背景:早期剂量发现(EPDF)研究对于开发新的治疗方法至关重要,直接影响化合物或干预措施是否可以在进一步的试验中进行研究,以确认其安全性和有效性.标准方案项目:2013年干预试验建议(SPIRIT)和2010年随机试验报告合并标准(CONSORT)声明中存在临床试验方案和已完成试验报告的指南。然而,原始声明及其扩展均未充分涵盖EPDF试验的特定功能.DEFINE(DosE-FIndiNg扩展)研究旨在提高透明度,完整性,EPDF试验方案(SPIRIT-DEFINE)及其完成后的报告(CONSORT-DEFINE)的可重复性和解释,在所有疾病领域,基于原始的SPIRIT2013和CONSORT2010声明。
方法:将对已发表的EPDF试验进行方法学审查,以确定报告中的特征和缺陷,并告知候选项目的初始生成。早期的清单草案将通过对已发表和灰色文献的审查来丰富,真实世界的例子分析,引用和参考搜索以及与国际专家的咨询,包括监管机构和期刊编辑。CONSORT-DEFINE的开发于2021年3月开始,随后从2022年1月开始进行SPIRIT-DEFINE。一个改进的Delphi过程,涉及全世界,多学科和跨部门的关键利益相关者,将运行以细化清单。2022年秋季的国际共识会议将最终确定两项指南扩展中的项目清单。
背景:该项目已获得ICR临床研究委员会的批准。卫生研究机构确认不需要研究伦理批准。传播战略旨在最大限度地提高指导方针的认识和吸收,包括但不限于在利益相关者会议中传播,会议,同行评审的出版物以及EQUATOR网络和定义研究网站。
背景:SPIRIT-DEFINE和CONSORT-DEFINE已在EQUATOR网络中注册。
Early phase dose-finding (EPDF) studies are critical for the development of new treatments, directly influencing whether compounds or interventions can be investigated in further trials to confirm their safety and efficacy. There exists guidance for clinical trial protocols and reporting of completed trials in the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 and CONsolidated Standards Of Reporting Randomised Trials (CONSORT) 2010 statements. However, neither the original statements nor their extensions adequately cover the specific features of EPDF trials. The DEFINE (DosE-FIndiNg Extensions) study aims to enhance transparency, completeness, reproducibility and interpretation of EPDF trial protocols (SPIRIT-DEFINE) and their reports once completed (CONSORT-DEFINE), across all disease areas, building on the original SPIRIT 2013 and CONSORT 2010 statements.
A methodological review of published EPDF trials will be conducted to identify features and deficiencies in reporting and inform the initial generation of the candidate items. The early draft checklists will be enriched through a review of published and grey literature, real-world examples analysis, citation and reference searches and consultation with international experts, including regulators and journal editors. Development of CONSORT-DEFINE commenced in March 2021, followed by SPIRIT-DEFINE from January 2022. A modified Delphi process, involving worldwide, multidisciplinary and cross-sector key stakeholders, will be run to refine the checklists. An international consensus meeting in autumn 2022 will finalise the list of items to be included in both guidance extensions.
This project was approved by ICR\'s Committee for Clinical Research. The Health Research Authority confirmed Research Ethics Approval is not required. The dissemination strategy aims to maximise guideline awareness and uptake, including but not limited to dissemination in stakeholder meetings, conferences, peer-reviewed publications and on the EQUATOR Network and DEFINE study websites.
SPIRIT-DEFINE and CONSORT-DEFINE are registered with the EQUATOR Network.