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.

中文翻译：

---

用于治疗先天性代谢障碍的证据创造的发展

先天性代谢障碍 (IEM) 代表了第一组遗传疾病，适合因果疗法。除了传统的医学饮食和辅因子治疗外，新的治疗策略如酶替代和小分子疗法、实体器官移植以及基于细胞和基因的疗法已经可用。由于单一条件的罕见性质，在临床试验和现实世界条件下为这些治疗生成高质量的证据一直具有挑战性。使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。自适应试验设计允许随着试验的进行而改变样本量、组分配和试验持续时间。当参与者临床异质性时，n-of-1 研究可用于小样本。通过国际研究网络促进多中心观察和基于注册的临床试验。核心结果和标准数据元素集将加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以患者为主导的研究计划将进一步加速 IEM 疗法的开发。