Swiss Foundation for Research on Muscle Diseases, 2016 Cortaillod, Switzerland.
John Walton Muscular Dystrophy Research Centre, Centre for Life, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne NE7 7DN, UK.
Dis Model Mech. 2020 Feb 7;13(2):dmm042903. doi: 10.1242/dmm.042903.
Clinical trials for rare neuromuscular diseases imply, among other investments, a high emotional burden for the whole disease community. Translation of data from preclinical studies to justify any clinical trial must be carefully pondered in order to minimize the risk of clinical trial withdrawal or failure. A rigorous distinction between proof-of-concept and preclinical efficacy studies using animal models is key to support the rationale of a clinical trial involving patients. This Review evaluates the experience accumulated by the TREAT-NMD Advisory Committee for Therapeutics, which provides detailed constructive feedback on clinical proposals for neuromuscular diseases submitted by researchers in both academia and industry, and emphasizes that a timely critical review of preclinical efficacy data from animal models, including biomarkers for specific diseases, combined with adherence to existing guidelines and standard protocols, can significantly help to de-risk clinical programs and prevent disappointments and costly engagement.
罕见神经肌肉疾病的临床试验除了其他投入外,还会给整个疾病群体带来沉重的精神负担。为了尽量降低临床试验撤回或失败的风险,必须仔细考虑将临床前研究数据转化为支持任何临床试验的依据。使用动物模型进行概念验证和临床前疗效研究之间的严格区分,是支持涉及患者的临床试验的基本要素。这篇综述评估了 TREAT-NMD 治疗咨询委员会积累的经验,该委员会对学术界和工业界的研究人员提交的神经肌肉疾病的临床建议提供了详细的建设性反馈,并强调及时对动物模型的临床前疗效数据进行批判性审查,包括针对特定疾病的生物标志物,同时遵循现有的指南和标准方案,可显著降低临床项目的风险,避免失望和昂贵的投入。