Abstract:Objective To systematically analyze the current status，risk factors and root causes of protocol deviation（PD）in drug clinical trials，and construct risk control strategies to reduce the incidence of PD and improve the quality of clinical trials. Methods A retrospective collection was conducted on PD reports（351 cases in total）from 105 drug clinical trial projects carried out in Zhongda Hospital Affiliated to Southeast University from January to December 2024.Pareto chart was used to identify the main types of PD and responsible subjects，and fishbone diagram was applied to trace and analyze multi-dimensional causes including personnel ，processes and mechanisms. Results The main responsible subjects of PD were subjects（52.99%）and investigators（29.06%）. The primary types of PD included window violations（30.20%），examination/visit-related deviations（28.21%）and medication-related deviations（17.38%）. The root causes were concentrated in insufficient personnel compliance（lack of subject cognition and weak Good Clinical Practice awareness of investigators），process defects（absence of standardization）and unreasonable design by sponsors.Conclusion Based on the multi-dimensional causes of PD，a whole-process risk control strategy featuring“subject-centered，investigator-focused and clinical research coordinator-supported”is proposed. By optimizing protocol design，strengthening compliance management and improving quality control mechanisms，the incidence of PD can be significantly reduced，so as to ensure the authenticity of trial data and the safety of subjects.