选择性地 使用远离神经的单个电极激活靶向纤维。在另一项为期两周的主场试验中 所有完成试验的受试者都经历了有临床意义的临时性经皮刺激 疼痛缓解(平均为76%)，同时接受24小时/天的刺激，证实疼痛缓解可以持续为 只要有刺激就行。第二阶段项目是一个早期开发的最后一年 植入式脉冲发生器(IPG)旨在提供新的PNS治疗长期治疗 截肢后疼痛减轻。该疗法被设计为使用灵活的自固定电极，以避免 需要开放手术和精确的导线放置，并最大限度地降低并发症(骨折和 迁移)以前限制了现有PNS系统的使用。这些风险通过IPG进一步降低 足够薄，可以放置在残肢中，消除了导线穿过髋关节的需要 避免经常导致现有商业系统故障的重复弯曲和弯曲。 拟议的中央应急计划项目是将该系统从早期阶段(第二阶段)推进到最后的后期阶段所必需的。 阶段(商业)设计，通过增强系统，使疼痛医生能够快速采用临床 植入工具(目标1)，以降低复杂性和对支持人员的需求，同时利用熟悉的 这些医生中的绝大多数人已经精通的程序性方法。该项目也是 需要从早期阶段推进系统生产(计划在第二阶段项目中用于 每个IPG由熟练的技术人员在时间密集的过程中制造)到后期开发 可持续的、质量受控的、符合良好制造规范(GMP)的大批量生产 实现成功的商业化。如果所有验证/确认测试都成功，则每个目标都被认为是成功的 都通过了。如果成功，最终产品将有潜力满足截肢者和他们的需求 在FDA批准后，医生通过一种商业上可行和可持续的疗法。

Abstract: The goal of the presently proposed Commercialization Readiness Pilot (CRP) Program project is to prepare for commercialization of an implantable system (developed in Phase II) that is capable of delivering a novel peripheral nerve stimulation (PNS) therapy shown to be highly effective in treating intractable pain in a majority of amputees in previous studies (including Phase I). Approximately 1.8 million individuals in the U.S. are living with an amputation, and about 185,000 individuals undergo an amputation each year. Post- amputation pain has a high incidence (95%) and frequently causes further disability, depression, and reductions in quality of life. Existing long-term pain therapies are inadequate long-term and are expensive (totaling up to $2.7-13 Billion/year in the U.S.). The previous Phase I project successfully demonstrated the feasibility of relieving post-amputation pain in 88% of subjects during in-clinic testing with a method of peripheral nerve stimulation (PNS) that selectively activates target fibers using a single electrode inserted remote from the nerve. In an additional 2-wk home trial of temporary percutaneous stimulation, all subjects that completed the trial experienced clinically significant pain relief (average=76%) while receiving 24hr/day stimulation, confirming that pain relief can be sustained as long as stimulation is delivered. The Phase II project is in the final year of the early-stage development of an implantable pulse generator (IPG) designed to be capable of delivering the novel PNS therapy long-term for post-amputation pain relief. The therapy is designed to use a flexible, self-anchoring electrode that avoids the need for open surgery and precise lead placement, and minimizes the risk of complications (fracture & migration) that previously limited use of existing PNS systems. These risks are further reduced by an IPG that is sufficiently thin to be placed in the residual limb, eliminating the need for the lead to cross the hip joint and avoiding the repeated flexing and bending that frequently causes failures with existing commercial systems. The proposed CRP project is needed to advance the system from an early stage (Phase II) to its final late- stage (commercial) design to enable rapid clinical adoption among pain physicians by enhancing the system implantation tools (Aim 1) to reduce complexity and the need for support staff, while leveraging a familiar procedural approach in which the vast majority of these physicians are already proficient. The project is also needed to advance system production from early-stage (intended in the Phase II project for low-volumes in which each IPG is manufactured by skilled technicians in a time-intensive process) to late-stage development of sustainable, quality controlled, high volume production in line with Good Manufacturing Practices (GMP) to enable successful commercialization. Each aim will be considered successful if all verification/validation tests are passed. If successful, the final product will have the potential to meet the needs of amputees and their physicians through a commercially viable and sustainable therapy following FDA approval.