Rekowski Jan, Guo Christina, Solovyeva Olga, Dimairo Munyaradzi, Rouhifard Mahtab, Patel Dhrusti, Alger Emily, Ashby Deborah, Berlin Jordan, Boix Oliver, Calvert Melanie, Chan An-Wen, Coschi Courtney H, de Bono Johann, Evans Thomas R Jeffry, Garrett-Mayer Elizabeth, Golub Robert M, Hayward Kathryn S, Hopewell Sally, Isaacs John D, Ivy S Percy, Jaki Thomas, Kholmanskikh Olga, Kightley Andrew, Lee Shing, Liu Rong, Maia Israel, Mander Adrian, Marshall Lynley V, Matcham James, Peck Richard, Rantell Khadija Rerhou, Richards Dawn P, Seymour Lesley, Tanaka Yoshiya, Ursino Moreno, Weir Christopher J, Yap Christina
Clinical Trials and Statistics Unit at the Institute of Cancer Research, London, UK.
The Institute of Cancer Research, London, UK.
EClinicalMedicine. 2025 Jan 10;79:102987. doi: 10.1016/j.eclinm.2024.102987. eCollection 2025 Jan.
Early phase dose-finding (EPDF) trials are key in the development of novel therapies, with their findings directly informing subsequent clinical development phases and providing valuable insights for reverse translation. Comprehensive and transparent reporting of these studies is critical for their accurate and critical interpretation, which may improve and expedite therapeutic development. However, quality of reporting of design characteristics and results from EPDF trials is often variable and incomplete. The international consensus-based CONSORT-DEFINE (Consolidated Standards for Reporting Trials Dose-finding Extension) statement, an extension of the CONSORT statement for randomised trials, was developed to improve the reporting of EPDF trials. The CONSORT-DEFINE statement introduced 21 new items and modified 19 existing CONSORT items.This CONSORT-DEFINE Explanation and Elaboration (E&E) document provides important information to enhance understanding and facilitate the implementation of the CONSORT-DEFINE checklist. For each new or modified checklist item, we provide a detailed description and its rationale with supporting evidence, and present examples from EPDF trial reports published in peer-reviewed scientific journals. When reporting the results of EPDF trials, authors are encouraged to consult the CONSORT-DEFINE E&E document, together with the CONSORT and CONSORT-DEFINE statement papers, and adhere to their recommendations. Widespread adoption of the CONSORT-DEFINE statement is likely to enhance the reporting quality of EPDF trials, thus facilitating the peer review of such studies and their appraisal by researchers, regulators, ethics committee members, and funders.
This work is a further extension of the CONSORT-DEFINE study, which was funded by the UK Medical Research Council (MRC)-National Institute for Health and Care Research (NIHR) Methodology Research Programme (MR/T044934/1). The Clinical Trials and Statistics Unit at The Institute of Cancer Research (ICR-CTSU) receives programmatic infrastructure funding from Cancer Research UK (C1491/A25351; CTUQQR-Dec 22/100 004), which has contributed to accelerating the advancement and successful completion of this work.
早期剂量探索（EPDF）试验是新型疗法开发的关键，其结果直接为后续临床开发阶段提供信息，并为反向翻译提供有价值的见解。对这些研究进行全面且透明的报告对于准确且批判性地解读它们至关重要，这可能会改善并加速治疗开发。然而，EPDF试验设计特征和结果的报告质量往往参差不齐且不完整。基于国际共识的CONSORT-DEFINE（报告试验剂量探索扩展的统一标准）声明是随机试验CONSORT声明的扩展，旨在改善EPDF试验的报告。CONSORT-DEFINE声明引入了21个新项目并修改了19个现有的CONSORT项目。这份CONSORT-DEFINE解释与阐述（E&E）文件提供了重要信息，以增进理解并促进CONSORT-DEFINE清单的实施。对于每个新的或修改的清单项目，我们提供详细描述及其依据和支持证据，并展示同行评审科学期刊上发表的EPDF试验报告中的示例。在报告EPDF试验结果时，鼓励作者参考CONSORT-DEFINE E&E文件以及CONSORT和CONSORT-DEFINE声明文件，并遵循其建议。广泛采用CONSORT-DEFINE声明可能会提高EPDF试验的报告质量，从而促进对此类研究的同行评审以及研究人员、监管机构、伦理委员会成员和资助者对其的评估。
这项工作是CONSORT-DEFINE研究的进一步扩展，该研究由英国医学研究理事会（MRC）-国家卫生与保健研究机构（NIHR）方法学研究计划（MR/T044934/1）资助。癌症研究所（ICR-CTSU）的临床试验与统计单位获得了英国癌症研究协会（C1491/A25351；CTUQQR-2022年12月/100004）的计划性基础设施资助，这有助于加速这项工作的推进和成功完成。
