PDF(Pubmed)
Abstract：
Age-related macular degeneration (AMD) is the leading cause of blindness for the elderly in high-income countries. Although multivitamin antioxidant nutrients can slow the progression of intermediate \"dry\" or nonneovascular AMD, no treatment can halt or reverse any stage of dry disease. Multiple biologic pathways have been implicated in AMD pathobiology, including the complement pathway. These pathways have been targeted by various approaches in clinical trials. To date, no treatment has reached their prespecified primary end point in 2 phase III trials, a requirement by the US Food and Drug Administration for a new drug approval. Here, we describe perspectives on the failures and possible successes of various clinical trials that will guide further investigation. These perspectives will also discuss clinical trial design issues to consider in future investigations, and how recent insights into AMD pathobiology might both provide additional explanation for trials not reaching the prespecified primary end points and offer direction for identifying prioritized treatment targets.
摘要：
年龄相关性黄斑变性(AMD)是高收入国家老年人失明的主要原因。尽管多种维生素抗氧化营养素可以减缓中间“干性”或非新生血管性AMD的进展，任何治疗都不能阻止或逆转干病的任何阶段。多种生物学途径与AMD病理生物学有关，包括补体途径。这些途径已经在临床试验中被各种方法靶向。迄今为止,在2项III期试验中,没有治疗达到他们预设的主要终点,美国食品和药物管理局对新药批准的要求。这里,我们描述了各种临床试验的失败和可能成功的观点,这将指导进一步的研究.这些观点还将讨论临床试验设计问题，以便在未来的调查中考虑。以及最近对AMD病理生物学的认识如何为未达到预设主要终点的试验提供额外的解释,并为确定优先治疗目标提供指导.
