ABSTRACT
OBJECTIVE To learn the common proto col deviation （PD）in the process of drug clinical trials and discuss the methods and precautions for preventing and reducing PD so as to provide reference for the standardization of drug clinical trials. METHODS According to Good Clinical Practice ，Notice on Issuing Guidelines for Planning and Reporting of Data Management and Statistical Analysis of Drug Clinical Trials ，Guidelines for Ethical Review of Drug Clinical Trials ，ICH E 3，ICH E 6（R2）and other regulations ，the PD reported in the relevant projects managed by the author from March 2017 to February 2022，as well as the PD found in the submission materials and project quality control ，were sorted out and statistically analyzed. RESULTS & CONCLUSIONS A total of 39 drug clinical trials were included ，and 212 subjects were selected. In all projects ，258 PDs were reported，including 28 major PD （accounting for 10.85％）and 230 ordinary PD （accounting for 89.15％）. The report of PD mainly included missed inspections/tests （93 reports，accounting for 36.05％），lack of visits （36 reports，accounting for 13.95％）， inspection/testing out-of-window （29 reports，accounting for 11.24％），dosage and usage of test drugs （28 reports，accounting for 10.85％），drug over-temperature/missing temperature （21 reports，accounting for 8.14％），etc. Avoiding and reducing the occurrence of PD requires the efforts of multiple parties ：the sponsor designs a reasonable protocol with appropriate interview rate and window period after listening to the opinions of multiple parties ；the investigators and clinical research coordinator should strengthen their own learning and training ，and be familiar with the protocol ，Good Clinical Practice and corresponding regulations；the compliance education of the subjects should be strengthened ；the institutional offices and ethics committees should conduct multi-angle and whole-process supervision and management when a drug clinical trial is approved ，in progress ，and jsyj- concluded，to ensure the safety rights and interests of the zdcxX0079） subjects and the quality of clinical trials. On this basis ，all parties should communicate effectively and timely ，report PD in time ，and conduct special studies on major PD that have com occurred and key links that are prone to PD.
ABSTRACT
OBJECTIVE：To study the effects of protocol deviation on the results of clinical trials ，and to provide reference for rising the quality management of drug clinical trials. METHODS ：Blind data review forms for clinical trials of a contract research organzation （CRO） company in Guangzhou from 2010 to 2019 were collected to analyze general characteristics of protocol deviation，the situation of protocol deviation before and after the “722 announcement”（Announcement on Carrying Out Self-inspection and Verification of Drug Clinical Trial Data issued by CFDA on July 22，2015）as well as the effects of protocol deviation on full analysis set （FAS）population division. The suggestions were put forward. RESULTS ：A total of 45 trials were included，involving 454 centers，14 304 disease cases and 5 562 cases of protocol deviation. The most common types of protocol deviations were over-window ，violation of criteria of the inclusion and exclusion ，and drop-out ，which accounted for 36.88％， 20.71％ and 18.43％ respectively. There was no statistical significance in protocol deviation degree of clinical trials with different stages or drug types （P＞0.05）；there was significant difference in the degree of protocol deviations in clinical trials with different stages before and after the “722 announcement”（P＜0.05）；the incidence of deviations from over-window ，violation of cirteria of the inclusion and exclusion ，and medication compliance had increased after the “722 announcement”；82.07％ of cases with protocol deviations could enter FAS ，and the population who included in FAS but did not enter per protocol set （PPS）accounted for 53.99％ of the total deviation ，of which deviations from drop-out and combined medication accounted for 19.51％ and 4.29％ respectively. All cases with deviation from medication compliance did not enter PPS. CONCLUSIONS ：Drop-out，violation of criteria of the inclusion and exclusion ，and over-window are the main factors that cause clinical trial protocol deviations. The “722 announcement”played a certain role on improving the quality management awareness of the personnel in drug clinical trial. Appropriate statistical methods should be selected to control bias ，and to strengthen the quality management of drug clinical trials and reduce protocol deviations ，by paying attention to trial design， staff training ， institutional management and 85223869。
ABSTRACT
With the promulgation of a series of laws and regulations in our country, the requirement for stand-ardized management of clinical research process are gradually clear, and higher requirements on the following-up review management of ethics committee also are put forward. Through concluding and summarizing 128 noncompli-ance/violation or protocol deviation reports accepted by a hospital in recent two years, this paper analyzed four main problems including that the researchers at management level failed to report or report timely; the researchers reported in irregular filling;the same type of violation/deviation program happened repeatedly and the rectification to the review opinions of ethics committee was ineffective, and also put forward the corresponding suggestions, in order to strengthen and perfect the standard management of noncompliance/violation or protocol deviation report.
ABSTRACT
OBJECTIVE:To study the influencing factors of protocol deviation in drug clinical trial implementation,and pro-vide reference for improving the quality of drug clinical trial. METHODS:Quality verification was conducted for the drug clinical trial projects in the First Affiliated Hospital of Chongqing Medical University during 2010-2016,and protocol deviations in each year were retrospectively studied,classified and analyzed. Category,frequency,international and domestic pilot projects and the differences of protocol deviation after full-time research nurse participating in trail management were explored,and the measures were put forward. RESULTS:27 drug clinical trials were implemented in our hospital during 2010-2016,including 949 cases,176 cases with protocol deviation,accounting for 18.55％. Deviation protocol in drug clinical trial was decreased year by year for 7 years. The categories were mainly incompleteness of observation/records (30.11％),checking omission/broaden the window(28.41％),adverse drug events and improper combined medication (14.20％) and omission in drug management (11.93％). The proportion of protocol deviation with full-time research nurse participated was lower than the projects without full-time research nurse(11.11％ vs. 28.67％,P<0.01),and proportion of deviation protocol in international multi-center project was lower than the domestic projects(6.60％ vs. 28.84％,P<0.01). CONCLUSIONS:It is suggested to pointedly strengthen the weak links of drug clinical trial. For example,clinical trial institutions should establish the clinical trial data retention system,electronic data should be timely backed up in a different places,etc. Besides,clinical trial institutions should equip professional full-time research nurses as much as possible,learn the rigorous scientific experimental design,standard operational procedures and the authenticity of data pro-cessing from the international multi-center clinical trial projects to effectively reduce the incidence of deviation protocol and im-prove the quality of drug clinical trials.