Cardiovascular Institute, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Am J Ther. 2010 Jan-Feb;17(1):2-7. doi: 10.1097/MJT.0b013e3181ca8105.
The quality of clinical data submitted by manufacturers to support Food and Drug Administration cardiovascular device premarket approval (PMA) applications varies widely and formal quality assessment has not been previously performed. This study evaluated all original cardiovascular device PMAs with Food and Drug Administration decisions between January 1, 2000, and December 31, 2007, to assess the quality of clinical investigations submitted by manufacturers. Effectiveness and safety end points were judged high quality if they were clearly defined and associated with a specific time point for analysis. Subject accounting was high quality if 90% or greater of the original cohort was accounted for at study conclusion. In total, 88 cardiovascular device PMAs (77.3% permanent implants), 132 clinical studies, 37,328 study subjects (age 61.0 +/- 14.5 years, 33.9% women, 86.3% white), and 29,408 device recipients were analyzed. All PMAs contained clinical data. Primary effectiveness end points, primary safety end points, and subject accounting were deemed high quality in 81.8%, 60.2%, and 77.3% of pivotal studies, respectively. Key cardiovascular comorbidities (coronary artery disease 51.1%, diabetes 36.6%, hypertension 35.2%, heart failure 37.5%, tobacco use 31.8%) and race (14.8%) were infrequently reported, and studies rarely included patients younger than 18 years of age (10.2% of studies). Poorly defined safety and effectiveness end points, poor patient accounting, and incomplete collection of important patient comorbidities make device safety and effectiveness assessments more challenging. Women, pediatric, and nonwhite populations are underrepresented in premarket cardiovascular clinical trials. Manufacturers, regulators, and the clinical community should collaborate to address these study shortcomings to ensure that patients are treated with reliable, safe, and clinically useful medical devices.
制造商提交的支持食品和药物管理局心血管设备上市前批准 (PMA) 申请的临床数据质量差异很大，以前没有进行过正式的质量评估。本研究评估了 2000 年 1 月 1 日至 2007 年 12 月 31 日期间所有获得食品和药物管理局批准的心血管设备原始 PMA，以评估制造商提交的临床研究质量。如果有效性和安全性终点定义明确，并与特定的分析时间点相关，则判断为高质量。如果原始队列中有 90%或更多的患者在研究结束时得到了统计，则认为患者纳入情况是高质量的。共有 88 项心血管设备 PMA（77.3%为永久性植入物）、132 项临床研究、37328 名研究对象（年龄 61.0 ± 14.5 岁，33.9%为女性，86.3%为白人）和 29408 名设备接受者进行了分析。所有 PMA 均包含临床数据。主要有效性终点、主要安全性终点和患者纳入情况在关键性研究中分别有 81.8%、60.2%和 77.3%被认为是高质量的。主要心血管合并症（冠状动脉疾病 51.1%、糖尿病 36.6%、高血压 35.2%、心力衰竭 37.5%、吸烟 31.8%）和种族（14.8%）的报告频率较低，且研究中很少包括 18 岁以下的患者（10.2%的研究）。安全性和有效性终点定义不明确、患者纳入情况不佳以及重要患者合并症数据收集不完整，使得设备安全性和有效性评估更加具有挑战性。女性、儿科和非白人人群在心血管设备上市前临床试验中代表性不足。制造商、监管机构和临床社区应合作解决这些研究缺陷，以确保患者接受可靠、安全和临床有用的医疗器械治疗。
