Villani Edoardo, Massaro Domenico, Scaramuzzi Matteo, Hamrah Pedram, Medeiros Felipe A, Nucci Paolo
Department of Clinical Sciences and Community Health, University of Milan, Eye Clinic San Giuseppe Hospital, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Multimedica, Milan, Italy.
Department of Ophthalmology, Cornea Service and Boston Image Reading Center, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts, United States.
Invest Ophthalmol Vis Sci. 2017 May 1;58(6):BIO76-BIO81. doi: 10.1167/iovs.17-21790.
The purpose of this study was to investigate the use of imaging biomarkers in published clinical trials (CTs) in ophthalmology and its eventual changes during the past 10 years.
We sampled from published CTs in the fields of cornea, retina, and glaucoma between 2005-2006 and 2015-2016. Data collected included year of publication, phase, subspecialty, location, compliance with Consolidated Standards for Reporting Trials, impact factor, presence and use of imaging biomarkers (diagnostic, prognostic and predictive; primary and secondary surrogate endpoints), and use of centralized reading centers.
We included 652 articles for analysis, equally distributed in three timeframes (2005-2006, 2010-2011, and 2015-2016), mainly reporting phase IV CTs and trials on procedures (42.2% and 35.4%, respectively). Imaging biomarkers were included in 46.3% of the analyzed CTs and their use significantly increased over time (P < 0.05). Optical coherence tomography was the most frequently used device (27.7%), whereas diagnostic biomarkers and secondary surrogate endpoints were the most frequent biomarker types (19.5% and 22.5%, respectively). Early-phase CTs showed an increase in the use of biomarkers for patient selection and stratification over time (P < 0.05), but not in the use of imaging surrogate endpoints (P = 0.90). Only 3 of 59 (5.1%) of phase III CTs included primary surrogate imaging endpoints, whereas secondary surrogate imaging endpoints were present in 50.8% of these trials (P < 0.001). Retinal CTs had the highest prevalence for each type of imaging biomarker (P < 0.001). Reading centers were used in 52 of 302 CTs (17.2%), with no significant time-related increase.
Imaging biomarkers are increasingly used in published CTs in ophthalmology. Additional efforts, including centralized reading centers, are needed to improve their validation and use, allowing a wider use of these tools as primary surrogate endpoints in phase III CTs.
本研究旨在调查眼科已发表临床试验（CT）中影像生物标志物的使用情况及其在过去10年中的最终变化。
我们从2005 - 2006年和2015 - 2016年期间发表的角膜、视网膜和青光眼领域的CT中进行抽样。收集的数据包括发表年份、阶段、亚专业、地点、是否符合试验报告统一标准、影响因子、影像生物标志物的存在和使用情况（诊断、预后和预测；主要和次要替代终点）以及集中阅片中心的使用情况。
我们纳入652篇文章进行分析，平均分布在三个时间段（2005 - 2006年、2010 - 2011年和2015 - 2016年），主要报告IV期CT和手术试验（分别占42.2%和35.4%）。46.3%的分析CT纳入了影像生物标志物，其使用随时间显著增加（P < 0.05）。光学相干断层扫描是最常用的设备（27.7%），而诊断生物标志物和次要替代终点是最常见的生物标志物类型（分别为19.5%和22.5%）。早期CT显示，随着时间推移，用于患者选择和分层的生物标志物使用增加（P < 0.05），但影像替代终点的使用未增加（P = 0.90）。59项III期CT中只有3项（5.1%）纳入了主要替代影像终点，而这些试验中有50.8%存在次要替代影像终点（P < 0.001）。视网膜CT中每种影像生物标志物的患病率最高（P < 0.001）。302项CT中有52项（17.2%）使用了阅片中心，且与时间无显著相关增加。
影像生物标志物在眼科已发表的CT中使用越来越多。需要做出额外努力，包括集中阅片中心，以改善其验证和使用，使这些工具能更广泛地用作III期CT的主要替代终点。
