One of the most challenges for rare disease clinical trials is probably the availability of a small patient population. It is then a great concern on how to conduct clinical trials with a small number of subjects available for obtaining substantial evidence regarding safety and effectiveness for approval of the rare disease drug product under investigation. FDA, however, does not have the intention to create a statutory standard for approval of orphan drugs that are different from the standard for approval of drugs in common conditions. Thus, it is suggested that innovative trial designs such as a complete n-of-1 trial design or an adaptive design should be used for an accurate and reliable assessment of rare disease drug products under investigation. In this article, basic considerations, innovative trial designs, and statistical methods for data analysis are discussed. In addition, some innovative thinking for the evaluation of rare disease drug products is proposed.

罕见病临床试验面临的最大挑战之一可能是患者人数少。因此，非常关注如何对少数受试者进行临床试验，以获取有关批准所研究的罕见病药物产品的安全性和有效性的大量证据。但是，FDA无意创建与孤儿药批准的法定标准不同的法定标准，该标准与普通情况下的药物批准标准不同。因此，建议将创新的试验设计（例如完整的n-of-1试验设计或自适应设计）用于对所研究的稀有疾病药物产品进行准确而可靠的评估。本文介绍了基本注意事项，创新的试验设计，讨论了用于数据分析的统计方法。此外，提出了一些罕见病药物产品评价的创新思路。