A framework for the definition and interpretation of the use of surrogate endpoints in interventional trials.
A framework for the definition and interpretation of the use of surrogate endpoints in interventional trials.
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DOI：
10.1016/j.eclinm.2023.102283
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发表时间：
2023-11
影响因子：
15.1
通讯作者：
Taylor, Rod S.
中科院分区：
文献类型：
--
作者：
Ciani, Oriana;Manyara, Anthony M.;Davies, Philippa;Stewart, Derek;Weir, Christopher J.;Young, Amber E.;Blazeby, Jane;Butcher, Nancy J.;Bujkiewicz, Sylwia;Chan, An-Wen;Dawoud, Dalia;Offringa, Martin;Ouwens, Mario;Hrobjartssson, Asbjorn;Amstutz, Alain;Bertolaccini, Luca;Bruno, Vito Domenico;Devane, Declan;Faria, Christina D. C. M.;Gilbert, Peter B.;Harris, Ray;Lassere, Marissa;Marinelli, Lucio;Markham, Sarah;Powers, John H.;Rezaei, Yousef;Richert, Laura;Schwendicke, Falk;Tereshchenko, Larisa G.;Thoma, Achilles;Turan, Alparslan;Worrall, Andrew;Christensen, Robin;Collins, Gary S.;Ross, Joseph S.;Taylor, Rod S.
使用替代终点评价治疗效果的干预性试验越来越普遍。本文介绍了四个相关的实证研究和开发的框架定义，解释和报告替代终点的试验。作为发展CONSORT的一部分，（报告试验的统一标准）和SPIRIT（标准协议项目：对于报告替代终点的随机试验，我们进行了范围审查、e-Delphi研究、共识会议和网络调查，以检查当前的定义和利益相关者（包括临床医生、试验研究者、患者和公共合作伙伴、期刊编辑和卫生技术专家）将替代终点解释为试验中的主要结局指标。目前的替代终点定义框架不一致且不明确。替代终点在试验中用作干预对最终关注的目标结局的治疗效果的替代，这些事件测量患者的感觉、功能或生存情况。传统上，试验中替代终点的考虑集中在生物标志物（例如，高密度脂蛋白胆固醇、血压、肿瘤反应），尤其是在医疗产品监管环境中。然而，在试验中代孕的概念可能更广泛。包括功能或症状测量的中间结果（例如，心绞痛频率，运动耐量）也可以用作目标结果的替代（例如，全因死亡率）-从而作为替代终点。然而，我们发现利益相关者在接受和解释试验中的中间结局作为替代终点或目标结局方面缺乏共识。在我们的评估中，患者和卫生技术评估专家似乎比临床医生和监管机构更有可能将中间结局视为替代终点。迫切需要更好地理解和报告替代终点的使用，特别是在干预性试验的背景下。我们为替代终点（生物标志物和中间结局）和试验目标结局的定义提供了一个框架，以改善未来的报告，并帮助利益相关者解释和使用试验替代终点证据。SPIRIT-SURROGATE/CONSORT-SURROGATE项目获得（MR/V038400/1）资助。
Interventional trials that evaluate treatment effects using surrogate endpoints have become increasingly common. This paper describes four linked empirical studies and the development of a framework for defining, interpreting and reporting surrogate endpoints in trials. As part of developing the CONSORT (Consolidated Standards of Reporting Trials) and SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) extensions for randomised trials reporting surrogate endpoints, we undertook a scoping review, e-Delphi study, consensus meeting, and a web survey to examine current definitions and stakeholder (including clinicians, trial investigators, patients and public partners, journal editors, and health technology experts) interpretations of surrogate endpoints as primary outcome measures in trials. Current surrogate endpoint definitional frameworks are inconsistent and unclear. Surrogate endpoints are used in trials as a substitute of the treatment effects of an intervention on the target outcome(s) of ultimate interest, events measuring how patients feel, function, or survive. Traditionally the consideration of surrogate endpoints in trials has focused on biomarkers (e.g., HDL cholesterol, blood pressure, tumour response), especially in the medical product regulatory setting. Nevertheless, the concept of surrogacy in trials is potentially broader. Intermediate outcomes that include a measure of function or symptoms (e.g., angina frequency, exercise tolerance) can also be used as substitute for target outcomes (e.g., all-cause mortality)—thereby acting as surrogate endpoints. However, we found a lack of consensus among stakeholders on accepting and interpreting intermediate outcomes in trials as surrogate endpoints or target outcomes. In our assessment, patients and health technology assessment experts appeared more likely to consider intermediate outcomes to be surrogate endpoints than clinicians and regulators. There is an urgent need for better understanding and reporting on the use of surrogate endpoints, especially in the setting of interventional trials. We provide a framework for the definition of surrogate endpoints (biomarkers and intermediate outcomes) and target outcomes in trials to improve future reporting and aid stakeholders' interpretation and use of trial surrogate endpoint evidence. SPIRIT-SURROGATE/CONSORT-SURROGATE project is (MR/V038400/1) funded.
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DOI：
10.1136/bmj.f457
发表时间：
2013-01-29
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Ciani O;Buyse M;Garside R;Pavey T;Stein K;Sterne JA;Taylor RS
通讯作者：
Taylor RS
DOI：
10.1136/bmj.k211
发表时间：
2018-02-07
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Adab P;Pallan MJ;Lancashire ER;Hemming K;Frew E;Barrett T;Bhopal R;Cade JE;Canaway A;Clarke JL;Daley A;Deeks JJ;Duda JL;Ekelund U;Gill P;Griffin T;McGee E;Hurley K;Martin J;Parry J;Passmore S;Cheng KK
通讯作者：
Cheng KK
影响因子：
2.9
作者：
Llor, Carl;Moragas, Ana;Robles, Purificacion
通讯作者：
Robles, Purificacion
影响因子：
4
作者：
Lassere, Marissa N.;Johnson, Kent R.;Rees, David
通讯作者：
Rees, David
影响因子：
1.7
作者：
Campbell, M J;Lancaster, G A;Eldridge, S M
通讯作者：
Eldridge, S M