Willink Unit, Genetic Medicine, Manchester Academic Health Science Centre, Central Manchester University Hospitals NHS Foundation Trust, St Marys Hospital, Manchester, UK.
Paediatr Drugs. 2011 Feb 1;13(1):33-47. doi: 10.2165/11586860-000000000-00000.
Assessing medicines specifically for use in children has been neglected in the past, with the majority of formal clinical studies being conducted in adults. Clinical trials are a pivotal part of the drug approval process; however, they are not always applicable to the diverse populations - including children - that receive the drug after approval. They may not be the most informative assessment tool, especially in rare (or orphan) disorders where there are few patients, due to a lack of existing natural history data and the challenges of designing appropriately powered statistical analyses. Disease registries, which can collect clinical information in larger, more heterogeneous populations than can be included in a clinical trial, are becoming increasingly valuable. Their use is particularly beneficial for diseases affecting very small patient populations, such as lysosomal storage disorders (LSDs), and for looking at specific populations, for example, children. Such disease registries can provide natural history data as well as enable the impact of therapy to be examined. Moreover, despite potential limitations of enrollment bias and unmonitored data, patient registries can play a valuable role in assuring pediatric health, providing longitudinal data that can be used to monitor developmental outcomes in chronic lifelong diseases, and assessing the effectiveness of treatment. This review describes the role of registries in drug development and regulatory approval, the impact of global registry programs on pediatric research, with some examples from the field of LSDs, and how registries are impacting the clinical care such children receive.
过去,专门针对儿童使用的药物评估一直被忽视,大多数正式的临床研究都是在成年人中进行的。临床试验是药物审批过程的关键部分;然而,它们并不总是适用于批准后使用药物的不同人群,包括儿童。由于缺乏现有自然史数据以及设计适当的统计分析的挑战,它们可能不是最具信息性的评估工具,尤其是在罕见(或孤儿)疾病中,因为患者较少。疾病登记处可以在比临床试验中更大、更多样化的人群中收集临床信息,其作用变得越来越有价值。它们的使用对于影响非常小的患者人群的疾病,例如溶酶体贮积症(LSD),以及对于特定人群,例如儿童,特别有益。这种疾病登记处可以提供自然史数据,并能够检查治疗的效果。此外,尽管存在入组偏倚和未监测数据的潜在局限性,但患者登记处可以在确保儿科健康方面发挥宝贵作用,提供可用于监测慢性终身疾病发育结果的纵向数据,并评估治疗效果。这篇综述描述了登记处在药物开发和监管审批中的作用、全球登记处计划对儿科研究的影响,以及登记处如何影响此类儿童的临床护理。