Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
Dutch Medicines Evaluation Board, Utrecht, The Netherlands.
Clin Pharmacol Ther. 2019 Feb;105(2):426-435. doi: 10.1002/cpt.1169. Epub 2018 Aug 12.
When medicines are granted a Conditional Marketing Authorisation (CMA) in Europe, specific obligations are requested to obtain comprehensive data on benefits and risks. We performed a retrospective cohort study to characterize obligations, examine changes to their description and due dates after initial authorization, determine timing of data submission relative to due dates, and identify drug-related, procedure-related, and obligation-related factors associated with change. We identified 69 obligations for 26 medicines conditionally authorized between 2006 and 2016. We found 39 changes to 27 obligations (39% of obligations), of which four substantially changed the obligation. For 55% of obligations, data submission was delayed. Eleven factors were associated with change, including the use of CMA as a rescue option. The results are potentially indicative of a continuous search by regulators to reduce uncertainties. Submission delays impact public health negatively by prolonging exposure of patients to unknown risks, particularly when the level of uncertainty is high.
当药品在欧洲获得有条件上市许可（CMA）时，会被要求承担具体的义务，以获取关于获益和风险的全面数据。我们进行了一项回顾性队列研究，以描述义务的特征，检查初始授权后其描述和截止日期的变化，确定数据提交相对于截止日期的时间，并确定与变化相关的与药物、程序和义务相关的因素。我们确定了 26 种在 2006 年至 2016 年期间有条件获得批准的药品的 69 项义务。我们发现 27 项义务中的 39 项（占义务的 39%）发生了变化，其中 4 项实质性地改变了义务。55%的义务都出现了数据提交延迟的情况。有 11 个因素与变化相关，包括将 CMA 作为抢救方案的使用。研究结果可能表明监管机构在不断寻求降低不确定性。提交延迟会延长患者接触未知风险的时间，从而对公共健康产生负面影响，尤其是当不确定性水平较高时。
