Study on the Emotional Status and Rights Protection of Participants in Drug Clinical Trials during Epidemic Prevention and Control / 中国医学伦理学

【Objective:】 To analyze the emotional status and follow-up status of the participants in the drug clinical trials in a hospital during the epidemic prevention and control, with a view to maximizing the protection of participants’ rights and interests under special circumstances. 【Methods:】 The general information, depression screening scale (PHQ-9), anxiety screening scale (GAD-7) and subject compliance assessment scale were completed online by participants with gold data questionnaire. At the same time, the status of drug clinical trials under study and the follow-up status of participants under study were collected from November 1, 2021 to December 8, 2021 and from December 9, 2021 to January 24, 2022. Excel software and SPSS18.0 software were used for data statistics and analysis. 【Results:】 During the epidemic prevention and control, there were 20 drug clinical trial projects under way in the hospital. From December 9, 2021 to January 24, 2022, the planned number of visits was 161, and the actual number of visits to the hospital was 84 (52.2%). Plus 24 participants who mailed drugs, the overall visit rate was 67.1%, among which the visit rates of oral drugs, non-oral drugs, and oral drugs combined with non-oral drugs were 79.3%, 71.9%, and 41.0% respectively. From November 1, 2021 to December 8, 2021, the planned number of visits was 166, the actual number of visits to the hospital was 157 (94.6%), and the number of telephone visits accounted for 1.8% of the total planned number of visits. The number of participants who did not take the drug and those who delayed taking the drug were both 0. The total compliance of participants was as high as 80.0%. A total of 40 valid questionnaires were retrieved, and the detection rates of depression and anxiety were 42.5% and 30.0% respectively. 【Conclusion:】 The epidemic prevention and control has a large short-term impact on the follow-up of the participants under study. The formulation of relevant follow-up measures and the conduction of classification management can not only improve the emotions of the participants to a certain extent, but also protect the rights and interests of participants, providing suggestions for the follow-up of participants under emergencies in the future.

Procedures for application of the extended dosing after antitumor drug clinical trials / 中南大学学报(医学版)

New drug clinical trials have been considered as a positive way for treating cancer by cancer patients and doctors, and the extended dosing is a special way for patients' withdrawal from antitumor clinical trials to obtain investigational new drugs. However, neither the regulations of expanded dosing nor the detail documents for expanded dosing have been officially published in China. At present, expanded dosing of investigational drugs is still at the exploratory stage in various medical institutions, and a complete management system has not been established to meet patients' urgent needs for drug use. Based on the practical experience of extended dosing in Hunan Cancer Hospital, this paper preliminarily explored the application procedures and ethical review requirements of extended dosing for subjects in antitumor clinical trials. It is necessary to clarify the responsibilities of all patients in the procedure and establish a patient-medical institution-sponsor joint application system. In the process of ethical review, it is recommended that all parties fully consider the risks and benefits of extended dosing for patients, and then the ethics committee makes a comprehensive assessment to decide whether to approve extended dosing.

Case analysis and management of research-related injury compensation of drug clinical trials / 中华医学科研管理杂志

Objective:To propose suggestions on the prevention and treatment measures of drug clinical trial research-related injury from the research center perspective, and improve the protection of the rights of human subjects.Methods:Analyze three representative cases of drug clinical trial research-related injury compensation in a hospital, and put forward suggestions for the project management of the research center.Results:By reviewing informed consent forms and clinical trial liability insurance, actively participating in research-related injury treatment and implementation supervision, paying attention to safety information and risk monitoring, ethics committees, clinical trial institutions and investigators can play more proactive roles in protecting the rights and interests of human subjects.Conclusions:The research center could better control the risks of clinical trials and improve the protection of human subjects by strengthening the prevention and treatment measures for clinical trial research-related injury.

Discussion of GCP Trial Drug Dispensing Workflow in PIVAS of Daytime Chemotherapy Center / 中国药房

OBJECTIVE：To explore the new management model of Good Clinical Practice （GCP）trial drug dispensing . METHODS：Base on the relevant experience of Pharmacy Intravenous Admixture Services （PIVAS）in daytime chemotherapy center（“daytime PIVAS ”for short ）of our hospital ，the nodes and other matters needing attention were discussed in the workflow of confirmation and development of drug dispensing tasks for clinical trials. RESULTS ：After the successful approval of the new clinical trial ，the supervisor of the sponsor and the principal investigator should first confirm whether the drugs involved in the project needed to be centrally dispensed in the daytime PIVAS ，and then submitted the relevant data to PIVAS for filing. Daytime PIVAS pharmacists could participate in trial drug dispensing of relevant projects only after starting training and authorization. After the doctor issued the medical order for the subjects in the hospital information system ，the research nurse took the drugs out of the GCP pharmacy and handed them to the daytime PIVAS drug receiving window. After receiving the drugs ，the pharmacist would check the dispensing ，and then the preparation pharmacist trained and authorized by the project team would mix and dispense the drugs. The reviewed pharmacist would check and label the prepared infusion. In addition ，daytime PIVAS would regularly summarize the feedback information on the trial drug dispensing and fund management in all links of dispensing process ，so as to improve the standardization of the process. CONCLUSIONS ：Daytime PIVAS for clinical trial drug can arrange batches more rationally，ensure smooth and orderly infusion ，and meet different drug stability requirements ，which can improve trial drug dispensing management and further promote the development of drug clinical trial projects in China.

Data Analysis on Protocol Deviation in Blind Review of Drug Clinical Trials of a CRO Company from 2010 to 2019 / 中国药房

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。

Brief analysis on the measures for the management of instruments and equipment in phase drug clinical trials / 中国临床药理学与治疗学

AIM: To discuss the standardized management methods of drug clinical trial instruments and equipment based on the analysis of current situation of the management in drug clinical trial instruments and equipment in institutions. METHODS: Through literature searching and our experience, we analyzed the nowadays problems in management of instruments and equipment, established and improved the management system, refined the standard operating procedures, promoted information management, and strengthened the construction of professional team of instrument and equipment management or database. RESULTS: The implementation of dedicated management ensured the whole implementation management, reduced the frequency in management problems, and improved the professional level of instrument and equipment management. CONCLUSION: The construction of standardized instrument and equipment management system is the premise of standardized development of drug clinical trials, which improves the management level of drug clinical trial instruments and equipment, ensures the authenticity and accuracy of trial data, and effectively enhances the quality of following drug clinical trials.

Interprestation of the key review points of human genetic resources application / 中华医学科研管理杂志

Objective To strengthen human genetic resource management in clinical trials.Methods This article analyzes the common problems in the process of reviewing human genetic resources application by the drug clinical trial institute in our hospital,and proposes solutions for solving the problems.Results Common questions are also the key points for future review of human genetic resources applications,including the collection of sample and consistency with clinical trial plan,ethical review and informed consent,intellectual property rights etc.Conclusions Strictly reviewing applications of human genetic resources,as well as strengthen the management of human genetic resources in clinical trials,are not only make traceability of human genetic resources traceable,but also have important significance for the authenticity and scientific validity of trial results.

Talking about the Key Points and Notices of Drug Management in Clinical Trials / 中国药房

OBJECTIVE： To provide references for improving the standard operating procedures of drug management in clinical trials and drug management in clinical trials. METHODS： According to Good Clinical Practice （GCP）， Data On-site Verification Points of Drugs Clinical Trial， Qualification Examination Rules of Drug Clinical Trial Institution， based on the quality control project carried out in our hospital since July 2016， the matters needing attention in the non-standard operation and key process of drug management in clinical trial were summarized， and the improvement measures were discussed. RESULTS & CONCLUSIONS： Non-standard drug management is a high-incidence link of non-standard operation in the trial process. Among them， the acceptance， distribution and use of drugs are the three links with the highest incidence of non-standard operation of drug management in the trial process. Therefore， when formulating the relevant management system， each institution should pay attention to it according to its own situation； such as， when accepting drugs in clinical trials， attention should be paid to checking the intact degree of drug packaging； drugs transported in cold chain should also be checked for temperature records and rejected in case of over-temperature； the copies of the waybill should be kept in file with the original to avoid fading of the thermosensitive paper； whether the relevant characteristics of the control drugs and placebos meet the requirements. Institutions can standardize the key links of drug management in the trial process， the time of project establishment， project start-up， quality control and supervision， formulate and constantly improve the relevant drug management system and standard operating procedures （SOP）. For example， when starting a project， attention should be paid to the participation of drug administrators in the training and signature of start-up meeting， whether the design of the form is complete， standardized and operable. It is necessary for clinical trial institutions to pay attention to the standardization and precision of drug management and the key links in clinical trials.

Influence and Reflections on the Work of Drug Clinical Trial Institutions in China after Joining in ICH / 中国药房

OBJECTIVE： To summarize the problems and countermeasures which the construction of drug clinical trial institutions face after China Food and Drug Administration （CFDA） join in ICH， and its effects on clinical study management in China. METHODS： Combined with the experience on Good Clinical Practice （GCP） in our hospital during recent years， reviewing related content of ICH-GCP， the differences between China’s GCP （CFDA-GCP） and ICH-GCP， the problems faced by drug clinical trial institutions after joining in ICH， and the thinking of China’s clinical research were discussed. RESULTS & CONCLUSIONS： There were differences between CFDA-GCP and ICH-GCP in the management concept of clinical drug trials， the structure and function of ethical committees， the protection of the rights and interests of subjects， the choice of researchers and research institutions， management requirements of experimental drugs and the management of documents and data. After joining in ICH， the current organization and management structure， system and standard operating procedures， ethics committee， GCP training and continuing education， professional quality control system， experimental drug management， data management and information system construction and upgrading， clinical research coordinator management and other aspects of the drug clinical trial institutions were far from the requirements of ICH. The standardization of drug clinical trial institutions in China can be further promoted by revising regulations and guidelines， formulating standard operating procedures in line with ICH-GCP， building standardized ethics committees， implementing GCP training and continuing education， improving quality control system and drug management in clinical trials， strengthening hardware and software construction and clinical coordinator management， etc. At the same time， problems such as fewer full-time personnel and weak implementation of the system can be improved by strengthening project management， improving the quality of employees and building normal cross-regional cooperation.

Construction and Thinking of Pediatric Clinical Trial Training System / 中国药房

OBJECTIVE： To improve the quality of pediatric clinical trials， and establish the clinical trial training system for pediatric. METHODS： By consulting the literature， referring to the clinical research and training system of the United States and the European Union （mainly including initiators， training objects， training contents and time， training methods and assessment methods）， and combining with the characteristics of pediatric clinical trials in China， the pediatric clinical trial training system was built. RESULTS & CONCLUSIONS： The training system of clinical drug trials in the United States and the European Union is relatively perfect. Taking the United States as an example， clinical drug trials in the United States were initiated by the National Institutes of Health （NIH）， mainly for clinical researchers and other health technicians engaged in clinical research. The training contents included pharmacology， clinical research principle and practice， bioethics， etc. The training time was usually not indicated. The main methods included distance education and online network training， and assessment through online network examination. The author suggests that a collaborative network of pediatric clinical trials should be established in China. For clinical researchers， training courses should be developed at different levels （e.g. basic classes， promotion classes， advanced classes） and corresponding time should be set up （e.g. 2， 3， 4 d）. Various training methods should be set up （e.g. online， face-to-face， assignment， etc.） and assessment methods should changed （be changed to face-to-face assessment and formulate unified assessment criteria）. The training system of pediatric drug clinical trials in China can be gradually built and improved through the above ways.

Risk assessment, prevention and control of drug clinical trial institutions / 肿瘤研究与临床

The management of drug clinical trial institutions from the risk management point of view is investigated. According to the technology of risk assessment in risk management, taking the project audit as an example, basing on the basic procedures of risk identification, risk assessment and risk control, making 8 risk factors into the table of risk management for project approval of clinical trial in order to initially establish a risk management of drug clinical trial institutions. In this way, the management quality of project for drug clinical trials will be probably improved, so that the risk incidence rate will be effectively reduced in the later phase of clinical trial.

Practice of PDCA Method in the New Specialties Accreditation of Drug Clinical Trial Institution / 中国药房

OBJECTIVE:To explore the effects of PDCA method in the new specialties accreditation of drug clinical trial institution. METHODS:PDCA method was used for drug clinical trial institution office and 9 newly applied majors in our hospital. Total score of each major were compared before and after intervention,in order to make the newly applied major meet the standard of specialties accreditation of drug clinical trial. RESULTS:After conducting PDCA related training,establishing new specialties accreditation work group,formulating work goals and plans,9 new majors of our hospital were all approved by CFDA for new specialties accreditation;after intervention total score of each accreditation item for newly applied major were all higher than before intervention,with statistical significance(P<0.05),improved by more than 45.57%. CONCLUSIONS:It is feasible to adopt PDCA method in the preparation of new specialty accreditation of drug clinical trials. It is of significance to guarantee scientific and reliable drug clinical trial results and protect the rights and interests of the subjects.

Improving the management level of clinical trial based on the establishment of drug clinical trial center pharmacy / 中华医学科研管理杂志

Objective To discuss our drug clinical trial institution's experience and findings during the process of establishing drug clinical trial central pharmacy.Methods Analyze the previous key issues identified during the drug management under different modes,discuss the necessity and feasibility of establishing drug clinical trial central pharmacy.Meanwhile,discuss the planning and construction of hardware including location site of the central pharmacy,equipment and facilities,staff,as well as software such as electronic management system and standard operation procedures.Results After the adoption of central trial pharmacy,space and energy are saved,manpower and material resources are saved,the quality of clinical trials also improved.Conclusions Standardized and unified management of investigational drugs through establishing drug clinical trial central pharmacy,is the strong guarantee for the drug safety of human subject,as well as the accuracy and scientificity of trial results.

Clinical trial investigators′ satisfaction with clinical research coordinators and discussion on managing strategy / 中华医院管理杂志

Objective To learn the investigators′ satisfaction with CRCs and to identify the shortcomings with the CRC industry or institutional management for improvement. Methods A questionnaire survey was conducted among 120 clinical trial investigators at three tertiary general hospitals in January 2018. The questionnaire covered the basics, satisfaction with CRC, and comments of the investigator on other works of the CRC. The data acquired were subject to descriptive analysis, and the count data comparison method was Fisher precise test. Results The investigators were satisfied with CRCs in general. Specifically, their satisfaction with the " sense of responsibility" , " work hours" , and " command of GCP protocols"ranged 72.6% to 83.2% . That with " initiative" , " work stability" , and " rich clinical trial experience" fell below 60.0%. Affiliation of CRCs was correlated to "initiative"(P=0.007), and "command of clinical trial schemes and trial procedures" ( P =0.043), while investigators′ satisfaction with CRCs of uncertain affiliation fell significantly. Investigators′ experience was correlated to the " command of GCP protocols" of CRCs(P=0.035 ), as the more experienced the investigator, the less their satisfaction with the CRC. Conclusions Hospitals are expected to build a CRC standardized training system and hierarchical certification system; to standardize their CRC recruitment mechanism for overall management; to enhance their budgeting capability for sufficient CRC expenses, higher investigator efficiency and assured clinical trial quality.

Application and Efficacy of 6S Quality Management Methods in Drug Clinical Trials of Oncology Department / 医药导报

Objective To evaluate the application and efficacy of 6S quality management methods in drug clinical trials of oncology department.Methods By using 6S (Seiri,Seiton,Seiso,Seiketsu,Shitsuke,Safety) quality management methods,quality about mastering level of good clinical practice (GCP) knowledge,sample collection and drug management etc.were controlled,and efficacy after the quality control was evaluated.Results After implemention of 6S quality management,rate of achieving GCP certificate was increased to 77.80％,accuracy rate of sample collection and accuracy rate of medicine preparation were increased to 100.00％,and the rate of relearning study protocol was increased to 100.00％,and subjects' satisfaction was improved significantly.Conclusion The implementation of 6S quality management methods could effectively enhance the quality of drug clinical trials in oncology department.

Retrospective Study on the Protocol Deviation in Drug Clinical Trial Implementation of Our Hospital / 中国药房

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.

How to Protect the Vulnerable Groups in Drug Clinical Trials / 中国医学伦理学

Objective:To find a better way to protect the security and interests of vulnerable groups by exploring the problem of protecting the vulnerable groups in drug clinical trial from the perspectives of ethics committees,organization and researchers.Methods:According to the relevant literature and the actual situation of the hospital,this paper analyzed the security issues of vulnerable groups comprehensively.Results:Only the ethics committees,organization and researchers work together,can it protect the security and interests of vulnerable groups to the greatest extents.Conclusion:Further research on the security of vulnerable groups not only promotes the development of human health,but also plays a decisive role in improving the protection of subjects in drug clinical trial.

Analysis and Intervention on the Key Links of the Quality of Drug Clinical Trials in Our Hospital / 中国药房

OBJECTIVE:To discuss the countermeasure on the quality improvement of the drug clinical trials in our hospital based on the discovery of key links of the quality of clinical trials. METHODS:Quality results of 14 drug clinical trials in 10 ma-jors from the drug clinical trial institute in our hospital in 2014 were investigated. Referring to the grading and classifying methods of the inspection problems in European Medicines Agency,the key links of occurring problems were analyzed,and the effects of interventions for key links were evaluated. RESULTS:In 2014,totally 125 important and general problems were found,in which, the numbers of problems occurred in case report form filling,informed consent of subjects,enrolling and screening of subjects,in-vestigational products management accounted for 79.20%. The above 4 links were the key links affecting quality of drug clinical tri-als. According to strengthening the training about relevant knowledge of the researchers,improving system and standard operation procedures management,enhancing link quality control,introducing project clinical research coordinator,developing centralized drug management and other interventions,the total numbers of found important and general problems in 2015 and 2016 were 68 and 59,respectively. Compared with 2014,the differences were statistically significant(P0.05). There were no severe problems during 2014-2016. After interventions,numbers of occurring prob-lems in majors with less complex drug clinical trial had obviously declined in 2016. Compared with 2014,the differences were sta-tistically significant (P0.05). CONCLUSIONS:Controlling the key links in drug clinical trial process can obviously reduce the occurrence of general problems while has little effect on the occurrence of im-portant problems. It is different for different majors in undertaking drug clinical trial projects,so as the links and degree of occur-ring problems. It should be distinguished in quality control checking.

Study on the Differences of Pregnancy Informs between Chinese and Foreign Informed Consent Form in Drug Clinical Trial / 中国医学伦理学

Objective:To explore and discuss the differences of pregnancy contents and inform formats in in-formed consent form ( ICF) for the drug clinical trial between China and foreign countries. Methods:We collected Chinese and foreign ICFs for drug clinical trial that had been audited by the Ethics Committee of the third Xiangya Hospital for the past five years. Based on the relevant domestic and foreign law, we concluded the element stand-ards and inform formats about pregnancy inform. By analyzing the integrity of the whole elements, the inform rate of every element and the using rate of every inform format, we compared the differences of pregnancy contents and in-form formats between Chinese ICFs and foreign ICFs. Results:The total number of ICFs was 177 in this study, in-cluding 107 Chinese ICFs and 70 foreign ICFs. The integrity rate of pregnancy in Chinese ICFs was statistically lower than them in foreign ICFs (19% vs. 56%, P=0. 000). Compared with foreign ICFs, the low informed ele-ments were the study of the pregnancy risk (32% vs. 73%, P=0. 000), the pregnancy test during the following-up period (33% vs. 56%, P=0. 002) and the measurements for contraception (22% vs. 53%, P=0. 000). Conclusion:The integrity level of pregnancy content in Chinese ICFs was lower than that of the foreign ICFs. And the three elements including pregnancy risk study, pregnancy test during the following-up period and measure-ments for contraception was obviously defected. Pregnancy informing forms of informed consent in China was inferi-or to abroad.

Analysis and Countermeasures of Common Ethical Issues in the Medical Clinical Trial Implementation in Oncology Department / 中国医学伦理学

This paper reviewed the common ethical issues in oncology drug clinical trials implementation of one hospital, such as the auditing and implementation of research protocols were not strict, the quality of research-ers needed to be improved, the hardware facilities for drug clinical trial was lacking, the informed consent signature was not standard, and the professional quality control was lacking. After corresponding countermeasures had been taken, such as the strict examination of research programs, strengthening the research team construction, taking the focus of GCP and SOP training, equipping hardware facilities for drug clinical trials, standardizing of ICF signa-ture, and the joint implementation of the quality control in hospital and departments, the researchers′ professional quality was further improved, which established a good foundation for better implementation of the drugs clinical tri-als and protection of the participants′interests.