Gryaznov Dmitry, Odutayo Ayodele, von Niederhäusern Belinda, Speich Benjamin, Kasenda Benjamin, Ojeda-Ruiz Elena, Blümle Anette, Schandelmaier Stefan, Mertz Dominik, Tomonaga Yuki, Amstutz Alain, Pauli-Magnus Christiane, Gloy Viktoria, Bischoff Karin, Wollmann Katharina, Rehner Laura, Lohner Szimonetta, Meerpohl Joerg J, Nordmann Alain, Klatte Katharina, Ghosh Nilabh, Heravi Ala Taji, Wong Jacqueline, Chow Ngai, Hong Patrick Jiho, Cord Kimberly Mc, Sricharoenchai Sirintip, Busse Jason W, Agarwal Arnav, Saccilotto Ramon, Schwenkglenks Matthias, Moffa Giusi, Hemkens Lars G, Hopewell Sally, von Elm Erik, Briel Matthias
Department of Clinical Research, Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel and University of Basel, Spitalstrasse 12, 4031, Basel, Switzerland.
Applied Health Research Centre, Li Ka Shing Knowledge Instiute of St Michael's Hospital, Toronto, Canada.
Trials. 2020 Oct 28;21(1):896. doi: 10.1186/s13063-020-04808-y.
Clearly structured and comprehensive protocols are an essential component to ensure safety of participants, data validity, successful conduct, and credibility of results of randomized clinical trials (RCTs). Funding agencies, research ethics committees (RECs), regulatory agencies, medical journals, systematic reviewers, and other stakeholders rely on protocols to appraise the conduct and reporting of RCTs. In response to evidence of poor protocol quality, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guideline was published in 2013 to improve the accuracy and completeness of clinical trial protocols. The impact of these recommendations on protocol completeness and associations between protocol completeness and successful RCT conduct and publication remain uncertain.
Aims of the Adherence to SPIrit REcommendations (ASPIRE) study are to investigate adherence to SPIRIT checklist items of RCT protocols approved by RECs in the UK, Switzerland, Germany, and Canada before (2012) and after (2016) the publication of the SPIRIT guidelines; determine protocol features associated with non-adherence to SPIRIT checklist items; and assess potential differences in adherence across countries. We assembled an international cohort of RCTs based on 450 protocols approved in 2012 and 402 protocols approved in 2016 by RECs in Switzerland, the UK, Germany, and Canada. We will extract data on RCT characteristics and adherence to SPIRIT for all included protocols. We will use multivariable regression models to investigate temporal changes in SPIRIT adherence, differences across countries, and associations between SPIRIT adherence of protocols with RCT registration, completion, and publication of results. We plan substudies to examine the registration, premature discontinuation, and non-publication of RCTs; the use of patient-reported outcomes in RCT protocols; SPIRIT adherence of RCT protocols with non-regulated interventions; the planning of RCT subgroup analyses; and the use of routinely collected data for RCTs.
The ASPIRE study and associated substudies will provide important information on the impact of measures to improve the reporting of RCT protocols and on multiple aspects of RCT design, trial registration, premature discontinuation, and non-publication of RCTs observing potential changes over time.
结构清晰、内容全面的方案是确保随机临床试验（RCT）参与者安全、数据有效性、试验顺利开展以及结果可信度的重要组成部分。资助机构、研究伦理委员会（REC）、监管机构、医学期刊、系统评价者以及其他利益相关者都依赖方案来评估RCT的实施情况和报告质量。针对方案质量欠佳的证据，《标准方案项目：干预性试验建议》（SPIRIT）指南于2013年发布，以提高临床试验方案的准确性和完整性。这些建议对方案完整性的影响以及方案完整性与RCT成功实施和发表之间的关联仍不明确。
遵循SPIRIT建议（ASPIRE）研究的目的是调查英国、瑞士、德国和加拿大的REC在《SPIRIT指南》发布之前（2012年）和之后（2016年）批准的RCT方案对SPIRIT清单项目的遵循情况；确定与不遵循SPIRIT清单项目相关的方案特征；并评估各国在遵循情况方面的潜在差异。我们根据瑞士、英国、德国和加拿大的REC在2012年批准的450个方案和2016年批准的402个方案组建了一个国际RCT队列。我们将提取所有纳入方案的RCT特征和对SPIRIT的遵循情况的数据。我们将使用多变量回归模型来研究SPIRIT遵循情况的时间变化、各国之间的差异以及方案的SPIRIT遵循情况与RCT注册、完成和结果发表之间的关联。我们计划进行子研究，以检查RCT的注册、提前终止和未发表情况；RCT方案中患者报告结局的使用情况；非规范干预的RCT方案对SPIRIT的遵循情况；RCT亚组分析的规划；以及RCT中常规收集数据的使用情况。
ASPIRE研究及相关子研究将提供重要信息，说明改善RCT方案报告的措施的影响，以及RCT设计、试验注册、提前终止和未发表等多个方面随时间观察到的潜在变化情况。
