Edward Tobinick, Danielle Ucci, Kirsten Bermudo, Samantha Asseraf
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引用次数: 0
Abstract
Introduction: 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.
Areas covered: Scientific background and essential elements of PSE RCT design.
Expert opinion: 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.
简介脑膜外依那普利（PSE）是一种创新疗法，旨在通过治疗中风后的慢性神经炎症来改善中风的恢复。基础科学证据、随机临床试验（RCT）证据和 14 年的良好临床经验都支持使用 PSE 治疗慢性中风。本文根据目前美国食品药品管理局的建议，为未来 PSE RCT 的设计提供指导：科学背景和 PSE RCT 设计的基本要素：专家观点：设计未来 PSE 中风试验的人员必须熟悉 PSE、其新颖的给药方法以及理想的富集研究人群的特征。使 PSE RCT 产生有效结果所需的设计要素包括：合适的研究问题；采用前瞻性增量策略选择的同质研究人群；与 PSE 带来的神经系统改善相适应的主要结果测量指标；在围手术期给药方面具有专长的试验人员；最佳的依那西普剂量；以及为尽量减少安慰剂应答者数量而采取的措施。未纳入这些要素的 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，因此不适合用作 PSE RCT 的主要结果测量指标。
期刊介绍：
Expert Opinion on Biological Therapy (1471-2598; 1744-7682) is a MEDLINE-indexed, international journal publishing peer-reviewed research across all aspects of biological therapy.
Each article is structured to incorporate the author’s own expert opinion on the impact of the topic on research and clinical practice and the scope for future development.
The audience consists of scientists and managers in the healthcare and biopharmaceutical industries and others closely involved in the development and application of biological therapies for the treatment of human disease.
The journal welcomes:
Reviews covering therapeutic antibodies and vaccines, peptides and proteins, gene therapies and gene transfer technologies, cell-based therapies and regenerative medicine
Drug evaluations reviewing the clinical data on a particular biological agent
Original research papers reporting the results of clinical investigations on biological agents and biotherapeutic-based studies with a strong link to clinical practice
Comprehensive coverage in each review is complemented by the unique Expert Collection format and includes the following sections:
Expert Opinion – a personal view of the data presented in the article, a discussion on the developments that are likely to be important in the future, and the avenues of research likely to become exciting as further studies yield more detailed results;
Article Highlights – an executive summary of the author’s most critical points.
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