Thông tư 03/2012/TT-BYT hướng dẫn thử thuốc trên lâm sàng

MINISTRY OF HEALTH --------	SOCIALIST REPUBLIC OF VIETNAM Independence - Freedom - Happiness ----------------
No.: 03/2012/TT-BYT	Hanoi, February 02, 2012

 

CIRCULAR

GUIDING CLINICAL DRUG TRIAL

Pursuant to the Pharmacy Law dated 14/6/2005 and the Decree No.79/2006/ND-CP dated 09/08/2006 of the Government detailing the implementation of some Articles of the Pharmacy Law;

Pursuant to Decree No.188/2007/ND-CP dated 27/12/2007 of the Government regulating functions, duties, powers and organizational structure of Ministry of Health,

Ministry of Health guides clinical trial on drugs as follows:

Chapter I

GENERAL PROVISIONS

Article 1. Scope of governing

This Circular guides on the drugs required to be conducted clinical trial, exempted from clinical trial, exempted from some stages of clinical trial, conditions of clinical drugs trial; registration, evaluation and approval of clinical drugs trial, the clinical drug trial stages, rights and obligations of the stakeholders; supervision, inspection, acceptance and evaluation of clinical drug trial in Vietnam for the study, permission of the circulation of pharmaceutical drugs, medical biological products, vaccines and traditional medicines or drugs from medicinal plants used in the diagnosis, treatment and disease prevention directly on human (hereinafter referred to as drugs).

Article 2. Interpretation of terms

In this Circular, the following terms are construed as follows:

1. A reference country means one of the countries as UK, France, Germany, USA, Japan, Australia, Canada or management bodies of medical products in Europe (European Medicines Agency - EMA).

2. Multi-center research means a clinical trial which is conducted in two or more research centers to ensure the universality of the number of participants in clinical drug trial, more diversity of elements of demography, anthropology.

3. Agencies, organizations and individuals having drugs required to be conducted  clinical trial mean the agencies, organizations and individuals that undertake research, production, import, export, distribution of drugs wishing for their drugs to be conducted clinical trial.

4. Organizations undertaking clinical drug trial mean the health facility with function of science research that are eligible for professional personnel, material facilities, equipment for conducting clinical drug trial and to be evaluated, permitted by the Health Ministry.

5. Participants in the clinical drug trial mean patients or healthy volunteers participating voluntarily in the research.

6. Clinical Research Organization (Contract Research Organization: CRO) means an organization with legal entity status, professional capacity in accordance with the provisions of the Health Ministry, independent of agencies, organizations and individuals with drugs of clinical trial, contracted with organizations, individuals with drugs of clinical trial to perform the works of research support such as writing research outline, research monitoring, data analysis.

7. Management organization of research sites (Site Management Organization: SMO) means an organization with legal entity status, full capacity in accordance with provisions of the Ministry of Health, independent of agencies, organizations and individuals with drugs of clinical trial, organizations undertaking clinical drugs trial, contracted with organizations, individuals with drugs of clinical trial or organizations undertaking clinical drug trial to perform the works of supporting the research site management .

8. Foreign clinical data means the method and results of clinical research which have been done abroad.

9. Racial factors mean the factors related to group of large populations with common genetic characteristics, culture, traditions, and environment.

10. The international regulations for clinical drug trial accredited by the Health Ministry means good clinical practice guidelines of the blocks of regions located in the meeting of international harmonization of pharmaceutical use in humans (ICH) and good clinical practice guidelines (Good Clinical Practice - GCP) of the World Health Organization (WHO).

Article 3. Principles of clinical drugs trial

1. The clinical drug trial must comply with the provisions of this Circular, the provisions of law on science and technology, good clinical practice and the international treaties to which Vietnam is a member.

2. Participants in clinical drug trial must be selected in accordance with the principles of ethics in biomedical research.

Article 4. Prohibited Acts

1. Conduct clinical drug trial without permission of the Ministry of Health.

2. Arbitrarily amend or supplement records, research outline which were approved by the Health Ministry.

3. Using drugs in clinical trial for other purposes.

4. Force subjects to participate in research or hide information or fail to provide for information prescribed for research participants.

Chapter II

DRUGS OF CLINICAL TRIAL, EXEMPTED FROM CLINICAL TRIAL AND EXEMPTED FROM SOME STAGES OF CLINICAL TRIAL

Article 5. Drugs of clinical trial of complete stages

1. For pharmaceutical drugs, medical biological products:

a) Pharmaceutical drugs containing new substance, drugs with new combination of drugs circulated.

b) Medical biological products first invented or with new combination of components that have been circulated.

c) Pharmaceutical drugs, foreign medical biological products which have been circulated legally but not enough 05 years in the country of origin (or reference country if international treaties to which Vietnam is a member allow).

d) Pharmaceutical drugs, medical biological products which have been conducted clinical trials before the effective date of this Circular but not yet met the provisions of good clinical practice of the Ministry of Health or the international guidelines on good clinical practice accredited by the Health Ministry.

2. For vaccines:

a) Vaccine newly-researched, produced, and firstly used.

b) Foreign vaccine which have been circulated legally but not enough 05 years in the country of origin (or reference country if international treaties to which Vietnam is a member allow).

c) Vaccine that has been conducted clinical trial before the effective date of this Circular but not yet met the provisions of good clinical practice of the Ministry of Health or the international guidelines on good clinical practice accredited by the Health Ministry.

3. For traditional medicines or drugs from medicinal plants:

a) Drugs containing new pharmaceuticals firstly used in humans.

b) Drugs that have been conducted clinical trial before the effective date of this Circular but not yet met the provisions of good clinical practice of the Ministry of Health or the international guidelines on good clinical practice accredited by the Health Ministry.

Article 6. Drugs exempted from clinical trial

1. For pharmaceutical drugs, medical biological products:

a) Pharmaceutical drugs called original name (generic drugs).

b) Foreign drugs that have not been issued registration numbers for circulation in Vietnam but have been circulated legally for at least 05 years in the country of origin (or reference country if international treaties to which Vietnam is a member allow) and have been certified by competent state agencies as safe and effective, with the same use, and content and indicated in Vietnam as specified in that country.

c) Foreign drugs that have been issued registration numbers for circulation in Vietnam, but there are changes or supplements of new indications, new use, new dosage forms as same as those drugs which have been circulated legally for at least 05 years in the country of origin (or reference country if international treaties to which Vietnam is a member allow).

2. For vaccines:

a) Foreign vaccines that have been issued valid registration numbers for circulation in Vietnam, are imported into Vietnam to complete the stage of labeling, putting in the box.

b) Re-registered vaccines in Vietnam due to expiration of the registration numbers and without any changes.

3. For traditional medicines or drugs from medicinal plants:

a) The herbal remedies accredited by the Health Ministry.

b) Traditional medicines or drugs from foreign material herbs which have not been granted registration numbers for circulation in Vietnam but have been circulated legally for at least 05 years in the country of origin (or reference country if international treaties to which Vietnam is a member allow) and have been certified by competent state agencies of that country as safe and effective, with the same use, and content and indicated in Vietnam as specified in that country.

Article 7. Drugs exempted from some clinical trial stages

1. For pharmaceutical drugs, medical biological products:

Foreign drugs that have been issued registration numbers for circulation in Vietnam, but there are changes or supplements of new indications, new use, new dosage forms other than indications, use, dosage forms of the drugs which have been circulated legally for at least 05 years in the country of origin (or reference country if international treaties to which Vietnam is a member allow) must be:

a) Conducted clinical trial to assess the safety;

b) Conducted clinical trial to assess efficacy in case of not yet conducted that trial or completion of clinical trial but not yet met the provisions of good clinical practice of the Ministry of Health or the international guidelines on good clinical practice accredited by the Health Ministry.

2. For vaccines:

a) Clinical trial to assess safety for:

- Foreign vaccines that have not been issued registration numbers for circulation in Vietnam but have been circulated legally for at least 05 years in the country of origin (or reference country if international treaties to which Vietnam is a member allow) and have been certified by competent state agencies as safe and effective, with the same use, and content and indicated in Vietnam as specified in that country.

- Vaccines produced in Vietnam and made from products awaiting for import packaging from abroad that their finished products have been circulated legally for at least 05 years in the country of origin (or reference country if the international treaties to which Vietnam is a member allow).

- Vaccines which have been granted registration numbers for circulation in Vietnam, but there are changes or supplements of excipients, preservatives, change of production facilities (not changing the production process).

b) Clinical trial to assess the safety and immunogenicity in stage 3 for:

- Foreign vaccines which have been circulated legally for at least 05 years in the country of origin (or reference country if international treaties to which Vietnam is a member allow) transferred production technology in Vietnam.

- Vaccines produced in Vietnam made from imported intermediate products that their finished products have been circulated legally for at least 05 years in the country of origin (or reference country if the international treaties to which Vietnam is a member allow).

- Vaccines which have been granted registration numbers for circulation in Vietnam, but there are changes or addition of the contents such as: production processes, dosage forms, indications, using subjects (age, gender, nation), use, dosage, vaccination schedule.

3. For medicines or drugs from medicinal herbs:

Clinical trial to assess the safety of drugs which have been granted registration numbers for circulation in Vietnam and other herbal remedies accredited by the Health Ministry but there are changes or supplements of indication, use, dosage forms other than indication, use, dosage forms of the drugs which have been circulated legally for at least 05 years in the country of origin (or reference country if international treaties to which Vietnam is a member allow).

Article 8. Clinical drug trial in some special cases, emergency related to health security

Minister of Health considers and makes decision to exempt certain stages of clinical drug trial on the basis of advice of the Advisory Council for Granting Drug Circuation registration numbers and the Council of Ethics in biomedical research - Ministry of Health for the following cases:

1. Drugs used in special cases, emergency related to health security include:

a) Pharmaceutical drugs, medical biological products, vaccines which have been circulated legally but not enough 05 years in the country of origin (or reference country if international treaties to which Vietnam is a member allow), which clinical trial data of multi-centers conducted in Vietnam and Asia has, the research results proved to achieve safety and effectiveness, with the same content, indication and use in Vietnam as indicated in that country.

b) Pharmaceutical drugs, traditional medicines or drugs from medicinal herbs meeting the requirements for special treatment on the list of rare drugs issued by the Health Ministry, with special dosage forms which have not been produced domestically, have no any alternative medicine and if this kind of drugs are not used, will affect the life of the patients, have not been granted registration numbers for circulation in Vietnam but has been circulated legally but not enough 05 years in the country of origin (or the reference country if international treaties to which Vietnam is a member allow) and have been certified by competent state agencies to be safe and effective, with the same use, and content and indicated in Vietnam as specified in that country.

c) Vaccines used to prevent dangerous infections newly arisen and unknown its pathogen or infectious diseases especially dangerous, capable of rapid spread, wide spread and high mortality, have not been granted registration numbers for circulation in Vietnam, have been circulated legally but not enough 05 years in the country of origin (or the reference country if international treaties to which Vietnam is a member allow) and have been certified by competent state agencies to be safe and effective, with the same use, and content and indicated in Vietnam as specified in that country.

2. The drugs which have resulted from research projects, research theme of ministerial level or similar and above and are made before the effective date of this Circular and complied with the provisions of this Circular and the directions on good clinical practice, to be accepted and assessed satisfactory by the council of science and technology of equivalent or ministerial-level and recommended for wide application.

Chapter III

CONDITIONS OF CLINICAL DRUG TRIAL

Article 9. Conditions for drugs of clinical trial

Drugs of clinical trials must meet the following requirements:

1. Have been researched in pre-clinical stage; have documents to prove the safety to be able to test the next stages.

2. Have formulations, dosage forms and stabled dosage process.

3. Have results of clinical trial studies of the previous stages if it is proposed clinical drug trial for the next stages.

4. Get standards of quality according to registration dossier for clinical drugs trial.

5. Medicine label of clinical trial with the words "Product used for clinical trial; it is forbidden to use for other purposes."

Article 10. Conditions on dossiers of clinical trial

Dossier of registration for clinical trial is in Vietnamese (01 original with signature, legal stamp and 03 copies), including:

1. Application for clinical drug trial of agencies, organizations and individuals with drugs requesting for clinical trial (Appendix 1 attached to this Circular).

2. Dossiers of products for researchers in Vietnamese or in English accompanied by a summary in Vietnamese (Appendix 2 attached herewith).

3. Application for evaluation and research proposals approved clinical trial of institutions undertaking test (Appendix 3 attached to this Circular).

4. Cooperation contract of researching clinical drug trial among agencies, organizations, individuals with drugs requested for clinical trial and organizations undertaking trial and cooperation contracts between agencies, organizations and individuals with drugs requested for clinical trial and clinical research organization, clinical site management organization if any (Annex 4, issued together with this Circular).

5. Explanation for the research scheme of clinical trial (Appendix 5, issued together with this Circular).

6. Scientific curriculum vitae and certificates of good clinical practice of the prime researcher/subject chairman issued by the Health Ministry or by organizations recognized by the Health Ministry.

7. The written provision of information on research and slip of volunteer participating in the research (Appendix 6, issued together with this Circular).

8. Minute of evaluating the science and ethics in research of the ethics Council in biomedical research of basic level (organization undertaking clinical drugs trial).

9. Written certification of the participation of research institutions over multi-center research in Vietnam.

10. Written approval of the research of People’s Committee of province or city directly under the Central Government for research in the field.

11. The documents on the clinical drugs trial include:

a) Drug researching documents recipe ingredients, production processes, quality standards, drug testing slip (for pharmaceutical drugs, traditional medicines or drugs from medicinal plants: testing slip of the agency of central drug testing or of the manufacturers achieved standards of good manufacturing practice (GMP); for vaccines: quality testing slip of national testing agencies or certification of shipments for lot of vaccines, biological products of the National Drug Administration of home country).

b) Document of pre-clinical research of drugs need to be tested: reports of research on the pharmacological effects, toxicity, safety and suggestions on dosage, route of administration, use.

c) Research documents of clinical drug trial of the previous stages (if it is proposed clinical drug trial for the next stages).

12. A certified copy of the certificate of product (CPP) or permit for the circulation of drugs (FSC) and certificate of achieving standards of good manufacturing practice (GMP) of the competent State management agencies for drugs suggested for research of clinical trials, evaluating the safety, clinical trial of stage 4.

13. Label of research drug as prescribed in Clause 5 of Article 9 of this Circular and photos of samples of research drugs.

Article 11. Conditions of institutions undertaking clinical trial, the prime researchers and researchers participating in clinical drug trial

1. Organizations undertaking clinical drug trial must meet the criteria of good clinical practice (GCP); be independent of economy, of personnel organization against individuals and organizations with drugs of clinical trial and commit that the clinical trial totally do not have any conflicts of interest between the parties.

2. Pime researchers in the clinical trial must have the level of specialized knowledge, clinical experience, practical ability to ensure the principles of good clinical practice, master the rules of clinical drugs trial, capable of implementing the research outline which was approved in full and on schedule, with GCP certificate issued by the Ministry of Health or by organizations recognized by the Health Ministry.

3. Researcher must have appropriate expertise, to be trained in the necessary contents and skills to undertake research, have GCP certificate issued by the Ministry of Health or by organizations recognized by the Health Ministry.

Article 12. Conditions of participants of clinical drug trial

1. Participants in clinical drug trial must be volunteers meeting professional requirements and must sign a commitment with the organization undertaking clinical dugs trial, except for those who are restricted civil act capacity, lose civil act capacity or have no capacity for civil acts.

2. Where the participants in clinical drug trial are less than 18 years old, restricted civil act capacity, lost civil act capacity or have no capacity for civil acts, it must be approved by their representatives in accordance with the law provisions.

3. Where the participants in clinical drug trial are women who are pregnant or breast-feeding: research dossiers must be clearly stated the reasons for selecting this subject and must be approved by the Minister of Health on the basis of consideration and evaluation of research outline for scientific, moral aspects of the Council of Ethics in biomedical research - Ministry of Health.

Article 13. Conditions for funding clinical drug trial

1. Funding must be sufficient to complete the activities in the whole process of clinical drug trial (including items: funding for conducting research and funding for management, supervision, inspection) funded by the agencies, organizations and individuals with drugs of clinical trial shown by research contracts between agencies, organizations, individuals with drugs of clinical trial and organizations undertaking clinical drug trials.

2. For the study drugs funded by the program, themes using the state budget or the themes in cooperation with other foreign and domestic organizations and individuals, chairmen and organizations undertaking clinical drug trial need to estimate funds for clinical trials in total funds allocated for research.

3. Organizations undertaking clinical testing and researchers are responsible for managing their allocated funds to spend on research with the proper content and cost norms prescribed by law or contract signed by both parties.

Chapter IV

REGISTRATION, EVALUATION AND APPROVAL OF RESEARCH OF CLINICAL DRUG TRIAL

Article 14. Registration for research of clinical drug trial

1. Agencies, organizations and individuals with drugs of clinical trial apply for registration including documents specified in Clause 1, Clause 2 of Article 10 of this Circular to the Ministry of Health.

2. Within 15 working days after receipt of registration dossier, the Ministry of Health shall send written response as a basis for agencies, organizations and individuals with drugs of clinical trial to deploy next steps.

Article 15. Building research profile

Based on the written approval of the Ministry of Health, agencies, organizations and individuals with drugs of clinical trial collaborate with prime researchers and organizations undertaking clinical drug trials to prepare clinical drug trial research profile include:

1. Agencies, organizations and individuals with drugs of clinical trial provide for the documents specified in clauses 1, 2, 7, 11, 12 and 13, Article 10 of this Circular to the prime researchers and organizations undertaking clinical drug trials.

2. Prime researcher collaborate with agencies, organizations and individuals with drugs of clinical trial and members of research team to design research outline, prepare complete dossiers in accordance with provisions in Article 10 of this Circular.

Article 16. Application for research and clinical drug trial

1. Dossier of research and clinical drug trial is in accordance with provisions in Article 10 of this Circular and sent to the Ministry of Health as a basis for the evaluation, review and approval.

2. The dossier submitted to the Health Ministry before the 20th of each month will be considered for evaluation in that month. The dossier submitted after the above deadline will be transferred to the next month for evaluation.

3. For information regarding registration, compilation and dossier submission can be accessed at web portal of the Ministry of Health www.moh.gov.vn or via website of the Council of ethics in biomedical research - Ministry of Health www.iecmoh.vn.

Article 17. Evaluation and approval of researches of the clinical drug trial

1. Evaluation of research profile:

Within 30 working days after undertaking complete dossiers as prescribed in Article 10 of this Circular, the Ministry of Health shall organize meeting of Council of Ethics in biomedical research.

2. Announcement of results:

Within 15 working days after having the evaluation results of the Council of Ethics in biomedical research, Department of Science and Training will aggregate to complete the records and notify in writing the results to agencies, organizations and individuals with drugs of clinical trial, organizations undertaking clinical drug trial.

3. Approval:

Within 15 working days after the notification of results and receiving complete additional documents (if any), Department of Science and Training will synthesize, submit to the Minister of Health for approval.

Chapter V

CLINICAL DRUG TRIAL STAGES AND CONDUCTING EXPERIMENT

Article 18. The stages of clinical pharmaceutical drugs, medical biological products trial

1. Stage 1:

a) As the first stage to test new active elements or new formulations of the drugs in humans (usually done in the healthy volunteers).

b) Research purpose of stage 1: to establish a preliminary evaluation of the safety and initial assessment of pharmacokinetics and pharmacodynamics of the active element in humans.

c) Sample size: should be considered carefully based on results of preclinical research, sample sizes of 10-30 subjects.

2. Stage 2:

a) As the test stage to be conducted on a limited number of patients.

b) Research purpose of stage 2: to evaluate the therapeutic effect and safety of active elements in the patients, determine the use dose and appropriate dose regime to provide optimal treatment for clinical trials.

c) Sample size: at least 50 patients.

3. Stage 3:

a) As the test stage to be studied on a larger number of patients. The clinical trial conditions during this period are conducted close to the normal conditions of use. It is often conducted multicenter, randomization, with placebo.

b) Research purpose of stage 3: to determine the stability of the formula, the safety and effectiveness of short and long term of active substance, evaluate the effectiveness of treatment at the overall level. To research the adverse reactions often occurring, detect the special characteristics of researched products.

c) Sample size: at least 200 patients.

4. Stage 4:

a) As the clinical studies to be conducted after the drug has been put into circulation. Study design may vary but the scientific standards and ethical standards are similar to the one before drug is circulated.

b) Research purpose of stage 4: clinical trial of this stage is conducted on the basis of the characteristics of the product allowed for circulation, usually in the form of monitoring after the circulation or evaluation of effect of therapy or evaluation of treatment strategies.

c) Sample size: at least 1,000 patients.

Article 19. The stages of clinical vaccines trial

1. Stage 1:

a) As the first stage of testing new vaccine in the small-scale for preliminary assessment of the safety of the vaccine through the preliminary information collection on drug tolerance. Stage 1 is usually performed on adult healthy volunteers, at risk of infection and low complication before use for the target subjects.

b) Stage 1 is usually open research, non-randomized with a placebo of pharmaceutical fake can be done with some particular age or population groups to determine dose, safety, vaccine schedule, the route of vaccination.

c) The attenuated live vaccines (virus or bacteria) capable of infecting recipients or contacting persons must be evaluated and closely monitored on the dose, clinical signs of infection and response (immediate, early and late). Stage 1 research can provide preliminary information on the dispersion, transmission to contacting persons and the genetic stability of vaccine.

d) Sample size: should be considered carefully based on results of preclinical studies, sample sizes of 30-50 subjects.

2. Stage 2:

a) Is conducted after the completion of Stage 1 with the results approved by the Council of Ethics in biomedical research - Ministry of Health. Purpose of stage 2 is to demonstrate the immunogenicity of the active ingredients, the safety of the vaccines tested on target subjects. Stage 2 research is to evaluate the immune response related to age, race, and gender. Study of design has placebo and randomization.

b) For attenuated live vaccines, in addition to the monitoring of parameters such as stage 1, it needs to pay attention to the presence and existence of antibodies titers: neutralizing antibodies or fixation cross antibodies or cell-mediated immune and interactions affecting the immune system (eg pre-existing antibodies, immunization made at the same time with vaccines or other drugs).

c) Sample size: at least 200 subjects.

3. Stage 3:

a) Stage 3 research is done on a large scale, multi-center to evaluate the protective effect (efficacy) and safety of the active ingredients of immunity in the vaccine on the target subjects.

b) Sample size: at least 500 subjects.

4. Stage 4:

a) Stage 4 research is conducted after the vaccines have been licensed for distribution. Stage 4 is considered as monitoring after granting license or research after granting license for the purpose of determining adverse effects and monitoring protective effect after vaccines are widely used in the population community under conditions of use. Stage 4 can be held to assess:

- The optimal conditions for the use of vaccines (optimal age for vaccination, concomitant use with other vaccine and other conditions).

- Protective effect of risk groups (elderly, immune injury patients, people with certain diseases).

- Maintenance of level of protection and long-term safety.

b) Sample size: at least 10,000 subjects.

Article 20. The stages of testing traditional medicines or drugs from clinical medicinal herbs

1. Stage 1:

a) Research is often conducted on volunteers who meet clinical trial criteria for the purpose of determining safe dose (maximum dose that the dose does not cause serious side effects), as follows:

b) The first dose must be equal to 1/3 - 1/5 of dose expected from preclinical studies. From the first dose to the maximum dose, it may be divided many doses. This stage is ended when the safe dose is determined.

c) Sample size: should be considered carefully based on results of preclinical studies, sample sizes of 10-30 subjects.

2. Stage 2:

a) The study evaluates the safety and efficacy of drugs. Study design has a placebo, randomization, each group has at least 25 patients.

b) Therapeutic dose: dose of drug used in this stage must be based on research results of stage 1.

c) Sample size: at least 50 patients.

3. Stage 3:

a) To confirm the safety and efficacy of drugs in the extended conditions. Study subjects were selected by random method with control or self-control.

b) Sample size: at least 100 patients.

4. Stage 4:

a) Applying as for pharmaceutical drugs.

b) Sample size: at least 200 patients.

Article 21. Clinical drug trial at several different establishments

1. When conducting research in many different establishments, organizations undertaking clinical drug trial need to establish joint steering committee consisting of prime researchers, prime researchers of branches and representatives of the units presiding over research to unify objectives, content, evaluation criteria, plans and research progress.

2. For multinational clinical research, in which Vietnam is a participant, the procedures, dossiers must comply with the provisions of this Circular. Objectives and content of research, trial in Vietnam, and the joint activities to implement the research with other nations must be detailed in the research outline.

Article 22. The objectives, contents and sample sizes of research

Minister of Health specifies objectives, contents and sample sizes of research specified in Article 18, 19, 20 and 21 of this Circular based on the advice of the Council of Ethics in bio-medical research for each case of dossier, research outline.

Article 23. Handling cases of complications during the clinical drug trial

Handling of irregularities in the research process is as follows:

1. In case of dangerous complications threatening the lives of participants in clinical drug trial, the prime researchers and organizations undertaking clinical trials must stop testing on the participants, hold the first aid, recovery and deal with the consequences, make records, and urgently report to the grassroots Council of Ethics, Council of Ethics - Ministry of Health, Department of Science and Training, Ministry of Health.

2. In cases of clinical trial leading to damage the health of participants in clinical drug trial, prime researchers must stop the research for the treatment and monitor the health happening of clinical trial participants and review and decide on continuty or stopping clinical trials.

3. Abnormal cases anticipated and adopted handling measures effectively shall be continued to conduct clinical drug trial.

Article 24. Collection of information and data

1. The information recorded in the course of researching clinical drug trial must be recorded in clinical research files (CRFs). CRF is considered as the original document, preserved, stored in accordance with provisions for used a basis for monitoring, evaluation and acceptance of testing results.

2. The relevant documents required for the clinical assessment process (testing slip, diagnostic imaging results, prescriptions) must be copied from the original writing full name of cross-check examiner, stating clearly the origin and must be managed, stored according to regulations.

Article 25. Data processing

1. The research data of clinical drug trial must be treated by biologic statistical methods and must be processed by an agency or organization independent of the agency or organization undertaking data processing to ensure the objectivity, honesty and trust.

2. Results of statistical analysis must be clearly presented to help identification of differences in clinical outcome; when evaluating treatment effects, it must be based on reliability and the results obtained from statistical analysis. Report on final conclusion of clinical study should be consistent with the results of statistical analysis.

Article 26. Documents archive on clinical drug trial

1. The data, the original document, testing slip, image diagnostic results, the collected documents related to clinical drug trial, minutes of meetings of the boards, supervision records, progress reports, trial registration documents and other trial-related materials must be preserved completely, stored at least 15 years at the research establishments, from the time the study is ended.

2. Prime researcher is responsible for the entire process of preservation and archive of research documentation and for presenting them upon request of the delegations of inspection, supervision and competent state management agencies.

Article 27. Report of research result of clinical drug trial

1. Report of result of clinical drug trial is in compliance with prescribed form (Appendix 7, issued together with this Circular), including full information on the drug, description of the research method, testing process, data analysis, result evaluation, comparison with the research objectives and research tasks; provide honest and objective, accurate conclusions. Contents of report must be consistent with the objectives and content of research in the approved outline.

2. Prime researcher is responsible for the science, accuracy and truthfulness of the data, conclusions, judgment and other contents of the report.

Article 28. Management of drugs of clinical trial

1. The import and export of drugs of clinical trial shall comply with current regulations on import and export of drugs.

2. The management of drugs of clinical trial must comply with current regulations from the stages of sampling, quality testing, packaging, transportation, delivery, storage, labeling, and distribution.

3. It must have a logbook to track the use of drugs of clinical trial together with information on the quantity and quality of drugs.

4. Un-used up drugs and stored drugs must be strictly managed, separated and stored according to the right regulations. Unused up drugs must be handed over to organizations and individuals with drugs of clinical trial.

5. It must be made handling records for the drugs not guaranteed quality in accordance with provisions of the Ministry of Health.

6. Stored drug samples (03 smallest packaging unit) must be preserved at least three years (36 months) in the organizations undertaking clinical drug trial after the end of the research.

Chapter VI

RIGHTS AND OBLIGATIONS OF PARTICIPANTS, THE ORGANIZATIONS HAVING DRUGS OF CLINICAL TRIAL AND THE ORGANIZATIONS UNDERTAKING CLINICAL DRUG TRIAL

Article 29. Rights of participants in clinical drug trial

1. Be provided with full and truthful information before the clinical trials on the process of trial and the risks that may occur.

2. Be compensated damages by agencies, organizations, and individuals with drugs of clinical trial if they are caused by clinical trials.

3. Be kept confidential on concerned individual information.

4. Not be responsible for the unilateral termination of contract for participation in clinical drug trial.

5 Lodge complaints and denunciations for acts of law violations of organizations or individuals with drugs of clinical trial and organizations undertaking clinical trial.

6. Be cared for Healthcare in the process of trial by the research outline to be approved.

Article 30. Rights of agencies, organizations and individuals with drugs of clinical trial

1. Be selected and proposed the organization to meet the regulations on material facilities and expertise officials to conduct clinical drug trial.

2. Be owned all of the research results of drugs of clinical trial.

3. Be applied for the termination of the research if the organization undertaking drug trial commits serious violations of outline.

Article 31. Obligations of agencies, organizations and individuals with drugs of clinical trial

1. To apply for permission and agreed by the Minister of Health in writing prior to clinical trial.

2. To pay compensation for damages to participants in clinical drug trial if the risk occurs due to clinical drug trial in accordance with provisions of current legislation.

3. To sign contracts for clinical drug trial with the organizations undertaking clinical drug trial and clinical research organization (if any).

4. To take responsibility before law for the safety and quality of drugs supplied by them.

Article 32. Rights of the organizations undertaking clinical drug trial

1. Be supplied drugs, funds by agencies, organizations and individuals with drugs of clinical trial to conduct clinical trials in accordance with the law provisions.

2. Be used research results of clinical drug trial under agreements with agencies, organizations and individuals with drugs of clinical trial.

Article 33. Obligations of the organizations undertaking clinical drug trial

1. To comply with good clinical practice; report to the Ministry of Health on the process, results of clinical drug trial and report irregularly for the necessary cases.

2. To sign the contract on the clinical drug trial with agencies, organizations and individuals with drugs of clinical trial and with participants in clinical trial.

3. To continue to monitor health and disease of participants in clinical trial as agreed in the contract or the research outline.

Chapter VII

SUPERVISION AND INSPECTION OF RESEARCH QUALITY ASSURANCE

Article 34. Supervision, inspection of clinical drug trial process

1. Supervision and inspection to ensure the rights and interests and health of participants in clinical drug trial; ensure the recorded data of the research to be conducted fully and accurately, timely and in accordance with regulations of the research outline approved.

2. Ministry of Health establishes the delegation of monitoring, period, and irregular inspection for each specific case.

3. Competent state management agencies, organizations and individuals with drugs of clinical trial, clinical research organization (CRO) or research site management organization (SMO) approved by the Health Ministry in writing may propose the appointment of persons for systematic monitoring and supervision of the research process. The person who is assigned the task of supervision is not a member of the research team, complies with regulations on security of research data and other information related to clinical trial participants and take responsibility before the management agencies for their works.

4. Major researchers and the researchers are responsible for creating conditions for the supervisor to refer the research data upon request.

5. Delegation of supervision, inspection is responsible for checking the report, proposing by the minutes of supervision and inspection of the supervision contents with competent state management agencies as the basis for the consideration and handling according to the provisions of law.

Article 35. Assurance of the reliability of research results of clinical drug trial

1. To ensure research with sufficient reliability, the analysis and judgment, conclusions on the results must be derived from the original data. In each research stage, it should examine all the clinical data and testing criteria.

2. In necessary cases, the acceptance councils at all levels will invite experts for evaluating results, checking data, testing products of research or establish the board of monitoring data (DSMB) at the request of the management agency.

Chapter VIII

ACCEPTANCE OF EVALUATION OF RESULTS OF CLINICAL DRUG TRIAL

Article 36. Procedures for accepting the results of clinical drug trial

1. Acceptance of the research results of clinical drug trial is done under the current regulations on assessment, acceptance of research themes of science, technology and good clinical practice guidelines.

2. The acceptance is conducted at two levels: grassroots level and Ministry of Health level. At the end of the research, the prime researcher is responsible for reporting to the organizations undertaking clinical drug trial to evaluate the research results at grassroots level and completing the dossier to report to the Ministry of Health for acceptance at Ministry level.

Article 37. Acceptance dossier at level of Ministry of Health

Dossier of report for acceptance at level of Ministry (01 original set signed, sealed legally and 03 copies), includes:

1. Official dispatch of the organization undertaking clinical drug trial proposing for the acceptance at level of Ministry.

2. Copy of research outline to be approved.

3. Decision on approving research outline.

4. Decision on establishing Council of acceptance at grassroots level.

5. Minutes of meetings of Council of acceptance at grassroots level.

6. Full-text reports of research results of clinical drug trial as prescribed and may add other relevant information as it deems necessary.

Article 38. End of research of clinical drug trial

1. Within 30 working days after receiving complete dossiers applied for acceptance, the Ministry of Health will hold a Council of acceptance of the results of research under current regulations.

2. Research of clinical drug trial is considered as completed only when report on results finally assessed and accepted by the Council and accepted the additions of prime researcher in accordance with the comments of the Council (if any).

3. The data and results of clinical trials are published only when they were assessed and accepted by the Council of Ethics in biomedical research - Ministry of Health.

Chapter IX

ORGANIZATION OF IMPLEMENTATION

Article 39. Responsibility for implementation

The Department of Science and Training shall preside over and coordinate with the concerned Departments:

1. To receive and examine registration dossiers and guide organizations and individuals with drugs of clinical trial and organizations undertaking clinical drug trial to comply with the provisions of this Circular and other concerned provisions of law.

2. To appraise the conditions for clinical drug trial dossiers, professional capacity, material facilities and legality of the organizations undertaking clinical drug trial, clinical research organization (CRO), the management organization of research sites (SMO) and report to leader of the Ministry for permission to conduct trial.

3. To organize the meetings of the Council of Ethics in biomedical research - Ministry of Health to review for approval of research outlines, evaluation of the contents of ethics in research and specialized science; to assess the results of research of clinical drug trial, synthesize and submit to leader of the Ministry for approval.

4. To organize period or irregular supervision, inspection during the course of research.

5. To disseminate and guide implementation of the contents of this Circular and guide good clinical practice and ethics in biomedical research for the concerned units, organizations and individuals.

Article 40. Transitional provisions

The registration dossiers for clinical drug trial submitted before the effective date of this Circular are reviewed and evaluated according to "Regulation on clinical drug trial" issued together with Decision No.01/2007/QD -BYT dated 11/01/2007 of the Minister of Health.

Article 41. Effect

1. This Circular takes effect from 20/03/2012.

2. To annul the Decision No.01/2007/QD-BYT dated 11/01/2007 of the Minister of Health promulgating the "Regulations on clinical drug trial" from the effective date of this Circular.

3. Heads of agencies, organizations and concerned units are responsible for organizing the propagation, dissemination and implementation of this Circular to the subjects for implementation.

In the implementation process if there are any problems, the concerned organizations, individuals should report them promptly to the Health Ministry for reviewing amendment and supplement accordingly.

 

MINISTER Nguyen Thi Kim Tien