To establish an evaluation system by learning experience from abroad

The benefits and risks of the public health expectation and the subjects should be weighed, and the expected benefits should exceed the possible damage. Thus, the assessment on safety and risk of medicine is the basis for the safety of clinical trial. In other countries, there are safety reporting and evaluation system. Compared with those countries, China has not yet established a sound safety evaluation system. According to the development of clinical trials in China, if the safety evaluation system is established by enterprises, the enterprises may have a false assessment for the security risk of clinical drugs so that they can make more money. Therefore, it is necessary to establish a safety evaluation system from national level or it should be set up by an independent third party that should have staff in various fields such as medicine, pharmacy and law. According to previous results of animal and human studies, assessment on safety of the drug and expected risk should be conducted before the clinical trials. In the process of the test, they should also evaluate the safety of AEs. At the same time, they must provide the evaluation report of the assessment results, and the corresponding personnel for evaluation will bear the responsibility of explanation. If any false data of assessment are found, the corresponding personnel for evaluation will be punished, and their certificates will be revoked.

To establish a management system of AEs

Monitoring the AE in clinical trials is a core part that is directly related to the safety of subjects and the quality of clinical trials. Therefore, to strengthen the monitoring of AEs is to protect the rights and interests of subjects^[4]. The establishment of a management system for AE includes the following parts:

(1) To establish the central ethics committee

Protecting the rights and interests of subjects is the greatest responsibility of the ethics committee. However, many ethics committee are attached to the hospital, and most of the members of the ethics committee are hospital personnel such as the director of hospital department or executive director except few individuals. In order to protect the interests of the hospital, they are unwilling to protect the interests of subjects. In addition, individual ethics committee of hospital and research institutions are combined together and it means they are both the referee and athletes. Therefore, it can not guarantee the quality of clinical trials. To establish the central ethics committee can not only avoid this problem, but also can ensure the fair decision.

(2) To control quality by all three parties

The safety of clinical trials must be monitored by all three parties consisting of hospital departments, managerial staff and enterprises. Each unit should assign a few people to form a team to monitor the safety factors of clinical trials so that the progress of clinical trial can be ensured.

(3) To report AE regularly

Safety reporting system in foreign countries has been set up, according to the 18th clauses in the Drafted Guidelines of the European Commission Directive 2001/20/EC, which required pharmaceutical enterprises should provide annual safety report^[5] for the clinical trials, while the 21st chapter 312.33 in the annual report of application of clinical trial^[6] from the United States Federal Regulations regulated the basic requirements and format of application of the annual report of clinical trial. But there are no reporting requirements for AE in clinical trials in China now, even if some individual research centers report the AEs that are only the case reports and we can not use them as references. Due to the effect on the test evaluation, a regular reporting of AEs should be established and AEs for each project should be summarized regularly and recorded in the file. If the safety problem of clinical drugs is found, the test should stop immediately, and the related researchers can cooperate to solve it.

To build a compensation system for the subjects

Strengthening the capacity of national regulatory and research centers can reduce the incidence of AEs, but it can’t completely avoid the occurrence of AEs. In the United States, there is a special protection act Protection of Human Subjects (Informed Consent) (21 CFR Parts 5) for the subjects. In China, research institutions are responsible for the treatment of the AEs and the sponsor is responsible for the costs. But there are no specific regulations about the terms of compensation. In the informed consent, the Ethics Committee clearly requires to write down the responsible party for the costs of the AEs.  However, much consent wrote “if drug-related AEs occurred, the sponsor is responsible for the expense”. The costs and whether the determination related to the drug AE is fair or not can cause damage to the subjects and bring a devastating blow to the clinical trials. Once a serious AE occurs, the sponsor is unable to provide adequate compensation to the subjects in time. The best solution is to establish an insurance system, namely, the enterprise purchases an accident insurance for the upcoming clinical trials. If the injury-related incidents occur in clinical trials, the insurance company will provide compensation to better protect the rights of the subjects. In addition, the government should establish a unified fund for new drugs test to support clinical trials. It can not only reduce costs for companies and promote the development of clinical trials, but also provide a further protection for the safety of subjects.

To strengthen training and improve expertise

(1) Clear concept of AEs

The reason for the phenomenon that some AEs are not recorded is that researchers do not have a clear concept of AEs. They think that they should only report the serious AEs and it is not necessary to record all the AEs. Some researchers think that the AEs are adverse reactions related to drugs that lead to the omission of the report. Therefore, researchers and clinical research associate should have professional training and they must pass the corresponding test before test. In this way, the qualified persons can participate in clinical trials researches.

(2) Setting up a central laboratory

Researchers should have professional judgment about the abnormal value of laboratory examination and other AEs. But due to various factors such as the researchers’ educational background and professional knowledge, the judgment about drug AEs is different in the same test. So, a central laboratory should be set up for quality control of the clinical trials and the report of the safety index outliers. The difference of the researchers’ judgment about laboratory examination and AEs can be avoided and the safety of the test can be guaranteed as well.

(3) Qualification certificates for researchers

The expertise of clinical research associate is also an important part to ensure the safety of clinical trails. Because the clinical research associates have different education degree and different level of profession at present, it’s necessary to implement the qualification certificates for them. Each clinical research associate must be subject to professional training and pass the test, and then they can be permitted to participate in clinical trials. If serious problems happen in the process of the test, their certificates should be revoked as the punishment.

To improve the researchers’ qualification and cultivate a strong sense of responsibility

Professional knowledge must be supported by a strong sense of responsibility, and SOP should be established before the trial. All the researchers should have certain training so that they can operate in accordance with the test specifications. At the same time, relevant departments should also organize occasional teaching and learning AEs recording, reporting and security checks through meetings, newspapers, special knowledge contests and other ways so that the relevant personnels can improve their sense of responsibility and realize the importance and necessity of AEs. Then researchers can achieve accurate and complete records timely, auditors can inspect carefully and each data has the traceability. Therefore, the clinical trials can be completed perfectly. In addition, some companies think too many AEs will have a bad impact on drug sales and new drug’s approval^[7]. This philosophy should be changed because the recording of AEs and grasping drug safety information can not only reduce potential risks, but also have possibility of finding out the other applicable symptoms of drugs. And it is good for companies’ long-term development.

Strengthening the supervision

Strengthening supervision is the key to assure the quality of clinical trials. Firstly, the government should increase the frequency and intensity of the on-site inspection and special team should be formed to check the clinical trials irregularly, especially when the subjects are old, weak, and pregnant or they must have longer observation period with special inspection test, etc. Secondly, as to the supervision of organization, the frequency of inspection should be increased. At the same time, when the first to be tested in the group, half of the group and the whole group are tested, supervision and management must be carried out to ensure the safety of the subjects. Finally, for the supervision of the inspector, all the documents in the process of inspection should be put into the folder, including inspection report and supervision table to guarantee the quality of clinical trials.

Setting up a record of credit assessment

Clinical trials can be accomplished with multilateral coordination. However, due to some relevant staff’s reasons such as attitude, position that lead to safety problems including records of AEs, serious AE reports as well as the accuracy of data. Enterprises, researchers and arbitrators may have such problems as not to comply with GCP or SOP. Therefore, a credit evaluation record should be set up to classify the credit rate for clinical trials. According to records of AEs, serious AE report and the nursing care of the subjects, individuals with high credit of should be rewarded. In contrast, individuals with low credit should be punished. For the organizations, once the credit is too low, they are not allowed to do the clinical trials, and pay for a certain amount of fine. At the same time the results should be publicized. As to individuals, credit should be related to their performance appraisal, promotion and salary increase. Once they get lower credits, besides the fine, their qualifications in the industry will be cancelled. Meanwhile, mutual supervision should be encouraged, and the reporting system should be established to improve the transparency of the test. If enterprises or individuals have some problems, everyone has the right to report. The corresponding management department should offer certain reward to the informers and keep secret for them. By doing so, the safety of clinical trials can be improved greatly

Information management

With the development of science and technology, network management has been popular in various fields. But China’s clinical trials are still in the preliminary stage of development, many research institutions have not set up network management, and they still use manual record. It’s not only a waste of time and energy, but also has shortcomings such as data lost and easy to modify. In addition, the accuracy of clinical trials requires that research institutions should establish an operation platform. The platform should manage all the clinical trials, including information of subjects, vital signs, test results and the progress of the test, etc. The laboratory project should connect with the clinical laboratory directly, the researchers check the subject’ voucher number after giving the medicines, and the test results will show directly on the platform. This not only saves time greatly, but also guarantees the accuracy of the data that is good for the management of clinical trials. Besides, the project should be connected to pharmacy network as well. Due to the large flow of drugs in hospital pharmacy, each institution should establish independent clinical trials pharmacy to better guarantee the quality of medicines. Researchers can learn the drug distribution and recycling through the network by managing pharmacy. If there is a problem in the test, it can be solved in time, and the related management departments can know the situation of drug test as well so that they will help to solve the problem. At the same time, the random drug clinical trials can effectively reduce the probability of damage with the help of pharmacy network management. In addition, subjects can receive the drugs after telling their names that will reduce the probability of taking the wrong medicines in the multiple drug clinical trials, and it ensures the safety of the subjects, and then the clinical trials can be completed quickly and efficiently.