Reporting of randomised trials using surrogate outcomes: development of extensions to the CONSORT 2010 and SPIRIT 2013 guidance statements

使用替代结果报告随机试验：开发 CONSORT 2010 和 SPIRIT 2013 指导声明的扩展

• 批准号: MR/V038400/1
• 负责人: Rod Taylor
• 金额: $ 12.17万
• 依托单位: University of Glasgow
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FV038400%2F1
• 关键词: Reporting; randomised; trials; using; surrogate

OUR AIM: To improve the accuracy and reporting of surrogate outcomes in randomised trials through the development of an extension to current reporting checklists.WHY THIS RESEARCH IS IMPORTANT: Evidence for the effectiveness of treatments ideally comes from well-designed randomised controlled trials that assess patient-centred outcomes that directly measures how a patient feels, functions, or survives. Widely adopted and evidence-based, SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) and CONSORT (Consolidated Standards of Reporting Trials) statements provide minimum recommendations for reporting protocols and results of randomised trials. In drive to make treatments available more quickly to patients, surrogate endpoints are increasing used as the main outcomes in randomised trials. A surrogate endpoint becomes a 'substitute' for patient centred outcomes, e.g. a trial of a new drug for particular type of life-limiting cancer ultimately seeking to improve patient survival, will assess tumour size within the clinical trial instead of death (that would take much longer to occur). Advantages of trials based on a surrogate endpoint is that they are shorter, smaller, and less expensive. However, an important potential down-side of such trials is that the therapy may turn out not to have the benefit predicted by a surrogate, e.g. the drug is licensed and made available based to patients based on evidence of a reduction in tumour size (compared to placebo) but turns out not to improve (or even worsen) patient mortality. It is therefore recommended that trials using surrogate endpoints only use endpoints that have been proven ('validated') to predict patient centred outcomes. However, this infrequently seems to happen in practice leading to potential misleading conclusions drawn from published studies. Therefore, better reporting is needed. Improving the reporting of trials with surrogate endpoints as its outcome will add value to the existing extensions to SPIRIT and CONSORT Standards. WHAT WE PLAN TO DO: We will adopt similar methods as used previously to develop SPIRIT and CONSORT main statements and extensions. We have already conducted a scoping review of the literature that we will use to draw up a long list of items that we consider may be useful in reporting surrogate endpoints trials. We will then conduct a Delphi, a quantitative method aimed at generating consensus comprising (1) an online survey, and (2) a virtual consensus meeting. For the online survey, we will contact stakeholders including clinical trials researchers with experience in the design/conduct/analysis/reporting of surrogate endpoints trials, knowledge users, representatives from funding bodies, journal editors, and patient and public involvement representatives. We will identify individuals from relevant publications and through our extensive research networks. The final phase of the study involves writing and disseminating SPIRIT and CONSORT extension guidance and checklists, and an 'Explanation and Elaboration' document that provides a more detailed guide of how to use the checklists, and examples of protocol and trial reporting good practice. One of the study group who has extensive experience in acting as lay contributor to trial methodological research has been involved in writing of this application and will help us ensure public involvement in our study, if funded. BENEFITS OF THE STUDY: CONSORT and SPIRIT extensions for surrogate primary endpoints will aid in critical appraisal and interpretation for grant reviewers, funding bodies, trial methodologists, journal editors, reviewers, and readers (including patients and members of the public). The outputs of this research are expected to reduce incomplete, unclear, or inaccurate reporting of protocols and trials assessing surrogate endpoints thus limiting erroneous conclusions about the long-term safety and efficacy of treatments.

我们的目的是：通过开发扩展到当前的报告清单，在随机试验中提高替代结果的准确性和报告。为什么这项研究很重要：理想情况下，理想的治疗有效性的证据来自精心设计的随机对照试验，这些试验良好地评估了患者中心的癌症，这些试验评估了直接测量患者的感觉，功能，功能或生存。广泛采用和基于证据的精神（标准协议项目：介入的建议）和配偶（报告试验的合并标准）声明为报告协议和随机试验结果结果提供了最低建议。为了使患者更快地提供治疗的动力，替代终点正在增加用作随机试验的主要结果。替代端点成为以患者为中心的结果的“替代”，例如针对特定类型的生命癌症类型的新药的试验最终试图改善患者的生存，将评估临床试验中的肿瘤大小，而不是死亡（这需要更长的时间）。基于代理端点的试验的优点是它们较短，较小且价格较低。但是，此类试验的一个重要潜在的下降是，该疗法可能不会具有替代物所预测的益处，例如该药物是根据患者获得许可并根据肿瘤大小减少的证据（与安慰剂相比）获得的，但事实证明并不能改善（甚至恶化）患者死亡率。因此，建议使用替代端点的试验仅使用已证明（“验证”）来预测患者以患者为中心的终点。但是，这种情况似乎很少发生在实践中，从而得出了从发表的研究中得出的潜在误导性结论。因此，需要更好的报告。改善具有替代端点的试验的报告，因为其结果将为现有的延期增值，并为精神和配偶标准增添价值。我们打算做的事情：我们将采用类似的方法来发展精神和配偶的主要陈述和扩展。我们已经对文献进行了范围的评论，我们将用来绘制一长串我们认为可能对替代端点试验有用的项目。然后，我们将进行Delphi，这是一种定量方法，旨在产生包括（1）在线调查的共识，以及（2）虚拟共识会议。对于在线调查，我们将联系利益相关者，包括临床试验研究人员，具有在设计/行为/分析/报告替代端点试验中经验的经验，知识用户，资助机构的代表，期刊编辑以及患者和公众参与代表的代表。我们将通过相关出版物和广泛的研究网络确定个人。该研究的最后阶段涉及写作和传播精神和配偶扩展指导和清单，以及一个“解释和详细说明”文件，提供了更详细的指南，以说明如何使用清单，以及协议和审判报告良好实践的示例。在作为试验方法研究的外行贡献方面拥有丰富经验的研究小组之一已经参与了本应用程序的撰写，并将帮助我们确保公众参与研究（如果资助）。研究的好处：代理主要终点的配偶和精神扩展将有助于赠款审稿人，资助机构，试验方法，期刊编辑，审阅者和读者（包括患者和公众）的批准评估和解释。预计这项研究的输出将减少评估替代终点的方案和试验的不完整，不清楚或不准确的报告，从而限制了有关治疗的长期安全性和功效的错误结论。

项目成果

A framework for the definition and interpretation of the use of surrogate endpoints in interventional trials.

• DOI: 10.1016/j.eclinm.2023.102283
• 发表时间: 2023-11
• 期刊: ECLINICALMEDICINE
• 影响因子: 15.1
• 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.
• 通讯作者: Taylor, Rod S.

Scoping and targeted reviews to support development of SPIRIT and CONSORT extensions for randomised controlled trials with surrogate primary endpoints: protocol.

• DOI: 10.1136/bmjopen-2022-062798
• 发表时间: 2022-10-13
• 期刊: BMJ open
• 影响因子: 2.9

A call for better reporting of trials using surrogate primary endpoints.

• DOI: 10.1002/trc2.12340
• 发表时间: 2022
• 期刊: ALZHEIMERS & DEMENTIA-TRANSLATIONAL RESEARCH & CLINICAL INTERVENTIONS
• 影响因子: 4.8
• 作者: Manyara, Anthony Muchai;Ciani, Oriana;Taylor, Rod S
• 通讯作者: Taylor, Rod S

Surrogate endpoints in trials: a call for better reporting.

• DOI: 10.1186/s13063-022-06904-7
• 发表时间: 2022-12-12
• 期刊: TRIALS
• 影响因子: 2.5
• 作者: Ciani, Oriana;Manyara, Anthony M.;Chan, An-Wen;Taylor, Rod S.
• 通讯作者: Taylor, Rod S.

Need for better reporting of trials with surrogate endpoints: SPIRIT|CONSORT-SURROGATE extensions.

• DOI: 10.1136/jech-2022-219294
• 发表时间: 2022-06-24
• 期刊: JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH
• 影响因子: 6.3
• 作者: Ciani, Oriana;Manyara, Anthony;Taylor, Rod S.
• 通讯作者: Taylor, Rod S.