Institute of Neurological Recovery, Boca Raton, FL, USA.
Expert Opin Biol Ther. 2024 Oct;24(10):1095-1108. doi: 10.1080/14712598.2024.2390636. Epub 2024 Aug 23.
Perispinal etanercept (PSE) is an innovative treatment designed to improve stroke recovery by addressing chronic post-stroke neuroinflammation. Basic science evidence, randomized clinical trial (RCT) evidence and 14 years of favorable clinical experience support the use of PSE to treat chronic stroke. This article provides guidance for the design of future PSE RCTs in accordance with current FDA recommendations.
Scientific background and essential elements of PSE RCT design.
Intimate familiarity with PSE, its novel method of drug delivery, and the characteristics of ideal enriched study populations are necessary for those designing future PSE stroke trials. The design elements needed to enable a PSE RCT to generate valid results include a suitable research question; a homogeneous study population selected using a prospective enrichment strategy; a primary outcome measure responsive to the neurological improvements that result from PSE; trialists with expertise in perispinal delivery; optimal etanercept dosing; and steps taken to minimize the number of placebo responders. RCTs failing to incorporate these elements, such as the PESTO trial, are incapable of reaching reliable conclusions regarding PSE efficacy. SF-36 has not been validated in PSE trials and is unsuitable for use as a primary outcome measure in PSE RCTs.
鞘内注射依那西普（PSE）是一种创新的治疗方法，旨在通过解决慢性卒中后神经炎症来改善卒中康复。基础科学证据、随机临床试验（RCT）证据和 14 年的良好临床经验支持使用 PSE 治疗慢性卒中。本文根据当前 FDA 的建议，为未来的 PSE RCT 设计提供了指导。
PSE RCT 设计的科学背景和基本要素。
对于设计未来 PSE 卒中试验的人员来说，需要对 PSE 及其新型药物输送方法以及理想的富集研究人群的特征有深入的了解。能够产生有效结果的 PSE RCT 设计要素包括：合适的研究问题；使用前瞻性富集策略选择的同质研究人群；对 PSE 带来的神经改善有反应的主要结局测量指标；在鞘内给药方面具有专业知识的试验人员；最佳依那西普剂量；以及采取措施尽量减少安慰剂反应者的数量。未能纳入这些要素的 RCT，如 PESTO 试验，无法就 PSE 的疗效得出可靠的结论。SF-36 尚未在 PSE 试验中得到验证，不适合作为 PSE RCT 的主要结局测量指标。
