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Abstract：
Neurofibromatosis (NF) is the umbrella term for neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2) and schwannomatosis (SWN). EU-PEARL aims to create a framework for platform trials in NF. The aim of this systematic review is to create an overview of recent clinical drug trials in NF, to identify learning points to guide development of the framework. We searched Embase, Medline and Cochrane register of trials on October 1, 2020 for publications of clinical drug trials in NF patients. We excluded publications published before 2010, systematic reviews, secondary analyses and studies with <10 patients. Data was extracted on manifestations studied, study design, phase, number of participating centres and population size. Full-text review resulted in 42 articles: 31 for NF1, 11 for NF2, none for SWN. Most NF1 trials focused on plexiform neurofibromas (32%). Trials in NF2 solely studied vestibular schwannomas. In NF1, single-arm trials (58%) were most common, and the majority was phase II (74%). For NF2 most trials were single-arm (55%) and exclusively phase II. For both diseases, trials were predominantly single-country and included five centres or less. Study population sizes were small, with the majority including ≤50 patients (74%). In conclusion, NF research is dominated by studies on a limited number out of the wide range of manifestations. We need more trials for cutaneous manifestations and high-grade gliomas in NF1, manifestations other than vestibular schwannoma in NF2 and trials for SWN. Drug development in NF may profit from innovative trials on multiple interventions and increased international collaboration.
摘要：
神经纤维瘤病（NF）是1型神经纤维瘤病（NF1）的总称，2型神经纤维瘤病（NF2）和神经鞘瘤病（SWN）。EU-PEARL旨在为NF平台试验创建一个框架。本系统综述的目的是对NF，确定学习点以指导框架的开发。我们搜查了Embase,Medline和Cochrane于2020年10月1日注册了NF患者临床药物试验的出版物。我们排除了2010年之前出版的出版物，系统评价，对<10例患者进行二次分析和研究。数据是根据所研究的表现提取的，研究设计，阶段,参与中心的数量和人口规模。全文共42篇：NF1为31篇，NF2为11篇，SWN为无。大多数NF1试验集中在丛状神经纤维瘤(32%)。NF2的试验仅研究前庭神经鞘瘤。在NF1中，单臂试验(58%)最常见，大多数是第二阶段(74%)。对于NF2，大多数试验是单臂(55%)，完全是II期。对于这两种疾病，试验主要是单一国家,包括5个或更少中心.研究人群规模很小，大多数包括≤50名患者（74%）。总之,NF研究主要是对有限数量的广泛表现进行研究。我们需要更多关于NF1的皮肤表现和高级别神经胶质瘤，NF2的前庭神经鞘瘤以外的表现和SWN的试验。NF中的药物开发可能受益于多种干预措施的创新试验和增加的国际合作。
