Over the last few decades there has been a paradigm shift in orphan drug research and development. The development of the regulatory framework, establishment of rare disease global networks that support drug developments, and advances in technology, has resulted in tremendous growth in orphan drug development. Nevertheless, several challenges during orphan drug development such as economic constraints; insufficient clinical information; fewer patients and thus inadequate power; etc. still exist. While the standard regulatory requirements for drug approval stays the same, applications of scientific judgment and regulatory flexibility is significantly important to help meeting some of the immense unmet medical need in rare diseases. Clinical pharmacology presents a vital role in accelerating orphan drug development and overcoming some of these challenges. This review highlights the critical contributions of clinical pharmacology in orphan drug development; for example, dose finding, optimizing clinical trial design, indication expansion, and population extrapolation. Examples of such applications are reviewed in this article.

中文翻译：

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孤儿药物的开发：临床药理作用的增加。

在过去的几十年中，孤儿药的研发发生了范式转变。监管框架的发展，支持药物开发的罕见病全球网络的建立以及技术的进步，导致了孤儿药物开发的巨大增长。然而，在孤儿药开发过程中仍面临一些挑战，例如经济限制；临床信息不足；更少的病人，因此力量不足；等仍然存在。尽管药品批准的标准法规要求保持不变，但科学判断和法规灵活性的应用对于帮助满足罕见病中某些未满足的巨大医疗需求非常重要。临床药理学在加速孤儿药物开发和克服其中一些挑战方面发挥着至关重要的作用。这篇综述强调了临床药理学在孤儿药物开发中的关键作用；例如，剂量查找，优化临床试验设计，适应症扩展和人群外推。本文介绍了此类应用程序的示例。