Challenges Faced by "Young" Ethics Committees under the Mode of Collaborative Review / 中国医学伦理学

In the process of exploring standardized and efficient ethical review models for multi-center drug clinical trials, the ethical review alliance emerged as the times require. Compared with mature ethics committees, higher requirements have been put forward for the "young" ethics committees. By analyzing problems existing in review work of "young" ethics committees in the ethics review alliance, this paper discussed the measures to improve the review quality of "young" ethics committees and promote the standardized and efficient operation of the alliance, and put forward countermeasures and suggestions for improving the homogenization of ethics review and accelerating the clinical research process of innovative drugs.

Consideration of Ethical Protection in Drug Clinical Trials for Rare Diseases in Children / 中国医学伦理学

Children with rare disease belong to a vulnerable group. When China’s current medical security system cannot provide comprehensive health care, they not only face physical and mental torture, but also have a higher risk of children participating in clinical trials than adults. So, adequate protection of children’s safety and rights is the key to ethical review. This paper analyzed the current status of drugs clinical trials for rare disease in children, including trial difficulties and guarantee system; explained the ethical principles that should be followed in clinical trials, such as the principle of informed consent and the principle of no harm; and discussed the path of protecting children’s safety and rights, so as to raise awareness and attention of the importance of ethical review of clinical trials.

Common problems and suggestions of biological sample management in drug clinical trials / 中国药房

OBJECTIVE To provide a reference for improving the relevant standard operating procedures （SOP） and biological sample management in drug clinical trials. METHODS According to Good Clinical Practice， Data On-site Verification Points of Drugs Clinical Trials， Human Genetic Resources Management Regulations Implementation Rules， Qualification Examination Rules of Drug Clinical Trials Institution， based on the experience of managing clinical trials programs， the irregularities in biological samples management were analyzed by using statistical quality control tables and protocol deviation （PD） reported by sponsors， in the context of the quality control of drug clinical trials projects managed by the author from July 2016 to May 2023. The precautions in various aspects of sample management were put forward. RESULTS & CONCLUSIONS A total of 101 biospecimen- related irregularities were found in the 60 drug clinical trials projects. Biological sample collection， preservation， and handling were the aspects with the highest incidence of irregular operations in biological sample management， accounting for 37.62%， 25.74%， and 21.78%， respectively. Regulating the management of biospecimens requires multiple efforts. The institutional office and the ethics committee carefully reviewed the consistency of the protocols， informed consent， and genetic office application involving biospecimen collection and handling when the project was initiated. Institutional office quality controllers should pay attention to the attendance and training of authorized personnel at project initiation. The principal investigator， research nurse， collector， handler， transporter， relevant personnel of the central laboratory， and institutional office quality controller have their roles during the project implementation phase. On this basis， all parties involved in the management of biological samples should do a good job of effective communication， find problems and report them in time， and conduct special studies on key aspects.

Research on Influencing Factors of Drug Clinical Trial Risks in China Based on Literature Analysis / 中国医学伦理学

【Objective:】 To sort out the influencing factors of drug clinical trial risks and improve the risk management level of drug clinical trials in China. 【Methods:】 The literature analysis method was used to sort out the literature related to the risk management of drug clinical trials in China, and the text analysis method was used to summarize and refine the influencing factors of drug clinical trial risks. 【Results:】 The risk categories of drug clinical trials were divided into 5 parts, namely drug clinical trial institution management, ethics committee management, clinical trial designs, researchers, and subjects, involving 13 main risk influencing factors and 21 specific risk points. 【Conclusion:】 By strengthening the construction of drug clinical trial institutions and ethical management capabilities, optimizing research protocol design, enhancing researchers’ awareness and ability, and establishing a subject management system to improve the quality of drug clinical trials.

Protection of Informed Consent Rights for Subjects in Drug Clinical Trials / 中国医学伦理学

The right to informed consent is the basic right of subjects in drug clinical trials. International treaties and domestic laws have successively formed a basic right protection framework, while there are still some problems such as imperfect legal norms and incomplete practical operations. To meet future challenges, it is necessary to further improve legislation, standardize notification procedures, improve notification content, expand dynamic notification methods, and strengthen ethical review, so as to build a standardized and modern system for protecting the right to informed consent of subjects.

Research Status and Suggestion of Drug Clinical Trial Risk Management in China: Based on Co-word Analysis and Social Network Analysis Perspective / 中国医学伦理学

【Objective:】 To deeply understand the current situation and hotspots of drug clinical trials risk management in China. 【Methods:】 Co-word analysis and social network analysis were used to sort out the study results of risk management in drug clinical trials in China. 【Results:】 The trend of risk research of drug clinical trials in China was generally on the rise. The research hotspots focused on four areas: drug supervision and pharmacovigilance, risk management of drug clinical trial institutions, ethical review of drug clinical trials, and risk management of drug clinical trials. 【Conclusion:】 In the future, China should gradually improve the risk management system and supervision system of drug clinical trials, explore to establish a risk-based quality management and ethical review system of drug clinical trials, and enhance the risk assessment and coping ability of institutions.

Main Problems and Ethical Review Points of Subject Recruitment in Drug Clinical Trials / 中国医学伦理学

Drug clinical trials need to recruit suitable subjects to verify the safety and effectiveness of new drugs. Subject recruitment is a very important and challenging link in the whole process of drug clinical trials, and even directly affects the progress and final results of the trials. The medical ethics committee should give full play to the important function of ethical review, carefully review the whole process of subject recruitment from the perspective of science and ethics, and do a good job in the protection of the health and rights of subjects. This paper mainly discussed the basic principles of subject recruitment, the main problems existing in the recruitment process and the key contents of ethical review, so as to provide scientific references and suggestions for standardizing subject recruitment, protecting the rights and interests of subjects, and promoting the efficient and high-quality completion of drug clinical trials.

Analysis of the progress of clinical trials for ophthalmic drug in China, 2022 / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To explore the progress of clinical trials for ophthalmic drugs in China in 2022 and discuss its changes with 2014 to 2021, thus providing the latest data reference for the development of new drug and the implementation of clinical trials, and a basis for decision-making.METHODS: In this cross-sectional study, we retrieved the drug clinical trials registration and information disclosure platform of National Medical Products Administration database. Drug clinical trials for eye diseases registered from January 1 to December 31, 2022 were included. Number(proportion)was used to describe the characteristics of clinical trials for ophthalmic drug, the indication, the trial phase, the efficacy and the geographical distribution.RESULTS:A total of 55 clinical trials for ophthalmic drug were included, which accounted for 1.66% of all clinical trials, showing a steady growth trend. Main drug type was chemical drugs with the highest proportion of 58.18%. The top three indications with the most clinical trials were age-related macular degeneration, myopia and dry eye. Two gene drugs emerged in 2022, and 7 drugs carried out ≥2 trials, of which atropine sulfate and recombinant anti-vascular endothelial growth factor(VEGF)humanized monoclonal antibody were the most(7 and 5 respectively). Most trials were in phase I and phase III stages, accounting for 36.36% and 27.27% respectively. The median start-up time of phase I trials in 2022 was 2.72(0.77, 3.47)mo, which was significantly shorter than 3.87(3.00, 6.30)mo of 2014～2021(Z=-2.630, P=0.009), and there were no significant differences between BE, phase II, III, IV comparing with 2014～2021(P>0.05).CONCLUSIONS: In 2022, the number and implementation efficiency of clinical trials for ophthalmic drugs in China increased steadily. The indications are mainly fundus disease, myopia and dry eye. Most new drugs are in the early stage of research and development or close to market. Gene therapy drugs began to emerge.

Ethical analysis and countermeasures of artificial intelligence application in clinical trials / 中国临床药理学与治疗学

The development of artificial intelligence is becoming more and more mature, and has penetrated into every field of clinical trials. Artificial intelligence has brought new development opportunities for clinical trials. However, the application of artificial intelligence in clinical trials is still in the exploratory stage, facing many ethical issues, including trial risk caused by data quality, privacy protection caused by data regulation, and contradiction between data authorization and informed consent. We should precisely position the realizable application of artificial intelligence in clinical trials, understand its practical ethical issues, and formulate corresponding coping strategies to ensure the maximum improvement of the whole process performance of clinical trials, including strengthening data quality management and reducing clinical trial risks; optimizing data monitoring mechanisms to ensure data security and privacy; building a data authorization platform and improving judicial protection of informed consent, etc.

Common protocol deviations and improvement methods and precautions in drug clinical trials / 中国药房

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.

Ethical management of subjects′ complaints in drug clinical trials in a cancer hospital / 中华医学科研管理杂志

Objective:To analyze ethical management of subjects′ complaints in drug clinical trials in a cancer hospital.Methods:A retrospective analysis of the complaints of subjects received and properly handled by the ethics committee through telephone, e-mail and on-site reception during the drug clinical trial in our hospital. Case studies were conducted to analyze the reasons for the occurrence of some particular subjects′ complaints, processing procedures and resolution processes.Results:The number of subjects' complaints in clinical trials in our hospital decreased year by year. The ethics committee of our hospital would check it immediately and review it carefully after receiving the subjects′ complaints, and return the review decisions to the subjects and researchers, at the same time, follow up with board meeting report and documentation. Regarding to the reasons of the subject complaint, mainly identified were the failure to participate in clinical trials due to inclusion and exclusion criteria, withdraw by investigators due to safety concerns, and not satisfied with the compensation.Conclusions:When receiving subjects′ complaints, the ethics committee should manage them seriously, verify the reasons in time and follow up properly, act as a communication bridge between subjects, researchers and sponsors, try their best to resolve subjects′ complaints, and protect the rights and interests of subjects.

The Role and Function of Clinical Research Nurses in Anti-tumor Drug Clinical Trials for Lung Cancer Patients / 中国肺癌杂志

Clinical trials of anti-tumor drugs is not only the important way to develop new drugs, but also the most advanced treatment methods for malignant tumors, bringing survival benefits to patients. There are a large number of new anti-tumor drug clinical trials for lung cancer patients, covering a wide variety of anti-tumor drugs, and with rapid progress and high efficiency of clinical transformation. These trials could not be carried out successfully without the joint efforts of the research team, in which the research nurses also played a role that should not be underestimated. Combined with the work content of clinical research nurses, this paper introduced the post management, role function, core competence and career development prospect of clinical research nurses in the process of carrying out clinical trial of lung cancer drugs in detail. In order to provide reference for more medical institutions to carry out related work, and promote the further development of clinical research nurses to standardization and specialization.
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Information construction of drug clinical trials based on literature analysis / 中国临床药理学与治疗学

AIM: To sort out the research context of information construction of drug clinical trials and understand the hot spots and development trend of informatization construction of drug clinical trials. METHODS: The knowledge map CiteSpace software was applied to analyze the 391 items of literature collected from China CNKI database during the year of 2000 to 2020. A thorough investigation was conducted from the perspectives of quantitative analysis, research institutes, author, research hot topics and the research trend. A knowledge map was generated to sort out the main ideas of the research of the drug clinical trial information construction. RESULTS: The results showed that in the past 20 years, the number of published papers related to the construction of clinical information of drugs fluctuated, and most of the major research institutions had strong research ability in this field. But the interactions within research institutions remained improved, and the academic exchanges between scholars still needed to be strengthened. The shift in hot-spot research reflected a greater focus on systematizing and protecting subjects' rights. CONCLUSION: The research of information construction of drug clinical trial mainly focuses on clinical trial, drug clinical trial, quality control and other aspects. It is the trend of future research to further improve the efficacy of trial management through information construction, ensure the reliability and standard of drug clinical trials, and effectively reduce the risks and hidden dangers of drug clinical trials.

Effectiveness analysis of the clinical research coordinators management carried out by drug clinical trial institutions / 中华医学科研管理杂志

Objective:To analyze the problems existing in the management mode of clinical research coordinator (CRC) in the new context, propose improvement measures and analyze the effectiveness of improvement.Methods:Four types of stakeholders related to CRC, including investigators, clinical research associates(CRA), institutional managers and human subjects were investigated in regular monthly questionnaire survey on the basis of CRC management comparasionat home and abroad. The new CRC management countermeasures implemented by our institution in July 2020 were taken as the time node, and the data from January to June 2020 were taken as the pre-implementation group, and the data from July to December 2020 were taken as the post-implementation group. Compare the monthly scores of CRCs′ work effect for 30 projects in the institution before and after the implementation of such countermeasures.Results:The scores of CRCs′ working effectiveness were improved after the implementation of CRC management countermeasures, whcih including standardizing the entry of CRC, updating of the training and assessment mechanisms, conducting regular communication meetings and developing reward and punishment measures. The scores from investigators increased by 20.17%, scores from CRAs increased by 11.54%, scores from institutional managers increased by 14.26%, scores from subjects increased by 10.64%, and the total scores increased by 14.13%( P<0.01). Conclusions:Countermeasures to optimize CRC management taken by drug clinical trial institutions can significantly improve CRCs′ working effectiveness in multiple dimensions.

Application of PDCA cycle method in improving the quality management of drug clinical trials / 中华医学科研管理杂志

Objective:To strengthen the quality management of drug clinical trials to ensure that the clinical trial data obtained is true, accurate, complete and standardized.Methods:By review literatures and the data published in NMPA and survey the problems in the drug clinical trials in some hospitals, etc, we summarized the common problems of drug clinical trials in China.At the same time, using PDCA cycle theory, we sorted out the problems in the drug clinical trials in Taizhou People's Hospital, conducted root-cause analysis of the problems, put forward suggestions and measures on how to strengthen the quality management of drug clinical trials.Results:The incidence of quality problems in clinical trials was significantly reduced from 105.6% to 37.4% by formulating relevant incentive policies, strengthening training, strengthening the supervision function of institutions to researchers, and improving the awareness of GCP of researchers.Conclusions:The implementation of PDCA cycle quality management model can effectively improve the quality of drug clinical trials.

Study on Quality Risk Management of Ethical Review of Dr ug Clin ical Trials / 中国药房

OBJECTIVE：To pro vide suggestions for imp roving the quality of ethical review of drug clinical trials in China and protecting the rights and interests of subjects. METHODS ：Guided by risk management theory ，the literature research method ， expert opinion method and analytic hierarchy process method were used to sort out the ethical review process of drug clinical trials ， extract and determine the risk factors that affect the quality of ethical review ，and determine the weight of each risk factor. Suggestions were put forward improving the ethical review of drug clinical trials in China. RESULTS & CONCLUSIONS ： Established ethical review risk index system of drug clinical trials included 31 influential factors of 5 aspects；the order of importance（weights）of 5 aspects affecting the quality of ethical review of drug clinical trials was as follows ：the construction of the medical ethics committee （0.263 5），the management of review meetings （0.251 4），follow-up review （0.194 5），the acceptance and processing of review applications （0.189 2），and the management of documents and files （0.101 4）. The influential factors with high weight included “withdrawal of people with conflict of interest in the discussion and voting process （0.078 7）” “timely review or conference discussion of scheme modification ，informed consent modification ，serious adverse events ，etc. （0.070 5）”“clarification and external exhibition of the work process and time of ethical review （0.059 8）”“unified and standardized review standards and approval standards （0.052 1）”，etc. The quality of ethical review can be improved by avoiding people with conflict of interest in the discussion and voting process ，timely reviewing or holding ethics meetings on scheme modification ， informed consent modification ，serious adverse events ，etc.，clarifying the working process and time of ethical review ，and establishing unified and standardized review standards and approval standards.

Characteristics Analysis of Pediatric Drug Clinical Trials Registered in Chinese Clinical Trial Registry / 中国药房

OBJECTIVE：To provi de reference for standardizing pediatric clinical trials and promoting the development and application of pediatric medication in China. METHODS ：Chinese Clinical Trial Registry （Chi CTR ）database were searched to collect all clinical trials related to pediatric population under 18 years old from the inception to Oct. 1st，2019. Those clinical trials were analyzed statistically in respect of name of registered project ，involved disease/system ，research stage ，registration time ， registration status ，regional distribution of research institutions ，source of funds ，research type ，whether data management committee was set up ，situation of recruited research objects ，ethics committee approval status ，whether blind method was adopted ， whether to collect human specimens and whereabouts of human specimens. RESULTS ：A total of 231 pediatric drug clinical trials were included. The clinical trials involved 21 kinds of diseases/systems ，mainly were tumors and tumor-like lesions ，ophthalmic diseases and allergic disease. The research stage has the most items （85 trials，36.80％）in post-marketing drug clinical trials ；there were 77 items of phase Ⅰ-Ⅳ clinical trials （33.33％）. The number of pediatric drug clinical trials was increased year by year ，and among which 179 trials were pre-registered （77.49％），52 trials were supplementary registration （22.51％）. Beijing ，Shanghai， Guangdong，Chongqing and Zhejiang were the major regions where pediatric drug clinical trials were carried out ，and the clinical trial projects of which accounted for 66.23％（153/231）of the total number of included projects. The funding sources were mainly self-financing（57.85％），hospital finance （20.18％），and local government finance （10.31％）. The main type of research was intervention study and observational study ，accounting for 88.31％ in total. Totally 145 trials（62.77％）had not yet determined whether to set up a data management committee ；201 trials（87.01％）had passed the review of the ethics committee of the relevant institution；168 trials（72.73％）did not clarify whether the blind method was used ；133 trials（57.58％）had collected 001-001） human specimens ，and the collected human specimens were 3360875。E-mail：794446155@qq.com mainly destroyed after use. CONCLUSIONS ：The number of pediatric drug clinical trials registered in Chi CTR is increasing but there i s regional imbalance. Researchers have gradually established the concept of pediatric clinical trial registration ，and have realized the importance of data management to research quality ，and the management of collected trial specimens is relatively standardized. It is suggested that relevant departments increase the publicity of clinical trial registration and improve the clinical trial registration management system ； relevant researchers should increase the awareness of clinical trial registration ，standardize registration application and trial project management.

Investigation and Analysis of the Influencing Factors of Informed Consent of Subjects in Drug Clinical Trial / 中国医学伦理学

Taking a class A tertiary hospital in Shanghai as center, this paper understood the awareness of the subjects of drug clinical trials on their participation in the research and their own rights as subjects after the end of research (6～18 months) by questionnaire survey completed by telephone interview, analyzed the problems existing in the process of informed consent, compared with the foreign status, and summed up a variety of feasible ways of subject' s own right to be informed, to put forward feasible suggestions for the development and improvement of medical scientific research management and the ethical work in China.

Establishment and Application of Electronic Data Capture System in Drug Clinical Trials of Our Hospital / 中国药房

OBJECTIVE:To ensure the stability of electronic data capture(EDC)system in drug clinical trials and to improve the quality of drug clinical trials. METHODS:The quality control system for EDC system was established and introduced from the formulation of quality control process,establishment of data standard,trial project management,daily management,trial project design,system operation,system function,etc. RESULTS & CONCLUSIONS:Data standard have been achieved through estab-lishing EDC quality control system by our hospital based on attributable,legible,contemporaneous,original and accurate principle. The management of trial project and daily management are conducted through data registration,staff training,the formulation of da-ta management plan,fault emergency treatment,database backup;multiple verification of support data,data lock and export,trial report autogeneration and other functions have been realized by formulating related standard operation instruction,program file,op-eration manual and quality record. Those aspects improve facticity,accuracy and integrality of data in clinical trials,and lay a foun-dation for further data mining.

Analysis of 233 Cases of Severe Adverse Events in Drug Clinical Trials of Our Hospital / 中国药房

OBJECTIVE:To provide reference for performing quality control and protecting the subjects’rights and interests. METHODS:233 severe adverse events (SAE) cases reported by our hospital during Jan. 2012-Jun. 2015 were collected and ana-lyzed statistically in respects of subjects’gender and age,department,drug/equipment types,SAE types,relationship of SAE with drug/equipment,comorbidities,etc. RESULTS:The incidence of SAE in male was higher than female(71.2% vs. 28.8%);SAE mainly occurred in people over the age of 50(189 cases,81.1%);the incidence of SAE in cardiology department was the highest (137 cases,58.8%);main SAE type was hospitalization(183 cases,78.5%);most of SAE had nothing to do with studied drugs (164 cases,70.4%);more than half of the subjects suffered from other comorbidities(128 cases,54.9%). CONCLUSIONS:In order to ensure the quality of drug clinical trial data and safety of subjects,the investigator should strengthen the management of the elderly subjects and those suffering from comorbidities,to ensure that each SAE case is timely processed and accurately record-ed and reported.