Guidelines for drug clinical trial management (trial) announced during the outbreak of new crown pneumonia!

On July 14, CDE issued the Guidelines for the Management of Clinical Trials of Drugs during the Outbreak of New Crown Pneumonia (Trial), effective.
as follows: Drug clinical trial management guidelines (trial) during the new crown pneumonia outbreak are facing many difficulties and challenges.
drug clinical trials require some special considerations from the start-up and implementation to the completion of the study.
in order to protect the safety of the subjects, implement the main responsibility of the applicant for clinical trials (hereinafter referred to as the applicant), ensure that the quality and data of clinical trials are true, accurate, complete and traceable, and the drug regulatory department and the applicant and researchers jointly discuss and formulate relevant measures to improve the management of drug clinical trials in special periods.
guidelines for emergency approval during the outbreak of new coronary pneumonia drugs (including vaccines) clinical trials and other clinical trials of drugs in the study for reference by sponsors and researchers.
. Basic Principles (1) Subject protection principles Drug clinical trials shall give priority to protecting the rights and interests of subjects, and shall strictly abide by the Relevant Technical Guidelines issued by the Drug Administration Law of the People's Republic of China, the Code of Quality Management of Drug Clinical Trials (hereinafter referred to as the GCP) and the International Coordinating Committee on The Registration of Human Drugs (ICH) and implement them in clinical trial institutions that meet the corresponding requirements.
the bidder stake sits on the main responsibility for clinical trials and safety risk control, and takes overall responsibility for the safety and quality of clinical trials, and the parties involved in clinical trials.
drug clinical trial institution is the subject of the protection of the rights and interests of subjects in drug clinical trials. the
Ethics Committee is responsible for reviewing the scientific and ethical rationality of drug clinical trial programs, reviewing and supervising the qualifications of drug clinical trial researchers, and supervising the conduct of drug clinical trials.
researchers are in charge of the trial site where clinical trials are conducted and are responsible for the quality of clinical trials and the rights and safety of subjects.
bidders shall conduct clinical trials in accordance with the relevant requirements in the clinical trial notice, the approval of the drug clinical trial, or the drug clinical trial filing information.
the applicant shall assess the impact of the experimental drug on the subjects and, if necessary, take measures and report the results to the Drug Review Centre of the State Drug Administration (hereinafter referred to as the Drug Review Center). During the
outbreak, all personnel participating in clinical trials should take personal protective measures in accordance with the requirements of the prevention and control of the new coronary pneumonia outbreak issued by the State, in particular, the subject's personal protection management should be strengthened to effectively protect the subjects.
(2) The applicant for drug alert and risk management should strengthen the construction of drug alert system during clinical trials.
shall carry out safety signal monitoring, risk identification, risk assessment and risk control in strict accordance with the requirements of drug alert work, timely report suspicious and unexpected adverse reactions (SUSAR), other potential serious safety risk information, and implement effective risk control measures.
should develop a sound risk management plan for known and potential risks, develop a scientificand and rigorous clinical trial plan and informed consent, and continuously update and improve the outbreak and research progress.
the applicant shall establish a clear standard for discontinuation of drugs, and if safety problems or other risks are found, the clinical trial plan shall be adjusted, clinical trials suspended or terminated, and reported to researchers, clinical trial institutions and drug review centers in a timely manner.
recommends timely communication with the Drug Review Center on safety risks.
bidders should consider establishing a Data and Safety Monitoring Committee (DSMB) to regularly assess progress, safety data and significant endpoints of effectiveness in clinical trials.
(3) All parties involved in clinical trials in accordance with the drug clinical trial quality management norms shall strictly comply with the requirements of the drug clinical trial quality management practices to ensure that the test data are true, complete and reliable.
parties should take the responsibilities of clinical trials seriously to ensure that either party is in place during the outbreak.
the project deviation caused by the direct or indirect cause of the outbreak, the
applicant and the researcher shall assess the risk in a timely manner and record it truthfully in accordance with the relevant requirements, and report to the ethics committee in a timely manner concerning the safety of the subjects. The
Ethics Committee shall review and draw conclusions on all kinds of reports received in a timely manner in accordance with the standard operating procedures, and shall fulfill its responsibility to protect the rights and interests of the subjects, and shall not delay the timely treatment, examination and evaluation of the subjects due to the failure to review them in a timely manner.
during the outbreak will face changes in clinical trial programs, changes in test sites, the addition of new researchers, unplanned communication between the parties, etc., which should be truthfully documented and documented for reference.
shall promptly report changes to clinical trial programmes, informed consent s/he and other documents required by the Ethics Committee to perform their duties for review. The original documents recorded during the
clinical trial shall be kept intact, and in addition to the normal recording of the subject's relevant information on various trials, any deviation, withdrawal or termination of the trial, safety information, etc. of the subject due to the outbreak due to the outbreak shall be recorded, modified and reported in accordance with the requirements of the original documents in the GCP.
II. Clinical trial management of new coronary pneumonia drugs (i) Enhanced drug clinical trial information timely reporting and risk assessment for the new crown pneumonia drug clinical trial approved by the State Food and Drug Administration Drug Special Approval Procedure (Bureau Order No. 21), the Drug Review Center organizes the development of a daily summary research information report template.
the applicant shall report daily to the Drug Review Center the progress of clinical trials and the summary information on safety, and take the initiative to carry out risk assessments and develop corresponding risk control measures, in accordance with the relevant requirements.
if there is no progress or new information on the day, it will also need to be explained briefly.
the drug review center to the applicant daily report of clinical trial progress, safety information and risk control measures to carry out risk identification and assessment, according to the review, the applicant is required to adjust the reporting cycle, timely submission of the research and development period safety update report, if necessary, to propose risk control recommendations or risk communication.
the applicant should improve and submit to the Drug Review Center important technical and compliance documents such as clinical trial programs, researcher manuals, informed consent sisions, and approvals from the Ethics Committee before the clinical trial is initiated.
if the relevant documents are updated during the clinical trial, they shall be submitted to the Drug Review Center in time for review by the Ethics Committee.
(ii) Consideration of clinical trial design and implementation In the course of clinical trial design and implementation, the applicant should give full consideration to the problems that may be faced in clinical trial sunder, combine the progress of disease cognition and scientific evaluation, and elaborate the participants' integration, evaluation indicators and evaluation methods, follow-up strategies, etc. in clinical trial design to ensure the safety of the subjects and the smooth conduct of the experiment.
communicate with the Drug Review Centre as necessary.
(3) The management of the place where the clinical trial is implemented shall be completed in accordance with the Regulations on the Administration of Drug Clinical Trial Institutions for the treatment of the new crown pneumonia treatment and treatment of the new crown pneumonia fixed-point hospital that has not been recorded by the drug clinical trial institution.
for special circumstances such as square cabin hospitals, medical treatment teams, etc., if necessary, may communicate with the relevant management departments in advance to confirm.
(4) Special considerations for clinical trial supervision and inspection In the field of clinical trial supervision and inspection, if on-site inspection can be run, the scope of supervision shall take full account of the limitations of relevant laws and regulations, the urgency of the inspection and the feasibility of the staff of the clinical trial institution, and should be carried out with the consent of the clinical trial institution.
temporary alternatives may include the cancellation or postponement of on-site visits, the extension of the interval between visits, telephone and video visits, the adoption of centralized and remote surveillance.
central monitoring can be conducted through electronic systems (e.g. electronic data acquisition systems, etc.) to dynamically monitor the implementation of clinical trials to ensure data quality.
remote monitoring focuses on the origin of raw data, as it may involve the privacy of the subject, should be carefully selected under the premise of ensuring the privacy of the subject.
any alternative measures should be taken without placing an additional burden on clinical trial agency staff and equipment.
the applicant shall carefully record the situation, the results and related measures that cannot or have to delay the monitoring of the clinical trial institution, and formulate measures to strengthen the follow-up inspection when the situation returns to normal.
inspections should usually be postponed or cancelled.
critical tests that are considered essential for inspection, on-site or remote inspections may be considered after agreement has been reached with researchers and clinical trial institutions.
3. Other clinical trial management of drugs in the study is affected by the outbreak, and the implementation process of clinical trials that are currently under way or that is about to be conducted may face many practical difficulties.
If a clinical trial agency person or subject is infected with the new coronary pneumonia virus (2019-nCoV), this will face challenges from human isolation, the closure of clinical trial facilities, the failure to send and use experimental drugs, the loss of subjects, and the failure to complete the relevant tests as required, which can lead to inevitable deviations from the trial program.
therefore, risk and quality management should be strengthened throughout the process from the beginning of subject recruitment to the end of clinical trials.
all measures taken to respond to the outbreak should be aimed at maximizing the safety of subjects, ensuring the quality of test data to the extent possible, and minimizing the impact of the outbreak on the integrity of clinical trials.
Based on some of the improvements being tried by domestic clinical trial institutions, researchers and bidders in recent times, consider the following clinical trial safety management measures: (i) re-evaluate the initiation and conduct of clinical trials 1. The feasibility of initiating new clinical trials and recruiting new subjects should be rigorously assessed, with a focus on the safety impact on subjects, taking into account the characteristics of the experimental drugs, the potential impact of the clinical trial stakes, the potential impact of the outbreak on the supply chain of experimental drugs, and the potential impact of the test drug supply.
encourage bidders to establish DSMbs to maximize the safety of subjects by maximizing the safety of subjects in assessing the safety of subjects,such as whether the impact of the outbreak on the implementation of clinical trials by plan poses new safety risks to subjects, the impact of changes in clinical trial implementation on the safety of subjects, and so on.
2. Closing clinical trial institutions and initiating new clinical trial institutions If an institution is unable to continue to participate in clinical studies because of the outbreak, the sponsor should consider whether to close it and how to proceed without compromising the safety and data quality of the enrolled subjects.
If the laboratory must be closed, the subject should be transferred, with the consent of the subject, to a clinical trial facility where the trial can be carried out, such as a trial facility far from the risk zone or closer to home, a pilot institution that has conducted the trial, or a possible new laboratory.
in an emergency situation, new clinical trial sorups are generally not recommended unless there is no other solution.
if a new clinical trial institution needs to be urgently launched for a critical trial visit, it can be implemented as an emergency safety measure, updated and submitted to the Drug Review Center Drug Clinical Trial Registration and Information Disclosure Platform.
in case of significant programme changes, a supplementary application should be submitted.
if the subjects need to be transferred, the subjects, the applicants, the researchers (receiving and transferring) and the clinical trial institutions shall agree on the transfer and clarify the responsibilities of the researchers of the two institutions.
transfer of the subject shall be subject to the consent of the ethics committee of both parties and, if necessary, the form of informed consent may be re-signed.
transfer agencies should provide information and data prior to transfer to ensure that the receiving institution continues to conduct experiments under conditions that ensure the safety of the subjects, and that the receiving institution is responsible for providing information and data after the transfer.
should consider the impact of the transfer process on the subject and make reasonable arrangements.
3. Suspended or terminated treatment applicants should consult with the researchers to decide whether to suspend or terminate treatment and report to the Ethics Committee in a timely manner to ensure the safety of the subjects.
should consider whether the subject may benefit from experimental drug treatment, whether there is an appropriate alternative treatment, the severity of the disease or state being treated, the risks involved in replacing other treatments, etc.
in some cases, even if the trial drug is only suspended, it may be detrimental to the safety of the subject, and measures should be considered to avoid it.
may necessitate the use of experimental drugs due to the lack of a supply of experimental drugs, the inability to manage them or ensure the safe use of experimental drugs.
for individual subjects, if the researcherbelieves that the experimental drug has clinical benefits to them, stopping the trial drug may pose a significant risk, the applicant should communicate with the supervisory authority in this regard in a timely manner, confirm and consider modifying the program so that the trial drug is used only for those subjects who have significant benefits, while stopping treatment for other subjects.
subjects are given appropriate management after they have been discontinued from experimental drug treatment to ensure their safety.
(ii) Possible measures to improve the safety management of clinical trials, the outbreak of new crown pneumonia, will result in traffic restrictions and limitations in clinical trial institutions.
When clinical trials face practical difficulties such as sending experimental drugs, post-drug examination, follow-up, etc., it is suggested that the applicant proposes feasible alternatives, which should ensure the safety and rights of the subjects, ensure that research data are available, and ensure its quality and traceability.
1. Strengthen the attention of subjects during clinical trials should strengthen attention to subjects, can be closely informed by telephone, WeChat and other ways to understand the health status of subjects, confirm whether the subjects have a high incidence of the epidemic area residence or travel history, whether there is a confirmed or suspected infection of the population contact history, fever outpatient visit history, etc. , in the event of safety should be dealt with in a timely manner.
2. If the subject's visit is requested by the applicant or the clinical trial institution to screen the subject for COVID-19, unless the applicant makes the data collected a new research target, it is not required to report as a change of protocol, even during a clinical study visit, but should be documented.
if the subject is diagnosed with a new type of coronavirus pneumonia, the expected risks and benefits of the subject need to be weighed against whether to interrupt the trial until the infection is cured or the infection is ruled out.
for safety assessment indicators, the applicant should determine whether on-site visits are necessary to fully ensure the safety of the subjects.
after a risk assessment.