Hoekman Jarno, Klamer Thea T, Mantel-Teeuwisse Aukje K, Leufkens Hubert G M, De Bruin Marie L
Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
Innovation Studies Group, Copernicus Institute for Sustainable Development, Utrecht University, Utrecht, The Netherlands.
Br J Clin Pharmacol. 2016 Jul;82(1):213-26. doi: 10.1111/bcp.12940. Epub 2016 Apr 22.
The aim of the present study was to provide an insight into the characteristics and follow-up of postmarketing studies of medicines that were conditionally authorized in the European Union (EU).
We compiled a list of all postmarketing studies attached as specific obligations to the licence of medicines that were granted conditional marketing authorization from January 2006 to April 2014. Studies were characterized based on their objective, design, status upon marketing authorization (MA) and due data set by authorities. They were linked to online study registrations (Clinicaltrials.gov, ENCePP) to determine completion date. We described and associated characteristics of studies and medicines, and determined whether studies were completed on time.
A total of 59 postmarketing studies were requested for 21 conditionally authorized medicines. Most studies had an interventional study design (73%), were ongoing upon MA (61%) and aimed to provide additional data on efficacy (45%). Interventional studies were more often ongoing and providing efficacy data, while observational and other studies were more often new and providing safety data. Frequent grounds for requesting postmarketing studies were 'long-term follow-up' and 'increase data on subpopulations'. Of the 34 studies eligible for follow-up analysis, 26 (76%) were completed and 17 (50%) completed on time. Actual completion time took a median (interquartile range) of 274 (-121 to 556) days longer than expected.
Our results indicated that most postmarketing studies attached to a conditional marketing authorization were eventually completed but that half were completed with a substantial delay. The observations suggest caution when broadening the use of postmarketing studies for resolving uncertainties about benefits and risks after MA.
本研究旨在深入了解在欧盟（EU）获得有条件批准的药品的上市后研究特征及随访情况。
我们编制了一份清单，列出了2006年1月至2014年4月期间获得有条件上市许可的药品所附带的所有作为特定义务的上市后研究。根据研究目的、设计、上市许可（MA）时的状态以及当局规定的预期数据集对研究进行特征描述。将这些研究与在线研究注册平台（Clinicaltrials.gov、ENCEPP）关联，以确定完成日期。我们描述并关联了研究和药品的特征，并确定研究是否按时完成。
21种有条件批准的药品共要求进行59项上市后研究。大多数研究采用干预性研究设计（73%），在获得MA时正在进行（61%），旨在提供更多疗效数据（45%）。干预性研究更常处于进行中并提供疗效数据，而观察性研究和其他研究更常是新开展的并提供安全性数据。要求进行上市后研究的常见理由是“长期随访”和“增加亚组数据”。在34项 eligible for follow-up analysis的研究中，26项（76%）完成，17项（50%）按时完成。实际完成时间比预期中位数（四分位间距）长274（-121至556）天。
我们的结果表明，大多数附属于有条件上市许可的上市后研究最终完成，但有一半完成时出现了大幅延迟。这些观察结果表明，在扩大使用上市后研究以解决MA后效益和风险的不确定性时应谨慎。
