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Good Clinical Practice of Pharmaceutical Products
http://www.lnph.com   来源:   2017-03-10 23:42
Good Clinical Practice of Pharmaceutical Products
[SFDA order No. 3, Effective on September 1, 2003]

 

Chapter 1:  General Provisions

 

Article 1:  This Good Clinical Practice of Pharmaceutical Products (hereinafter “GCP”) is promulgated in accordance with the Drug Administration Law of PRC and Implementing Regulation of Drug Administration Law of PRC, making reference to internationally recognized principles to ensure the standardization of clinical trials of drugs which will result in scientific reliability, and the protection of the interests and safety of the human subject.

 

Article 2:  This GCP is a regulation for the standardization of the whole process of a clinical trial, including protocol design, organizing implementation, monitoring, auditing, recording, analysis, summarization and reporting.

 

Article 3:  This GCP is to be observed in all phases of a clinical trial, the bioavailability trial or biological equivalence trial on the human body.

 

Article 4:  All research involving human subjects must conform to the Declaration of Helsinki of World Medical Association (Appendix 1) i.e.  fairness, respect of human integrity, maximize the benefits and minimize any harm to the human subject.   

 

 

Chapter 2:  Preparations and Prerequisites

for Conducting a Clinical Trial

 

Article 5:  Sufficient scientific basis must be provided for conducting clinical trials of drugs.  The purpose of a clinical trial, the problems to be solved,  must be considered before conducting a trial on human subjects.  The anticipted benefits and risks for the human subjects and public health must be balanced.  The anticipated benefits must exceed the possible harm.  The selection of clinical trial methods must conform to scientific and ethical criteria.

 

Article 6:  The drugs to be used in a clinical trial shall be prepared and supplied by the sponsor. Before conducting a clinical trial, the sponsor must provide the pre-clinical study documents, including the formulation, manufacturing process and the quality inspection results of the drug.  All pre-clinical study information supplied by the sponsor must conform to the requirements of the respective corresponding phase(s) of the clinical trial.  The sponsor shall also provide the documents relating to the effectiveness and safety of the drug obtained from clinical trials already completed or being conducted in other places.  GMP shall be conformed for manufacturing the investigational product.

 

Article 7:  The equipment and conditions of the institution where the clinical trial will be conducted shall meet requirements for safety and efficacy. All investigators shall be qualified for undertaking the trial by their specialty and ability, and have received training.  Before starting a clinical trial, a written agreement shall be reached between the investigator and the sponsor upon trial protocol, monitoring, auditing and standard operating procedures, as well as the responsibilities of each party in the trial.

 

 

Chapter 3:  Protection of a Human Subject’s Interests

 

Article 8:  In a drug clinical trial, the human subject’s interests must be fully protected and the trial shall be scientific and reliable.  The human subject’s interests, safety and health must be higher than the consideration for science and social interests.  The use of an Ethics Committee and informed consent form are important methods to protect the human subject.

 

Article 9:  In order to protect the interests of human subjects, an independent Ethics Committee shall be formed and such information filed with SFDA.  The Ethics Committee shall consist of at least five people of different genders including those working in the medical profession, not working in the medical profession, law experts, and members from other units.  The structure and work of the Ethics Committee shall not be influenced by those participating in the trial.

 

Article 10:  The protocol of the trial must be reviewed and approved by the Ethics Committee..  When conducting a clinical trial, any amendment of the protocol may not be implemented without approval from the Ethics Committee.  Any serious adverse events that occur during the trial shall be reported to the Ethics Committee..

 

Article 11:  The decisions regarding review and approval of the protocol by the Ethics Committee shall be decided through discussion and voting.  Ethnics Committee members shall avoid participating in the clinical trial.  Experts who are not members of the committee may be invited to attend the meeting when necessary, but may not vote.  The Ethics Committee shall establish its working procedures.  Written records for all meetings and the resolutions adopted during meetings shall be kept for five years after the completion of a clinical trial.

 

Article 12:  The Ethics Committee  shall strictly examine the following aspects of the protocol in order to protect the interests of human subjects:

1.     the qualifications and experience of investigators and whether they will have enough time to participate in the clinical trial, and whether the staff and equipment conform with the requirements of the trial;

2.     whether the ethical principles are fully considered in the protocol, including the purpose of the investigation, the anticipated risks and benefits to the human subject and other people, and whether the trial is scientifically designed;

3.     whether the method of human subject admission and the information about the trial provided to the human subject, or their families or legal guardians or legal representatives, is complete and easy to understand, and whether the method used to obtain informed consent  form is proper;

4.     the treatment or insurance provided to a human subject who  is harmed or even dies due to his participation in the clinical trial.

5.     whether the recommendations to modify the protocol are acceptable; and,

6.     periodic examination of the degree of risks to human subjects participating in the clinical trial.

 

Article 13:  After receiving the application, the Ethics Committee shall hold a meeting as soon as possible to review and discuss it.  The recommendation shall be issued in writing, including listing the attendance of committee members, their specialties and their signatures.  The recommendation may:

1.     approve;

2.     approve after necessary modifications;

3.     disapprove;

4.     terminate or suspend an already approved trial.

 

Article 14:  The investigator or its designated representative must explain to the human subject the following clinical trial matters in detail:

1.   Participation by the human subject is voluntary.  The human subject has the right to withdraw from the trial at any time during any phase and shall not be subject to discrimination or retaliation. The human subject’s medical treatment and interests shall not be affected.

2.   The human subject shall be informed that his participation and personal trial data are confidential.  The Ethics Committee, drug administration authorities and the sponsor, when necessary, may check the human subject’s data according to regulations.

3.   The human subject shall be informed of the purpose of the trial, the procedures and duration of the trial, examination and operational procedures, the predicted possible benefits and risks that the human subject may suffer, and different groups in the trial in which the human subject may be placed.

4.   Enough time must be given to the human subject to consider whether to participate in the trial or not.  For a human subject who is unable to express his approval, his legal representative shall be informed of the above introduction and explanations.  The explanation regarding the process of obtaining informed consent shall be made to the human subject or his legal representative orally or, in a written language he can understand.  During the trial, a human subject has the right to know the trial information concerning himself at any time. 

5.   If any harm results because of the trial, the human subject may receive medical treatment and appropriate insurance compensation.

 

Article 15:  The signature on the informed consent form shall be obtained only after the clinical trial has been explained in detail.

1.   The human subject or his legal representative as well as the investigator responsible for the informed consent process shall sign and date the informed consent form.

2.   A human subject who is incompetent may participate in a trial on the condition that the Ethics Committee approves such participation in principle and the investigator considers that the trial will be beneficial for the human subject.  The informed consent form must be signed and dated by the legal guardian of the human subject.

3.   If the human subject is a child, the informed consent form must be signed by the legal guardian of the child. If the child can decide whether he is willing to participate, the informed consent form shall also be approved by the child.

4.   If in emergency, the informed consent form has not been obtained from the human subject or legal representative, if an effective treatment is lacking but the investigational product could save life, recover health, or alleviate pain, the clinical trial may be conducted.  However, the method used on the human subject shall be explained clearly in the protocol of the trial as well as the relevant file, and approved by the Ethics Committee in advance.

5.   If new information regarding the drug used in the trial is discovered, a written amendment of the informed consent form must be submitted to the Ethics Committee for approval, afterwhich the human subject agreement must be obtained.

 

 

Chapter 4:  Protocol for a Clinical Trial

 

Article 16:  The protocol for a clinical trial shall be formulated before starting a clinical trial.  The protocol shall be jointly discussed and signed by the investigator and sponsor, then submitted to the Ethics Committee for approval before implementation.

 

Article 17:  The protocol for a clinical trial shall contain the following:

1.     The topic of the clinical trial.

2.     The purpose(s) and objective(s) of the trial, the background for the trial, findings regarding the investigational product before the clinical trial that are of clinical significance; results of other clinical trials related to the proposed trial, the possible risks and benefits for human subjects known to date, and the possible ethnic difference of the investigational product.

3.     Name and address of the sponsor; the place where the clinical trial will be conducted; name, qualification and address of the investigator.

4.     The type of the design of the clinical trial, the random selection method, and the level of the blinding.

5.     The inclusion criteria, exclusion and removal of human subjects, the procedures for human subject inclusion, the method of grouping human subject.

6.     The number of cases needed statistically to accomplish the purposes of the trial.

7.     Form, dosage, route of administration, method and frequency of administration, period of treatment, order of usage of concomitant medicines, and explanation for package and label.

8.     Clinical and laboratory check to be conducted, testing frequency and analysis of pharmacokinetics.

9.     The registration, usage record, delivery and handing and storage conditions of the investigational products.

10.  Clinical observation, on-site visit and measures to ensure the human subject’s compliance of trial procedures.

11.  Rules regarding termination of the clinical trial and rules for the completion of the clinical trial.

12.  The standards for evaluating therapeutic efficacy, including the method for evaluating parameters, time of observation, recording and analysis.

13.  Procedures to maintain the coding of human subject, table of random numbers and case report form.

14.  Requirements for the recording of adverse events and methods for serious adverse event reporting; measures to handle, methods and time for monitor and outcome.

15.  Establishment and maintenance of trial codes, methods to break the blind and rules concerning how codes may be accessed in emergency situations.

16.  The plan of the statistical analysis, the definition and selection for the data package of the statistical analysis.

17.  Rules for data administration and data traced to the source.

18.  Quality control and quality assurance of clinical trial.

19.  Ethics related to trial.

20.  Tentative schedule and completion date of clinical trial.

21.  On-site visit and medical treatment after the clinical trial is completed.

22.  Each party’s responsibility and other relevant stipulations.

23.  Literature.

 

Article 18:  During the trial, the protocol may be modified according to its procedures, if it is really necessary.

 

 

Chapter 5:  The Investigator’s Responsibilities

 

Article 19:  The investigator responsible for the clinical trial shall:

1.     be qualified in a specialized technical position and as a doctor in a medical institution;

2.     have the relevant specialized knowledge and experience required in the protocol;

3.     have experience in clinical trial research methods or be able to obtain professional assistance from experienced investigator(s) in his institution;

4.     be familiar with the relevant information and literature provided by the sponsor of the clinical trial;

5.     have authorization to allocate the needed staff and facilities for the clinical trial.

 

Article 20:  The investigator shall read and understand the details of the protocol, and conduct the trial strictly according to the protocol. 

 

Article 21:  The investigator shall understand and be familiar with the properties, functions, effects and safety of the drug to be used (including pre-clinical study documents).  He shall know well all new information about the product which information is discovered during the clinical trial.

 

Article 22:  The investigator shall conduct the clinical trial in a medical institution with good medical treatment facilities, laboratory equipment and personnel. The institution shall have all necessary facilities to handle emergency situations to ensure the safety of human subjects.  The result of laboratory evaluations must be correct and reliable.

 

Article 23:  The investigator must obtain approval from his hospital or governing unit to ensure that he has enough time to undertake and complete the clinical trial within the period stipulated in the protocol. The investigator shall explain the information, regulations and responsibility about the trial to all personnel participating in the clinical trial, and ensure a sufficient number of qualified human subjects in the clinical trial.

 

Article 24:  The investigator shall explain in detail to the human subjects about the trial as approved by the Ethics Committee and obtain the informed consent.

 

Article 25:  The investigator is responsible for making medical treatment decisions about the clinical trial, and shall ensure that the human subjects receive proper treatment when adverse event occurs during the trial.

 

Article 26:  The investigator has an obligation to adopt and make a record of  necessary measures to protect the safety of the human subjects.  If a serious adverse event occurs during a clinical trial, the investigator shall immediately provide appropriate medical treatment to the human subject and report to drug administration authorities, the sponsor and the Ethics Committee.. The investigator shall sign and date this report.

 

Article 27:  The investigator shall ensure that the data is duly written down on the case report form in a correct, complete and legal manner.

 

Article 28:  The investigator shall receive monitors and auditors sent by the sponsor for such purposes and auditing and inspection by drug administration authorities in order to ensure the quality of the clinical trial.

 

Article 29:  The investigator and sponsors shall negotiate and provide for the expenses of the clinical trial in a written contract.  The investigator may not charge the human subjects the investigational products expenses during the clinical trial.

 

Article 30:  After the clinical trial is completed, the investigator must prepare the final report with his signature and date, then forward it to the sponsor.

 

Article 31:  For a clinical trial which is terminated, the investigator must inform the human subjects, the sponsor, the Ethics Committee and State Drug Administration and explain the reason.

 

 

Chapter 6:  The Sponsor’s Responsibilities

 

Article 32:  The sponsor is responsible for initiating, applying for, organizing, monitoring, auditing a clinical trial and provides for the expenses of the trial.    The sponsor shall submit the application for a clinical trial to the State Drug Administration in accordance with relevant provisions in China’s laws, rules and regulations.  The sponsor can authorize its contract research organization (CRO) to carry out certain work and obligations regarding the clinical trial.

 

Article 33:  The sponsor shall select the institution and investigator for a clinical trial and confirm their qualifications and conditions to ensure the completion of the trial.

 

Article 34:  The sponsor shall provide the investigator’s brochure,  containing the chemical, pharmaceutical, toxicological, pharmacological and clinical (including trials already being done or in process) information and data of the investigational product. 

 

Article 35:  Upon obtaining approval from SFDA and agreement by the Ethics Committee, the sponsor shall start to organize the clinical trial in accordance with the protocol.

 

Article 36:  The sponsor and the investigator shall jointly design the clinical trial protocol, stipulate the agreed responsibilities of each party in protocol implementation, data management, statistical analysis, results reporting, thesis publishing, etc.  The protocol and contract shall be signed by both the sponsor and the investigator.

 

Article 37:  The sponsor shall provide the investigator with the investigational product, reference product, comparator or placebo.  These products shall be easy to recognize, correctly coded and marked with special labels.  The sponsor must also ensure the quality of these products.  The investigational products shall be properly packed and kept in accordance with the protocol.  The sponsor shall establish a management and filing system for the investigational products.

 

Article 38:  The sponsor shall appoint a qualified monitor, who must also be agreed to by the investigator.

 

Article 39:  The sponsor is responsible for the establishment of quality control and quality assurance systems for the clinical trial.  The sponsor may organize an audit group for the clinical trial to ensure the quality.

 

Article 40:  The sponsor and the investigator shall study the serious adverse events immediately after occurrence and take necessary measures to ensure the human subject’s safety and interests.  Adverse events shall be reported to drug administration authorities, health administrative authorities and the other investigators conducting clinical trials on the same drug.

 

Article 41:  If the sponsor terminates a clinical trial, it must immediately inform the investigator, the Ethics Committee and SFDA and explain the reason.

 

Article 42:  The sponsor shall submit the final report of the clinical trial to the SFDA.

 

Article 43:  The sponsor shall provide the human subject with insurance for harm or death occurring during or caused by the clinical trial, which covers the expenses of the treatment and the economic compensation, and provides the investigator with a legal and economic guarantee, but not including harm and death from medical treatment accidents.

 

Article 44:  If the investigator does not conduct the clinical trial in accordance with the approved protocol, or relevant rules and regulations, the sponsor must identify such and ask for correction.  If the situation is serious or the investigator does not correct, the sponsor shall terminate his participation in the clinical trial and report to the SFDA.

 

 

Chapter 7:  The Monitor’s  Responsibilities

 

Article 45:  The monitor’s responsibility is to protect the human subject’s rights and interests in the clinical trial, ensure the record and data of the trial are correct and complete, make certain that the trial is conducted according to the approved protocol, and relevant rules and regulations.

 

Article 46:  The monitor is the major intermediary between the sponsor and the investigator.  The number of monitors depends on the complexity of the clinical trial and the number of medical institutions participating in the trial.  The monitor shall be qualified in medicine, pharmacy or relevant specialties and properly trained for the trial.  He shall be familiar with the relevant drug administration rules and regulations, familiar with the pre-clinical information of investigational product, information concerning the clinical trial, the protocol of the trial and relevant documents.

 

Article 47:  The monitor shall supervise and urge that the clinical trial be conducted according to the standard operating procedures (SOP), in order that the clinical trial comply with the protocol, including:

1.     Before the trial starts, confirm that the institution undertaking the trial already meets the appropriate requirements, including recruitment and training of the staff, the equipment of the laboratory is completed, the working conditions are good, all checks related to the trial have been made, estimate whether the number of human subjects is adequate, study and become familiar with the requirements stipulated in the protocol together with the investigator.

2.     Monitor the institution and investigator undertaking the trial before, during and after the trial.  Confirm that the informed consent form is obtained from all human subjects before the trial.  Learn of the recruitment rate of the human subjects and the progress of the trial.  Confirm that the records and report of all data are correct and complete. 

3.     Confirm that all case reports are correctly filled out and in compliance with the source documents.  Make certain that all errors or omission have been rectified or marked with the investigator’s signature and date.  The change of dosage, alternative treatment, concomitant medicine, intercurrent diseases, missed monitoring and checking of every human subject shall be confirmed and written down. The verification of the selected human subject’s withdrawal and missed monitoring shall be stated in the case report form.

4.     Confirm that all adverse events have been recorded and serious adverse events have been reported within the required time period and filed.

5.     Verify whether the investigational product is supplied, stored, distributed and returned in accordance with relevant regulations, and correspondingly recorded.

6.     Assist the investigator in providing necessary notices and applications, and report the data and results of the trial to the sponsor.

7.     Should record clearly and exactly failures by the investigator during an on-site visit, trial, examination, and whether errors, omissions have been rectified.

8.     After every visit, a written report shall be submitted to the sponsor with the date of monitoring, time, monitor’s name, the findings of the monitoring.

 

Chapter 8:  Records and Reports

 

Article 48:  The case report form shall be kept completely as original material of the clinical trial.  The data of the case report form is from the original material and in compliance with the original material.  All observations and results of the trial shall be recorded on the case report immediately, accurately, completely, standardized, truthfully, and be written in the case report form correctly.  The case report and case report form may not be changed.  In making any modification due to the written mistake, the original record shall be kept easy to recognize and the modification shall be signed and dated by the investigator.

 

Article 49:  The laboratory data of the clinical trial shall be recorded or the copy of the original report shall be pasted onto the case report form.  Data within normal ranges must also be recorded.  For data that noticeably deviates or data beyond the acceptable range, the investigator must verify it.  Each type of test must clearly state the units of measurement.

 

Article 50:  The human subject names should not be on the case report form in order to protect the human subject privacy.  The investigator should identify the human subject in accordance with his code and keep record.

 

Article 51:  The final report of the clinical trial shall conform to the protocol and contain the following:

1.     The actual number of subjects/cases that randomly participated in each treatment group, and subject dropouts or removed during the trial and the reason.

2.     Compare the baseline characteristics among different medical treatment groups in order to determine their comparability.

3.     Conduct statistical and clinical analysis for all the indexes of the therapeutic effects evaluation.  The explanation of statistical results shall focus on the significance of the clinical trial.

4.     The reasonable statistical analysis for adverse events and the laboratory indexes shall be included in the safety evaluation.  The adverse events shall be described and evaluated in detail.

5.     In assessing therapeutic effects in a multicentre trial, the differences and their effects among each center must be taken into account.

6.     Relationship between the therapeutic effects and safety as well as risks and benefits for the investigational products shall be briefly summarized and discussed.

 

Article 52:  All data of the clinical trial shall be kept and managed in accordance with regulations (Appendix 2).  The investigator shall keep the documents of the clinical trial for five years after the completion of the trial.  The sponsor shall keep the clinical trial data for five years after the investigational product has been approved for marketing.

 

Chapter 9:  Data Management and Statistical Analysis

  

Article 53:  The purpose of data management is to promptly, completely and accurately record the data. All steps involved in the data management shall be recorded in order to check the quality of the data and the implementation of the trial. The confidentiality of the database shall be protected through appropriate procedures.  Maintenance and support programs for computerized databases are required.

 

Article 54:  The human subject in the clinical trial must be grouped according to a randomized plan stipulated in the design of the trial. Either the sponsor or the investigator shall keep the grouping code of each human subject as blinding record. In a blind trial, the condition and the procedure for accessing the code shall be stipulated clearly in the protocol, and a letter with the code to be used in emergencies should be enclosed. In any emergency, the code of a human subject may be accessed in order to know the treatment he received, but the reason must be clearly recorded in the case report form.

 

Article 55:  Standard statistical methods must be applied to express the statistical analysis process and statistical results for the clinical trial data.  Professional biostatisticians shall participate in every phase of the clinical trial.  The statistical analysis plan shall be included in the protocol and should be confirmed and specified before the formal start of statistical analysis. If an analysis during the middle of trial is needed, the reason and the procedures of analysis must be explained. When evaluating therapeutic efficacy, the reliability range and hypothetic result should be considered together. The selected statistical analysis data package should be explained. The missing, unused or redundant material must be explained clearly. The statistical report of the clinical trial must be in conformity with the final report.

 

   Chapter 10:  Administration of Investigational Product

 

Article 56:  Investigational product for a clinical trial may not be sold.

 

Article 57:  The sponsor is responsible for properly packing and labeling the investigational product and marking that the drug is specially to be used in a clinical trial.  In a double blind clinical trial, the drug to be investigated and comparator or placebo shall be uniform in shape, smell, packaging, labeling and other features.

 

Article 58:  The use record of the investigational product shall include the information of quantity, loading, shipment, receipt, dispensing/handling, and the reclaim and destruction of unused drug.

 

Article 59:  The investigator is responsible for the administration of the investigational product. He must make certain all investigational products are only administered to the human subjects of the clinical trial, and the dosage and method of use conform to the protocol. The surplus products shall be returned to the sponsor. The above procedures shall be handled and recorded by a specified individual. The investigational product should be managed by a specified individual. The investigator may not transfer the investigational product to any non-participant in the clinical trial.

 

Article 60:  The supply, usage, storage, return of unused investigational product should accept checking from relevant person.

 

 

Chapter 11:  Quality Assurance

 

Article 61:  The sponsor and investigator shall fulfill respective duty, comply with protocol strictly and adopt Standard Operating Procedure (SOP) to ensure the implementation of the quality control and quality assurance system of the clinical trial.

 

Article 62:  In order to assure the completeness, accurateness, truthfulness and reliableness of data, all observation results and findings in the clinical trial must be verified and each phase for data processing must involve quality assurance.

 

Article 63:  Drug administration authorities and the sponsor may authorize an auditor to execute systematic checks for operation and document file of clinical trial in order to evaluate whether the trial is conducted in compliance with the protocol, SOP and relevant regulations, whether the data is recorded timely, factually, accurately and completely.  The audit shall be conducted by personnel not directly involved in the clinical trial. 

 

Article 64:  Drug administration authorities shall inspect the investigator and sponsor regarding their respective tasks and implementation of such tasks in the trial. All medical institutions participating in the clinical trial and all documents and files (including medical records) shall accept inspection from drug administration authorities.

 

 

Chapter 12:  Multicentre Trial

 

Article 65:  A multicentre trial consists of several clinical trials conducted by several investigators in different places and institutions in accordance with the same protocol.  Each center starts and completes the clinical trial simultaneously.  There is a principal investigator who is also the coordinating investigator of every center in the trial with overall responsibility of the multicentre trial. 

 

Article 66:  The planning and implementation of a multicentre trial should consider the following:

1.  The protocol shall be jointly discussed and made by the principal investigators of each center and sponsor. Before it is implemented, approval from the ethics committee must be obtained.

2.  Investigators meetings shall be held during the initial and middle stages of a clinical trial.

3.  The clinical trial shall be simultaneously conducted in each center.

4.  The sample size and case allocation in each center must meet statistical requirements.

5.  The investigational product shall be administered, dispensed and stored, with the same procedures in different centers.

6.  The investigators participating in the trial shall be trained in accordance with the same protocol.

7.  A standardized assessment method shall be established.  The laboratory and clinical methods of assessment applied in the trial shall be of the same quality control system. Laboratory inspection may be conducted by the central laboratory.

8.  The data shall be centrally managed and analyzed. A program for data transmission, management, inspection and inquiry shall be established.

9.  Ensure that investigators of each trial center observe the protocol and that an investigator’s participation is terminated if he violates the protocol.

 

Article 67:  A multicentre trial shall establish a management system based on the number of centers participating in the trial, the requirements of the trial and the familiarity of the drug to be investigated. A coordinating investigator shall be responsible for implementing the whole trial.


  Chapter 13:  Miscellaneous

 

Article 68: Explanation of terms of this GCP:

Clinical Trial: A Clinical Trial is a systematical investigation of drugs conducted on any human body (patient or healthy volunteer) in order to prove or reveal the function, adverse reaction and/or absorption, distribution, metabolism and excretion of the drug being investigated.  The purpose of a clinical trial is to define the therapeutic efficacy and safety of the drug.

Protocol:  A document that describes the background, rational, objectives design, method and organization of the trial, including statistical considerations and requirements for conducting and completing the trial.  The protocol must be signed and dated by sponsor, principal investigator and the institution in which the investigation is conducted.

Investigator’s Brochure:  A compilation of the clinical and non-clinical data on the investigational product already obtained before the clinical trial that will be conducted in human subjects.

Informed Consent:  A process by which a subject voluntarily confirms his or her willingness to participate in a particular trial, after having been informed of all aspects of the trial that are relevant to the subject’s decision to participate. Informed consent is documented by means of a written, signed, and dated informed consent form.

Informed Consent Form:  An Informed Consent Form is a certification to prove that each human subject is voluntarily participating in a certain trial.  The investigator must explain to the human subject about the nature and purpose of the trial, the anticipated risks and benefits, the alternative medical treatments, and the human subject’s rights and obligations stipulated in the Declaration of Helsinki, in order that the agreement to participate is based on a good understanding of the trial.

Ethics Committee:  The Ethics Committee is an independent organization consisting of people specialized in the medical field, legal experts and other people from non-medical fields whose responsibility it is to ensure the protocol and its appendix are ethical and to provide a public guarantee to ensure the protection of the rights, safety and well-being of human subjects. Organizations and persons who conduct the clinical trial shall not interfere or affect the structure and activities of the committee.

Investigator:  The Investigator is responsible for conducting the clinical trial and for the quality of the trial and the human subject’s safety and interests.  The investigator must be qualified for conducting the trial by his specialty, qualifications, and capability.  In a multicentre clinical trial, a chief investigator is appointed to take charge of the overall implementation of the clinical trial and act as the coordinator among each center.

Coordinating Investigator:  An investigator assigned the responsibility for the coordination of investigators at different centers participating in a multicentre trial. 

Sponsor:  The Sponsor is a company, institution or organization who initiates a clinical trial and is responsible for initiating, managing, financing and monitoring the trial.

Monitor:  Person appointed by and responsible to the sponsor who is responsible for monitoring and reporting the situation of the trial which is being conducted and verifying the data.

Audit:  Audit is a type of systematic check conducted by persons who are not directly involved in the trial.  The purpose of an audit is to determine whether the implementation of the trial, the recording and analysis of data comply with the protocol, SOP and relevant regulations.

Inspection:  The act by drug administration authorities in conducting an official review of documents, facilities, records and other aspects of a clinical trial.  Inspection can be done in the institution where the trial is conducted, or in the locality of the sponsor or the contract research organization.

Case Report Form (CRF):  The Case Report Form is a kind of document designed according to the protocol to record data of each human subject during the conducting of the trial.

Investigational Product:  Study drug, comparator and placebo used in a clinical trial.

Adverse Event:  An untoward medical event in a patient or clinical investigation subject administered a drug and which does not necessarily have a causal relationship with this treatment.

Serious Adverse Event:  A Serious Adverse Event includes inpatient hospitalization, prolongation of hospitalization, disability/incapacity, effect on work capability, life threatening, death, congenital anomaly etc., which occur during a clinical trial.

Standard Operating Procedures (SOP):  Standard and detailed written instructions made to ensure every function in a certain clinical trial is conducted and completed effectively.

Blinding/Masking   A procedure in which one or more parties to the trial are kept unaware of the treatment assignments. Single blinding refers to the subjects being unaware, and double-blinding refers to the subjects, investigators, monitor or data analyst being unaware of the treatment assignments. 

Contract Research Organization (CRO): Contract Research Organization is technical or commercial institution.  The sponsor may authorize the CRO to conduct some work and tasks in a clinical trial.  This authorization must be stipulated in writing.

 

Article 69:  The State Food and Drug Administration shall be responsible for interpretation of this GCP.

 

Article 70:  This GCP shall be effective from September 1, 2003, simultaneously, the former GCP issued on September 1, 1999 is annulled. 

 


 

Appendix 1

WORLD MEDICAL ASSOCIATION

DECLARATION OF HELSINKI


Ethical Principles for Medical Research Involving Human Subjects

Adopted by the 18th World Medical Association (WMA) General Assembly, Helsinki, Finland, June 1964

Amended by the 29th WMA General Assembly, Tokyo, Japan, October 1975
35th WMA General Assembly, Venice, Italy, October 1983
41st WMA General Assembly, Hong Kong, September 1989
48th WMA General Assembly, Somerset West, Republic of South Africa, October 1996
52nd WMA General Assembly, Edinburgh, Scotland, October 2000

 A.  INTRODUCTION

  1. The World Medical Association has developed the Declaration of Helsinki as a statement of ethical principles to provide guidance to physicians and other participants in medical research involving human subjects. Medical research involving human subjects includes research on identifiable human material or identifiable data.
  2. It is the duty of the physician to promote and safeguard the health of the people. The physician's knowledge and conscience are dedicated to the fulfillment of this duty.
  3. The Declaration of Geneva of the World Medical Association binds the physician with the words, "The health of my patient will be my first consideration," and the International Code of Medical Ethics declares that, "A physician shall act only in the patient's interest when providing medical care which might have the effect of weakening the physical and mental condition of the patient."
  4. Medical progress is based on research which ultimately must rest in part on experimentation involving human subjects.
  5. In medical research on human subjects, considerations related to the well-being of the human subject should take precedence over the interests of science and society.
  6. The primary purpose of medical research involving human subjects is to improve prophylactic, diagnostic and therapeutic procedures and the understanding of the aetiology and pathogenesis of disease. Even the best proven prophylactic, diagnostic, and therapeutic methods must continuously be challenged through research for their effectiveness, efficiency, accessibility and quality.
  7. In current medical practice and in medical research, most prophylactic, diagnostic and therapeutic procedures involve risks and burdens.
  8. Medical research is subject to ethical standards that promote respect for all human beings and protect their health and rights. Some research populations are vulnerable and need special protection. The particular needs of the economically and medically disadvantaged must be recognized. Special attention is also required for those who cannot give or refuse consent for themselves, for those who may be subject to giving consent under duress, for those who will not benefit personally from the research and for those for whom the research is combined with care.
  9. Research Investigators should be aware of the ethical, legal and regulatory requirements for research on human subjects in their own countries as well as applicable international requirements. No national ethical, legal or regulatory requirement should be allowed to reduce or eliminate any of the protections for human subjects set forth in this Declaration.

B.  BASIC PRINCIPLES FOR ALL MEDICAL RESEARCH

  1. It is the duty of the physician in medical research to protect the life, health, privacy, and dignity of the human subject.
  2. Medical research involving human subjects must conform to generally accepted scientific principles, be based on a thorough knowledge of the scientific literature, other relevant sources of information, and on adequate laboratory and, where appropriate, animal experimentation.
  3. Appropriate caution must be exercised in the conduct of research which may affect the environment, and the welfare of animals used for research must be respected.
  4. The design and performance of each experimental procedure involving human subjects should be clearly formulated in an experimental protocol. This protocol should be submitted for consideration, comment, guidance, and where appropriate, approval to a specially appointed ethical review committee, which must be independent of the investigator, the sponsor or any other kind of undue influence. This independent committee should be in conformity with the laws and regulations of the country in which the research experiment is performed. The committee has the right to monitor ongoing trials. The researcher has the obligation to provide monitoring information to the committee, especially any serious adverse events. The researcher should also submit to the committee, for review, information regarding funding, sponsors, institutional affiliations, other potential conflicts of interest and incentives for subjects.
  5. The research protocol should always contain a statement of the ethical considerations involved and should indicate that there is compliance with the principles enunciated in this Declaration.
  6. Medical research involving human subjects should be conducted only by scientifically qualified persons and under the supervision of a clinically competent medical person. The responsibility for the human subject must always rest with a medically qualified person and never rest on the subject of the research, even though the subject has given consent.
  7. Every medical research project involving human subjects should be preceded by careful assessment of predictable risks and burdens in comparison with foreseeable benefits to the subject or to others. This does not preclude the participation of healthy volunteers in medical research. The design of all studies should be publicly available.
  8. Physicians should abstain from engaging in research projects involving human subjects unless they are confident that the risks involved have been adequately assessed and can be satisfactorily managed. Physicians should cease any investigation if the risks are found to outweigh the potential benefits or if there is conclusive proof of positive and beneficial results.
  9. Medical research involving human subjects should only be conducted if the importance of the objective outweighs the inherent risks and burdens to the subject. This is especially important when the human subjects are healthy volunteers.
  10. Medical research is only justified if there is a reasonable likelihood that the populations in which the research is carried out stand to benefit from the results of the research.
  11. The subjects must be volunteers and informed participants in the research project.
  12. The right of research subjects to safeguard their integrity must always be respected. Every precaution should be taken to respect the privacy of the subject, the confidentiality of the patient's information and to minimize the impact of the study on the subject's physical and mental integrity and on the personality of the subject.
  13. In any research on human beings, each potential subject must be adequately informed of the aims, methods, sources of funding, any possible conflicts of interest, institutional affiliations of the researcher, the anticipated benefits and potential risks of the study and the discomfort it may entail. The subject should be informed of the right to abstain from participation in the study or to withdraw consent to participate at any time without reprisal. After ensuring that the subject has understood the information, the physician should then obtain the subject's freely-given informed consent, preferably in writing. If the consent cannot be obtained in writing, the non-written consent must be formally documented and witnessed.
  14. When obtaining informed consent for the research project the physician should be particularly cautious if the subject is in a dependent relationship with the physician or may consent under duress. In that case the informed consent should be obtained by a well-informed physician who is not engaged in the investigation and who is completely independent of this relationship.
  15. For a research subject who is legally incompetent, physically or mentally incapable of giving consent or is a legally incompetent minor, the investigator must obtain informed consent from the legally authorized representative in accordance with applicable law. These groups should not be included in research unless the research is necessary to promote the health of the population represented and this research cannot instead be performed on legally competent persons.
  16. When a subject deemed legally incompetent, such as a minor child, is able to give assent to decisions about participation in research, the investigator must obtain that assent in addition to the consent of the legally authorized representative.
  17. Research on individuals from whom it is not possible to obtain consent, including proxy or advance consent, should be done only if the physical/mental condition that prevents obtaining informed consent is a necessary characteristic of the research population. The specific reasons for involving research subjects with a condition that renders them unable to give informed consent should be stated in the experimental protocol for consideration and approval of the review committee. The protocol should state that consent to remain in the research should be obtained as soon as possible from the individual or a legally authorized surrogate.
  18. Both authors and publishers have ethical obligations. In publication of the results of research, the investigators are obliged to preserve the accuracy of the results. Negative as well as positive results should be published or otherwise publicly available. Sources of funding, institutional affiliations and any possible conflicts of interest should be declared in the publication. Reports of experimentation not in accordance with the principles laid down in this Declaration should not be accepted for publication.

C.  ADDITIONAL PRINCIPLES FOR MEDICAL RESEARCH
     COMBINED WITH MEDICAL CARE

  1. The physician may combine medical research with medical care, only to the extent that the research is justified by its potential prophylactic, diagnostic or therapeutic value. When medical research is combined with medical care, additional standards apply to protect the patients who are research subjects.
  2. The benefits, risks, burdens and effectiveness of a new method should be tested against those of the best current prophylactic, diagnostic, and therapeutic methods. This does not exclude the use of placebo, or no treatment, in studies where no proven prophylactic, diagnostic or therapeutic method exists.
  3. At the conclusion of the study, every patient entered into the study should be assured of access to the best proven prophylactic, diagnostic and therapeutic methods identified by the study.
  4. The physician should fully inform the patient which aspects of the care are related to the research. The refusal of a patient to participate in a study must never interfere with the patient-physician relationship.
  5. In the treatment of a patient, where proven prophylactic, diagnostic and therapeutic methods do not exist or have been ineffective, the physician, with informed consent from the patient, must be free to use unproven or new prophylactic, diagnostic and therapeutic measures, if in the physician's judgement it offers hope of saving life, re-establishing health or alleviating suffering. Where possible, these measures should be made the object of research, designed to evaluate their safety and efficacy. In all cases, new information should be recorded and, where appropriate, published. The other relevant guidelines of this Declaration should be followed.

 

 

Appendix 2

Record Keeping for a Clinical Trial

 

1.  For Preparation phase of the Clinical Trial

 

Documents to be kept

Investigator

Sponsor

1

Investigator’s brochure

keep

keep

2

Protocol and its amendment (signed)

keep original

keep

3

Case report form (sample form)

keep

keep

4

Informed consent form

keep original

keep

5

Financial rules

keep

keep

6

Multi-party agreement (signed)

(Investigator, sponsor, contract research organization)

keep

keep

7

Written approval from ethics committee

keep original

keep

8

List of ethics committee members

keep original

keep

9

Application for the clinical trial

 

keep original

10

Laboratory information prior to the clinical trial

 

keep original

11

Written approval from State Food and Drug Administration

 

keep original

12

Investigator’s resume and relevant documents

keep

keep original

13

Normal value range of laboratory testing related to clinical trial

keep

keep

14

Quality control certificate for medical or laboratory operation

keep original

keep

15

Label of drug to be investigated

 

keep original

16

Shipping order for drug to be investigated and relevant materials of the trial

keep

keep

17

Testing certificate of investigational product

 

keep original

18

Procedures of breaking blind of trial

 

keep original

19

General randomization list

 

keep original

20

Monitoring report

 

keep original

 

2.  During the Conducting phase of the clinical trial

 

Documents to be kept

Investigator

Sponsor

21

Updated investigator’s brochure

keep

keep

22

Updated version of other documents (protocol, case report form, informed consent form, written situation notice)

keep

keep

23

Curriculum vitae of new investigator

keep

keep original

24

Updated normal value range of medical and laboratory tests

keep

keep

25

Shipping order for investigational products and relevant materials for clinical trial

keep

keep

26

Testing certificate of investigational product with new commission number.

 

keep original

27

Monitor’s visiting report

 

keep original

28

Signed informed consent form

keep original

 

29

Original documents of medical treatment

keep original

 

30

Case report form (filled out, signed and dated)

keep original

keep the copy

31

Investigator’s report of serious adverse event submitted to the sponsor

keep original

keep

32

Investigator’s report of unexpected serious adverse event submitted to State Drug Administration and ethics committee

keep

keep original

33

Mid-term or annual report

keep

keep

34

List of codes confirmed by human subject

keep original

 

35

Form of subject screening and inclusion

keep

keep

36

Registration form of investigational product

keep

keep

37

Signature sample of investigator

keep

keep

 


 

3.  After completion of the clinical trial

 

Documents to be kept

Investigator

Sponsor

38

Certificate for destruction of investigational product

keep

keep

39

Category of codes of the human subject who completed the trial

keep

keep

40

Audit certificate

 

keep original

41

Final monitoring report

 

keep original

42

Certificate of treatment group and accessing the code

 

keep original

43

Report of the completion of the trial submitted to the ethics committee and State Food and Drug Administration

 

keep original

44

Final report

keep

keep original

 

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