Circular No. 03/2012/TT-BYT guiding clinical drug trials

CIRCULAR

Guidelines for Clinical Drug Trials

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Based on the Medicine Law dated June 14, 2005 and the Government Decree No. 79/2006/NĐ-CP dated August 9, 2006 detailing the implementation of certain provisions of the Medicine Law;

Based on the Government Decree No. 188/2007/NĐ-CP dated December 27, 2007 stipulating the functions, tasks, authorities, and organizational structure of the Ministry of Health,

The Ministry of Health issues guidelines for clinical drug trials as follows:

PART I

GENERAL PROVISIONS

Article 1. Scope of Regulation

These guidelines provide guidance on drugs that must undergo clinical trials, exemptions from clinical trials, exemptions from certain phases of clinical trials; conditions for conducting clinical drug trials; registration, evaluation, approval of clinical drug trials, stages of clinical drug trials; rights and obligations of related parties; supervision, inspection, acceptance, and evaluation of clinical trial results in Vietnam to serve research purposes and permit circulation of chemical medicines, medical biological products, vaccines, traditional medicine, and herbal medicines used directly for diagnosis, treatment, and prevention of diseases (hereinafter referred to collectively as drugs).

Article 2. Interpretation of Terms

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

1. Reference country is one of the United Kingdom, France, Germany, the United States, Japan, Australia, Canada, or the European Medicines Agency (EMA).

2. Multicenter study is a clinical trial conducted at two or more research centers to ensure the universality of the number of participants in clinical drug trials, with more diverse demographic or ethnic factors.

3. Organizations, entities, individuals conducting clinical drug trials are organizations, entities, individuals with the function of researching, producing, importing, exporting, distributing drugs that require their own clinical trials.

4. Organizations accepting clinical drug trials are healthcare facilities with scientific research functions, having sufficient conditions in terms of professional staff, infrastructure, equipment for conducting clinical drug trials, and have been evaluated and approved by the Ministry of Health.

5. Participants in clinical drug trials are patients or healthy volunteers who voluntarily participate in the research.

6. Clinical Research Organization (CRO) is an entity with legal personality, possessing appropriate professional capacity according to the regulations of the Ministry of Health, independent from organizations, entities, individuals conducting clinical drug trials, contracted by organizations, individuals conducting clinical drug trials to perform support work for research such as writing research protocols, monitoring research, analyzing data.

7. Site Management Organization (SMO) is an entity with legal personality, possessing adequate capacity according to the regulations of the Ministry of Health, independent from organizations, entities, individuals conducting clinical drug trials, organizations accepting clinical drug trials, contracted by organizations, individuals conducting clinical drug trials or organizations accepting clinical drug trials to perform support work for managing research sites.

8. Foreign clinical data is the method and results of clinical studies already conducted abroad.

9. Ethnic factor refers to characteristics related to large groups of people sharing genetic, cultural, customary, and living environment traits.

10. International regulations on clinical drug trials recognized by the Ministry of Health are Good Clinical Practice (GCP) guidelines of the International Conference on Harmonisation (ICH) and World Health Organization (WHO).

Article 3. Principles for Clinical Drug Testing

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

2. Participants in clinical drug testing must be selected according to ethical principles in biomedical research.

Article 8. Prohibited acts

1. Conducting clinical drug testing without permission from the Ministry of Health.

2. Unilaterally modifying or supplementing the contents of the dossier or research protocol already approved by the Ministry of Health.

3. Using clinical trial drugs for purposes other than intended.

4. Coercing research participants or concealing information or failing to provide information as required for participants.

Chapter II

DRUGS THAT MUST UNDERGO CLINICAL TRIALS, EXEMPTION FROM CLINICAL TRIALS AND EXEMPTION FROM CERTAIN STAGES OF CLINICAL TRIALS

Article 5. Drugs that Must Undergo Full Stages of Clinical Trials

1. For chemical drugs and medical biological products:

a) New chemical drugs containing new active ingredients or new combinations of existing active ingredients.

b) Medical biological products that are newly invented or have new combinations of existing components.

c) Foreign chemical drugs and medical biological products that have been legally marketed but have not yet been on the market for five years in their country of origin (or reference country if international treaties to which Vietnam is a member allow).

d) Chemical drugs and medical biological products that were previously tested clinically before the effective date of this Circular but did not meet the Ministry of Health's guidelines on good clinical practice or internationally recognized guidelines on good clinical practice.

2. For vaccines:

a) Newly researched and produced vaccines being used for the first time.

b) Foreign vaccines that have been legally marketed but have not yet been on the market for five years in their country of origin (or reference country if international treaties to which Vietnam is a member allow).

c) Vaccines that were previously tested clinically before the effective date of this Circular but did not meet the Ministry of Health's guidelines on good clinical practice or internationally recognized guidelines on good clinical practice.

3. For traditional medicine and herbal drugs:

a) Traditional medicines and herbal drugs containing new herbs used for the first time on humans.

b) Traditional medicines and herbal drugs that were previously tested clinically before the effective date of this Circular but did not meet the Ministry of Health's guidelines on good clinical practice or internationally recognized guidelines on good clinical practice.

Article 6. Drugs Exempted from Clinical Trials

1. For chemical drugs and medical biological products:

a) Generic chemical drugs.

b) Foreign drugs not yet registered for circulation in Vietnam but have been legally marketed for at least five years in their country of origin (or reference country if international treaties to which Vietnam is a member allow), and have been confirmed by the competent authority of that country as safe and effective, with the same route of administration, dosage, and indications in Vietnam as in that country.

c) Foreign drugs that have been registered for circulation in Vietnam but have undergone changes or additions to their indications, routes of administration, or formulations similar to those of the drugs that have been legally marketed for at least five years in their 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 registered for circulation in Vietnam and are still valid, imported into Vietnam to complete labeling and packaging stages.

b) Vaccines re-registered in Vietnam due to expiration of registration number and without any changes.

3. For traditional medicine and herbal drugs:

a) Traditional medicine formulas recognized by the Ministry of Health.

b) Traditional medicines and herbal drugs from foreign countries not yet registered for circulation in Vietnam but have been legally marketed for at least five years in their country of origin (or reference country if international treaties to which Vietnam is a member allow), and have been confirmed by the competent authority of that country as safe and effective, with the same route of administration, dosage, and indications in Vietnam as in that country.

Article 7. Medicines exempted from some clinical trial phases

1. For chemical drugs and medical biological products:

Foreign medicines that have been registered for circulation in Vietnam but have changes or additions to new indications, new routes of administration, or new formulations different from those of the legally circulating medicines in their country of origin (or reference country if international treaties to which Vietnam is a member allow) for at least five years must implement:

a) Clinical trials to evaluate safety;

b) Clinical trials to evaluate efficacy if they have not undergone clinical trials to evaluate efficacy or if such trials have been conducted but did not meet the Good Clinical Practice guidelines for clinical trials issued by the Ministry of Health or internationally recognized Good Clinical Practice guidelines.

2. For vaccines:

a) Safety clinical trials for:

- Foreign vaccines that have not been granted registration numbers for circulation in Vietnam but have been legally circulated in their country of origin (or reference country if international treaties to which Vietnam is a member allow) for at least five years, confirmed by the competent authority of that country to be safe and effective, with the same route of administration, dosage, and indication as in that country.

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

- Vaccines that have been granted registration numbers for circulation in Vietnam but have changes or additions to excipients, preservatives, or production sites (without changing the production process).

b) Phase 3 clinical trials to evaluate safety and immunogenicity for:

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

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

- Vaccines that have been granted registration numbers for circulation in Vietnam but have changes or additions to production processes, formulations, indications, target populations (age, gender, ethnicity), routes of administration, dosages, or vaccination schedules.

3. For traditional medicine and herbal drugs:

Safety clinical trials for medicines that have been granted registration numbers for circulation in Vietnam and traditional herbal formulas recognized by the Ministry of Health but have changes or additions to indications, routes of administration, formulas, or formulations different from those of the legally circulating medicines in their country of origin (or reference country if international treaties to which Vietnam is a member allow) for at least five years.

Article 8. Clinical trials for certain special and urgent cases related to health security

The Minister of Health shall consider and decide to exempt some clinical trial phases based on the advice of the Advisory Council for Granting Registration Numbers for Medicines and the Bioethics Council in Medical Research - Ministry of Health in the following cases:

1. Medicines used in special and urgent cases related to health security include:

a) Chemical drugs, medical biological products, and vaccines that have been legally circulated but less than five years in their country of origin (or reference country if international treaties to which Vietnam is a member allow), have multi-center clinical trial data conducted in Vietnam and Asia, research results proving safety and efficacy, with the same dosage, indications, and routes of administration in Vietnam as in that country.

b) Chemical drugs, traditional herbal medicines, and medicines derived from medicinal herbs meeting special treatment requirements listed in the rare medicine directory issued by the Ministry of Health, with special formulations not yet produced domestically and without substitutes that would affect patients' lives, not yet granted registration numbers for circulation in Vietnam, legally circulated but less than five years in their country of origin (or reference country if international treaties to which Vietnam is a member allow), and confirmed by the competent authority of that country to be safe and effective, with the same routes of administration, dosages, and indications in Vietnam as in that country.

c) Vaccines used to prevent newly emerging infectious diseases with unknown causative agents or particularly dangerous infectious diseases with high transmission rates, wide spread, and high mortality rates, not yet granted registration numbers for circulation in Vietnam, legally circulated but less than five years in their country of origin (or reference country if international treaties to which Vietnam is a member allow), and confirmed by the competent authority of that country to be safe and effective, with the same routes of administration, dosages, and indications in Vietnam as in that country.

2. Medicines that have research results from projects or topics researched at the ministry level or higher implemented before this Circular takes effect, conducted according to the provisions of this Circular and Good Clinical Practice guidelines, and evaluated and approved by a scientific and technological council at the ministry level or higher to meet requirements and recommended for widespread application.

Chapter III

PROVISIONS ON CLINICAL TRIAL DRUG TESTING

Article 9. Conditions for Clinical Trial Drugs

Clinical trial drugs must meet the following requirements:

1. They must have been studied in preclinical stages, with documentation proving their safety to proceed with subsequent phases of testing.

2. Have a stable formula, dosage form, and manufacturing process.

3. Have results from previous clinical trial phases if requesting to conduct the next phase of clinical trials.

4. Meet quality standards according to the clinical trial drug registration dossier.

5. The label of clinical trial drugs must include the phrase "Product for clinical trial use only. Prohibited for other purposes."

Article 10. Conditions for Clinical Trial Drug Registration Dossier

The clinical trial drug registration dossier in Vietnamese (one original copy with signature and legal stamp, and three copies) includes:

1. The application for clinical trial drug testing submitted by the entity, organization, or individual holding the clinical trial drug (Annex 1 issued together with this Circular).

2. Product dossier for researchers in Vietnamese or English accompanied by a summary in Vietnamese (Annex 2 issued together with this Circular).

3. Application for review and approval of the clinical trial research protocol by the organization conducting the trial (Annex 3 issued together with this Circular).

4. Research collaboration agreement between the entity, organization, or individual holding the clinical trial drug and the organization conducting the trial, and cooperation agreement between the entity, organization, or individual holding the clinical trial drug and the clinical research organization, research site management organization if applicable (Annex 4 issued together with this Circular).

5. Detailed research protocol for clinical trial (Annex 5 issued together with this Circular).

6. Scientific curriculum vitae and Good Clinical Practice (GCP) certification of the principal investigator/project leader issued by the Ministry of Health or recognized organizations.

7. Information provision document and voluntary participation form (Annex 6 issued together with this Circular).

8. Scientific and ethical evaluation report of the institutional ethics committee in biological research (the organization conducting the clinical trial).

9. Confirmation documents of participating organizations for multi-center studies in Vietnam.

10. Approval documents for participation in research from the People's Committee of provinces or centrally-administered cities for field studies.

11. Documents related to clinical trial drugs, including:

a) Drug research documents: formula components, production process, quality standards, drug test reports (for chemical drugs, traditional medicine, herbal drugs: test reports from central drug inspection agencies or manufacturers meeting Good Manufacturing Practice (GMP) standards; for vaccines: quality test reports from national inspection agencies or certificates of release for vaccine batches from national drug regulatory authorities in the country of origin).

b) Preclinical research documents of the drug to be tested: reports on pharmacological effects, toxicity, safety, dosage recommendations, administration routes, and usage methods.

c) Clinical trial research documents from previous phases (if requesting to conduct the next phase of clinical trials).

12. Certified copies of product certification (CPP) or drug circulation permit (FSC) and Good Manufacturing Practice (GMP) certification from competent state management agencies for drugs proposed for clinical safety assessment and Phase 4 clinical trials.

13. Research drug labels as stipulated in Clause 5 of Article 9 of this Circular and photographs of research drug samples.

Article 11. Conditions for organizations receiving clinical drug trials, principal investigators, and investigators participating in clinical drug trials

1. Organizations receiving clinical drug trials must meet the criteria for good clinical practice (GCP); be economically and organizationally independent from individuals or organizations with drugs undergoing clinical trials, and commit to conducting clinical trials without any conflict of interest between the parties involved.

2. Principal investigators of clinical drug trials must have deep knowledge in their specialty, clinical experience, practical skills ensuring the principles of good clinical practice, a thorough understanding of clinical trial regulations, the ability to implement approved research protocols on schedule, and a GCP certificate issued by the Ministry of Health or recognized organizations by the Ministry of Health.

3. Investigators must have appropriate specialized knowledge, be trained in necessary contents and skills for conducting research, and hold a GCP certificate issued by the Ministry of Health or recognized organizations by the Ministry of Health.

Article 12. Conditions for participants in clinical drug trials

1. Participants in clinical drug trials must be voluntary, meet professional requirements, and sign a commitment with the organization receiving clinical drug trials, except in cases where they are restricted, incapacitated, or lack civil capacity.

2. In cases where participants in clinical drug trials are under 18 years old, restricted, incapacitated, or lack civil capacity, consent from a legally designated representative is required.

3. In cases where participants in clinical drug trials are pregnant women or nursing mothers: The research file must clearly state the reasons for selecting these subjects and must be approved by the Minister of Health based on the review and assessment of the scientific and ethical aspects of the research protocol by the Bioethics Committee in Medical Research - Ministry of Health.

Article 13. Financial conditions for clinical drug trials

1. Funding must be sufficient to cover all activities throughout the entire process of clinical drug trials (including research implementation costs; management, supervision, and inspection costs) provided by the entity, organization, or individual with drugs requiring clinical trials, evidenced by a research contract between the entity, organization, or individual with drugs and the organization receiving clinical trials.

2. For research drugs funded by national budget programs or collaborative projects with domestic and foreign organizations and individuals, the principal investigator and the organization receiving clinical drug trials need to budget for clinical trial expenses within the total funding allocated for research.

3. The organization receiving clinical drug trials and the principal investigator are responsible for managing the assigned funds to be spent on research according to the content and expenditure standards stipulated by law or the contract signed between both parties.

Chapter IV

REGISTRATION, REVIEW, AND APPROVAL OF CLINICAL DRUG TRIAL RESEARCH

Article 14. Registration for Clinical Drug Trials 1. Entities, organizations, or individuals conducting clinical drug trials shall submit registration files including the documents specified in Clause 1 and Clause 2 of Article 10 of this Circular issued by the Ministry of Health.

2. Within fifteen working days from the date of receipt of the registration file, the Ministry of Health shall issue a written response to serve as the basis for entities, organizations, or individuals conducting clinical drug trials to proceed with subsequent steps.

Article 15. Building Research Files

Based on the approval document of the Ministry of Health, entities, organizations, or individuals conducting clinical drug trials shall cooperate with the principal researcher and the organization receiving clinical drug trials to build the clinical drug trial research file, including:

1. Entities, organizations, or individuals conducting clinical drug trials shall provide the documents specified in Clauses 1, 2, 7, 11, 12, and 13 of Article 10 of this Circular to the principal researcher and the organization receiving clinical drug trials.

2. The principal researcher shall collaborate with entities, organizations, or individuals conducting clinical drug trials and other members of the research team to design the research outline and prepare the complete file in accordance with Article 10 of this Circular.

Article 16. Submission of Research Files for Clinical Drug Trials

1. The research file for clinical drug trials as stipulated in Article 10 of this Circular shall be submitted to the Ministry of Health as the basis for evaluation, review, and approval.

2. Research files submitted to the Ministry of Health before the 20th day of each month will be reviewed and evaluated in that month. Research files submitted after the deadline will be transferred to the next month's evaluation.

3. Information related to registration, construction, and submission of files can be accessed at the Ministry of Health’s electronic portal at www.moh.gov.vn or through the website of the Ministry of Health’s Bioethics Council at www.iecmoh.vn.

Article 17. Evaluation and Approval of Research

1. Evaluation of Research Files: 1. Entities, organizations, or individuals conducting clinical drug trials shall submit registration files including the documents specified in Clause 1 and Clause 2 of Article 10 of this Circular issued by the Ministry of Health.

Within thirty working days from the date of receipt of the complete file as stipulated in Article 10 of this Circular, the Ministry of Health shall convene the Bioethics Council in Medical Research.

Within fifteen working days from the date of the Bioethics Council's evaluation results, the Department of Science and Training shall compile and complete the file and notify the result in writing to entities, organizations, or individuals conducting clinical drug trials and the organization receiving clinical drug trials.

2. Notification of results:

3. Approval:

Within fifteen working days from the date of notification of the result and receipt of the completed supplementary file (if any), the Department of Science and Training shall compile and submit to the Minister of Health for approval.

STAGES OF CLINICAL DRUG TRIALS AND CONDUCTING EXPERIMENTS

Chapter V

Article 18. Stages of Clinical Trials for Chemical Drugs and Medical Biological Products

1. Stage 1:

a) This is the first stage of testing a new active substance or a new formula of a drug on humans (usually conducted on healthy volunteers).

b) Purpose of Stage 1 research: to establish an initial assessment of safety and preliminary evaluation of pharmacokinetics and pharmacodynamics of the active substance on humans.

c) Sample size: carefully considered based on preclinical study results, sample size of 10-30 subjects.

2. Stage 2:

a) This is the stage of testing conducted on a limited number of patients.

b) Purpose of Stage 2 research: to evaluate therapeutic efficacy, safety of the active substance on patients, determine appropriate dosage and dosing regimen for optimal therapy in clinical trials.

c) Sample size: minimum of fifty patients.

3. Stage 3:

a) This is the stage of testing conducted on a larger number of patients. Clinical trial conditions in this stage are carried out close to normal usage conditions. Usually conducted multicenter, randomized, with a control group.

b) Purpose of Stage 3 research: to determine the stability of the formula, safety, short-term and long-term efficacy of the active substance, assess overall therapeutic effectiveness. Study common adverse reactions, identify special characteristics of the research product.

c) Sample size: minimum of two hundred patients.

4. Stage 4:

a) These are clinical studies conducted after the drug has been put into circulation. The study design may differ but scientific and ethical standards remain the same as those prior to drug circulation.

b) Purpose of Stage 4 research: clinical trials at this stage are conducted based on the characteristics of the approved product, usually in the form of post-circulation monitoring or therapeutic efficacy evaluation or treatment strategy evaluation.

c) Sample size: minimum of one thousand patients.

c) Sample size: a minimum of 1,000 patients.

Article 19. Clinical trial phases for vaccines

a) This is the first stage of testing a new active substance or a new formula of a drug on humans (usually conducted on healthy volunteers).

a) Phase 1 is the initial phase of testing new vaccines on a small scale to preliminarily assess vaccine safety through preliminary information on drug tolerance. Typically, Phase 1 is conducted on healthy adult volunteers with low risk of infection and complications before being used on target populations.

b) Phase 1 is usually an open study, non-randomized with a placebo control group that may be carried out with different age groups or communities to determine dosage, safety, vaccination schedule, and route of administration of the vaccine.

c) Live attenuated vaccines (viruses or bacteria) that have the potential to infect recipients or contacts must be closely monitored for dosage, clinical signs of infection, and reactogenicity (immediate, early, and late). Phase 1 studies can provide preliminary information on spread, reversion characteristics, transmission to contacts, and genetic stability of the vaccine strain.

d) Sample size: carefully considered based on preclinical research results, with a sample size of 30-50 subjects.

a) This is the stage of testing conducted on a limited number of patients.

a) Conducted after completing Phase 1 with approval from the Ethics Review Board in Biomedical Research - Ministry of Health. The purpose of Phase 2 is to demonstrate the immunogenicity of active components and the safety of the test vaccine on target populations. Phase 2 studies evaluate immune response related to age, ethnicity, and gender. Studies are designed with a control group and randomization.

b) For live attenuated vaccines, in addition to monitoring parameters like Phase 1, attention should be given to the appearance and persistence of antibody levels: neutralizing antibodies, agglutination antibodies, or cell-mediated immunity and interactions affecting the immune system (e.g., prior antibodies, simultaneous vaccination with other vaccines or drugs).

c) Sample size: minimum of 200 subjects.

a) This is the stage of testing conducted on a larger number of patients. Clinical trial conditions in this stage are carried out close to normal usage conditions. Usually conducted multicenter, randomized, with a control group.

a) Phase 3 studies are conducted on a large scale, multi-center to evaluate the protective efficacy and safety of active immunogenic components in vaccines on target populations.

b) Sample size: minimum of 500 subjects.

a) These are clinical studies conducted after the drug has been put into circulation. The study design may differ but scientific and ethical standards remain the same as those prior to drug circulation.

a) Phase 4 studies are conducted after the vaccine is approved for circulation. Phase 4 is considered post-marketing surveillance or post-approval research aimed at determining adverse reactions and monitoring protective efficacy after widespread use of the vaccine in the community under usage conditions. Phase 4 may be organized to evaluate:

- Optimal conditions for vaccine use (optimal age for vaccination, concurrent use with another vaccine, and other conditions).

- Protective efficacy in high-risk groups (elderly, immunocompromised individuals, those with specific diseases).

- Long-term maintenance of protection level and safety.

b) Sample size: minimum of 10,000 subjects.

Article 20. Clinical trial phases for traditional medicine drugs and herbal medicines

a) This is the first stage of testing a new active substance or a new formula of a drug on humans (usually conducted on healthy volunteers).

a) Studies are typically conducted on volunteer subjects meeting clinical trial criteria to determine the safe dose (the maximum dose that does not cause serious side effects), specifically:

b) The first dose must be 1/3 to 1/5 of the expected dose from preclinical studies. From the first dose to the maximum dose, it can be divided into multiple doses. This phase ends when the safe dose is determined.

2. Stage 2:

a) This is the stage of testing conducted on a limited number of patients.

a) Studies evaluate the safety and efficacy of the drug. The study design includes a control group, randomization, with a minimum of 25 patients per group.

b) Treatment dose: the amount of drug used in this phase must be based on the results of Phase 1 studies.

3. Stage 3:

a) This is the stage of testing conducted on a larger number of patients. Clinical trial conditions in this stage are carried out close to normal usage conditions. Usually conducted multicenter, randomized, with a control group.

a) To reconfirm the safety and efficacy of the drug under expanded conditions. Study subjects are selected using randomized controlled or self-controlled methods.

b) Sample size: minimum of 100 patients.

a) These are clinical studies conducted after the drug has been put into circulation. The study design may differ but scientific and ethical standards remain the same as those prior to drug circulation.

a) Apply as for chemical drugs.

b) Sample size: minimum of 200 patients.

Article 21. Clinical drug trials at multiple facilities

1. When conducting research at multiple facilities, the organization responsible for clinical drug trials must establish a joint steering committee including the principal investigator, sub-investigators, and representatives from the main research units to unify the objectives, contents, evaluation criteria, plans, and progress of the research.

2. For multinational clinical studies where Vietnam is a participating member, the procedures and documentation must comply with the provisions of this Circular. The objectives, contents of the clinical trial in Vietnam, and cooperative activities with other countries must be detailed in the research outline.

Article 22. Objectives, Contents, and Sample Size of Research

The Minister of Health shall decide specifically on the objectives, contents, and sample size of the research stipulated in Articles 18, 19, 20, and 21 of this Circular based on the advisory opinions of the Bioethics Council for each case of application and research outline.

Article 23. Handling Adverse Events During Clinical Drug Trials

Handling abnormalities during the research process is carried out as follows:

1. In cases where adverse events occur that pose a danger to the life of the clinical trial participant, the principal investigator and the organization responsible for the clinical trial must immediately stop the trial for that participant, organize emergency care, rectify the situation, and address the consequences, prepare a report, and simultaneously report urgently to the Institutional Ethics Committee, the Ministry of Health's Bioethics Council, the Department of Science and Training, Ministry of Health.

2. If the trial leads to health damage to the clinical trial participant, the principal investigator must halt the study to treat and monitor the health condition of the participant, and consider and decide whether to continue or terminate the clinical trial.

3. In cases where abnormalities have been anticipated and effective measures have already been applied, the clinical drug trial may continue.

Article 24. Collection of Information and Data

1. Information recorded during the clinical drug trial process must be entered into the research medical record (CRFs). The research medical record is considered original documentation and must be stored according to regulations as the basis for monitoring, acceptance, and evaluation of the trial results.

2. Necessary related documents for the clinical evaluation process (test reports, imaging diagnostic results, prescriptions) must be photocopied from the original, clearly indicating the name of the person verifying them, specifying their source, and must be managed and stored according to regulations.

Article 25. Data Processing

1. Clinical trial data must be processed using biostatistical methods and must be handled by an independent agency or organization from the one responsible for the trial to ensure objectivity, truthfulness, and reliability.

2. Statistical analysis results must be presented clearly to help determine differences in clinical outcomes; when evaluating treatment effectiveness, reliance must be placed on the level of confidence and results obtained from statistical analysis. The final research report must be consistent with the statistical analysis results.

Article 26. Storage of clinical drug trial documents

1. All data, original documents, test reports, imaging diagnostic results, materials related to clinical drug trials, minutes of meetings of committees, monitoring records, progress reports, registration files for trials, and other relevant documents must be fully preserved and stored for at least fifteen years at the research facility, starting from the end date of the study.

2. The principal researcher is responsible for the entire process of preserving and storing research documents and must present them when requested by inspection teams, supervisory bodies, and competent state management agencies.

Article 27. Reporting on Clinical Drug Trial Results

1. Reports on clinical drug trial results must comply with the prescribed format (Annex 7 issued together with this Circular), including full information about the drug, research method description, trial process, data analysis, result evaluation, comparison with research objectives and tasks; providing accurate, truthful, and objective conclusions. The report content must align with the approved research objectives and content outlined in the research proposal.

2. The principal researcher is responsible for the scientific nature, accuracy, and truthfulness of the data, conclusions, assessments, and other contents of the report.

Article 28. Management of Clinical Trial Drugs

1. The import and export of clinical trial drugs must be carried out in accordance with current regulations on drug import and export.

2. The management of clinical trial drugs must strictly follow current regulations from sampling, quality testing, packaging, transportation, receipt and delivery, storage, labeling, to distribution.

3. A record book must be kept to track the use of drugs for clinical trials, along with information on quantity and quality of the drugs.

4. Unused drugs and retained drugs must be managed strictly, kept separately, and stored according to regulations. Unused drugs must be handed over to organizations or individuals with clinical trial drugs.

5. Drugs that do not meet quality standards must be handled according to the regulations of the Ministry of Health.

6. Retained drug samples (three smallest units of packaging) must be stored for at least three years (36 months) at the organization receiving clinical trial drugs after the completion of the study.

Chapter VI

RIGHTS AND OBLIGATIONS OF PARTICIPANTS, DRUG OWNERS, AND ORGANIZATIONS RECEIVING CLINICAL TRIALS

Article 29. Rights of Participants in Clinical Drug Trials

1. To be provided with complete and truthful information before clinical trials regarding the trial process and potential risks.

2. To be compensated for damages caused by clinical trials by the organization, entity, or individual owning the clinical trial drugs.

3. To maintain confidentiality of personal information related to the trial.

4. Not to bear responsibility when unilaterally terminating the participation contract in clinical drug trials.

5. To lodge complaints and denunciations against violations of laws by organizations, individuals owning clinical trial drugs, and those accepting clinical trials.

6. To receive health care during the trial period according to the approved research plan.

Article 30. Rights of Organizations, Entities, and Individuals Owning Clinical Trial Drugs

1. To select and propose organizations meeting the requirements for facilities and specialized staff for clinical drug trials.

2. To own all research results of clinical drug trials.

3. To have the right to request termination of the research if the organization accepting the trial seriously violates the research outline.

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

1. Apply for permission and obtain written approval from the Minister of Health before conducting clinical trials.

2. Compensate participants in clinical drug trials for damages resulting from risks occurring during such trials in accordance with current laws.

3. Enter into contracts regarding clinical drug trials with organizations receiving clinical trial drugs and clinical research organizations (if applicable).

4. Bear legal responsibility for the quality and safety of drugs provided by themselves.

Article 32. Rights of organizations receiving clinical trial drugs

1. Receive drugs and funding from agencies, organizations, and individuals with clinical trial drugs to conduct clinical trials in accordance with the law.

2. Use the results of clinical drug trials according to agreements with agencies, organizations, and individuals with clinical trial drugs.

Article 33. Obligations of organizations receiving clinical trial drugs

1. Adhere to good clinical practice guidelines, report to the Ministry of Health on the process and results of clinical trials, and submit urgent reports when necessary.

2. Enter into contracts regarding clinical drug trials with agencies, organizations, and individuals with clinical trial drugs and with participants in clinical trials.

3. Continue to monitor the health and illness of participants in clinical trials according to agreements in the contract or research protocol.

Chapter VII

SUPERVISION AND INSPECTION TO ENSURE RESEARCH QUALITY

Article 34. Supervision and inspection of clinical drug trials

1. Supervision and inspection aim to ensure the rights, interests, and health of participants in clinical drug trials, ensuring that research data are recorded fully, accurately, promptly, and in compliance with approved research protocols.

2. The Ministry of Health establishes regular and ad hoc supervision and inspection teams for each specific case.

3. State management agencies with authority, agencies, organizations, and individuals with clinical trial drugs, clinical research organizations (CROs), or site management organizations (SMOs) approved in writing by the Ministry of Health may propose to appoint observers to systematically monitor the research process. Monitors assigned to supervise must not be members of the research team, must comply with confidentiality regulations concerning research data and information related to participants in clinical trials, and are responsible to the management agency for their work.

4. Principal investigators and other researchers have the responsibility to facilitate access to research data for monitors upon request.

5. Inspection teams are responsible for reporting and proposing supervisory and inspection contents through inspection records to state management agencies with authority as a basis for examination and handling in accordance with legal provisions.

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

1. To ensure sufficient reliability of research, analyses and conclusions about results must be based on original data. All clinical data and test indicators must be verified at each stage of research.

2. In cases where necessary, acceptance committees at various levels will invite experts to evaluate results, check data, and inspect products of the research or establish a Data Safety Monitoring Board (DSMB) as required by the management agency.

Chapter VIII

ACCEPTANCE AND EVALUATION OF CLINICAL DRUG TRIAL RESULTS

Article 36. Procedure for Acceptance of Clinical Trial Results

1. The acceptance of clinical trial research results shall be carried out in accordance with current regulations on scientific and technological research project evaluation and acceptance, and good clinical practice guidelines.

2. The acceptance process will be conducted at two levels: institutional level and Ministry of Health level. Upon completion of the study, the principal investigator is responsible for reporting to the organization conducting the clinical trial to evaluate the research results at the institutional level and completing the report file for submission to the Ministry of Health for acceptance at the ministry level.

Article 37. File for Ministry of Health Acceptance

The file for acceptance at the Ministry of Health (one original copy with signatures and legal stamps and three copies) includes:

1. A letter from the organization conducting the clinical trial requesting acceptance at the Ministry of Health level.

2. A copy of the approved research outline.

3. Decision approving the research outline.

4. Decision establishing the institutional acceptance board.

5. Minutes of the institutional acceptance board meeting.

6. Full report on the clinical trial research results as prescribed and may include additional relevant information when necessary.

Article 38. Completion of Clinical Trial Research

1. Within thirty working days from the date of receipt of the complete application file for acceptance, the Ministry of Health will organize a meeting of the acceptance board to review the research results according to current regulations.

2. A clinical trial research is only considered completed when the final result report has been evaluated and accepted by the acceptance board and the principal investigator's supplements have been accepted based on the board's comments (if any).

3. Data and clinical trial results can only be published after being reviewed and accepted by the Ministry of Health Bioethics Review Board.

Chapter IX

IMPLEMENTATION

Article 39. Responsibility for Implementation

The Department of Science and Training shall take the lead and coordinate with related Departments and Agencies:

1. To receive, examine registration files, guide organizations and individuals with trial drugs and organizations conducting clinical trials to comply with the provisions of this Circular and other relevant laws.

2. To assess the conditions regarding clinical trial file, professional capacity, infrastructure, and legal status of organizations conducting clinical trials, clinical research organizations (CROs), site management organizations (SMOs), and report to the leadership of the Ministry for permission to proceed with the trial.

3. To organize meetings of the Ministry of Health Bioethics Review Board to review research outlines, assess ethical and specialized scientific contents, evaluate the acceptance of clinical trial research results, compile and submit to the Ministry leadership for approval.

4. To supervise and inspect the research process regularly or at random.

5. To disseminate and guide the implementation of the contents of this Circular, good clinical practices, and bioethics in research for relevant units, organizations, and individuals.

Article 40. Transitional Provisions

Registration files for clinical trials submitted before the effective date of this Circular shall be examined and assessed according to the "Clinical Trial Regulations" issued by Decision No. 01/2007/QĐ-BYT dated January 11, 2007, of the Minister of Health.

Article 41. Effective Date

1. This Circular takes effect from March 20, 2012.

2. Abolish Decision No. 01/2007/QĐ-BYT dated January 11, 2007, of the Minister of Health on issuing the "Clinical Trial Regulations" from the date this Circular takes effect.

3. Heads of agencies, organizations, and units concerned are responsible for organizing publicity, dissemination, and implementation of this Circular so that the relevant parties are aware and comply with it.

In the course of implementation, if there are difficulties, they should be promptly reported to the Ministry of Health for consideration and appropriate amendments and supplements./.