In order to strengthen the guidance and standardization of the ethics Committee on the ethical review of drug clinical trials and effectively protect the safety and rights of subjects. The National Bureau organized and formulated the Guiding Principles for Ethical Review of Drug Clinical Trials (hereinafter referred to as the Guiding Principles), aiming at improving the ability of ethical review of drug clinical trials in China, giving full play to the role of ethics committees in protecting the safety and rights of subjects, and further standardizing the research behavior of drug clinical trials. Clinical trials of drugs should follow two basic principles-scientific research and ethical rationality. Ethics Committee review is one of the important measures to protect the safety and rights of subjects and ensure the ethical rationality of drug clinical trials, which plays an important role in drug clinical research. For biomedical research and clinical trials involving human body, all countries in the world have issued ethical guidelines and normative documents. The United States has promulgated federal laws and regulations for the protection of biomedical research subjects, among which 2 1CFR56 describes the review of ethics committees, and has set up a special office for the protection of human subjects in the US Department of Health and Human Services. Compared with the previous regulations, the new clinical research directive issued in Europe in 2005 has an important change: clinical research needs the approval of both the pharmaceutical administration department and the ethics Committee; In Singapore, 1997, an ethical guide for research involving human subjects was issued.
In 2003, the National Bureau promulgated "Quality Management Standard for Drug Clinical Trials (GCP)", which endowed the Ethics Committee with the important function of ethical review and approval of drug clinical trials applications. Since then, medical institutions and medical universities in China have set up ethics committees to conduct ethical review of drug clinical trials. However, the operating rules of the ethics committee and the examination points of major ethical issues in clinical trials have not yet issued corresponding guiding documents. As far as the overall situation is concerned, the level is uneven, the role is limited, and even it becomes a mere formality. There is still a big gap between the review of ethics committees and international norms.
In addition, with the internationalization and industrialization of drug clinical trials, there are more and more international multi-center drug clinical trials in China. In order to protect the rights and safety of subjects in China, the examination of ethics committee should conform to international norms. Therefore, the National Bureau has formulated the Guiding Principles for Ethical Review of Drug Clinical Trials, aiming at improving the ethical review ability of the ethics committee and standardizing the ethical review work. Article 1 In order to strengthen the guidance, supervision and management of ethical review of drug clinical trials, standardize the ethical review of drug clinical trials by ethics committees, and ensure that drug clinical trials meet scientific and ethical requirements, these guiding principles are formulated in accordance with GCP, Helsinki Declaration of the World Medical Association and Ethical Guidelines for International Biomedical Research Involving People.
Article 2 The Ethics Committee shall review the scientific rationality and ethical rationality of drug clinical trials, aiming at safeguarding the dignity, safety and rights of the subjects, promoting the scientific and healthy development of drug clinical trials, and enhancing the public's trust and support for drug clinical trials.
Article 3 The ethics committee shall, on the premise of observing the national constitution, laws, regulations and relevant provisions, independently conduct ethical review of drug clinical trials, and accept the guidance and supervision of the drug supervision and administration department.
Article 4 The pharmaceutical supervisory and administrative department shall establish an inspection and evaluation system for the ethical review of drug clinical trials by the ethics committee, and guide, supervise and manage the ethical review by the ethics committee. Article 5 The establishment of an ethics committee shall conform to the provisions of relevant administrative regulations of the state. The Ethics Committee shall be composed of personnel with multidisciplinary backgrounds, including medical professionals, non-medical professionals, legal experts and personnel independent of research/experimental units, with at least 5 persons, with gender balance. Ensure that the Ethics Committee has the qualifications and experience to review and evaluate the scientific and ethical rationality of experiments. The composition and work of the ethics committee should not be influenced by any experimental participants.
Article 6 The ethics committee shall have written documents explaining the organizational structure of the ethics committee, the responsibilities of the competent department and the ethics committee, the qualification requirements, qualifications and term of office of the members, and the responsibilities of the office, and establishing the selection and appointment procedures for members and secretaries of the ethics committee.
Article 7 An institution/department that establishes an ethics committee shall provide necessary support for the ethics committee. Set up an independent office with necessary office conditions to ensure communication with the applicant and confidentiality of relevant documents.
Article 8 Members of the Ethics Committee may be selected by recruitment or recommendation. The Ethics Committee shall have a chairman and several vice-chairmen elected by the members of the Ethics Committee.
Article 9 Members of the Ethics Committee shall agree to disclose their names, occupations and affiliation, sign confidentiality agreements on examination items, information of subjects and related matters, and sign a conflict of interest statement.
Article 10 The ethics committee may employ independent consultants or appoint permanent independent consultants. At the invitation of the Ethics Committee, independent consultants provide suggestions to the Ethics Committee on some issues in the pilot program, but independent consultants have no right to vote in the ethical review. Independent consultants can be experts in ethics or law, specific diseases or methodologies, or representatives of people with special diseases, people/ethnic groups in specific areas or other specific interest groups.
Article 11 The Ethics Committee shall establish a training mechanism for the continuing education of new members and members, and organize the training of GCP and other relevant laws and regulations, the ethical review technology of drug clinical trials and the standard operating procedures of the Ethics Committee.
Twelfth ethics committee shall formulate standard operating procedures and systems to ensure the standardization and consistency of ethical review. The content at least includes the following aspects:
(1) Formulating standard operating procedures and guidelines for ethical review applications;
(2) Organization and management of ethics committee: establishment of ethics committee, confidentiality measures for ethics review, management of conflicts of interest, training of members and staff, and selection of independent consultants;
(3) Ways of ethical review: meeting review, emergency meeting review and quick review;
(4) The process of ethical review: acceptance and handling of review application, preliminary review, follow-up review and communication of review decision;
(5) Meeting management: meeting preparation, meeting procedures and meeting minutes;
(6) Management of documents and archives: filing, preservation, consulting and copying. Thirteenth ethics committee shall, according to the needs of ethical review, constantly improve the organization and management and system construction, and perform the duties of protecting the safety and rights and interests of subjects.
Article 14 The Ethics Committee shall conduct an independent, impartial, fair and timely review of the ethical issues of the drug clinical trial projects submitted by the applicants. In addition to reviewing and supervising all drug clinical trials undertaken by this institution, the Ethics Committee may also review clinical trials entrusted by other institutions.
Article 15 The Ethics Committee may exercise the following functions and powers in reviewing and supervising the clinical trials of drugs:
(a) Approval/disapproval of drug clinical trials;
(2) Follow-up review of approved clinical trials;
(3) Termination or suspension of approved clinical trials.
Article 16 After the establishment of the ethics committee, it shall promptly report to the State Food and Drug Administration and the local provincial food and drug supervision and administration departments for the record. When filing, the following materials shall be submitted: the list of the chairman and members of the ethics Committee (with resumes), the articles of association of the ethics Committee, and the relevant working procedures and systems of the ethics Committee.
Article 17 The ethics committee shall report the annual ethics review to the State Food and Drug Administration of the United States and the local provincial food and drug supervision and administration department.
Chapter IV Application and Acceptance of Ethical Review
Article 18 The Ethics Committee shall provide the applicants for ethical review with consulting services on ethical review matters, and provide sample application forms, informed consent forms and other documents required for the review of applications; The ethics committee shall make clear provisions on matters related to accepting applications for ethical review.
(1) The list of documents submitted for ethical review and the number of documents required for the review shall be clearly defined;
(2) Defining the basic requirements, forms, standards, time limits and procedures for accepting applications for examination;
(three) to clarify the basic requirements, time limit, procedures, conditions and documentation requirements for the submission and acceptance of change applications and supplementary applications.
Article 19 After receiving the application from the applicant for ethical review, the Ethics Committee shall inform the applicant for ethical review of the contents that need to be corrected once if the review documents submitted are incomplete or do not meet the specified requirements.
After accepting the application for ethics review, the ethics committee shall notify the applicant of the estimated time for convening the ethics review meeting.
Article 20 An applicant for ethical review shall submit an application for ethical review to the Ethics Committee in accordance with the regulations and requirements of the Ethics Committee. Documents submitted for ethical review, including (but not limited to) the following documents:
(1) ethics review application form (signed and dated);
(2) Clinical trial plan (indicating version number and date);
(three) informed consent (indicating the version number and date);
(4) Relevant materials of the recruitment target;
(5) Case report form;
(6) Handbook for researchers;
(7) Resumes of the main researchers;
(8) Approval Document of Drug Clinical Trials issued by the US Food and Drug Administration;
(nine) the explanation of the important decisions of other ethics committees to apply for research projects, and the reasons for the previous negative conclusions shall be provided;
(ten) the consistency test report of the experimental drug.
Article 21 The Ethics Committee decides to accept the examination method of the project, select the presiding member, and hire independent consultants when necessary. Article 22 The Ethics Committee shall stipulate the quorum required for convening the review meeting. The number of members present at the meeting should be at least half and not less than five. Members attending the meeting should include medical professionals, non-medical professionals, people independent of research/experimental units and people of different sexes.
Article 23 The meeting of the Ethics Committee shall be presided over by the chairman (or authorized person). When necessary, independent consultants may be invited to attend the meeting to provide advice; Principal researchers/applicants may attend the meeting as nonvoting delegates to explain the scheme or elaborate on specific issues. The secretary of the Ethics Committee shall summarize the discussion contents and deliberation decisions of the meeting and form the minutes of the meeting. Meeting minutes should have approval procedures.
Article 24 The Ethics Committee may establish a "presiding judge system": the Ethics Committee may appoint one or two presiding judges for each project according to the principles of professional relevance and ethical issues.
Twenty-fifth ethics committee review to review the meeting as the main way. In any of the following circumstances, a quick review can be implemented:
(1) Minor modifications to the clinical trial plan approved by the Ethics Committee will not affect the risk-benefit ratio of the trial;
(two) the annual/regular follow-up review of the experimental projects that have not included the subjects or have completed the intervention measures;
(iii) The anticipated serious adverse events review.
Twenty-sixth fast review by one or two members responsible for the review. The pilot projects that have passed the quick review will be notified at the next meeting of the Ethics Committee. In any of the following circumstances, the quick review project shall be handed over to the meeting for review:
(a) The review is negative;
(2) The opinions of the two members are inconsistent;
(three) members put forward the need to convene a meeting for deliberation.
Twenty-seventh major or serious problems in the process of research, endangering the safety of subjects, the ethics committee shall convene an emergency meeting to review, and take corresponding measures to protect the safety and rights of subjects when necessary.
Article 28 The main contents of ethical review (with 1):
(a) the design and implementation of the research plan;
(2) Risks and benefits of testing;
(3) subject recruitment;
(four) the information informed by the informed consent;
(5) The process of informed consent;
(6) Medical treatment and protection of subjects;
(7) Privacy and confidentiality;
(eight) research involving vulnerable groups.
Article 29 In order to ensure the quality of ethics review and review meeting, the ethics committee shall manage and control the quality of ethics review, and the ethics review meeting shall be conducted in accordance with the prescribed procedures and agenda, and the review documents shall be fully discussed to ensure that members can fully express different opinions on the issues discussed.
Thirtieth ethics review meeting should pay special attention to scientific, safety, fairness, subject protection, informed consent documents and informed consent procedures, conflicts of interest and other issues.
Article 31 The ethical review of multi-center clinical trials should be based on the consistency and timeliness of the review. Multi-center clinical trials can establish collaborative review procedures;
(a) the ethics committee of the lead unit is responsible for reviewing the scientific and ethical rationality of the experimental scheme.
(2) Under the premise of accepting the review opinions of the ethics committee of the lead unit, the ethics committee of each participating unit is responsible for reviewing the feasibility of the experiment of this institution, including qualification, experience and whether there is enough time to participate in clinical trials, staffing, equipment conditions, etc. The ethics committees of participating units have the right to approve or disapprove the research conducted in their institutions.
(3) The suggestions on the modification scheme deemed necessary by the ethics committee of the participating units shall be notified in writing to the applicant or the experimental institution in charge of the whole experimental scheme for deliberation and agreement, so as to ensure that all centers follow the same experimental scheme.
(four) the ethics committee of each center should follow up and review the implementation of clinical trials in this institution. In case of serious adverse events, the ethics committee of the institution shall be responsible for timely review and inform the applicant of the review opinions. Considering the safety of the subjects, the ethics committee of each center has the right to suspend the experiment and continue it in its institution.
(five) the team leader's follow-up review opinions on clinical trials should be filed by all participating units in a timely manner. Thirty-second ethics review meeting to make a decision by voting, more than half of the members present as the ethics committee's review decision.
Article 33 When making a review decision, the ethics committee shall meet the following conditions:
(1) The application documents are complete;
(2) The members attending the meeting meet the quorum requirements;
(3) Follow the review procedure and conduct a comprehensive review and full discussion on the review points;
(4) When discussing and voting, the applicant and members with conflicts of interest leave the venue;
(five) members who did not attend the review meeting shall not be replaced by other members to vote.
Article 34 The approval of clinical trial projects must at least meet the following standards:
(1) Take corresponding risk control and management measures for the expected test risks;
(2) The risk of the subject is reasonable relative to the expected return;
(3) The choice of subjects is fair and just;
(4) The information in the informed consent form is sufficient, and the process of obtaining informed consent conforms to the regulations;
(five) when necessary, the test plan should have enough data and safety monitoring plan to ensure the safety of the subjects;
(six) to protect the privacy of subjects and ensure the confidentiality of data;
(seven) research involving vulnerable groups, with corresponding special protection measures.
Article 35 The review opinions of the Ethics Committee are under the following circumstances:
(1) agree;
(2) Consent after necessary modification;
(3) Retrial after making necessary amendments;
(4) Disagree;
(5) Termination or suspension of approved clinical trials.
Article 36 The secretary of the Ethics Committee shall sort out the minutes of the meeting in time after the meeting, and form a written ethical review opinion/reply according to the minutes of the meeting and the review conclusion. The ethics review opinions/documents shall be signed by the chairman (or authorized person) and sealed by the ethics committee. Information for ethical review opinions/approvals includes:
(1) Basic information
1. pilot project information: project name, applicant, review opinion/approval number;
2. Clinical trial institutions and researchers;
3. Meeting information: meeting time, place, review category and reviewed documents, in which the version number/date shall be indicated on the clinical trial plan and informed consent;
4. Release date of ethical review documents/opinions;
5. Contact person and contact information of the Ethics Committee.
(2) Review opinions and decisions
1. When the review decision is "Agree", inform the Ethics Committee of the requirements for subsequent review;
2. When the review decision is "agree after making necessary changes" and "try again after making necessary changes", explain the modification opinions in detail and inform the requirements and process of resubmitting the scheme;
3. When the review decision is "disapproval" and "termination or suspension of the approved clinical trial", the reasons must be fully explained, and the applicant can explain or lodge a complaint about the relevant matters.
Thirty-seventh ethics review opinions/documents shall be promptly communicated to the applicant after being reviewed and signed by the chairman (or authorized person) of the ethics committee. Article 38 The Ethics Committee shall follow up and review all approved clinical trials until the end of the trials.
Thirty-ninth revision review refers to the review of the revision of the test plan during the test. Any modification to the test plan during the test period shall be submitted to the Ethics Committee for approval before implementation. The Ethics Committee shall require the applicant and/or researcher to submit relevant information for revision review, including (but not limited to):
(a) the contents of the amendment and the reasons for the amendment;
(two) the impact of the revised plan on the expected risks and benefits;
(three) the impact of the revised scheme on the rights and interests and safety of the subjects.
The Ethics Committee mainly evaluates the test risks and benefits of the revised scheme, and puts forward review opinions. In order to avoid causing urgent harm to the subjects, researchers can modify the scheme before submitting it to the ethics Committee for approval, and make a written report to the ethics Committee in time afterwards.
Fortieth annual/periodic follow-up review. During the initial review, the Ethics Committee shall decide the frequency of annual/regular follow-up review according to the risk degree of the trial, at least once a year. The Ethics Committee shall require researchers to submit reports on time, and the information in the annual/regular follow-up review report shall include (but not limited to):
(a) the progress of the test;
(2) The number of subjects included, completed and withdrawn;
(three) to confirm that serious adverse events has been reported in a timely manner and properly handled;
(four) any risk of events or new information that may affect the research income.
After reviewing the research progress, the Ethics Committee reassessed the risks and benefits of the experiment.
Article 41 serious adverse events review refers to the review of serious adverse events reported by the applicant and/or researcher, including the degree and scope of serious adverse events, the impact on the benefit of trial risk, and the medical protection measures for the subjects.
Article 42 The review of noncompliance/violation of protocols refers to the review of noncompliance/violation of protocols during clinical trials. The ethics committee shall require the sponsor and/or researcher to explain the cause, influence and treatment measures of the incident, and examine whether the incident affects the safety and rights of the subjects and the risk and benefit of the experiment.
Article 43 The review of early termination of experiments refers to the review of early termination of experiments by applicants and/or researchers. The Ethics Committee shall require the applicant and/or researcher to report the reasons for terminating the trial and the follow-up treatment of the subjects in advance, and review whether the safety and rights of the subjects are guaranteed.
Article 44 The conclusion review refers to the review of the conclusion report of clinical trials. The ethics committee shall require the applicant and/or researcher to report the completion of the experiment and review the safety and rights protection of the subjects.
Forty-fifth follow-up review decisions and reasons shall promptly inform the applicant. Forty-sixth ethics committee should have an independent file management system. The documents filed by the Ethics Committee include management documents and project review documents.
Article 47 The management documents of the ethics committee include (but are not limited to):
(a) the work system, job responsibilities, standard operating procedures and application guidelines for the ethical review of the Ethics Committee;
(2) Appointment documents of members of the Ethics Committee, resumes and training records of members, and confidentiality agreements and conflict of interest statements signed by members;
(3) The annual work plan and summary of the Ethics Committee.
Forty-eighth ethics committee test project review documents include:
(a) All materials submitted by the researcher/applicant;
(2) Ethics review worksheet, meeting sign-in form, voting sheet, meeting minutes, approval/opinions of ethics committee and relevant communication letters.
The ethical review documents shall be properly kept for five years after the end of clinical trials, or the storage period shall be extended according to relevant requirements. See Appendix 2 for the list of archived documents.
Article 49 The Ethics Committee shall make relevant provisions on the inspection and reproduction of documents to ensure the safety and confidentiality of documents and archives. Article 50 An ethics committee may establish a mechanism for information exchange and work cooperation, so as to promote the improvement of ethics review ability.
Article 51 An ethics committee established before the implementation of these Guiding Principles shall, within one year from the date of implementation of these Guiding Principles, improve its organizational management and system construction with reference to the relevant requirements of these Guiding Principles, and report to the State Food and Drug Administration of the United States and the local provincial food and drug supervision and administration departments for the record.
Article 52 These Guidelines shall come into force as of the date of promulgation.