Ludwig Boltzmann Institute for Health Technology Assessment (LBI-HTA), Vienna, Austria; Department of Health Economics, Center for Public Health, Medical University of Vienna, Vienna, Austria.
Ludwig Boltzmann Institute for Health Technology Assessment (LBI-HTA), Vienna, Austria; Austria and Lower Austrian Sickness Fund, St. Pölten, Austria.
Eur J Cancer. 2019 Mar;110:1-7. doi: 10.1016/j.ejca.2018.12.026. Epub 2019 Feb 5.
The introduction provisional approval strategies increases the approval of anticancer drugs with ambiguous benefit-risk profiles. Thus, in many instances, there is lacking evidence about overall survival (OS) at the time of marketing authorisation. Our objective was to monitor and characterise therapies with ambiguous benefit-risk profiles and identify any postapproval updates on median OS after at least 3 years of approval by the European Medicines Agency (EMA).
We included all originator anticancer drugs with initially ambiguous benefit-risk profiles that received marketing authorisation by the EMA between January 1, 2009 and May 31, 2015. Our monitoring timeframe was at least 3 years after EMA approval. To identify study updates, the following three sources were included: clinicaltrials.gov, European Public Assessments Reports and PubMed.
In total, we identified 102 eligible approval studies. Out of these, a negative difference in median OS or no information was available in 43 (42.2%) instances. During monitoring, 14 updates with accessible positive information on OS could be identified. Including monitoring results, there are still 29 remaining therapies (28.4%) where no or negative information (n = 24 [23.5%] and n = 5 [4.9%], respectively) regarding OS is present at least 3 years after EMA approval.
One-third of oncology drugs with ambiguous benefit-risk profiles at the time of approval fail to demonstrate a survival benefit even after several years of marketing authorisation. Systematic and transparent postapproval monitoring mechanisms will be of high relevance to assure a clinically relevant patient benefit, since the trend towards faster access to medicines with uncertain benefit is increasing rather than declining.
引入临时批准策略增加了具有不确定获益-风险特征的抗癌药物的批准率。因此，在许多情况下，在获得上市许可时，关于总生存期（OS）的数据证据不足。我们的目标是监测和描述具有不确定获益-风险特征的治疗方法，并确定在欧洲药品管理局（EMA）批准至少 3 年后对 OS 中位数的任何后续批准更新。
我们纳入了 2009 年 1 月 1 日至 2015 年 5 月 31 日期间EMA 批准的具有初始获益-风险特征不明确的所有原研抗癌药物。我们的监测时间框架至少为 EMA 批准后 3 年。为了识别研究更新，我们纳入了以下三个来源：clinicaltrials.gov、欧洲公共评估报告和 PubMed。
总共确定了 102 项符合条件的批准研究。其中，43 项（42.2%）存在 OS 中位数的负差异或无信息。在监测期间，我们发现了 14 项关于 OS 的阳性信息更新。包括监测结果在内，仍有 29 种治疗方法（28.4%）在 EMA 批准后至少 3 年内存在 OS 方面的无信息或负面信息（n=24[23.5%]和 n=5[4.9%]）。
在批准时具有不确定获益-风险特征的肿瘤学药物中，有三分之一在获得上市许可后数年仍未显示生存获益。系统透明的上市后监测机制对于确保具有临床相关性的患者获益非常重要，因为具有不确定获益的药物更快获得批准的趋势在增加，而不是在减少。
