Sean M. Healey and AMG Center for ALS & the Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Muscle Nerve. 2023 Jun;67(6):456-463. doi: 10.1002/mus.27819. Epub 2023 Apr 5.
INTRODUCTION/AIMS: Expanded access protocols (EAPs) are a Food and Drug Administration (FDA)-regulated pathway for granting access to investigational products (IPs) to individuals with serious diseases who are ineligible for clinical trials. There is limited information about the use of EAPs in amyotrophic lateral sclerosis (ALS); the aim of this report is to share the design, operational features, and costs of an EAP program for ALS.
The program was launched in 2018 at a single center. In alignment with FDA guidance, protocols were designed as individual (single participant) or intermediate size. Inclusion criteria were broad (e.g., no restrictions due to long disease duration or low vital capacity). Safety information was collected in all EAPs. Selected biomarkers were collected in nine of the EAPs.
From July 2018 through February 2022, 17 EAPs were submitted for FDA and institutional review board (IRB) approval. The mean time from submission to approval from the FDA and IRB were 24 days and 37 days, respectively. A total of 164 participants were enrolled and, of these, 77 participants were still receiving IP as of February 2022. The mean duration of participation in an EAP was 12.6 mo. No drug-related serious adverse events were reported from any of the EAPs. Average site cost was $613.47 per participant per month, not including IP costs.
EAPs provide a framework through which access to IP can be safely provided to people with ALS who do not qualify for clinical trials. Site resources are needed to launch and maintain these programs.
介绍/目的：扩大准入方案（EAPs）是食品和药物管理局（FDA）监管的一种途径，旨在向不符合临床试验条件的患有严重疾病的个体提供研究性产品（IP）。关于肌萎缩侧索硬化症（ALS）中使用 EAP 的信息有限；本报告的目的是分享 ALS 的 EAP 计划的设计、运营特点和成本。
该计划于 2018 年在一个单一中心启动。根据 FDA 的指导原则，方案设计为个体（单个参与者）或中等规模。纳入标准很宽泛（例如，由于疾病持续时间长或肺活量低，没有限制）。所有 EAP 均收集安全性信息。在 9 个 EAP 中收集了选定的生物标志物。
从 2018 年 7 月到 2022 年 2 月，提交了 17 个 EAP 以获得 FDA 和机构审查委员会（IRB）的批准。从提交到 FDA 和 IRB 批准的平均时间分别为 24 天和 37 天。共招募了 164 名参与者，截至 2022 年 2 月，仍有 77 名参与者正在接受 IP。EAP 参与的平均持续时间为 12.6 个月。从任何 EAP 中均未报告与药物相关的严重不良事件。每个参与者每月的平均站点成本为 613.47 美元，不包括 IP 成本。
EAP 为向不符合临床试验条件的 ALS 患者提供 IP 提供了一个安全的框架。需要站点资源来启动和维持这些计划。
