Detection and measurement of clinically meaningful visual field progression in clinical trials for glaucoma.
Detection and measurement of clinically meaningful visual field progression in clinical trials for glaucoma.
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DOI：
10.1016/j.preteyeres.2016.10.001
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发表时间：
2017-01
影响因子：
17.8
通讯作者：
Levin LA
中科院分区：
文献类型：
--
作者：
De Moraes CG;Liebmann JM;Levin LA
青光眼视野进展会造成个人和社会成本，因此对生活质量产生严重影响。目前，眼内压（IOP）被认为是青光眼发病和进展最重要的可改变危险因素。降低眼压已被反复证明是对各种青光眼的有效干预措施，无论亚型或疾病阶段如何。在批准降低眼压治疗的情况下，预计对眼压的影响将转化为患者报告的长期结果的益处。尽管如此，这些药物对眼压的影响及其相关风险是可以一致且客观地测量的。这有助于解释为什么监管部门批准青光眼新疗法历来使用眼压作为结果变量。尽管所有批准的青光眼治疗方法都涉及降低眼压，但患者在接受治疗后常常会继续病情进展。因此，开发通过降低眼压以外的机制来保留视觉功能的治疗方法将是有益的。美国食品和药物管理局 (FDA) 表示，他们将接受使用青光眼变化概率标准对视野进展进行具有临床意义的定义。尽管如此，这些标准没有考虑到实现重大变革所需的时间（以及速度）。在本文中，我们根据现有文献进行了分析，以支持这样的假设：在持续 12-18 个月的试验中，将视野进展率降低 30% 具有临床意义。我们证明，根据旨在测量该终点的经过验证的仪器的定义，视野进展率下降 30% 可以可靠地预测对健康相关的生活质量产生重大影响。
Glaucomatous visual field progression has both personal and societal costs and therefore has a serious impact on quality of life. At the present time, intraocular pressure (IOP) is considered to be the most important modifiable risk factor for glaucoma onset and progression. Reduction of IOP has been repeatedly demonstrated to be an effective intervention across the spectrum of glaucoma, regardless of subtype or disease stage. In the setting of approval of IOP-lowering therapies, it is expected that effects on IOP will translate into benefits in long-term patient-reported outcomes. Nonetheless, the effect of these medications on IOP and their associated risks can be consistently and objectively measured. This helps to explain why regulatory approval of new therapies in glaucoma has historically used IOP as the outcome variable. Although all approved treatments for glaucoma involve IOP reduction, patients frequently continue to progress despite treatment. It would therefore be beneficial to develop treatments that preserve visual function through mechanisms other than lowering IOP. The United States Food and Drug Administration (FDA) has stated that they will accept a clinically meaningful definition of visual field progression using Glaucoma Change Probability criteria. Nonetheless, these criteria do not take into account the time (and hence, the speed) needed to reach significant change. In this paper we provide an analysis based on the existing literature to support the hypothesis that decreasing the rate of visual field progression by 30% in a trial lasting 12–18 months is clinically meaningful. We demonstrate that a 30% decrease in rate of visual field progression can be reliably projected to have a significant effect on health-related quality of life, as defined by validated instruments designed to measure that endpoint.