Exploration On Quality Control Before And After The Start-Up Of Drug Clinical Trial Project

Objective:The selection and initiation of sites is an important part of drug clinical trial project initiation management.The purpose of this study is to design a reliable and feasible scale for the selection and assessment of drug clinical trials in the phase Ⅱ of the innovative drug nitro-hydrazine(TBN)for the treatment of amyotrophic lateral sclerosis(ALS),and to further improve and optimize the standard operating procedures for the initiation of sites,so as to ensure and improve the quality management level of drug clinical trial initiation.Methods:1.Literature research method was used to search relevant literature of clinical trial quality management.Through CNKI,Pub Med and other databases,the main influencing factors are extracted.SPSS software was used to statistically analyze the Cronbach coefficient of the scale to determine the reliability level.Expert evaluation method was used to evaluate the content validity of the scale.2.The scale was applied in the phase Ⅱ clinical trial of TBN for ALS,and the performance of different sites obtained by the scale tool in clinical operation was examined,thereby verifying the feasibility of the scale.3.With the help of the PDCA cycle method,the quality management SOP process of the start-up work was established.Conducted empirical analysis of the quality management strategy and SOP in the start-up stage to achieve the goal of continuous improvement of quality management.Results:1.The "site selection and assessment scale" was preliminarily constructed,with 4dimensions and 26 indicators.The results of the scale pre-experiment collected data from 41 sites,and the results showed that the overall Cronbach α of the scale was0.939,after the expert content validity evaluation,the overall content validity level of the scale was 0.84,and the validity level met the requirements,while the ICVI of the M1-1,M2-4,M2-10,M3-2,and M3-6 indicators was less than 1,so it was excluded,and the official scale finally retained 4 dimensions and 21 indicators.2.The site selection of TBN treatment ALS Clinical Phase Ⅱ Trial was taken as an example,a total of 90 sites scale evaluation tables were collected,of which 74 sites ALS specialty have GCP qualifications.The official scale has an overall Cronbach αof 0.927,with a high level of reliability;the scale validity level can be guaranteed after pre-evaluation and expert evaluation.According to the scale score,the sites were divided into three groups,3 high groups(≥17),34 middle groups(≥13 and<17 points),and 37 low groups(<13 points).Comparing and analyzing the progress and quality of the three sites that actually started A(18 points),B(17 points),and C(13 points),the results showed that the time spent before the start-up of the sites is A<B<C;the training frequency of site personnel is A>B>C;the frequency of file filing errors is A<C<B;the screening failure rate of subjects is A<B<C;and the subject enrollment rate is B>A>C.As the site score increases,the progress of the site experiment accelerates;the training frequency of high-group sites(A and B)is higher,the screening failure rate of subjects is lower,the enrollment rate of highgrouping sites is greater than that of medium-grouping,however,the frequency of file filing errors showed the opposite trend.3.In view of the mechanical application of trial document templates,irregular process operations,insufficient personnel training and other problems before the site startup.The pre-project work SOP was implemented and developed,achieved continuous improvement of quality by PDCA cycle method,optimized the document management system,and formulated and improved a new project operation system,the implementation of personnel training diversification model and other measures.Comparing the work results of the A,B and C sites before and after the intervention,it is suggested that the training frequency of the site personnel after the intervention had generally increased,the error rate of trial document filing and the screening failure rate of subjects have decreased significantly,while the enrollment rate of subjects has increased.The quality of project management work has been effectively guaranteed.Conclusion:1.Based on the clinical study of the real-world new drug TBN,the quantifiable "site selection and assessment scale" formulated for the impact index of clinical trial site selection management in this study had guiding significance for the clinical trial site selection management.2.The PDCA cycle method continued to effectively identify quality risks and optimized multiple SOPs in the project start-up stage,the start-up schedule of the site and the quality of the project were improved,which ensured the progress of clinical trial enrollment and data quality.3.Combined with the site selection scale tool and the PDCA cycle method,it could effectively improve the selection quality of the site and improve the management level of the start-up work.