Chong Victor
UCL Institute of Ophthalmology, London, UK.
University of Utah, Salt Lake City, UT, USA.
Eye (Lond). 2025 Feb;39(3):484-487. doi: 10.1038/s41433-024-03520-4. Epub 2024 Dec 5.
This article provides a comprehensive overview of clinical trial design and regulatory pathways essential for drug development, specifically in the context of retinal diseases. Key concepts include trial structure, efficacy and safety endpoints, and regulatory expectations from agencies like the FDA. It delves into recent regulatory advancements, such as the inclusion of low-luminance vision as a secondary endpoint and analyses case studies from age-related macular degeneration (AMD) trials. Approvals for key retinal drugs, such as ranibizumab and aflibercept, treatments for AMD and diabetic macular oedema, are discussed highlighting criteria like the 15-letter gain/loss in visual acuity as approvable/clinical meaningful efficacy endpoints. Insights into geographic atrophy (GA) and diabetic retinopathy trials showcase the evolving landscape, where anatomical endpoints and new drugs bring fresh challenges and opportunities. It also emphasizes the importance of academic-industry collaboration, citing instances of gene therapy development and innovative endpoint measures like the Multi-Luminance Mobility Test for retinal dystrophies. The overarching aim of this lecture was to demystify the process that spans the design of clinical trials to regulatory approval of drugs so that clinicians understand these complexities. In particular, it is important to understand the reasons behind selection of trial design, inclusion and exclusion criteria, primary and secondary efficacy endpoints and safety endpoints. Since this lecture, there have been important changes in this field including new guidance from the Food and Drug Administration (FDA) as well as lessons learnt from recent drug approvals that are included in this manuscript.
本文全面概述了药物研发，特别是视网膜疾病背景下的临床试验设计和监管途径。关键概念包括试验结构、疗效和安全性终点，以及美国食品药品监督管理局（FDA）等机构的监管期望。文章深入探讨了近期的监管进展，如将低亮度视力纳入次要终点，并分析了年龄相关性黄斑变性（AMD）试验的案例研究。文中讨论了雷珠单抗和阿柏西普等关键视网膜药物的批准情况，这些药物用于治疗AMD和糖尿病性黄斑水肿，并强调了视力提高/降低15个字母作为可批准/具有临床意义的疗效终点等标准。对地理性萎缩（GA）和糖尿病视网膜病变试验的见解展示了不断变化的格局，其中解剖学终点和新药带来了新的挑战和机遇。文章还强调了学术-产业合作的重要性，列举了基因治疗开发的实例以及视网膜营养不良的多亮度移动测试等创新终点测量方法。本次讲座的总体目标是揭开从临床试验设计到药物监管批准这一过程的神秘面纱，以便临床医生理解这些复杂性。特别是，理解试验设计、纳入和排除标准、主要和次要疗效终点以及安全性终点选择背后的原因非常重要。自本次讲座以来，该领域发生了重要变化，包括美国食品药品监督管理局（FDA）的新指南以及从近期药物批准中吸取的经验教训，本文都有所涵盖。
