Paediatric Medicines, Human Medicines Special Areas Sector, European Medicines Agency, 7 Westferry Circus, Canary Wharf, London, E14 4HB, UK.
Eur J Clin Pharmacol. 2011 Mar;67(3):245-52. doi: 10.1007/s00228-011-0997-4. Epub 2011 Feb 1.
To investigate whether the Paediatric Regulation has already succeeded in addressing the needs of the paediatric population both quantitatively with respect to paediatric development plans and trials, and qualitatively with respect to the content of the plans. The Paediatric Regulation No 1901/2006 entered into force in Europe on 26 January 2007, with the aim to improve the development of medicinal products, to address the lack of age-appropriate formulations and to provide information on efficacy, safety and dosing for the paediatric population. The Regulation requires applications for marketing authorisations to be accompanied by either a product-specific waiver or a paediatric investigation plan, to be agreed by the Paediatric Committee (PDCO) of the European Medicines Agency (EMA).
A retrospective analysis of the applications for Paediatric Investigation Plans (PIPs) and Waivers submitted to the EMA, from 2007 until end of 2009, was performed. The content of scientific opinions adopted by the Paediatric Committee was compared to the proposals submitted by industry, and the paediatric clinical trials registered in the European Union Drug Regulating Authorities Clinical Trials (EudraCT) database were examined.
An increasing paediatric medicine development can be expected following the adoption of this legal framework. The highest number of PIPs was in the fields of endocrinology (13.4%), oncology (11%) and infectious (10.8%) and cardiovascular diseases (7.1%), but most therapeutic areas now benefit from paediatric development. A large number of PIPs include measures for the development of age-appropriate formulations (23%), and most include studies on dosing, efficacy and safety to cover the respective paediatric subsets, including the mostly neglected neonates (26%). In many proposals (38%), however, the PDCO had to request major modifications to the proposed PIPs to ensure that the results will meet the needs, in particular by requesting better methodology. The proportion of paediatric trials as a percentage of all clinical trials has moderately increased (from 8.2 to 9.4% of all trials), and this may reflect the fact that paediatric trials are generally deferred (82%) until after adult development.
This is the first analysis of the general impact of the Paediatric Regulation on the development of medicinal products in Europe. Three years after the implementation of the Paediatric Regulation, we were able to identify that the PIPs address the main gaps in knowledge on paediatric medicines. The key objective of the Paediatric Regulation, namely, the availability of medicines with age-appropriate information, is going to be achieved. It is clear also that modifications of the initial proposals as requested by the PDCO are necessary to ensure the quality of paediatric developments. The impact on the number of clinical trials performed remains modest at this point in time, and it will be of high interest to monitor this performance indicator, which will also inform us whether paediatric medicine research takes place in Europe or elsewhere.
研究《儿科规定》是否已成功解决儿科人群在儿科发展计划和试验方面的数量需求，以及在计划内容方面的质量需求。2006 年第 1901/2006 号儿科法规于 2007 年 1 月 26 日在欧洲生效，目的是改善药物的开发，解决缺乏适合年龄的配方的问题，并为儿科人群提供有关疗效、安全性和剂量的信息。该法规要求营销许可申请必须附有产品特定的豁免或儿科研究计划，该计划必须由欧洲药品管理局（EMA）的儿科委员会（PDCO）同意。
对 2007 年至 2009 年底提交给 EMA 的儿科研究计划（PIP）和豁免申请进行了回顾性分析。比较了儿科委员会通过的科学意见的内容与行业提交的建议，并检查了在欧盟药品监管机构临床试验（EudraCT）数据库中登记的儿科临床试验。
预计在采用这一法律框架后，儿科医学的发展将有所增加。数量最多的 PIP 是内分泌学（13.4%）、肿瘤学（11%）、传染病（10.8%）和心血管疾病（7.1%），但现在大多数治疗领域都受益于儿科发展。大量 PIP 包括开发适合年龄的配方的措施（23%），并且大多数包括剂量、疗效和安全性研究，以涵盖各自的儿科亚组，包括最被忽视的新生儿（26%）。然而，在许多提案（38%）中，PDCO 必须对拟议的 PIP 进行重大修改，以确保结果满足需求，特别是通过要求更好的方法学。儿科试验占所有临床试验的比例适度增加（从所有试验的 8.2%增加到 9.4%），这可能反映出儿科试验通常会推迟（82%）直到成人开发完成。
这是首次分析《儿科规定》对欧洲药品开发的总体影响。在实施《儿科规定》三年后，我们能够确定 PIP 解决了儿科药物知识方面的主要差距。《儿科规定》的主要目标，即提供具有适合年龄信息的药物，即将实现。显然，PDCO 要求的对初始提案的修改也是必要的，以确保儿科开发的质量。目前，这对进行临床试验的数量的影响仍然不大，监测这一绩效指标将很有趣，这也将告诉我们儿科医学研究是在欧洲还是其他地方进行的。
