Italian Medicines Agency (AIFA), via della Sierra Nevada 60, 00144 Rome, Italy.
Eur J Cancer. 2010 Feb;46(3):471-5. doi: 10.1016/j.ejca.2009.11.021. Epub 2009 Dec 26.
The regulatory route leading to the definition of therapeutic indications of new compounds as well as extensions of indication (EoI) of already approved ones is a challenging process. If new anticancer drugs reach the market with a lack of complete evidence, this usually leads regulators to request additional data, post approval commitments or restrictions in therapeutic indications. This study aims at quantifying the time needed for anticancer drugs approved by the EMEA to get an extension, the rates and characteristics of extensions approved, and at exploring the regulatory process leading to the definition of new indications. A total of 103 therapeutic oncological indications, related to a cohort of 43 anticancer drugs, were retrieved between 1995 and 2008. The median time occurring between different indications for the same compound (defined as Time to New Extension, TtNE) significantly decrease from about 81 months in 1996 to 6 months in 2006. Twenty-four out of 43 approved anticancer medicines (about 56%) have only a single therapeutic indication, 12 of which were approved before 2005. When considering two different cohorts of drugs in relation to the time of approval (1995-2004 versus 2005-2008), although not statistically significant, the older cohort tended to have a decreased probability of having EoI when compared to the new cohort (OR=0.27; 95% confidence interval (CI): 0.07-1.04). With regard to the type of EoI (n=60), our findings showed that in 48% of cases the initially approved indication was extended to treat a different tumour, in 37% of cases the extension consisted in a switch of line within the same therapeutic indication. The other two types of indication broadening refer to a different tumour stage (8%) and to the inclusion of a new patient population (7%). The analysis of indication restrictions showed that in 20 cases out of 50 (40%) therapeutic indications were restricted by the Committee for Medicinal Products for Human Use (CHMP) during the assessment, with 60% of the restrictions occurring in 2006-2007. This study adds three main pieces of information: (i) the majority of anticancer drugs still have a single indication regardless of the year of approval; (ii) the time needed to obtain an extension of indication has decreased significantly over the last decade and (iii) a highest rate of regulatory restrictions is matched to shorter clinical developments.
将新化合物的治疗适应症定义以及已批准药物的适应症扩展（EoI）的监管途径是一个具有挑战性的过程。如果新的抗癌药物缺乏完整的证据就进入市场，这通常会导致监管机构要求提供额外的数据、批准后承诺或治疗适应症限制。本研究旨在量化 EMEA 批准的抗癌药物获得扩展的时间、批准扩展的比例和特征，并探索定义新适应症的监管过程。在 1995 年至 2008 年间，共检索到与 43 种抗癌药物相关的 103 种治疗肿瘤的适应症。对于同一化合物的不同适应症之间的中位时间（定义为新扩展时间，TtNE）从 1996 年的约 81 个月显著减少到 2006 年的 6 个月。在 43 种批准的抗癌药物中，有 24 种（约 56%）只有单一的治疗适应症，其中 12 种是在 2005 年之前批准的。当考虑与批准时间相关的两个不同药物队列（1995-2004 年与 2005-2008 年）时，尽管没有统计学意义，但与新队列相比，旧队列的 EoI 可能性较低（OR=0.27；95%置信区间（CI）：0.07-1.04）。关于 EoI 的类型（n=60），我们的研究结果表明，在 48%的情况下，最初批准的适应症扩展到治疗不同的肿瘤，在 37%的情况下，扩展包括在同一治疗适应症内的治疗线切换。另外两种适应症扩展类型是不同的肿瘤阶段（8%）和纳入新的患者群体（7%）。对适应症限制的分析表明，在 50 例中有 20 例（40%）适应症在评估过程中受到人类用药品委员会（CHMP）的限制，60%的限制发生在 2006-2007 年。本研究增加了三条主要信息：（i）大多数抗癌药物无论批准年份如何，仍然只有单一适应症；（ii）获得适应症扩展的时间在过去十年中显著缩短；（iii）监管限制的最高比例与较短的临床开发相匹配。
