What Does a Clinical Trial Manager Do?
Drug clinical trial management specifications are the requirements for the management and standardization of pharmaceutical clinical trials.
Pharmaceutical Clinical Trial Management Practices (GCP)
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Drug clinical trial management specifications are the requirements for the management and standardization of pharmaceutical clinical trials.
- Chinese name
- Pharmaceutical Clinical Trial Management Practices (GCP)
- Meaning
- Manage and standardize clinical trials of drugs
- According to law
- Drug Administration Law of the People's Republic of China
- Nature
- file
Chapter I General Provisions
Article 1 In order to ensure the standardization of the clinical trial process of the drug, the results are scientific and reliable, protect the rights and interests of the subjects, and ensure their safety. Principles, formulate this specification.
Article 2 The specifications for the quality management of drug clinical trials are standard provisions for the entire clinical trial process, including protocol design, organization and implementation, monitoring, auditing, recording, analysis, and reporting.
Article 3 All clinical trials, human bioavailability tests, or bioequivalence tests must be performed in accordance with this specification.
Article 4 All human-oriented research must conform to the Helsinki Declaration of the World Medical Assembly (Appendix 1), that is, fairness, respect for personality, and strive to maximize the benefit of the subjects and avoid harm as much as possible.
Chapter II Preparations and Necessary Conditions Before Clinical Trials
Article 5 There must be sufficient scientific basis for conducting clinical trials of drugs. Before conducting a human test, the purpose of the test and the problems to be solved must be carefully considered. The expected benefits and risks to the health of the subject and the public should be weighed. The expected benefits should exceed the possible damage. The selection of clinical trial methods must meet scientific and ethical requirements.
Article 6 Drugs for clinical trials shall be prepared and provided by the sponsor. Before conducting a clinical trial, the sponsor must provide preclinical research data for the test drug, including prescription composition, manufacturing process, and quality inspection results. The pre-clinical information provided must meet the requirements for conducting each phase of clinical trials. At the same time, the efficacy and safety data related to the completion of the test drug and ongoing clinical trials in other regions should also be provided. The preparation of drugs for clinical trials shall comply with the "Good Manufacturing Practice for Drugs".
Article 7 The facilities and conditions of drug clinical trial institutions shall meet the needs of conducting clinical trials safely and effectively. All investigators should have the professional expertise, qualifications, and abilities to undertake the clinical trial and be trained. Before a clinical trial begins, the investigator and sponsor should reach a written agreement on the trial protocol, trial monitoring, audit, and standard operating procedures, and division of responsibilities in the trial.
Chapter III Protection of Rights and Interests of Subjects
Article 8 In the process of clinical trials of drugs, the personal rights of the subjects must be fully protected, and the scientificity and reliability of the trials must be ensured. Subjects' rights, safety, and health must take into consideration scientific and social interests. Ethics committee and informed consent are the main measures to protect the rights of the subjects.
Article 9 In order to ensure the rights and interests of subjects in clinical trials, an independent ethics committee must be established and filed with the State Food and Drug Administration. The ethics committee shall consist of at least five persons engaged in medicine-related professionals, non-medical professionals, legal experts and other units, and members of different genders. The composition and work of the ethics committee should not be influenced by any participant.
Article 10 The test plan can only be implemented after it has been reviewed and agreed by the ethics committee and signed approval opinions. During the test, any modification of the test protocol should be approved by the ethics committee; serious adverse events during the test should be reported to the ethics committee in a timely manner.
Article 11 The review opinion of the ethics committee on the clinical trial plan shall be decided by voting after discussion, and members participating in the clinical trial shall withdraw. Experts who are not members may be invited to attend the meeting due to work needs, but do not vote. The ethics committee shall establish working procedures, and all meetings and their resolutions shall have written records, which shall be kept for five years after the end of the clinical trial.
Article 12 The ethics committee shall consider the test plan strictly from the perspective of protecting the rights and interests of the subjects:
(1) Qualifications, experience of investigators, whether there is sufficient time to participate in clinical trials, and whether staffing and equipment conditions meet the requirements of the trials;
(2) Whether the test plan fully considers the ethical principles, including the research purpose, the risks and benefits that subjects and other personnel may suffer, and the scientific nature of the test design;
(3) The method of the subject selection, whether the information provided by the subject (or his family members, guardians, legal representatives) about the test is complete and understandable, and whether the method of obtaining informed consent is appropriate;
(4) Treatment and / or insurance measures given to subjects who have suffered damage or even died as a result of participating in clinical trials;
(5) Whether the amendments to the test plan are acceptable;
(6) Periodically review the risk level of subjects during clinical trials.
Article 13 After receiving the application, the ethics committee shall promptly convene a meeting, review the discussion, issue written opinions, and attach the list of members attending the meeting, their professional situation, and their signatures. The opinion of the ethics committee can be:
(A) agree;
(2) agreeing after making necessary amendments;
(3) disagree;
(4) Terminate or suspend approved tests.
Article 14 The investigator or his designated representative must explain the details of the clinical trial to the subject:
(1) Participants in the trial shall be voluntary, and shall have the right to withdraw from the trial at any time without any discrimination or retaliation, and their medical treatment and rights shall not be affected;
(2) The subject must be made aware that the personal data of participating in the trial and during the trial are confidential. When necessary, the drug regulatory department, ethics committee, or sponsor can check the data of the participants in the trial as required;
(3) the purpose of the test, the process and duration of the test, the inspection operation, the expected benefits and risks of the subject, and inform the subject that they may be assigned to different groups of the test;
(4) Subjects must be given sufficient time to consider whether they are willing to participate in the trial. For subjects who are unable to express consent, they should provide the above-mentioned introduction and explanation to their legal representatives. The informed consent process should be in a language and language that the subject or legal representative can understand. During the trial, the subject can always know the information related to it;
(E) Subjects may receive treatment and corresponding compensation if trial-related damage occurs.
Article 15 The informed consent is obtained after a full and detailed explanation of the test:
(1) Signed and dated by the subject or his legal representative on the informed consent form, and the researcher performing the informed consent process must also sign the name and date on the informed consent form;
(2) For incompetent subjects, if the ethics committee agrees in principle and the researcher believes that the subjects' participation in the trial is in their own interest, these patients can also enter the trial, and should be approved and signed by their legal guardian And dated;
(3) As a subject, the child must obtain the informed consent of his legal guardian and sign the informed consent. When the child can make a decision to participate in the research, he must also obtain his own consent;
(4) In an emergency situation, the informed consent of the person and his legal representative cannot be obtained. If there is no proven effective treatment method, and the test drug is expected to save lives, restore health, or reduce pain, it can be considered as a test However, it is necessary to clearly indicate the method of accepting these subjects in the test protocol and related documents, and to obtain the consent of the ethics committee in advance;
(5) If important new information related to the test drug is found, the informed consent form must be modified in writing and submitted to the ethics committee for approval before obtaining the subject's consent again.
Chapter IV Test Plan
Article 16 A trial protocol shall be formulated before the start of a clinical trial. This protocol shall be mutually agreed and signed by the investigator and the sponsor, and implemented after being submitted to the ethics committee for approval.
Article 17 The clinical trial protocol shall include the following:
(1) Test topics;
(2) the purpose of the test, the background of the test, the findings of clinical significance in the preclinical research and the results of the clinical trials related to the test, the known possible risks and benefits to the human body, and the possibility of ethnic differences in the test drugs;
(3) the name and address of the sponsor, the place where the test is conducted, the name, qualifications and address of the researcher;
(4) the type of experimental design, the randomized grouping method and the level of blindness;
(5) selection criteria, exclusion criteria and exclusion criteria for the subjects, steps for selecting subjects, and methods for assigning subjects;
(6) Calculate the number of cases required to achieve the intended purpose of the trial based on statistical principles;
(7) The dosage form, dosage, route of administration, method of administration, frequency of administration, duration of treatment, and regulations on combined use of the test drug, as well as instructions on packaging and labeling;
(8) Projects to be carried out for clinical and laboratory inspections, the number of measurements and pharmacokinetic analysis;
(9) Registration and use records, delivery, distribution methods and storage conditions of test drugs;
(10) Measures for clinical observation, follow-up and ensuring subject compliance;
(11) Criteria for suspending clinical trials and ending clinical trials;
(12) Evaluation criteria for curative effect, including methods for assessing parameters, observation time, recording and analysis;
(13) Procedures for keeping the subject's code, random number table and case report form;
(14) Recording requirements of adverse events and reporting methods, handling measures, follow-up methods, time and outcome of serious adverse events;
(15) Provisions for establishment and preservation of test drug codes, methods for unblinding, and regulations for breaking blindness in emergency situations;
(16) Statistical analysis plan, definition and selection of statistical analysis data sets;
(17) Provisions on data management and data traceability;
(18) Quality control and quality assurance of clinical trials;
(19) Test-related ethics;
(20) the expected progress and completion date of the clinical trial;
(21) Follow-up and medical measures after the end of the trial;
(22) the responsibilities and other relevant provisions assumed by the parties;
(23) References.
Article 18 In clinical trials, if it is really necessary, the test plan may be amended according to prescribed procedures.
Chapter V Duties of the Researcher
Article 19 The researchers responsible for clinical trials shall meet the following requirements:
(1) Having the relevant professional and technical positions and medical qualifications in medical institutions;
(2) Having the professional knowledge and experience required in the test plan;
(3) Those who have rich experience in clinical trial methods or can obtain academic guidance from researchers with experience in the unit;
(4) Familiar with the clinical trial-related data and literature provided by the sponsor;
(5) The right to control the personnel involved in the test and the equipment required to use the test.
Article 20 The researcher must read and understand the content of the test protocol in detail and implement it strictly.
Article 21 Investigators should understand and be familiar with the nature, effects, efficacy, and safety of the test drug (including relevant information about the preclinical study of the drug). new information.
Article 22 A researcher must conduct clinical trials in a medical institution with good medical facilities, laboratory equipment, and personnel. The institution should have all facilities for emergency situations to ensure the safety of the subjects. The results of laboratory tests should be accurate and reliable.
Article 23 The investigator shall obtain the consent of the medical institution or the competent unit where he is located to ensure that he has sufficient time to be responsible for and complete the clinical trial within the time limit specified in the plan. The investigator must explain the trial data, regulations, and responsibilities to all staff participating in the clinical trial to ensure that a sufficient number of subjects who meet the trial protocol enter the clinical trial.
Article 24 The investigator shall explain the details of the relevant test approved by the ethics committee to the subject, and obtain the informed consent.
Article 25 The investigator is responsible for making medical decisions related to clinical trials to ensure that subjects receive appropriate treatment in the event of adverse events during the trial.
Article 26 The investigator is obliged to take necessary measures to ensure the safety of the subject and keep it on file. If a serious adverse event occurs during the clinical trial, the investigator should immediately take appropriate treatment measures for the subject, and report to the drug supervision and administration department, health administration department, sponsor and ethics committee, and sign and report the report date.
Article 27 The researcher shall ensure that the data is truthful, accurate, complete, timely and legally loaded into the medical records and case report forms.
Article 28 The investigator shall accept the supervision and inspection by the inspector or auditor dispatched by the sponsor and the inspection and inspection by the drug supervision and administration department to ensure the quality of clinical trials.
Article 29 The investigator shall agree with the sponsor on the cost of the clinical trial and specify it in the contract. During the clinical trial, the investigator must not charge the subject the cost of the test drug.
Article 30 After the clinical trial is completed, the researcher must write a summary report, sign it and date it, and send it to the sponsor.
Article 31: An investigator must notify the subject, the sponsor, the ethics committee, and the drug regulatory authority of the suspension of a clinical trial, and explain the reasons.
Chapter VI Duties of the Sponsor
Article 32 The sponsor is responsible for initiating, applying, organizing, monitoring, and inspecting a clinical trial, and providing the funding for the trial. The sponsor may submit an application for clinical trials to the State Food and Drug Administration in accordance with relevant laws and regulations, and may also entrust contract research organizations to perform certain tasks and tasks in clinical trials.
Article 33 The sponsor selects the institution and investigator of the clinical trial and recognizes its qualifications and conditions to ensure the completion of the trial.
Article 34 The sponsor provides the investigator's manual, which includes chemical, pharmacological, toxicological, pharmacological, and clinical (including previous and ongoing trials) data and data on the test drug.
Article 35 The sponsor may organize clinical trials according to the plan after obtaining the approval of the State Food and Drug Administration and the approval of the ethics committee.
Article 36 The sponsor and the investigator jointly design the clinical trial protocol, stating the responsibilities and division of labor in the aspects of protocol implementation, data management, statistical analysis, result reporting, and method of publishing thesis. Sign the agreed test plan and contract.
Article 37 The sponsor provides the researcher with a test drug, standard, control drug or placebo that is easy to identify, correctly coded, and labeled with a special label, and guarantees that the quality is acceptable. Test drugs shall be appropriately packed and stored as required by the test plan. The sponsor should establish a management system and record system for the drugs used in the trial.
Article 38 The sponsor appoints a qualified supervisor and is accepted by the researcher.
Article 39 The sponsor shall establish a quality control and quality assurance system for clinical trials, and may organize audits of clinical trials to ensure quality.
Article 40 The sponsor and the researcher should quickly investigate the serious adverse events that have occurred, take necessary measures to ensure the safety and rights of the subject, and report to the drug supervision and administration department and the health administration department in a timely manner, and at the same time Other investigators of clinical trials of the drug were notified.
Article 41 Before suspending a clinical trial, the sponsor must notify the researcher, the ethics committee, and the State Food and Drug Administration, and state the reasons.
Article 42 The sponsor is responsible for submitting the summary report of the trial to the State Food and Drug Administration.
Article 43 The sponsor shall provide insurance for the subjects participating in the clinical trial, and shall bear the cost of treatment and corresponding financial compensation for the subjects who have suffered damage or death related to the trial. The sponsor should provide researchers with legal and financial guarantees, except for those caused by medical accidents.
Article 44 When a researcher fails to comply with an approved protocol or relevant regulations for conducting a clinical trial, the sponsor should point out that for correction, if the situation is serious or persists, the researcher should be terminated from participating in the clinical trial and submit to the drug supervision and management Department report.
Chapter VII Duties of the Auditor
Article 45 The purpose of the inspection is to ensure that the rights and interests of the subjects in the clinical trial are protected, the data of the trial records and reports are accurate and complete, and to ensure that the trial follows the approved scheme and relevant regulations.
Article 46 The supervisor is the main contact between the sponsor and the researcher. The number and number of visits depend on the complexity of the clinical trial and the number of medical institutions participating in the trial. The inspector shall have appropriate medical, pharmacy or related professional qualifications and undergo the necessary training, be familiar with relevant drug management regulations, be familiar with preclinical and clinical information about the test drug, and clinical trial protocols and related documents.
Article 47 The inspector shall follow the standard operating procedures and urge the clinical trial to be carried out to ensure that the clinical trial is carried out according to the plan. The specific content includes:
(1) Before the test, confirm that the test bearer has the appropriate conditions, including staffing and training, the laboratory is fully equipped and running well, and has various test-related inspection conditions. It is estimated that there are a sufficient number of subjects. Participating researchers are familiar with the requirements in the trial protocol;
(2) Monitor the researcher's implementation of the test protocol during the test, confirm that the informed consent of all subjects has been obtained before the test, understand the enrollment rate of the subjects and the progress of the test, and confirm the selected test subjects Are qualified;
(3) Confirm that all data records and reports are correct and complete, and all case report forms are filled in correctly and consistent with the original data. All errors or omissions have been corrected or noted, signed and dated by the researcher. Each subject's dose changes, treatment changes, concomitant medications, intercurrent diseases, lost follow-up, omissions to check, etc. should be confirmed and recorded. Verify that the withdrawal and loss of follow-up of the selected subjects are explained in the case report form;
(4) confirming that all adverse events are recorded, and serious adverse events are reported and recorded within the prescribed time;
(5) verify that the test drugs are supplied, stored, distributed, and recovered in accordance with relevant regulations, and make corresponding records;
(6) assisting the researcher in making necessary notifications and application matters, and reporting test data and results to the sponsor;
(7) It shall clearly record the follow-up, failure to carry out tests, failure to check, and whether to correct errors and omissions;
(8) Make a written report to the sponsor after each visit. The report should state the date and time of the inspection, the name of the inspector, and the findings of the inspection.
Chapter VIII Records and Reports
Article 48 The medical records shall be kept intact as the original files of clinical trials. The data in the case report form comes from the original file and is consistent with the original file. Any observations and inspection results in the test should be timely, accurate, complete, standardized and truthfully recorded in the medical record and correctly filled in the case report form. Changes are made due to incorrect entries. The original record should be kept clear and legible when making any corrections, and the name and time of the correction should be signed by the corrector.
Article 49. Various laboratory data in clinical trials shall be recorded or a copy of the original report shall be pasted on the case report form, and data within the normal range shall also be specifically recorded. Data that significantly deviate or are outside the clinically acceptable range must be verified. The test item must indicate the unit of measurement used.
Article 50 To protect the privacy of the subject, the subject's name should not appear on the case report form. The investigator should identify and record the subject's code.
Article 51 The content of the summary report of a clinical trial shall be consistent with the requirements of the trial protocol, including:
(1) the actual number of cases randomly entered into each group, the cases that fell out and eliminated, and the reasons therefor;
(2) comparison of baseline characteristics between different groups to determine comparability;
(3) Statistical analysis and clinical significance analysis of all efficacy evaluation indicators. The interpretation of statistical results should focus on its clinical significance;
(4) The safety evaluation should have reasonable statistical analysis of clinical adverse events and laboratory indicators, and serious adverse events should be described and evaluated in detail;
(5) Multi-center trials to evaluate the efficacy, should consider the differences between the centers and their impact;
(6) Briefly summarize and discuss the efficacy and safety of the test drug and the relationship between risk and benefit.
Article 52 The data in clinical trials shall be kept (Appendix 2) and managed in accordance with regulations. The investigator should keep clinical trial data for five years after the termination of the clinical trial. The sponsor should keep clinical trial data until five years after the trial drug is approved for marketing.
Chapter Nine Data Management and Statistical Analysis
Article 53 The purpose of data management is to quickly, completely and error-freely incorporate the test data into the report. All steps involving data management need to be documented in order to check the quality of the data and test implementation. Appropriate procedures should be used to ensure the confidentiality of the database. Computer database maintenance and support procedures should be in place.
Article 54 The allocation of subjects in a clinical trial must be performed according to a random allocation scheme determined by the design of the trial. The processing group code of each subject should be kept separately by the sponsor and the researcher as a blind bottom. The blinding test shall stipulate the conditions and procedures for unblinding in the plan, and shall be equipped with corresponding emergency codes for processing. In emergencies, it is permissible for an individual to evacuate blindly to understand the treatment they have received, but the reasons must be stated on the case report form.
Article 55 The statistical analysis process of clinical trial data and the expression of its results must adopt standardized statistical methods. Biostatistical professionals are required at all stages of clinical trials. The clinical trial plan needs a statistical analysis plan, which is confirmed and detailed before the formal statistical analysis. If an interim analysis is required, the reasons and operating procedures should be stated. The evaluation of the therapeutic effect should consider the confidence interval and the results of the hypothesis test. The selected statistical analysis data set needs to be explained. Missing, unused or redundant data must be explained, and the statistical report of the clinical trial must be consistent with the clinical trial summary report.
Chapter X Administration of Test Drugs
Article 56 Drugs for clinical trials may not be sold.
Article 57 The sponsor is responsible for proper packaging and labeling of the drugs used in clinical trials, and labeling them for clinical trials. In a double-blind clinical trial, the test drug should be consistent with the control or placebo in appearance, odor, packaging, labeling, and other characteristics.
Article 58 The record of the use of the test drug shall include information on the quantity, shipment, delivery, acceptance, distribution, and recovery and destruction of the remaining drug after application.
Article 59 The use of test drugs is the responsibility of the investigator. The researcher must ensure that all test drugs are used only in the subjects of the clinical trial. The dosage and usage of the test drugs should be in accordance with the test plan. However, the above process must be responsible for and documented by the person, and the drug for the test must be managed by the person. Investigators must not forward trial drugs to any non-clinical trial participants.
Article 60 The supply, use, storage and disposal of remaining drugs for testing shall be subject to inspection by relevant personnel.
Chapter XI Quality Assurance
Article 61 Both the sponsor and the researcher shall perform their respective duties, strictly follow the clinical trial plan, and adopt standard operating procedures to ensure the quality control of the clinical trial and the implementation of the quality assurance system.
Article 62 All relevant observations and findings in clinical trials should be verified, and quality control must be performed at each stage of data processing to ensure that the data is complete, accurate, truthful and reliable.
Article 63 The drug regulatory department and the sponsor may entrust auditors to conduct a systematic inspection of clinical trial-related activities and documents to evaluate whether the trial is conducted in accordance with the test plan, standard operating procedures and relevant regulations, and whether the test data is timely True, accurate and complete records. The audit should be performed by personnel who are not directly involved in the clinical trial.
Article 64 The drug supervision and administration department shall inspect the respective tasks and execution status of the researcher and the sponsor in the implementation of the trial. Relevant information and documents (including medical records) of medical institutions and laboratories participating in clinical trials shall be inspected by the drug regulatory department.
Chapter 12 Multicenter Trials
Article 65 A multi-center trial is a clinical trial conducted simultaneously by multiple researchers in different locations and units according to the same test protocol. Each center started and ended the test at the same time. Multicenter trials are overseen by a lead investigator and serve as coordinating investigators between the centers of the clinical trial.
Article 66 The following points shall be considered in the planning and organization of the multi-center trial:
(1) The test plan shall be discussed and confirmed by the main investigator and sponsor of each center, and it shall be implemented after approval by the ethics committee;
(2) Researcher meetings shall be organized at the beginning and mid-term of a clinical trial;
(3) clinical trials in each center;
(4) The size of the clinical trial samples in each center and the distribution among the centers should meet the requirements of statistical analysis;
(5) ensuring that the test drugs are managed in the same center in different centers, including distribution and storage;
(6) training researchers participating in the trial according to the same trial scheme;
(7) Establish a standardized evaluation method. The laboratory and clinical evaluation methods used in the test should have unified quality control, and the laboratory inspection can also be performed by the central laboratory;
(8) Data and materials shall be centrally managed and analyzed, and data transmission, management, verification and inquiry procedures shall be established;
(9) Ensuring that the researchers in each test center comply with the test plan, including termination of their participation in the test when they violate the plan.
Article 67 A multi-center trial shall establish a management system based on the number of participating centers and the requirements of the trial, as well as the level of understanding of the drugs used in the trial, and coordinate the researcher to take charge of the entire trial.
Chapter XIII Supplementary Provisions
Article 68 The meanings of the following terms in this specification are:
Clinical Trial means any systematic study of drugs in humans (patients or healthy volunteers) to confirm or reveal the effects, adverse reactions, and / or absorption, distribution, metabolism and excretion of test drugs. It is to determine the efficacy and safety of the test drug.
Protocol, which describes the background, theoretical basis, and purpose of the experiment, the design, method, and organization of the experiment, including statistical considerations, conditions for test execution, and completion. The protocol must be signed and dated by the principal investigator, research institution, and sponsor participating in the trial.
Investigator's Handbook (Investigator ?, sBrochure), is the clinical and non-clinical research data on experimental drugs in human research.
Informed Consent: After the subject is informed of all aspects of a trial, the subject voluntarily confirms his or her consent to participate in the clinical trial, which must be documented by a signed and dated informed consent.
Informed ConsentForm is the documentary proof that each subject indicated that he or she would voluntarily participate in a trial. The investigator needs to explain the nature of the trial, the purpose of the trial, possible benefits and risks, other treatment options available, and the rights and obligations of the subject in accordance with the Helsinki Declaration, so that the subject can fully understand the subject After expressing his consent.
Ethics Committee is an independent organization composed of medical professionals, legal experts, and non-medical personnel. Its role is to verify the ethics of clinical trial protocols and attachments and provide public guarantees to ensure the safety and health of the subjects. And rights are protected. The composition of the committee and all activities should not be disturbed or affected by clinical trial organizations and implementers.
Investigator, who is responsible for conducting clinical trials and for the quality of clinical trials and the safety and rights of subjects. Investigators must be qualified and possess the professional expertise, qualifications, and abilities of clinical trials.
Coordinating Investigator, a researcher in a multi-center clinical trial who is responsible for coordinating the work of researchers at each center.
Sponsor A company, institution, or organization that initiates a clinical trial and is responsible for its initiation, management, finance, and audit.
Monitor, a person with relevant knowledge appointed by the sponsor and responsible for the sponsor, whose task is to monitor and report the progress of the trial and verify the data.
Audit refers to a systematic inspection performed by personnel who are not directly involved in the trial to evaluate whether the implementation of the trial, the recording and analysis of the data are consistent with the requirements of the trial protocol, standard operating procedures, and relevant regulations of the drug clinical trial.
Inspection (Inspection). The drug regulatory authority conducts an official review of the relevant documents, facilities, records and other aspects of a clinical trial. Inspections can be conducted at the site of the trial unit, sponsor, or contract research organization.
Case report form (CRF) refers to a file designed according to the test protocol to record the data of each subject during the test.
Investigational Product, used in clinical trials as a test drug, control drug, or placebo.
Adverse Event: An adverse medical event that occurs after a patient or clinical trial subject receives a drug, but it does not necessarily have a causal relationship with the treatment.
Serious adverse event (SeriousAdverseEvent). During the clinical trial, events such as hospitalization, prolonged hospital stay, disability, impact on work ability, life-threatening or death, and congenital malformation occurred.
Standard Operating Procedures (SOPs) are standard and detailed written procedures developed to effectively implement and complete each task in a clinical trial.
Blinding / Masking. A procedure in clinical trials that makes one or more parties unaware of the subject's treatment allocation. Single-blind means that the subjects do not know, and double-blind means that the subjects, researchers, monitors, or data analysts do not know the treatment allocation.
Contract Research Organization (CRO), an academic or commercial scientific institution. The sponsor may delegate certain tasks and tasks in the clinical trial, and such delegation must be made in writing.
Article 69 The interpretation of these specifications is the responsibility of the State Food and Drug Administration.
Article 70 These specifications shall be implemented as of September 1, 2003, and the former "Specifications for the Administration of Drug Clinical Trials" issued by the former State Drug Administration on September 1, 1999 shall be abolished at the same time.
Appendix 1:
Declaration of the World Medical Congress Helsinki
Ethical guidelines for human medical research
Adopted: The 18th World Medical Congress, Helsinki, Finland. June 1964
Revised: The 29th World Medical Congress, Tokyo, Japan, October 1975
35th World Congress of Medicine, Venice, Italy, October 1983
41st World Medical Congress, Hong Kong, September 1989
48th World Medical Congress, South Africa, October 1996
52nd World Medical Congress, Edinburgh, Scotland, October 2000
I. Introduction
1. The Helsinki Declaration, drafted by the World Medical Congress, is a statement of ethical guidelines for human medical research to guide doctors and other participants in human medical research. Human medical research includes research on the human body and related data or information.
2. It is the doctor's responsibility to promote and protect human health. The doctor's knowledge and ethics are designed to fulfill this role.
3 The Geneva Declaration of the World Medical Congress constrains doctors with the language "Patient health must be our first consideration." The international code of medical ethics declares: "Only in the interests of patients, doctors can provide medical measures that may adversely affect the patient's physiology and psychology."
4 Advances in medicine are based on research that ultimately depends to some extent on trials involving humans as subjects.
5. In human medical research, the health of the subject should take precedence over scientific and social interests.
6. The main purpose of human medical research is to improve prevention, diagnosis and treatment methods, and to improve the understanding of the etiology and pathogenesis of the disease. Even the best proven prevention, diagnosis and treatment methods should be continuously researched to test their effectiveness, efficiency, feasibility and quality.
7. In current medical practice and medical research, most prevention, diagnosis, and treatment involve risks and burdens.
8. Medical research should comply with ethical standards, respect all people and protect their health and rights. Some test groups are vulnerable and need special protection. The special needs of those who are economically and medically disadvantaged must be recognized. Particular attention should be paid to subjects who are unable or unable to give informed consent, subjects who may be able to give informed consent under duress, subjects who have not benefited from the study themselves, and those receiving concurrent treatment. Tester.
9. Researchers must be aware of the ethical, legal, and regulatory requirements for human research in their country and must comply with international requirements. No country's ethics, laws, and regulations allow the reduction or removal of the protection provided to subjects in this declaration.
Second, the basic principles of medical research
10 In medical research, it is the doctor's responsibility to protect the life and health of the subjects and maintain their privacy and dignity.
11. Human medical research must follow generally accepted scientific principles, and be based on a comprehensive understanding of the scientific literature and related information, and adequate laboratory and animal tests (if necessary).
12. Research that may affect the environment must be carried out with due care, and the rights of laboratory animals used for research must be respected.
13. The design and implementation of each human test should be clearly stated in the test plan, and the test plan should be submitted to the ethical review and approval committee for review, comment, and guidance, and where appropriate, review and approval. The ethics committee must be independent of the investigator and sponsor and not affected by any other aspect. The ethics committee shall comply with the laws and regulations of the country in which the trial is conducted. The Commission has the power to monitor ongoing trials. Researchers are responsible for submitting audit data to the committee, especially for all serious adverse events. Researchers should also submit other information to the committee for approval, including information about funding, sponsors, research institutions, and other potential conflicts of interest or encouragement for the subject.
14. The research protocol must have a statement of ethical considerations and demonstrate that the protocol complies with the principles stated in this declaration.
15. Human medical research can only be performed by qualified personnel and under the supervision of clinical medical experts. It must always be the medically qualified person who is responsible for the subject, and never the subject itself, even if the subject has informed consent to participate in the study.
16. Before each human medical study begins, the expected risk, burden, and benefit ratio of the subject or other person should be carefully evaluated. This does not preclude healthy subjects from participating in medical research. All study designs should be publicly available.
17. Doctors should only conduct this human study if they are confident that they can adequately anticipate the risks in the trial and manage them well. The physician should stop the study if the risks are found to outweigh the possible benefits or if positive conclusions and favorable results have been reached.
18. Human medical research may only be performed when the purpose of the trial exceeds the subject's own risks and burdens. This is particularly important when the subject is a healthy volunteer.
19. Medical research can only be carried out if the test population can benefit from the results of the research.
20. Participants must be volunteers and have sufficient knowledge of the research project.
twenty one. Subjects must always respect their rights to protect themselves. Take measures as far as possible to respect the subject's privacy, the confidentiality of patient information, and minimize the impact on the subject's physical and mental and personality.
twenty two. In any human body study, each candidate should be fully informed of the purpose, method, source of funding, possible conflict of interest, research affiliation of the researcher, expected benefits and potential risks of the research, and Possible discomfort. Subjects should be informed of their right to refuse to participate in the trial or to withdraw from the trial at any time without retaliation. After confirming that the subject understands this information, the doctor should obtain the informed consent voluntarily given by the subject, preferably in writing. If written consent cannot be obtained, the process of obtaining unwritten consent must be formally documented and witnessed.
twenty three. When obtaining informed consent for a research project, special attention should be paid to whether the subject has a dependent relationship with the doctor or may be forced to consent to participate. In this case, informed consent should be obtained by a physician who is fully aware but does not participate in the study and who is completely independent of the subject.
twenty four. For research subjects who are not legally qualified, have no physical or mental condition to give informed consent, or are underage study subjects, the researcher must comply with relevant laws and obtain informed consent from their legal plenipotentiary. Only if the study is necessary to promote the health of the group they represent, or cannot be conducted in a legally qualified population, can these people be included in the study.
25. When an unqualified subject, such as a minor child, can actually make a decision to participate in a study, the researcher must obtain his or her consent in addition to the consent of the legally authorized representative.
26. Some studies cannot obtain consent from subjects, including clients or prior consent, and can only be performed if the subject's physical / mental conditions do not allow informed consent to be a necessary feature of this population. The special reasons that prevent the subjects participating in the study from giving informed consent should be stated in the test protocol and submitted to the ethics committee for review and approval. The protocol should also state that informed consent should be obtained from the subject or the legally authorized agent as soon as possible in the continuing study.
27. Authors and publishers have an ethical responsibility. When publishing research results, it is the responsibility of the researcher to ensure the accuracy of the results. Like positive results, negative results should be published or otherwise made public. Publications should state funding sources, research affiliates, and any possible conflicts of interest. Research reports that are inconsistent with the principles published in this declaration cannot be accepted and published.
Third, the additional principle of combining medical research with medical treatment
28. Doctors can combine medical research with medical measures, but only if the research has proven to be potentially preventive, diagnostic, and therapeutic. When medical research is combined with medical measures, patients as research subjects must be protected by additional regulations.
29. The benefits, risks, burdens, and effectiveness of the new approach should be compared to the best prevention, diagnosis, and treatment methods available. This does not preclude the use of placebo or no treatment as a control in studies that do not currently have effective prevention, diagnosis and treatment.
30. At the end of the study, each enrolled patient should ensure that they have the most effective preventive, diagnostic, and therapeutic method proven by the study.
31. The doctor should fully inform the patient about the part of the treatment he is receiving that is relevant to the study. A patient's refusal to participate in a study should never affect the patient's relationship with the doctor.
32. In the treatment of patients, if there is no proven prevention, diagnosis and treatment method, or in the case of ineffective use, if the doctor determines that an unproven or new prevention, diagnosis and treatment method is expected to save lives and recover Health and pain relief, this method should be applied without restriction, with the patient's informed consent. Wherever possible, these methods should be considered as research objects and their safety and effectiveness should be evaluated systematically. New information from all relevant cases is recorded and published as appropriate. At the same time follow other relevant principles of this declaration.
Appendix 2:
Clinical trial save file
I. Clinical trial preparation stage
Clinical trial save file | Researcher | Sponsor |
1 | Researcher's Handbook | save | save |
2 | Test protocol and amendments (signed) | Save the original | save |
3 | Case report form (sample form) | save | save |
4 | Informed consent | Save the original | save |
5 | Financial regulations | save | save |
6 | Multi-party agreement (signed) (researcher, sponsor, contract research organization) | save | save |
7 | Ethics Committee Approval | Save the original | save |
8 | Ethics Committee Membership Form | Save the original | save |
9 | Clinical trial application form | | Save the original |
10 | Preclinical laboratory data | | Save the original |
11 | Approved by the State Food and Drug Administration | | Save the original |
12 | Researcher biographies and related documents | save | Save the original |
13 | Normal range of laboratory tests related to clinical trials | save | save |
14 | Medical or laboratory quality control certificate | Save the original | save |
15 | Labelling of test drugs | | Save the original |
Clinical trial save file | Researcher | Sponsor |
16 | Waybills for test drugs and test-related materials | save | save |
17 | Test certificate of test drug | | Save the original |
18 | Blind-breaking procedures | | Save the original |
19 | Total random table | | Save the original |
20 | Audit report | | Save the original |
Clinical trials
Clinical trial save file | Researcher | Sponsor |
twenty one | Updated Researcher's Manual | save | save |
twenty two | Update of other documents (protocol, case report form, informed consent, written notification) | save | save |
twenty three | Biography of new researchers | save | Save the original |
twenty four | Updated normal range of medical and laboratory tests | save | save |
25 | Waybills for test drugs and test-related materials | save | save |
26 | New batch of test drugs | | Save the original |
27 | Auditor visit report | | Save the original |
28 | Signed informed consent | Save the original | |
29 | Original medical file | Save the original | |
30 | Case report form (filled, signed, dated) | Save copy | Save the original |
31 | Serious Adverse Event Report from Researcher to Sponsor | Save the original | save |
Clinical trial save file | Researcher | Sponsor |
32 | Report of serious adverse events by the sponsor to the Drug Administration | save | Save the original |
33 | Interim or annual report | save | save |
34 | Subject Identification Code Table | Save the original | |
35 | Subject Screening and Selection Form | save | save |
36 | Test Drug Registration Form | save | save |
37 | Researcher Signature Sample | save | save |
After the clinical trial is completed
Clinical trial save file | Researcher | Sponsor |
38 | Test drug destruction certificate | save | save |
39 | Completed trial subject code list | save | save |
40 | Audit certificate | | Save the original |
41 | Final audit report | | Save the original |
42 | Treatment allocation and proof of blindness | | Save the original |
43 | Trial Completion Report (To the Ethics Committee of the State Food and Drug Administration) | | Save the original |
44 | summary report | save | Save the original |
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