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替代终点:临床流行病学中的一个关键概念。

Surrogate endpoints: a key concept in clinical epidemiology.

机构信息

Section for Biostatistics and Evidence-Based Research, The Parker Institute, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark; Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense University Hospital, Odense, Denmark.

Centre for Research on Health and Social Care Management, SDA Bocconi School of Management, Milan, Italy.

出版信息

J Clin Epidemiol. 2024 Mar;167:111242. doi: 10.1016/j.jclinepi.2023.111242. Epub 2023 Dec 22.

Abstract

Surrogate endpoints are biomarkers or intermediate outcomes that are used as substitutes for clinical outcomes of interest, often to expedite research or decision-making. In contrast, patient-important (or patient-centered) outcomes are health outcomes that are of direct relevance and importance to patients themselves; clinical trials may have measured the impact of the intervention on other endpoints related to, but different from, those of primary importance to patients. This article aims to elaborate on the use and understanding of surrogate endpoints. There should be a well-understood and scientifically grounded relationship between the surrogate (replacement) and the patient-important (target) endpoint it is intended to represent. It should be biologically plausible that changes in the surrogate will consistently and predictably reflect changes in the patient-important endpoint. The surrogate endpoint should show a threshold effect, meaning that a specific change (or state) in the surrogate with an intervention (relative to the comparator) is associated with a predictable (change in the) patient-important outcome. This helps establish a meaningful cutoff or target for the treatment effect on the surrogate endpoint. While surrogate endpoints offer advantages in certain situations, it is important to remember that their use requires careful validation to ensure they reliably predict the true clinical outcome. The validity of "surrogate endpoints" should be supported by robust scientific evidence and rigorous evaluation before these can be considered and labeled as surrogate endpoints.

摘要

替代终点是生物标志物或中间结果,可作为感兴趣的临床结果的替代物,常用于加速研究或决策。相比之下,患者重要(或以患者为中心)的结局是与患者自身直接相关且重要的健康结局;临床试验可能已经测量了干预对与患者最重要的结局相关但不同的其他结局的影响。本文旨在阐述替代终点的使用和理解。替代(替代)终点与其旨在代表的患者重要(目标)终点之间应该存在明确且有科学依据的关系。替代终点的变化能够一致且可预测地反映患者重要终点的变化,这在生物学上应该是合理的。替代终点应该显示出阈值效应,这意味着干预(相对于比较剂)中替代终点的特定变化(或状态)与可预测的(患者重要结局的)变化相关。这有助于为替代终点的治疗效果建立有意义的截止值或目标。虽然替代终点在某些情况下具有优势,但需要记住,它们的使用需要仔细验证,以确保它们可靠地预测真实的临床结局。“替代终点”的有效性应在考虑并将其标记为替代终点之前,通过强有力的科学证据和严格的评估来支持。

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