Marketing Authorization Applications Made to the European Medicines Agency in 2018-2019:What was the Contribution of Real-World Evidence?

Information derived from routinely collected real-world data has for a long time been used to support regulatory decision making on the safety of drugs and has more recently been used to support marketing authorization submissions to regulators. There is a lack of detailed information on the use and types of this real-world evidence (RWE) as submitted to regulators. We used resources held by the European Medicines Agency (EMA) to describe the characteristics of RWE included in new marketing authorization applications (MAAs) and extensions of indication (EOIs) for already authorized products submitted to the EMA in 2018 and 2019. For MAAs, 63 of 158 products (39.9%) contained RWE with a total of 117 studies. For 31.7% of these products, the RWE submitted was derived from data collected before the planned authorization. The most common data sources were registries (60.3%) followed by hospital data (31.7%). RWE was mainly included to support safety (87.3%) and efficacy (49.2%) with cohort studies being the most frequently used study design (88.9%). For EOIs, 28 of 153 products (18.3%) contained RWE with a total of 36 studies. For 57.1% of these products, studies were conducted prior to the EOIs. RWE sources were mainly registries (35.6%) and hospital data (27.0%). RWE was typically used to support safety (82.1%) and efficacy (53.6%). Cohort studies were the most commonly used study design (87.6%). We conclude that there is widespread use of RWE to support evaluation of MAAs and EOIs submitted to the EMA and identify areas where further research is required

Editor's Choice - Outcomes After One Stage Versus Two Stage Open Repair of Type II Thoraco-abdominal Aortic Aneurysms

Objective: This study compared the outcomes of open one stage with open two stage repair of type II thoraco-abdominal aortic aneurysms (TAAA). Methods: This retrospective study included 94 patients (68 men) with a mean +/- SD age of 54.5 +/- 14 years who underwent open type II TAAA repair from March 2006 to January 2016. The mean aneurysm diameter was 65 +/- 14.4 mm. The median follow up was 42 months (range 12-96). Seventy-six patients received one stage open repair and 18 patients were treated in two steps: 12 received two open procedures (thoracic and abdominal) and six received hybrid repair (one open and one endovascular procedure). This study focused on the comparison of open one stage and open two stage TAAA repair. The median time between the two steps was 31.5 days (range 1-169). Results: In hospital mortality after open one stage repair versus open two stage type II repair was 22.4% versus 0% (odds ratio 7.352, 95% confidence interval [CI] 0.884-959.1]; p = .19). The one year survival rate after one stage repair versus open two stage repair was 74.7% (95% CI 62.7-83.3) versus 90.9% (95% CI 50.8-98.7 [p = .225]). The five year survival rate after one stage repair versus open two stage repair was 53.0% (95% CI 37.2-66.5) versus 90.9% (95% CI 50.8-98.7 [p = .141]). The hazard ratio for survival after one stage repair and after open two stage repair was 4.563 (95% CI 96.9-81.4 [p = .137]). Paraplegia was observed after open one stage repair versus open two stage in 10.5% vs. 8% (p = 1). Acute kidney injury requiring permanent dialysis and myocardial infarction were assessed for after open one stage repair and open two stage and were seen in 3.9% vs. 0% (p = 1) and in 5.3% vs. 0% (p = 1), respectively. Conclusion: Open two stage repair may be recommended as a treatment option for type II TAAAs if anatomically feasible, as it has a lower mortality and similar complication rates to one stage repair