While orphan diseases, which by definition affect less than 200 000 people in the United States,1 are individually rare, they are not rare in aggregate. Rather, they affect as many as 30 million people nationwide.1 Most rare diseases are genetic in origin,1 and as many as 50% of the people affected are children.1 Historically, there have been limited therapies available for treatment of these conditions, largely owing to the market disincentives pharmaceutical companies face in developing products for small, geographically dispersed populations. To counter this, Congress passed the Orphan Drug Act in 19831 to provide a number of financial incentives to sponsors developing drugs intended to treat orphan diseases. The act has been credited with successfully stimulating orphan drug development—38 orphan drugs were approved in the United States prior to 1983, and 365 have been approved from 1984 through 2016.2 The Orphan Drug Act, however, does not require that orphan drugs be tested in children. Requirements for pediatric drug development were not solidified until 2003, when the Pediatric Research Equity Act (PREA) was passed. This law mandates the testing of new products in children whenever the therapeutic indication is relevant to pediatric populations. Under PREA, new drug applications and supplemental applications for new active ingredients, indications, and dosage forms must contain pediatricstudydataandguidanceondosingandadministration in children. These requirements can be waived or deferred in certain cases, such as when the indications for a product are not relevant to pediatric patients, or when evidence demonstrates the drug would be ineffective or unsafe in children. In addition, orphan drugs are exempt from the requirements of PREA. In Europe, where similar pediatric legislation was enacted in 2007, no exceptions are made for orphan products to ensure evidence-based, safe use of these drugs in children.3 In July 2016, in accordance with provisions of the US Food and Drug Administration (FDA) Safety and Innovation Act, US Department of Health and Human Services Secretary Sylvia Mathews Burwell reported to Congress on the activities conducted under pediatric programs, including PREA.4 One of her key recommendations was to eliminate the testing exemption for drugs with certain orphan designations. A number of organizations, including the American Academy of Pediatrics and several pediatric advocacy groups, have also endorsed these changes to PREA. Political interest suggests the opportunity might arise to amend the legislation to authorize the FDA to require pediatric studies for all orphan drugs.

中文翻译：

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改进罕见病儿童新药研究

虽然根据定义影响美国不到 20 万人的孤儿病 1 个别罕见，但总体而言并不罕见。相反，它们影响了全国多达 3000 万人。1 大多数罕见疾病是遗传性的，1 并且多达 50% 的受影响人是儿童。1 从历史上看，可用于治疗这些疾病的疗法很有限，主要是因为制药公司在为地理上分散的小群体开发产品时面临市场抑制因素。为了解决这个问题，国会于 19831 年通过了《孤儿药法案》，为开发用于治疗孤儿疾病的药物的赞助商提供多项经济奖励。该法案被认为成功地刺激了孤儿药的开发——1983 年之前，美国批准了 38 种孤儿药，1984 年至 2016 年间批准了 365 种。2 然而，《孤儿药法案》并不要求孤儿药在孩子们。直到 2003 年，儿科研究公平法案 (PREA) 获得通过，儿科药物开发的要求才得到巩固。该法律规定，只要治疗适应症与儿科人群相关，就必须在儿童中测试新产品。根据PREA，新药申请和新活性成分、适应症和剂型的补充申请必须包含儿科研究数据以及儿童用药和给药指南。在某些情况下可以免除或推迟这些要求，例如，当产品的适应症与儿科患者无关时，或者当有证据表明该药物对儿童无效或不安全时。此外，孤儿药不受 PREA 的要求约束。在欧洲，类似的儿科立法于 2007 年颁布，孤儿产品没有例外，以确保这些药物在儿童中的循证、安全使用。 3 2016 年 7 月，根据美国食品和药物管理局的规定（ FDA) 安全与创新法案，美国卫生与公众服务部部长 Sylvia Mathews Burwell 向国会报告了在儿科项目下开展的活动，包括 PREA。4 她的主要建议之一是取消对具有某些孤儿药指定的药物的测试豁免. 多个组织，包括美国儿科学会和几个儿科倡导团体在内，也支持对 PREA 进行这些更改。政治利益表明，可能有机会修改立法，授权 FDA 要求对所有孤儿药进行儿科研究。