Biomarkers and surrogate endpoints in glaucoma clinical trials.
Biomarkers and surrogate endpoints in glaucoma clinical trials.
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DOI：
10.1136/bjophthalmol-2014-305550
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发表时间：
2015-05
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影响因子：
--
通讯作者：
Medeiros FA
中科院分区：
文献类型：
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作者：
Medeiros FA
在医学的几个领域中，代理终点经常被用作真正的临床相关终点的替代品，因为它们能够实现更快、更便宜的临床试验。然而，如果没有适当的验证，代用品的使用可能会导致关于治疗有效性和安全性的错误结论。本文综述了验证替代终点的一般要求，并对在青光眼临床试验中使用眼压(IOP)、视野和视神经结构测量作为替代终点进行了关键评估。有效的替代终点必须能够预测临床相关终点，并完全捕获干预对该终点的影响。尽管眼压在临床试验中被广泛使用，但在任何一类降眼压治疗中，都没有适当地验证眼压作为替代终点。关于视神经损伤的影像测量作为青光眼替代终点的作用的证据已经积累起来。这些测量可以预测疾病中的功能丧失，并至少部分解释临床相关终点的治疗效果。在青光眼试验中使用复合终点可以克服单独使用结构性或功能性终点的缺点。除非研究致力于充分开发和验证可用于青光眼临床试验的合适的终点，否则我们可能会对新疗法的价值做出不适当的判断。
Surrogate endpoints are often used as replacements for true clinically relevant endpoints in several areas of medicine, as they enable faster and less expensive clinical trials. However, without proper validation, the use of surrogates may lead to incorrect conclusions about the efficacy and safety of treatments. This article reviews the general requirements for validating surrogate endpoints and provides a critical assessment of the use of intraocular pressure (IOP), visual fields, and structural measurements of the optic nerve as surrogate endpoints in glaucoma clinical trials. A valid surrogate endpoint must be able to predict the clinically relevant endpoint and fully capture the effect of an intervention on that endpoint. Despite its widespread use in clinical trials, no proper validation of IOP as a surrogate endpoint has ever been conducted for any class of IOP-lowering treatments. Evidence has accumulated with regard to the role of imaging measurements of optic nerve damage as surrogate endpoints in glaucoma. These measurements are predictive of functional losses in the disease and may explain, at least in part, treatment effects on clinically relevant endpoints. The use of composite endpoints in glaucoma trials may overcome weaknesses of the use of structural or functional endpoints in isolation. Unless research is dedicated to fully develop and validate suitable endpoints that can be used in glaucoma clinical trials, we run the risk of inappropriate judgments about the value of new therapies.