Analysis of problems and countermeasures of researchers in drug clinical trials

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Time：2020-08-17Click：

Abstract: This paper analyzes the existing problems of researchers in clinical trials of drugs in China, and analyzes the countermeasures against the existing problems.

Key words: drug clinical trial; Quality control; Problems and countermeasures; Clinical trials of drugs; Quality management specification

Since July 22, 2015, the state food and drug supervision and administration bureau released no. 117, the state food and drug administration about a drug clinical trial data comprehensive inspections of announcement, thousands of drug clinical trial data verification, found problems with clinical trial data is untrue, incomplete, the poor quality of the clinical trials, and cannot be traced, and a series of problems. We look back at the whole process and analyze it at a deeper level. The main reason is that the people involved in clinical drug trials do not clearly understand the importance of the quality of clinical drug trials in ideology. At the same time, it also exposes some irregular habits of researchers in medical activities [1]. To solve these problems, it is necessary to form a unified consensus in the industry, so as to reveal the problems existing among researchers in drug clinical trials and explore solutions.

1. Existing problems

1.1 The design of the test scheme is not scientific and rigorous

The design level of the trial scheme directly affects the quality of the drug clinical trial. The importance of the research purpose should exceed the risk and burden brought to the subjects, and the research method must meet the requirements of science and ethics at the same time.

Article 36 of THE GCP, "The sponsors and researchers shall agree on the clinical trial protocol, and state their responsibilities and division of labor in the implementation of the protocol, data management, statistical analysis, results report, publication and other aspects [2]." Project leader (Project leader, PI) is the core personnel in clinical trials, is the primary responsible party, but we found that some of the PI GCP consciousness, rights and responsibilities, PI level is uneven, make plan in the process of research is not enough, on the basis of inadequate, evaluation index is not clear, do not conform to the ethics, as well as the quality problems of Adverse events (Adverse Event, AE) and severe Adverse events (Serious Adverse Event, SAE) description, records are not clear, make plan caocao, As a result, the design of the trial scheme is not scientific and rigorous, which seriously affects the quality of clinical trials, which is also the main reason for the gap between the quality of clinical trials in China and that in Europe and the United States.

1.2 The clinical trial research team is not well established and its responsibilities are not clear

One, for the moment, to undertake clinical trials of the clinical research center must have a good team, should be in the team project director, doctors, nurses, drug administrator, data administrators, data managers, quality control and the CRC, and everyone to have a clear division of responsibilities, solidarity, can smoothly and high quality to complete a clinical trial. But in the survey found a number of clinical trials program team organizational system is not complete, the responsibility is not clear, more than a man, even the researchers with 1 ~ 2 graduate students in clinical trials, moreover researchers regardless of everything, to a doctor or a graduate student at a lower level to do clinical trials, the team is in small, scattered, chaotic situation, management chaos, make it hard for drug clinical trial to achieve scientific, normalized operation, and the scientific nature of the test results, the reliability is affected.

1.3 Execution of clinical trials

Drug clinical trials required and there is a difference between the general clinical requirements, such as supervision over the problems of the window, in the general clinical work, a day earlier or later one day visit is fine as long as it's not emergency, but in the process of clinical trials is against the plan, is the researchers' poor execution, or the subjects' dependency is poor, the reason on the one hand, test scheme design itself not scientific, rigorous, lead to ethical, researchers can't accurately according to the plan to carry out the results appeared against testing scheme, the original data cannot be traced, subjects, visit window; On the other hand, the poor executive ability of researchers and their lack of scientific attitude towards clinical trials are also the main reasons for the low quality of clinical trials.

1.4 Problems in the informed consent

The purpose of the informed consent is to meet the ethical requirements and to protect the rights and interests of the subjects. The whole process is in the charge of the informed consent, in the survey found that most of the informed consent obtained through the motions become a mere formality, the researchers can't do in detail, the subjects were not abundant considering time, and the phenomenon of subjective influence decision making, there are incomplete informed consent, the screening of the subjects signed informed consent form lost not archive, although some subjects signed informed consent but did not obtain informed consent, seriously violated the ethical requirements.

1.5 Defects in clinical trial drug, data and data management

In clinical trial project check list checking survey found in the conclusion, some researchers do not distinguish between drug clinical trials and general clinical work, the test drug management chaos, do not conform to the regulations of GCP to test drugs, according to the requirement of temperature and humidity, drug storage, distribution, recycling, destruction, personnel, counters, personnel records such as incomplete, case report on the record is not timely, incomplete. Some hospitalization records did not record the process of the subjects' participation in the clinical trial, and the study records did not describe the relevant case records and combined medication in the hospitalization records, resulting in a series of problems such as protocol violation, incomplete records, AE omission, data missing and so on.

1.6 Application of CRC

Because researchers don't have plenty of time for Clinical trials, the team organizational system is not complete, forced most of the Clinical trial project must expatriate Clinical trials Coordinator (Clinical Research Coordinator, CRC) to assist the work, as a result, the hospital in a group of special groups, between don't know about CRC's actual ability to work, supervision and management mechanism is not sound, CRC source mixed and disorderly, change frequently, although researchers solved in a short period of time right now, but there are a number of researchers rely solely on CRC, essentially himself as a shopkeeper of cutting, To a large extent, the investigator lowered the level of responsibility and clinical trial, which led to the end of the trial project and the question of how to ensure the quality of the trial by finding the CRC that had left the office in order to understand the situation.

1.7 Adverse event management issues

Researchers of adverse events in clinical trials so far has not been caused widespread attention and the cause of this result is the lack of important to adverse events, adverse events, understanding of the concept of serious adverse events, and report the procedure of training, so that frequently appear in the process of clinical trials or omission, or report is not standard, can not reflect the incidence of adverse events and real safety evaluation indicators.

1.8 Hardware and facility conditions management

Undertake a multicenter clinical trial, should not only have a good team, also must have the implementation of clinical trials needed for the hardware conditions, in the survey found that although some professional department through the national certification, but in a clinical trial is not able to achieve resource sharing, sui generis, fight alone, the researchers in a serious violation of GCP regulations in the process of clinical trials, such as drug storage temperature and humidity is not standard, personnel, shop become a mere formality, data management is not standard, the subjects the phenomenon such as reception room is not in conformity with the requirements, the department staff do not GCP full knowledge popularization, As a result, some personnel do not support, do not cooperate with the work of clinical trials, seriously affect the quality of clinical trials.

2. Countermeasures analysis

2.1 Strengthen the systematic training and supervision of clinical trial PI

In strict accordance with the GCP principles, I have a broad grasp of GCP related knowledge. In line with the guiding principle that is based on clinical, higher than clinical, but not divorced from clinical, I encourage researchers to actively participate in the program design, AE analysis, methodology, data management, statistical analysis, summary report, and technical review. The hospital regularly organizes in-hospital and out-hospital training, and urges researchers to earnestly fulfill the task of PI, so that PI can become a qualified researcher, improve the level of PI comprehensively, and finally guarantee the standard and safe implementation of clinical trial projects [3].

2.2 Establish a qualified clinical trial team

In order to ensure the standard process and scientific and reliable results of drug clinical trials, and to protect the rights and interests of the subjects to the greatest extent and ensure their safety, it is necessary to establish a clinical trial team with professional quality, ideological quality, scientific style and earnest understanding of THE GCP spirit, so as to ensure the quality of clinical trials. But how to build a team that is a problem facing the current units, staff shortage, lack of sense of responsibility and responsibility consciousness, need your relevant professional support for hospital leadership, each department shall be in harmony, not only to give from the personnel, equipment, and to strengthen the professional quality of relevant personnel and the professional knowledge of regular hospital outside the hospital culture, ensure each professional clinical trials each work link, post responsibility system of the reasonable implementation, detail decides success or failure, attention to details in place, the quality of clinical trials is guaranteed the [4].

2.3 Improve the execution of clinical trials

Many quality problems found in the self-examination and verification of clinical trials are difficult for PI to take the blame. Due to the lack of in-depth understanding of GCP by clinical trial researchers, as well as the high pressure, lack of personnel, playing multiple roles and lack of ability to perform multiple tasks in the work, the execution ability of clinical trials is directly poor. Clinical trials in order to improve the executive ability, reduce the randomness in the PI in GCP implementation, multi-level and comprehensive strengthen the conduct propaganda of knowledge of GCP and learning is very important to enhance the consciousness of the GCP, only to understand the connotation of GCP, to design a scientific, rigorous, feasibility and good clinical trial scheme, in clinical trials in the concrete implementation, fully understand the purpose, significance of clinical trials and clinical trial scheme, set up perfect quality control system, the SOP and rewards and punishment system, and item by item, implement the responsibility to the people, to avoid a person more accountability, clear, can we improve the compliance of the researchers, Ensure the execution of clinical trials [5].

2.4 Strictly implement the SOP for Informed Consent

In the process of drug clinical trials must be on the subjects' personal rights and interests, security, therefore, must obtain written informed consent before clinical trials, in the process of signing only strictly enforced "SOP" informed consent can be truly content told, fully independent choice make participants fully understand the principle of clinical trial purpose, method, process, benefit and risk, voluntary participation in clinical trials, does the protection of the rights of the subjects, and ensure the scientific nature and reliability of clinical trials.

2.5 Strengthen the management of key links

The establishment of scientific and perfect drug management system and standard operating procedures is a necessary prerequisite to ensure the standardized management of experimental drugs. Meanwhile, the construction of clinical trial information can greatly improve the efficiency of clinical trials and realize the standardization, standardization and traceability of the whole process of clinical trials and drug management. Researchers have shifted the focus of drug clinical trial quality management from the evaluation of trial results to the pre-trial design and trial implementation to strengthen the management of key links [6].

2.6 Strengthen CRC management and improve work efficiency

In the process of the check list and verification, found that each unit of CRC source is multifarious, work ability, communication skills, coordination ability is uneven, appeared in a short period of time to solve the practical difficulties, some researchers do not solve the fundamental problem in the long run, in order to improve the work efficiency, guarantee the quality of clinical trials, Suggestions for clinical test units to form a batch of fairly regular/stable team of CRC and into hospital management category, CRC training and examination mechanism should be established in order to make the CRC specialization, long-term change, let the researchers from the tedious affairs freed, This will allow researchers more time to focus on the efficacy and safety of experimental drugs and better ensure the quality of clinical trials.

2.7 Attach importance to AE/SAE recording and evaluation

In before the start of every clinical trial must attach great importance to all participants in clinical trials relevant personnel of GCP knowledge training, strengthen the legal laws and regulations, the SOP training, work, realized the adverse event record and cause and effect evaluation is the key of the safety evaluation of each phase of clinical trial, adverse events, the definition of serious adverse events and record report, correct application of medical terminology and diagnosis and treatment norms. Adverse events and serious adverse events are described and continuously revised and supplemented. Therefore, the quality of tests is ensured and the safety of drugs after being marketed is ensured [7].