生物标志物与替代标志物：美国食品药品监督管理局的观点
Biomarkers and surrogate markers: an FDA perspective.
作者信息
Katz Russell
机构信息
Division of Neuropharmacological Drug Products, United States Food and Drug Administration, Rockville, Maryland 20852, USA.
出版信息
NeuroRx. 2004 Apr;1(2):189-95. doi: 10.1602/neurorx.1.2.189.
Interest is increasing rapidly in the use of surrogate markers as primary measures of the effectiveness of investigational drugs in definitive drug trials. Many such surrogate markers have been proposed as potential candidates for use in definitive effectiveness trials of agents to treat neurologic or psychiatric disease, but as of this date, there are no such markers that have been adequately "validated," that is, shown to predict the effect of the treatment on the clinical outcome of interest. While the current law and regulations permit the United States Food and Drug Administration to base the approval of a drug product on a determination the effect of the drug on an unvalidated surrogate marker (that is, one for which it is not known that an effect on the surrogate actually predicts the desired clinical benefit), there are a number of difficulties in interpreting trials that use surrogate markers as primary measures of drug effect. In this article, the relevant regulatory context will be discussed, as well as the epistemological problems related to the interpretation of clinical trials in which unvalidated surrogate markers are used as primary outcomes.
在确定性药物试验中，将替代标志物用作研究药物有效性的主要衡量指标的兴趣正在迅速增加。许多此类替代标志物已被提议作为治疗神经或精神疾病药物的确定性有效性试验的潜在候选指标，但截至目前，尚无此类标志物得到充分“验证”，即尚未证明其能预测治疗对感兴趣的临床结局的影响。虽然现行法律法规允许美国食品药品监督管理局基于对药物对未经验证的替代标志物的影响的判定（即尚不清楚对替代标志物的影响实际上是否能预测预期的临床益处）来批准药品，但在解释将替代标志物用作药物效果主要衡量指标的试验时存在诸多困难。本文将讨论相关的监管背景，以及与解释将未经验证的替代标志物用作主要结局的临床试验相关的认识论问题。
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