Insights from the FDA Guidance on Protocol Deviation for the management of Investigator-Initiated Trials in Beijing
10.3760/cma.j.cn113565-20250326-00080
- VernacularTitle:FDA方案偏离指南对研究者发起的临床研究管理的启示
- Author:
Xiayan CHEN
1
;
Meirong WANG
;
Huijuan LI
Author Information
1. 北京大学第一医院 100034
- Publication Type:Journal Article
- Keywords:
Investigator-Initiated Trials;
Protocol deviation;
FDA Guidance;
Quality management
- From:
Chinese Journal of Medical Science Research Management
2025;38(4):284-290
- CountryChina
- Language:Chinese
-
Abstract:
Objective:Comparison of the U. S. Food and Drug Administration (FDA) Protocol Deviations for Clinical Investigation of Drugs, Biological Products, and Devices Guidance for Industry (Draft Guidance) and the Beijing Investigator-Initiated Trial (IIT) Supervision and Inspection Content and Assessment Principles with recommendations for managing protocol deviations in IITs.Methods:A comparative analysis was conducted focusing on the terminology, definitions, classifications, determination criteria, and management requirements for protocol deviations. The analysis was supplemented by practical experience from the 2024 IIT supervision and inspection in Beijing to explore the applicability of the FDA guidance in the local context.Results:The FDA guidance clearly defined the terminology and scope of protocol deviations, distinguishes between important and other deviations, emphasized the principle of quality by design, and clarified the responsibilities of relevant stakeholders and reporting procedures. The Beijing IIT Supervision and Inspection Assessment Principles, for the first time from a government regulatory perspective, introduced a quantitative classification system for determining the severity of protocol deviations. However, they had not fully addressed issues such as participant privacy protection and premature unblinding, and the management requirements remain to be refined. Findings from the 2024 IIT supervision and inspection in Beijing indicate that the most common protocol deviations were failure to follow the protocol-defined schedule or procedures for visits, tests, or outcome assessments; failure to collect critical data; and violations of inclusion/exclusion criteria.Conclusions:While Beijing has made progress in institutionalizing IIT management, the overall protocol deviation management system remains underdeveloped. This paper proposes the following recommendations: First, clearly define the responsibilities of various stakeholders within research institutions, strengthen coordination among administrative departments, ethics committees, and research teams, and fully leverage the support role of the Beijing Center for Advancing Quality in Clinical Research in methodological guidance and quality control. Second, enhance the capacity and ongoing training of research teams, and encourage medical institutions to provide methodological consultation and technical support. Third, improve the scientific rigor and feasibility of protocol design by tailoring inclusion/exclusion criteria and follow-up strategies to the specific study type and target population, optimizing study procedures, and developing risk-based management plans. Fourth, refine the classification criteria, reporting procedures, and timelines for protocol deviations, and implement a tiered management system based on the nature and severity of the deviation.
