Division of Biochemical Genetics, Department of Pediatrics, and BC Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada.
J Inherit Metab Dis. 2021 Jan;44(1):88-98. doi: 10.1002/jimd.12315. Epub 2020 Oct 4.
Inborn errors of metabolism (IEM) represent the first group of genetic disorders, amenable to causal therapies. In addition to traditional medical diet and cofactor treatments, new treatment strategies such as enzyme replacement and small molecule therapies, solid organ transplantation, and cell-and gene-based therapies have become available. Inherent to the rare nature of the single conditions, generating high-quality evidence for these treatments in clinical trials and under real-world conditions has been challenging. Guidelines developed with standardized methodologies have contributed to improve the practice of care and long-term clinical outcomes. Adaptive trial designs allow for changes in sample size, group allocation and trial duration as the trial proceeds. n-of-1 studies may be used in small sample sized when participants are clinically heterogeneous. Multicenter observational and registry-based clinical trials are promoted via international research networks. Core outcome and standard data element sets will enhance comparative analysis of clinical trials and observational studies. Patient-centered outcome-research as well as patient-led research initiatives will further accelerate the development of therapies for IEM.
先天性代谢缺陷（IEM）是第一组遗传性疾病，可采用病因治疗。除了传统的医学饮食和辅助因子治疗外，新的治疗策略，如酶替代和小分子治疗、实体器官移植以及基于细胞和基因的治疗已经可用。由于单一疾病的罕见性质，在临床试验和真实环境中为这些治疗方法生成高质量的证据具有挑战性。采用标准化方法制定的指南有助于改善护理实践和长期临床结果。适应性试验设计允许随着试验的进行改变样本量、分组和试验持续时间。当参与者具有临床异质性时，n-of-1 研究可用于小样本量。通过国际研究网络促进多中心观察性和基于登记的临床试验。核心结局和标准数据元素集将增强临床试验和观察性研究的比较分析。以患者为中心的结果研究以及患者主导的研究计划将进一步加速 IEM 治疗方法的发展。
