0A4F4F9BD490A749D5437F821CF06DF1
Regulation No. 31 from 12 August 2007 for Determining the Principles of Good Clinical Practice (2012)
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| Indicators in focus are typically shown highlighted in yellow; |
Peer Indicators (that share the same Vulnerability association) are shown highlighted in pink; |
"Outside" Indicators (those that do NOT share the same Vulnerability association) are shown highlighted in green; |
Trigger Words/Phrases are shown highlighted in gray. |
Link to Orphaned Trigger Words (Appendix (Indicator List, Indicator Peers, Trigger Words, Type/Vulnerability/Indicator Overlay)
Applicable Type / Vulnerability / Indicator Overlay for this Input
Political / political affiliation
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p.000004: a written explanation of termination or withdrawal.
p.000004: 4.13. Final reports from the researcher
p.000004: Upon completion of the clinical trial, the researcher shall notify the medical establishment, submit to the
p.000004: ethics committee summary of test results and all required reports of regulatory
p.000004: organs.
p.000004: 5. Contracting authority
p.000004: 5.1. Quality assurance and control
p.000004: 5.1.1. The contracting authority is responsible for the implementation and maintenance of quality and control systems
p.000004: through written standard operating procedures to ensure that the clinical trial is also conducted
p.000004: the data is collected, documented (recorded) and reported in accordance with the plan, GCP and applicable regulations
p.000004: requirements.
p.000004: 5.1.2. The contracting authority is responsible for securing an agreement between the researchers, Contract Research
p.000004: organization (DIO) and regulatory authorities to gain direct access to all sites
p.000004: the conduct of the clinical trial,
p.000004: sources / documents of information and reports from monitoring and verifications by the contracting authority, as well as
p.000004: inspections by local or foreign regulatory authorities.
p.000004: 5.1.3. At each stage of data processing, quality control is applied to confirm that all data is
p.000004: reliable and handled properly.
p.000004: 5.1.4. The contracts concluded between the sponsor and the researcher and any other party to the clinical trial are written,
p.000004: as part of the plan or in an additional agreement.
p.000004: 5.2. Contract research organization
p.000004: 5.2.1. The contracting authority may delegate all or part of its obligations to other physical and / or physical persons
p.000004: legal entities referred to as DIOs. Notwithstanding the assignment of obligations to other persons, the contracting authority
p.000004: bears the overall responsibility for conducting the study in accordance with the DCT and the validity of the findings
p.000004: data.
p.000004: The contracting research organization is obliged to put in place quality control and assurance procedures
p.000004: quality.
p.000004: 5.2.2. All contracts between the sponsor and other parties involved in the clinical trial are written and part of
p.000004: from the plan or other separate part.
p.000004: Any transfer of a clinical trial related DIO obligation and function shall be documented in writing.
p.000004: 5.2.3. All clinical-related duty and function not specifically assigned,
p.000004: remain with the contracting authority.
p.000004: 5.2.4. All instructions to the contracting authority in this guide also apply to the DIO to the extent that the DIO has accepted
p.000004: the clinical trial's duties and functions by the sponsor.
p.000004: 5.3. Medical examination
p.000004: The contracting authority appoints qualified medical personnel who are available for consultation on related issues
p.000004: clinical trial medical problems and issues. For this purpose, external may be appointed if necessary
p.000004: consultants.
p.000004: 5.4. Test design
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p.000004: packing, unpacking
p.000004: night test materials (if shedding and dispensing
p.000004: of tests
p.000004: are not included in the product brochure and related
p.000004: the clinical
p.000004: researcher) testing materials.
p.000004: 8.2.15. Shipping and Delivery Documents- Document X X dates
p.000004: of consignments,
p.000004: of the product under test and the batch numbers of
p.000004: tests
p.000004: clinical trial product and method of dispatch. Call-
p.000004: materials left tracking batch of pro-
p.000004: the terms of delivery and accountability.
p.000004: 8.2.16. Certificate of analysis of the document- 0
p.000004: X
p.000004: identity, number-
p.000004: the product of potency and the strength of
p.000004: the product to be
p.000004: used in the clinical trial.
p.000004: 2/8/17 Recognition Procedures in Documenting How, in X X
p.000004: emergency
p.000004: blind trials, the identity of the masked pro-
p.000004: a duct will be recognized without being revealed
p.000004: masking the treatment for others
p.000004: participants.
p.000004: 8.2.18. Main Random List- Document the Random Method-
p.000004: the thinking of the participants in
p.000004: the clinical
p.000004: testing.
p.000004: 8.2.19. Report from the person conducting the Documentation that
p.000004: the center is suitable-
p.000004: pre-clinical monitoring for clinical
p.000004: test (can
p.000004: this test shall be combined with paragraph 8.2.20)
p.000004: 8.2.20. Report from the person conducting the Documentation that
p.000004: the procedures under
p.000004: monitoring, to start the clinical trial are
p.000004: commented
p.000004: of the clinical trial with the researcher and his team
p.000004: (may be combined with item 8.2.19)
p.000004: 8.3. During the clinical trial
p.000004: (and to a third party, if applicable)
p.000004: 0 X
p.000004: 0 X
p.000004: X X
p.000004: In addition to the abovementioned documents, the following documents should also be kept during the
p.000004: the clinical trial as evidence, any new relevant information is documented after
p.000004: become available.
p.000004: Document Purpose Stored
p.000004: in the documentation of the assigning researcher
p.000004: 1 2 3
p.000004: 4
p.000004: 8.3.1
p.000004: 8.3.2
p.000004: 8.3.3
p.000004: Researcher's Brochure Updates
p.000004: All protocol changes /
p.000004: the changes and the CCP; the format for
p.000004: written informed consent;
p.000004: any other written information,
p.000004: presented to the participants; patient recruitment ad (if used)
p.000004: Dated, documented positive opinion of
p.000004: Document that X X is the relevant in-
p.000004: formation is timely presented
p.000004: to the researcher.
p.000004: Document changes
p.000004: in those X X
p.000004: related to the clinical trial and the impact of
p.000004: clinical trial documents, documents.
p.000004: Document that X X changes and / or
p.000004: the reworks were
p.000004: considered in the com-
p.000004: ethics mission for the following: this ethics and have received
p.000004: positive
p.000004: 8.3.3.1 Changes to the Protocol Statement.
p.000004: 8.3.3.2 Changes to the information form- Identify the number
p.000004: and the date
p.000004: peace of mind of the version.
p.000004: 8.3.3.3 Changes in any other information presented to participants
p.000004: 8.3.3.4 Changes to the recruitment announcement (if used)
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Political / vulnerable
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p.000004: Art. 3. The information about a participant under Art. 110, para. 1, item 2 of LMPHM contains:
p.000004: 1. patient / participant information;
p.000004: 2. informed consent form;
p.000004: 3. description of patient / participant recruitment procedures;
p.000004: 4. a description of the procedures for obtaining informed consent from a lawful person
p.000004: a representative, where foreseen;
p.000004: 5. ethical justification in the case of recruitment of participants who are unable to give informed consent, in accordance with
p.000004: Art. 98 CLPM;
p.000004: 6. a copy of any other information that will be used to recruit participants and / or provide a participant
p.000004: before or during the clinical trial.
p.000004: Art. 4. (1) The documentation for the test report under Art. 110, para. 1, item 3 of LMPHM contains:
p.000004: 1. test report with all current changes;
p.000004: 2. summary of the minutes in Bulgarian;
p.000004: 3. an assessment of the scientific value of the test by a specialist in the relevant field, where available;
p.000004: 4. an ethical evaluation of the protocol by the principal or coordinating investigator when not part of the protocol.
p.000004: (2) The protocol shall be drawn up in accordance with the rules of the DCP and shall contain at least the following:
p.000004: 1. assessment of the expected benefits and risks in accordance with Art. 90, Vol. 1 of ZLPHM;
p.000004: 2. defining the inclusion and exclusion criteria;
p.000004: 3. justification for the choice of patients, especially in the case of envisaged inclusion of patients who are not in
p.000004: able to give informed consent and other vulnerable patient groups;
p.000004: 4. a description of the procedures for recruiting patients and obtaining informed consent when
p.000004: envisages the inclusion of patients who are temporarily or permanently unable to provide personally informed information
p.000004: consent, and when obtaining the consent of an independent witness;
p.000004: 5. description of the plan and procedures for providing additional medical care to the participants after the end of
p.000004: the study;
p.000004: 6. monitoring procedures;
p.000004: 7. plan for publishing the data.
p.000004: (3) The protocol must be signed by the contracting authority and the principal investigator for each of the proposed centers.
p.000004: Art. 5. (1) The documentation for the tested medicinal product under Art. 110, para. 1, item 4 of the LMPHM contains:
p.000004: 1. Researcher's booklet;
p.000004: 2. a summary of all ongoing clinical trials with the medicinal product.
p.000004: (2) Where the investigational medicinal product is authorized in a Member State of the European Union, and
p.000004: the test provides for its use in accordance with the conditions laid down in the marketing authorization,
p.000004: instead of the document under Art. 1, item 1 a summary of the product characteristics may be provided.
p.000004: (3) The researcher's booklet and any update thereof must provide scientifically substantiated and complete information
p.000004: for the product that is needed for an objective assessment of the risk / benefit ratio of the proposed clinical trial.
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p.000004: the contracting authority is both that of the contracting authority and that of the researcher.
p.000004: 1.52. Standard Operating Procedures (SOPs)
p.000004: Written detailed instructions for achieving uniformity in the performance of a specific function.
p.000004: 1.53. Co-researcher
p.000004: Any member of the clinical research team appointed and supervised by the principal investigator at
p.000004: the location of the clinical trial to perform the basic test-related actions
p.000004: and / or make important decisions (eg, associates, graduate students, doctoral students).
p.000004: 1.54. Test participant
p.000004: A person who is enrolled in a clinical trial by receiving or participating in a test drug
p.000004: controlling.
p.000004: 1.55. Participant identification code
p.000004: Unique identifier code for the designation of each participant in a clinical trial by the researcher in order to preserve
p.000004: his identity and used in place of the participant's name
p.000004: when reporting adverse events and / or other test-related data.
p.000004: 1.56. Clinical trial center
p.000004: The location (s) of study-related activities.
p.000004: 1.57. Unexpected side effect
p.000004: For unauthorized products - an adverse reaction whose nature, severity or outcome do not match
p.000004: of the information on the tested medicinal product referred to in the investigator's leaflet. They are allowed
p.000004: use of products - an adverse reaction not listed in the summary of product characteristics or
p.000004: whose character, weight or output do not correspond to the information given in the summary of product characteristics.
p.000004: 1.58. Vulnerable groups
p.000004: Individuals whose desire to participate in a clinical trial may be influenced by the expectation of benefit or by
p.000004: their position vis-à-vis senior officials in the hierarchy related to participation or non-participation, for example:
p.000004: medical, dental, pharmacy, or nursing students in pharmacy
p.000004: industry, serving in the military, and persons deprived of their liberty.
p.000004: Other vulnerable participants are patients with incurable diseases, people in nursing homes, the unemployed or
p.000004: beggars, emergency patients, ethnic minority groups, street children, vagrants, minors and such,
p.000004: who are unable to consent.
p.000004: 1.59. Well-being (of clinical trial participants)
p.000004: Physical and mental integrity of participants in the clinical trial
p.000004: 2. PRC principles
p.000004: 2.1. Clinical trials shall be conducted in accordance with the ethical principles set out in the Declaration of Conformity
p.000004: Helsinki and comply with DCT and applicable regulatory requirements.
p.000004: 2.2. Before starting a test, all the foreseeable risks are compared with the expected benefit
p.000004: individually for the participant and for the community. A clinical trial can only begin and continue if foreseeable
p.000004: the benefits justify the risks.
p.000004: 2.3. The rights, safety and well-being of test participants are paramount and
p.000004: stand above the interests of science and society.
p.000004: 2.4. Available non-clinical and clinical information on the investigational medicinal product should be sufficient
p.000004: support for the proposed clinical trial.
p.000004: 2.5. Clinical trials must be scientifically relevant and described in a clear and detailed manner
p.000004: protocol.
p.000004: 2.6. A clinical trial shall be conducted in accordance with a protocol that has been approved in advance
p.000004: by the Ethics Committee.
p.000004: 2.7. Medical monitoring and medical decisions, with regard to participants, are taken by the doctor or, where appropriate
p.000004: necessary - by a dentist.
p.000004: 2.8. Each person charged with conducting a clinical trial has education, qualification
p.000004: and attempting to fulfill the relevant test obligations.
p.000004: 2.9. Before entering a clinical trial, each participant is freely informed
p.000004: consent.
p.000004: 2.10. All clinical trial information must be recorded, maintained and stored in a manner permitting
p.000004: its accurate reporting, interpretation and verification.
p.000004: 2.11. The confidentiality of documents which may reveal the identity of the participants is retained,
p.000004: subject to the applicable regulatory requirements for secrecy and confidentiality.
p.000004: 2.12. The tested medicinal products are manufactured, maintained and stored in
p.000004: compliance with the applicable GMP. They shall be used in accordance with an approved protocol.
p.000004: 2.13. Procedures are in place at all stages of the clinical trial to ensure the quality of each stage of
p.000004: conducting the study.
p.000004: 3. Ethics Committee
p.000004: 3.1. Obligations
p.000004: 3.1.1. Each Ethics Committee protects the rights, safety and well - being of all participants in the
p.000004: the clinical trial. Particular attention is paid to clinical trials involving vulnerable groups
p.000004: patients.
p.000004: 3.1.2. The Ethics Committee receives the following documents: Clinical Trial Protocol / Changes, Form for
p.000004: written informed consent and changes to those forms that the researcher proposes to use in
p.000004: clinical trial, patient recruitment procedures (eg announcements), written information on
p.000004: participants, researcher's brochure, available safety information, billing information and compensation
p.000004: of patients, insurance for patients / volunteers and researchers, up-to-date CV of
p.000004: the researcher (s) and / or other documents proving their qualifications and other supporting documents
p.000004: documents which the commission may require to carry out its functions.
p.000004: It reviews the proposed clinical trial within the time limit set by law and documents its own
p.000004: written opinion with clearly stated clinical trial topic and documents reviewed and dated with respect to
p.000004: the following:
p.000004: 3.1.2.1. positive opinion;
p.000004: 3.1.2.2. amendments requested before a favorable opinion;
p.000004: 3.1.2.3. negative opinion;
p.000004: 3.1.2.4. amendment of a positive opinion already issued.
p.000004: 3.1.3. The Ethics Committee evaluates the researcher 's qualification for the proposed clinical trial by
p.000004: an up-to-date CV of the researcher and / or other relevant documents as may be required.
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Health / Cognitive Impairment
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p.000004: the systemic bioavailability of the investigational medicinal product and its metabolites and their relationship with
p.000004: pharmacological and toxicological findings in animal species.
p.000004: 7.3.5.3. Toxicology
p.000004: A summary of the toxicological effects found in relevant studies conducted on different subjects shall be provided
p.000004: animal species, including the following: single dose toxicity; repeated dose toxicity
p.000004: dosing; carcinogenicity; special tests (eg irritability and sensitivity); reproductive toxicity;
p.000004: genotoxicity (mutagenicity).
p.000004: 7.3.6. Effects in humans
p.000004: A full description of the known effects of the tested product (s) on humans, including information on
p.000004: pharmacokinetics, metabolism, pharmacodynamics, dose response, safety, efficacy and other pharmacological
p.000004: actions. Whenever possible, a summary of each completed clinical trial as well as
p.000004: information regarding the results of any use of the test medicinal product to be tested
p.000004: different from clinical trials (eg post-market experience).
p.000004: 7.3.6.1. Pharmacokinetics and metabolism of the product in humans
p.000004: A summary of the pharmacokinetics of the investigational medicinal product shall be provided,
p.000004: which, if possible, includes the following: pharmacokinetics (including metabolism and absorption, binding to
p.000004: plasma proteins, distribution and elimination); bioavailability (where possible absolute and / or relative),
p.000004: using a dosage form for comparison; subgroups of the population (eg gender, age and impaired function)
p.000004: to an authority); interactions (eg product-product interactions or food effects); others
p.000004: pharmacokinetic data (eg, results from population-based studies conducted in clinical trials).
p.000004: 7.3.6.2. Safety and efficiency
p.000004: A summary of information obtained from previous human clinical trials (healthy volunteers) is provided
p.000004: and / or patients) for the safety, pharmacodynamics, efficacy and dose response of the product (s) tested
p.000004: (and their metabolites where appropriate). The conclusions of this information are commented. Where they are
p.000004: completed a large number of clinical trials, the use of safety and efficacy summaries of
p.000004: multiple sub-group indication tests may be representative of the data. Summaries can
p.000004: also be presented in tabular form for adverse reactions for all clinical trials (incl.
p.000004: those for all testimony tested). Important differences in trends / incidence of
p.000004: side effects against indications or subgroups.
p.000004: A description of the potential risks and undesirable effects is provided
p.000004: reactions based on direct experience with the study drug
p.000004: product and related products, as well as precautions or special observations that
p.000004: to be carried out during the tested use of the medicinal product (s).
p.000004: 7.3.6.3. Experience after authorization for use
p.000004: Indicate the countries in which the test medicinal product is authorized. Commented
p.000004: any relevant information obtained from use after authorization (eg formulas, doses, routes of administration or administration)
p.000004: side effects). The countries in which the test medicinal product has not been authorized shall also be indicated
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Searching for indicator impairment:
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p.000004: any other written information has been properly explained and understood by the participants or their legal information
p.000004: representatives and consent was given by the participants themselves or their legal representatives.
p.000004: 4.8.10. The written informed consent form and any other written information provided to participants,
p.000004: contains explanations for the following:
p.000004: 4.8.10.1. that the clinical trial is a scientific research process;
p.000004: 4.8.10.2. the purpose of the clinical trial;
p.000004: 4.8.10.3. the treatment (s) tested and the likelihood of any treatment being randomly assigned;
p.000004: 4.8.10.4. the procedures to be performed during the clinical trial, including
p.000004: invasive manipulations;
p.000004: 4.8.10.5. the obligations of the participants;
p.000004: 4.8.10.6. those aspects of the clinical trial that are experimental;
p.000004: 4.8.10.7. reasonably foreseeable risks or inconveniences to participants, as well as to an embryo, fetus or infant,
p.000004: when necessary;
p.000004: 4.8.10.8. reasonably expected benefits; participants are informed of cases where no clinical benefit is expected;
p.000004: 4.8.10.9. the alternative procedures and treatment courses that are possible for the participants and important
p.000004: their potential risks and benefits;
p.000004: 4.8.10.10. compensation and / or possible treatment for participants in case of clinical trial related impairment;
p.000004: 4.8.10.11. anticipated, in proportion to time participation, payment for volunteers / patients
p.000004: their participation in the clinical trial, if any;
p.000004: 4.8.10.12. estimated costs for participants to participate in the clinical trial;
p.000004: 8/4/13 explanation that participation in the clinical trial is voluntary and that the participant may refuse to participate
p.000004: or withdraw at any time without the penalty or loss of benefits that the participant may
p.000004: to receive otherwise;
p.000004: 4.8.10.14. indicate that the monitoring, reviewing, ethics committee and regulatory bodies are
p.000004: provided access to the participant's original medical records for verification of clinical procedures
p.000004: testing and / or data, ensuring that the patient's personal data is protected in accordance with applicable laws and
p.000004: regulations, and by signing the written informed consent form, the participant or his or her legal
p.000004: the representative agrees to such access;
p.000004: 8/4/15 that the identification documents of the participant will be kept confidential and the data
p.000004: they will not be disclosed in accordance with applicable laws and regulations; in case of publication of
p.000004: results of the clinical trial of
p.000004: participants will remain confidential;
p.000004: 8/4/16 explanation that the participant or his legal representative will be notified in a timely manner if any
p.000004: new information that may influence their desire to continue participating in the clinical trial;
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Health / Drug Usage
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p.000004: the conduct of the clinical trial non-material and material damage to the participants;
p.000004: 2. information on the anticipated benefits and compensations in the event of death or damage to the health of
p.000004: the participant in conducting the clinical trial;
p.000004: 3. (Supplemented, SG No. 77/2016, effective 04.10.2016) draft contract between the assignor and
p.000004: the participants in the trial, which also determines the remuneration for participation, where provided for;
p.000004: 4. (suppl., SG 77/2016, in force from 04.10.2016) draft contract between the assignor and
p.000004: the researcher;
p.000004: 5. (suppl. - SG 77/16, in force from 04.10.2016) draft contract between the assignor and
p.000004: the medical establishment - the center of the clinical trial;
p.000004: 6. written consent under Art. 87, para. 3 CLPM;
p.000004: 7. data on the source of financing of the study, where the assignor is a legal entity with
p.000004: non-agricultural aim;
p.000004: 8. document for paid fee.
p.000004: Art. 8. (1) For clinical trial of a medicinal product under Art. 88 of the LPPMM the contracting entity or a person authorized by it
p.000004: submit to the Executive Agency for Medicinal Products an application for a clinical trial using a specimen.
p.000004: (2) The documents under art. 2, 3, 4, 5, 6, 7, 9 and Art. 19, para. 3, as well as the declarations under art. 122
p.000004: and 123 ZLPHM.
p.000004: (3) (Repealed, SG No. 14/2012, New SG No. 25/2018) The Executive Agency for Medicines shall perform
p.000004: verification by official means for the presence of the circumstances under Art. 87, para. 1 of
p.000004: CLPM.
p.000004: Art. 9. The sponsor or the person authorized by him / her shall submit to the Drug Enforcement Agency
p.000004: the following documentation under Art. 116, para. 4, Vol. 4 of ZLPHM:
p.000004: 1. dossier of the tested medicinal product;
p.000004: 2. documentation certifying the production of the tested products under the conditions of Good
p.000004: manufacturing practice;
p.000004: 3. analytical certificate of the product under test where impurities are not justified in the specification or when
p.000004: identify uncharacterized impurities;
p.000004: 4. results of viral safety tests;
p.000004: 5. certificate for the absence of causative agents of portable spongiform encephalopathy;
p.000004: 6. models on the label in Bulgarian;
p.000004: 7. opinion from the Ministry of Environment and Water regarding the potential risk for
p.000004: the environment when the test medicinal product contains genetically modified organisms.
p.000004: Art. 10. (1) The dossier of the tested medicinal product shall be prepared in accordance with the published ones
p.000004: European Commission guides in format and content according to Annex 2.
p.000004: (2) Where the investigational medicinal product is manufactured within the European Union and does not exist
p.000004: authorization for use, instead of the document under Art. 9, item 2 shall be submitted a copy of the manufacturing authorization for
p.000004: medicinal products under development and research issued by a Member State of the European Union.
p.000004: (3) Where the investigational medicinal product is not manufactured within the European Union and
p.000004: not authorized, the following production documents must be submitted:
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p.000004: the Executive Director of the Executive Agency for Medicinal Products.
p.000004: (4) The control, carried out by the state inspectors, shall be carried out:
p.000004: 1. as a preliminary, current and follow-up in a clinical trial of a medicinal product;
p.000004: 2. in the course of a marketing authorization procedure;
p.000004: 3. as follow-up measures after authorization for use.
p.000004: (5) The contracting authority, the principal investigator and the researchers contracted shall be subject to control
p.000004: research organization, ethics committees, test center, manufacturing sites and control center
p.000004: the investigational medicinal product, the laboratories and any site and facility used during the test,
p.000004: as well as all clinical trial documentation.
p.000004: Art. 21. (1) Control over clinical trials shall be conducted in accordance with standard operating procedures
p.000004: procedures approved by the Executive Director of the Executive Agency for Medicinal Products. The standard ones
p.000004: operational procedures shall be developed in accordance with the guidance documents of the European Commission.
p.000004: (2) Each examination in connection with a clinical trial of a medicinal product shall end with a report to be submitted to the
p.000004: the contracting authority.
p.000004: (3) A clinical trial verification report may be provided to the investigators,
p.000004: the ethics committee under art. 103 LPPMM, other Member States of the European Union, and the European Union
p.000004: drug agency.
p.000004: Art. 22. When finding discrepancies requiring the suspension or termination of a study,
p.000004: The Executive Agency for Medicinal Products shall inform the European Medicines Agency, Member States, c
p.000004: the European Commission and the Ethics Committee under Art. 103 CLPM.
p.000004: Art. 23. The Executive Agency for Medicinal Products shall enter into the European Clinical Trials Database
p.000004: information on planned and performed clinical trial checks.
p.000004: Transitional and Final Provisions
p.000004: § 1. This Regulation establishes the provisions of Commission Directive 2005/28 / EC of 8 April 2005 on
p.000004: defining principles and detailed guidelines for good clinical practice for medicinal products for
p.000004: humane use intended for research as well as requirements for the granting of a marketing authorization
p.000004: the manufacture or import of such products.
p.000004: § 2. To the applications, submitted before the entry into force of this Ordinance, for significant changes in the permit for holding
p.000004: the clinical trial of a medicinal product on the territory of the Republic of Bulgaria shall be submitted by the contracting authorities on time
p.000004: for three months the documentation provided for in the regulation.
p.000004: § 3. This Ordinance is issued on the grounds of Art. 82, para. 3, Art. 110, para. 2, Art. 116, para. 5, Art.
p.000004: 129, para. 3, Art. 142, para. 2 and Art. 145, para. 2 of the LPPHM and repeals Ordinance No. 14 of 2000 on the Terms and Conditions for Conducting
p.000004: clinical trials of medicines on humans (SG 73/00).
p.000004: Final provisions
p.000004: TO THE ORDER FOR AMENDING AND SUPPLEMENTING REGULATION No. 31 OF 2007 ON DEFINING THE RULES FOR GOOD CLINICAL PRACTICE
p.000004: (Official Gazette, issue 77 of 2016, effective 04.10.2016)
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p.000004: community, Japan and the United States, as well as those of Australia, Canada, Scandinavian countries and World Health
p.000004: organization.
p.000004: These rules must be followed when generating data from clinical trials that will
p.000004: be submitted to the regulatory authorities.
p.000004: The principles laid down in these rules may also apply to others
p.000004: clinical trials that could have an impact on human safety and health.
p.000004: 1. Definitions
p.000004: 1.1. Adverse Reaction (ADR)
p.000004: "Undesirable effect" is any undesirable and unintended response to a medicinal product that occurs with
p.000004: administration of the product at doses normally used for the treatment, prophylaxis or diagnosis of disease in
p.000004: people or for recovery, correction or
p.000004: modification of physiological function. In the case of a clinical trial - any undesirable or unforeseen
p.000004: response to the investigational medicinal product, regardless of the dose administered. The phrase "answered one
p.000004: "means that the cause and effect relationship is between the medicinal product and the adverse reaction
p.000004: at least a reasonable possibility, that is, the connection cannot be denied.
p.000004: 1.2. Adverse event
p.000004: Adverse event is any adverse change in health status observed with the administration of a medicinal product.
p.000004: to a patient or participant in a clinical trial that is not necessarily causally related to this treatment.
p.000004: An adverse event may therefore be any adverse and unintended physical finding (incl.
p.000004: laboratory deviation), symptom, or illness associated with the use of (tested) drug over time
p.000004: product, whether or not it is causally related to the product.
p.000004: 1.3. Applicable requirements
p.000004: All regulatory requirements for conducting clinical trials with medicinal products.
p.000004: 1.4. Approval by the Ethics Committee
p.000004: Positive opinion from the Ethics Committee confirming that the clinical trial has been evaluated and can
p.000004: to be conducted at the established center under the conditions laid down by the Ethics Committee, the medical establishment, the CPT, and
p.000004: the applicable requirements.
p.000004: 1.5. Independent verification (audit)
p.000004: Systematic and independent evaluation of test-related obligations and assessment documents
p.000004: whether these obligations have been fulfilled, whether the data have been recorded, analyzed, carefully reported, in accordance with
p.000004: the protocol, standard operating procedures (SOPs) of the contracting entity, DCT and applicable regulatory requirements.
p.000004: 1.6. Certificate of verification
p.000004: Document from the verifier confirming that an inspection has been carried out.
p.000004: 1.7. Verification report
p.000004: Written evaluation of the verifier by the contracting authority for the results of the inspection.
p.000004: 1.8. Track for verification
p.000004: Documentation to track the sequence of events.
p.000004: 1.9. Blinding / masking
p.000004: A procedure in which one or more of the parties remain unaware of their assigned treatment
p.000004: preliminary agreement. Single-blind are usually trials in which patients remain unknown, a
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p.000004: testing and materials for obtaining and documenting informed consent of participants and
p.000004: assessment of whether the researchers, the conditions, the methods for conducting the test are appropriate.
p.000004: 1.28. An informed consent
p.000004: Informed consent is a statement of will that must be written, personally dated and signed in order to participate in
p.000004: a clinical trial taken completely free after being duly informed of its nature,
p.000004: significance, consequences and risks and appropriately documented by any person who is able to give
p.000004: his consent, or when the person is unable to give his consent, from his legal representative.
p.000004: 1.29. Inspection
p.000004: Official inspection of the inspection bodies for documents, conditions, records and any other data sources provided
p.000004: are considered by them to be related to the clinical trial and may be stored at the clinical venue
p.000004: testing, the office of the contracting authority / DIO or other places deemed appropriate by these inspection bodies.
p.000004: 1.30. Institution (medical)
p.000004: Medical establishments where clinical trials are conducted.
p.000004: 1.31. Interim clinical trial report
p.000004: Report on the provisional results of the study and their evaluation based on analyzes made during the
p.000004: conducting the clinical trial.
p.000004: 1.32. Tested medicinal product
p.000004: Test drug is a formulation of an active substance or a placebo,
p.000004: which is being tested or used as a comparison in a clinical trial, including products for which it has been issued
p.000004: marketing authorization, but are used for unauthorized use or for the purpose of obtaining an additional one
p.000004: information on the authorized form, or supplied (in dosage form or packaged) in a way other than
p.000004: the authorized form.
p.000004: 1.33. Principal Investigator
p.000004: The principal investigator is the physician or dental practitioner designated by the contracting authority who is in charge
p.000004: the complete conduct of the clinical trial at the center in accordance with the approved protocol and
p.000004: the DCM manual and is responsible for the work of the researchers.
p.000004: 1.34. Explorer
p.000004: The researcher is the doctor or dentist designated by the sponsor and the principal investigator who
p.000004: practically conducts the clinical trial under the direction of the principal investigator according to the approved protocol and
p.000004: the DCT manual at the clinical trial research center. If the clinical
p.000004: testing is conducted by a team, the researcher is the team leader responsible for the team and is called the principal
p.000004: Explorer.
p.000004: 1.35. Researcher's brochure
p.000004: Document containing all clinical and non-clinical trial data (s) for medicinal product (s)
p.000004: refer to the administration of the tested medicinal products to humans.
p.000004: 1.36. Legal representative
p.000004: An individual who, under applicable law, is a legal representative and can agree to participate
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p.000004: 1.43. QA
p.000004: Any planned and systematic actions that are put in place to ensure that data is received,
p.000004: documented (recorded) and reported and that the test is conducted in accordance with the DCT and applicable
p.000004: regulations.
p.000004: 1.44. Quality control
p.000004: Work techniques and actions undertaken within the framework of the
p.000004: quality in order to verify that the quality requirements of the test-related activities are fulfilled.
p.000004: 1.45. Randomization
p.000004: Process for allocating test participants or control groups using an element of
p.000004: chance to avoid deviations.
p.000004: 1.46. Regulatory bodies
p.000004: National competent authorities for quality, efficiency and safety control of
p.000004: medicinal products, as well as the bodies evaluating and submitting clinical documentation
p.000004: inspections.
p.000004: 1.47. Serious adverse event (SNA) or serious adverse reaction
p.000004: (SNLR)
p.000004: Any adverse effect or change in health that has become the cause
p.000004: for death, imminent danger of death, hospitalization or prolongation of hospitalization,
p.000004: significant or permanent damage, disability and congenital anomalies.
p.000004: 1.48. Output data
p.000004: All information in the original records and certified copies of the original clinical records, observations and
p.000004: other activities in one clinical trial necessary to recreate and evaluate the trial.
p.000004: 1.49. Source documents (source documents)
p.000004: Original documents and records in which data are first recorded after being received (e.g.
p.000004: hospital records, clinical and work plans, lab notes, notes, patient logs, or patient lists
p.000004: inspection, drug dispensing records from the pharmacy, automated device records, certified
p.000004: copies of records after confirmation that they are true copies, microfiche, photographic negatives,
p.000004: microfilms and tape recordings, x-rays, participant files, recordings stored in
p.000004: the pharmacy, the laboratory, and the medical and technical services involved in the test).
p.000004: 1.50. Contracting authority
p.000004: The natural or legal person, institution or organization responsible for initiating,
p.000004: management and / or funding of the clinical trial.
p.000004: 1.51. Investigator
p.000004: An individual who simultaneously initiates and conducts one clinical trial, alone or with others
p.000004: persons, and under whose immediate direction the investigational medicinal product is administered, dispensed or administered
p.000004: used by a patient. The definition does not include legal entities and scientific organizations. The obligations of
p.000004: the contracting authority is both that of the contracting authority and that of the researcher.
p.000004: 1.52. Standard Operating Procedures (SOPs)
p.000004: Written detailed instructions for achieving uniformity in the performance of a specific function.
p.000004: 1.53. Co-researcher
p.000004: Any member of the clinical research team appointed and supervised by the principal investigator at
p.000004: the location of the clinical trial to perform the basic test-related actions
p.000004: and / or make important decisions (eg, associates, graduate students, doctoral students).
p.000004: 1.54. Test participant
p.000004: A person who is enrolled in a clinical trial by receiving or participating in a test drug
p.000004: controlling.
p.000004: 1.55. Participant identification code
p.000004: Unique identifier code for the designation of each participant in a clinical trial by the researcher in order to preserve
p.000004: his identity and used in place of the participant's name
p.000004: when reporting adverse events and / or other test-related data.
p.000004: 1.56. Clinical trial center
p.000004: The location (s) of study-related activities.
p.000004: 1.57. Unexpected side effect
p.000004: For unauthorized products - an adverse reaction whose nature, severity or outcome do not match
p.000004: of the information on the tested medicinal product referred to in the investigator's leaflet. They are allowed
p.000004: use of products - an adverse reaction not listed in the summary of product characteristics or
p.000004: whose character, weight or output do not correspond to the information given in the summary of product characteristics.
p.000004: 1.58. Vulnerable groups
p.000004: Individuals whose desire to participate in a clinical trial may be influenced by the expectation of benefit or by
p.000004: their position vis-à-vis senior officials in the hierarchy related to participation or non-participation, for example:
p.000004: medical, dental, pharmacy, or nursing students in pharmacy
p.000004: industry, serving in the military, and persons deprived of their liberty.
p.000004: Other vulnerable participants are patients with incurable diseases, people in nursing homes, the unemployed or
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p.000004: on its decisions / opinions and the procedures for appealing the decisions / opinions of the
p.000004: ethics.
p.000004: 3.4. Documents
p.000004: The Ethics Committee shall keep all relevant documents (eg written standard operating procedures, lists of records)
p.000004: members, appointment orders, members' job listings, conflicts of interest declarations and
p.000004: confidentiality, documents submitted, meeting minutes and correspondence) for the period no
p.000004: less than three years after termination of the clinical trial and make them available on request to the regulatory ones
p.000004: organs.
p.000004: The Ethics Committee shall provide the investigator, the sponsor or the regulatory authorities with its written documents
p.000004: procedures and orders determining the list of members upon request.
p.000004: 4. Researcher
p.000004: 4.1. Qualification and responsibilities of the researcher
p.000004: 4.1.1. The researcher (s) have the appropriate education, qualifications and experience to assess responsibility for the
p.000004: the proper conduct of the clinical trial; meets all regulatory requirements
p.000004: authorities, and provides proof of his / her qualification through an updated CV and / or others
p.000004: documents required by the contracting authority, the ethics committee and / or regulatory authorities.
p.000004: 4.1.2. The researcher is familiar with the proper use of the test drug as it is
p.000004: referred to in the protocol, the researcher's current brochure, product information and any other sources
p.000004: information provided by the contracting authority.
p.000004: 4.1.3. The researcher knows and complies with the requirements of the DCT and the applicable regulatory requirements.
p.000004: 4.1.4. The researcher permits monitoring, verification by the contracting authority and inspection by
p.000004: the relevant regulatory authorities.
p.000004: 4.1.5. The researcher shall keep a list of the persons with the necessary qualifications to whom he has delegated responsible duties,
p.000004: related to the clinical trial.
p.000004: 4.2. Test Opportunities
p.000004: 4.2.1. The researcher must be able to show the ability to dial the required number
p.000004: appropriate patients within the agreed period (eg based on retrospective data).
p.000004: 4.2.2. The investigator has sufficient time to conduct and complete the clinical trial within the agreed timeframe.
p.000004: 4.2.3. The researcher has the necessary number of qualified personnel and the appropriate equipment for the foreseen
p.000004: the duration of the clinical trial for proper and safe conduct.
p.000004: 4.2.4. The researcher shall ensure that all persons participating in the clinical trial are sufficiently informed about
p.000004: the protocol, the investigational medicinal product (s), and the clinical trial's duties and functions.
p.000004: 4.3. Medical care for participants
p.000004: 4.3.1. Responsibility for all clinical trial related medical decisions lies with a qualified physician, or
p.000004: where appropriate, by a dentist who is a researcher or co-investigator in a clinical trial.
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p.000004: 4.6. Tested medicinal product
p.000004: 4.6.1. Responsibility for the accountability of the investigational medicinal product at the clinical site
p.000004: the test is carried out by the researcher.
p.000004: 4.6.2. The researcher may assign some or all of his reporting responsibilities to
p.000004: the pharmacist's or other appropriate person's place (s) under the direction of the researcher,
p.000004: when permissible or required.
p.000004: 4.6.3. The researcher and / or pharmacist or other person designated by the researcher shall keep the records for
p.000004: medicines received at the venue, inventory of products at the center, the quantities used by each
p.000004: participant and the quantities returned to the contracting authority or at an additional place. These documents contain dates, quantities,
p.000004: batches and numbers, expiry date (where possible) and unique code numbers indicating the medicinal products
p.000004: products and participants. The researchers keep documents stating that the participants have received
p.000004: the relevant doses specified in the plan and confirmation and reporting of all medicinal products received by the contracting entity
p.000004: products.
p.000004: 4.6.4. The tested medicinal product (s) shall be stored in a manner determined by the contracting entity, in accordance with paragraph 2.
p.000004: 5.13.2 and 5.14.3, and in accordance with applicable regulatory requirements.
p.000004: 4.6.5. The researcher confirms that the tested medicinal products are used only in accordance with
p.000004: approved protocol.
p.000004: 4.6.6. The investigator, or a person designated by him, explains the proper use of the test drug
p.000004: product of each individual participant and at appropriate intervals and checks that each participant complies
p.000004: correct instructions.
p.000004: 4.7. Randomization and disclosure procedures
p.000004: The researcher must follow the randomization procedures of the clinical trial, if any
p.000004: such, and must confirm that code disclosure is made only in accordance with the protocol. If the clinical
p.000004: the test is blinded, the researcher documents and explains to the client any premature disclosure
p.000004: code (e.g., accidental detection, detection as a result of a serious unwanted event) of
p.000004: the investigational medicinal product (s).
p.000004: 4.8. Informed consent of participants
p.000004: 4.8.1. During the receipt and documentation of informed consent, the researcher complies
p.000004: the applicable regulatory requirements, the principles of the CPT and the ethical principles enshrined in the Declaration of
p.000004: Helsinki. In order to begin the clinical trial, the researcher must have a positive opinion in writing
p.000004: of the Ethics Committee on the written informed consent and any other written information to be provided
p.000004: provided to participants.
p.000004: 4.8.2. The written informed consent form and any other written information provided to participants shall be
p.000004: updates when important new information becomes available that may affect their consent. Each
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p.000004: 5.11.2. If the Ethics Committee gives a favorable opinion, provided that changes are made to
p.000004: some aspect of the clinical trial (eg protocol modification, informed consent form, and
p.000004: any other information that will be provided to the participants and / or other procedures) shall be provided by the contracting authority
p.000004: a copy of the modification made by the researcher and the date of issue of a favorable opinion by the
p.000004: ethics.
p.000004: 5.11.3. The contracting authority shall provide the researcher with documents and dates for any new positive opinions
p.000004: for changes, and any withdrawal or termination of a favorable opinion.
p.000004: 5.12. Information on the investigational medicinal product
p.000004: 5.12.1. When planning a clinical trial, the contracting authority shall ensure that sufficient data are available,
p.000004: demonstrating the safety and efficacy of non-clinical and / or clinical trials of the product in support
p.000004: of its administration to humans by route, dosage, duration and test group of patients to be
p.000004: study.
p.000004: 5.12.2. The contracting authority shall update the researcher's brochure when new and relevant information becomes available.
p.000004: 5.13. Production, packaging, labeling and coding of the test drug
p.000004: product
p.000004: 5.13.1. The sponsor shall ensure that the investigational medicinal product (including
p.000004: comparator and placebo medicinal product, if used) is characterized in accordance with the development stage of
p.000004: a medicinal product that is manufactured in accordance with the applicable GMP and is coded and labeled in a manner that preserves
p.000004: blinding, if any. The contracting entity shall prepare a labeling of the tested medicinal product in accordance
p.000004: with the requirements of Good Manufacturing Practice rules for medicinal products under development and
p.000004: study and applicable regulatory requirements.
p.000004: 5.13.2. The contracting authority determines the storage temperature and conditions (eg light protection), storage time,
p.000004: dissolution fluids and procedures, as well as infusion products, if any.
p.000004: The sponsor notifies all parties involved in the clinical trial (i.e., monitoring, investigators,
p.000004: pharmacists, storage officers) for certain conditions.
p.000004: 5.13.3. It is necessary to protect the packaging of the tested medicinal product from contamination and unacceptable
p.000004: degradation of quality during transport and storage.
p.000004: 5.13.4. In blind trials, the coding system for the investigational medicinal product must be included
p.000004: mechanism for immediate disclosure of the medicinal product in case of emergency, but not allowing for imperceptible detection
p.000004: on the code.
p.000004: 5.13.5. If significant changes are made to the composition of the trials during the clinical trial
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p.000004: severity, expectation and cause and effect in accordance with published International Guidelines
p.000004: harmonization conference, the European Commission and the European Medicines Agency.
p.000004: 5.16.5. The contracting authority shall actively collect any additional information that is necessary to evaluate the
p.000004: individual reports of adverse events.
p.000004: 5.1.6.6. All adverse events rated by the researcher or assignor as least likely to be related
p.000004: with the test product, are treated and reported as adverse reactions.
p.000004: 5.17. Reporting side effects
p.000004: 5.17.1. Reports of suspected serious and unexpected adverse reactions under Art. 138 LPPM are submitted by
p.000004: the sponsor of the clinical trial.
p.000004: The contracting authority is responsible for reporting serious adverse reactions, including when
p.000004: reactions are to an authorized test medicinal product used in the test as a product for
p.000004: a comparison for which the contracting authority does not hold the marketing authorization. In these cases the contracting authority
p.000004: inform the marketing authorization holder of the product for the territory of Bulgaria of the reaction and of the submission of the product
p.000004: information to the BDA.
p.000004: Where the investigational medicinal product is not authorized, the sponsor shall notify the BDA and
p.000004: the Ethics Committee, in addition to the communications under Art. 138, para. 1 and 3 of ZLPHM and for all suspects
p.000004: serious and unexpected side effects when using the test drug regardless of origin
p.000004: them.
p.000004: Serious and unexpected adverse reaction reports are submitted to the Medicines Executive Agency and
p.000004: the ethics committee immediately and no later than 15 days after receipt of information on their occurrence. At
p.000004: explicit written consent of the Ethics Committee reports of suspected serious and unexpected undesirable
p.000004: reactions may be reported at larger intervals, but not less than once every six months.
p.000004: The contracting authority is responsible for submitting reports to all interested researchers,
p.000004: ethics and regulatory authorities for any side effects that are serious and unexpected.
p.000004: 5.17.2. Serious and unexpected adverse reaction reports should comply with applicable regulatory requirements
p.000004: requirements and guidance of the International Harmonization Conference on the processing of safety data
p.000004: Clinical Trials - "Definitions and Standards for Emergency Reporting" (ICH Guideline for Clinical Safety Data
p.000004: Management: Definitions and Standards for Expedited Reporting).
p.000004: 5.17.3. The contracting authority shall submit to the regulatory authorities all updates of
p.000004: safety data and periodic reports. The contracting authority shall provide the Executive Agency once a year
p.000004: medicines and ethics committee list all suspected serious side effects that are
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p.000004: after the end of the period covered by the report.
p.000004: For clinical trials of less than one year duration, an annual safety report shall be submitted to
p.000004: term up to 90 days after the end of the test with the notification under art. 142, para. 2 CLPM.
p.000004: When conducting more than one clinical trial with the same test product, the contracting authority shall submit a total annual
p.000004: safety report. In such cases, the report shall contain data on the safety profile of the product tested and annual
p.000004: safety reports on each of the clinical trials conducted in Bulgaria.
p.000004: 5.17.5. The contracting authority shall provide an annual safety report beyond the deadline requested by the BDA and / or
p.000004: the ethics committee.
p.000004: 5.18. Monitoring
p.000004: 5.18.1. The purpose of monitoring is to verify that the rights and well-being of
p.000004: people; the reported data are accurate, complete and consistent with the original documents; conducting the clinical
p.000004: testing is in accordance with the approved plan and changes, DCT and applicable regulatory requirements.
p.000004: 5.18.2. Selection and qualification of monitoring entities
p.000004: 5.18.2.1. The persons conducting the monitoring are appointed by the contracting authority.
p.000004: 5.18.2.2. The monitoring personnel are trained and have the necessary scientific and / or medical knowledge,
p.000004: to properly monitor the clinical trial. Qualification of the practitioners
p.000004: monitoring, is documented.
p.000004: 5.18.2.3. Monitoring persons should be fully aware of the drug tested
p.000004: the product, the minutes, the written informed consent form and any other written information to be provided
p.000004: of the participants, the SOP of the contracting authority, the CPT and the applicable regulatory requirements.
p.000004: 5.18.3. Scope and nature of monitoring
p.000004: The contracting entity shall ensure that the tests are properly monitored. The contracting authority is obliged to
p.000004: determine the scope and manner of monitoring, taking into account the purpose, design, complexity, blinding, size
p.000004: and clinical trial endpoints. On-site monitoring is generally performed before, during and
p.000004: after the clinical trial. By way of exception, the contracting authority may determine that central monitoring,
p.000004: involving procedures such as training and meetings of researchers and the use of advanced written manuals,
p.000004: Ensure that the clinical trial is conducted in accordance with DCT. Acceptable method for selecting verification data
p.000004: is the method of statistically controlled samples.
p.000004: 5.18.4. Obligations of monitoring persons
p.000004: In accordance with the requirements of the contracting entity, the monitoring entity shall ensure that the clinical
p.000004: the test shall be conducted and properly documented by performing the following:
p.000004: 5.18.4.1. acts as the main link for correspondence between the sponsor and the researcher;
p.000004: 5.18.4.2. determine whether the researcher has the relevant qualifications and resources,
p.000004: which will remain appropriate throughout the test that the conditions including the laboratory, equipment and
p.000004: staff, are appropriate and will remain so throughout the clinical trial for his or her own
p.000004: safe and proper conduct;
p.000004: 5.18.4.3. establishes that with regard to the investigational medicinal product:
p.000004: 5.18.4.3.1. storage time and conditions are appropriate and deliveries are sufficient for the whole test;
p.000004: 5.18.4.3.2. the test drug is only delivered to participants who are eligible for the preparation
p.000004: his dose, as determined by the protocol;
p.000004: 5.18.4.3.3. members of the research team are provided with the necessary instructions for proper use, handling,
p.000004: storage and return of the test medicinal product;
p.000004: 5.18.4.3.4. the receipt, use and return of the test medicinal product at the venues of
p.000004: the clinical trial is properly controlled and documented;
p.000004: 5.18.4.3.5. handling unused quantities of the tested medicinal product is relevant
p.000004: regulatory requirements and agreed with the contracting authority;
p.000004: 5.18.4.4. determine whether the researcher follows the approved protocol and any approved changes, if any;
p.000004: 5.18.4.5. determine whether informed consent has been obtained from each participant prior to its inclusion in the clinical setting
p.000004: testing;
p.000004: 5.18.4.6. ensure that the researcher receives the researcher 's current brochure, all documents and
p.000004: all clinical trial supplies necessary for its proper conduct and in accordance with
p.000004: applicable regulatory requirements;
p.000004: 5.18.4.7. ensure that the researcher and his or her team are sufficiently familiar with the clinical trial;
p.000004: 5.18.4.8. verifies that the researcher and his or her team perform the identified clinical activities
p.000004: testing in accordance with the protocol and all other written contracts between the sponsor and the researcher and that
p.000004: have not transferred these activities to other unauthorized persons;
p.000004: 5.18.4.9. checks that the researcher includes only suitable persons;
p.000004: 5.18.4.10. report the status of involvement of participants;
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p.000004: included in the clinical trial.
p.000004: 6.2. Basic information
p.000004: 6.2.1. Name and description of the product (s) tested.
p.000004: 6.2.2. Summary of non - clinical trial data of clinical relevance and of
p.000004: clinical trials related to the present.
p.000004: 6.2.3. Summary of identified and potential risks and benefits, if any, to humans.
p.000004: 6.2.4. Description and rationale for route of administration, dose, dosage regimen and treatment
p.000004: period.
p.000004: 6.2.5. The view that the clinical trial will be conducted in accordance with the protocol,
p.000004: DCT and applicable regulatory requirements.
p.000004: 6.2.6. Description of the category of persons to be tested.
p.000004: 6.2.7. Used literature and data that are relevant to the clinical trial and provide the basis for
p.000004: the clinical trial.
p.000004: 6.3. Tasks and purpose
p.000004: A detailed description of the tasks and purpose of the clinical trial.
p.000004: 6.4. Test design
p.000004: The scientific value of the clinical trial and the reliability of the data depend significantly on the design of the clinical trial
p.000004: the clinical trial. The design description includes:
p.000004: 6.4.1. Explicit indication of primary and secondary endpoints to be used as indicators for
p.000004: efficacy and safety to be evaluated during the clinical trial.
p.000004: 6.4.2. Description of the type / design of the clinical trial to be conducted (e.g., double-blind,
p.000004: placebo-controlled, parallel design) and schematic diagram of clinical design, procedures, and steps
p.000004: testing.
p.000004: 6.4.3. Description of measures taken to reduce / avoid deviations, incl. randomization and
p.000004: blinding.
p.000004: 6.4.4. Description of study treatment (s), dose and dosage regimen of test drug; includes
p.000004: a description of the dosage form, packaging and labeling of the test product.
p.000004: 6.4.5. The expected length of participation of the persons as well as a description of the sequence
p.000004: and the duration of all clinical trial periods, including follow-up, if any.
p.000004: 6.4.6. Description of the "stopping rules" and "removal criteria" for specific individuals in clinical stages
p.000004: test and throughout the test.
p.000004: 6.4.7. Reporting procedures for the test product, including placebo and the medicinal product for
p.000004: comparison, if any.
p.000004: 6.4.8. Retention of randomization codes and procedures for revealing treatment codes in
p.000004: the clinical trial.
p.000004: 6.4.9. Indication of all data that will be directly recorded in the CCP (ie without direct written information
p.000004: or electronic recording) and which are considered original data.
p.000004: 6.5. Selection and removal of participants
p.000004: 6.5.1. Eligibility criteria for participants.
p.000004: 6.5.2. Exclusion criteria for participants.
p.000004: 6.5.3. Exclusion criteria for participants (ie termination of treatment with trials
p.000004: product / treatment tested) and procedures specifying:
p.000004: 6.5.3.1. when and how participants will be excluded from the trial / treatment with the test product;
p.000004: 6.5.3.2. the type of data and the period for which the data on the removed participants will be collected;
p.000004: 6.5.3.3. whether and how the dropped participants will be replaced;
p.000004: 6.5.3.4. follow-up of drop-outs from test treatment / treatment with test product.
p.000004: 6.6. Treatment of participants
p.000004: 6.6.1. The treatment (s) prescribed, including the names of all products, dose (s), dosage regimens, routes / routes
...
p.000004: which, if possible, includes the following: pharmacokinetics (including metabolism and absorption, binding to
p.000004: plasma proteins, distribution and elimination); bioavailability (where possible absolute and / or relative),
p.000004: using a dosage form for comparison; subgroups of the population (eg gender, age and impaired function)
p.000004: to an authority); interactions (eg product-product interactions or food effects); others
p.000004: pharmacokinetic data (eg, results from population-based studies conducted in clinical trials).
p.000004: 7.3.6.2. Safety and efficiency
p.000004: A summary of information obtained from previous human clinical trials (healthy volunteers) is provided
p.000004: and / or patients) for the safety, pharmacodynamics, efficacy and dose response of the product (s) tested
p.000004: (and their metabolites where appropriate). The conclusions of this information are commented. Where they are
p.000004: completed a large number of clinical trials, the use of safety and efficacy summaries of
p.000004: multiple sub-group indication tests may be representative of the data. Summaries can
p.000004: also be presented in tabular form for adverse reactions for all clinical trials (incl.
p.000004: those for all testimony tested). Important differences in trends / incidence of
p.000004: side effects against indications or subgroups.
p.000004: A description of the potential risks and undesirable effects is provided
p.000004: reactions based on direct experience with the study drug
p.000004: product and related products, as well as precautions or special observations that
p.000004: to be carried out during the tested use of the medicinal product (s).
p.000004: 7.3.6.3. Experience after authorization for use
p.000004: Indicate the countries in which the test medicinal product is authorized. Commented
p.000004: any relevant information obtained from use after authorization (eg formulas, doses, routes of administration or administration)
p.000004: side effects). The countries in which the test medicinal product has not been authorized shall also be indicated
p.000004: for use or has been withdrawn from the market.
p.000004: 7.3.7. Summary of data and recommendations to the researcher
p.000004: This section shall, as far as possible, provide a comprehensive commentary on non - clinical and non - clinical settings
p.000004: clinical data and summarizes information from different sources on different aspects of the product tested.
p.000004: In this way, the researcher may be familiar with the most informative interpretation of the available data and
p.000004: assessing the conclusions of the information for future clinical trials.
p.000004: Commented on published reports of relevant medicinal products to help the researcher
p.000004: predicted side effects or other problems in clinical trials.
p.000004: The main purpose of this section is to provide the researcher with a clear understanding of the possible risks,
p.000004: side effects and specific tests, observations and precautions that may be required to
p.000004: clinical trial. This understanding needs to be based on accessible physical, chemical,
p.000004: pharmaceutical, pharmacological, toxicological and clinical information on the study (s) medicinal product (s).
p.000004: A guide is also provided to the investigating physician to identify and treat possible overdose
...
p.000000: documentation.
p.000000: 8.4.6 Treatment allocation and
p.000000: To document that X X has been returned to
p.000000: documents for decoding the contracting authority, if any
p.000000: has arisen
p.000000: (when treating-
p.000000: some decoding. this is known to the research team)
p.000000: 8.4.7 Final research report
p.000000: to the Ethics Committee
p.000000: and regulators, in the
p.000000: tea that this is required
p.000000: To document X 0
p.000000: completion of
p.000000: the clinical trial.
p.000000: 8.4.8 Clinical report To document 0
p.000000: X
p.000000: results and in-
p.000000: trial interpretation of the clinical trial.
p.000000: Annex No. 2 to Art. 10, para. 1
p.000000: Content and format of the dossier of the tested medicinal product
p.000000: 1. Introduction
p.000000: 2. Product details
p.000000: 2.1. Chemical-pharmaceutical data
p.000000: 2.1.1. Details of the substance
p.000000: 2.1.1.1. General information
p.000000: 2.1.1.1.1. Nomenclature
p.000000: 2.1.1.1.2. Structure
p.000000: 2.1.1.1.3. General properties
p.000000: 2.1.1.2. Production
p.000000: 2.1.1.2.1. Manufacturer (s)
p.000000: 2.1.1.2.2. Description of production process and control
p.000000: 2.1.1.2.3. Control of raw materials
p.000000: 2.1.1.2.4. Control of critical and intermediate stages
p.000000: 2.1.1.2.5. Validation and evaluation of production processes
p.000000: 2.1.1.2.6. Development of the production process
p.000000: 2.1.1.3. Characterization
p.000000: 2.1.1.3.1. Methods for determining the structure and other characteristics
p.000000: 2.1.1.3.2. Impurities
p.000000: 2.1.1.3.3. Control of the drug substance
p.000000: 2.1.1.3.4. Specification
p.000000: 2.1.1.3.5. Analytical procedures
p.000000: 2.1.1.3.6. Validation of analytical procedures
p.000000: 2.1.1.3.7. Batch analysis
p.000000: 2.1.1.3.8. Validation of specifications
p.000000: 2.1.1.4. Reference standard substances and materials
p.000000: 2.1.1.5. Packing and sealing system
p.000000: 2.1.1.6. Stability
p.000000: 2.1.2. Data on the medicinal product
p.000000: 2.1.2.1. Description and composition of the medicinal product
p.000000: 2.1.2.2. Pharmaceutical development
p.000000: 2.1.2.2.1. Components of the medicinal product
p.000000: 2.1.2.2.2. Medicine
p.000000: 2.1.2.2.3. Development of the production process
p.000000: 2.1.2.2.4. Packing and sealing system
p.000000: 2.1.2.2.5. Microbiological indicators
p.000000: 2.1.2.2.6. Compatibility
p.000000: 2.1.2.3. Production
p.000000: 2.1.2.3.1. Manufacturer (s)
p.000000: 2.1.2.3.2. Production recipe
p.000000: 2.1.2.3.3. Description and control of the production process
p.000000: 2.1.2.3.4. Control of critical and intermediate parameters
p.000000: 2.1.2.3.5. Process validation and / or evaluation
p.000000: 2.1.2.4. Excipient control
p.000000: 2.1.2.4.1. Specifications
p.000000: 2.1.2.4.2. Analytical procedures
p.000000: 2.1.2.4.3. Validation of analytical procedures
p.000000: 2.1.2.4.4. Validation of specifications
p.000000: 2.1.2.4.5. Excipients of human and animal origin
p.000000: 2.1.2.4.6. Newly introduced excipients
p.000000: 2.1.2.5. Control of the medicinal product
p.000000: 2.1.2.5.1. Release specification (s) and expiry date
p.000000: 2.1.2.5.2. Analytical procedures
p.000000: 2.1.2.5.3. Validation of analytical procedures
p.000000: 2.1.2.5.4. Batch analysis
p.000000: 2.1.2.5.5. Characterization of impurities
p.000000: 2.1.2.5.6. Validation of specifications
...
p.000000: 1.6. Change in plan for taking biological research materials.
p.000000: 1.7. Add or remove studies and / or tests.
p.000000: 1.8. Changing age ranges for participation.
p.000000: 1.9. Change in inclusion and exclusion criteria.
p.000000: 1.10. Change in safety monitoring procedures.
p.000000: 1.11. Change in the duration of use of the test product.
p.000000: 1.12. Change in the way the test product is used.
p.000000: 1.13. Change medicine for comparison.
p.000000: 1.14. Change in statistical plan.
p.000000: 1.15. Any change related to the safety and physical and / or intellectual integrity of the participants
p.000000: or the risk / benefit ratio of the study.
p.000000: 1.16. Change in end of study definition.
p.000000: 2. Changes in the administrative organization of the study:
p.000000: 2.3. Change of sponsor and / or his authorized representative.
p.000000: 2.4. Change of approved research center.
p.000000: 2.5. Appointment of a new principal investigator.
p.000000: 2.6. Inclusion of a new research center.
p.000000: 2.7. Appointment of a new principal investigator at an approved research center.
p.000000: 2.8. Change in the terms of the insurance or the procedure for indemnification of the study participants.
p.000000: 2.9. Other significant changes to the protocol and / or accompanying application initially
p.000000: documentation.
p.000000: 3. Changes concerning the quality of the investigational medicinal product:
p.000000: 3.3. Changing the name of the tested product from the code of the assignor to an international non-patent name.
p.000000: 3.4. Changes in primary packaging materials.
p.000000: 3.5. Change of importer for medicinal products made outside the EU.
p.000000: 3.6. Change of manufacturer of the drug substance.
p.000000: 3.7. Change in the manufacturing process of the drug substance.
p.000000: 3.8. A change in the specification of a medicinal substance when it involves an extension of acceptable limits and / or
p.000000: dropping out of tests.
p.000000: 3.9. Significant changes in the manufacturing process of the product under test.
p.000000: 3.10. Modification of the specification of the test product when it involves the extension of acceptable limits and / or dropping
p.000000: of tests.
p.000000: 3.11. Change in the specification for excipients when they can affect the properties of the product.
p.000000: 3.12. Significant change in production formulation.
p.000000: 3.13. Limitation of storage conditions.
p.000000: 3.14. Reduced shelf life after opening or opening.
p.000000: 3.15. Change in procedures for testing the active substance when a new test is added
p.000000: method.
p.000000: 3.16. Change in testing procedures for test product when new product is added
p.000000: test method.
p.000000: 3.17. Change in procedures for testing non-pharmacopoeial adjuvants when adding a new test method.
p.000000: 4. Any changes to the non-clinical data for the product under test that may alter the ratio
p.000000: risk / benefit
...
Searching for indicator influence:
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p.000004: relevant to the risk to humans, but at least once a year.
p.000004: 3.1.5. The Ethics Committee may, at its discretion, require the submission of more information than described
p.000004: in clause 4.8.10, where this addition is relevant for the protection of the rights and safety and / or health of
p.000004: the patients.
p.000004: 3.1.6. In the cases of items 4.8.12 and 4.8.14, when it is necessary to conduct a non-therapeutic test
p.000004: the consent of the legal representative of the participant, the Ethics Committee decides whether the proposed protocol
p.000004: and / or other documents comply with ethical standards and whether they meet the applicable regulatory requirements for that type
p.000004: tests.
p.000004: 3.1.7. In the cases of item 4.8.15, where the clinical trial protocol permits patient involvement,
p.000004: without the immediate written consent or consent of his legal representative,
p.000004: the ethics committee decides whether the proposed plan and / or other documents are ethical
p.000004: and whether they meet the applicable regulatory requirements for this type of test.
p.000004: 3.1.8. The Ethics Committee assesses the size and method of payment for the healthy
p.000004: volunteers / patients influence their consent to participate and whether their decision will be made freely.
p.000004: Payments per participant must be apportioned in proportion and not entirely dependent on
p.000004: completion of the test by the participant.
p.000004: 3.1.9. The Ethics Committee shall ensure that written informed consent is included in any other written consent
p.000004: information for the participant of information regarding payment for healthy volunteers / patients, incl.
p.000004: quantity, method of payment and periodicity. The way the payment will be distributed should be
p.000004: indicated.
p.000004: 3.2. Composition, functions and actions
p.000004: 3.2.1. The Ethics Committee is composed of members who, as a team, have sufficient qualifications and experience
p.000004: to consider and evaluate the scientific, medical and ethical aspects of the proposed clinical trial. The Commission
p.000004: Ethics includes at least 7 members, of which at least two are non-medical, financial and
p.000004: administratively independent of the clinical trial site.
p.000004: Only those members who are independent of the Assembly may vote and vote
p.000004: the principal investigator and the assignor.
p.000004: The Ethics Committee shall keep a list of the members and their qualifications as well as the official documents for the
p.000004: its creation.
...
p.000004: 4.8.10.11. anticipated, in proportion to time participation, payment for volunteers / patients
p.000004: their participation in the clinical trial, if any;
p.000004: 4.8.10.12. estimated costs for participants to participate in the clinical trial;
p.000004: 8/4/13 explanation that participation in the clinical trial is voluntary and that the participant may refuse to participate
p.000004: or withdraw at any time without the penalty or loss of benefits that the participant may
p.000004: to receive otherwise;
p.000004: 4.8.10.14. indicate that the monitoring, reviewing, ethics committee and regulatory bodies are
p.000004: provided access to the participant's original medical records for verification of clinical procedures
p.000004: testing and / or data, ensuring that the patient's personal data is protected in accordance with applicable laws and
p.000004: regulations, and by signing the written informed consent form, the participant or his or her legal
p.000004: the representative agrees to such access;
p.000004: 8/4/15 that the identification documents of the participant will be kept confidential and the data
p.000004: they will not be disclosed in accordance with applicable laws and regulations; in case of publication of
p.000004: results of the clinical trial of
p.000004: participants will remain confidential;
p.000004: 8/4/16 explanation that the participant or his legal representative will be notified in a timely manner if any
p.000004: new information that may influence their desire to continue participating in the clinical trial;
p.000004: 8/4/17 contact persons for further information regarding the clinical trial, contact persons for
p.000004: information on the rights of participants and those responsible for a clinical trial related disability;
p.000004: 4.8.10.18. the foreseeable circumstances and / or reasons why the participation may be terminated;
p.000004: 8/4/19/19 the expected duration of patient / healthy volunteer participation in the clinical trial;
p.000004: 4.8.10.20. the approximate number of participants.
p.000004: 4.8.11. Prior to participating in the clinical trial, each participant or his legal representative receives
p.000004: a copy of the signed and dated written informed consent form and any other
p.000004: information provided to participants. During the clinical trial, each participant or his or her
p.000004: the legal representative receives a copy of the modified informed consent form as well as the changes
p.000004: in any other written information provided to participants.
p.000004: 4.8.12. When a clinical trial (therapeutic or non-therapeutic) requires the inclusion of participants only
p.000004: with the consent of their legal representatives, participants are informed of the clinical trial at the
p.000004: according to their ability to understand and personally sign and date the written informed
p.000004: consent (if able).
p.000004: 4.8.13. Except as indicated in section 4.8.14, a non-therapeutic trial (ie, a trial in which
...
Searching for indicator substance:
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p.000004: assessment of whether the researchers, the conditions, the methods for conducting the test are appropriate.
p.000004: 1.28. An informed consent
p.000004: Informed consent is a statement of will that must be written, personally dated and signed in order to participate in
p.000004: a clinical trial taken completely free after being duly informed of its nature,
p.000004: significance, consequences and risks and appropriately documented by any person who is able to give
p.000004: his consent, or when the person is unable to give his consent, from his legal representative.
p.000004: 1.29. Inspection
p.000004: Official inspection of the inspection bodies for documents, conditions, records and any other data sources provided
p.000004: are considered by them to be related to the clinical trial and may be stored at the clinical venue
p.000004: testing, the office of the contracting authority / DIO or other places deemed appropriate by these inspection bodies.
p.000004: 1.30. Institution (medical)
p.000004: Medical establishments where clinical trials are conducted.
p.000004: 1.31. Interim clinical trial report
p.000004: Report on the provisional results of the study and their evaluation based on analyzes made during the
p.000004: conducting the clinical trial.
p.000004: 1.32. Tested medicinal product
p.000004: Test drug is a formulation of an active substance or a placebo,
p.000004: which is being tested or used as a comparison in a clinical trial, including products for which it has been issued
p.000004: marketing authorization, but are used for unauthorized use or for the purpose of obtaining an additional one
p.000004: information on the authorized form, or supplied (in dosage form or packaged) in a way other than
p.000004: the authorized form.
p.000004: 1.33. Principal Investigator
p.000004: The principal investigator is the physician or dental practitioner designated by the contracting authority who is in charge
p.000004: the complete conduct of the clinical trial at the center in accordance with the approved protocol and
p.000004: the DCM manual and is responsible for the work of the researchers.
p.000004: 1.34. Explorer
p.000004: The researcher is the doctor or dentist designated by the sponsor and the principal investigator who
p.000004: practically conducts the clinical trial under the direction of the principal investigator according to the approved protocol and
p.000004: the DCT manual at the clinical trial research center. If the clinical
p.000004: testing is conducted by a team, the researcher is the team leader responsible for the team and is called the principal
p.000004: Explorer.
p.000004: 1.35. Researcher's brochure
p.000004: Document containing all clinical and non-clinical trial data (s) for medicinal product (s)
p.000004: refer to the administration of the tested medicinal products to humans.
p.000004: 1.36. Legal representative
p.000004: An individual who, under applicable law, is a legal representative and can agree to participate
p.000004: of the future participant in the clinical trial on his behalf.
p.000004: 1.37. Monitoring
...
p.000004: The researcher's booklet contains the following sections, each of which, if possible, has one
p.000004: literary reference:
p.000004: 7.3.1. Table of Contents:
p.000004: Privacy Statement Signature Page
p.000004: 1. Content
p.000004: 2. Summary
p.000004: 3. Introduction
p.000004: 4. Physical, chemical and pharmaceutical properties and formula
p.000004: 5. Non-clinical trials
p.000004: 5.1. Non-clinical pharmacology
p.000004: 5.2. Pharmacokinetics and metabolism of the product in animals
p.000004: 5.3. Toxicology
p.000004: 6. Effects in humans
p.000004: 6.1. Pharmacokinetics and metabolism of the product in humans
p.000004: 6.2. Safety and efficiency
p.000004: 6.3. Experience after marketing authorization
p.000004: 7. Summary of data and recommendations to the researcher
p.000004: 1. Publications
p.000004: 2. Reports
p.000004: Applications (if any)
p.000004: 7.3.2. Summary
p.000004: A brief summary (not exceeding two pages) is given indicating an important physical, chemical,
p.000004: pharmaceutical, pharmacological, toxicological, pharmacokinetic, metabolic and clinical information that
p.000004: corresponds to the stage of clinical development of the test product.
p.000004: 7.3.3. Introduction
p.000004: A brief introductory description containing the chemical name (as well as the generic and trade name) is included
p.000004: name, when approved) of the product (s) tested, all active ingredients, pharmacological class and
p.000004: the expected place in this class (eg benefits), the rationale for the study and the expected (s)
p.000004: indications (s) for prophylaxis, therapy or diagnosis. Finally an introductory description including the main one
p.000004: the approach to be followed in evaluating the product (s) tested.
p.000004: 7.3.4. Chemical, physical, pharmaceutical properties and composition
p.000004: A description of the substance (s) (including chemical and / or structural formula (s)) and a brief summary of relevant
p.000004: chemical, physical, pharmaceutical properties.
p.000004: A description (if clinically relevant) of the composition (s) to be used shall be provided and commented on, including
p.000004: excipients in order to take appropriate safety measures. Instructions are given for the storage and use of
p.000004: dosage forms. All structural similarities to other known substances are mentioned.
p.000004: 7.3.5. Non-clinical trials
p.000004: The results of all relevant non-clinical pharmacological, toxicological,
p.000004: pharmacokinetic and metabolism studies of the product under test. This summary
p.000004: describes the methodology used, the results and a discussion of the significance of the findings for the product under test
p.000004: and the possible adverse and side effects in humans.
p.000004: The information provided includes the species tested; the number and sex of animals in each group; dosage units
p.000004: (eg milligrams / kilograms, mg / kg); dose interval; application method; duration of dosing;
p.000004: system allocation information; duration of follow-up after administration; results,
p.000004: incorporating the following aspects: nature and frequency of pharmacological or toxic effects; weight and
p.000004: intensity of pharmacological or toxic effects; time for the effects to occur; duration of effects;
p.000004: dose response.
p.000004: A spreadsheet or list can be used to improve the clarity of the presentation.
p.000004: The following sections of the researcher's booklet present the most important findings from
p.000004: tests, including the dose response to the effects observed, the relevance to humans and any effects that will
p.000004: to be studied on humans. If possible, compare the effective and non-toxic dose in animals of one and
...
p.000000: 8.4.3 Completed code list for To be possible
p.000000: recognition of
p.000000: face recognition all involved in the clinical
p.000000: experience-
p.000000: not persons, if necessary
p.000000: tracking. The list should be kept-
p.000000: is not confidential and within the agreed period.
p.000000: X X
p.000000: X X
p.000000: If destroyed in the center
p.000000: X 0
p.000000: 8.4.4 Certificate of verification To document that it is 0
p.000000: X
p.000000: done
p.000000: (if available) check.
p.000000: 8.4.5 Final report by the person,
p.000000: monitoring for
p.000000: To document that they are
p.000000: 0 X performed
p.000000: all necessary closing activities-
p.000000: closing the center net center and that copies of
p.000000: basic-
p.000000: these documents are stored in accordance with
p.000000: documentation.
p.000000: 8.4.6 Treatment allocation and
p.000000: To document that X X has been returned to
p.000000: documents for decoding the contracting authority, if any
p.000000: has arisen
p.000000: (when treating-
p.000000: some decoding. this is known to the research team)
p.000000: 8.4.7 Final research report
p.000000: to the Ethics Committee
p.000000: and regulators, in the
p.000000: tea that this is required
p.000000: To document X 0
p.000000: completion of
p.000000: the clinical trial.
p.000000: 8.4.8 Clinical report To document 0
p.000000: X
p.000000: results and in-
p.000000: trial interpretation of the clinical trial.
p.000000: Annex No. 2 to Art. 10, para. 1
p.000000: Content and format of the dossier of the tested medicinal product
p.000000: 1. Introduction
p.000000: 2. Product details
p.000000: 2.1. Chemical-pharmaceutical data
p.000000: 2.1.1. Details of the substance
p.000000: 2.1.1.1. General information
p.000000: 2.1.1.1.1. Nomenclature
p.000000: 2.1.1.1.2. Structure
p.000000: 2.1.1.1.3. General properties
p.000000: 2.1.1.2. Production
p.000000: 2.1.1.2.1. Manufacturer (s)
p.000000: 2.1.1.2.2. Description of production process and control
p.000000: 2.1.1.2.3. Control of raw materials
p.000000: 2.1.1.2.4. Control of critical and intermediate stages
p.000000: 2.1.1.2.5. Validation and evaluation of production processes
p.000000: 2.1.1.2.6. Development of the production process
p.000000: 2.1.1.3. Characterization
p.000000: 2.1.1.3.1. Methods for determining the structure and other characteristics
p.000000: 2.1.1.3.2. Impurities
p.000000: 2.1.1.3.3. Control of the drug substance
p.000000: 2.1.1.3.4. Specification
p.000000: 2.1.1.3.5. Analytical procedures
p.000000: 2.1.1.3.6. Validation of analytical procedures
p.000000: 2.1.1.3.7. Batch analysis
p.000000: 2.1.1.3.8. Validation of specifications
p.000000: 2.1.1.4. Reference standard substances and materials
p.000000: 2.1.1.5. Packing and sealing system
p.000000: 2.1.1.6. Stability
p.000000: 2.1.2. Data on the medicinal product
p.000000: 2.1.2.1. Description and composition of the medicinal product
p.000000: 2.1.2.2. Pharmaceutical development
p.000000: 2.1.2.2.1. Components of the medicinal product
p.000000: 2.1.2.2.2. Medicine
p.000000: 2.1.2.2.3. Development of the production process
p.000000: 2.1.2.2.4. Packing and sealing system
p.000000: 2.1.2.2.5. Microbiological indicators
p.000000: 2.1.2.2.6. Compatibility
p.000000: 2.1.2.3. Production
p.000000: 2.1.2.3.1. Manufacturer (s)
p.000000: 2.1.2.3.2. Production recipe
p.000000: 2.1.2.3.3. Description and control of the production process
p.000000: 2.1.2.3.4. Control of critical and intermediate parameters
p.000000: 2.1.2.3.5. Process validation and / or evaluation
p.000000: 2.1.2.4. Excipient control
p.000000: 2.1.2.4.1. Specifications
p.000000: 2.1.2.4.2. Analytical procedures
p.000000: 2.1.2.4.3. Validation of analytical procedures
p.000000: 2.1.2.4.4. Validation of specifications
p.000000: 2.1.2.4.5. Excipients of human and animal origin
p.000000: 2.1.2.4.6. Newly introduced excipients
p.000000: 2.1.2.5. Control of the medicinal product
p.000000: 2.1.2.5.1. Release specification (s) and expiry date
p.000000: 2.1.2.5.2. Analytical procedures
p.000000: 2.1.2.5.3. Validation of analytical procedures
p.000000: 2.1.2.5.4. Batch analysis
p.000000: 2.1.2.5.5. Characterization of impurities
p.000000: 2.1.2.5.6. Validation of specifications
p.000000: 2.1.2.6. Reference standard substances and materials
p.000000: 2.1.2.7. Packing system
p.000000: 2.1.2.8. Stability
...
p.000000: 1.8. Changing age ranges for participation.
p.000000: 1.9. Change in inclusion and exclusion criteria.
p.000000: 1.10. Change in safety monitoring procedures.
p.000000: 1.11. Change in the duration of use of the test product.
p.000000: 1.12. Change in the way the test product is used.
p.000000: 1.13. Change medicine for comparison.
...
...
Health / Healthy People
Searching for indicator healthy volunteers:
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p.000004: and / or other documents comply with ethical standards and whether they meet the applicable regulatory requirements for that type
p.000004: tests.
p.000004: 3.1.7. In the cases of item 4.8.15, where the clinical trial protocol permits patient involvement,
p.000004: without the immediate written consent or consent of his legal representative,
p.000004: the ethics committee decides whether the proposed plan and / or other documents are ethical
p.000004: and whether they meet the applicable regulatory requirements for this type of test.
p.000004: 3.1.8. The Ethics Committee assesses the size and method of payment for the healthy
p.000004: volunteers / patients influence their consent to participate and whether their decision will be made freely.
p.000004: Payments per participant must be apportioned in proportion and not entirely dependent on
p.000004: completion of the test by the participant.
p.000004: 3.1.9. The Ethics Committee shall ensure that written informed consent is included in any other written consent
p.000004: information for the participant of information regarding payment for healthy volunteers / patients, incl.
p.000004: quantity, method of payment and periodicity. The way the payment will be distributed should be
p.000004: indicated.
p.000004: 3.2. Composition, functions and actions
p.000004: 3.2.1. The Ethics Committee is composed of members who, as a team, have sufficient qualifications and experience
p.000004: to consider and evaluate the scientific, medical and ethical aspects of the proposed clinical trial. The Commission
p.000004: Ethics includes at least 7 members, of which at least two are non-medical, financial and
p.000004: administratively independent of the clinical trial site.
p.000004: Only those members who are independent of the Assembly may vote and vote
p.000004: the principal investigator and the assignor.
p.000004: The Ethics Committee shall keep a list of the members and their qualifications as well as the official documents for the
p.000004: its creation.
p.000004: 3.2.2. The Ethics Committee shall perform its functions in accordance with written standard operating procedures, with the DCP and
p.000004: applicable regulatory requirements and keep records of its activities and minutes of meetings.
p.000004: 3.2.3. The Ethics Committee shall take its decisions at pre-announced meetings in the presence of a quorum set out in
p.000004: standard operating procedures.
p.000004: 3.2.4. Only members of the Ethics Committee who participated in the discussions and opinions may vote / express an opinion.
p.000004: reviewing the study documentation.
...
p.000004: dosing; carcinogenicity; special tests (eg irritability and sensitivity); reproductive toxicity;
p.000004: genotoxicity (mutagenicity).
p.000004: 7.3.6. Effects in humans
p.000004: A full description of the known effects of the tested product (s) on humans, including information on
p.000004: pharmacokinetics, metabolism, pharmacodynamics, dose response, safety, efficacy and other pharmacological
p.000004: actions. Whenever possible, a summary of each completed clinical trial as well as
p.000004: information regarding the results of any use of the test medicinal product to be tested
p.000004: different from clinical trials (eg post-market experience).
p.000004: 7.3.6.1. Pharmacokinetics and metabolism of the product in humans
p.000004: A summary of the pharmacokinetics of the investigational medicinal product shall be provided,
p.000004: which, if possible, includes the following: pharmacokinetics (including metabolism and absorption, binding to
p.000004: plasma proteins, distribution and elimination); bioavailability (where possible absolute and / or relative),
p.000004: using a dosage form for comparison; subgroups of the population (eg gender, age and impaired function)
p.000004: to an authority); interactions (eg product-product interactions or food effects); others
p.000004: pharmacokinetic data (eg, results from population-based studies conducted in clinical trials).
p.000004: 7.3.6.2. Safety and efficiency
p.000004: A summary of information obtained from previous human clinical trials (healthy volunteers) is provided
p.000004: and / or patients) for the safety, pharmacodynamics, efficacy and dose response of the product (s) tested
p.000004: (and their metabolites where appropriate). The conclusions of this information are commented. Where they are
p.000004: completed a large number of clinical trials, the use of safety and efficacy summaries of
p.000004: multiple sub-group indication tests may be representative of the data. Summaries can
p.000004: also be presented in tabular form for adverse reactions for all clinical trials (incl.
p.000004: those for all testimony tested). Important differences in trends / incidence of
p.000004: side effects against indications or subgroups.
p.000004: A description of the potential risks and undesirable effects is provided
p.000004: reactions based on direct experience with the study drug
p.000004: product and related products, as well as precautions or special observations that
p.000004: to be carried out during the tested use of the medicinal product (s).
p.000004: 7.3.6.3. Experience after authorization for use
p.000004: Indicate the countries in which the test medicinal product is authorized. Commented
p.000004: any relevant information obtained from use after authorization (eg formulas, doses, routes of administration or administration)
p.000004: side effects). The countries in which the test medicinal product has not been authorized shall also be indicated
p.000004: for use or has been withdrawn from the market.
p.000004: 7.3.7. Summary of data and recommendations to the researcher
p.000004: This section shall, as far as possible, provide a comprehensive commentary on non - clinical and non - clinical settings
p.000004: clinical data and summarizes information from different sources on different aspects of the product tested.
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p.000004: consent.
p.000004: 2.10. All clinical trial information must be recorded, maintained and stored in a manner permitting
p.000004: its accurate reporting, interpretation and verification.
p.000004: 2.11. The confidentiality of documents which may reveal the identity of the participants is retained,
p.000004: subject to the applicable regulatory requirements for secrecy and confidentiality.
p.000004: 2.12. The tested medicinal products are manufactured, maintained and stored in
p.000004: compliance with the applicable GMP. They shall be used in accordance with an approved protocol.
p.000004: 2.13. Procedures are in place at all stages of the clinical trial to ensure the quality of each stage of
p.000004: conducting the study.
p.000004: 3. Ethics Committee
p.000004: 3.1. Obligations
p.000004: 3.1.1. Each Ethics Committee protects the rights, safety and well - being of all participants in the
p.000004: the clinical trial. Particular attention is paid to clinical trials involving vulnerable groups
p.000004: patients.
p.000004: 3.1.2. The Ethics Committee receives the following documents: Clinical Trial Protocol / Changes, Form for
p.000004: written informed consent and changes to those forms that the researcher proposes to use in
p.000004: clinical trial, patient recruitment procedures (eg announcements), written information on
p.000004: participants, researcher's brochure, available safety information, billing information and compensation
p.000004: of patients, insurance for patients / volunteers and researchers, up-to-date CV of
p.000004: the researcher (s) and / or other documents proving their qualifications and other supporting documents
p.000004: documents which the commission may require to carry out its functions.
p.000004: It reviews the proposed clinical trial within the time limit set by law and documents its own
p.000004: written opinion with clearly stated clinical trial topic and documents reviewed and dated with respect to
p.000004: the following:
p.000004: 3.1.2.1. positive opinion;
p.000004: 3.1.2.2. amendments requested before a favorable opinion;
p.000004: 3.1.2.3. negative opinion;
p.000004: 3.1.2.4. amendment of a positive opinion already issued.
p.000004: 3.1.3. The Ethics Committee evaluates the researcher 's qualification for the proposed clinical trial by
p.000004: an up-to-date CV of the researcher and / or other relevant documents as may be required.
p.000004: 3.1.4. The Ethics Committee conducts ongoing oversight of every ongoing clinical trial at intervals,
p.000004: relevant to the risk to humans, but at least once a year.
p.000004: 3.1.5. The Ethics Committee may, at its discretion, require the submission of more information than described
p.000004: in clause 4.8.10, where this addition is relevant for the protection of the rights and safety and / or health of
p.000004: the patients.
p.000004: 3.1.6. In the cases of items 4.8.12 and 4.8.14, when it is necessary to conduct a non-therapeutic test
p.000004: the consent of the legal representative of the participant, the Ethics Committee decides whether the proposed protocol
p.000004: and / or other documents comply with ethical standards and whether they meet the applicable regulatory requirements for that type
p.000004: tests.
p.000004: 3.1.7. In the cases of item 4.8.15, where the clinical trial protocol permits patient involvement,
p.000004: without the immediate written consent or consent of his legal representative,
p.000004: the ethics committee decides whether the proposed plan and / or other documents are ethical
p.000004: and whether they meet the applicable regulatory requirements for this type of test.
p.000004: 3.1.8. The Ethics Committee assesses the size and method of payment for the healthy
p.000004: volunteers / patients influence their consent to participate and whether their decision will be made freely.
p.000004: Payments per participant must be apportioned in proportion and not entirely dependent on
p.000004: completion of the test by the participant.
p.000004: 3.1.9. The Ethics Committee shall ensure that written informed consent is included in any other written consent
p.000004: information for the participant of information regarding payment for healthy volunteers / patients, incl.
p.000004: quantity, method of payment and periodicity. The way the payment will be distributed should be
p.000004: indicated.
p.000004: 3.2. Composition, functions and actions
p.000004: 3.2.1. The Ethics Committee is composed of members who, as a team, have sufficient qualifications and experience
p.000004: to consider and evaluate the scientific, medical and ethical aspects of the proposed clinical trial. The Commission
p.000004: Ethics includes at least 7 members, of which at least two are non-medical, financial and
p.000004: administratively independent of the clinical trial site.
p.000004: Only those members who are independent of the Assembly may vote and vote
p.000004: the principal investigator and the assignor.
...
p.000004: any other written information has been properly explained and understood by the participants or their legal information
p.000004: representatives and consent was given by the participants themselves or their legal representatives.
p.000004: 4.8.10. The written informed consent form and any other written information provided to participants,
p.000004: contains explanations for the following:
p.000004: 4.8.10.1. that the clinical trial is a scientific research process;
p.000004: 4.8.10.2. the purpose of the clinical trial;
p.000004: 4.8.10.3. the treatment (s) tested and the likelihood of any treatment being randomly assigned;
p.000004: 4.8.10.4. the procedures to be performed during the clinical trial, including
p.000004: invasive manipulations;
p.000004: 4.8.10.5. the obligations of the participants;
p.000004: 4.8.10.6. those aspects of the clinical trial that are experimental;
p.000004: 4.8.10.7. reasonably foreseeable risks or inconveniences to participants, as well as to an embryo, fetus or infant,
p.000004: when necessary;
p.000004: 4.8.10.8. reasonably expected benefits; participants are informed of cases where no clinical benefit is expected;
p.000004: 4.8.10.9. the alternative procedures and treatment courses that are possible for the participants and important
p.000004: their potential risks and benefits;
p.000004: 4.8.10.10. compensation and / or possible treatment for participants in case of clinical trial related impairment;
p.000004: 4.8.10.11. anticipated, in proportion to time participation, payment for volunteers / patients
p.000004: their participation in the clinical trial, if any;
p.000004: 4.8.10.12. estimated costs for participants to participate in the clinical trial;
p.000004: 8/4/13 explanation that participation in the clinical trial is voluntary and that the participant may refuse to participate
p.000004: or withdraw at any time without the penalty or loss of benefits that the participant may
p.000004: to receive otherwise;
p.000004: 4.8.10.14. indicate that the monitoring, reviewing, ethics committee and regulatory bodies are
p.000004: provided access to the participant's original medical records for verification of clinical procedures
p.000004: testing and / or data, ensuring that the patient's personal data is protected in accordance with applicable laws and
p.000004: regulations, and by signing the written informed consent form, the participant or his or her legal
p.000004: the representative agrees to such access;
p.000004: 8/4/15 that the identification documents of the participant will be kept confidential and the data
p.000004: they will not be disclosed in accordance with applicable laws and regulations; in case of publication of
p.000004: results of the clinical trial of
p.000004: participants will remain confidential;
p.000004: 8/4/16 explanation that the participant or his legal representative will be notified in a timely manner if any
p.000004: new information that may influence their desire to continue participating in the clinical trial;
p.000004: 8/4/17 contact persons for further information regarding the clinical trial, contact persons for
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p.000004: Explorer. Research centers may be located in the territory of one Member State, at
p.000004: more than one Member State and / or Member States and third countries.
p.000004: 1.40. Non-clinical trial
p.000004: Non-human biomedical trial.
p.000004: 1.41. Minutes
p.000004: Clinical trial protocol is a document that describes the purpose (s), project, methodology, statistical
p.000004: the processing and organization of the test. The minutes shall also include any subsequent amendments thereto.
p.000004: 1.42. Change protocol
p.000004: A written description of the amendment (s) or formal explanation of the minutes.
p.000004: 1.43. QA
p.000004: Any planned and systematic actions that are put in place to ensure that data is received,
p.000004: documented (recorded) and reported and that the test is conducted in accordance with the DCT and applicable
p.000004: regulations.
p.000004: 1.44. Quality control
p.000004: Work techniques and actions undertaken within the framework of the
p.000004: quality in order to verify that the quality requirements of the test-related activities are fulfilled.
p.000004: 1.45. Randomization
p.000004: Process for allocating test participants or control groups using an element of
p.000004: chance to avoid deviations.
p.000004: 1.46. Regulatory bodies
p.000004: National competent authorities for quality, efficiency and safety control of
p.000004: medicinal products, as well as the bodies evaluating and submitting clinical documentation
p.000004: inspections.
p.000004: 1.47. Serious adverse event (SNA) or serious adverse reaction
p.000004: (SNLR)
p.000004: Any adverse effect or change in health that has become the cause
p.000004: for death, imminent danger of death, hospitalization or prolongation of hospitalization,
p.000004: significant or permanent damage, disability and congenital anomalies.
p.000004: 1.48. Output data
p.000004: All information in the original records and certified copies of the original clinical records, observations and
p.000004: other activities in one clinical trial necessary to recreate and evaluate the trial.
p.000004: 1.49. Source documents (source documents)
p.000004: Original documents and records in which data are first recorded after being received (e.g.
p.000004: hospital records, clinical and work plans, lab notes, notes, patient logs, or patient lists
p.000004: inspection, drug dispensing records from the pharmacy, automated device records, certified
p.000004: copies of records after confirmation that they are true copies, microfiche, photographic negatives,
p.000004: microfilms and tape recordings, x-rays, participant files, recordings stored in
p.000004: the pharmacy, the laboratory, and the medical and technical services involved in the test).
p.000004: 1.50. Contracting authority
p.000004: The natural or legal person, institution or organization responsible for initiating,
p.000004: management and / or funding of the clinical trial.
p.000004: 1.51. Investigator
p.000004: An individual who simultaneously initiates and conducts one clinical trial, alone or with others
p.000004: persons, and under whose immediate direction the investigational medicinal product is administered, dispensed or administered
p.000004: used by a patient. The definition does not include legal entities and scientific organizations. The obligations of
p.000004: the contracting authority is both that of the contracting authority and that of the researcher.
p.000004: 1.52. Standard Operating Procedures (SOPs)
...
p.000004: 8/4/13 explanation that participation in the clinical trial is voluntary and that the participant may refuse to participate
p.000004: or withdraw at any time without the penalty or loss of benefits that the participant may
p.000004: to receive otherwise;
p.000004: 4.8.10.14. indicate that the monitoring, reviewing, ethics committee and regulatory bodies are
p.000004: provided access to the participant's original medical records for verification of clinical procedures
p.000004: testing and / or data, ensuring that the patient's personal data is protected in accordance with applicable laws and
p.000004: regulations, and by signing the written informed consent form, the participant or his or her legal
p.000004: the representative agrees to such access;
p.000004: 8/4/15 that the identification documents of the participant will be kept confidential and the data
p.000004: they will not be disclosed in accordance with applicable laws and regulations; in case of publication of
p.000004: results of the clinical trial of
p.000004: participants will remain confidential;
p.000004: 8/4/16 explanation that the participant or his legal representative will be notified in a timely manner if any
p.000004: new information that may influence their desire to continue participating in the clinical trial;
p.000004: 8/4/17 contact persons for further information regarding the clinical trial, contact persons for
p.000004: information on the rights of participants and those responsible for a clinical trial related disability;
p.000004: 4.8.10.18. the foreseeable circumstances and / or reasons why the participation may be terminated;
p.000004: 8/4/19/19 the expected duration of patient / healthy volunteer participation in the clinical trial;
p.000004: 4.8.10.20. the approximate number of participants.
p.000004: 4.8.11. Prior to participating in the clinical trial, each participant or his legal representative receives
p.000004: a copy of the signed and dated written informed consent form and any other
p.000004: information provided to participants. During the clinical trial, each participant or his or her
p.000004: the legal representative receives a copy of the modified informed consent form as well as the changes
p.000004: in any other written information provided to participants.
p.000004: 4.8.12. When a clinical trial (therapeutic or non-therapeutic) requires the inclusion of participants only
p.000004: with the consent of their legal representatives, participants are informed of the clinical trial at the
p.000004: according to their ability to understand and personally sign and date the written informed
p.000004: consent (if able).
p.000004: 4.8.13. Except as indicated in section 4.8.14, a non-therapeutic trial (ie, a trial in which
p.000004: direct clinical benefit is provided for participants) is conducted on individuals who have personally signed and dated
p.000004: of the informed consent form.
p.000004: 4.8.14. Non-therapeutic trials may be conducted on individuals with the consent of their legal representatives
p.000004: only when:
...
p.000004: 8.2. Before starting the clinical phase of the clinical trial
p.000004: During the planning of this stage and before the formal start of the clinical trial, it is necessary to
p.000004: draw up and keep the following documents:
p.000004: Document Purpose Stored
p.000004: in the documentation of the assigning researcher
p.000004: 1 2 3
p.000004: 4
p.000004: 8.2.1. Researcher's Brochure Document that X
p.000004: X
p.000004: the corresponding and ac-
p.000004: complete scientific test information
p.000004: the product is presented to the researcher.
p.000004: 8.2.2. Minutes signed and changes Documented X
p.000004: X
p.000004: the contract between
p.000004: (if any) and a sample from the clinician and sponsor for
p.000004: protocol /
p.000004: The patient's card changes and CCP.
p.000004: 8.2.3.
p.000004: 8.2.3.1.
p.000004: 8.2.3.1.
p.000004: 8.2.3.2.
p.000004: 8.2.4.
p.000004: 8.2.5.
p.000004: Information given to subjects in the clinical trial
p.000004: Informed consent form (incl. Applicable translations)
p.000004: Any other written information
p.000004: Recruitment ad (if any)
p.000004: Financial aspects of the clinical trial
p.000004: Insurance policy
p.000004: Document X X informed compliance
p.000004: participant lassi.
p.000004: Document that the X X participants will
p.000004: be presented
p.000004: relevant information (such as content and style).
p.000004: Document that X 0
p.000004: recruitment measures-
p.000004: not patients
p.000004: appropriate and involuntary.
p.000004: Document X X
p.000004: financial contracts-
p.000004: between the researcher and the assignor
p.000004: for the clinical trial.
p.000004: Document that in X X
p.000004: case of contact
p.000004: but with the clinical trial the disability will be compensated.
p.000004: 8.2.6. Signed contract between the parties To be documented
p.000004: contracts.
p.000004: participants
p.000004: 8.2.6.1.
p.000004: 8.2.6.2.
p.000004: 8.2.6.3.
p.000004: 8.2.7.
p.000004: 8.2.7.1.
p.000004: 8.2.7.2.
p.000004: 8.2.7.3.
p.000004: 8.2.7.4.
p.000004: 8.2.7.5.
p.000004: 8.2.7.6.
p.000004: 8.2.7.7.
p.000004: 8.2.8.
p.000004: 8.2.9.
p.000004: 8.2.10.
p.000004: between the researcher and the contracting authority / contracting research organization;
p.000004: between the client and the medical center - the center of the study; between contracting authority and contract research
p.000004: organization
p.000004: Dated, documented permission / affirmative opinion of
p.000004: CE for the following:
p.000004: Protocol and amendments to the CCP
p.000004: Informed Consent Form Any other information provided to participants
p.000004: Recruitment announcement (if used)
p.000004: Participant compensation All other documents subject to approval / opinion
p.000004: Composition of the Ethics Committee / Appointment Order
p.000004: Authorization / notification of regulatory authorities
p.000004: CV and / or other document
p.000004: ment proving the qualifications of the principal investigator and
p.000004: X
p.000004: X 0
p.000004: Document that the X clinical exam-
p.000004: This was considered by a committee on
p.000004: ethics and has received
p.000004: positively-
p.000004: will. To identify the number and date-
p.000004: and the version of the documents.
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p.000004: The DCT rules have been developed taking into account current good clinical practice in the European Union
p.000004: community, Japan and the United States, as well as those of Australia, Canada, Scandinavian countries and World Health
p.000004: organization.
p.000004: These rules must be followed when generating data from clinical trials that will
p.000004: be submitted to the regulatory authorities.
p.000004: The principles laid down in these rules may also apply to others
p.000004: clinical trials that could have an impact on human safety and health.
p.000004: 1. Definitions
p.000004: 1.1. Adverse Reaction (ADR)
p.000004: "Undesirable effect" is any undesirable and unintended response to a medicinal product that occurs with
p.000004: administration of the product at doses normally used for the treatment, prophylaxis or diagnosis of disease in
p.000004: people or for recovery, correction or
p.000004: modification of physiological function. In the case of a clinical trial - any undesirable or unforeseen
p.000004: response to the investigational medicinal product, regardless of the dose administered. The phrase "answered one
p.000004: "means that the cause and effect relationship is between the medicinal product and the adverse reaction
p.000004: at least a reasonable possibility, that is, the connection cannot be denied.
p.000004: 1.2. Adverse event
p.000004: Adverse event is any adverse change in health status observed with the administration of a medicinal product.
p.000004: to a patient or participant in a clinical trial that is not necessarily causally related to this treatment.
p.000004: An adverse event may therefore be any adverse and unintended physical finding (incl.
p.000004: laboratory deviation), symptom, or illness associated with the use of (tested) drug over time
p.000004: product, whether or not it is causally related to the product.
p.000004: 1.3. Applicable requirements
p.000004: All regulatory requirements for conducting clinical trials with medicinal products.
p.000004: 1.4. Approval by the Ethics Committee
p.000004: Positive opinion from the Ethics Committee confirming that the clinical trial has been evaluated and can
p.000004: to be conducted at the established center under the conditions laid down by the Ethics Committee, the medical establishment, the CPT, and
p.000004: the applicable requirements.
p.000004: 1.5. Independent verification (audit)
p.000004: Systematic and independent evaluation of test-related obligations and assessment documents
p.000004: whether these obligations have been fulfilled, whether the data have been recorded, analyzed, carefully reported, in accordance with
p.000004: the protocol, standard operating procedures (SOPs) of the contracting entity, DCT and applicable regulatory requirements.
p.000004: 1.6. Certificate of verification
p.000004: Document from the verifier confirming that an inspection has been carried out.
p.000004: 1.7. Verification report
p.000004: Written evaluation of the verifier by the contracting authority for the results of the inspection.
p.000004: 1.8. Track for verification
p.000004: Documentation to track the sequence of events.
p.000004: 1.9. Blinding / masking
p.000004: A procedure in which one or more of the parties remain unaware of their assigned treatment
...
p.000004: 4.1.4. The researcher permits monitoring, verification by the contracting authority and inspection by
p.000004: the relevant regulatory authorities.
p.000004: 4.1.5. The researcher shall keep a list of the persons with the necessary qualifications to whom he has delegated responsible duties,
p.000004: related to the clinical trial.
p.000004: 4.2. Test Opportunities
p.000004: 4.2.1. The researcher must be able to show the ability to dial the required number
p.000004: appropriate patients within the agreed period (eg based on retrospective data).
p.000004: 4.2.2. The investigator has sufficient time to conduct and complete the clinical trial within the agreed timeframe.
p.000004: 4.2.3. The researcher has the necessary number of qualified personnel and the appropriate equipment for the foreseen
p.000004: the duration of the clinical trial for proper and safe conduct.
p.000004: 4.2.4. The researcher shall ensure that all persons participating in the clinical trial are sufficiently informed about
p.000004: the protocol, the investigational medicinal product (s), and the clinical trial's duties and functions.
p.000004: 4.3. Medical care for participants
p.000004: 4.3.1. Responsibility for all clinical trial related medical decisions lies with a qualified physician, or
p.000004: where appropriate, by a dentist who is a researcher or co-investigator in a clinical trial.
p.000004: 4.3.2. During and after the participation of the subjects in the clinical trial, the researcher guarantees the provision
p.000004: sufficient medical surveillance of the participants in relation to any adverse event, incl. clinically important
p.000004: laboratory test related results. The researcher informs the patient of the need for medical
p.000004: monitoring for the additional illness he has identified.
p.000004: 4.3.3. If the participant has a physician and if his or her physician has agreed to
p.000004: be informed, the investigator informs him or her of the patient's involvement in the clinical trial.
p.000004: 4.3.4. Although the participant is not required to explain the reasons for withdrawal from the clinical trial,
p.000004: the researcher may endeavor to identify these causes, while fully respecting the patient's rights.
p.000004: 4.4. Correspondence with the Ethics Committee
p.000004: 4.4.1. Before starting the clinical trial, the researcher must have a written date
p.000004: a positive opinion from the Ethics Committee on the clinical trial protocol, the form in writing
p.000004: consent, changes to consent form, patient recruitment procedures (eg announcements) and any other written
p.000004: information to be provided to the participant.
p.000004: 4.4.2. The researcher shall submit to the Ethics Committee a copy of the current brochure of the investigating physician as
p.000004: application of the written request to the Ethics Committee for opinion. If changes occur during the clinical trial
p.000004: in the booklet, the researcher presents to the Ethics Committee a new copy including the changes.
p.000004: 4.4.3. During the clinical trial, the investigator shall submit to the Ethics Committee for review
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p.000004: according to their ability to understand and personally sign and date the written informed
p.000004: consent (if able).
p.000004: 4.8.13. Except as indicated in section 4.8.14, a non-therapeutic trial (ie, a trial in which
p.000004: direct clinical benefit is provided for participants) is conducted on individuals who have personally signed and dated
p.000004: of the informed consent form.
p.000004: 4.8.14. Non-therapeutic trials may be conducted on individuals with the consent of their legal representatives
p.000004: only when:
p.000004: 4.8.14.1. test objectives cannot be achieved by testing participants who
p.000004: may personally give informed consent;
p.000004: 4.8.14.2. the foreseeable risks to persons are small;
p.000004: 4.8.14.3. the negative impact on participants is minimal and low;
p.000004: 4.8.14.4. the clinical trial is not prohibited by law;
p.000004: 4.8.14.5. the authorization / opinion of the Ethics Committee explicitly mentions the inclusion of
p.000004: it is precisely such persons and the written permission / affirmation covers this aspect.
p.000004: Such trials (to the extent that the exception is justified) shall be conducted on patients suffering from
p.000004: disease or condition for which the investigational medicinal product is intended. The participants in these
p.000004: tests shall be strictly monitored and withdrawn in the event of undue damage.
p.000004: 8/4/15 In emergencies where the immediate consent of the participant is not possible, it is required
p.000004: the consent of his legal representative, if any. When the direct consent of the participant and of
p.000004: its legal representative cannot be obtained, inclusion can be made if necessary
p.000004: an immediate decision to save the patient's life as required by the protocol and / or other
p.000004: place, through the written favorable opinion of the Ethics Committee, with a view to retaining rights,
p.000004: the safety and well-being of the individual and ensuring compliance with applicable regulatory requirements.
p.000004: The person or his legal representative shall be informed as soon as possible of the clinical trial and should
p.000004: be asked to document their agreement
p.000004: to continue participation in the clinical trial according to the procedure of item 4.8.10.
p.000004: 4.9. Documents and reports
p.000004: 4.9.1. The researcher ensures the accuracy, completeness, legibility and timely reporting of the data
p.000004: of the client in the clinical patient records (CCPs), as well as in all required reports.
p.000004: 4.9.2. The data obtained from source documents and recorded in the CCP is contained in these
p.000004: source documents, and discrepancies are explained.
p.000004: 4.9.3. Any change or correction to the CCP shall be dated, initials and (if necessary) shall be dated
p.000004: explains and should not doubt the original entry (ie, the trace of the check is kept).
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p.000004: analyzes integrated into a single report.
p.000004: 1.13. Medicinal product for comparison
p.000004: Tested or authorized medicinal product (aka active control) or placebo used for
p.000004: comparison during a clinical trial.
p.000004: 1.14. Conformity (as regards test)
p.000004: Compliance with all requirements - related to the test, the requirements of the DCT and the applicable ones
p.000004: regulations.
p.000004: 1.15. Confidentiality
p.000004: Preventing the disclosure by persons other than authorized persons of information belonging to
p.000004: the contracting authority or the identity of the participants.
p.000004: 1.16. Contract
p.000004: A written, dated and signed agreement between two or more parties setting out all the measures under
p.000004: assignment, assignment of tasks and responsibilities and, if applicable, financial matters. The protocol may
p.000004: to serve as the basis of a contract.
p.000004: 1.17. Coordinating committee
p.000004: Commissioner-designate committee to coordinate multicenter activities
p.000004: clinical trials.
p.000004: 1.18. Coordinating researcher
p.000004: Researcher appointed to coordinate researchers from the various multicenter centers
p.000004: testing.
p.000004: 1.19. Contract Research Organization (DIO)
p.000004: A natural or legal person or scientific organization that has contracted with the contracting authority to perform one or
p.000004: more than the test-related functions and duties of the contracting authority.
p.000004: 1.20. Direct access
p.000004: Permission to examine, analyze, verify and reproduce all records and reports that are relevant for evaluation
p.000004: of one clinical trial after authorization. Each country (e.g., local or foreign regulatory authorities,
p.000004: the contracting authorities and the contracting authorities) with direct access shall take all necessary precautions
p.000004: measures in accordance with the applicable regulatory requirements to preserve the confidentiality of
p.000004: the participants and the information held by the client.
p.000004: 1.21. Documentation
p.000004: All recordings in any form (including, but not limited to, written, electronic, magnetic, optical,
p.000004: electroencephalography, radiography, electrocardiograms, chromatograms) describing or recording the method,
p.000004: the conduct and / or outcome of the test, the factors affecting the test and the action taken.
p.000004: 1.22. Basic clinical trial dossier
p.000004: The main dossier of a clinical trial consists of basic documents that are either self-contained or
p.000004: together they allow evaluation of the clinical trial and the quality of the results obtained.
p.000004: 1.23. Basic documents
p.000004: Documents that, individually or together, allow evaluation of the conduct of the clinical trial and
p.000004: the quality of the results obtained.
p.000004: 1.24. Good Clinical Practice (DCT)
p.000004: The set of internationally recognized ethical and scientific quality requirements that are respected in planning,
p.000004: conducting, reporting and reporting clinical trials to ensure that data and reporting
p.000004: the results are plausible and accurate and that the rights, privacy and confidentiality of the participants are preserved.
p.000004: 1.25. Independent Evaluation Committee
p.000004: Independent evaluation committee that can be set up by the contracting authority to evaluate certain
p.000004: time intervals of a clinical trial, safety data, baseline parameters
p.000004: efficiency and to formulate recommendations to the contracting authority whether to continue, change or terminate
p.000004: the test.
...
p.000004: 4.8.10.4. the procedures to be performed during the clinical trial, including
p.000004: invasive manipulations;
p.000004: 4.8.10.5. the obligations of the participants;
p.000004: 4.8.10.6. those aspects of the clinical trial that are experimental;
p.000004: 4.8.10.7. reasonably foreseeable risks or inconveniences to participants, as well as to an embryo, fetus or infant,
p.000004: when necessary;
p.000004: 4.8.10.8. reasonably expected benefits; participants are informed of cases where no clinical benefit is expected;
p.000004: 4.8.10.9. the alternative procedures and treatment courses that are possible for the participants and important
p.000004: their potential risks and benefits;
p.000004: 4.8.10.10. compensation and / or possible treatment for participants in case of clinical trial related impairment;
p.000004: 4.8.10.11. anticipated, in proportion to time participation, payment for volunteers / patients
p.000004: their participation in the clinical trial, if any;
p.000004: 4.8.10.12. estimated costs for participants to participate in the clinical trial;
p.000004: 8/4/13 explanation that participation in the clinical trial is voluntary and that the participant may refuse to participate
p.000004: or withdraw at any time without the penalty or loss of benefits that the participant may
p.000004: to receive otherwise;
p.000004: 4.8.10.14. indicate that the monitoring, reviewing, ethics committee and regulatory bodies are
p.000004: provided access to the participant's original medical records for verification of clinical procedures
p.000004: testing and / or data, ensuring that the patient's personal data is protected in accordance with applicable laws and
p.000004: regulations, and by signing the written informed consent form, the participant or his or her legal
p.000004: the representative agrees to such access;
p.000004: 8/4/15 that the identification documents of the participant will be kept confidential and the data
p.000004: they will not be disclosed in accordance with applicable laws and regulations; in case of publication of
p.000004: results of the clinical trial of
p.000004: participants will remain confidential;
p.000004: 8/4/16 explanation that the participant or his legal representative will be notified in a timely manner if any
p.000004: new information that may influence their desire to continue participating in the clinical trial;
p.000004: 8/4/17 contact persons for further information regarding the clinical trial, contact persons for
p.000004: information on the rights of participants and those responsible for a clinical trial related disability;
p.000004: 4.8.10.18. the foreseeable circumstances and / or reasons why the participation may be terminated;
p.000004: 8/4/19/19 the expected duration of patient / healthy volunteer participation in the clinical trial;
p.000004: 4.8.10.20. the approximate number of participants.
p.000004: 4.8.11. Prior to participating in the clinical trial, each participant or his legal representative receives
p.000004: a copy of the signed and dated written informed consent form and any other
p.000004: information provided to participants. During the clinical trial, each participant or his or her
p.000004: the legal representative receives a copy of the modified informed consent form as well as the changes
p.000004: in any other written information provided to participants.
p.000004: 4.8.12. When a clinical trial (therapeutic or non-therapeutic) requires the inclusion of participants only
...
p.000004: applicable regulations.
p.000004: The researcher shall take measures to prevent the accidental or premature destruction of these documents.
p.000004: Upon completion of the study, the investigator shall provide the contracting entity with some of the clinical documentation
p.000004: testing as specified in the protocol and / or other contract with the contracting entity.
p.000004: 4.9.5. The main documents are kept for the longest of the specified periods:
p.000004: 4.9.5.1. fifteen years after the end of the clinical trial;
p.000004: 4.9.5.2. two years after the last marketing authorization in a region covered by the International Conference
p.000004: on harmonization, or until the procedure has been completed or the intention is not to obtain
p.000004: authorization for use in the region covered by the International Conference on Harmonization;
p.000004: 4.9.5.3. two years from the formal completion of the clinical development of the test product.
p.000004: Storage periods may be longer if required by other applicable regulatory requirements or if
p.000004: this is agreed with the contracting authority. The contracting authority shall inform the researcher in writing when the documents need not be submitted
p.000004: are stored more according to item 5.5.12.
p.000004: 4.9.6. The clinical trial financial issues shall be documented by contract between the sponsor and the
p.000004: the researcher.
p.000004: 4.9.7. At the request of the monitoring person,
p.000004: the auditor / reviewer, ethics committee or regulatory authority, the researcher shall provide direct access to all
p.000004: clinical trial related documents.
p.000004: 4.10. Clinical trial progress reports
p.000004: 4.10.1. The researcher submits written reports on the progress of the clinical trial to the Ethics Committee once
p.000004: annually or more often if the Ethics Committee so requests.
p.000004: 4.10.2. The researcher shall promptly submit written reports to the contracting authority, the ethics committee and
p.000004: regulatory authorities for any changes that significantly affect the conduct of the clinical trial and / or
p.000004: increasing the risk for participants.
p.000004: 4.11. Safety reports
p.000004: 4.11.1. All serious adverse events shall be reported immediately to the contracting authority, except for those for
p.000004: which is not required by the protocol or other document (eg, the researcher's manual)
p.000004: immediate reporting. Immediate reporting is followed by detailed written reports. Instant and
p.000004: follow-up reports identify individuals by unique code numbers that identify participants in
p.000004: the clinical trial, instead of their names, personal identification numbers and / or addresses.
p.000004: The researcher complies with the applicable regulatory requirements for reporting to
p.000004: the unexpected serious adverse reactions of the regulatory authorities and the ethics committee.
p.000004: 4.11.2. Adverse events and / or laboratory results beyond the reference limits specified in the protocol as
...
p.000004: the medical establishment, the ethics committee and the regulatory body of the country where the center of the
p.000004: the study by providing them with a detailed written explanation of the suspension or closure.
p.000004: 4.12.3. If the Ethics Committee withdraws or terminates its affirmative opinion on a test in accordance with para.
p.000004: 3.1.2.4. and 3.3.8 the researcher informs the respective medical institution and the client, presenting them in detail
p.000004: a written explanation of termination or withdrawal.
p.000004: 4.13. Final reports from the researcher
p.000004: Upon completion of the clinical trial, the researcher shall notify the medical establishment, submit to the
p.000004: ethics committee summary of test results and all required reports of regulatory
p.000004: organs.
p.000004: 5. Contracting authority
p.000004: 5.1. Quality assurance and control
p.000004: 5.1.1. The contracting authority is responsible for the implementation and maintenance of quality and control systems
p.000004: through written standard operating procedures to ensure that the clinical trial is also conducted
p.000004: the data is collected, documented (recorded) and reported in accordance with the plan, GCP and applicable regulations
p.000004: requirements.
p.000004: 5.1.2. The contracting authority is responsible for securing an agreement between the researchers, Contract Research
p.000004: organization (DIO) and regulatory authorities to gain direct access to all sites
p.000004: the conduct of the clinical trial,
p.000004: sources / documents of information and reports from monitoring and verifications by the contracting authority, as well as
p.000004: inspections by local or foreign regulatory authorities.
p.000004: 5.1.3. At each stage of data processing, quality control is applied to confirm that all data is
p.000004: reliable and handled properly.
p.000004: 5.1.4. The contracts concluded between the sponsor and the researcher and any other party to the clinical trial are written,
p.000004: as part of the plan or in an additional agreement.
p.000004: 5.2. Contract research organization
p.000004: 5.2.1. The contracting authority may delegate all or part of its obligations to other physical and / or physical persons
p.000004: legal entities referred to as DIOs. Notwithstanding the assignment of obligations to other persons, the contracting authority
p.000004: bears the overall responsibility for conducting the study in accordance with the DCT and the validity of the findings
p.000004: data.
p.000004: The contracting research organization is obliged to put in place quality control and assurance procedures
p.000004: quality.
p.000004: 5.2.2. All contracts between the sponsor and other parties involved in the clinical trial are written and part of
p.000004: from the plan or other separate part.
p.000004: Any transfer of a clinical trial related DIO obligation and function shall be documented in writing.
p.000004: 5.2.3. All clinical-related duty and function not specifically assigned,
p.000004: remain with the contracting authority.
...
p.000004: 5.5. Conduct clinical trial, data processing and recordkeeping
p.000004: 5.5.1. The contracting authority shall employ persons with appropriate qualifications to supervise the overall conduct of the
p.000004: clinical trial, data processing and verification, statistical analysis and
p.000004: the preparation of the reports.
p.000004: 5.5.2. The contracting authority may appoint an independent committee to evaluate the results in order to track the progress of one
p.000004: clinical trial, incl. safety data and critical performance parameters for certain
p.000004: intervals, and which recommends that the contracting entity continue, modify, or terminate the clinical trial.
p.000004: The Commission must have and follow written standard operating procedures for its work and yes
p.000004: keep written records of all its meetings.
p.000004: 5.5.3. In the case of electronic support for clinical trial records and / or remote documents
p.000004: electronic data systems of the contracting authority:
p.000004: 5.5.3.1. guarantees and documents that electronic data processing systems
p.000004: comply with the approved requirements of the contracting authority for completeness, accuracy, reliability and have been validated;
p.000004: 5.5.3.2. maintains a SEN for the use of these systems;
p.000004: 5.5.3.3. ensure that systems are prepared to allow data to be changed as you change
p.000004: document, and it is not possible to delete the entered data (ie, a trace is maintained for verifying the data and
p.000004: for editing);
p.000004: 5.5.3.4. maintains a security system that prevents unauthorized access to the data;
p.000004: 5.5.3.5. maintains a list of authorized persons entitled to make changes to the data referred to in points 4.1.5 and 4.9.3;
p.000004: 5.5.3.6. maintains adequate maintenance and storage of data backups;
p.000004: 5.5.3.7. supports a system that prevents code from being detected.
p.000004: 5.5.4. In the case of data transformation during processing it is always necessary
p.000004: make it possible to compare and monitor the original data with the processed data.
p.000004: 5.5.5. The contracting authority shall use the unambiguous participant identification code in accordance with paragraph 1.55, which
p.000004: allows recognition of all reported data for each individual participant.
p.000004: 5.5.6. The contracting entity or other data holder shall retain all specific basic documents relating to it
p.000004: to the clinical trial referred to in item 8 "Basic documents for conducting a clinical trial".
p.000004: The contracting authority shall ensure that appropriate storage conditions are in place to ensure that the documentation is maintained
p.000004: unchanged within the set deadlines.
p.000004: The contracting authority shall designate in writing the persons responsible for the archiving. The access to the archived documentation is
p.000004: limited except for specified persons.
p.000004: 5.5.7. The contracting authority shall keep all original documentation of the clinical trial referred to in paragraph 2.
p.000004: 8, and patient identification codes for at least 15 years after completion or termination
p.000004: the test.
p.000004: The contracting authority shall keep all specific basic documents in accordance with the applicable regulations
p.000004: requirements of the country (s) in which the medicinal product is authorized and / or where
p.000004: the contracting authority intends to apply for a permit (s).
p.000004: 5.5.8. Upon termination of the study program for the investigational medicinal product, the contracting entity shall keep
p.000004: the documentation at least two years after the end of the last study with the product under test.
p.000004: These documents shall be kept for a longer period if required by other regulations or by
p.000004: the contracting authority.
p.000004: 5.5.9. If the sponsor discontinues the clinical development of the investigational medicinal product, it is obliged to
p.000004: notified all clinical trial investigators and all regulatory authorities.
p.000004: 5.5.10. Any transfer of ownership of the data shall be documented and reported to the relevant regulatory authorities
p.000004: bodies and as indicated in the applicable regulatory requirements. The new data owner is responsible for
p.000004: the storage and archiving of the documentation in accordance with 5.5.7, 5.5.8 and 5.5.9.
...
p.000004: collecting unused quantities from patients and returning the unused quantities to the client
p.000004: the investigational medicinal product (or destruction or otherwise absorption, if authorized by
p.000004: the contracting authority and complies with the applicable regulatory requirements).
p.000004: 5.14.4. The contracting authority:
p.000004: 5.14.4.1. guarantee the timely delivery of the investigational medicinal product to the investigators;
p.000004: 5.14.4.2. keeps records documenting the sending, receiving, distribution,
p.000004: the return and destruction of the tested medicinal product in accordance with item 8;
p.000004: 5.14.4.3. maintains a system for recovering and documenting tested medicinal products
p.000004: reimbursement (ie for insufficient return of the medicinal product, return upon completion of
p.000004: clinical trial, expiry date);
p.000004: 5.14.4.4. maintains a system for destroying / transmitting to other persons unused quantities and documentation thereof
p.000004: destruction / transmission.
p.000004: 5.14.5. The contracting authority:
p.000004: 5.14.5.1. ensure that the medicinal product is stable throughout its use;
p.000004: 5.14.5.2. stores sufficient quantities of the investigational medicinal product used during the clinical trial
p.000004: testing to confirm the specifications if necessary and keep records of
p.000004: analysis and characteristics of the test batch;
p.000004: 5.14.5.3. store the samples to the extent that stability allows, until the analyzes of the data from the
p.000004: the clinical trial or for a longer period if required by other applicable regulatory requirements.
p.000004: 5.15. Access to documentation
p.000004: 5.15.1. The contracting entity shall document in the record or other written agreement that the principal investigator / institution,
p.000004: the study center will provide direct access to clinical data sources / documents
p.000004: testing for monitoring, verification, review by the ethics committee and inspection by the regulatory authorities.
p.000004: 5.15.2. The Contracting Authority verifies that all participants have given their written consent for direct access to theirs
p.000004: original medical records for conducting clinical-related monitoring, inspections,
p.000004: review by ethics and inspection committee of
p.000004: regulatory authorities.
p.000004: 5.16. Safety information
p.000004: 5.16.1. The contracting authority is responsible for the continuous safety assessment of the investigational medicinal product
p.000004: product.
p.000004: 5.16.2. The sponsor shall inform the BDA, the Ethics Committee and the researchers of any new information that
p.000004: may pose a threat to the health and well - being of patients, affecting the course of
p.000004: study or change the BDA's authorization to conduct the study and / or change the positive
p.000004: opinion of the ethics committee to continue the clinical trial.
p.000004: 5.16.3. The contracting authority shall keep detailed records of all reports of suspected adverse events that have occurred
p.000004: when using the investigational medicinal product for which it has been informed by the investigator or from another source
p.000004: of information.
p.000004: 5.16.4. The assignor evaluates the adverse events in terms of severity, expectation and
p.000004: causal connection. The contracting authority shall develop and implement procedures for evaluating adverse events for
p.000004: severity, expectation and cause and effect in accordance with published International Guidelines
p.000004: harmonization conference, the European Commission and the European Medicines Agency.
...
p.000004: 5.19.1. Purpose
p.000004: The purpose of the verification of the contracting entity, which is independent and separate from the routine functions of the executing entity
p.000004: monitoring or quality control functions should be an assessment of the conduct of the clinical trial and
p.000004: compliance with the protocol, SOP, DCT and applicable regulatory requirements.
p.000004: 5.19.2. Selection and qualifications of examiners
p.000004: 5.19.2.1. The contracting authority appoints persons who are independent of the clinical trials / systems to carry out the checks.
p.000004: 5.19.2.2. The contracting authority must ensure that the examiners are qualified in training and training
p.000004: an attempt to properly conduct checks. The qualifications of the examiners are documented.
p.000004: 5.19.3. Verification procedures
p.000004: 5.19.3.1. The sponsor shall ensure that the verification of clinical trials / systems is carried out in accordance with
p.000004: written procedures of the contracting authority as to what and how to check, frequency of inspection, form and
p.000004: the content of the inspection reports.
p.000004: 5.19.3.2. The plan and procedures for verifying a clinical trial by the sponsor are guided by the importance
p.000004: the clinical trial, the number of participants in the clinical trial, the type and complexity of the clinical trial
p.000004: testing, the degree of risk to participants and any problems identified.
p.000004: 5.19.3.3. The examiner's observations and findings shall be documented.
p.000004: 5.19.3.4. Regulatory authorities may require access to an audit report for each
p.000004: a particular case where there is evidence of a serious non-compliance with the DCT or in administrative or
p.000004: court proceedings.
p.000004: 5.19.3.5. When required by applicable law or regulation, the contracting authority shall submit a certificate of inspection.
p.000004: 5.20. Violation
p.000004: 5.20.1. In the event of a breach by the researcher or by the research member (s)
p.000004: the contracting authority shall take immediate action on the protocol, SOP, DCP and / or applicable regulatory requirements
p.000004: intervention to maintain compliance.
p.000004: 5.20.2. If, during monitoring and / or inspection, it is found that a material breach of
p.000004: the fault of the researcher, the contracting authority shall terminate his participation in the clinical trial and shall inform in due time
p.000004: regulatory authorities where the breach results in termination of the investigator's involvement.
p.000004: 5.21. Premature termination or termination of testing
p.000004: If a test is prematurely terminated or discontinued, the contracting authority shall be bound
p.000004: inform the investigator and the regulatory authorities in a timely manner of termination or termination and the reasons
p.000004: for that. The researcher or the contracting authority shall, in due time, comply with the applicable regulatory requirements
p.000004: inform the Ethics Committee, giving the reasons for termination or termination.
p.000004: 5.22. Clinical trial / study reports
...
p.000004: time of the clinical trial.
p.000004: 6.6.3. Procedures to monitor participants' assistance with treatment.
p.000004: 6.7. Evaluation of efficacy
p.000004: 6.7.1. Definition of efficacy parameters.
p.000004: 6.7.2. Methods and time for evaluating, recording and analyzing performance parameters.
p.000004: 6.8. Safety assessment
p.000004: 6.8.1. Definition of safety parameters.
p.000004: 6.8.2. Methods and time for evaluating, recording and analyzing safety parameters.
p.000004: 6.8.3. Procedures for obtaining reports and for recording and reporting adverse events and related events
p.000004: diseases.
p.000004: 6.8.4. The type and continuation of follow-up of participants after adverse events.
p.000004: 6.9. Statistics
p.000004: 6.9.1. Description of the statistical methods to be used, incl. all planned in time
p.000004: interim analyzes.
p.000004: 6.9.2. Number of persons envisaged to be included. In the case of multicenter
p.000004: test indicates the estimated number of persons for each individual center. Reason for choosing the size of
p.000004: the sample, including the impact on (or the calculation of) the power of the clinical trial and the reason for the
p.000004: holding it.
p.000004: 6.9.3. Significance level used.
p.000004: 6.9.4. Criteria for termination of the clinical trial.
p.000004: 6.9.5. Procedures for reporting missing, unused or incorrect data.
p.000004: 6.9.6. Procedures for reporting all deviations from the original statistical plan (all required)
p.000004: deviations from the original statistical plan should be described and justified in the protocol and / or in the final
p.000004: report).
p.000004: 6.9.7. Choosing the participants to be included in the analysis (e.g., all randomized participants,
p.000004: all dose recipients, all relevant participants, evaluable participants).
p.000004: 6.10. Direct access to original data / documents
p.000004: The sponsor shall ensure that the record or other written agreement states that the investigator will authorize
p.000004: monitoring, review, review by the Ethics Committee and inspection by regulatory authorities through
p.000004: providing direct access to the original documents / data.
p.000004: 6.11. Quality control and quality assurance
p.000004: 6.12. Ethics
p.000004: Description of ethical aspects relevant to the clinical trial.
p.000004: 6.13. Maintaining data and storing documentation
p.000004: 6.14. Method of financing and insurance Indicate if not stated in a separate contract.
p.000004: 6.15. Data publication plan
p.000004: Indicate if not stated in a separate contract.
p.000004: 6.16. Applications
p.000004: 7. Researcher's brochure
p.000004: 7.1. Introduction
p.000004: The researcher's brochure is a collection of clinical and non-clinical data for the test product that
p.000004: are applicable in the process of testing medicinal products on humans. The purpose is to provide information to
p.000004: researchers and others involved in the clinical trial to facilitate understanding of the motives for
p.000004: study, to ensure compliance with the essential features of the protocol as they are
p.000004: dose, dose frequency / interval, route of administration of the product and monitoring procedures
p.000004: of safety. The researcher's brochure also provides information to support the clinical behavior of individuals
p.000004: - participants in the clinical trial. The information is presented in a concise, simple, balanced way
p.000004: and non-promotional form in a way that allows the physician or potential researcher to understand
p.000004: and be able to make a personal judgment as to the purpose of the proposed test to be accurate with respect to
p.000004: risk - benefit. A medical person is involved in the publication of the researcher's booklet
p.000004: qualification, and approval of the content is done by specialists in the relevant medical
p.000004: majors who compiled the data described.
...
p.000004: 8.3.6 Changes in Normal Values- Document changes X X
p.000004: in the norm-
p.000004: you / limits for medical / laboratory values and / or
p.000004: boundaries for
p.000004: rotary / technical procedures tests. and / or tests included in the plan
p.000004: 8.3.7 Changes in medical / laboratory - Document that X
p.000004: X
p.000004: the tests remain
p.000004: rotary / technical procedures / applicable throughout
p.000004: period
p.000004: tests: certificate; accreditation - in the clinical trial. tion; established quality con-
p.000004: troll and / or external quality assessment; any other validation
p.000004: 8.3.8
p.000004: Documents for sending the test product and links
p.000004: According to item 8.2.15 X X
p.000004: clinical trial materials
p.000004: 8.3.9 Certificate of analysis of new According to item 8.2.16 batches of test product
p.000004: 8.3.10 Visits per person reports - To be documented
p.000004: visits and
p.000004: the person monitoring the movements of the person,
p.000004: monitors
p.000004: toriing.
p.000004: 8.3.11 Additional correspondence, Document all
p.000004: agreements
p.000004: other than visits to valuable or meaningful comments on
p.000004: regarding of
p.000004: : letters, meeting reports, administration, minutes,
p.000004: violations,
p.000004: notes from telephone conversations conducting clinical
p.000004: testing and
p.000004: reporting of adverse events.
p.000004: 8.3.12 Signed forms of information- Document that
p.000004: consent is semi-
p.000004: early consent in accordance with the DCP and the Plan and is
p.000004: dated just before participation
p.000004: for each participant in the clinical exam-
p.000004: bath. Document permission as well
p.000004: for direct access (8.2.3).
p.000004: 8.3.13 Background documents Document the existence of
p.000004: and confirm the completeness of the semi-
p.000004: data. Include original
p.000004: documents related to the clinical exam-
p.000004: bath, medical treatment and history
p.000004: of the disease.
p.000004: 8.3.14 Signed, dated and completed - Document that
p.000004: the researcher or
p.000004: their clinical records of a patient-authorized team member
p.000004: confirms
p.000004: Entities (CCP) recorded observations.
p.000004: 8.3.15 Documenting Adjustments Document all
p.000004: changes / until-
p.000004: in the CCP, additions or corrections made to the CCP
p.000004: after filling in
p.000004: initial data.
p.000000: 0
p.000000: 0
p.000000: X
p.000000: X
p.000000: X
p.000000: X
p.000000: (copy)
p.000000: X
p.000000: (copy)
p.000000: X
p.000000: X
p.000000: X
p.000000: 0
p.000000: 0
p.000000: X
p.000000: (originals)
p.000000: X
p.000000: (originals)
p.000000: 8.3.16 Notice to the Contracting Authority Notification to the Contracting Authority X X by
p.000000: research-
p.000000: from the explorer for serious waders for serious unwanted
p.000000: events and
p.000000: adverse events and relevant relevant reports in
p.000000: in accordance with items 4, 11.
p.000000: reports
p.000000: 8.3.17 Notification by the Contracting Authority Notification by the Contracting Authority
p.000000: and / or from
p.000000: and / or by the investigator's investigator, where applicable
p.000000: applicable, to re-
p.000000: the regulatory bodies and the commission the regulatory bodies and the commission
p.000000: ethics for
...
Social / Age
Searching for indicator age:
(return to top)
p.000004: medicinal product in all species tested. The commentary on the findings includes absorption, local and
p.000004: the systemic bioavailability of the investigational medicinal product and its metabolites and their relationship with
p.000004: pharmacological and toxicological findings in animal species.
p.000004: 7.3.5.3. Toxicology
p.000004: A summary of the toxicological effects found in relevant studies conducted on different subjects shall be provided
p.000004: animal species, including the following: single dose toxicity; repeated dose toxicity
p.000004: dosing; carcinogenicity; special tests (eg irritability and sensitivity); reproductive toxicity;
p.000004: genotoxicity (mutagenicity).
p.000004: 7.3.6. Effects in humans
p.000004: A full description of the known effects of the tested product (s) on humans, including information on
p.000004: pharmacokinetics, metabolism, pharmacodynamics, dose response, safety, efficacy and other pharmacological
p.000004: actions. Whenever possible, a summary of each completed clinical trial as well as
p.000004: information regarding the results of any use of the test medicinal product to be tested
p.000004: different from clinical trials (eg post-market experience).
p.000004: 7.3.6.1. Pharmacokinetics and metabolism of the product in humans
p.000004: A summary of the pharmacokinetics of the investigational medicinal product shall be provided,
p.000004: which, if possible, includes the following: pharmacokinetics (including metabolism and absorption, binding to
p.000004: plasma proteins, distribution and elimination); bioavailability (where possible absolute and / or relative),
p.000004: using a dosage form for comparison; subgroups of the population (eg gender, age and impaired function)
p.000004: to an authority); interactions (eg product-product interactions or food effects); others
p.000004: pharmacokinetic data (eg, results from population-based studies conducted in clinical trials).
p.000004: 7.3.6.2. Safety and efficiency
p.000004: A summary of information obtained from previous human clinical trials (healthy volunteers) is provided
p.000004: and / or patients) for the safety, pharmacodynamics, efficacy and dose response of the product (s) tested
p.000004: (and their metabolites where appropriate). The conclusions of this information are commented. Where they are
p.000004: completed a large number of clinical trials, the use of safety and efficacy summaries of
p.000004: multiple sub-group indication tests may be representative of the data. Summaries can
p.000004: also be presented in tabular form for adverse reactions for all clinical trials (incl.
p.000004: those for all testimony tested). Important differences in trends / incidence of
p.000004: side effects against indications or subgroups.
p.000004: A description of the potential risks and undesirable effects is provided
p.000004: reactions based on direct experience with the study drug
p.000004: product and related products, as well as precautions or special observations that
p.000004: to be carried out during the tested use of the medicinal product (s).
p.000004: 7.3.6.3. Experience after authorization for use
p.000004: Indicate the countries in which the test medicinal product is authorized. Commented
p.000004: any relevant information obtained from use after authorization (eg formulas, doses, routes of administration or administration)
...
p.000000: 2.2. Non-clinical pharmacology, pharmacokinetics and toxicology
p.000000: 2.2.1. Reagents and consumables used in toxicity tests
p.000000: 2.2.2. Integrated assessment of the data set
p.000000: 2.2.3. List of tests performed and bibliography
p.000000: 2.2.4. Opinion on compliance with Good laboratory practice and bioanalytical methods
p.000000: 2.2.5. Bibliography
p.000000: 2.3. Clinical data
p.000000: 2.3.1. Clinical pharmacology
p.000000: 2.3.2. Clinical pharmacokinetics
p.000000: 2.3.3. Application to humans
p.000000: 2.4. Benefit and risk assessment
p.000000: 3. List of figures (It is advisable to attach a list of figures with their titles and number
p.000000: page)
p.000000: 4. List of tables
p.000000: Annex No. 3 to Art. 12
p.000000: (Amended, SG No. 77/2016, effective 04.10.2016) Changes in the data leading to a significant change
p.000000: 1. Protocol related changes
p.000000: 1.1. Change in the purpose of the study.
p.000000: 1.2. Change in the design and / or methodology of the study or in the preliminary information provided
p.000000: bases its scientific value.
p.000000: 1.3. Changes to the following survey documents:
p.000000: 1.3.1. an informed consent;
p.000000: 1.3.2. participant information;
p.000000: 1.3.3. information about the legal representative and / or carer of the participant;
p.000000: 1.3.4. questionnaires, letters of invitation, letters to the doctor and other researchers.
p.000000: 1.4. Change in patient recruitment procedure.
p.000000: 1.5. Change in performance metrics.
p.000000: 1.6. Change in plan for taking biological research materials.
p.000000: 1.7. Add or remove studies and / or tests.
p.000000: 1.8. Changing age ranges for participation.
p.000000: 1.9. Change in inclusion and exclusion criteria.
p.000000: 1.10. Change in safety monitoring procedures.
p.000000: 1.11. Change in the duration of use of the test product.
p.000000: 1.12. Change in the way the test product is used.
p.000000: 1.13. Change medicine for comparison.
p.000000: 1.14. Change in statistical plan.
p.000000: 1.15. Any change related to the safety and physical and / or intellectual integrity of the participants
p.000000: or the risk / benefit ratio of the study.
p.000000: 1.16. Change in end of study definition.
p.000000: 2. Changes in the administrative organization of the study:
p.000000: 2.3. Change of sponsor and / or his authorized representative.
p.000000: 2.4. Change of approved research center.
p.000000: 2.5. Appointment of a new principal investigator.
p.000000: 2.6. Inclusion of a new research center.
p.000000: 2.7. Appointment of a new principal investigator at an approved research center.
p.000000: 2.8. Change in the terms of the insurance or the procedure for indemnification of the study participants.
p.000000: 2.9. Other significant changes to the protocol and / or accompanying application initially
p.000000: documentation.
p.000000: 3. Changes concerning the quality of the investigational medicinal product:
p.000000: 3.3. Changing the name of the tested product from the code of the assignor to an international non-patent name.
p.000000: 3.4. Changes in primary packaging materials.
p.000000: 3.5. Change of importer for medicinal products made outside the EU.
p.000000: 3.6. Change of manufacturer of the drug substance.
...
Social / Child
Searching for indicator child:
(return to top)
p.000004: organization
p.000004: Dated, documented permission / affirmative opinion of
p.000004: CE for the following:
p.000004: Protocol and amendments to the CCP
p.000004: Informed Consent Form Any other information provided to participants
p.000004: Recruitment announcement (if used)
p.000004: Participant compensation All other documents subject to approval / opinion
p.000004: Composition of the Ethics Committee / Appointment Order
p.000004: Authorization / notification of regulatory authorities
p.000004: CV and / or other document
p.000004: ment proving the qualifications of the principal investigator and
p.000004: X
p.000004: X 0
p.000004: Document that the X clinical exam-
p.000004: This was considered by a committee on
p.000004: ethics and has received
p.000004: positively-
p.000004: will. To identify the number and date-
p.000004: and the version of the documents.
p.000004: Document that the X Ethics Committee
p.000004: It is compiled in accordance with the DCT.
p.000004: Document that X permission is
p.000004: received / the notice period expired before the clinical start
p.000004: testing and in accordance with
p.000004: you have regulatory requirements.
p.000004: Document the X qualifications and
p.000004: reliability for
p.000004: conducting the clinical trial and / or for
p.000004: X
p.000004: X X
p.000004: X
p.000004: (If required)
p.000004: X
p.000004: X
p.000004: rendering me-
p.000004: Researchers' child monitoring of participants.
p.000004: 8.2.11. Reference values / limits for Documentation X X
p.000004: normal stand-
p.000004: medical / laboratory / technical and / or boundaries for
p.000004: the tests.
p.000004: procedures and / or tests included in the protocol
p.000004: 8.2.12. Medical / laboratory / technical- Document X X
p.000004: the competence of
p.000004: procedures / tests: certificate; the labs for
p.000004: carrying out the necessary
p.000004: accreditation; established quality smoke tests and
p.000004: keeping hope-
p.000004: control and / or external evaluation of the reliability of the results. quality; other validation
p.000004: 8.2.13. Label template (s) to be documented 0
p.000004: X
p.000004: compliance with
p.000004: attached to the package of test regulations for
p.000004: labeling and that in-
p.000004: the product structure presented to the participants,
p.000004: are appropriate.
p.000004: 8.2.14. Exam Instructions - Document X
p.000004: X
p.000004: instructions necessary
p.000004: and related storage clips,
p.000004: packing, unpacking
p.000004: night test materials (if shedding and dispensing
p.000004: of tests
p.000004: are not included in the product brochure and related
p.000004: the clinical
p.000004: researcher) testing materials.
p.000004: 8.2.15. Shipping and Delivery Documents- Document X X dates
p.000004: of consignments,
p.000004: of the product under test and the batch numbers of
p.000004: tests
p.000004: clinical trial product and method of dispatch. Call-
p.000004: materials left tracking batch of pro-
p.000004: the terms of delivery and accountability.
p.000004: 8.2.16. Certificate of analysis of the document- 0
p.000004: X
p.000004: identity, number-
p.000004: the product of potency and the strength of
p.000004: the product to be
p.000004: used in the clinical trial.
p.000004: 2/8/17 Recognition Procedures in Documenting How, in X X
...
Searching for indicator children:
(return to top)
p.000004: his identity and used in place of the participant's name
p.000004: when reporting adverse events and / or other test-related data.
p.000004: 1.56. Clinical trial center
p.000004: The location (s) of study-related activities.
p.000004: 1.57. Unexpected side effect
p.000004: For unauthorized products - an adverse reaction whose nature, severity or outcome do not match
p.000004: of the information on the tested medicinal product referred to in the investigator's leaflet. They are allowed
p.000004: use of products - an adverse reaction not listed in the summary of product characteristics or
p.000004: whose character, weight or output do not correspond to the information given in the summary of product characteristics.
p.000004: 1.58. Vulnerable groups
p.000004: Individuals whose desire to participate in a clinical trial may be influenced by the expectation of benefit or by
p.000004: their position vis-à-vis senior officials in the hierarchy related to participation or non-participation, for example:
p.000004: medical, dental, pharmacy, or nursing students in pharmacy
p.000004: industry, serving in the military, and persons deprived of their liberty.
p.000004: Other vulnerable participants are patients with incurable diseases, people in nursing homes, the unemployed or
p.000004: beggars, emergency patients, ethnic minority groups, street children, vagrants, minors and such,
p.000004: who are unable to consent.
p.000004: 1.59. Well-being (of clinical trial participants)
p.000004: Physical and mental integrity of participants in the clinical trial
p.000004: 2. PRC principles
p.000004: 2.1. Clinical trials shall be conducted in accordance with the ethical principles set out in the Declaration of Conformity
p.000004: Helsinki and comply with DCT and applicable regulatory requirements.
p.000004: 2.2. Before starting a test, all the foreseeable risks are compared with the expected benefit
p.000004: individually for the participant and for the community. A clinical trial can only begin and continue if foreseeable
p.000004: the benefits justify the risks.
p.000004: 2.3. The rights, safety and well-being of test participants are paramount and
p.000004: stand above the interests of science and society.
p.000004: 2.4. Available non-clinical and clinical information on the investigational medicinal product should be sufficient
p.000004: support for the proposed clinical trial.
p.000004: 2.5. Clinical trials must be scientifically relevant and described in a clear and detailed manner
p.000004: protocol.
p.000004: 2.6. A clinical trial shall be conducted in accordance with a protocol that has been approved in advance
p.000004: by the Ethics Committee.
p.000004: 2.7. Medical monitoring and medical decisions, with regard to participants, are taken by the doctor or, where appropriate
p.000004: necessary - by a dentist.
p.000004: 2.8. Each person charged with conducting a clinical trial has education, qualification
p.000004: and attempting to fulfill the relevant test obligations.
p.000004: 2.9. Before entering a clinical trial, each participant is freely informed
...
Social / Ethnicity
Searching for indicator ethnic:
(return to top)
p.000004: controlling.
p.000004: 1.55. Participant identification code
p.000004: Unique identifier code for the designation of each participant in a clinical trial by the researcher in order to preserve
p.000004: his identity and used in place of the participant's name
p.000004: when reporting adverse events and / or other test-related data.
p.000004: 1.56. Clinical trial center
p.000004: The location (s) of study-related activities.
p.000004: 1.57. Unexpected side effect
p.000004: For unauthorized products - an adverse reaction whose nature, severity or outcome do not match
p.000004: of the information on the tested medicinal product referred to in the investigator's leaflet. They are allowed
p.000004: use of products - an adverse reaction not listed in the summary of product characteristics or
p.000004: whose character, weight or output do not correspond to the information given in the summary of product characteristics.
p.000004: 1.58. Vulnerable groups
p.000004: Individuals whose desire to participate in a clinical trial may be influenced by the expectation of benefit or by
p.000004: their position vis-à-vis senior officials in the hierarchy related to participation or non-participation, for example:
p.000004: medical, dental, pharmacy, or nursing students in pharmacy
p.000004: industry, serving in the military, and persons deprived of their liberty.
p.000004: Other vulnerable participants are patients with incurable diseases, people in nursing homes, the unemployed or
p.000004: beggars, emergency patients, ethnic minority groups, street children, vagrants, minors and such,
p.000004: who are unable to consent.
p.000004: 1.59. Well-being (of clinical trial participants)
p.000004: Physical and mental integrity of participants in the clinical trial
p.000004: 2. PRC principles
p.000004: 2.1. Clinical trials shall be conducted in accordance with the ethical principles set out in the Declaration of Conformity
p.000004: Helsinki and comply with DCT and applicable regulatory requirements.
p.000004: 2.2. Before starting a test, all the foreseeable risks are compared with the expected benefit
p.000004: individually for the participant and for the community. A clinical trial can only begin and continue if foreseeable
p.000004: the benefits justify the risks.
p.000004: 2.3. The rights, safety and well-being of test participants are paramount and
p.000004: stand above the interests of science and society.
p.000004: 2.4. Available non-clinical and clinical information on the investigational medicinal product should be sufficient
p.000004: support for the proposed clinical trial.
p.000004: 2.5. Clinical trials must be scientifically relevant and described in a clear and detailed manner
p.000004: protocol.
p.000004: 2.6. A clinical trial shall be conducted in accordance with a protocol that has been approved in advance
p.000004: by the Ethics Committee.
p.000004: 2.7. Medical monitoring and medical decisions, with regard to participants, are taken by the doctor or, where appropriate
p.000004: necessary - by a dentist.
p.000004: 2.8. Each person charged with conducting a clinical trial has education, qualification
...
Social / Fetus/Neonate
Searching for indicator fetus:
(return to top)
p.000004: sets the date of the written informed consent form after it, as well as any other written consent
p.000004: information is presented, read and explained to participants or their legal representatives and after
p.000004: having verbally confirmed their participation in the clinical trial and (if able) signed and
p.000004: personally set a date. By his signature, the witness confirms that the written informed consent form as well
p.000004: any other written information has been properly explained and understood by the participants or their legal information
p.000004: representatives and consent was given by the participants themselves or their legal representatives.
p.000004: 4.8.10. The written informed consent form and any other written information provided to participants,
p.000004: contains explanations for the following:
p.000004: 4.8.10.1. that the clinical trial is a scientific research process;
p.000004: 4.8.10.2. the purpose of the clinical trial;
p.000004: 4.8.10.3. the treatment (s) tested and the likelihood of any treatment being randomly assigned;
p.000004: 4.8.10.4. the procedures to be performed during the clinical trial, including
p.000004: invasive manipulations;
p.000004: 4.8.10.5. the obligations of the participants;
p.000004: 4.8.10.6. those aspects of the clinical trial that are experimental;
p.000004: 4.8.10.7. reasonably foreseeable risks or inconveniences to participants, as well as to an embryo, fetus or infant,
p.000004: when necessary;
p.000004: 4.8.10.8. reasonably expected benefits; participants are informed of cases where no clinical benefit is expected;
p.000004: 4.8.10.9. the alternative procedures and treatment courses that are possible for the participants and important
p.000004: their potential risks and benefits;
p.000004: 4.8.10.10. compensation and / or possible treatment for participants in case of clinical trial related impairment;
p.000004: 4.8.10.11. anticipated, in proportion to time participation, payment for volunteers / patients
p.000004: their participation in the clinical trial, if any;
p.000004: 4.8.10.12. estimated costs for participants to participate in the clinical trial;
p.000004: 8/4/13 explanation that participation in the clinical trial is voluntary and that the participant may refuse to participate
p.000004: or withdraw at any time without the penalty or loss of benefits that the participant may
p.000004: to receive otherwise;
p.000004: 4.8.10.14. indicate that the monitoring, reviewing, ethics committee and regulatory bodies are
p.000004: provided access to the participant's original medical records for verification of clinical procedures
p.000004: testing and / or data, ensuring that the patient's personal data is protected in accordance with applicable laws and
p.000004: regulations, and by signing the written informed consent form, the participant or his or her legal
p.000004: the representative agrees to such access;
...
Social / Incarcerated
Searching for indicator liberty:
(return to top)
p.000004: the location of the clinical trial to perform the basic test-related actions
p.000004: and / or make important decisions (eg, associates, graduate students, doctoral students).
p.000004: 1.54. Test participant
p.000004: A person who is enrolled in a clinical trial by receiving or participating in a test drug
p.000004: controlling.
p.000004: 1.55. Participant identification code
p.000004: Unique identifier code for the designation of each participant in a clinical trial by the researcher in order to preserve
p.000004: his identity and used in place of the participant's name
p.000004: when reporting adverse events and / or other test-related data.
p.000004: 1.56. Clinical trial center
p.000004: The location (s) of study-related activities.
p.000004: 1.57. Unexpected side effect
p.000004: For unauthorized products - an adverse reaction whose nature, severity or outcome do not match
p.000004: of the information on the tested medicinal product referred to in the investigator's leaflet. They are allowed
p.000004: use of products - an adverse reaction not listed in the summary of product characteristics or
p.000004: whose character, weight or output do not correspond to the information given in the summary of product characteristics.
p.000004: 1.58. Vulnerable groups
p.000004: Individuals whose desire to participate in a clinical trial may be influenced by the expectation of benefit or by
p.000004: their position vis-à-vis senior officials in the hierarchy related to participation or non-participation, for example:
p.000004: medical, dental, pharmacy, or nursing students in pharmacy
p.000004: industry, serving in the military, and persons deprived of their liberty.
p.000004: Other vulnerable participants are patients with incurable diseases, people in nursing homes, the unemployed or
p.000004: beggars, emergency patients, ethnic minority groups, street children, vagrants, minors and such,
p.000004: who are unable to consent.
p.000004: 1.59. Well-being (of clinical trial participants)
p.000004: Physical and mental integrity of participants in the clinical trial
p.000004: 2. PRC principles
p.000004: 2.1. Clinical trials shall be conducted in accordance with the ethical principles set out in the Declaration of Conformity
p.000004: Helsinki and comply with DCT and applicable regulatory requirements.
p.000004: 2.2. Before starting a test, all the foreseeable risks are compared with the expected benefit
p.000004: individually for the participant and for the community. A clinical trial can only begin and continue if foreseeable
p.000004: the benefits justify the risks.
p.000004: 2.3. The rights, safety and well-being of test participants are paramount and
p.000004: stand above the interests of science and society.
p.000004: 2.4. Available non-clinical and clinical information on the investigational medicinal product should be sufficient
p.000004: support for the proposed clinical trial.
p.000004: 2.5. Clinical trials must be scientifically relevant and described in a clear and detailed manner
p.000004: protocol.
p.000004: 2.6. A clinical trial shall be conducted in accordance with a protocol that has been approved in advance
...
Social / Infant
Searching for indicator infant:
(return to top)
p.000004: sets the date of the written informed consent form after it, as well as any other written consent
p.000004: information is presented, read and explained to participants or their legal representatives and after
p.000004: having verbally confirmed their participation in the clinical trial and (if able) signed and
p.000004: personally set a date. By his signature, the witness confirms that the written informed consent form as well
p.000004: any other written information has been properly explained and understood by the participants or their legal information
p.000004: representatives and consent was given by the participants themselves or their legal representatives.
p.000004: 4.8.10. The written informed consent form and any other written information provided to participants,
p.000004: contains explanations for the following:
p.000004: 4.8.10.1. that the clinical trial is a scientific research process;
p.000004: 4.8.10.2. the purpose of the clinical trial;
p.000004: 4.8.10.3. the treatment (s) tested and the likelihood of any treatment being randomly assigned;
p.000004: 4.8.10.4. the procedures to be performed during the clinical trial, including
p.000004: invasive manipulations;
p.000004: 4.8.10.5. the obligations of the participants;
p.000004: 4.8.10.6. those aspects of the clinical trial that are experimental;
p.000004: 4.8.10.7. reasonably foreseeable risks or inconveniences to participants, as well as to an embryo, fetus or infant,
p.000004: when necessary;
p.000004: 4.8.10.8. reasonably expected benefits; participants are informed of cases where no clinical benefit is expected;
p.000004: 4.8.10.9. the alternative procedures and treatment courses that are possible for the participants and important
p.000004: their potential risks and benefits;
p.000004: 4.8.10.10. compensation and / or possible treatment for participants in case of clinical trial related impairment;
p.000004: 4.8.10.11. anticipated, in proportion to time participation, payment for volunteers / patients
p.000004: their participation in the clinical trial, if any;
p.000004: 4.8.10.12. estimated costs for participants to participate in the clinical trial;
p.000004: 8/4/13 explanation that participation in the clinical trial is voluntary and that the participant may refuse to participate
p.000004: or withdraw at any time without the penalty or loss of benefits that the participant may
p.000004: to receive otherwise;
p.000004: 4.8.10.14. indicate that the monitoring, reviewing, ethics committee and regulatory bodies are
p.000004: provided access to the participant's original medical records for verification of clinical procedures
p.000004: testing and / or data, ensuring that the patient's personal data is protected in accordance with applicable laws and
p.000004: regulations, and by signing the written informed consent form, the participant or his or her legal
p.000004: the representative agrees to such access;
p.000004: 8/4/15 that the identification documents of the participant will be kept confidential and the data
...
Social / Laboratory Staff
Searching for indicator research staff:
(return to top)
p.000004: 4.8. Informed consent of participants
p.000004: 4.8.1. During the receipt and documentation of informed consent, the researcher complies
p.000004: the applicable regulatory requirements, the principles of the CPT and the ethical principles enshrined in the Declaration of
p.000004: Helsinki. In order to begin the clinical trial, the researcher must have a positive opinion in writing
p.000004: of the Ethics Committee on the written informed consent and any other written information to be provided
p.000004: provided to participants.
p.000004: 4.8.2. The written informed consent form and any other written information provided to participants shall be
p.000004: updates when important new information becomes available that may affect their consent. Each
p.000004: an updated form of written informed consent and written information should have a positive opinion of
p.000004: the ethics committee prior to its implementation. The participant or his legal representative shall be promptly informed
p.000004: notify when important new information becomes available that may affect their desire to
p.000004: continue to participate in the clinical trial. Communications regarding new information shall be documented
p.000004: timely.
p.000004: 4.8.3. Neither the principal investigator nor the research staff can coerce or give in
p.000004: mislead the person to participate or continue to participate in the clinical trial.
p.000004: 4.8.4. No oral or written information pertaining to the clinical trial, including the format for
p.000004: written informed consent may not contain words and expressions that coerce or sound coercive to the participant
p.000004: or his legal representative to waive any of his legal rights or to release or to impose
p.000004: discharge for negligence of the researcher, contracting authority, institution or
p.000004: their representatives.
p.000004: 4.8.5. The researcher or the person authorized by him / her shall inform the participant or in case he / she cannot give
p.000004: his consent, his legal representative for all aspects of the clinical trial, including
p.000004: the provision of written information and the favorable opinion of the Ethics Committee.
p.000004: 4.8.6. The language used in the oral or written information for the clinical trial, including the written form
p.000004: informed consent must be without medical terms and sufficiently accessible to be
p.000004: understood by the participant or his legal representative and, where appropriate, by the independent witness.
p.000004: 4.8.7. Prior to obtaining written informed consent, the Principal Investigator or a person authorized by him or her
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Social / Linguistic Proficiency
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p.000004: the ethics committee prior to its implementation. The participant or his legal representative shall be promptly informed
p.000004: notify when important new information becomes available that may affect their desire to
p.000004: continue to participate in the clinical trial. Communications regarding new information shall be documented
p.000004: timely.
p.000004: 4.8.3. Neither the principal investigator nor the research staff can coerce or give in
p.000004: mislead the person to participate or continue to participate in the clinical trial.
p.000004: 4.8.4. No oral or written information pertaining to the clinical trial, including the format for
p.000004: written informed consent may not contain words and expressions that coerce or sound coercive to the participant
p.000004: or his legal representative to waive any of his legal rights or to release or to impose
p.000004: discharge for negligence of the researcher, contracting authority, institution or
p.000004: their representatives.
p.000004: 4.8.5. The researcher or the person authorized by him / her shall inform the participant or in case he / she cannot give
p.000004: his consent, his legal representative for all aspects of the clinical trial, including
p.000004: the provision of written information and the favorable opinion of the Ethics Committee.
p.000004: 4.8.6. The language used in the oral or written information for the clinical trial, including the written form
p.000004: informed consent must be without medical terms and sufficiently accessible to be
p.000004: understood by the participant or his legal representative and, where appropriate, by the independent witness.
p.000004: 4.8.7. Prior to obtaining written informed consent, the Principal Investigator or a person authorized by him or her
p.000004: obliged to provide the participant or his or her legal
p.000004: representative sufficient time and opportunity to discuss the details of the clinical trial and yes
p.000004: decide whether or not to participate. All questions asked by the participant or his legal representative must
p.000004: replied in full.
p.000004: 4.8.8. Before engaging the participant, written informed consent must be signed personally and
p.000004: set the date by the participant or his legal representative and by the person interviewing the
p.000004: of the participant.
p.000004: 4.8.9. In case the participant or his legal representative cannot read during the discussion
p.000004: informed consent shall be provided by the presence of an independent witness. The witness also signs personally
p.000004: sets the date of the written informed consent form after it, as well as any other written consent
p.000004: information is presented, read and explained to participants or their legal representatives and after
p.000004: having verbally confirmed their participation in the clinical trial and (if able) signed and
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p.000004: 4. the significance of the data leading to the termination of the trial for other authorized clinical trials of
p.000004: the territory of the Republic of Bulgaria.
p.000004: Art. 17. All documents submitted to the Ethics Committee under Art. 103 LPPMM and the Executive Agency of the
p.000004: medicines bearing at least the following identification elements:
p.000004: 1. trial number from the European Clinical Trials Database;
p.000004: 2. protocol code;
p.000004: 3. version and date of the document.
p.000004: Art. 18. (1) The documentation for authorization, change and termination of a clinical trial shall be submitted to
p.000004: Bulgarian and / or English.
p.000004: (2) (amend. - SG 14/2012, amend. - SG 25/08) The documentation under art. 2, items 1, 2 and 5, art. 3, items 1, 2 and
p.000004: 6, Art. 4, para. 1, Vol. 2, Art. 6, para. 1, items 1 and 3, art. 7, items 1, 2, 3, 5 and 6, Art. 8, para. 1, Art. 9, Vol. 6, Art. 13, para. 1 and para.
p.000004: 2, items 1 and 2, art. 14, para. 1, Art. 15b, items 1, 2 and 3, art. 15c, items 1, 2 and 6, Art. 15d, para. 1, Vol. 2, Art. 15f, para. 1, Vol. 1, Art.
p.000004: 15g, items 1, 2 and 3, Art. 15h, para. 1 and para. 2, items 1 and 3 and Art. 16, para. 1 shall also be provided in Bulgarian.
p.000004: (3) (Amended, SG No. 14/2012) The documentation under Art. 8, para. 1, Art. 14, para. 1 and 3, Art. 15a, Art. 15h, para. 1, Art. 16,
p.000004: para. 1 shall also be provided in English.
p.000004: Art. 19. (1) (Amended, SG No. 14/2012) The Executive Director of the Executive Agency for Medicines
p.000004: approve by order samples of the applications under Art. 2, 8, 13, 14 and 15a and 15h, para. 1 and the notification under Art. 16.
p.000004: (2) The applications shall be submitted in a single copy, in paper and electronic form.
p.000004: (3) Applications in electronic form must be submitted in a format compatible with the requirements for entry into the European database.
p.000004: clinical trial data.
p.000004: (4) The contracting authority or the authorized person shall declare that the applications on electronic and hard copy contain identical
p.000004: information.
p.000004: Section V. Control
p.000004: Art. 20. (1) The control over the clinical trials conducted in the Republic of Bulgaria shall be exercised by the
p.000004: Art. 267, para. 3 ZLPHM State Inspectors.
p.000004: (2) Control over clinical trials conducted in the Republic of Bulgaria may also be exercised by
p.000004: officials of the Member States of the European Union and designated by the European Medicines Agency
p.000004: and its Scientific Committees.
p.000004: (3) Where necessary, inspectors may be assisted and assisted by experts designated by
p.000004: the Executive Director of the Executive Agency for Medicinal Products.
p.000004: (4) The control, carried out by the state inspectors, shall be carried out:
p.000004: 1. as a preliminary, current and follow-up in a clinical trial of a medicinal product;
p.000004: 2. in the course of a marketing authorization procedure;
p.000004: 3. as follow-up measures after authorization for use.
p.000004: (5) The contracting authority, the principal investigator and the researchers contracted shall be subject to control
p.000004: research organization, ethics committees, test center, manufacturing sites and control center
p.000004: the investigational medicinal product, the laboratories and any site and facility used during the test,
...
p.000004: § 2. To the applications, submitted before the entry into force of this Ordinance, for significant changes in the permit for holding
p.000004: the clinical trial of a medicinal product on the territory of the Republic of Bulgaria shall be submitted by the contracting authorities on time
p.000004: for three months the documentation provided for in the regulation.
p.000004: § 3. This Ordinance is issued on the grounds of Art. 82, para. 3, Art. 110, para. 2, Art. 116, para. 5, Art.
p.000004: 129, para. 3, Art. 142, para. 2 and Art. 145, para. 2 of the LPPHM and repeals Ordinance No. 14 of 2000 on the Terms and Conditions for Conducting
p.000004: clinical trials of medicines on humans (SG 73/00).
p.000004: Final provisions
p.000004: TO THE ORDER FOR AMENDING AND SUPPLEMENTING REGULATION No. 31 OF 2007 ON DEFINING THE RULES FOR GOOD CLINICAL PRACTICE
p.000004: (Official Gazette, issue 77 of 2016, effective 04.10.2016)
p.000004: § 3. The ordinance shall enter into force on the day of its promulgation in the State Gazette.
p.000004: Annex No. 1 to Art. 1, para. 1 (Amended, SG No. 14/2012)
p.000004: GOOD CLINICAL PRACTICE RULES
p.000004: Introduction
p.000004: Good clinical practice is the set of internationally recognized ethical and scientific quality requirements,
p.000004: which are adhered to in the design, conduct, reporting and reporting of clinical trials.
p.000004: Compliance with these requirements ensures public protection and protection of the rights, safety and health of
p.000004: test participants in accordance with the principles set out in the Helsinki Declaration and scientific
p.000004: value and reproducibility of clinical trial data.
p.000004: The purpose of DCP rules is to provide a single standard for the European Community, Japan and the United States in order to facilitate
p.000004: the mutual recognition of clinical trial data by their respective regulatory authorities.
p.000004: The DCT rules have been developed taking into account current good clinical practice in the European Union
p.000004: community, Japan and the United States, as well as those of Australia, Canada, Scandinavian countries and World Health
p.000004: organization.
p.000004: These rules must be followed when generating data from clinical trials that will
p.000004: be submitted to the regulatory authorities.
p.000004: The principles laid down in these rules may also apply to others
p.000004: clinical trials that could have an impact on human safety and health.
p.000004: 1. Definitions
p.000004: 1.1. Adverse Reaction (ADR)
p.000004: "Undesirable effect" is any undesirable and unintended response to a medicinal product that occurs with
p.000004: administration of the product at doses normally used for the treatment, prophylaxis or diagnosis of disease in
p.000004: people or for recovery, correction or
p.000004: modification of physiological function. In the case of a clinical trial - any undesirable or unforeseen
p.000004: response to the investigational medicinal product, regardless of the dose administered. The phrase "answered one
p.000004: "means that the cause and effect relationship is between the medicinal product and the adverse reaction
p.000004: at least a reasonable possibility, that is, the connection cannot be denied.
p.000004: 1.2. Adverse event
p.000004: Adverse event is any adverse change in health status observed with the administration of a medicinal product.
p.000004: to a patient or participant in a clinical trial that is not necessarily causally related to this treatment.
...
p.000004: product, whether or not it is causally related to the product.
p.000004: 1.3. Applicable requirements
p.000004: All regulatory requirements for conducting clinical trials with medicinal products.
p.000004: 1.4. Approval by the Ethics Committee
p.000004: Positive opinion from the Ethics Committee confirming that the clinical trial has been evaluated and can
p.000004: to be conducted at the established center under the conditions laid down by the Ethics Committee, the medical establishment, the CPT, and
p.000004: the applicable requirements.
p.000004: 1.5. Independent verification (audit)
p.000004: Systematic and independent evaluation of test-related obligations and assessment documents
p.000004: whether these obligations have been fulfilled, whether the data have been recorded, analyzed, carefully reported, in accordance with
p.000004: the protocol, standard operating procedures (SOPs) of the contracting entity, DCT and applicable regulatory requirements.
p.000004: 1.6. Certificate of verification
p.000004: Document from the verifier confirming that an inspection has been carried out.
p.000004: 1.7. Verification report
p.000004: Written evaluation of the verifier by the contracting authority for the results of the inspection.
p.000004: 1.8. Track for verification
p.000004: Documentation to track the sequence of events.
p.000004: 1.9. Blinding / masking
p.000004: A procedure in which one or more of the parties remain unaware of their assigned treatment
p.000004: preliminary agreement. Single-blind are usually trials in which patients remain unknown, a
p.000004: double-blind are trials in which patients, researchers, monitors, and sometimes
p.000004: data subjects remain unfamiliar with the treatment prescribed.
p.000004: 1.10. Clinical Patient Card (CCP)
p.000004: Printed, optical or electronic media prepared to record all the information required by the plan to report to
p.000004: the contracting authority for each individual participant.
p.000004: 1.11. Clinical trial / study
p.000004: Clinical trial of a medicinal product is any human study designed to
p.000004: the clinical, pharmacological and / or other pharmacodynamic effects of one or
p.000004: more tested medicinal products, and / or to identify adverse reactions to one or more tested
p.000004: medicinal products, and / or to study the absorption, distribution, metabolism and excretion of one or
p.000004: more medicinal products tested in order to ascertain their safety and / or efficacy.
p.000004: The definitions of clinical trial and clinical trial are synonymous.
p.000004: Non-interventional study is a study in which the medicinal product (s) is prescribed as usual
p.000004: in accordance with the conditions laid down in the Marketing Authorization. The appointment of the patient to
p.000004: a specific therapeutic strategy is not predefined by a test protocol, but falls within
p.000004: the established practice and the decision to prescribe the medicinal product is clearly distinguished from the decision to
p.000004: included the patient in the trial. No additional treatment should be applied to patients
p.000004: diagnostic or monitoring procedures and epidemiological methods are used to analyze the data collected.
p.000004: 1.12. Clinical trial / study report
p.000004: Written description of each trial / study of a therapeutic, prophylactic or diagnostic tool,
p.000004: applied to humans, which includes full clinical and statistical results, descriptions and
p.000004: analyzes integrated into a single report.
p.000004: 1.13. Medicinal product for comparison
p.000004: Tested or authorized medicinal product (aka active control) or placebo used for
p.000004: comparison during a clinical trial.
p.000004: 1.14. Conformity (as regards test)
p.000004: Compliance with all requirements - related to the test, the requirements of the DCT and the applicable ones
p.000004: regulations.
p.000004: 1.15. Confidentiality
p.000004: Preventing the disclosure by persons other than authorized persons of information belonging to
p.000004: the contracting authority or the identity of the participants.
p.000004: 1.16. Contract
p.000004: A written, dated and signed agreement between two or more parties setting out all the measures under
p.000004: assignment, assignment of tasks and responsibilities and, if applicable, financial matters. The protocol may
p.000004: to serve as the basis of a contract.
p.000004: 1.17. Coordinating committee
p.000004: Commissioner-designate committee to coordinate multicenter activities
p.000004: clinical trials.
p.000004: 1.18. Coordinating researcher
p.000004: Researcher appointed to coordinate researchers from the various multicenter centers
p.000004: testing.
p.000004: 1.19. Contract Research Organization (DIO)
p.000004: A natural or legal person or scientific organization that has contracted with the contracting authority to perform one or
p.000004: more than the test-related functions and duties of the contracting authority.
p.000004: 1.20. Direct access
p.000004: Permission to examine, analyze, verify and reproduce all records and reports that are relevant for evaluation
...
p.000004: of the test reports annexed to the application for authorization with the standards set out in
p.000004: the guidance of the International Harmonization Conference on the structure and content of
p.000004: clinical trial reports.
p.000004: 5.23. Multicenter tests
p.000004: In the case of multi-center tests, the contracting entity shall ensure that:
p.000004: 5.23.1. All researchers carry out the clinical trial in strict accordance with the approved by the client
p.000004: minutes and after a favorable opinion from the Ethics Committee, if required by the regulatory authorities.
p.000004: 5.23.2. Patients' clinical records are compiled to capture data from all centers
p.000004: of the multicenter test. Those researchers who collect additional data are sourced
p.000004: with additional CCPs designed to capture this additional data.
p.000004: 5.23.3. The responsibilities of the coordinating researcher and the participating researchers are documented directly
p.000004: before starting the clinical trial.
p.000004: 5.23.4. All researchers were instructed to follow the protocol to comply with
p.000004: standards set by the contracting authority for the evaluation of clinical and laboratory findings and for completing the clinical
p.000004: map of the patient.
p.000004: 5.23.5. Communication between researchers is facilitated.
p.000004: 6. Clinical trial protocol and protocol changes
p.000004: The clinical trial protocol should mainly contain the listed data. The specific information that
p.000004: applicable only to individual clinical trial centers, may be included on a single page / pages
p.000004: or be included in a separate agreement. Some of the information listed below may be contained in others,
p.000004: protocol related documents such as the researcher's brochure.
p.000004: 6.1. General information
p.000004: 6.1.1. Protocol title, identification code and date. Each change / changes includes a number and a date.
p.000004: 6.1.2. Name and address of the contracting entity and the monitoring entity and the contracting research organization, if any
p.000004: included in the clinical trial.
p.000004: 6.1.3. Name and position of the person (s) authorized to sign the protocol and its amendment (s)
p.000004: the name of the contracting authority.
p.000004: 6.1.4. Name, position, address and telephone number (s) of the medical examiner by the client (or dentist)
p.000004: medicine) for the clinical trial.
p.000004: 6.1.5. Name and position of the investigator (s) responsible for conducting the clinical trial,
p.000004: as well as the addresses and telephone numbers of the clinical trial center (s).
p.000004: 6.1.6. Name, position, address and telephone number (s) of the physician or dentist who is
p.000004: responsible for any clinical (or dental) decision-making (if different) from the clinical trial
p.000004: researcher).
p.000004: 6.1.7. Name (s) and address (es) of the clinical laboratory (s) and other health and / or technical departments and / or institutions,
p.000004: included in the clinical trial.
p.000004: 6.2. Basic information
p.000004: 6.2.1. Name and description of the product (s) tested.
p.000004: 6.2.2. Summary of non - clinical trial data of clinical relevance and of
p.000004: clinical trials related to the present.
p.000004: 6.2.3. Summary of identified and potential risks and benefits, if any, to humans.
...
p.000004: The following sections of the researcher's booklet present the most important findings from
p.000004: tests, including the dose response to the effects observed, the relevance to humans and any effects that will
p.000004: to be studied on humans. If possible, compare the effective and non-toxic dose in animals of one and
p.000004: of the same type (ie the therapeutic index should be provided). The significance of
p.000004: this information to
p.000004: the proposed dosage in humans. Whenever possible, comparisons should be made with respect to blood-tissue
p.000004: levels instead of on a mg / kg basis.
p.000004: 7.3.5.1. Non-clinical pharmacology
p.000004: The section shall include a summary of the pharmacological aspects of the product tested and, where appropriate, of
p.000004: its important metabolic studies in animals. Such a summary includes the studies they evaluate
p.000004: potential therapeutic activity (eg models of efficacy, receptor binding and specificity),
p.000004: as such, evaluating safety (eg special studies evaluating pharmacological actions other than
p.000004: the proposed therapeutic effects).
p.000004: 7.3.5.2. Pharmacokinetics and metabolism of the product in animals
p.000004: Summary of pharmacokinetics and biological transformation and test layout presented
p.000004: medicinal product in all species tested. The commentary on the findings includes absorption, local and
p.000004: the systemic bioavailability of the investigational medicinal product and its metabolites and their relationship with
p.000004: pharmacological and toxicological findings in animal species.
p.000004: 7.3.5.3. Toxicology
p.000004: A summary of the toxicological effects found in relevant studies conducted on different subjects shall be provided
p.000004: animal species, including the following: single dose toxicity; repeated dose toxicity
p.000004: dosing; carcinogenicity; special tests (eg irritability and sensitivity); reproductive toxicity;
p.000004: genotoxicity (mutagenicity).
p.000004: 7.3.6. Effects in humans
p.000004: A full description of the known effects of the tested product (s) on humans, including information on
p.000004: pharmacokinetics, metabolism, pharmacodynamics, dose response, safety, efficacy and other pharmacological
p.000004: actions. Whenever possible, a summary of each completed clinical trial as well as
p.000004: information regarding the results of any use of the test medicinal product to be tested
p.000004: different from clinical trials (eg post-market experience).
p.000004: 7.3.6.1. Pharmacokinetics and metabolism of the product in humans
p.000004: A summary of the pharmacokinetics of the investigational medicinal product shall be provided,
p.000004: which, if possible, includes the following: pharmacokinetics (including metabolism and absorption, binding to
p.000004: plasma proteins, distribution and elimination); bioavailability (where possible absolute and / or relative),
p.000004: using a dosage form for comparison; subgroups of the population (eg gender, age and impaired function)
p.000004: to an authority); interactions (eg product-product interactions or food effects); others
p.000004: pharmacokinetic data (eg, results from population-based studies conducted in clinical trials).
p.000004: 7.3.6.2. Safety and efficiency
p.000004: A summary of information obtained from previous human clinical trials (healthy volunteers) is provided
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p.000004: 3.3.7. confirmation that no deviations or changes can be applied to the protocol before
p.000004: the immediate affirmative affirmative of the change, except where
p.000004: it is necessary to avoid immediate risks for participants or when changes affect them
p.000004: logistical and administrative aspects of the test (e.g. change of monitoring person,
p.000004: telephone numbers) according to the obligations of the researcher under item 4.5.2;
p.000004: 3.3.8. a requirement that the researcher immediately notify the Ethics Committee of any deviations or changes to the protocol,
p.000004: when it is necessary to avoid the immediate risks to participants in accordance with 3.3.7 and
p.000004: the obligations of the researcher under 4.5.2 and 4.5.4; changes that increase the risk to participants and / or
p.000004: significantly affecting the conduct of the clinical trial (see 4.10.2); all the side effects
p.000004: reactions that are both serious and unexpected; new information that may incorrectly affect the safety of individuals
p.000004: or conducting the clinical trial;
p.000004: 3.3.9. a requirement that the Ethics Committee immediately notify in writing
p.000004: the researcher / institution for the clinical trial decisions / opinions; the reasons
p.000004: on its decisions / opinions and the procedures for appealing the decisions / opinions of the
p.000004: ethics.
p.000004: 3.4. Documents
p.000004: The Ethics Committee shall keep all relevant documents (eg written standard operating procedures, lists of records)
p.000004: members, appointment orders, members' job listings, conflicts of interest declarations and
p.000004: confidentiality, documents submitted, meeting minutes and correspondence) for the period no
p.000004: less than three years after termination of the clinical trial and make them available on request to the regulatory ones
p.000004: organs.
p.000004: The Ethics Committee shall provide the investigator, the sponsor or the regulatory authorities with its written documents
p.000004: procedures and orders determining the list of members upon request.
p.000004: 4. Researcher
p.000004: 4.1. Qualification and responsibilities of the researcher
p.000004: 4.1.1. The researcher (s) have the appropriate education, qualifications and experience to assess responsibility for the
p.000004: the proper conduct of the clinical trial; meets all regulatory requirements
p.000004: authorities, and provides proof of his / her qualification through an updated CV and / or others
p.000004: documents required by the contracting authority, the ethics committee and / or regulatory authorities.
p.000004: 4.1.2. The researcher is familiar with the proper use of the test drug as it is
p.000004: referred to in the protocol, the researcher's current brochure, product information and any other sources
p.000004: information provided by the contracting authority.
p.000004: 4.1.3. The researcher knows and complies with the requirements of the DCT and the applicable regulatory requirements.
p.000004: 4.1.4. The researcher permits monitoring, verification by the contracting authority and inspection by
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p.000004: 4.8.1. During the receipt and documentation of informed consent, the researcher complies
p.000004: the applicable regulatory requirements, the principles of the CPT and the ethical principles enshrined in the Declaration of
p.000004: Helsinki. In order to begin the clinical trial, the researcher must have a positive opinion in writing
p.000004: of the Ethics Committee on the written informed consent and any other written information to be provided
p.000004: provided to participants.
p.000004: 4.8.2. The written informed consent form and any other written information provided to participants shall be
p.000004: updates when important new information becomes available that may affect their consent. Each
p.000004: an updated form of written informed consent and written information should have a positive opinion of
p.000004: the ethics committee prior to its implementation. The participant or his legal representative shall be promptly informed
p.000004: notify when important new information becomes available that may affect their desire to
p.000004: continue to participate in the clinical trial. Communications regarding new information shall be documented
p.000004: timely.
p.000004: 4.8.3. Neither the principal investigator nor the research staff can coerce or give in
p.000004: mislead the person to participate or continue to participate in the clinical trial.
p.000004: 4.8.4. No oral or written information pertaining to the clinical trial, including the format for
p.000004: written informed consent may not contain words and expressions that coerce or sound coercive to the participant
p.000004: or his legal representative to waive any of his legal rights or to release or to impose
p.000004: discharge for negligence of the researcher, contracting authority, institution or
p.000004: their representatives.
p.000004: 4.8.5. The researcher or the person authorized by him / her shall inform the participant or in case he / she cannot give
p.000004: his consent, his legal representative for all aspects of the clinical trial, including
p.000004: the provision of written information and the favorable opinion of the Ethics Committee.
p.000004: 4.8.6. The language used in the oral or written information for the clinical trial, including the written form
p.000004: informed consent must be without medical terms and sufficiently accessible to be
p.000004: understood by the participant or his legal representative and, where appropriate, by the independent witness.
p.000004: 4.8.7. Prior to obtaining written informed consent, the Principal Investigator or a person authorized by him or her
p.000004: obliged to provide the participant or his or her legal
p.000004: representative sufficient time and opportunity to discuss the details of the clinical trial and yes
p.000004: decide whether or not to participate. All questions asked by the participant or his legal representative must
p.000004: replied in full.
p.000004: 4.8.8. Before engaging the participant, written informed consent must be signed personally and
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p.000004: use, a booklet for the researcher specific to this new use is prepared. Researcher's brochure
p.000004: it shall be reviewed once a year and modified, where necessary, in accordance with the contracting entity's written procedures.
p.000004: More frequent changes can be made depending on the stage of product development and the type of new product
p.000004: information. Relevant new information, in line with good clinical practice, may be such
p.000004: the importance of discussing it with researchers and, if possible, in the Ethics Committee
p.000004: and / or regulatory authorities before being included in a researcher's brochure.
p.000004: The contracting authority is responsible for ensuring that researchers are aware of the updated brochure
p.000004: and researchers are required to submit a new booklet to the researcher
p.000004: the relevant ethics committees. In the case of a test commissioned by a researcher, the contracting authority is
p.000004: obliged to provide assurance that the manufacturer's brochure may be obtained from the manufacturer. If
p.000004: the test product is manufactured by the researcher, he is obliged to provide the necessary information
p.000004: in front of the test team. In case the preparation of an official booklet of the researcher is impossible,
p.000004: as a substitute, the contracting authority shall provide in the protocol a detailed basic information section containing
p.000004: a minimum of up-to-date data described in this Annex.
p.000004: 7.2. Basic considerations
p.000004: The researcher's brochure includes:
p.000004: 7.2.1. Home page
p.000004: It includes: name of the contracting authority, characteristic of each product tested, ie. research code, chemical
p.000004: or an approved generic name and trade name (if any), date of issue, edition number and reference number
p.000004: and the release date it replaces. Sample:
p.000004: HOME PAGE
p.000004: NAME OF THE CONTRACTING AUTHORITY
p.000004: Medicine:
p.000004: Test number:
p.000004: Name (s): Chemical, INN (if approved): Trade name
p.000004: Researcher's brochure Edition number:
p.000004: Release Date:
p.000004: Replaces previous edition number: Date:
p.000004: 7.2.2. Privacy Statement
p.000004: The contracting authority may include an opinion giving instructions to
p.000004: the researcher / recipients to accept the researcher's brochure as confidential throughout
p.000004: information and use by the researcher team and the ethics / regulatory committee.
p.000004: 7.3. Content of the researcher's brochure
p.000004: The researcher's booklet contains the following sections, each of which, if possible, has one
p.000004: literary reference:
p.000004: 7.3.1. Table of Contents:
p.000004: Privacy Statement Signature Page
p.000004: 1. Content
p.000004: 2. Summary
p.000004: 3. Introduction
p.000004: 4. Physical, chemical and pharmaceutical properties and formula
p.000004: 5. Non-clinical trials
p.000004: 5.1. Non-clinical pharmacology
p.000004: 5.2. Pharmacokinetics and metabolism of the product in animals
p.000004: 5.3. Toxicology
p.000004: 6. Effects in humans
p.000004: 6.1. Pharmacokinetics and metabolism of the product in humans
p.000004: 6.2. Safety and efficiency
p.000004: 6.3. Experience after marketing authorization
p.000004: 7. Summary of data and recommendations to the researcher
p.000004: 1. Publications
p.000004: 2. Reports
p.000004: Applications (if any)
p.000004: 7.3.2. Summary
p.000004: A brief summary (not exceeding two pages) is given indicating an important physical, chemical,
...
Social / Racial Minority
Searching for indicator minority:
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p.000004: Unique identifier code for the designation of each participant in a clinical trial by the researcher in order to preserve
p.000004: his identity and used in place of the participant's name
p.000004: when reporting adverse events and / or other test-related data.
p.000004: 1.56. Clinical trial center
p.000004: The location (s) of study-related activities.
p.000004: 1.57. Unexpected side effect
p.000004: For unauthorized products - an adverse reaction whose nature, severity or outcome do not match
p.000004: of the information on the tested medicinal product referred to in the investigator's leaflet. They are allowed
p.000004: use of products - an adverse reaction not listed in the summary of product characteristics or
p.000004: whose character, weight or output do not correspond to the information given in the summary of product characteristics.
p.000004: 1.58. Vulnerable groups
p.000004: Individuals whose desire to participate in a clinical trial may be influenced by the expectation of benefit or by
p.000004: their position vis-à-vis senior officials in the hierarchy related to participation or non-participation, for example:
p.000004: medical, dental, pharmacy, or nursing students in pharmacy
p.000004: industry, serving in the military, and persons deprived of their liberty.
p.000004: Other vulnerable participants are patients with incurable diseases, people in nursing homes, the unemployed or
p.000004: beggars, emergency patients, ethnic minority groups, street children, vagrants, minors and such,
p.000004: who are unable to consent.
p.000004: 1.59. Well-being (of clinical trial participants)
p.000004: Physical and mental integrity of participants in the clinical trial
p.000004: 2. PRC principles
p.000004: 2.1. Clinical trials shall be conducted in accordance with the ethical principles set out in the Declaration of Conformity
p.000004: Helsinki and comply with DCT and applicable regulatory requirements.
p.000004: 2.2. Before starting a test, all the foreseeable risks are compared with the expected benefit
p.000004: individually for the participant and for the community. A clinical trial can only begin and continue if foreseeable
p.000004: the benefits justify the risks.
p.000004: 2.3. The rights, safety and well-being of test participants are paramount and
p.000004: stand above the interests of science and society.
p.000004: 2.4. Available non-clinical and clinical information on the investigational medicinal product should be sufficient
p.000004: support for the proposed clinical trial.
p.000004: 2.5. Clinical trials must be scientifically relevant and described in a clear and detailed manner
p.000004: protocol.
p.000004: 2.6. A clinical trial shall be conducted in accordance with a protocol that has been approved in advance
p.000004: by the Ethics Committee.
p.000004: 2.7. Medical monitoring and medical decisions, with regard to participants, are taken by the doctor or, where appropriate
p.000004: necessary - by a dentist.
p.000004: 2.8. Each person charged with conducting a clinical trial has education, qualification
p.000004: and attempting to fulfill the relevant test obligations.
...
Social / Soldier
Searching for indicator military:
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p.000004: Any member of the clinical research team appointed and supervised by the principal investigator at
p.000004: the location of the clinical trial to perform the basic test-related actions
p.000004: and / or make important decisions (eg, associates, graduate students, doctoral students).
p.000004: 1.54. Test participant
p.000004: A person who is enrolled in a clinical trial by receiving or participating in a test drug
p.000004: controlling.
p.000004: 1.55. Participant identification code
p.000004: Unique identifier code for the designation of each participant in a clinical trial by the researcher in order to preserve
p.000004: his identity and used in place of the participant's name
p.000004: when reporting adverse events and / or other test-related data.
p.000004: 1.56. Clinical trial center
p.000004: The location (s) of study-related activities.
p.000004: 1.57. Unexpected side effect
p.000004: For unauthorized products - an adverse reaction whose nature, severity or outcome do not match
p.000004: of the information on the tested medicinal product referred to in the investigator's leaflet. They are allowed
p.000004: use of products - an adverse reaction not listed in the summary of product characteristics or
p.000004: whose character, weight or output do not correspond to the information given in the summary of product characteristics.
p.000004: 1.58. Vulnerable groups
p.000004: Individuals whose desire to participate in a clinical trial may be influenced by the expectation of benefit or by
p.000004: their position vis-à-vis senior officials in the hierarchy related to participation or non-participation, for example:
p.000004: medical, dental, pharmacy, or nursing students in pharmacy
p.000004: industry, serving in the military, and persons deprived of their liberty.
p.000004: Other vulnerable participants are patients with incurable diseases, people in nursing homes, the unemployed or
p.000004: beggars, emergency patients, ethnic minority groups, street children, vagrants, minors and such,
p.000004: who are unable to consent.
p.000004: 1.59. Well-being (of clinical trial participants)
p.000004: Physical and mental integrity of participants in the clinical trial
p.000004: 2. PRC principles
p.000004: 2.1. Clinical trials shall be conducted in accordance with the ethical principles set out in the Declaration of Conformity
p.000004: Helsinki and comply with DCT and applicable regulatory requirements.
p.000004: 2.2. Before starting a test, all the foreseeable risks are compared with the expected benefit
p.000004: individually for the participant and for the community. A clinical trial can only begin and continue if foreseeable
p.000004: the benefits justify the risks.
p.000004: 2.3. The rights, safety and well-being of test participants are paramount and
p.000004: stand above the interests of science and society.
p.000004: 2.4. Available non-clinical and clinical information on the investigational medicinal product should be sufficient
p.000004: support for the proposed clinical trial.
p.000004: 2.5. Clinical trials must be scientifically relevant and described in a clear and detailed manner
p.000004: protocol.
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Social / Threat of Stigma
Searching for indicator threat:
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p.000004: 4.5. Protocol compliance
p.000004: 4.5.1. The researcher shall carry out the clinical trial in accordance with a protocol previously approved by
p.000004: the contracting authority and the regulatory authority and who has received a favorable opinion from the ethics committee. The researcher and
p.000004: the contracting authority shall sign the protocol or supplementary agreement, by which the researcher confirms his / her agreement to
p.000004: compliance with it.
p.000004: 4.5.2. The researcher may not make any deviations or changes to the protocol without the consent of
p.000004: the contracting authority and the preliminary examination and documented positive opinion of the changes by the commission
p.000004: ethics. Deviations from the requirements of the plan can only be made when there are good reasons for being
p.000004: endangering the life, health and rights of the persons surveyed, or where the changes involve only organizational or
p.000004: administrative aspects of the clinical trial (eg change of monitoring person, change of telephone
p.000004: numbers).
p.000004: 4.5.3. The researcher or his authorized representative shall document and explain any deviation from the approvals
p.000004: protocol.
p.000004: 4.5.4. The researcher may make a deviation or change in the avoidance protocol
p.000004: an imminent threat to patients without the immediate positive opinion of the Ethics Committee.
p.000004: The deviation, change or plan with proposed changes shall be submitted to the committee as soon as possible
p.000004: assessment ethics and opinion, consenting authority and regulatory authorities.
p.000004: 4.6. Tested medicinal product
p.000004: 4.6.1. Responsibility for the accountability of the investigational medicinal product at the clinical site
p.000004: the test is carried out by the researcher.
p.000004: 4.6.2. The researcher may assign some or all of his reporting responsibilities to
p.000004: the pharmacist's or other appropriate person's place (s) under the direction of the researcher,
p.000004: when permissible or required.
p.000004: 4.6.3. The researcher and / or pharmacist or other person designated by the researcher shall keep the records for
p.000004: medicines received at the venue, inventory of products at the center, the quantities used by each
p.000004: participant and the quantities returned to the contracting authority or at an additional place. These documents contain dates, quantities,
p.000004: batches and numbers, expiry date (where possible) and unique code numbers indicating the medicinal products
p.000004: products and participants. The researchers keep documents stating that the participants have received
p.000004: the relevant doses specified in the plan and confirmation and reporting of all medicinal products received by the contracting entity
p.000004: products.
...
p.000004: analysis and characteristics of the test batch;
p.000004: 5.14.5.3. store the samples to the extent that stability allows, until the analyzes of the data from the
p.000004: the clinical trial or for a longer period if required by other applicable regulatory requirements.
p.000004: 5.15. Access to documentation
p.000004: 5.15.1. The contracting entity shall document in the record or other written agreement that the principal investigator / institution,
p.000004: the study center will provide direct access to clinical data sources / documents
p.000004: testing for monitoring, verification, review by the ethics committee and inspection by the regulatory authorities.
p.000004: 5.15.2. The Contracting Authority verifies that all participants have given their written consent for direct access to theirs
p.000004: original medical records for conducting clinical-related monitoring, inspections,
p.000004: review by ethics and inspection committee of
p.000004: regulatory authorities.
p.000004: 5.16. Safety information
p.000004: 5.16.1. The contracting authority is responsible for the continuous safety assessment of the investigational medicinal product
p.000004: product.
p.000004: 5.16.2. The sponsor shall inform the BDA, the Ethics Committee and the researchers of any new information that
p.000004: may pose a threat to the health and well - being of patients, affecting the course of
p.000004: study or change the BDA's authorization to conduct the study and / or change the positive
p.000004: opinion of the ethics committee to continue the clinical trial.
p.000004: 5.16.3. The contracting authority shall keep detailed records of all reports of suspected adverse events that have occurred
p.000004: when using the investigational medicinal product for which it has been informed by the investigator or from another source
p.000004: of information.
p.000004: 5.16.4. The assignor evaluates the adverse events in terms of severity, expectation and
p.000004: causal connection. The contracting authority shall develop and implement procedures for evaluating adverse events for
p.000004: severity, expectation and cause and effect in accordance with published International Guidelines
p.000004: harmonization conference, the European Commission and the European Medicines Agency.
p.000004: 5.16.5. The contracting authority shall actively collect any additional information that is necessary to evaluate the
p.000004: individual reports of adverse events.
p.000004: 5.1.6.6. All adverse events rated by the researcher or assignor as least likely to be related
p.000004: with the test product, are treated and reported as adverse reactions.
p.000004: 5.17. Reporting side effects
p.000004: 5.17.1. Reports of suspected serious and unexpected adverse reactions under Art. 138 LPPM are submitted by
p.000004: the sponsor of the clinical trial.
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Social / Trade Union Membership
Searching for indicator union:
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p.000004: (2) The ordinance shall also determine the requirements for the content and format of the documentation,
p.000004: which is submitted for clinical trial authorization and non-interventionally
p.000004: study, change and termination of clinical trial and non-interventional study.
p.000004: Section II.
p.000004: Requirements to the documentation for authorization for conducting clinical trials (Title amend. - SG 14/2012)
p.000004: Art. 2. The administrative documentation under Art. 110, para. 1, item 1 of the Law on Medicinal Products in Human Medicine
p.000004: (CLPM) contains:
p.000004: 1. cover letter;
p.000004: 2. application form;
p.000004: 3. confirmation of a number obtained from the European Clinical Trials Database;
p.000004: 4. a list of regulatory bodies and ethics committees to which an application has been submitted and their decision;
p.000004: 5. a list of all planned centers, principal researchers and research teams for the territory of the Republic
p.000004: Bulgaria;
p.000004: 6. a copy of the recommendations of the Scientific Committee of the European Medicines Agency for planning advice
p.000004: tests undergoing a procedure;
p.000004: 7. a letter of attorney or contract for the authorization of the person submitting the application on behalf
p.000004: the contracting authority where the applicant is not the contracting authority;
p.000004: 8. (supplemented, SG No. 14/2012) document for current registration, issued by a competent
p.000004: authority, the contracting authority and the applicant within the territory of the European Union. Where the contracting authority or the applicant is
p.000004: data subject - names, address, telephone, fax;
p.000004: 9. the declaration under art. 122 CLPM.
p.000004: Art. 3. The information about a participant under Art. 110, para. 1, item 2 of LMPHM contains:
p.000004: 1. patient / participant information;
p.000004: 2. informed consent form;
p.000004: 3. description of patient / participant recruitment procedures;
p.000004: 4. a description of the procedures for obtaining informed consent from a lawful person
p.000004: a representative, where foreseen;
p.000004: 5. ethical justification in the case of recruitment of participants who are unable to give informed consent, in accordance with
p.000004: Art. 98 CLPM;
p.000004: 6. a copy of any other information that will be used to recruit participants and / or provide a participant
p.000004: before or during the clinical trial.
p.000004: Art. 4. (1) The documentation for the test report under Art. 110, para. 1, item 3 of LMPHM contains:
p.000004: 1. test report with all current changes;
p.000004: 2. summary of the minutes in Bulgarian;
p.000004: 3. an assessment of the scientific value of the test by a specialist in the relevant field, where available;
p.000004: 4. an ethical evaluation of the protocol by the principal or coordinating investigator when not part of the protocol.
p.000004: (2) The protocol shall be drawn up in accordance with the rules of the DCP and shall contain at least the following:
p.000004: 1. assessment of the expected benefits and risks in accordance with Art. 90, Vol. 1 of ZLPHM;
p.000004: 2. defining the inclusion and exclusion criteria;
p.000004: 3. justification for the choice of patients, especially in the case of envisaged inclusion of patients who are not in
p.000004: able to give informed consent and other vulnerable patient groups;
p.000004: 4. a description of the procedures for recruiting patients and obtaining informed consent when
p.000004: envisages the inclusion of patients who are temporarily or permanently unable to provide personally informed information
p.000004: consent, and when obtaining the consent of an independent witness;
p.000004: 5. description of the plan and procedures for providing additional medical care to the participants after the end of
p.000004: the study;
p.000004: 6. monitoring procedures;
p.000004: 7. plan for publishing the data.
p.000004: (3) The protocol must be signed by the contracting authority and the principal investigator for each of the proposed centers.
p.000004: Art. 5. (1) The documentation for the tested medicinal product under Art. 110, para. 1, item 4 of the LMPHM contains:
p.000004: 1. Researcher's booklet;
p.000004: 2. a summary of all ongoing clinical trials with the medicinal product.
p.000004: (2) Where the investigational medicinal product is authorized in a Member State of the European Union, and
p.000004: the test provides for its use in accordance with the conditions laid down in the marketing authorization,
p.000004: instead of the document under Art. 1, item 1 a summary of the product characteristics may be provided.
p.000004: (3) The researcher's booklet and any update thereof must provide scientifically substantiated and complete information
p.000004: for the product that is needed for an objective assessment of the risk / benefit ratio of the proposed clinical trial.
p.000004: (4) The contracting authority shall re-evaluate the researcher's brochure and supplement it with new data in the presence of at least once
p.000004: per year.
p.000004: Art. 6. (1) The documentation on the technical requirements and the personnel under Art. 110, para. 1, item 5 of the LMPHM contains:
p.000004: 1. description of the necessary equipment and / or technical requirements for the implementation of the protocol;
p.000004: 2. documents certifying the available technical capabilities for the implementation of the protocol for each of the
p.000004: the centers offered, including documents for certification, accreditation and established quality control and / or
p.000004: external quality assessment;
p.000004: 3. CV and / or other documents certifying the education and qualification of
p.000004: the members of the research team and compliance with the requirements of Art. 86, para. 2 CLPM.
p.000004: 4. (Repealed, SG No. 25/2018)
p.000004: (2) The documents under item 2 shall be prepared by a specialized independent organization and / or the head of the
p.000004: the medical establishment and / or structure in which each specific procedure is planned to be performed
p.000004: equipment described in the protocol.
...
p.000004: (2) The documents under art. 2, 3, 4, 5, 6, 7, 9 and Art. 19, para. 3, as well as the declarations under art. 122
p.000004: and 123 ZLPHM.
p.000004: (3) (Repealed, SG No. 14/2012, New SG No. 25/2018) The Executive Agency for Medicines shall perform
p.000004: verification by official means for the presence of the circumstances under Art. 87, para. 1 of
p.000004: CLPM.
p.000004: Art. 9. The sponsor or the person authorized by him / her shall submit to the Drug Enforcement Agency
p.000004: the following documentation under Art. 116, para. 4, Vol. 4 of ZLPHM:
p.000004: 1. dossier of the tested medicinal product;
p.000004: 2. documentation certifying the production of the tested products under the conditions of Good
p.000004: manufacturing practice;
p.000004: 3. analytical certificate of the product under test where impurities are not justified in the specification or when
p.000004: identify uncharacterized impurities;
p.000004: 4. results of viral safety tests;
p.000004: 5. certificate for the absence of causative agents of portable spongiform encephalopathy;
p.000004: 6. models on the label in Bulgarian;
p.000004: 7. opinion from the Ministry of Environment and Water regarding the potential risk for
p.000004: the environment when the test medicinal product contains genetically modified organisms.
p.000004: Art. 10. (1) The dossier of the tested medicinal product shall be prepared in accordance with the published ones
p.000004: European Commission guides in format and content according to Annex 2.
p.000004: (2) Where the investigational medicinal product is manufactured within the European Union and does not exist
p.000004: authorization for use, instead of the document under Art. 9, item 2 shall be submitted a copy of the manufacturing authorization for
p.000004: medicinal products under development and research issued by a Member State of the European Union.
p.000004: (3) Where the investigational medicinal product is not manufactured within the European Union and
p.000004: not authorized, the following production documents must be submitted:
p.000004: 1. a document from the qualified person of a natural or legal person holding a permit for import into the territory
p.000004: of the European Union certifying compliance of the conditions of manufacture, control and storage with
p.000004: standards equivalent to the requirements of Good manufacturing practice for medicinal products in the process
p.000004: development and research valid for the territory of the European Union;
p.000004: 2. a copy of the import authorization for the territory of the European Union;
p.000004: 3. Certificate of Good Manufacturing Practice for active substances of biological origin.
p.000004: (4) Where the investigational medicinal product is manufactured within the European Union and is available
p.000004: authorization for use, instead of the document under Art. 9, item 2, a declaration of origin shall be submitted by the manufacturer
p.000004: the product from standard batches manufactured under the terms of the marketing authorization at the place of manufacture,
p.000004: included in the marketing authorization in the territory of a Member State of the European Union.
p.000004: (5) Where the investigational medicinal product is authorized in a Member State of the European Union,
p.000004: and / or approved clinical trial in the Republic of Bulgaria, under Art. 9, item 1 a condensed test file shall be submitted
p.000004: medicine.
p.000004: Art. 11. (Repealed, SG No. 14/2012)
p.000004: Section III.
p.000004: Requirements to the documentation for changing the authorization for conducting clinical trials (Title amended - SG, issue 14 of
p.000004: 2012)
p.000004: Art. 12. Substantial change under Art. 127, para. 2 LPPM is present when there is a change in the data specified in
p.000004: Annex 3.
p.000004: Art. 13. (1) When planning significant changes in the clinical trial and in the documentation under
p.000004: Art. 110 LPPMH the contracting authority or a person authorized by it submits a written application in the form to the committee on
p.000004: ethics under art. 103 CLPM.
p.000004: (2) The application shall be accompanied by the following documentation:
p.000004: 1. cover letter;
p.000004: 2. summary of the planned change;
p.000004: 3. a list of the updated documents;
p.000004: 4. the updated documentation under Art. 2, 3, 4, 5, 6 and 7 reflecting changes;
p.000004: 5. pages of documentation with marked changes comparing current and proposed new ones
p.000004: texts;
p.000004: 6. justification of the changes;
p.000004: 7. copy of the application for conducting a clinical trial under Art. 2 with tagged changes, electronic and
p.000004: paper;
p.000004: 8. document for paid fee.
p.000004: Art. 14. (1) When planning significant changes in the clinical trial and in the documentation under
p.000004: Art. 116 of the LPPHM the contracting entity or a person authorized by it submits to the Executive Agency for Medicines
p.000004: a written application for a model change.
...
p.000004: (4) In case of changes under Art. 127, para. 1 LPPMM application must be submitted within 14 days of receipt
p.000004: Notification from the Medicines Executive Agency of the necessary change.
p.000004: Art. 15. (Repealed, SG No. 14/2012)
p.000004: Section III "a".
p.000004: Requirements to the documentation for conducting non-interventional research and changes thereto (New, SG No. 14/2012)
p.000004: d)
p.000004: Art. 15a. (New, SG No. 14/2012) For non-interventional study of a medicinal product under Art. 145
p.000004: The CLPMM, the sponsor or the authorized person, represents in the Executive Agency for Medicines and in
p.000004: the ethics committee under art. 103 LMPHM application form for conducting non-interventional study.
p.000004: Art. 15b. (New, SG No. 14/2012) The administrative documentation for the studies under Art. 145 LPPMM contains:
p.000004: 1. cover letter;
p.000004: 2. application form;
p.000004: 3. a list of all planned centers and principal investigators for the territory of the Republic of Bulgaria;
p.000004: 4. a copy of the recommendations of the Scientific Committee of the European Medicines Agency for planning advice
p.000004: studies undergoing a procedure;
p.000004: 5. a letter of attorney or contract for the authorization of the person submitting the application on behalf of
p.000004: the contracting authority where the applicant is not the contracting authority;
p.000004: 6. a document for up-to-date registration, issued by a competent authority, to the assignor and the applicant in the territory
p.000004: the European Union; when the contracting authority or the applicant is an individual, information is provided - names, address, telephone,
p.000004: fax;
p.000004: 7. a statement that the documentation submitted to the BDA and to the Ethics Committee contains the same information.
p.000004: Art. 15c. (New, SG No. 14/2012) The information on a participant in a non-interventional study shall include:
p.000004: 1. patient / participant information;
p.000004: 2. informed consent form, except where it is processed retrospectively and anonymously
p.000004: medical information;
p.000004: 3. description of patient / participant recruitment procedures;
p.000004: 4. a description of the procedures for obtaining informed consent from a legal representative, where applicable
p.000004: provides;
p.000004: 5. ethical justification in case of recruitment of patients / participants who are unable to give
p.000004: informed consent in accordance with Art. 98 CLPM;
p.000004: 6. a copy of any other information that will be used to recruit patients / participants
p.000004: and / or provided to a patient / participant before or during the non-interventional study.
p.000004: Art. 15g. (New, SG No. 14/2012) (1) The documentation of the protocol of
p.000004: non-interventional study or guidance for conducting a non-interventional study with retrospective
p.000004: and anonymous processing of medical information contains:
p.000004: 1. protocol or manual for carrying out the non-interventional study with all current changes;
p.000004: 2. summary of the protocol or the guide for conducting the study in Bulgarian;
p.000004: 3. a plan for publishing the data.
...
p.000004: 6, Art. 4, para. 1, Vol. 2, Art. 6, para. 1, items 1 and 3, art. 7, items 1, 2, 3, 5 and 6, Art. 8, para. 1, Art. 9, Vol. 6, Art. 13, para. 1 and para.
p.000004: 2, items 1 and 2, art. 14, para. 1, Art. 15b, items 1, 2 and 3, art. 15c, items 1, 2 and 6, Art. 15d, para. 1, Vol. 2, Art. 15f, para. 1, Vol. 1, Art.
p.000004: 15g, items 1, 2 and 3, Art. 15h, para. 1 and para. 2, items 1 and 3 and Art. 16, para. 1 shall also be provided in Bulgarian.
p.000004: (3) (Amended, SG No. 14/2012) The documentation under Art. 8, para. 1, Art. 14, para. 1 and 3, Art. 15a, Art. 15h, para. 1, Art. 16,
p.000004: para. 1 shall also be provided in English.
p.000004: Art. 19. (1) (Amended, SG No. 14/2012) The Executive Director of the Executive Agency for Medicines
p.000004: approve by order samples of the applications under Art. 2, 8, 13, 14 and 15a and 15h, para. 1 and the notification under Art. 16.
p.000004: (2) The applications shall be submitted in a single copy, in paper and electronic form.
p.000004: (3) Applications in electronic form must be submitted in a format compatible with the requirements for entry into the European database.
p.000004: clinical trial data.
p.000004: (4) The contracting authority or the authorized person shall declare that the applications on electronic and hard copy contain identical
p.000004: information.
p.000004: Section V. Control
p.000004: Art. 20. (1) The control over the clinical trials conducted in the Republic of Bulgaria shall be exercised by the
p.000004: Art. 267, para. 3 ZLPHM State Inspectors.
p.000004: (2) Control over clinical trials conducted in the Republic of Bulgaria may also be exercised by
p.000004: officials of the Member States of the European Union and designated by the European Medicines Agency
p.000004: and its Scientific Committees.
p.000004: (3) Where necessary, inspectors may be assisted and assisted by experts designated by
p.000004: the Executive Director of the Executive Agency for Medicinal Products.
p.000004: (4) The control, carried out by the state inspectors, shall be carried out:
p.000004: 1. as a preliminary, current and follow-up in a clinical trial of a medicinal product;
p.000004: 2. in the course of a marketing authorization procedure;
p.000004: 3. as follow-up measures after authorization for use.
p.000004: (5) The contracting authority, the principal investigator and the researchers contracted shall be subject to control
p.000004: research organization, ethics committees, test center, manufacturing sites and control center
p.000004: the investigational medicinal product, the laboratories and any site and facility used during the test,
p.000004: as well as all clinical trial documentation.
p.000004: Art. 21. (1) Control over clinical trials shall be conducted in accordance with standard operating procedures
p.000004: procedures approved by the Executive Director of the Executive Agency for Medicinal Products. The standard ones
p.000004: operational procedures shall be developed in accordance with the guidance documents of the European Commission.
p.000004: (2) Each examination in connection with a clinical trial of a medicinal product shall end with a report to be submitted to the
p.000004: the contracting authority.
p.000004: (3) A clinical trial verification report may be provided to the investigators,
p.000004: the ethics committee under art. 103 LPPMM, other Member States of the European Union, and the European Union
p.000004: drug agency.
p.000004: Art. 22. When finding discrepancies requiring the suspension or termination of a study,
p.000004: The Executive Agency for Medicinal Products shall inform the European Medicines Agency, Member States, c
p.000004: the European Commission and the Ethics Committee under Art. 103 CLPM.
p.000004: Art. 23. The Executive Agency for Medicinal Products shall enter into the European Clinical Trials Database
p.000004: information on planned and performed clinical trial checks.
p.000004: Transitional and Final Provisions
p.000004: § 1. This Regulation establishes the provisions of Commission Directive 2005/28 / EC of 8 April 2005 on
p.000004: defining principles and detailed guidelines for good clinical practice for medicinal products for
p.000004: humane use intended for research as well as requirements for the granting of a marketing authorization
p.000004: the manufacture or import of such products.
p.000004: § 2. To the applications, submitted before the entry into force of this Ordinance, for significant changes in the permit for holding
p.000004: the clinical trial of a medicinal product on the territory of the Republic of Bulgaria shall be submitted by the contracting authorities on time
p.000004: for three months the documentation provided for in the regulation.
p.000004: § 3. This Ordinance is issued on the grounds of Art. 82, para. 3, Art. 110, para. 2, Art. 116, para. 5, Art.
p.000004: 129, para. 3, Art. 142, para. 2 and Art. 145, para. 2 of the LPPHM and repeals Ordinance No. 14 of 2000 on the Terms and Conditions for Conducting
p.000004: clinical trials of medicines on humans (SG 73/00).
p.000004: Final provisions
p.000004: TO THE ORDER FOR AMENDING AND SUPPLEMENTING REGULATION No. 31 OF 2007 ON DEFINING THE RULES FOR GOOD CLINICAL PRACTICE
p.000004: (Official Gazette, issue 77 of 2016, effective 04.10.2016)
p.000004: § 3. The ordinance shall enter into force on the day of its promulgation in the State Gazette.
p.000004: Annex No. 1 to Art. 1, para. 1 (Amended, SG No. 14/2012)
p.000004: GOOD CLINICAL PRACTICE RULES
p.000004: Introduction
p.000004: Good clinical practice is the set of internationally recognized ethical and scientific quality requirements,
p.000004: which are adhered to in the design, conduct, reporting and reporting of clinical trials.
p.000004: Compliance with these requirements ensures public protection and protection of the rights, safety and health of
p.000004: test participants in accordance with the principles set out in the Helsinki Declaration and scientific
p.000004: value and reproducibility of clinical trial data.
p.000004: The purpose of DCP rules is to provide a single standard for the European Community, Japan and the United States in order to facilitate
p.000004: the mutual recognition of clinical trial data by their respective regulatory authorities.
p.000004: The DCT rules have been developed taking into account current good clinical practice in the European Union
p.000004: community, Japan and the United States, as well as those of Australia, Canada, Scandinavian countries and World Health
p.000004: organization.
p.000004: These rules must be followed when generating data from clinical trials that will
p.000004: be submitted to the regulatory authorities.
p.000004: The principles laid down in these rules may also apply to others
p.000004: clinical trials that could have an impact on human safety and health.
p.000004: 1. Definitions
p.000004: 1.1. Adverse Reaction (ADR)
p.000004: "Undesirable effect" is any undesirable and unintended response to a medicinal product that occurs with
p.000004: administration of the product at doses normally used for the treatment, prophylaxis or diagnosis of disease in
p.000004: people or for recovery, correction or
p.000004: modification of physiological function. In the case of a clinical trial - any undesirable or unforeseen
p.000004: response to the investigational medicinal product, regardless of the dose administered. The phrase "answered one
p.000004: "means that the cause and effect relationship is between the medicinal product and the adverse reaction
p.000004: at least a reasonable possibility, that is, the connection cannot be denied.
p.000004: 1.2. Adverse event
p.000004: Adverse event is any adverse change in health status observed with the administration of a medicinal product.
p.000004: to a patient or participant in a clinical trial that is not necessarily causally related to this treatment.
p.000004: An adverse event may therefore be any adverse and unintended physical finding (incl.
p.000004: laboratory deviation), symptom, or illness associated with the use of (tested) drug over time
p.000004: product, whether or not it is causally related to the product.
p.000004: 1.3. Applicable requirements
...
p.000004: 8, and patient identification codes for at least 15 years after completion or termination
p.000004: the test.
p.000004: The contracting authority shall keep all specific basic documents in accordance with the applicable regulations
p.000004: requirements of the country (s) in which the medicinal product is authorized and / or where
p.000004: the contracting authority intends to apply for a permit (s).
p.000004: 5.5.8. Upon termination of the study program for the investigational medicinal product, the contracting entity shall keep
p.000004: the documentation at least two years after the end of the last study with the product under test.
p.000004: These documents shall be kept for a longer period if required by other regulations or by
p.000004: the contracting authority.
p.000004: 5.5.9. If the sponsor discontinues the clinical development of the investigational medicinal product, it is obliged to
p.000004: notified all clinical trial investigators and all regulatory authorities.
p.000004: 5.5.10. Any transfer of ownership of the data shall be documented and reported to the relevant regulatory authorities
p.000004: bodies and as indicated in the applicable regulatory requirements. The new data owner is responsible for
p.000004: the storage and archiving of the documentation in accordance with 5.5.7, 5.5.8 and 5.5.9.
p.000004: 5.5.11. When including the data in the marketing authorization documentation, the contracting authority shall keep it
p.000004: the documentation not less than two years after the last marketing authorization was obtained
p.000004: the territory of the European Union.
p.000004: The specific basic documents of the contracting entity shall be kept for at least two years after the last authorization for
p.000004: use, or at least two years after
p.000004: the official cessation of the clinical development of the investigational medicinal product. These documents are
p.000004: stored for a longer period if required by other regulatory requirements or by
p.000004: the contracting authority.
p.000004: 5.5.12. The contracting authority shall inform the principal investigator and the clinic in which the clinic is conducted in writing.
p.000004: testing for the storage period of the documentation.
p.000004: The contracting authority shall inform the principal investigator and the medical establishment in writing of the moment of the drop - off
p.000004: the need to keep the documentation.
p.000004: 5.6. Choosing a researcher
p.000004: 5.6.1. The sponsor is responsible for selecting the investigator and the venue for the clinical trial.
p.000004: Each researcher needs to be qualified by training and experience and have the right conditions
p.000004: according to points 4.1 and 4.2 for the proper conduct of the clinical trial for which he was selected. IN
p.000004: the case of using an organization with a coordinating committee and / or coordinating researcher in
p.000004: multi-center tests, the contracting authority is responsible for organizing and / or selecting them.
p.000004: 5.6.2. Prior to entering into a contractual relationship with the investigator to conduct the test
p.000004: provide the researcher with the protocol and the current brochure of the researcher and sufficient time for them
p.000004: viewing.
...
p.000004: reactions may be reported at larger intervals, but not less than once every six months.
p.000004: The contracting authority is responsible for submitting reports to all interested researchers,
p.000004: ethics and regulatory authorities for any side effects that are serious and unexpected.
p.000004: 5.17.2. Serious and unexpected adverse reaction reports should comply with applicable regulatory requirements
p.000004: requirements and guidance of the International Harmonization Conference on the processing of safety data
p.000004: Clinical Trials - "Definitions and Standards for Emergency Reporting" (ICH Guideline for Clinical Safety Data
p.000004: Management: Definitions and Standards for Expedited Reporting).
p.000004: 5.17.3. The contracting authority shall submit to the regulatory authorities all updates of
p.000004: safety data and periodic reports. The contracting authority shall provide the Executive Agency once a year
p.000004: medicines and ethics committee list all suspected serious side effects that are
p.000004: occurred during the previous period, and a safety report of the test participants.
p.000004: 5.17.4. The annual safety report contains a summary of the safety of the tested medicinal product for
p.000004: the last one-year period from the date of the first authorization to conduct a clinical trial with
p.000004: test product in the territory of the European Union.
p.000004: The contracting authority submits the annual safety report to the BDA and the Ethics Committee within 60 calendar days
p.000004: after the end of the period covered by the report.
p.000004: For clinical trials of less than one year duration, an annual safety report shall be submitted to
p.000004: term up to 90 days after the end of the test with the notification under art. 142, para. 2 CLPM.
p.000004: When conducting more than one clinical trial with the same test product, the contracting authority shall submit a total annual
p.000004: safety report. In such cases, the report shall contain data on the safety profile of the product tested and annual
p.000004: safety reports on each of the clinical trials conducted in Bulgaria.
p.000004: 5.17.5. The contracting authority shall provide an annual safety report beyond the deadline requested by the BDA and / or
p.000004: the ethics committee.
p.000004: 5.18. Monitoring
p.000004: 5.18.1. The purpose of monitoring is to verify that the rights and well-being of
p.000004: people; the reported data are accurate, complete and consistent with the original documents; conducting the clinical
p.000004: testing is in accordance with the approved plan and changes, DCT and applicable regulatory requirements.
p.000004: 5.18.2. Selection and qualification of monitoring entities
p.000004: 5.18.2.1. The persons conducting the monitoring are appointed by the contracting authority.
p.000004: 5.18.2.2. The monitoring personnel are trained and have the necessary scientific and / or medical knowledge,
...
Social / Unemployment
Searching for indicator unemployed:
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p.000004: A person who is enrolled in a clinical trial by receiving or participating in a test drug
p.000004: controlling.
p.000004: 1.55. Participant identification code
p.000004: Unique identifier code for the designation of each participant in a clinical trial by the researcher in order to preserve
p.000004: his identity and used in place of the participant's name
p.000004: when reporting adverse events and / or other test-related data.
p.000004: 1.56. Clinical trial center
p.000004: The location (s) of study-related activities.
p.000004: 1.57. Unexpected side effect
p.000004: For unauthorized products - an adverse reaction whose nature, severity or outcome do not match
p.000004: of the information on the tested medicinal product referred to in the investigator's leaflet. They are allowed
p.000004: use of products - an adverse reaction not listed in the summary of product characteristics or
p.000004: whose character, weight or output do not correspond to the information given in the summary of product characteristics.
p.000004: 1.58. Vulnerable groups
p.000004: Individuals whose desire to participate in a clinical trial may be influenced by the expectation of benefit or by
p.000004: their position vis-à-vis senior officials in the hierarchy related to participation or non-participation, for example:
p.000004: medical, dental, pharmacy, or nursing students in pharmacy
p.000004: industry, serving in the military, and persons deprived of their liberty.
p.000004: Other vulnerable participants are patients with incurable diseases, people in nursing homes, the unemployed or
p.000004: beggars, emergency patients, ethnic minority groups, street children, vagrants, minors and such,
p.000004: who are unable to consent.
p.000004: 1.59. Well-being (of clinical trial participants)
p.000004: Physical and mental integrity of participants in the clinical trial
p.000004: 2. PRC principles
p.000004: 2.1. Clinical trials shall be conducted in accordance with the ethical principles set out in the Declaration of Conformity
p.000004: Helsinki and comply with DCT and applicable regulatory requirements.
p.000004: 2.2. Before starting a test, all the foreseeable risks are compared with the expected benefit
p.000004: individually for the participant and for the community. A clinical trial can only begin and continue if foreseeable
p.000004: the benefits justify the risks.
p.000004: 2.3. The rights, safety and well-being of test participants are paramount and
p.000004: stand above the interests of science and society.
p.000004: 2.4. Available non-clinical and clinical information on the investigational medicinal product should be sufficient
p.000004: support for the proposed clinical trial.
p.000004: 2.5. Clinical trials must be scientifically relevant and described in a clear and detailed manner
p.000004: protocol.
p.000004: 2.6. A clinical trial shall be conducted in accordance with a protocol that has been approved in advance
p.000004: by the Ethics Committee.
p.000004: 2.7. Medical monitoring and medical decisions, with regard to participants, are taken by the doctor or, where appropriate
p.000004: necessary - by a dentist.
...
Social / education
Searching for indicator education:
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p.000004: Art. 5. (1) The documentation for the tested medicinal product under Art. 110, para. 1, item 4 of the LMPHM contains:
p.000004: 1. Researcher's booklet;
p.000004: 2. a summary of all ongoing clinical trials with the medicinal product.
p.000004: (2) Where the investigational medicinal product is authorized in a Member State of the European Union, and
p.000004: the test provides for its use in accordance with the conditions laid down in the marketing authorization,
p.000004: instead of the document under Art. 1, item 1 a summary of the product characteristics may be provided.
p.000004: (3) The researcher's booklet and any update thereof must provide scientifically substantiated and complete information
p.000004: for the product that is needed for an objective assessment of the risk / benefit ratio of the proposed clinical trial.
p.000004: (4) The contracting authority shall re-evaluate the researcher's brochure and supplement it with new data in the presence of at least once
p.000004: per year.
p.000004: Art. 6. (1) The documentation on the technical requirements and the personnel under Art. 110, para. 1, item 5 of the LMPHM contains:
p.000004: 1. description of the necessary equipment and / or technical requirements for the implementation of the protocol;
p.000004: 2. documents certifying the available technical capabilities for the implementation of the protocol for each of the
p.000004: the centers offered, including documents for certification, accreditation and established quality control and / or
p.000004: external quality assessment;
p.000004: 3. CV and / or other documents certifying the education and qualification of
p.000004: the members of the research team and compliance with the requirements of Art. 86, para. 2 CLPM.
p.000004: 4. (Repealed, SG No. 25/2018)
p.000004: (2) The documents under item 2 shall be prepared by a specialized independent organization and / or the head of the
p.000004: the medical establishment and / or structure in which each specific procedure is planned to be performed
p.000004: equipment described in the protocol.
p.000004: (3) (Amended, SG No. 25/2018) The documents under item 3 shall be submitted to the coordinating researcher,
p.000004: principal investigator for each of the centers offered. At the request of the Ethics Committee
p.000004: the documents under item 4 shall also be presented to the other persons of the research team.
p.000004: (4) (New, SG No. 25/2018) The Ethics Committee shall carry out an ex officio verification of the circumstances
p.000004: under Art. 87, para. 1 of the LMPHM.
p.000004: Art. 7. The data for financing and administrative organization of the survey under Art.
p.000004: 110, para. 1, item 6 of LMPHM contain:
p.000004: 1. insurance covering the liability of the contracting authority and the principal investigator (s) for the reasons caused on or in connection with
p.000004: the conduct of the clinical trial non-material and material damage to the participants;
p.000004: 2. information on the anticipated benefits and compensations in the event of death or damage to the health of
p.000004: the participant in conducting the clinical trial;
p.000004: 3. (Supplemented, SG No. 77/2016, effective 04.10.2016) draft contract between the assignor and
p.000004: the participants in the trial, which also determines the remuneration for participation, where provided for;
...
p.000004: who are unable to consent.
p.000004: 1.59. Well-being (of clinical trial participants)
p.000004: Physical and mental integrity of participants in the clinical trial
p.000004: 2. PRC principles
p.000004: 2.1. Clinical trials shall be conducted in accordance with the ethical principles set out in the Declaration of Conformity
p.000004: Helsinki and comply with DCT and applicable regulatory requirements.
p.000004: 2.2. Before starting a test, all the foreseeable risks are compared with the expected benefit
p.000004: individually for the participant and for the community. A clinical trial can only begin and continue if foreseeable
p.000004: the benefits justify the risks.
p.000004: 2.3. The rights, safety and well-being of test participants are paramount and
p.000004: stand above the interests of science and society.
p.000004: 2.4. Available non-clinical and clinical information on the investigational medicinal product should be sufficient
p.000004: support for the proposed clinical trial.
p.000004: 2.5. Clinical trials must be scientifically relevant and described in a clear and detailed manner
p.000004: protocol.
p.000004: 2.6. A clinical trial shall be conducted in accordance with a protocol that has been approved in advance
p.000004: by the Ethics Committee.
p.000004: 2.7. Medical monitoring and medical decisions, with regard to participants, are taken by the doctor or, where appropriate
p.000004: necessary - by a dentist.
p.000004: 2.8. Each person charged with conducting a clinical trial has education, qualification
p.000004: and attempting to fulfill the relevant test obligations.
p.000004: 2.9. Before entering a clinical trial, each participant is freely informed
p.000004: consent.
p.000004: 2.10. All clinical trial information must be recorded, maintained and stored in a manner permitting
p.000004: its accurate reporting, interpretation and verification.
p.000004: 2.11. The confidentiality of documents which may reveal the identity of the participants is retained,
p.000004: subject to the applicable regulatory requirements for secrecy and confidentiality.
p.000004: 2.12. The tested medicinal products are manufactured, maintained and stored in
p.000004: compliance with the applicable GMP. They shall be used in accordance with an approved protocol.
p.000004: 2.13. Procedures are in place at all stages of the clinical trial to ensure the quality of each stage of
p.000004: conducting the study.
p.000004: 3. Ethics Committee
p.000004: 3.1. Obligations
p.000004: 3.1.1. Each Ethics Committee protects the rights, safety and well - being of all participants in the
p.000004: the clinical trial. Particular attention is paid to clinical trials involving vulnerable groups
p.000004: patients.
p.000004: 3.1.2. The Ethics Committee receives the following documents: Clinical Trial Protocol / Changes, Form for
p.000004: written informed consent and changes to those forms that the researcher proposes to use in
p.000004: clinical trial, patient recruitment procedures (eg announcements), written information on
...
p.000004: significantly affecting the conduct of the clinical trial (see 4.10.2); all the side effects
p.000004: reactions that are both serious and unexpected; new information that may incorrectly affect the safety of individuals
p.000004: or conducting the clinical trial;
p.000004: 3.3.9. a requirement that the Ethics Committee immediately notify in writing
p.000004: the researcher / institution for the clinical trial decisions / opinions; the reasons
p.000004: on its decisions / opinions and the procedures for appealing the decisions / opinions of the
p.000004: ethics.
p.000004: 3.4. Documents
p.000004: The Ethics Committee shall keep all relevant documents (eg written standard operating procedures, lists of records)
p.000004: members, appointment orders, members' job listings, conflicts of interest declarations and
p.000004: confidentiality, documents submitted, meeting minutes and correspondence) for the period no
p.000004: less than three years after termination of the clinical trial and make them available on request to the regulatory ones
p.000004: organs.
p.000004: The Ethics Committee shall provide the investigator, the sponsor or the regulatory authorities with its written documents
p.000004: procedures and orders determining the list of members upon request.
p.000004: 4. Researcher
p.000004: 4.1. Qualification and responsibilities of the researcher
p.000004: 4.1.1. The researcher (s) have the appropriate education, qualifications and experience to assess responsibility for the
p.000004: the proper conduct of the clinical trial; meets all regulatory requirements
p.000004: authorities, and provides proof of his / her qualification through an updated CV and / or others
p.000004: documents required by the contracting authority, the ethics committee and / or regulatory authorities.
p.000004: 4.1.2. The researcher is familiar with the proper use of the test drug as it is
p.000004: referred to in the protocol, the researcher's current brochure, product information and any other sources
p.000004: information provided by the contracting authority.
p.000004: 4.1.3. The researcher knows and complies with the requirements of the DCT and the applicable regulatory requirements.
p.000004: 4.1.4. The researcher permits monitoring, verification by the contracting authority and inspection by
p.000004: the relevant regulatory authorities.
p.000004: 4.1.5. The researcher shall keep a list of the persons with the necessary qualifications to whom he has delegated responsible duties,
p.000004: related to the clinical trial.
p.000004: 4.2. Test Opportunities
p.000004: 4.2.1. The researcher must be able to show the ability to dial the required number
p.000004: appropriate patients within the agreed period (eg based on retrospective data).
p.000004: 4.2.2. The investigator has sufficient time to conduct and complete the clinical trial within the agreed timeframe.
p.000004: 4.2.3. The researcher has the necessary number of qualified personnel and the appropriate equipment for the foreseen
p.000004: the duration of the clinical trial for proper and safe conduct.
...
Social / embryo
Searching for indicator embryo:
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p.000004: sets the date of the written informed consent form after it, as well as any other written consent
p.000004: information is presented, read and explained to participants or their legal representatives and after
p.000004: having verbally confirmed their participation in the clinical trial and (if able) signed and
p.000004: personally set a date. By his signature, the witness confirms that the written informed consent form as well
p.000004: any other written information has been properly explained and understood by the participants or their legal information
p.000004: representatives and consent was given by the participants themselves or their legal representatives.
p.000004: 4.8.10. The written informed consent form and any other written information provided to participants,
p.000004: contains explanations for the following:
p.000004: 4.8.10.1. that the clinical trial is a scientific research process;
p.000004: 4.8.10.2. the purpose of the clinical trial;
p.000004: 4.8.10.3. the treatment (s) tested and the likelihood of any treatment being randomly assigned;
p.000004: 4.8.10.4. the procedures to be performed during the clinical trial, including
p.000004: invasive manipulations;
p.000004: 4.8.10.5. the obligations of the participants;
p.000004: 4.8.10.6. those aspects of the clinical trial that are experimental;
p.000004: 4.8.10.7. reasonably foreseeable risks or inconveniences to participants, as well as to an embryo, fetus or infant,
p.000004: when necessary;
p.000004: 4.8.10.8. reasonably expected benefits; participants are informed of cases where no clinical benefit is expected;
p.000004: 4.8.10.9. the alternative procedures and treatment courses that are possible for the participants and important
p.000004: their potential risks and benefits;
p.000004: 4.8.10.10. compensation and / or possible treatment for participants in case of clinical trial related impairment;
p.000004: 4.8.10.11. anticipated, in proportion to time participation, payment for volunteers / patients
p.000004: their participation in the clinical trial, if any;
p.000004: 4.8.10.12. estimated costs for participants to participate in the clinical trial;
p.000004: 8/4/13 explanation that participation in the clinical trial is voluntary and that the participant may refuse to participate
p.000004: or withdraw at any time without the penalty or loss of benefits that the participant may
p.000004: to receive otherwise;
p.000004: 4.8.10.14. indicate that the monitoring, reviewing, ethics committee and regulatory bodies are
p.000004: provided access to the participant's original medical records for verification of clinical procedures
p.000004: testing and / or data, ensuring that the patient's personal data is protected in accordance with applicable laws and
p.000004: regulations, and by signing the written informed consent form, the participant or his or her legal
p.000004: the representative agrees to such access;
...
Social / gender
Searching for indicator gender:
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p.000004: Summary of pharmacokinetics and biological transformation and test layout presented
p.000004: medicinal product in all species tested. The commentary on the findings includes absorption, local and
p.000004: the systemic bioavailability of the investigational medicinal product and its metabolites and their relationship with
p.000004: pharmacological and toxicological findings in animal species.
p.000004: 7.3.5.3. Toxicology
p.000004: A summary of the toxicological effects found in relevant studies conducted on different subjects shall be provided
p.000004: animal species, including the following: single dose toxicity; repeated dose toxicity
p.000004: dosing; carcinogenicity; special tests (eg irritability and sensitivity); reproductive toxicity;
p.000004: genotoxicity (mutagenicity).
p.000004: 7.3.6. Effects in humans
p.000004: A full description of the known effects of the tested product (s) on humans, including information on
p.000004: pharmacokinetics, metabolism, pharmacodynamics, dose response, safety, efficacy and other pharmacological
p.000004: actions. Whenever possible, a summary of each completed clinical trial as well as
p.000004: information regarding the results of any use of the test medicinal product to be tested
p.000004: different from clinical trials (eg post-market experience).
p.000004: 7.3.6.1. Pharmacokinetics and metabolism of the product in humans
p.000004: A summary of the pharmacokinetics of the investigational medicinal product shall be provided,
p.000004: which, if possible, includes the following: pharmacokinetics (including metabolism and absorption, binding to
p.000004: plasma proteins, distribution and elimination); bioavailability (where possible absolute and / or relative),
p.000004: using a dosage form for comparison; subgroups of the population (eg gender, age and impaired function)
p.000004: to an authority); interactions (eg product-product interactions or food effects); others
p.000004: pharmacokinetic data (eg, results from population-based studies conducted in clinical trials).
p.000004: 7.3.6.2. Safety and efficiency
p.000004: A summary of information obtained from previous human clinical trials (healthy volunteers) is provided
p.000004: and / or patients) for the safety, pharmacodynamics, efficacy and dose response of the product (s) tested
p.000004: (and their metabolites where appropriate). The conclusions of this information are commented. Where they are
p.000004: completed a large number of clinical trials, the use of safety and efficacy summaries of
p.000004: multiple sub-group indication tests may be representative of the data. Summaries can
p.000004: also be presented in tabular form for adverse reactions for all clinical trials (incl.
p.000004: those for all testimony tested). Important differences in trends / incidence of
p.000004: side effects against indications or subgroups.
p.000004: A description of the potential risks and undesirable effects is provided
p.000004: reactions based on direct experience with the study drug
p.000004: product and related products, as well as precautions or special observations that
p.000004: to be carried out during the tested use of the medicinal product (s).
p.000004: 7.3.6.3. Experience after authorization for use
p.000004: Indicate the countries in which the test medicinal product is authorized. Commented
...
Social / philosophical differences/differences of opinion
Searching for indicator opinion:
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p.000004: the medical establishment - the center of the clinical trial;
p.000004: 6. written consent under Art. 87, para. 3 CLPM;
p.000004: 7. data on the source of financing of the study, where the assignor is a legal entity with
p.000004: non-agricultural aim;
p.000004: 8. document for paid fee.
p.000004: Art. 8. (1) For clinical trial of a medicinal product under Art. 88 of the LPPMM the contracting entity or a person authorized by it
p.000004: submit to the Executive Agency for Medicinal Products an application for a clinical trial using a specimen.
p.000004: (2) The documents under art. 2, 3, 4, 5, 6, 7, 9 and Art. 19, para. 3, as well as the declarations under art. 122
p.000004: and 123 ZLPHM.
p.000004: (3) (Repealed, SG No. 14/2012, New SG No. 25/2018) The Executive Agency for Medicines shall perform
p.000004: verification by official means for the presence of the circumstances under Art. 87, para. 1 of
p.000004: CLPM.
p.000004: Art. 9. The sponsor or the person authorized by him / her shall submit to the Drug Enforcement Agency
p.000004: the following documentation under Art. 116, para. 4, Vol. 4 of ZLPHM:
p.000004: 1. dossier of the tested medicinal product;
p.000004: 2. documentation certifying the production of the tested products under the conditions of Good
p.000004: manufacturing practice;
p.000004: 3. analytical certificate of the product under test where impurities are not justified in the specification or when
p.000004: identify uncharacterized impurities;
p.000004: 4. results of viral safety tests;
p.000004: 5. certificate for the absence of causative agents of portable spongiform encephalopathy;
p.000004: 6. models on the label in Bulgarian;
p.000004: 7. opinion from the Ministry of Environment and Water regarding the potential risk for
p.000004: the environment when the test medicinal product contains genetically modified organisms.
p.000004: Art. 10. (1) The dossier of the tested medicinal product shall be prepared in accordance with the published ones
p.000004: European Commission guides in format and content according to Annex 2.
p.000004: (2) Where the investigational medicinal product is manufactured within the European Union and does not exist
p.000004: authorization for use, instead of the document under Art. 9, item 2 shall be submitted a copy of the manufacturing authorization for
p.000004: medicinal products under development and research issued by a Member State of the European Union.
p.000004: (3) Where the investigational medicinal product is not manufactured within the European Union and
p.000004: not authorized, the following production documents must be submitted:
p.000004: 1. a document from the qualified person of a natural or legal person holding a permit for import into the territory
p.000004: of the European Union certifying compliance of the conditions of manufacture, control and storage with
p.000004: standards equivalent to the requirements of Good manufacturing practice for medicinal products in the process
p.000004: development and research valid for the territory of the European Union;
p.000004: 2. a copy of the import authorization for the territory of the European Union;
...
p.000004: Art. 11. (Repealed, SG No. 14/2012)
p.000004: Section III.
p.000004: Requirements to the documentation for changing the authorization for conducting clinical trials (Title amended - SG, issue 14 of
p.000004: 2012)
p.000004: Art. 12. Substantial change under Art. 127, para. 2 LPPM is present when there is a change in the data specified in
p.000004: Annex 3.
p.000004: Art. 13. (1) When planning significant changes in the clinical trial and in the documentation under
p.000004: Art. 110 LPPMH the contracting authority or a person authorized by it submits a written application in the form to the committee on
p.000004: ethics under art. 103 CLPM.
p.000004: (2) The application shall be accompanied by the following documentation:
p.000004: 1. cover letter;
p.000004: 2. summary of the planned change;
p.000004: 3. a list of the updated documents;
p.000004: 4. the updated documentation under Art. 2, 3, 4, 5, 6 and 7 reflecting changes;
p.000004: 5. pages of documentation with marked changes comparing current and proposed new ones
p.000004: texts;
p.000004: 6. justification of the changes;
p.000004: 7. copy of the application for conducting a clinical trial under Art. 2 with tagged changes, electronic and
p.000004: paper;
p.000004: 8. document for paid fee.
p.000004: Art. 14. (1) When planning significant changes in the clinical trial and in the documentation under
p.000004: Art. 116 of the LPPHM the contracting entity or a person authorized by it submits to the Executive Agency for Medicines
p.000004: a written application for a model change.
p.000004: (2) The application shall be accompanied by the documentation under Art. 13, para. 2, items 1, 2, 3, 4, 5, 6 and 8, the declaration under art. 123
p.000004: LMPHM and a copy of the positive opinion of the Ethics Committee, when available.
p.000004: (3) The application under Art. 8, para. 1, complete with updated information reflecting the proposed change,
p.000004: as well as a copy of the marked changes, in electronic and hard copy.
p.000004: (4) In case of changes under Art. 127, para. 1 LPPMM application must be submitted within 14 days of receipt
p.000004: Notification from the Medicines Executive Agency of the necessary change.
p.000004: Art. 15. (Repealed, SG No. 14/2012)
p.000004: Section III "a".
p.000004: Requirements to the documentation for conducting non-interventional research and changes thereto (New, SG No. 14/2012)
p.000004: d)
p.000004: Art. 15a. (New, SG No. 14/2012) For non-interventional study of a medicinal product under Art. 145
p.000004: The CLPMM, the sponsor or the authorized person, represents in the Executive Agency for Medicines and in
p.000004: the ethics committee under art. 103 LMPHM application form for conducting non-interventional study.
p.000004: Art. 15b. (New, SG No. 14/2012) The administrative documentation for the studies under Art. 145 LPPMM contains:
p.000004: 1. cover letter;
p.000004: 2. application form;
p.000004: 3. a list of all planned centers and principal investigators for the territory of the Republic of Bulgaria;
p.000004: 4. a copy of the recommendations of the Scientific Committee of the European Medicines Agency for planning advice
p.000004: studies undergoing a procedure;
p.000004: 5. a letter of attorney or contract for the authorization of the person submitting the application on behalf of
p.000004: the contracting authority where the applicant is not the contracting authority;
...
p.000004: retrospectively and anonymously medical information;
p.000004: 2. contract between the assignor and the researcher;
p.000004: 3. an agreement between the assignor and the test participants, which also determines the remuneration for
p.000004: participation where foreseen;
p.000004:
p.000004: non-agricultural aim;
p.000004: 5. document for paid state fee.
p.000004: Art. 15h. (New, SG No. 14/2012) (1) When planning significant changes in non-interventional
p.000004: study under art. 145 LPPMM the assignor or the authorized person submits to the Executive Agency under
p.000004: medicines and the Ethics Committee under Art. 103 LPPMM written application for change in the model.
p.000004: (2) To the application under para. 1, the following documentation shall be attached:
p.000004: 1. cover letter;
p.000004: 2. summary and justification of the planned changes;
p.000004: 3. a list of the updated documents;
p.000004: 4. the updated documentation under Art. 15b - 15g reflecting changes;
p.000004: 5. pages of documentation with marked changes comparing current and proposed new ones
p.000004: texts;
p.000004: 6. a statement that the documentation submitted to the Medicines Executive Agency and the Ethics Committee contains one
p.000004: and the same information;
p.000004: 7. document for paid state fee.
p.000004: (3) The contracting authority may apply a planned change to a non-interventional study under Art. 145 CLPM, if
p.000004: within one month of submitting the application for change did not receive an explicit refusal by the Director of the Executive
p.000004: medicines agency, respectively negative opinion from the ethics committee under art. 103 CLPM.
p.000004: Section IV.
p.000004: Requirements for documentation of test completion notification
p.000004: Art. 16. (1) The notification under art. 142, para. 2 LPPMM shall be submitted in a format approved by the Executive Director of
p.000004: The Executive Agency for Medicines, in paper and electronic form.
p.000004: (2) When the study is terminated before the condition stipulated in the protocol for the completion of the study is completed
p.000004: the test, the notification shall contain the following additional information:
p.000004: 1. justification for termination;
p.000004: 2. number of participants receiving the tested products in the centers on the territory of the Republic of Bulgaria, and a plan for
p.000004: medical care for them after termination of the study;
p.000004: 3. the impact of the discontinuation on the data evaluation and the risk / benefit ratio of the investigational medicinal product;
p.000004: 4. the significance of the data leading to the termination of the trial for other authorized clinical trials of
p.000004: the territory of the Republic of Bulgaria.
p.000004: Art. 17. All documents submitted to the Ethics Committee under Art. 103 LPPMM and the Executive Agency of the
p.000004: medicines bearing at least the following identification elements:
p.000004: 1. trial number from the European Clinical Trials Database;
p.000004: 2. protocol code;
p.000004: 3. version and date of the document.
p.000004: Art. 18. (1) The documentation for authorization, change and termination of a clinical trial shall be submitted to
p.000004: Bulgarian and / or English.
p.000004: (2) (amend. - SG 14/2012, amend. - SG 25/08) The documentation under art. 2, items 1, 2 and 5, art. 3, items 1, 2 and
...
p.000004: The principles laid down in these rules may also apply to others
p.000004: clinical trials that could have an impact on human safety and health.
p.000004: 1. Definitions
p.000004: 1.1. Adverse Reaction (ADR)
p.000004: "Undesirable effect" is any undesirable and unintended response to a medicinal product that occurs with
p.000004: administration of the product at doses normally used for the treatment, prophylaxis or diagnosis of disease in
p.000004: people or for recovery, correction or
p.000004: modification of physiological function. In the case of a clinical trial - any undesirable or unforeseen
p.000004: response to the investigational medicinal product, regardless of the dose administered. The phrase "answered one
p.000004: "means that the cause and effect relationship is between the medicinal product and the adverse reaction
p.000004: at least a reasonable possibility, that is, the connection cannot be denied.
p.000004: 1.2. Adverse event
p.000004: Adverse event is any adverse change in health status observed with the administration of a medicinal product.
p.000004: to a patient or participant in a clinical trial that is not necessarily causally related to this treatment.
p.000004: An adverse event may therefore be any adverse and unintended physical finding (incl.
p.000004: laboratory deviation), symptom, or illness associated with the use of (tested) drug over time
p.000004: product, whether or not it is causally related to the product.
p.000004: 1.3. Applicable requirements
p.000004: All regulatory requirements for conducting clinical trials with medicinal products.
p.000004: 1.4. Approval by the Ethics Committee
p.000004: Positive opinion from the Ethics Committee confirming that the clinical trial has been evaluated and can
p.000004: to be conducted at the established center under the conditions laid down by the Ethics Committee, the medical establishment, the CPT, and
p.000004: the applicable requirements.
p.000004: 1.5. Independent verification (audit)
p.000004: Systematic and independent evaluation of test-related obligations and assessment documents
p.000004: whether these obligations have been fulfilled, whether the data have been recorded, analyzed, carefully reported, in accordance with
p.000004: the protocol, standard operating procedures (SOPs) of the contracting entity, DCT and applicable regulatory requirements.
p.000004: 1.6. Certificate of verification
p.000004: Document from the verifier confirming that an inspection has been carried out.
p.000004: 1.7. Verification report
p.000004: Written evaluation of the verifier by the contracting authority for the results of the inspection.
p.000004: 1.8. Track for verification
p.000004: Documentation to track the sequence of events.
p.000004: 1.9. Blinding / masking
p.000004: A procedure in which one or more of the parties remain unaware of their assigned treatment
p.000004: preliminary agreement. Single-blind are usually trials in which patients remain unknown, a
p.000004: double-blind are trials in which patients, researchers, monitors, and sometimes
p.000004: data subjects remain unfamiliar with the treatment prescribed.
p.000004: 1.10. Clinical Patient Card (CCP)
p.000004: Printed, optical or electronic media prepared to record all the information required by the plan to report to
...
p.000004: conducting, reporting and reporting clinical trials to ensure that data and reporting
p.000004: the results are plausible and accurate and that the rights, privacy and confidentiality of the participants are preserved.
p.000004: 1.25. Independent Evaluation Committee
p.000004: Independent evaluation committee that can be set up by the contracting authority to evaluate certain
p.000004: time intervals of a clinical trial, safety data, baseline parameters
p.000004: efficiency and to formulate recommendations to the contracting authority whether to continue, change or terminate
p.000004: the test.
p.000004: 1.26. Independent witness
p.000004: A person who: does not participate and has no interest in the clinical trial; cannot be influenced by
p.000004: test participants; be present at the signing of the informed consent if the participant or his / her
p.000004: legal representative cannot read, and reads informed consent form and any other
p.000004: written information provided to participants.
p.000004: 1.27. Ethics Committee
p.000004: Independent structure (institutional, regional, national or supranational committee or committee) composed
p.000004: by medical / scientific professionals and non-medical / non-scientific members. The primary responsibility of the Ethics Committee is to
p.000004: preserve the rights and safety of the people involved in the test and provide public assurance to
p.000004: this protection. The defense is realized by reviewing and giving an opinion on the clinical protocol
p.000004: testing and materials for obtaining and documenting informed consent of participants and
p.000004: assessment of whether the researchers, the conditions, the methods for conducting the test are appropriate.
p.000004: 1.28. An informed consent
p.000004: Informed consent is a statement of will that must be written, personally dated and signed in order to participate in
p.000004: a clinical trial taken completely free after being duly informed of its nature,
p.000004: significance, consequences and risks and appropriately documented by any person who is able to give
p.000004: his consent, or when the person is unable to give his consent, from his legal representative.
p.000004: 1.29. Inspection
p.000004: Official inspection of the inspection bodies for documents, conditions, records and any other data sources provided
p.000004: are considered by them to be related to the clinical trial and may be stored at the clinical venue
p.000004: testing, the office of the contracting authority / DIO or other places deemed appropriate by these inspection bodies.
p.000004: 1.30. Institution (medical)
p.000004: Medical establishments where clinical trials are conducted.
p.000004: 1.31. Interim clinical trial report
p.000004: Report on the provisional results of the study and their evaluation based on analyzes made during the
p.000004: conducting the clinical trial.
p.000004: 1.32. Tested medicinal product
...
p.000004: 2.12. The tested medicinal products are manufactured, maintained and stored in
p.000004: compliance with the applicable GMP. They shall be used in accordance with an approved protocol.
p.000004: 2.13. Procedures are in place at all stages of the clinical trial to ensure the quality of each stage of
p.000004: conducting the study.
p.000004: 3. Ethics Committee
p.000004: 3.1. Obligations
p.000004: 3.1.1. Each Ethics Committee protects the rights, safety and well - being of all participants in the
p.000004: the clinical trial. Particular attention is paid to clinical trials involving vulnerable groups
p.000004: patients.
p.000004: 3.1.2. The Ethics Committee receives the following documents: Clinical Trial Protocol / Changes, Form for
p.000004: written informed consent and changes to those forms that the researcher proposes to use in
p.000004: clinical trial, patient recruitment procedures (eg announcements), written information on
p.000004: participants, researcher's brochure, available safety information, billing information and compensation
p.000004: of patients, insurance for patients / volunteers and researchers, up-to-date CV of
p.000004: the researcher (s) and / or other documents proving their qualifications and other supporting documents
p.000004: documents which the commission may require to carry out its functions.
p.000004: It reviews the proposed clinical trial within the time limit set by law and documents its own
p.000004: written opinion with clearly stated clinical trial topic and documents reviewed and dated with respect to
p.000004: the following:
p.000004: 3.1.2.1. positive opinion;
p.000004: 3.1.2.2. amendments requested before a favorable opinion;
p.000004: 3.1.2.3. negative opinion;
p.000004: 3.1.2.4. amendment of a positive opinion already issued.
p.000004: 3.1.3. The Ethics Committee evaluates the researcher 's qualification for the proposed clinical trial by
p.000004: an up-to-date CV of the researcher and / or other relevant documents as may be required.
p.000004: 3.1.4. The Ethics Committee conducts ongoing oversight of every ongoing clinical trial at intervals,
p.000004: relevant to the risk to humans, but at least once a year.
p.000004: 3.1.5. The Ethics Committee may, at its discretion, require the submission of more information than described
p.000004: in clause 4.8.10, where this addition is relevant for the protection of the rights and safety and / or health of
p.000004: the patients.
p.000004: 3.1.6. In the cases of items 4.8.12 and 4.8.14, when it is necessary to conduct a non-therapeutic test
p.000004: the consent of the legal representative of the participant, the Ethics Committee decides whether the proposed protocol
p.000004: and / or other documents comply with ethical standards and whether they meet the applicable regulatory requirements for that type
p.000004: tests.
p.000004: 3.1.7. In the cases of item 4.8.15, where the clinical trial protocol permits patient involvement,
p.000004: without the immediate written consent or consent of his legal representative,
p.000004: the ethics committee decides whether the proposed plan and / or other documents are ethical
...
p.000004: quantity, method of payment and periodicity. The way the payment will be distributed should be
p.000004: indicated.
p.000004: 3.2. Composition, functions and actions
p.000004: 3.2.1. The Ethics Committee is composed of members who, as a team, have sufficient qualifications and experience
p.000004: to consider and evaluate the scientific, medical and ethical aspects of the proposed clinical trial. The Commission
p.000004: Ethics includes at least 7 members, of which at least two are non-medical, financial and
p.000004: administratively independent of the clinical trial site.
p.000004: Only those members who are independent of the Assembly may vote and vote
p.000004: the principal investigator and the assignor.
p.000004: The Ethics Committee shall keep a list of the members and their qualifications as well as the official documents for the
p.000004: its creation.
p.000004: 3.2.2. The Ethics Committee shall perform its functions in accordance with written standard operating procedures, with the DCP and
p.000004: applicable regulatory requirements and keep records of its activities and minutes of meetings.
p.000004: 3.2.3. The Ethics Committee shall take its decisions at pre-announced meetings in the presence of a quorum set out in
p.000004: standard operating procedures.
p.000004: 3.2.4. Only members of the Ethics Committee who participated in the discussions and opinions may vote / express an opinion.
p.000004: reviewing the study documentation.
p.000004: 3.2.5. The researcher can provide information in any aspect regarding the clinical trial, but it cannot
p.000004: to participate in the deliberations or to give opinions / votes during the meetings of the Ethics Committee.
p.000004: 3.2.6. The Ethics Committee may invite experts in various specialties to assist.
p.000004: 3.3. Procedures
p.000004: The Ethics Committee shall develop, document and follow standard operating procedures, which include the following:
p.000004: 3.3.1. determining the composition (names and positions of members) and the reason for appointment;
p.000004: 3.3.2. planning meetings, notifying members and conducting meetings;
p.000004: 3.3.3. conducting initial and ex-post evaluation of studies;
p.000004: 3.3.4. determining the frequency of periodic ex-post reassessment of studies;
p.000004: 3.3.5. providing an accelerated assessment of minimum changes for on-going clinical trials already approved, c
p.000004: compliance with regulatory requirements;
p.000004: 3.3.6. confirmation that no participant can be enrolled in a clinical trial before the
p.000004: ethics to issue a positive opinion;
p.000004: 3.3.7. confirmation that no deviations or changes can be applied to the protocol before
p.000004: the immediate affirmative affirmative of the change, except where
p.000004: it is necessary to avoid immediate risks for participants or when changes affect them
p.000004: logistical and administrative aspects of the test (e.g. change of monitoring person,
p.000004: telephone numbers) according to the obligations of the researcher under item 4.5.2;
p.000004: 3.3.8. a requirement that the researcher immediately notify the Ethics Committee of any deviations or changes to the protocol,
p.000004: when it is necessary to avoid the immediate risks to participants in accordance with 3.3.7 and
p.000004: the obligations of the researcher under 4.5.2 and 4.5.4; changes that increase the risk to participants and / or
p.000004: significantly affecting the conduct of the clinical trial (see 4.10.2); all the side effects
p.000004: reactions that are both serious and unexpected; new information that may incorrectly affect the safety of individuals
p.000004: or conducting the clinical trial;
p.000004: 3.3.9. a requirement that the Ethics Committee immediately notify in writing
p.000004: the researcher / institution for the clinical trial decisions / opinions; the reasons
p.000004: on its decisions / opinions and the procedures for appealing the decisions / opinions of the
p.000004: ethics.
p.000004: 3.4. Documents
p.000004: The Ethics Committee shall keep all relevant documents (eg written standard operating procedures, lists of records)
...
p.000004: 4.2.3. The researcher has the necessary number of qualified personnel and the appropriate equipment for the foreseen
p.000004: the duration of the clinical trial for proper and safe conduct.
p.000004: 4.2.4. The researcher shall ensure that all persons participating in the clinical trial are sufficiently informed about
p.000004: the protocol, the investigational medicinal product (s), and the clinical trial's duties and functions.
p.000004: 4.3. Medical care for participants
p.000004: 4.3.1. Responsibility for all clinical trial related medical decisions lies with a qualified physician, or
p.000004: where appropriate, by a dentist who is a researcher or co-investigator in a clinical trial.
p.000004: 4.3.2. During and after the participation of the subjects in the clinical trial, the researcher guarantees the provision
p.000004: sufficient medical surveillance of the participants in relation to any adverse event, incl. clinically important
p.000004: laboratory test related results. The researcher informs the patient of the need for medical
p.000004: monitoring for the additional illness he has identified.
p.000004: 4.3.3. If the participant has a physician and if his or her physician has agreed to
p.000004: be informed, the investigator informs him or her of the patient's involvement in the clinical trial.
p.000004: 4.3.4. Although the participant is not required to explain the reasons for withdrawal from the clinical trial,
p.000004: the researcher may endeavor to identify these causes, while fully respecting the patient's rights.
p.000004: 4.4. Correspondence with the Ethics Committee
p.000004: 4.4.1. Before starting the clinical trial, the researcher must have a written date
p.000004: a positive opinion from the Ethics Committee on the clinical trial protocol, the form in writing
p.000004: consent, changes to consent form, patient recruitment procedures (eg announcements) and any other written
p.000004: information to be provided to the participant.
p.000004: 4.4.2. The researcher shall submit to the Ethics Committee a copy of the current brochure of the investigating physician as
p.000004: application of the written request to the Ethics Committee for opinion. If changes occur during the clinical trial
p.000004: in the booklet, the researcher presents to the Ethics Committee a new copy including the changes.
p.000004: 4.4.3. During the clinical trial, the investigator shall submit to the Ethics Committee for review
p.000004: all documents concerning the participants.
p.000004: 4.5. Protocol compliance
p.000004: 4.5.1. The researcher shall carry out the clinical trial in accordance with a protocol previously approved by
p.000004: the contracting authority and the regulatory authority and who has received a favorable opinion from the ethics committee. The researcher and
p.000004: the contracting authority shall sign the protocol or supplementary agreement, by which the researcher confirms his / her agreement to
p.000004: compliance with it.
p.000004: 4.5.2. The researcher may not make any deviations or changes to the protocol without the consent of
p.000004: the contracting authority and the preliminary examination and documented positive opinion of the changes by the commission
p.000004: ethics. Deviations from the requirements of the plan can only be made when there are good reasons for being
p.000004: endangering the life, health and rights of the persons surveyed, or where the changes involve only organizational or
p.000004: administrative aspects of the clinical trial (eg change of monitoring person, change of telephone
p.000004: numbers).
p.000004: 4.5.3. The researcher or his authorized representative shall document and explain any deviation from the approvals
p.000004: protocol.
p.000004: 4.5.4. The researcher may make a deviation or change in the avoidance protocol
p.000004: an imminent threat to patients without the immediate positive opinion of the Ethics Committee.
p.000004: The deviation, change or plan with proposed changes shall be submitted to the committee as soon as possible
p.000004: assessment ethics and opinion, consenting authority and regulatory authorities.
p.000004: 4.6. Tested medicinal product
p.000004: 4.6.1. Responsibility for the accountability of the investigational medicinal product at the clinical site
p.000004: the test is carried out by the researcher.
p.000004: 4.6.2. The researcher may assign some or all of his reporting responsibilities to
p.000004: the pharmacist's or other appropriate person's place (s) under the direction of the researcher,
p.000004: when permissible or required.
p.000004: 4.6.3. The researcher and / or pharmacist or other person designated by the researcher shall keep the records for
p.000004: medicines received at the venue, inventory of products at the center, the quantities used by each
p.000004: participant and the quantities returned to the contracting authority or at an additional place. These documents contain dates, quantities,
p.000004: batches and numbers, expiry date (where possible) and unique code numbers indicating the medicinal products
p.000004: products and participants. The researchers keep documents stating that the participants have received
p.000004: the relevant doses specified in the plan and confirmation and reporting of all medicinal products received by the contracting entity
p.000004: products.
p.000004: 4.6.4. The tested medicinal product (s) shall be stored in a manner determined by the contracting entity, in accordance with paragraph 2.
p.000004: 5.13.2 and 5.14.3, and in accordance with applicable regulatory requirements.
p.000004: 4.6.5. The researcher confirms that the tested medicinal products are used only in accordance with
p.000004: approved protocol.
p.000004: 4.6.6. The investigator, or a person designated by him, explains the proper use of the test drug
p.000004: product of each individual participant and at appropriate intervals and checks that each participant complies
p.000004: correct instructions.
p.000004: 4.7. Randomization and disclosure procedures
p.000004: The researcher must follow the randomization procedures of the clinical trial, if any
p.000004: such, and must confirm that code disclosure is made only in accordance with the protocol. If the clinical
p.000004: the test is blinded, the researcher documents and explains to the client any premature disclosure
p.000004: code (e.g., accidental detection, detection as a result of a serious unwanted event) of
p.000004: the investigational medicinal product (s).
p.000004: 4.8. Informed consent of participants
p.000004: 4.8.1. During the receipt and documentation of informed consent, the researcher complies
p.000004: the applicable regulatory requirements, the principles of the CPT and the ethical principles enshrined in the Declaration of
p.000004: Helsinki. In order to begin the clinical trial, the researcher must have a positive opinion in writing
p.000004: of the Ethics Committee on the written informed consent and any other written information to be provided
p.000004: provided to participants.
p.000004: 4.8.2. The written informed consent form and any other written information provided to participants shall be
p.000004: updates when important new information becomes available that may affect their consent. Each
p.000004: an updated form of written informed consent and written information should have a positive opinion of
p.000004: the ethics committee prior to its implementation. The participant or his legal representative shall be promptly informed
p.000004: notify when important new information becomes available that may affect their desire to
p.000004: continue to participate in the clinical trial. Communications regarding new information shall be documented
p.000004: timely.
p.000004: 4.8.3. Neither the principal investigator nor the research staff can coerce or give in
p.000004: mislead the person to participate or continue to participate in the clinical trial.
p.000004: 4.8.4. No oral or written information pertaining to the clinical trial, including the format for
p.000004: written informed consent may not contain words and expressions that coerce or sound coercive to the participant
p.000004: or his legal representative to waive any of his legal rights or to release or to impose
p.000004: discharge for negligence of the researcher, contracting authority, institution or
p.000004: their representatives.
p.000004: 4.8.5. The researcher or the person authorized by him / her shall inform the participant or in case he / she cannot give
p.000004: his consent, his legal representative for all aspects of the clinical trial, including
p.000004: the provision of written information and the favorable opinion of the Ethics Committee.
p.000004: 4.8.6. The language used in the oral or written information for the clinical trial, including the written form
p.000004: informed consent must be without medical terms and sufficiently accessible to be
p.000004: understood by the participant or his legal representative and, where appropriate, by the independent witness.
p.000004: 4.8.7. Prior to obtaining written informed consent, the Principal Investigator or a person authorized by him or her
p.000004: obliged to provide the participant or his or her legal
p.000004: representative sufficient time and opportunity to discuss the details of the clinical trial and yes
p.000004: decide whether or not to participate. All questions asked by the participant or his legal representative must
p.000004: replied in full.
p.000004: 4.8.8. Before engaging the participant, written informed consent must be signed personally and
p.000004: set the date by the participant or his legal representative and by the person interviewing the
p.000004: of the participant.
p.000004: 4.8.9. In case the participant or his legal representative cannot read during the discussion
p.000004: informed consent shall be provided by the presence of an independent witness. The witness also signs personally
p.000004: sets the date of the written informed consent form after it, as well as any other written consent
p.000004: information is presented, read and explained to participants or their legal representatives and after
...
p.000004: information provided to participants. During the clinical trial, each participant or his or her
p.000004: the legal representative receives a copy of the modified informed consent form as well as the changes
p.000004: in any other written information provided to participants.
p.000004: 4.8.12. When a clinical trial (therapeutic or non-therapeutic) requires the inclusion of participants only
p.000004: with the consent of their legal representatives, participants are informed of the clinical trial at the
p.000004: according to their ability to understand and personally sign and date the written informed
p.000004: consent (if able).
p.000004: 4.8.13. Except as indicated in section 4.8.14, a non-therapeutic trial (ie, a trial in which
p.000004: direct clinical benefit is provided for participants) is conducted on individuals who have personally signed and dated
p.000004: of the informed consent form.
p.000004: 4.8.14. Non-therapeutic trials may be conducted on individuals with the consent of their legal representatives
p.000004: only when:
p.000004: 4.8.14.1. test objectives cannot be achieved by testing participants who
p.000004: may personally give informed consent;
p.000004: 4.8.14.2. the foreseeable risks to persons are small;
p.000004: 4.8.14.3. the negative impact on participants is minimal and low;
p.000004: 4.8.14.4. the clinical trial is not prohibited by law;
p.000004: 4.8.14.5. the authorization / opinion of the Ethics Committee explicitly mentions the inclusion of
p.000004: it is precisely such persons and the written permission / affirmation covers this aspect.
p.000004: Such trials (to the extent that the exception is justified) shall be conducted on patients suffering from
p.000004: disease or condition for which the investigational medicinal product is intended. The participants in these
p.000004: tests shall be strictly monitored and withdrawn in the event of undue damage.
p.000004: 8/4/15 In emergencies where the immediate consent of the participant is not possible, it is required
p.000004: the consent of his legal representative, if any. When the direct consent of the participant and of
p.000004: its legal representative cannot be obtained, inclusion can be made if necessary
p.000004: an immediate decision to save the patient's life as required by the protocol and / or other
p.000004: place, through the written favorable opinion of the Ethics Committee, with a view to retaining rights,
p.000004: the safety and well-being of the individual and ensuring compliance with applicable regulatory requirements.
p.000004: The person or his legal representative shall be informed as soon as possible of the clinical trial and should
p.000004: be asked to document their agreement
p.000004: to continue participation in the clinical trial according to the procedure of item 4.8.10.
p.000004: 4.9. Documents and reports
p.000004: 4.9.1. The researcher ensures the accuracy, completeness, legibility and timely reporting of the data
p.000004: of the client in the clinical patient records (CCPs), as well as in all required reports.
p.000004: 4.9.2. The data obtained from source documents and recorded in the CCP is contained in these
p.000004: source documents, and discrepancies are explained.
p.000004: 4.9.3. Any change or correction to the CCP shall be dated, initials and (if necessary) shall be dated
p.000004: explains and should not doubt the original entry (ie, the trace of the check is kept).
p.000004: This applies to both the written and the electronic corrections according to item 5.18.4.14. The contracting authority supplies
p.000004: the researcher and / or the person designated by the researcher to make such adjustments with instructions.
p.000004: Contracting entities shall have written procedures certifying that changes or corrections have been made to
p.000004: The CCP was required, documented and signed by the contracting entity or its designees.
p.000004: the researcher. The researcher keeps records of changes and corrections in the CCP.
p.000004: 4.9.4. (amend. - SG 14/2012) The researcher / institution shall store
...
p.000004: 4.11.3. In the event of a reported death, the investigator submits to the sponsor and the ethics committee
p.000004: any additional information (eg autopsy protocol and final medical report).
p.000004: 4.12. Premature completion or termination of testing
p.000004: If the test is terminated prematurely or terminated for any reason, the investigator shall
p.000004: immediately notify trial participants and provide them with appropriate treatment and follow-up and, where appropriate
p.000004: requires the applicable regulatory requirements to notify regulatory authorities.
p.000004: 4.12.1. If the researcher discontinues or completes the clinical trial without prior consent
p.000004: of the contracting authority, is obliged to notify the medical institution, the contracting authority and the ethics committee, the regulatory body
p.000004: of the country where the study center is located by submitting them in writing in detail
p.000004: explanation for termination or termination.
p.000004: 4.12.2. If the contracting authority completes or suspends one test, the investigator shall inform in good time
p.000004: the medical establishment, the ethics committee and the regulatory body of the country where the center of the
p.000004: the study by providing them with a detailed written explanation of the suspension or closure.
p.000004: 4.12.3. If the Ethics Committee withdraws or terminates its affirmative opinion on a test in accordance with para.
p.000004: 3.1.2.4. and 3.3.8 the researcher informs the respective medical institution and the client, presenting them in detail
p.000004: a written explanation of termination or withdrawal.
p.000004: 4.13. Final reports from the researcher
p.000004: Upon completion of the clinical trial, the researcher shall notify the medical establishment, submit to the
p.000004: ethics committee summary of test results and all required reports of regulatory
p.000004: organs.
p.000004: 5. Contracting authority
p.000004: 5.1. Quality assurance and control
p.000004: 5.1.1. The contracting authority is responsible for the implementation and maintenance of quality and control systems
p.000004: through written standard operating procedures to ensure that the clinical trial is also conducted
p.000004: the data is collected, documented (recorded) and reported in accordance with the plan, GCP and applicable regulations
p.000004: requirements.
p.000004: 5.1.2. The contracting authority is responsible for securing an agreement between the researchers, Contract Research
p.000004: organization (DIO) and regulatory authorities to gain direct access to all sites
p.000004: the conduct of the clinical trial,
p.000004: sources / documents of information and reports from monitoring and verifications by the contracting authority, as well as
p.000004: inspections by local or foreign regulatory authorities.
p.000004: 5.1.3. At each stage of data processing, quality control is applied to confirm that all data is
p.000004: reliable and handled properly.
...
p.000004: damages arising from the clinical trial, except damages resulting from unlawful
p.000004: actions and / or negligence.
p.000004: 5.8.2. The contracting entity's internal procedures should describe the cost of treating participants in
p.000004: case of clinical trial related disabilities. These procedures must be in accordance with the applicable ones
p.000004: regulations.
p.000004: 5.8.3. The method and amount of compensation received by participants in the clinical trial are consistent with
p.000004: applicable regulatory requirements.
p.000004: 5.9. Financing
p.000004: The financial relations between the client and the researcher are documented by contract.
p.000004: 5.10. Notification / application to regulatory authorities
p.000004: Prior to the commencement of the clinical trial, the sponsor shall provide the documentation required by the regulatory authorities
p.000004: assessment, approval and / or authorization bodies to initiate the clinical trial. Each notification / application contains
p.000004: date and sufficient information to identify the protocol.
p.000004: The assignor shall notify the BDA in writing and the respective ethics committee under Art. 103 LPPMM at inclusion of the first
p.000004: patient in the trial on the territory of the Republic of Bulgaria.
p.000004: In the case of a multi-center survey, the contracting authority shall notify the BDA in writing and
p.000004: the relevant Ethics Committee under Art. 103 CLPM in case of discontinuation of the study
p.000004: to any of the study centers approved by the initial affirmative opinion.
p.000004: 5.11. Confirmation for consideration by the Ethics Committee
p.000004: 5.11.1. The contracting authority shall obtain from the researcher the following data and documents: name and address of the relevant ethics committee,
p.000004: opinion of the Ethics Committee that it has been drafted and operated in accordance with the CPT and applicable laws and
p.000004: by-laws; documented positive opinion from the Ethics Committee on the current
p.000004: version of the minutes, written informed consent form and any other information that will be provided
p.000004: provide the participants, patient recruitment procedures, payment documents and
p.000004: the compensation of participants and other documents requested by the committee.
p.000004: 5.11.2. If the Ethics Committee gives a favorable opinion, provided that changes are made to
p.000004: some aspect of the clinical trial (eg protocol modification, informed consent form, and
p.000004: any other information that will be provided to the participants and / or other procedures) shall be provided by the contracting authority
p.000004: a copy of the modification made by the researcher and the date of issue of a favorable opinion by the
p.000004: ethics.
p.000004: 5.11.3. The contracting authority shall provide the researcher with documents and dates for any new positive opinions
p.000004: for changes, and any withdrawal or termination of a favorable opinion.
p.000004: 5.12. Information on the investigational medicinal product
p.000004: 5.12.1. When planning a clinical trial, the contracting authority shall ensure that sufficient data are available,
p.000004: demonstrating the safety and efficacy of non-clinical and / or clinical trials of the product in support
p.000004: of its administration to humans by route, dosage, duration and test group of patients to be
p.000004: study.
p.000004: 5.12.2. The contracting authority shall update the researcher's brochure when new and relevant information becomes available.
p.000004: 5.13. Production, packaging, labeling and coding of the test drug
p.000004: product
p.000004: 5.13.1. The sponsor shall ensure that the investigational medicinal product (including
p.000004: comparator and placebo medicinal product, if used) is characterized in accordance with the development stage of
p.000004: a medicinal product that is manufactured in accordance with the applicable GMP and is coded and labeled in a manner that preserves
p.000004: blinding, if any. The contracting entity shall prepare a labeling of the tested medicinal product in accordance
p.000004: with the requirements of Good Manufacturing Practice rules for medicinal products under development and
p.000004: study and applicable regulatory requirements.
p.000004: 5.13.2. The contracting authority determines the storage temperature and conditions (eg light protection), storage time,
p.000004: dissolution fluids and procedures, as well as infusion products, if any.
...
p.000004: on the code.
p.000004: 5.13.5. If significant changes are made to the composition of the trials during the clinical trial
p.000004: medicinal product or medicinal product comparison, the results of any additional
p.000004: tests on medicinal products with a new composition (ie stability test, solubility profile,
p.000004: bioavailability) should be available before
p.000004: the use of the products in a clinical trial to assess whether the changes significantly affect the pharmacokinetic
p.000004: profile of the medicinal product.
p.000004: 5.14. Delivery and handling of the tested medicinal product
p.000004: 5.14.1. The sponsor is responsible for supplying the investigator with the investigational medicinal product.
p.000004: The sponsor shall provide the participants, free of charge, with the tested medicinal product (s) and each device,
p.000004: necessary for its implementation.
p.000004: In case the contracting authority is a non-profit organization, a clinical trial may be conducted with products that
p.000004: not provided by the contracting authority, with the explicit consent of the individual / legal entity financing
p.000004: the treatment.
p.000004: In the case of a non-interventional study, the study may be conducted with products not provided by
p.000004: the contracting authority.
p.000004: 5.14.2. The contracting entity does not deliver the investigational medicinal product to the investigator until they are available
p.000004: all necessary documents (ie positive opinion of Ethics Committee and Regulators).
p.000004: 5.14.3. The contracting entity shall ensure that the researcher is provided with written procedures including instructions,
p.000004: which he is obliged to follow when handling and storing the investigational medicinal product; and
p.000004: the documentation to it. Procedures include adequate and safe receipt, handling, storage, dispensing,
p.000004: collecting unused quantities from patients and returning the unused quantities to the client
p.000004: the investigational medicinal product (or destruction or otherwise absorption, if authorized by
p.000004: the contracting authority and complies with the applicable regulatory requirements).
p.000004: 5.14.4. The contracting authority:
p.000004: 5.14.4.1. guarantee the timely delivery of the investigational medicinal product to the investigators;
p.000004: 5.14.4.2. keeps records documenting the sending, receiving, distribution,
p.000004: the return and destruction of the tested medicinal product in accordance with item 8;
p.000004: 5.14.4.3. maintains a system for recovering and documenting tested medicinal products
p.000004: reimbursement (ie for insufficient return of the medicinal product, return upon completion of
p.000004: clinical trial, expiry date);
p.000004: 5.14.4.4. maintains a system for destroying / transmitting to other persons unused quantities and documentation thereof
p.000004: destruction / transmission.
p.000004: 5.14.5. The contracting authority:
p.000004: 5.14.5.1. ensure that the medicinal product is stable throughout its use;
p.000004: 5.14.5.2. stores sufficient quantities of the investigational medicinal product used during the clinical trial
...
p.000004: 5.15. Access to documentation
p.000004: 5.15.1. The contracting entity shall document in the record or other written agreement that the principal investigator / institution,
p.000004: the study center will provide direct access to clinical data sources / documents
p.000004: testing for monitoring, verification, review by the ethics committee and inspection by the regulatory authorities.
p.000004: 5.15.2. The Contracting Authority verifies that all participants have given their written consent for direct access to theirs
p.000004: original medical records for conducting clinical-related monitoring, inspections,
p.000004: review by ethics and inspection committee of
p.000004: regulatory authorities.
p.000004: 5.16. Safety information
p.000004: 5.16.1. The contracting authority is responsible for the continuous safety assessment of the investigational medicinal product
p.000004: product.
p.000004: 5.16.2. The sponsor shall inform the BDA, the Ethics Committee and the researchers of any new information that
p.000004: may pose a threat to the health and well - being of patients, affecting the course of
p.000004: study or change the BDA's authorization to conduct the study and / or change the positive
p.000004: opinion of the ethics committee to continue the clinical trial.
p.000004: 5.16.3. The contracting authority shall keep detailed records of all reports of suspected adverse events that have occurred
p.000004: when using the investigational medicinal product for which it has been informed by the investigator or from another source
p.000004: of information.
p.000004: 5.16.4. The assignor evaluates the adverse events in terms of severity, expectation and
p.000004: causal connection. The contracting authority shall develop and implement procedures for evaluating adverse events for
p.000004: severity, expectation and cause and effect in accordance with published International Guidelines
p.000004: harmonization conference, the European Commission and the European Medicines Agency.
p.000004: 5.16.5. The contracting authority shall actively collect any additional information that is necessary to evaluate the
p.000004: individual reports of adverse events.
p.000004: 5.1.6.6. All adverse events rated by the researcher or assignor as least likely to be related
p.000004: with the test product, are treated and reported as adverse reactions.
p.000004: 5.17. Reporting side effects
p.000004: 5.17.1. Reports of suspected serious and unexpected adverse reactions under Art. 138 LPPM are submitted by
p.000004: the sponsor of the clinical trial.
p.000004: The contracting authority is responsible for reporting serious adverse reactions, including when
p.000004: reactions are to an authorized test medicinal product used in the test as a product for
...
p.000004: 5.21. Premature termination or termination of testing
p.000004: If a test is prematurely terminated or discontinued, the contracting authority shall be bound
p.000004: inform the investigator and the regulatory authorities in a timely manner of termination or termination and the reasons
p.000004: for that. The researcher or the contracting authority shall, in due time, comply with the applicable regulatory requirements
p.000004: inform the Ethics Committee, giving the reasons for termination or termination.
p.000004: 5.22. Clinical trial / study reports
p.000004: If a test is completed or prematurely terminated or discontinued, the contracting authority
p.000004: ensure that the reports and ethics reports are prepared and presented to the regulatory authorities and the Ethics Committee
p.000004: the clinical trial in accordance with applicable regulatory requirements. The contracting authority also guarantees compliance
p.000004: of the test reports annexed to the application for authorization with the standards set out in
p.000004: the guidance of the International Harmonization Conference on the structure and content of
p.000004: clinical trial reports.
p.000004: 5.23. Multicenter tests
p.000004: In the case of multi-center tests, the contracting entity shall ensure that:
p.000004: 5.23.1. All researchers carry out the clinical trial in strict accordance with the approved by the client
p.000004: minutes and after a favorable opinion from the Ethics Committee, if required by the regulatory authorities.
p.000004: 5.23.2. Patients' clinical records are compiled to capture data from all centers
p.000004: of the multicenter test. Those researchers who collect additional data are sourced
p.000004: with additional CCPs designed to capture this additional data.
p.000004: 5.23.3. The responsibilities of the coordinating researcher and the participating researchers are documented directly
p.000004: before starting the clinical trial.
p.000004: 5.23.4. All researchers were instructed to follow the protocol to comply with
p.000004: standards set by the contracting authority for the evaluation of clinical and laboratory findings and for completing the clinical
p.000004: map of the patient.
p.000004: 5.23.5. Communication between researchers is facilitated.
p.000004: 6. Clinical trial protocol and protocol changes
p.000004: The clinical trial protocol should mainly contain the listed data. The specific information that
p.000004: applicable only to individual clinical trial centers, may be included on a single page / pages
p.000004: or be included in a separate agreement. Some of the information listed below may be contained in others,
p.000004: protocol related documents such as the researcher's brochure.
p.000004: 6.1. General information
p.000004: 6.1.1. Protocol title, identification code and date. Each change / changes includes a number and a date.
p.000004: 6.1.2. Name and address of the contracting entity and the monitoring entity and the contracting research organization, if any
p.000004: included in the clinical trial.
p.000004: 6.1.3. Name and position of the person (s) authorized to sign the protocol and its amendment (s)
...
p.000004: obliged to provide assurance that the manufacturer's brochure may be obtained from the manufacturer. If
p.000004: the test product is manufactured by the researcher, he is obliged to provide the necessary information
p.000004: in front of the test team. In case the preparation of an official booklet of the researcher is impossible,
p.000004: as a substitute, the contracting authority shall provide in the protocol a detailed basic information section containing
p.000004: a minimum of up-to-date data described in this Annex.
p.000004: 7.2. Basic considerations
p.000004: The researcher's brochure includes:
p.000004: 7.2.1. Home page
p.000004: It includes: name of the contracting authority, characteristic of each product tested, ie. research code, chemical
p.000004: or an approved generic name and trade name (if any), date of issue, edition number and reference number
p.000004: and the release date it replaces. Sample:
p.000004: HOME PAGE
p.000004: NAME OF THE CONTRACTING AUTHORITY
p.000004: Medicine:
p.000004: Test number:
p.000004: Name (s): Chemical, INN (if approved): Trade name
p.000004: Researcher's brochure Edition number:
p.000004: Release Date:
p.000004: Replaces previous edition number: Date:
p.000004: 7.2.2. Privacy Statement
p.000004: The contracting authority may include an opinion giving instructions to
p.000004: the researcher / recipients to accept the researcher's brochure as confidential throughout
p.000004: information and use by the researcher team and the ethics / regulatory committee.
p.000004: 7.3. Content of the researcher's brochure
p.000004: The researcher's booklet contains the following sections, each of which, if possible, has one
p.000004: literary reference:
p.000004: 7.3.1. Table of Contents:
p.000004: Privacy Statement Signature Page
p.000004: 1. Content
p.000004: 2. Summary
p.000004: 3. Introduction
p.000004: 4. Physical, chemical and pharmaceutical properties and formula
p.000004: 5. Non-clinical trials
p.000004: 5.1. Non-clinical pharmacology
p.000004: 5.2. Pharmacokinetics and metabolism of the product in animals
p.000004: 5.3. Toxicology
p.000004: 6. Effects in humans
p.000004: 6.1. Pharmacokinetics and metabolism of the product in humans
p.000004: 6.2. Safety and efficiency
p.000004: 6.3. Experience after marketing authorization
p.000004: 7. Summary of data and recommendations to the researcher
p.000004: 1. Publications
p.000004: 2. Reports
p.000004: Applications (if any)
p.000004: 7.3.2. Summary
p.000004: A brief summary (not exceeding two pages) is given indicating an important physical, chemical,
p.000004: pharmaceutical, pharmacological, toxicological, pharmacokinetic, metabolic and clinical information that
p.000004: corresponds to the stage of clinical development of the test product.
p.000004: 7.3.3. Introduction
p.000004: A brief introductory description containing the chemical name (as well as the generic and trade name) is included
p.000004: name, when approved) of the product (s) tested, all active ingredients, pharmacological class and
p.000004: the expected place in this class (eg benefits), the rationale for the study and the expected (s)
...
p.000004: 8.2.3.1.
p.000004: 8.2.3.2.
p.000004: 8.2.4.
p.000004: 8.2.5.
p.000004: Information given to subjects in the clinical trial
p.000004: Informed consent form (incl. Applicable translations)
p.000004: Any other written information
p.000004: Recruitment ad (if any)
p.000004: Financial aspects of the clinical trial
p.000004: Insurance policy
p.000004: Document X X informed compliance
p.000004: participant lassi.
p.000004: Document that the X X participants will
p.000004: be presented
p.000004: relevant information (such as content and style).
p.000004: Document that X 0
p.000004: recruitment measures-
p.000004: not patients
p.000004: appropriate and involuntary.
p.000004: Document X X
p.000004: financial contracts-
p.000004: between the researcher and the assignor
p.000004: for the clinical trial.
p.000004: Document that in X X
p.000004: case of contact
p.000004: but with the clinical trial the disability will be compensated.
p.000004: 8.2.6. Signed contract between the parties To be documented
p.000004: contracts.
p.000004: participants
p.000004: 8.2.6.1.
p.000004: 8.2.6.2.
p.000004: 8.2.6.3.
p.000004: 8.2.7.
p.000004: 8.2.7.1.
p.000004: 8.2.7.2.
p.000004: 8.2.7.3.
p.000004: 8.2.7.4.
p.000004: 8.2.7.5.
p.000004: 8.2.7.6.
p.000004: 8.2.7.7.
p.000004: 8.2.8.
p.000004: 8.2.9.
p.000004: 8.2.10.
p.000004: between the researcher and the contracting authority / contracting research organization;
p.000004: between the client and the medical center - the center of the study; between contracting authority and contract research
p.000004: organization
p.000004: Dated, documented permission / affirmative opinion of
p.000004: CE for the following:
p.000004: Protocol and amendments to the CCP
p.000004: Informed Consent Form Any other information provided to participants
p.000004: Recruitment announcement (if used)
p.000004: Participant compensation All other documents subject to approval / opinion
p.000004: Composition of the Ethics Committee / Appointment Order
p.000004: Authorization / notification of regulatory authorities
p.000004: CV and / or other document
p.000004: ment proving the qualifications of the principal investigator and
p.000004: X
p.000004: X 0
p.000004: Document that the X clinical exam-
p.000004: This was considered by a committee on
p.000004: ethics and has received
p.000004: positively-
p.000004: will. To identify the number and date-
p.000004: and the version of the documents.
p.000004: Document that the X Ethics Committee
p.000004: It is compiled in accordance with the DCT.
p.000004: Document that X permission is
p.000004: received / the notice period expired before the clinical start
p.000004: testing and in accordance with
p.000004: you have regulatory requirements.
p.000004: Document the X qualifications and
p.000004: reliability for
p.000004: conducting the clinical trial and / or for
p.000004: X
p.000004: X X
p.000004: X
p.000004: (If required)
p.000004: X
p.000004: X
p.000004: rendering me-
p.000004: Researchers' child monitoring of participants.
p.000004: 8.2.11. Reference values / limits for Documentation X X
p.000004: normal stand-
p.000004: medical / laboratory / technical and / or boundaries for
p.000004: the tests.
p.000004: procedures and / or tests included in the protocol
p.000004: 8.2.12. Medical / laboratory / technical- Document X X
p.000004: the competence of
p.000004: procedures / tests: certificate; the labs for
p.000004: carrying out the necessary
p.000004: accreditation; established quality smoke tests and
p.000004: keeping hope-
...
p.000004: blind trials, the identity of the masked pro-
p.000004: a duct will be recognized without being revealed
p.000004: masking the treatment for others
p.000004: participants.
p.000004: 8.2.18. Main Random List- Document the Random Method-
p.000004: the thinking of the participants in
p.000004: the clinical
p.000004: testing.
p.000004: 8.2.19. Report from the person conducting the Documentation that
p.000004: the center is suitable-
p.000004: pre-clinical monitoring for clinical
p.000004: test (can
p.000004: this test shall be combined with paragraph 8.2.20)
p.000004: 8.2.20. Report from the person conducting the Documentation that
p.000004: the procedures under
p.000004: monitoring, to start the clinical trial are
p.000004: commented
p.000004: of the clinical trial with the researcher and his team
p.000004: (may be combined with item 8.2.19)
p.000004: 8.3. During the clinical trial
p.000004: (and to a third party, if applicable)
p.000004: 0 X
p.000004: 0 X
p.000004: X X
p.000004: In addition to the abovementioned documents, the following documents should also be kept during the
p.000004: the clinical trial as evidence, any new relevant information is documented after
p.000004: become available.
p.000004: Document Purpose Stored
p.000004: in the documentation of the assigning researcher
p.000004: 1 2 3
p.000004: 4
p.000004: 8.3.1
p.000004: 8.3.2
p.000004: 8.3.3
p.000004: Researcher's Brochure Updates
p.000004: All protocol changes /
p.000004: the changes and the CCP; the format for
p.000004: written informed consent;
p.000004: any other written information,
p.000004: presented to the participants; patient recruitment ad (if used)
p.000004: Dated, documented positive opinion of
p.000004: Document that X X is the relevant in-
p.000004: formation is timely presented
p.000004: to the researcher.
p.000004: Document changes
p.000004: in those X X
p.000004: related to the clinical trial and the impact of
p.000004: clinical trial documents, documents.
p.000004: Document that X X changes and / or
p.000004: the reworks were
p.000004: considered in the com-
p.000004: ethics mission for the following: this ethics and have received
p.000004: positive
p.000004: 8.3.3.1 Changes to the Protocol Statement.
p.000004: 8.3.3.2 Changes to the information form- Identify the number
p.000004: and the date
p.000004: peace of mind of the version.
p.000004: 8.3.3.3 Changes in any other information presented to participants
p.000004: 8.3.3.4 Changes to the recruitment announcement (if used)
p.000004: 8.3.3.5 Amendments to all other documents requiring a favorable opinion
p.000004: 8.3.3.6 Changes in continuous over-
p.000004: the dawn of the clinical trial
p.000004: 8.3.4 Authorization / notification of re- Document that X X
p.000004: the permission is
p.000004: regulatory authorities for changes received / deadline for submission
p.000004: on the notification-
p.000004: expiration before application of the
p.000004: changes in the clinical trial and in the
p.000004: in accordance with applicable regulations
p.000004: requirements.
p.000004: 8.3.5 Curriculum Vitae of New Chief
p.000004: investigator and / or researchers
p.000004: Document X X qualifications and
p.000004: the reliability of the clinic-
p.000004: testing and / or medical monitoring of participants.
p.000004: 8.3.6 Changes in Normal Values- Document changes X X
p.000004: in the norm-
p.000004: you / limits for medical / laboratory values and / or
p.000004: boundaries for
p.000004: rotary / technical procedures tests. and / or tests included in the plan
p.000004: 8.3.7 Changes in medical / laboratory - Document that X
p.000004: X
p.000004: the tests remain
p.000004: rotary / technical procedures / applicable throughout
p.000004: period
p.000004: tests: certificate; accreditation - in the clinical trial. tion; established quality con-
p.000004: troll and / or external quality assessment; any other validation
p.000004: 8.3.8
p.000004: Documents for sending the test product and links
p.000004: According to item 8.2.15 X X
p.000004: clinical trial materials
p.000004: 8.3.9 Certificate of analysis of new According to item 8.2.16 batches of test product
p.000004: 8.3.10 Visits per person reports - To be documented
p.000004: visits and
p.000004: the person monitoring the movements of the person,
p.000004: monitors
p.000004: toriing.
p.000004: 8.3.11 Additional correspondence, Document all
p.000004: agreements
p.000004: other than visits to valuable or meaningful comments on
p.000004: regarding of
...
p.000000: 2.1.2.2.1. Components of the medicinal product
p.000000: 2.1.2.2.2. Medicine
p.000000: 2.1.2.2.3. Development of the production process
p.000000: 2.1.2.2.4. Packing and sealing system
p.000000: 2.1.2.2.5. Microbiological indicators
p.000000: 2.1.2.2.6. Compatibility
p.000000: 2.1.2.3. Production
p.000000: 2.1.2.3.1. Manufacturer (s)
p.000000: 2.1.2.3.2. Production recipe
p.000000: 2.1.2.3.3. Description and control of the production process
p.000000: 2.1.2.3.4. Control of critical and intermediate parameters
p.000000: 2.1.2.3.5. Process validation and / or evaluation
p.000000: 2.1.2.4. Excipient control
p.000000: 2.1.2.4.1. Specifications
p.000000: 2.1.2.4.2. Analytical procedures
p.000000: 2.1.2.4.3. Validation of analytical procedures
p.000000: 2.1.2.4.4. Validation of specifications
p.000000: 2.1.2.4.5. Excipients of human and animal origin
p.000000: 2.1.2.4.6. Newly introduced excipients
p.000000: 2.1.2.5. Control of the medicinal product
p.000000: 2.1.2.5.1. Release specification (s) and expiry date
p.000000: 2.1.2.5.2. Analytical procedures
p.000000: 2.1.2.5.3. Validation of analytical procedures
p.000000: 2.1.2.5.4. Batch analysis
p.000000: 2.1.2.5.5. Characterization of impurities
p.000000: 2.1.2.5.6. Validation of specifications
p.000000: 2.1.2.6. Reference standard substances and materials
p.000000: 2.1.2.7. Packing system
p.000000: 2.1.2.8. Stability
p.000000: 2.1.3. Applications
p.000000: 2.1.3.1. Equipment and apparatus
p.000000: 2.1.3.2. Impurity safety assessment
p.000000: 2.1.3.3. Newly introduced excipients
p.000000: 2.1.3.4. Solvents and Thinners
p.000000: 2.2. Non-clinical pharmacology, pharmacokinetics and toxicology
p.000000: 2.2.1. Reagents and consumables used in toxicity tests
p.000000: 2.2.2. Integrated assessment of the data set
p.000000: 2.2.3. List of tests performed and bibliography
p.000000: 2.2.4. Opinion on compliance with Good laboratory practice and bioanalytical methods
p.000000: 2.2.5. Bibliography
p.000000: 2.3. Clinical data
p.000000: 2.3.1. Clinical pharmacology
p.000000: 2.3.2. Clinical pharmacokinetics
p.000000: 2.3.3. Application to humans
p.000000: 2.4. Benefit and risk assessment
p.000000: 3. List of figures (It is advisable to attach a list of figures with their titles and number
p.000000: page)
p.000000: 4. List of tables
p.000000: Annex No. 3 to Art. 12
p.000000: (Amended, SG No. 77/2016, effective 04.10.2016) Changes in the data leading to a significant change
p.000000: 1. Protocol related changes
p.000000: 1.1. Change in the purpose of the study.
p.000000: 1.2. Change in the design and / or methodology of the study or in the preliminary information provided
p.000000: bases its scientific value.
p.000000: 1.3. Changes to the following survey documents:
p.000000: 1.3.1. an informed consent;
p.000000: 1.3.2. participant information;
p.000000: 1.3.3. information about the legal representative and / or carer of the participant;
p.000000: 1.3.4. questionnaires, letters of invitation, letters to the doctor and other researchers.
p.000000: 1.4. Change in patient recruitment procedure.
p.000000: 1.5. Change in performance metrics.
p.000000: 1.6. Change in plan for taking biological research materials.
p.000000: 1.7. Add or remove studies and / or tests.
p.000000: 1.8. Changing age ranges for participation.
p.000000: 1.9. Change in inclusion and exclusion criteria.
p.000000: 1.10. Change in safety monitoring procedures.
p.000000: 1.11. Change in the duration of use of the test product.
p.000000: 1.12. Change in the way the test product is used.
p.000000: 1.13. Change medicine for comparison.
...
General/Other / Dependent
Searching for indicator dependent:
(return to top)
p.000004: in clause 4.8.10, where this addition is relevant for the protection of the rights and safety and / or health of
p.000004: the patients.
p.000004: 3.1.6. In the cases of items 4.8.12 and 4.8.14, when it is necessary to conduct a non-therapeutic test
p.000004: the consent of the legal representative of the participant, the Ethics Committee decides whether the proposed protocol
p.000004: and / or other documents comply with ethical standards and whether they meet the applicable regulatory requirements for that type
p.000004: tests.
p.000004: 3.1.7. In the cases of item 4.8.15, where the clinical trial protocol permits patient involvement,
p.000004: without the immediate written consent or consent of his legal representative,
p.000004: the ethics committee decides whether the proposed plan and / or other documents are ethical
p.000004: and whether they meet the applicable regulatory requirements for this type of test.
p.000004: 3.1.8. The Ethics Committee assesses the size and method of payment for the healthy
p.000004: volunteers / patients influence their consent to participate and whether their decision will be made freely.
p.000004: Payments per participant must be apportioned in proportion and not entirely dependent on
p.000004: completion of the test by the participant.
p.000004: 3.1.9. The Ethics Committee shall ensure that written informed consent is included in any other written consent
p.000004: information for the participant of information regarding payment for healthy volunteers / patients, incl.
p.000004: quantity, method of payment and periodicity. The way the payment will be distributed should be
p.000004: indicated.
p.000004: 3.2. Composition, functions and actions
p.000004: 3.2.1. The Ethics Committee is composed of members who, as a team, have sufficient qualifications and experience
p.000004: to consider and evaluate the scientific, medical and ethical aspects of the proposed clinical trial. The Commission
p.000004: Ethics includes at least 7 members, of which at least two are non-medical, financial and
p.000004: administratively independent of the clinical trial site.
p.000004: Only those members who are independent of the Assembly may vote and vote
p.000004: the principal investigator and the assignor.
p.000004: The Ethics Committee shall keep a list of the members and their qualifications as well as the official documents for the
p.000004: its creation.
p.000004: 3.2.2. The Ethics Committee shall perform its functions in accordance with written standard operating procedures, with the DCP and
p.000004: applicable regulatory requirements and keep records of its activities and minutes of meetings.
...
General/Other / Public Emergency
Searching for indicator emergency:
(return to top)
p.000004: controlling.
p.000004: 1.55. Participant identification code
p.000004: Unique identifier code for the designation of each participant in a clinical trial by the researcher in order to preserve
p.000004: his identity and used in place of the participant's name
p.000004: when reporting adverse events and / or other test-related data.
p.000004: 1.56. Clinical trial center
p.000004: The location (s) of study-related activities.
p.000004: 1.57. Unexpected side effect
p.000004: For unauthorized products - an adverse reaction whose nature, severity or outcome do not match
p.000004: of the information on the tested medicinal product referred to in the investigator's leaflet. They are allowed
p.000004: use of products - an adverse reaction not listed in the summary of product characteristics or
p.000004: whose character, weight or output do not correspond to the information given in the summary of product characteristics.
p.000004: 1.58. Vulnerable groups
p.000004: Individuals whose desire to participate in a clinical trial may be influenced by the expectation of benefit or by
p.000004: their position vis-à-vis senior officials in the hierarchy related to participation or non-participation, for example:
p.000004: medical, dental, pharmacy, or nursing students in pharmacy
p.000004: industry, serving in the military, and persons deprived of their liberty.
p.000004: Other vulnerable participants are patients with incurable diseases, people in nursing homes, the unemployed or
p.000004: beggars, emergency patients, ethnic minority groups, street children, vagrants, minors and such,
p.000004: who are unable to consent.
p.000004: 1.59. Well-being (of clinical trial participants)
p.000004: Physical and mental integrity of participants in the clinical trial
p.000004: 2. PRC principles
p.000004: 2.1. Clinical trials shall be conducted in accordance with the ethical principles set out in the Declaration of Conformity
p.000004: Helsinki and comply with DCT and applicable regulatory requirements.
p.000004: 2.2. Before starting a test, all the foreseeable risks are compared with the expected benefit
p.000004: individually for the participant and for the community. A clinical trial can only begin and continue if foreseeable
p.000004: the benefits justify the risks.
p.000004: 2.3. The rights, safety and well-being of test participants are paramount and
p.000004: stand above the interests of science and society.
p.000004: 2.4. Available non-clinical and clinical information on the investigational medicinal product should be sufficient
p.000004: support for the proposed clinical trial.
p.000004: 2.5. Clinical trials must be scientifically relevant and described in a clear and detailed manner
p.000004: protocol.
p.000004: 2.6. A clinical trial shall be conducted in accordance with a protocol that has been approved in advance
p.000004: by the Ethics Committee.
p.000004: 2.7. Medical monitoring and medical decisions, with regard to participants, are taken by the doctor or, where appropriate
p.000004: necessary - by a dentist.
...
p.000004: 5.13. Production, packaging, labeling and coding of the test drug
p.000004: product
p.000004: 5.13.1. The sponsor shall ensure that the investigational medicinal product (including
p.000004: comparator and placebo medicinal product, if used) is characterized in accordance with the development stage of
p.000004: a medicinal product that is manufactured in accordance with the applicable GMP and is coded and labeled in a manner that preserves
p.000004: blinding, if any. The contracting entity shall prepare a labeling of the tested medicinal product in accordance
p.000004: with the requirements of Good Manufacturing Practice rules for medicinal products under development and
p.000004: study and applicable regulatory requirements.
p.000004: 5.13.2. The contracting authority determines the storage temperature and conditions (eg light protection), storage time,
p.000004: dissolution fluids and procedures, as well as infusion products, if any.
p.000004: The sponsor notifies all parties involved in the clinical trial (i.e., monitoring, investigators,
p.000004: pharmacists, storage officers) for certain conditions.
p.000004: 5.13.3. It is necessary to protect the packaging of the tested medicinal product from contamination and unacceptable
p.000004: degradation of quality during transport and storage.
p.000004: 5.13.4. In blind trials, the coding system for the investigational medicinal product must be included
p.000004: mechanism for immediate disclosure of the medicinal product in case of emergency, but not allowing for imperceptible detection
p.000004: on the code.
p.000004: 5.13.5. If significant changes are made to the composition of the trials during the clinical trial
p.000004: medicinal product or medicinal product comparison, the results of any additional
p.000004: tests on medicinal products with a new composition (ie stability test, solubility profile,
p.000004: bioavailability) should be available before
p.000004: the use of the products in a clinical trial to assess whether the changes significantly affect the pharmacokinetic
p.000004: profile of the medicinal product.
p.000004: 5.14. Delivery and handling of the tested medicinal product
p.000004: 5.14.1. The sponsor is responsible for supplying the investigator with the investigational medicinal product.
p.000004: The sponsor shall provide the participants, free of charge, with the tested medicinal product (s) and each device,
p.000004: necessary for its implementation.
p.000004: In case the contracting authority is a non-profit organization, a clinical trial may be conducted with products that
p.000004: not provided by the contracting authority, with the explicit consent of the individual / legal entity financing
p.000004: the treatment.
p.000004: In the case of a non-interventional study, the study may be conducted with products not provided by
p.000004: the contracting authority.
p.000004: 5.14.2. The contracting entity does not deliver the investigational medicinal product to the investigator until they are available
p.000004: all necessary documents (ie positive opinion of Ethics Committee and Regulators).
...
p.000004: inform the marketing authorization holder of the product for the territory of Bulgaria of the reaction and of the submission of the product
p.000004: information to the BDA.
p.000004: Where the investigational medicinal product is not authorized, the sponsor shall notify the BDA and
p.000004: the Ethics Committee, in addition to the communications under Art. 138, para. 1 and 3 of ZLPHM and for all suspects
p.000004: serious and unexpected side effects when using the test drug regardless of origin
p.000004: them.
p.000004: Serious and unexpected adverse reaction reports are submitted to the Medicines Executive Agency and
p.000004: the ethics committee immediately and no later than 15 days after receipt of information on their occurrence. At
p.000004: explicit written consent of the Ethics Committee reports of suspected serious and unexpected undesirable
p.000004: reactions may be reported at larger intervals, but not less than once every six months.
p.000004: The contracting authority is responsible for submitting reports to all interested researchers,
p.000004: ethics and regulatory authorities for any side effects that are serious and unexpected.
p.000004: 5.17.2. Serious and unexpected adverse reaction reports should comply with applicable regulatory requirements
p.000004: requirements and guidance of the International Harmonization Conference on the processing of safety data
p.000004: Clinical Trials - "Definitions and Standards for Emergency Reporting" (ICH Guideline for Clinical Safety Data
p.000004: Management: Definitions and Standards for Expedited Reporting).
p.000004: 5.17.3. The contracting authority shall submit to the regulatory authorities all updates of
p.000004: safety data and periodic reports. The contracting authority shall provide the Executive Agency once a year
p.000004: medicines and ethics committee list all suspected serious side effects that are
p.000004: occurred during the previous period, and a safety report of the test participants.
p.000004: 5.17.4. The annual safety report contains a summary of the safety of the tested medicinal product for
p.000004: the last one-year period from the date of the first authorization to conduct a clinical trial with
p.000004: test product in the territory of the European Union.
p.000004: The contracting authority submits the annual safety report to the BDA and the Ethics Committee within 60 calendar days
p.000004: after the end of the period covered by the report.
p.000004: For clinical trials of less than one year duration, an annual safety report shall be submitted to
p.000004: term up to 90 days after the end of the test with the notification under art. 142, para. 2 CLPM.
p.000004: When conducting more than one clinical trial with the same test product, the contracting authority shall submit a total annual
p.000004: safety report. In such cases, the report shall contain data on the safety profile of the product tested and annual
...
p.000004: normal stand-
p.000004: medical / laboratory / technical and / or boundaries for
p.000004: the tests.
p.000004: procedures and / or tests included in the protocol
p.000004: 8.2.12. Medical / laboratory / technical- Document X X
p.000004: the competence of
p.000004: procedures / tests: certificate; the labs for
p.000004: carrying out the necessary
p.000004: accreditation; established quality smoke tests and
p.000004: keeping hope-
p.000004: control and / or external evaluation of the reliability of the results. quality; other validation
p.000004: 8.2.13. Label template (s) to be documented 0
p.000004: X
p.000004: compliance with
p.000004: attached to the package of test regulations for
p.000004: labeling and that in-
p.000004: the product structure presented to the participants,
p.000004: are appropriate.
p.000004: 8.2.14. Exam Instructions - Document X
p.000004: X
p.000004: instructions necessary
p.000004: and related storage clips,
p.000004: packing, unpacking
p.000004: night test materials (if shedding and dispensing
p.000004: of tests
p.000004: are not included in the product brochure and related
p.000004: the clinical
p.000004: researcher) testing materials.
p.000004: 8.2.15. Shipping and Delivery Documents- Document X X dates
p.000004: of consignments,
p.000004: of the product under test and the batch numbers of
p.000004: tests
p.000004: clinical trial product and method of dispatch. Call-
p.000004: materials left tracking batch of pro-
p.000004: the terms of delivery and accountability.
p.000004: 8.2.16. Certificate of analysis of the document- 0
p.000004: X
p.000004: identity, number-
p.000004: the product of potency and the strength of
p.000004: the product to be
p.000004: used in the clinical trial.
p.000004: 2/8/17 Recognition Procedures in Documenting How, in X X
p.000004: emergency
p.000004: blind trials, the identity of the masked pro-
p.000004: a duct will be recognized without being revealed
p.000004: masking the treatment for others
p.000004: participants.
p.000004: 8.2.18. Main Random List- Document the Random Method-
p.000004: the thinking of the participants in
p.000004: the clinical
p.000004: testing.
p.000004: 8.2.19. Report from the person conducting the Documentation that
p.000004: the center is suitable-
p.000004: pre-clinical monitoring for clinical
p.000004: test (can
p.000004: this test shall be combined with paragraph 8.2.20)
p.000004: 8.2.20. Report from the person conducting the Documentation that
p.000004: the procedures under
p.000004: monitoring, to start the clinical trial are
p.000004: commented
p.000004: of the clinical trial with the researcher and his team
p.000004: (may be combined with item 8.2.19)
p.000004: 8.3. During the clinical trial
p.000004: (and to a third party, if applicable)
p.000004: 0 X
p.000004: 0 X
p.000004: X X
p.000004: In addition to the abovementioned documents, the following documents should also be kept during the
p.000004: the clinical trial as evidence, any new relevant information is documented after
p.000004: become available.
p.000004: Document Purpose Stored
p.000004: in the documentation of the assigning researcher
p.000004: 1 2 3
p.000004: 4
p.000004: 8.3.1
p.000004: 8.3.2
p.000004: 8.3.3
p.000004: Researcher's Brochure Updates
p.000004: All protocol changes /
p.000004: the changes and the CCP; the format for
p.000004: written informed consent;
p.000004: any other written information,
p.000004: presented to the participants; patient recruitment ad (if used)
p.000004: Dated, documented positive opinion of
...
General/Other / Relationship to Authority
Searching for indicator authority:
(return to top)
p.000004: Issued by the Minister of Health
p.000004: Refresh DV. issue 67 of 17 August 2007, amended. and ext. DV. 14 of February 17, 2012, amend. and ext. DV. Issue 77 of October 4
p.000004: 2016, ed. and ext. DV. issue 25 of March 20, 2018
p.000004: Section I.
p.000004: General
p.000004: Art. 1. (1) This regulation defines the rules of Good Clinical Practice (DCT) in accordance with Annex No 1 and regulates
p.000004: control over their implementation.
p.000004: (2) The ordinance shall also determine the requirements for the content and format of the documentation,
p.000004: which is submitted for clinical trial authorization and non-interventionally
p.000004: study, change and termination of clinical trial and non-interventional study.
p.000004: Section II.
p.000004: Requirements to the documentation for authorization for conducting clinical trials (Title amend. - SG 14/2012)
p.000004: Art. 2. The administrative documentation under Art. 110, para. 1, item 1 of the Law on Medicinal Products in Human Medicine
p.000004: (CLPM) contains:
p.000004: 1. cover letter;
p.000004: 2. application form;
p.000004: 3. confirmation of a number obtained from the European Clinical Trials Database;
p.000004: 4. a list of regulatory bodies and ethics committees to which an application has been submitted and their decision;
p.000004: 5. a list of all planned centers, principal researchers and research teams for the territory of the Republic
p.000004: Bulgaria;
p.000004: 6. a copy of the recommendations of the Scientific Committee of the European Medicines Agency for planning advice
p.000004: tests undergoing a procedure;
p.000004: 7. a letter of attorney or contract for the authorization of the person submitting the application on behalf
p.000004: the contracting authority where the applicant is not the contracting authority;
p.000004: 8. (supplemented, SG No. 14/2012) document for current registration, issued by a competent
p.000004: authority, the contracting authority and the applicant within the territory of the European Union. Where the contracting authority or the applicant is
p.000004: data subject - names, address, telephone, fax;
p.000004: 9. the declaration under art. 122 CLPM.
p.000004: Art. 3. The information about a participant under Art. 110, para. 1, item 2 of LMPHM contains:
p.000004: 1. patient / participant information;
p.000004: 2. informed consent form;
p.000004: 3. description of patient / participant recruitment procedures;
p.000004: 4. a description of the procedures for obtaining informed consent from a lawful person
p.000004: a representative, where foreseen;
p.000004: 5. ethical justification in the case of recruitment of participants who are unable to give informed consent, in accordance with
p.000004: Art. 98 CLPM;
p.000004: 6. a copy of any other information that will be used to recruit participants and / or provide a participant
p.000004: before or during the clinical trial.
p.000004: Art. 4. (1) The documentation for the test report under Art. 110, para. 1, item 3 of LMPHM contains:
p.000004: 1. test report with all current changes;
p.000004: 2. summary of the minutes in Bulgarian;
p.000004: 3. an assessment of the scientific value of the test by a specialist in the relevant field, where available;
p.000004: 4. an ethical evaluation of the protocol by the principal or coordinating investigator when not part of the protocol.
p.000004: (2) The protocol shall be drawn up in accordance with the rules of the DCP and shall contain at least the following:
p.000004: 1. assessment of the expected benefits and risks in accordance with Art. 90, Vol. 1 of ZLPHM;
p.000004: 2. defining the inclusion and exclusion criteria;
p.000004: 3. justification for the choice of patients, especially in the case of envisaged inclusion of patients who are not in
p.000004: able to give informed consent and other vulnerable patient groups;
p.000004: 4. a description of the procedures for recruiting patients and obtaining informed consent when
p.000004: envisages the inclusion of patients who are temporarily or permanently unable to provide personally informed information
p.000004: consent, and when obtaining the consent of an independent witness;
p.000004: 5. description of the plan and procedures for providing additional medical care to the participants after the end of
p.000004: the study;
p.000004: 6. monitoring procedures;
p.000004: 7. plan for publishing the data.
p.000004: (3) The protocol must be signed by the contracting authority and the principal investigator for each of the proposed centers.
p.000004: Art. 5. (1) The documentation for the tested medicinal product under Art. 110, para. 1, item 4 of the LMPHM contains:
p.000004: 1. Researcher's booklet;
p.000004: 2. a summary of all ongoing clinical trials with the medicinal product.
p.000004: (2) Where the investigational medicinal product is authorized in a Member State of the European Union, and
p.000004: the test provides for its use in accordance with the conditions laid down in the marketing authorization,
p.000004: instead of the document under Art. 1, item 1 a summary of the product characteristics may be provided.
p.000004: (3) The researcher's booklet and any update thereof must provide scientifically substantiated and complete information
p.000004: for the product that is needed for an objective assessment of the risk / benefit ratio of the proposed clinical trial.
p.000004: (4) The contracting authority shall re-evaluate the researcher's brochure and supplement it with new data in the presence of at least once
p.000004: per year.
p.000004: Art. 6. (1) The documentation on the technical requirements and the personnel under Art. 110, para. 1, item 5 of the LMPHM contains:
p.000004: 1. description of the necessary equipment and / or technical requirements for the implementation of the protocol;
p.000004: 2. documents certifying the available technical capabilities for the implementation of the protocol for each of the
p.000004: the centers offered, including documents for certification, accreditation and established quality control and / or
p.000004: external quality assessment;
p.000004: 3. CV and / or other documents certifying the education and qualification of
p.000004: the members of the research team and compliance with the requirements of Art. 86, para. 2 CLPM.
p.000004: 4. (Repealed, SG No. 25/2018)
p.000004: (2) The documents under item 2 shall be prepared by a specialized independent organization and / or the head of the
p.000004: the medical establishment and / or structure in which each specific procedure is planned to be performed
p.000004: equipment described in the protocol.
p.000004: (3) (Amended, SG No. 25/2018) The documents under item 3 shall be submitted to the coordinating researcher,
p.000004: principal investigator for each of the centers offered. At the request of the Ethics Committee
p.000004: the documents under item 4 shall also be presented to the other persons of the research team.
p.000004: (4) (New, SG No. 25/2018) The Ethics Committee shall carry out an ex officio verification of the circumstances
p.000004: under Art. 87, para. 1 of the LMPHM.
p.000004: Art. 7. The data for financing and administrative organization of the survey under Art.
p.000004: 110, para. 1, item 6 of LMPHM contain:
p.000004: 1. insurance covering the liability of the contracting authority and the principal investigator (s) for the reasons caused on or in connection with
p.000004: the conduct of the clinical trial non-material and material damage to the participants;
p.000004: 2. information on the anticipated benefits and compensations in the event of death or damage to the health of
p.000004: the participant in conducting the clinical trial;
p.000004: 3. (Supplemented, SG No. 77/2016, effective 04.10.2016) draft contract between the assignor and
p.000004: the participants in the trial, which also determines the remuneration for participation, where provided for;
p.000004: 4. (suppl., SG 77/2016, in force from 04.10.2016) draft contract between the assignor and
p.000004: the researcher;
p.000004: 5. (suppl. - SG 77/16, in force from 04.10.2016) draft contract between the assignor and
p.000004: the medical establishment - the center of the clinical trial;
p.000004: 6. written consent under Art. 87, para. 3 CLPM;
p.000004: 7. data on the source of financing of the study, where the assignor is a legal entity with
p.000004: non-agricultural aim;
p.000004: 8. document for paid fee.
p.000004: Art. 8. (1) For clinical trial of a medicinal product under Art. 88 of the LPPMM the contracting entity or a person authorized by it
p.000004: submit to the Executive Agency for Medicinal Products an application for a clinical trial using a specimen.
p.000004: (2) The documents under art. 2, 3, 4, 5, 6, 7, 9 and Art. 19, para. 3, as well as the declarations under art. 122
p.000004: and 123 ZLPHM.
p.000004: (3) (Repealed, SG No. 14/2012, New SG No. 25/2018) The Executive Agency for Medicines shall perform
p.000004: verification by official means for the presence of the circumstances under Art. 87, para. 1 of
p.000004: CLPM.
...
p.000004: development and research valid for the territory of the European Union;
p.000004: 2. a copy of the import authorization for the territory of the European Union;
p.000004: 3. Certificate of Good Manufacturing Practice for active substances of biological origin.
p.000004: (4) Where the investigational medicinal product is manufactured within the European Union and is available
p.000004: authorization for use, instead of the document under Art. 9, item 2, a declaration of origin shall be submitted by the manufacturer
p.000004: the product from standard batches manufactured under the terms of the marketing authorization at the place of manufacture,
p.000004: included in the marketing authorization in the territory of a Member State of the European Union.
p.000004: (5) Where the investigational medicinal product is authorized in a Member State of the European Union,
p.000004: and / or approved clinical trial in the Republic of Bulgaria, under Art. 9, item 1 a condensed test file shall be submitted
p.000004: medicine.
p.000004: Art. 11. (Repealed, SG No. 14/2012)
p.000004: Section III.
p.000004: Requirements to the documentation for changing the authorization for conducting clinical trials (Title amended - SG, issue 14 of
p.000004: 2012)
p.000004: Art. 12. Substantial change under Art. 127, para. 2 LPPM is present when there is a change in the data specified in
p.000004: Annex 3.
p.000004: Art. 13. (1) When planning significant changes in the clinical trial and in the documentation under
p.000004: Art. 110 LPPMH the contracting authority or a person authorized by it submits a written application in the form to the committee on
p.000004: ethics under art. 103 CLPM.
p.000004: (2) The application shall be accompanied by the following documentation:
p.000004: 1. cover letter;
p.000004: 2. summary of the planned change;
p.000004: 3. a list of the updated documents;
p.000004: 4. the updated documentation under Art. 2, 3, 4, 5, 6 and 7 reflecting changes;
p.000004: 5. pages of documentation with marked changes comparing current and proposed new ones
p.000004: texts;
p.000004: 6. justification of the changes;
p.000004: 7. copy of the application for conducting a clinical trial under Art. 2 with tagged changes, electronic and
p.000004: paper;
p.000004: 8. document for paid fee.
p.000004: Art. 14. (1) When planning significant changes in the clinical trial and in the documentation under
p.000004: Art. 116 of the LPPHM the contracting entity or a person authorized by it submits to the Executive Agency for Medicines
p.000004: a written application for a model change.
p.000004: (2) The application shall be accompanied by the documentation under Art. 13, para. 2, items 1, 2, 3, 4, 5, 6 and 8, the declaration under art. 123
p.000004: LMPHM and a copy of the positive opinion of the Ethics Committee, when available.
p.000004: (3) The application under Art. 8, para. 1, complete with updated information reflecting the proposed change,
p.000004: as well as a copy of the marked changes, in electronic and hard copy.
p.000004: (4) In case of changes under Art. 127, para. 1 LPPMM application must be submitted within 14 days of receipt
p.000004: Notification from the Medicines Executive Agency of the necessary change.
p.000004: Art. 15. (Repealed, SG No. 14/2012)
p.000004: Section III "a".
p.000004: Requirements to the documentation for conducting non-interventional research and changes thereto (New, SG No. 14/2012)
p.000004: d)
p.000004: Art. 15a. (New, SG No. 14/2012) For non-interventional study of a medicinal product under Art. 145
p.000004: The CLPMM, the sponsor or the authorized person, represents in the Executive Agency for Medicines and in
p.000004: the ethics committee under art. 103 LMPHM application form for conducting non-interventional study.
p.000004: Art. 15b. (New, SG No. 14/2012) The administrative documentation for the studies under Art. 145 LPPMM contains:
p.000004: 1. cover letter;
p.000004: 2. application form;
p.000004: 3. a list of all planned centers and principal investigators for the territory of the Republic of Bulgaria;
p.000004: 4. a copy of the recommendations of the Scientific Committee of the European Medicines Agency for planning advice
p.000004: studies undergoing a procedure;
p.000004: 5. a letter of attorney or contract for the authorization of the person submitting the application on behalf of
p.000004: the contracting authority where the applicant is not the contracting authority;
p.000004: 6. a document for up-to-date registration, issued by a competent authority, to the assignor and the applicant in the territory
p.000004: the European Union; when the contracting authority or the applicant is an individual, information is provided - names, address, telephone,
p.000004: fax;
p.000004: 7. a statement that the documentation submitted to the BDA and to the Ethics Committee contains the same information.
p.000004: Art. 15c. (New, SG No. 14/2012) The information on a participant in a non-interventional study shall include:
p.000004: 1. patient / participant information;
p.000004: 2. informed consent form, except where it is processed retrospectively and anonymously
p.000004: medical information;
p.000004: 3. description of patient / participant recruitment procedures;
p.000004: 4. a description of the procedures for obtaining informed consent from a legal representative, where applicable
p.000004: provides;
p.000004: 5. ethical justification in case of recruitment of patients / participants who are unable to give
p.000004: informed consent in accordance with Art. 98 CLPM;
p.000004: 6. a copy of any other information that will be used to recruit patients / participants
p.000004: and / or provided to a patient / participant before or during the non-interventional study.
p.000004: Art. 15g. (New, SG No. 14/2012) (1) The documentation of the protocol of
p.000004: non-interventional study or guidance for conducting a non-interventional study with retrospective
p.000004: and anonymous processing of medical information contains:
p.000004: 1. protocol or manual for carrying out the non-interventional study with all current changes;
p.000004: 2. summary of the protocol or the guide for conducting the study in Bulgarian;
p.000004: 3. a plan for publishing the data.
p.000004: (2) The protocol, respectively the management, must be signed by the contracting authority and the principal investigator for each of the
p.000004: the centers offered.
p.000004: Art. 15d. (New, SG No. 14/2012, amended, SG No. 25/2018) The Executive Agency for Medicines and the Commission
p.000004: ethically check the current summary of the observed medicinal product (s)
p.000004: product (s) for non-interventional study.
p.000004: Art. 15f. (1) (New, SG No. 14/2012, former text of Article 15f - SG, No. 25/2018)
p.000004: the technical requirements include:
p.000004: 1. a description of the necessary equipment and / or technical requirements for the implementation of the protocol or manual
p.000004: conducting a non-interventional study, where applicable in accordance with the relevant medical standard;
p.000004: 2. documents certifying the technical capabilities available for the implementation of the protocol or the manual,
p.000004: for each of the centers offered, including certification, accreditation and quality assurance documents
p.000004: control and / or external quality assessment, where applicable.
p.000004: 3. (Repealed, SG No. 25/2018)
p.000004: (2) (New, SG No. 25/2018) The Executive Agency for Medicines and the Ethics Committee shall check
p.000004: a business trip for the presence of a permit for carrying out medical activity under art. 47, para. 1, respectively
p.000004: certificate of registration under Art. 40, para. 1 of the Medical Institutions Act for the Medical Institution -
p.000004: center of non-interventional study.
p.000004: Art. 15g. (New, SG No. 14/2012) Data on financing and administrative organization for
p.000004: non-interventional studies include:
p.000004: 1. insurance covering the liability of the contracting authority and the principal investigator (s) for the causes caused by or under
p.000004: on the occasion of the non - interventional study of non - material and material damage to
p.000004: participants, except in the case of a non-interventional study in which they are being processed
p.000004: retrospectively and anonymously medical information;
p.000004: 2. contract between the assignor and the researcher;
p.000004: 3. an agreement between the assignor and the test participants, which also determines the remuneration for
p.000004: participation where foreseen;
p.000004:
p.000004: non-agricultural aim;
p.000004: 5. document for paid state fee.
p.000004: Art. 15h. (New, SG No. 14/2012) (1) When planning significant changes in non-interventional
p.000004: study under art. 145 LPPMM the assignor or the authorized person submits to the Executive Agency under
p.000004: medicines and the Ethics Committee under Art. 103 LPPMM written application for change in the model.
p.000004: (2) To the application under para. 1, the following documentation shall be attached:
p.000004: 1. cover letter;
p.000004: 2. summary and justification of the planned changes;
p.000004: 3. a list of the updated documents;
p.000004: 4. the updated documentation under Art. 15b - 15g reflecting changes;
p.000004: 5. pages of documentation with marked changes comparing current and proposed new ones
p.000004: texts;
p.000004: 6. a statement that the documentation submitted to the Medicines Executive Agency and the Ethics Committee contains one
p.000004: and the same information;
p.000004: 7. document for paid state fee.
p.000004: (3) The contracting authority may apply a planned change to a non-interventional study under Art. 145 CLPM, if
p.000004: within one month of submitting the application for change did not receive an explicit refusal by the Director of the Executive
p.000004: medicines agency, respectively negative opinion from the ethics committee under art. 103 CLPM.
p.000004: Section IV.
p.000004: Requirements for documentation of test completion notification
p.000004: Art. 16. (1) The notification under art. 142, para. 2 LPPMM shall be submitted in a format approved by the Executive Director of
p.000004: The Executive Agency for Medicines, in paper and electronic form.
p.000004: (2) When the study is terminated before the condition stipulated in the protocol for the completion of the study is completed
p.000004: the test, the notification shall contain the following additional information:
p.000004: 1. justification for termination;
p.000004: 2. number of participants receiving the tested products in the centers on the territory of the Republic of Bulgaria, and a plan for
p.000004: medical care for them after termination of the study;
p.000004: 3. the impact of the discontinuation on the data evaluation and the risk / benefit ratio of the investigational medicinal product;
p.000004: 4. the significance of the data leading to the termination of the trial for other authorized clinical trials of
p.000004: the territory of the Republic of Bulgaria.
p.000004: Art. 17. All documents submitted to the Ethics Committee under Art. 103 LPPMM and the Executive Agency of the
p.000004: medicines bearing at least the following identification elements:
p.000004: 1. trial number from the European Clinical Trials Database;
p.000004: 2. protocol code;
p.000004: 3. version and date of the document.
p.000004: Art. 18. (1) The documentation for authorization, change and termination of a clinical trial shall be submitted to
p.000004: Bulgarian and / or English.
p.000004: (2) (amend. - SG 14/2012, amend. - SG 25/08) The documentation under art. 2, items 1, 2 and 5, art. 3, items 1, 2 and
p.000004: 6, Art. 4, para. 1, Vol. 2, Art. 6, para. 1, items 1 and 3, art. 7, items 1, 2, 3, 5 and 6, Art. 8, para. 1, Art. 9, Vol. 6, Art. 13, para. 1 and para.
p.000004: 2, items 1 and 2, art. 14, para. 1, Art. 15b, items 1, 2 and 3, art. 15c, items 1, 2 and 6, Art. 15d, para. 1, Vol. 2, Art. 15f, para. 1, Vol. 1, Art.
p.000004: 15g, items 1, 2 and 3, Art. 15h, para. 1 and para. 2, items 1 and 3 and Art. 16, para. 1 shall also be provided in Bulgarian.
p.000004: (3) (Amended, SG No. 14/2012) The documentation under Art. 8, para. 1, Art. 14, para. 1 and 3, Art. 15a, Art. 15h, para. 1, Art. 16,
p.000004: para. 1 shall also be provided in English.
p.000004: Art. 19. (1) (Amended, SG No. 14/2012) The Executive Director of the Executive Agency for Medicines
p.000004: approve by order samples of the applications under Art. 2, 8, 13, 14 and 15a and 15h, para. 1 and the notification under Art. 16.
p.000004: (2) The applications shall be submitted in a single copy, in paper and electronic form.
p.000004: (3) Applications in electronic form must be submitted in a format compatible with the requirements for entry into the European database.
p.000004: clinical trial data.
p.000004: (4) The contracting authority or the authorized person shall declare that the applications on electronic and hard copy contain identical
p.000004: information.
p.000004: Section V. Control
p.000004: Art. 20. (1) The control over the clinical trials conducted in the Republic of Bulgaria shall be exercised by the
p.000004: Art. 267, para. 3 ZLPHM State Inspectors.
p.000004: (2) Control over clinical trials conducted in the Republic of Bulgaria may also be exercised by
p.000004: officials of the Member States of the European Union and designated by the European Medicines Agency
p.000004: and its Scientific Committees.
p.000004: (3) Where necessary, inspectors may be assisted and assisted by experts designated by
p.000004: the Executive Director of the Executive Agency for Medicinal Products.
p.000004: (4) The control, carried out by the state inspectors, shall be carried out:
p.000004: 1. as a preliminary, current and follow-up in a clinical trial of a medicinal product;
p.000004: 2. in the course of a marketing authorization procedure;
p.000004: 3. as follow-up measures after authorization for use.
p.000004: (5) The contracting authority, the principal investigator and the researchers contracted shall be subject to control
p.000004: research organization, ethics committees, test center, manufacturing sites and control center
p.000004: the investigational medicinal product, the laboratories and any site and facility used during the test,
p.000004: as well as all clinical trial documentation.
p.000004: Art. 21. (1) Control over clinical trials shall be conducted in accordance with standard operating procedures
p.000004: procedures approved by the Executive Director of the Executive Agency for Medicinal Products. The standard ones
p.000004: operational procedures shall be developed in accordance with the guidance documents of the European Commission.
p.000004: (2) Each examination in connection with a clinical trial of a medicinal product shall end with a report to be submitted to the
p.000004: the contracting authority.
p.000004: (3) A clinical trial verification report may be provided to the investigators,
p.000004: the ethics committee under art. 103 LPPMM, other Member States of the European Union, and the European Union
p.000004: drug agency.
p.000004: Art. 22. When finding discrepancies requiring the suspension or termination of a study,
p.000004: The Executive Agency for Medicinal Products shall inform the European Medicines Agency, Member States, c
p.000004: the European Commission and the Ethics Committee under Art. 103 CLPM.
p.000004: Art. 23. The Executive Agency for Medicinal Products shall enter into the European Clinical Trials Database
p.000004: information on planned and performed clinical trial checks.
p.000004: Transitional and Final Provisions
p.000004: § 1. This Regulation establishes the provisions of Commission Directive 2005/28 / EC of 8 April 2005 on
p.000004: defining principles and detailed guidelines for good clinical practice for medicinal products for
p.000004: humane use intended for research as well as requirements for the granting of a marketing authorization
p.000004: the manufacture or import of such products.
p.000004: § 2. To the applications, submitted before the entry into force of this Ordinance, for significant changes in the permit for holding
p.000004: the clinical trial of a medicinal product on the territory of the Republic of Bulgaria shall be submitted by the contracting authorities on time
p.000004: for three months the documentation provided for in the regulation.
p.000004: § 3. This Ordinance is issued on the grounds of Art. 82, para. 3, Art. 110, para. 2, Art. 116, para. 5, Art.
...
p.000004: to a patient or participant in a clinical trial that is not necessarily causally related to this treatment.
p.000004: An adverse event may therefore be any adverse and unintended physical finding (incl.
p.000004: laboratory deviation), symptom, or illness associated with the use of (tested) drug over time
p.000004: product, whether or not it is causally related to the product.
p.000004: 1.3. Applicable requirements
p.000004: All regulatory requirements for conducting clinical trials with medicinal products.
p.000004: 1.4. Approval by the Ethics Committee
p.000004: Positive opinion from the Ethics Committee confirming that the clinical trial has been evaluated and can
p.000004: to be conducted at the established center under the conditions laid down by the Ethics Committee, the medical establishment, the CPT, and
p.000004: the applicable requirements.
p.000004: 1.5. Independent verification (audit)
p.000004: Systematic and independent evaluation of test-related obligations and assessment documents
p.000004: whether these obligations have been fulfilled, whether the data have been recorded, analyzed, carefully reported, in accordance with
p.000004: the protocol, standard operating procedures (SOPs) of the contracting entity, DCT and applicable regulatory requirements.
p.000004: 1.6. Certificate of verification
p.000004: Document from the verifier confirming that an inspection has been carried out.
p.000004: 1.7. Verification report
p.000004: Written evaluation of the verifier by the contracting authority for the results of the inspection.
p.000004: 1.8. Track for verification
p.000004: Documentation to track the sequence of events.
p.000004: 1.9. Blinding / masking
p.000004: A procedure in which one or more of the parties remain unaware of their assigned treatment
p.000004: preliminary agreement. Single-blind are usually trials in which patients remain unknown, a
p.000004: double-blind are trials in which patients, researchers, monitors, and sometimes
p.000004: data subjects remain unfamiliar with the treatment prescribed.
p.000004: 1.10. Clinical Patient Card (CCP)
p.000004: Printed, optical or electronic media prepared to record all the information required by the plan to report to
p.000004: the contracting authority for each individual participant.
p.000004: 1.11. Clinical trial / study
p.000004: Clinical trial of a medicinal product is any human study designed to
p.000004: the clinical, pharmacological and / or other pharmacodynamic effects of one or
p.000004: more tested medicinal products, and / or to identify adverse reactions to one or more tested
p.000004: medicinal products, and / or to study the absorption, distribution, metabolism and excretion of one or
p.000004: more medicinal products tested in order to ascertain their safety and / or efficacy.
p.000004: The definitions of clinical trial and clinical trial are synonymous.
p.000004: Non-interventional study is a study in which the medicinal product (s) is prescribed as usual
p.000004: in accordance with the conditions laid down in the Marketing Authorization. The appointment of the patient to
p.000004: a specific therapeutic strategy is not predefined by a test protocol, but falls within
p.000004: the established practice and the decision to prescribe the medicinal product is clearly distinguished from the decision to
p.000004: included the patient in the trial. No additional treatment should be applied to patients
p.000004: diagnostic or monitoring procedures and epidemiological methods are used to analyze the data collected.
p.000004: 1.12. Clinical trial / study report
p.000004: Written description of each trial / study of a therapeutic, prophylactic or diagnostic tool,
p.000004: applied to humans, which includes full clinical and statistical results, descriptions and
p.000004: analyzes integrated into a single report.
p.000004: 1.13. Medicinal product for comparison
p.000004: Tested or authorized medicinal product (aka active control) or placebo used for
p.000004: comparison during a clinical trial.
p.000004: 1.14. Conformity (as regards test)
p.000004: Compliance with all requirements - related to the test, the requirements of the DCT and the applicable ones
p.000004: regulations.
p.000004: 1.15. Confidentiality
p.000004: Preventing the disclosure by persons other than authorized persons of information belonging to
p.000004: the contracting authority or the identity of the participants.
p.000004: 1.16. Contract
p.000004: A written, dated and signed agreement between two or more parties setting out all the measures under
p.000004: assignment, assignment of tasks and responsibilities and, if applicable, financial matters. The protocol may
p.000004: to serve as the basis of a contract.
p.000004: 1.17. Coordinating committee
p.000004: Commissioner-designate committee to coordinate multicenter activities
p.000004: clinical trials.
p.000004: 1.18. Coordinating researcher
p.000004: Researcher appointed to coordinate researchers from the various multicenter centers
p.000004: testing.
p.000004: 1.19. Contract Research Organization (DIO)
p.000004: A natural or legal person or scientific organization that has contracted with the contracting authority to perform one or
p.000004: more than the test-related functions and duties of the contracting authority.
p.000004: 1.20. Direct access
p.000004: Permission to examine, analyze, verify and reproduce all records and reports that are relevant for evaluation
p.000004: of one clinical trial after authorization. Each country (e.g., local or foreign regulatory authorities,
p.000004: the contracting authorities and the contracting authorities) with direct access shall take all necessary precautions
p.000004: measures in accordance with the applicable regulatory requirements to preserve the confidentiality of
p.000004: the participants and the information held by the client.
p.000004: 1.21. Documentation
p.000004: All recordings in any form (including, but not limited to, written, electronic, magnetic, optical,
p.000004: electroencephalography, radiography, electrocardiograms, chromatograms) describing or recording the method,
p.000004: the conduct and / or outcome of the test, the factors affecting the test and the action taken.
p.000004: 1.22. Basic clinical trial dossier
p.000004: The main dossier of a clinical trial consists of basic documents that are either self-contained or
p.000004: together they allow evaluation of the clinical trial and the quality of the results obtained.
p.000004: 1.23. Basic documents
p.000004: Documents that, individually or together, allow evaluation of the conduct of the clinical trial and
p.000004: the quality of the results obtained.
p.000004: 1.24. Good Clinical Practice (DCT)
p.000004: The set of internationally recognized ethical and scientific quality requirements that are respected in planning,
p.000004: conducting, reporting and reporting clinical trials to ensure that data and reporting
p.000004: the results are plausible and accurate and that the rights, privacy and confidentiality of the participants are preserved.
p.000004: 1.25. Independent Evaluation Committee
p.000004: Independent evaluation committee that can be set up by the contracting authority to evaluate certain
p.000004: time intervals of a clinical trial, safety data, baseline parameters
p.000004: efficiency and to formulate recommendations to the contracting authority whether to continue, change or terminate
p.000004: the test.
p.000004: 1.26. Independent witness
p.000004: A person who: does not participate and has no interest in the clinical trial; cannot be influenced by
p.000004: test participants; be present at the signing of the informed consent if the participant or his / her
p.000004: legal representative cannot read, and reads informed consent form and any other
p.000004: written information provided to participants.
p.000004: 1.27. Ethics Committee
p.000004: Independent structure (institutional, regional, national or supranational committee or committee) composed
p.000004: by medical / scientific professionals and non-medical / non-scientific members. The primary responsibility of the Ethics Committee is to
p.000004: preserve the rights and safety of the people involved in the test and provide public assurance to
p.000004: this protection. The defense is realized by reviewing and giving an opinion on the clinical protocol
p.000004: testing and materials for obtaining and documenting informed consent of participants and
p.000004: assessment of whether the researchers, the conditions, the methods for conducting the test are appropriate.
p.000004: 1.28. An informed consent
p.000004: Informed consent is a statement of will that must be written, personally dated and signed in order to participate in
p.000004: a clinical trial taken completely free after being duly informed of its nature,
p.000004: significance, consequences and risks and appropriately documented by any person who is able to give
p.000004: his consent, or when the person is unable to give his consent, from his legal representative.
p.000004: 1.29. Inspection
p.000004: Official inspection of the inspection bodies for documents, conditions, records and any other data sources provided
p.000004: are considered by them to be related to the clinical trial and may be stored at the clinical venue
p.000004: testing, the office of the contracting authority / DIO or other places deemed appropriate by these inspection bodies.
p.000004: 1.30. Institution (medical)
p.000004: Medical establishments where clinical trials are conducted.
p.000004: 1.31. Interim clinical trial report
p.000004: Report on the provisional results of the study and their evaluation based on analyzes made during the
p.000004: conducting the clinical trial.
p.000004: 1.32. Tested medicinal product
p.000004: Test drug is a formulation of an active substance or a placebo,
p.000004: which is being tested or used as a comparison in a clinical trial, including products for which it has been issued
p.000004: marketing authorization, but are used for unauthorized use or for the purpose of obtaining an additional one
p.000004: information on the authorized form, or supplied (in dosage form or packaged) in a way other than
p.000004: the authorized form.
p.000004: 1.33. Principal Investigator
p.000004: The principal investigator is the physician or dental practitioner designated by the contracting authority who is in charge
p.000004: the complete conduct of the clinical trial at the center in accordance with the approved protocol and
p.000004: the DCM manual and is responsible for the work of the researchers.
p.000004: 1.34. Explorer
p.000004: The researcher is the doctor or dentist designated by the sponsor and the principal investigator who
p.000004: practically conducts the clinical trial under the direction of the principal investigator according to the approved protocol and
p.000004: the DCT manual at the clinical trial research center. If the clinical
p.000004: testing is conducted by a team, the researcher is the team leader responsible for the team and is called the principal
p.000004: Explorer.
p.000004: 1.35. Researcher's brochure
p.000004: Document containing all clinical and non-clinical trial data (s) for medicinal product (s)
p.000004: refer to the administration of the tested medicinal products to humans.
p.000004: 1.36. Legal representative
p.000004: An individual who, under applicable law, is a legal representative and can agree to participate
p.000004: of the future participant in the clinical trial on his behalf.
p.000004: 1.37. Monitoring
p.000004: Action to monitor the development of the clinical trial and ensure that it is conducted, recorded and reported
p.000004: in accordance with the protocol, SOP, DCT and applicable regulatory requirements.
p.000004: 1.38. Monitoring report
p.000004: Written report from the monitoring person to the contracting authority after each site visit
p.000004: and / or any test related communication according to the contracting entity's SOP.
p.000004: 1.39. Multicenter testing
p.000004: Clinical trial conducted under one protocol but in more than one center and more than one
p.000004: Explorer. Research centers may be located in the territory of one Member State, at
p.000004: more than one Member State and / or Member States and third countries.
p.000004: 1.40. Non-clinical trial
p.000004: Non-human biomedical trial.
p.000004: 1.41. Minutes
p.000004: Clinical trial protocol is a document that describes the purpose (s), project, methodology, statistical
p.000004: the processing and organization of the test. The minutes shall also include any subsequent amendments thereto.
p.000004: 1.42. Change protocol
p.000004: A written description of the amendment (s) or formal explanation of the minutes.
p.000004: 1.43. QA
p.000004: Any planned and systematic actions that are put in place to ensure that data is received,
p.000004: documented (recorded) and reported and that the test is conducted in accordance with the DCT and applicable
p.000004: regulations.
p.000004: 1.44. Quality control
p.000004: Work techniques and actions undertaken within the framework of the
p.000004: quality in order to verify that the quality requirements of the test-related activities are fulfilled.
p.000004: 1.45. Randomization
p.000004: Process for allocating test participants or control groups using an element of
p.000004: chance to avoid deviations.
p.000004: 1.46. Regulatory bodies
p.000004: National competent authorities for quality, efficiency and safety control of
p.000004: medicinal products, as well as the bodies evaluating and submitting clinical documentation
p.000004: inspections.
p.000004: 1.47. Serious adverse event (SNA) or serious adverse reaction
p.000004: (SNLR)
p.000004: Any adverse effect or change in health that has become the cause
p.000004: for death, imminent danger of death, hospitalization or prolongation of hospitalization,
p.000004: significant or permanent damage, disability and congenital anomalies.
p.000004: 1.48. Output data
p.000004: All information in the original records and certified copies of the original clinical records, observations and
p.000004: other activities in one clinical trial necessary to recreate and evaluate the trial.
p.000004: 1.49. Source documents (source documents)
p.000004: Original documents and records in which data are first recorded after being received (e.g.
p.000004: hospital records, clinical and work plans, lab notes, notes, patient logs, or patient lists
p.000004: inspection, drug dispensing records from the pharmacy, automated device records, certified
p.000004: copies of records after confirmation that they are true copies, microfiche, photographic negatives,
p.000004: microfilms and tape recordings, x-rays, participant files, recordings stored in
p.000004: the pharmacy, the laboratory, and the medical and technical services involved in the test).
p.000004: 1.50. Contracting authority
p.000004: The natural or legal person, institution or organization responsible for initiating,
p.000004: management and / or funding of the clinical trial.
p.000004: 1.51. Investigator
p.000004: An individual who simultaneously initiates and conducts one clinical trial, alone or with others
p.000004: persons, and under whose immediate direction the investigational medicinal product is administered, dispensed or administered
p.000004: used by a patient. The definition does not include legal entities and scientific organizations. The obligations of
p.000004: the contracting authority is both that of the contracting authority and that of the researcher.
p.000004: 1.52. Standard Operating Procedures (SOPs)
p.000004: Written detailed instructions for achieving uniformity in the performance of a specific function.
p.000004: 1.53. Co-researcher
p.000004: Any member of the clinical research team appointed and supervised by the principal investigator at
p.000004: the location of the clinical trial to perform the basic test-related actions
p.000004: and / or make important decisions (eg, associates, graduate students, doctoral students).
p.000004: 1.54. Test participant
p.000004: A person who is enrolled in a clinical trial by receiving or participating in a test drug
p.000004: controlling.
p.000004: 1.55. Participant identification code
p.000004: Unique identifier code for the designation of each participant in a clinical trial by the researcher in order to preserve
p.000004: his identity and used in place of the participant's name
p.000004: when reporting adverse events and / or other test-related data.
p.000004: 1.56. Clinical trial center
p.000004: The location (s) of study-related activities.
p.000004: 1.57. Unexpected side effect
p.000004: For unauthorized products - an adverse reaction whose nature, severity or outcome do not match
p.000004: of the information on the tested medicinal product referred to in the investigator's leaflet. They are allowed
p.000004: use of products - an adverse reaction not listed in the summary of product characteristics or
p.000004: whose character, weight or output do not correspond to the information given in the summary of product characteristics.
p.000004: 1.58. Vulnerable groups
p.000004: Individuals whose desire to participate in a clinical trial may be influenced by the expectation of benefit or by
...
p.000004: or conducting the clinical trial;
p.000004: 3.3.9. a requirement that the Ethics Committee immediately notify in writing
p.000004: the researcher / institution for the clinical trial decisions / opinions; the reasons
p.000004: on its decisions / opinions and the procedures for appealing the decisions / opinions of the
p.000004: ethics.
p.000004: 3.4. Documents
p.000004: The Ethics Committee shall keep all relevant documents (eg written standard operating procedures, lists of records)
p.000004: members, appointment orders, members' job listings, conflicts of interest declarations and
p.000004: confidentiality, documents submitted, meeting minutes and correspondence) for the period no
p.000004: less than three years after termination of the clinical trial and make them available on request to the regulatory ones
p.000004: organs.
p.000004: The Ethics Committee shall provide the investigator, the sponsor or the regulatory authorities with its written documents
p.000004: procedures and orders determining the list of members upon request.
p.000004: 4. Researcher
p.000004: 4.1. Qualification and responsibilities of the researcher
p.000004: 4.1.1. The researcher (s) have the appropriate education, qualifications and experience to assess responsibility for the
p.000004: the proper conduct of the clinical trial; meets all regulatory requirements
p.000004: authorities, and provides proof of his / her qualification through an updated CV and / or others
p.000004: documents required by the contracting authority, the ethics committee and / or regulatory authorities.
p.000004: 4.1.2. The researcher is familiar with the proper use of the test drug as it is
p.000004: referred to in the protocol, the researcher's current brochure, product information and any other sources
p.000004: information provided by the contracting authority.
p.000004: 4.1.3. The researcher knows and complies with the requirements of the DCT and the applicable regulatory requirements.
p.000004: 4.1.4. The researcher permits monitoring, verification by the contracting authority and inspection by
p.000004: the relevant regulatory authorities.
p.000004: 4.1.5. The researcher shall keep a list of the persons with the necessary qualifications to whom he has delegated responsible duties,
p.000004: related to the clinical trial.
p.000004: 4.2. Test Opportunities
p.000004: 4.2.1. The researcher must be able to show the ability to dial the required number
p.000004: appropriate patients within the agreed period (eg based on retrospective data).
p.000004: 4.2.2. The investigator has sufficient time to conduct and complete the clinical trial within the agreed timeframe.
p.000004: 4.2.3. The researcher has the necessary number of qualified personnel and the appropriate equipment for the foreseen
p.000004: the duration of the clinical trial for proper and safe conduct.
p.000004: 4.2.4. The researcher shall ensure that all persons participating in the clinical trial are sufficiently informed about
p.000004: the protocol, the investigational medicinal product (s), and the clinical trial's duties and functions.
p.000004: 4.3. Medical care for participants
p.000004: 4.3.1. Responsibility for all clinical trial related medical decisions lies with a qualified physician, or
p.000004: where appropriate, by a dentist who is a researcher or co-investigator in a clinical trial.
p.000004: 4.3.2. During and after the participation of the subjects in the clinical trial, the researcher guarantees the provision
p.000004: sufficient medical surveillance of the participants in relation to any adverse event, incl. clinically important
p.000004: laboratory test related results. The researcher informs the patient of the need for medical
p.000004: monitoring for the additional illness he has identified.
p.000004: 4.3.3. If the participant has a physician and if his or her physician has agreed to
...
p.000004: the researcher may endeavor to identify these causes, while fully respecting the patient's rights.
p.000004: 4.4. Correspondence with the Ethics Committee
p.000004: 4.4.1. Before starting the clinical trial, the researcher must have a written date
p.000004: a positive opinion from the Ethics Committee on the clinical trial protocol, the form in writing
p.000004: consent, changes to consent form, patient recruitment procedures (eg announcements) and any other written
p.000004: information to be provided to the participant.
p.000004: 4.4.2. The researcher shall submit to the Ethics Committee a copy of the current brochure of the investigating physician as
p.000004: application of the written request to the Ethics Committee for opinion. If changes occur during the clinical trial
p.000004: in the booklet, the researcher presents to the Ethics Committee a new copy including the changes.
p.000004: 4.4.3. During the clinical trial, the investigator shall submit to the Ethics Committee for review
p.000004: all documents concerning the participants.
p.000004: 4.5. Protocol compliance
p.000004: 4.5.1. The researcher shall carry out the clinical trial in accordance with a protocol previously approved by
p.000004: the contracting authority and the regulatory authority and who has received a favorable opinion from the ethics committee. The researcher and
p.000004: the contracting authority shall sign the protocol or supplementary agreement, by which the researcher confirms his / her agreement to
p.000004: compliance with it.
p.000004: 4.5.2. The researcher may not make any deviations or changes to the protocol without the consent of
p.000004: the contracting authority and the preliminary examination and documented positive opinion of the changes by the commission
p.000004: ethics. Deviations from the requirements of the plan can only be made when there are good reasons for being
p.000004: endangering the life, health and rights of the persons surveyed, or where the changes involve only organizational or
p.000004: administrative aspects of the clinical trial (eg change of monitoring person, change of telephone
p.000004: numbers).
p.000004: 4.5.3. The researcher or his authorized representative shall document and explain any deviation from the approvals
p.000004: protocol.
p.000004: 4.5.4. The researcher may make a deviation or change in the avoidance protocol
p.000004: an imminent threat to patients without the immediate positive opinion of the Ethics Committee.
p.000004: The deviation, change or plan with proposed changes shall be submitted to the committee as soon as possible
p.000004: assessment ethics and opinion, consenting authority and regulatory authorities.
p.000004: 4.6. Tested medicinal product
p.000004: 4.6.1. Responsibility for the accountability of the investigational medicinal product at the clinical site
p.000004: the test is carried out by the researcher.
p.000004: 4.6.2. The researcher may assign some or all of his reporting responsibilities to
p.000004: the pharmacist's or other appropriate person's place (s) under the direction of the researcher,
p.000004: when permissible or required.
p.000004: 4.6.3. The researcher and / or pharmacist or other person designated by the researcher shall keep the records for
p.000004: medicines received at the venue, inventory of products at the center, the quantities used by each
p.000004: participant and the quantities returned to the contracting authority or at an additional place. These documents contain dates, quantities,
p.000004: batches and numbers, expiry date (where possible) and unique code numbers indicating the medicinal products
p.000004: products and participants. The researchers keep documents stating that the participants have received
p.000004: the relevant doses specified in the plan and confirmation and reporting of all medicinal products received by the contracting entity
p.000004: products.
p.000004: 4.6.4. The tested medicinal product (s) shall be stored in a manner determined by the contracting entity, in accordance with paragraph 2.
p.000004: 5.13.2 and 5.14.3, and in accordance with applicable regulatory requirements.
p.000004: 4.6.5. The researcher confirms that the tested medicinal products are used only in accordance with
p.000004: approved protocol.
p.000004: 4.6.6. The investigator, or a person designated by him, explains the proper use of the test drug
p.000004: product of each individual participant and at appropriate intervals and checks that each participant complies
p.000004: correct instructions.
p.000004: 4.7. Randomization and disclosure procedures
p.000004: The researcher must follow the randomization procedures of the clinical trial, if any
p.000004: such, and must confirm that code disclosure is made only in accordance with the protocol. If the clinical
p.000004: the test is blinded, the researcher documents and explains to the client any premature disclosure
p.000004: code (e.g., accidental detection, detection as a result of a serious unwanted event) of
p.000004: the investigational medicinal product (s).
p.000004: 4.8. Informed consent of participants
p.000004: 4.8.1. During the receipt and documentation of informed consent, the researcher complies
...
p.000004: provided to participants.
p.000004: 4.8.2. The written informed consent form and any other written information provided to participants shall be
p.000004: updates when important new information becomes available that may affect their consent. Each
p.000004: an updated form of written informed consent and written information should have a positive opinion of
p.000004: the ethics committee prior to its implementation. The participant or his legal representative shall be promptly informed
p.000004: notify when important new information becomes available that may affect their desire to
p.000004: continue to participate in the clinical trial. Communications regarding new information shall be documented
p.000004: timely.
p.000004: 4.8.3. Neither the principal investigator nor the research staff can coerce or give in
p.000004: mislead the person to participate or continue to participate in the clinical trial.
p.000004: 4.8.4. No oral or written information pertaining to the clinical trial, including the format for
p.000004: written informed consent may not contain words and expressions that coerce or sound coercive to the participant
p.000004: or his legal representative to waive any of his legal rights or to release or to impose
p.000004: discharge for negligence of the researcher, contracting authority, institution or
p.000004: their representatives.
p.000004: 4.8.5. The researcher or the person authorized by him / her shall inform the participant or in case he / she cannot give
p.000004: his consent, his legal representative for all aspects of the clinical trial, including
p.000004: the provision of written information and the favorable opinion of the Ethics Committee.
p.000004: 4.8.6. The language used in the oral or written information for the clinical trial, including the written form
p.000004: informed consent must be without medical terms and sufficiently accessible to be
p.000004: understood by the participant or his legal representative and, where appropriate, by the independent witness.
p.000004: 4.8.7. Prior to obtaining written informed consent, the Principal Investigator or a person authorized by him or her
p.000004: obliged to provide the participant or his or her legal
p.000004: representative sufficient time and opportunity to discuss the details of the clinical trial and yes
p.000004: decide whether or not to participate. All questions asked by the participant or his legal representative must
p.000004: replied in full.
p.000004: 4.8.8. Before engaging the participant, written informed consent must be signed personally and
p.000004: set the date by the participant or his legal representative and by the person interviewing the
p.000004: of the participant.
p.000004: 4.8.9. In case the participant or his legal representative cannot read during the discussion
...
p.000004: the consent of his legal representative, if any. When the direct consent of the participant and of
p.000004: its legal representative cannot be obtained, inclusion can be made if necessary
p.000004: an immediate decision to save the patient's life as required by the protocol and / or other
p.000004: place, through the written favorable opinion of the Ethics Committee, with a view to retaining rights,
p.000004: the safety and well-being of the individual and ensuring compliance with applicable regulatory requirements.
p.000004: The person or his legal representative shall be informed as soon as possible of the clinical trial and should
p.000004: be asked to document their agreement
p.000004: to continue participation in the clinical trial according to the procedure of item 4.8.10.
p.000004: 4.9. Documents and reports
p.000004: 4.9.1. The researcher ensures the accuracy, completeness, legibility and timely reporting of the data
p.000004: of the client in the clinical patient records (CCPs), as well as in all required reports.
p.000004: 4.9.2. The data obtained from source documents and recorded in the CCP is contained in these
p.000004: source documents, and discrepancies are explained.
p.000004: 4.9.3. Any change or correction to the CCP shall be dated, initials and (if necessary) shall be dated
p.000004: explains and should not doubt the original entry (ie, the trace of the check is kept).
p.000004: This applies to both the written and the electronic corrections according to item 5.18.4.14. The contracting authority supplies
p.000004: the researcher and / or the person designated by the researcher to make such adjustments with instructions.
p.000004: Contracting entities shall have written procedures certifying that changes or corrections have been made to
p.000004: The CCP was required, documented and signed by the contracting entity or its designees.
p.000004: the researcher. The researcher keeps records of changes and corrections in the CCP.
p.000004: 4.9.4. (amend. - SG 14/2012) The researcher / institution shall store
p.000004: documentation according to the approved plan, hospital documentation and signed informed consent forms,
p.000004: as well as the documents under item 8 "Basic documents for conducting a clinical trial" as specified in
p.000004: applicable regulations.
p.000004: The researcher shall take measures to prevent the accidental or premature destruction of these documents.
p.000004: Upon completion of the study, the investigator shall provide the contracting entity with some of the clinical documentation
p.000004: testing as specified in the protocol and / or other contract with the contracting entity.
p.000004: 4.9.5. The main documents are kept for the longest of the specified periods:
p.000004: 4.9.5.1. fifteen years after the end of the clinical trial;
p.000004: 4.9.5.2. two years after the last marketing authorization in a region covered by the International Conference
p.000004: on harmonization, or until the procedure has been completed or the intention is not to obtain
p.000004: authorization for use in the region covered by the International Conference on Harmonization;
p.000004: 4.9.5.3. two years from the formal completion of the clinical development of the test product.
p.000004: Storage periods may be longer if required by other applicable regulatory requirements or if
p.000004: this is agreed with the contracting authority. The contracting authority shall inform the researcher in writing when the documents need not be submitted
p.000004: are stored more according to item 5.5.12.
p.000004: 4.9.6. The clinical trial financial issues shall be documented by contract between the sponsor and the
p.000004: the researcher.
p.000004: 4.9.7. At the request of the monitoring person,
p.000004: the auditor / reviewer, ethics committee or regulatory authority, the researcher shall provide direct access to all
p.000004: clinical trial related documents.
p.000004: 4.10. Clinical trial progress reports
p.000004: 4.10.1. The researcher submits written reports on the progress of the clinical trial to the Ethics Committee once
p.000004: annually or more often if the Ethics Committee so requests.
p.000004: 4.10.2. The researcher shall promptly submit written reports to the contracting authority, the ethics committee and
p.000004: regulatory authorities for any changes that significantly affect the conduct of the clinical trial and / or
p.000004: increasing the risk for participants.
p.000004: 4.11. Safety reports
p.000004: 4.11.1. All serious adverse events shall be reported immediately to the contracting authority, except for those for
p.000004: which is not required by the protocol or other document (eg, the researcher's manual)
p.000004: immediate reporting. Immediate reporting is followed by detailed written reports. Instant and
p.000004: follow-up reports identify individuals by unique code numbers that identify participants in
p.000004: the clinical trial, instead of their names, personal identification numbers and / or addresses.
p.000004: The researcher complies with the applicable regulatory requirements for reporting to
p.000004: the unexpected serious adverse reactions of the regulatory authorities and the ethics committee.
p.000004: 4.11.2. Adverse events and / or laboratory results beyond the reference limits specified in the protocol as
p.000004: critical safety assessments shall be reported to the contracting authority in accordance with the requirements and within the time limits,
p.000004: determined by the contracting authority in the minutes.
p.000004: The researcher evaluates each adverse event in terms of causation and severity.
p.000004: 4.11.3. In the event of a reported death, the investigator submits to the sponsor and the ethics committee
p.000004: any additional information (eg autopsy protocol and final medical report).
p.000004: 4.12. Premature completion or termination of testing
p.000004: If the test is terminated prematurely or terminated for any reason, the investigator shall
p.000004: immediately notify trial participants and provide them with appropriate treatment and follow-up and, where appropriate
p.000004: requires the applicable regulatory requirements to notify regulatory authorities.
p.000004: 4.12.1. If the researcher discontinues or completes the clinical trial without prior consent
p.000004: of the contracting authority, is obliged to notify the medical institution, the contracting authority and the ethics committee, the regulatory body
p.000004: of the country where the study center is located by submitting them in writing in detail
p.000004: explanation for termination or termination.
p.000004: 4.12.2. If the contracting authority completes or suspends one test, the investigator shall inform in good time
p.000004: the medical establishment, the ethics committee and the regulatory body of the country where the center of the
p.000004: the study by providing them with a detailed written explanation of the suspension or closure.
p.000004: 4.12.3. If the Ethics Committee withdraws or terminates its affirmative opinion on a test in accordance with para.
p.000004: 3.1.2.4. and 3.3.8 the researcher informs the respective medical institution and the client, presenting them in detail
p.000004: a written explanation of termination or withdrawal.
p.000004: 4.13. Final reports from the researcher
p.000004: Upon completion of the clinical trial, the researcher shall notify the medical establishment, submit to the
p.000004: ethics committee summary of test results and all required reports of regulatory
p.000004: organs.
p.000004: 5. Contracting authority
p.000004: 5.1. Quality assurance and control
p.000004: 5.1.1. The contracting authority is responsible for the implementation and maintenance of quality and control systems
p.000004: through written standard operating procedures to ensure that the clinical trial is also conducted
p.000004: the data is collected, documented (recorded) and reported in accordance with the plan, GCP and applicable regulations
p.000004: requirements.
p.000004: 5.1.2. The contracting authority is responsible for securing an agreement between the researchers, Contract Research
p.000004: organization (DIO) and regulatory authorities to gain direct access to all sites
p.000004: the conduct of the clinical trial,
p.000004: sources / documents of information and reports from monitoring and verifications by the contracting authority, as well as
p.000004: inspections by local or foreign regulatory authorities.
p.000004: 5.1.3. At each stage of data processing, quality control is applied to confirm that all data is
p.000004: reliable and handled properly.
p.000004: 5.1.4. The contracts concluded between the sponsor and the researcher and any other party to the clinical trial are written,
p.000004: as part of the plan or in an additional agreement.
p.000004: 5.2. Contract research organization
p.000004: 5.2.1. The contracting authority may delegate all or part of its obligations to other physical and / or physical persons
p.000004: legal entities referred to as DIOs. Notwithstanding the assignment of obligations to other persons, the contracting authority
p.000004: bears the overall responsibility for conducting the study in accordance with the DCT and the validity of the findings
p.000004: data.
p.000004: The contracting research organization is obliged to put in place quality control and assurance procedures
p.000004: quality.
p.000004: 5.2.2. All contracts between the sponsor and other parties involved in the clinical trial are written and part of
p.000004: from the plan or other separate part.
p.000004: Any transfer of a clinical trial related DIO obligation and function shall be documented in writing.
p.000004: 5.2.3. All clinical-related duty and function not specifically assigned,
p.000004: remain with the contracting authority.
p.000004: 5.2.4. All instructions to the contracting authority in this guide also apply to the DIO to the extent that the DIO has accepted
p.000004: the clinical trial's duties and functions by the sponsor.
p.000004: 5.3. Medical examination
p.000004: The contracting authority appoints qualified medical personnel who are available for consultation on related issues
p.000004: clinical trial medical problems and issues. For this purpose, external may be appointed if necessary
p.000004: consultants.
p.000004: 5.4. Test design
p.000004: 5.4.1. The contracting authority uses qualified persons (eg biostatistics, clinical pharmacologists and physicians) to
p.000004: during all stages of the clinical trial from protocol and CCP preparation and planning
p.000004: analysis to the analysis and preparation of interim and final clinical trial reports.
p.000004: 5.4.2. The minutes shall be drawn up in accordance with paragraph 6 and with those issued by the International Conference on
p.000004: harmonization, the European Commission and the European Medicines Agency guides to the structure and
p.000004: the content of the protocol, the clinical trial reports, the design and conduct of the clinical trials.
p.000004: 5.5. Conduct clinical trial, data processing and recordkeeping
p.000004: 5.5.1. The contracting authority shall employ persons with appropriate qualifications to supervise the overall conduct of the
p.000004: clinical trial, data processing and verification, statistical analysis and
p.000004: the preparation of the reports.
p.000004: 5.5.2. The contracting authority may appoint an independent committee to evaluate the results in order to track the progress of one
p.000004: clinical trial, incl. safety data and critical performance parameters for certain
p.000004: intervals, and which recommends that the contracting entity continue, modify, or terminate the clinical trial.
p.000004: The Commission must have and follow written standard operating procedures for its work and yes
p.000004: keep written records of all its meetings.
p.000004: 5.5.3. In the case of electronic support for clinical trial records and / or remote documents
p.000004: electronic data systems of the contracting authority:
p.000004: 5.5.3.1. guarantees and documents that electronic data processing systems
p.000004: comply with the approved requirements of the contracting authority for completeness, accuracy, reliability and have been validated;
p.000004: 5.5.3.2. maintains a SEN for the use of these systems;
p.000004: 5.5.3.3. ensure that systems are prepared to allow data to be changed as you change
p.000004: document, and it is not possible to delete the entered data (ie, a trace is maintained for verifying the data and
p.000004: for editing);
p.000004: 5.5.3.4. maintains a security system that prevents unauthorized access to the data;
p.000004: 5.5.3.5. maintains a list of authorized persons entitled to make changes to the data referred to in points 4.1.5 and 4.9.3;
p.000004: 5.5.3.6. maintains adequate maintenance and storage of data backups;
p.000004: 5.5.3.7. supports a system that prevents code from being detected.
p.000004: 5.5.4. In the case of data transformation during processing it is always necessary
p.000004: make it possible to compare and monitor the original data with the processed data.
p.000004: 5.5.5. The contracting authority shall use the unambiguous participant identification code in accordance with paragraph 1.55, which
p.000004: allows recognition of all reported data for each individual participant.
p.000004: 5.5.6. The contracting entity or other data holder shall retain all specific basic documents relating to it
p.000004: to the clinical trial referred to in item 8 "Basic documents for conducting a clinical trial".
p.000004: The contracting authority shall ensure that appropriate storage conditions are in place to ensure that the documentation is maintained
p.000004: unchanged within the set deadlines.
p.000004: The contracting authority shall designate in writing the persons responsible for the archiving. The access to the archived documentation is
p.000004: limited except for specified persons.
p.000004: 5.5.7. The contracting authority shall keep all original documentation of the clinical trial referred to in paragraph 2.
p.000004: 8, and patient identification codes for at least 15 years after completion or termination
p.000004: the test.
p.000004: The contracting authority shall keep all specific basic documents in accordance with the applicable regulations
p.000004: requirements of the country (s) in which the medicinal product is authorized and / or where
p.000004: the contracting authority intends to apply for a permit (s).
p.000004: 5.5.8. Upon termination of the study program for the investigational medicinal product, the contracting entity shall keep
p.000004: the documentation at least two years after the end of the last study with the product under test.
p.000004: These documents shall be kept for a longer period if required by other regulations or by
p.000004: the contracting authority.
p.000004: 5.5.9. If the sponsor discontinues the clinical development of the investigational medicinal product, it is obliged to
p.000004: notified all clinical trial investigators and all regulatory authorities.
p.000004: 5.5.10. Any transfer of ownership of the data shall be documented and reported to the relevant regulatory authorities
p.000004: bodies and as indicated in the applicable regulatory requirements. The new data owner is responsible for
p.000004: the storage and archiving of the documentation in accordance with 5.5.7, 5.5.8 and 5.5.9.
p.000004: 5.5.11. When including the data in the marketing authorization documentation, the contracting authority shall keep it
p.000004: the documentation not less than two years after the last marketing authorization was obtained
p.000004: the territory of the European Union.
p.000004: The specific basic documents of the contracting entity shall be kept for at least two years after the last authorization for
p.000004: use, or at least two years after
p.000004: the official cessation of the clinical development of the investigational medicinal product. These documents are
p.000004: stored for a longer period if required by other regulatory requirements or by
p.000004: the contracting authority.
p.000004: 5.5.12. The contracting authority shall inform the principal investigator and the clinic in which the clinic is conducted in writing.
p.000004: testing for the storage period of the documentation.
p.000004: The contracting authority shall inform the principal investigator and the medical establishment in writing of the moment of the drop - off
p.000004: the need to keep the documentation.
p.000004: 5.6. Choosing a researcher
p.000004: 5.6.1. The sponsor is responsible for selecting the investigator and the venue for the clinical trial.
p.000004: Each researcher needs to be qualified by training and experience and have the right conditions
p.000004: according to points 4.1 and 4.2 for the proper conduct of the clinical trial for which he was selected. IN
p.000004: the case of using an organization with a coordinating committee and / or coordinating researcher in
p.000004: multi-center tests, the contracting authority is responsible for organizing and / or selecting them.
p.000004: 5.6.2. Prior to entering into a contractual relationship with the investigator to conduct the test
p.000004: provide the researcher with the protocol and the current brochure of the researcher and sufficient time for them
p.000004: viewing.
p.000004: 5.6.3. The contracting authority must obtain the consent of the researcher for:
p.000004: 5.6.3.1. conducting the clinical trial in accordance with the DCT, with applicable regulatory requirements, p
p.000004: the protocol approved by the sponsor and the ethics committee;
p.000004: 5.6.3.2. adherence to the procedures for recording and reporting data;
p.000004: 5.6.3.3. permitting monitoring, inspection and inspection;
p.000004: 5.6.3.4. preservation of the clinical trial key documents until the contracting authority notifies
p.000004: researcher that these documents are no longer needed.
p.000004: The sponsor and the researcher sign the protocol and / or other document to confirm this
p.000004: agreement.
p.000004: 5.7. Allocation of duties and functions
p.000004: Prior to commencing the clinical trial, the contracting authority shall identify, establish and distribute all related ones
p.000004: with clinical trial duties and functions.
p.000004: 5.8. Compensation for participants and researchers
p.000004: 5.8.1. The contracting authority insures or provides (through legal and financial coverage) the investigators against claims for
p.000004: damages arising from the clinical trial, except damages resulting from unlawful
p.000004: actions and / or negligence.
p.000004: 5.8.2. The contracting entity's internal procedures should describe the cost of treating participants in
p.000004: case of clinical trial related disabilities. These procedures must be in accordance with the applicable ones
p.000004: regulations.
p.000004: 5.8.3. The method and amount of compensation received by participants in the clinical trial are consistent with
p.000004: applicable regulatory requirements.
p.000004: 5.9. Financing
p.000004: The financial relations between the client and the researcher are documented by contract.
p.000004: 5.10. Notification / application to regulatory authorities
p.000004: Prior to the commencement of the clinical trial, the sponsor shall provide the documentation required by the regulatory authorities
p.000004: assessment, approval and / or authorization bodies to initiate the clinical trial. Each notification / application contains
p.000004: date and sufficient information to identify the protocol.
p.000004: The assignor shall notify the BDA in writing and the respective ethics committee under Art. 103 LPPMM at inclusion of the first
p.000004: patient in the trial on the territory of the Republic of Bulgaria.
p.000004: In the case of a multi-center survey, the contracting authority shall notify the BDA in writing and
p.000004: the relevant Ethics Committee under Art. 103 CLPM in case of discontinuation of the study
p.000004: to any of the study centers approved by the initial affirmative opinion.
p.000004: 5.11. Confirmation for consideration by the Ethics Committee
p.000004: 5.11.1. The contracting authority shall obtain from the researcher the following data and documents: name and address of the relevant ethics committee,
p.000004: opinion of the Ethics Committee that it has been drafted and operated in accordance with the CPT and applicable laws and
p.000004: by-laws; documented positive opinion from the Ethics Committee on the current
p.000004: version of the minutes, written informed consent form and any other information that will be provided
p.000004: provide the participants, patient recruitment procedures, payment documents and
p.000004: the compensation of participants and other documents requested by the committee.
p.000004: 5.11.2. If the Ethics Committee gives a favorable opinion, provided that changes are made to
p.000004: some aspect of the clinical trial (eg protocol modification, informed consent form, and
p.000004: any other information that will be provided to the participants and / or other procedures) shall be provided by the contracting authority
p.000004: a copy of the modification made by the researcher and the date of issue of a favorable opinion by the
p.000004: ethics.
p.000004: 5.11.3. The contracting authority shall provide the researcher with documents and dates for any new positive opinions
p.000004: for changes, and any withdrawal or termination of a favorable opinion.
p.000004: 5.12. Information on the investigational medicinal product
p.000004: 5.12.1. When planning a clinical trial, the contracting authority shall ensure that sufficient data are available,
p.000004: demonstrating the safety and efficacy of non-clinical and / or clinical trials of the product in support
p.000004: of its administration to humans by route, dosage, duration and test group of patients to be
p.000004: study.
p.000004: 5.12.2. The contracting authority shall update the researcher's brochure when new and relevant information becomes available.
p.000004: 5.13. Production, packaging, labeling and coding of the test drug
p.000004: product
p.000004: 5.13.1. The sponsor shall ensure that the investigational medicinal product (including
p.000004: comparator and placebo medicinal product, if used) is characterized in accordance with the development stage of
p.000004: a medicinal product that is manufactured in accordance with the applicable GMP and is coded and labeled in a manner that preserves
p.000004: blinding, if any. The contracting entity shall prepare a labeling of the tested medicinal product in accordance
p.000004: with the requirements of Good Manufacturing Practice rules for medicinal products under development and
p.000004: study and applicable regulatory requirements.
p.000004: 5.13.2. The contracting authority determines the storage temperature and conditions (eg light protection), storage time,
p.000004: dissolution fluids and procedures, as well as infusion products, if any.
p.000004: The sponsor notifies all parties involved in the clinical trial (i.e., monitoring, investigators,
p.000004: pharmacists, storage officers) for certain conditions.
p.000004: 5.13.3. It is necessary to protect the packaging of the tested medicinal product from contamination and unacceptable
p.000004: degradation of quality during transport and storage.
p.000004: 5.13.4. In blind trials, the coding system for the investigational medicinal product must be included
p.000004: mechanism for immediate disclosure of the medicinal product in case of emergency, but not allowing for imperceptible detection
p.000004: on the code.
p.000004: 5.13.5. If significant changes are made to the composition of the trials during the clinical trial
p.000004: medicinal product or medicinal product comparison, the results of any additional
p.000004: tests on medicinal products with a new composition (ie stability test, solubility profile,
p.000004: bioavailability) should be available before
p.000004: the use of the products in a clinical trial to assess whether the changes significantly affect the pharmacokinetic
p.000004: profile of the medicinal product.
p.000004: 5.14. Delivery and handling of the tested medicinal product
p.000004: 5.14.1. The sponsor is responsible for supplying the investigator with the investigational medicinal product.
p.000004: The sponsor shall provide the participants, free of charge, with the tested medicinal product (s) and each device,
p.000004: necessary for its implementation.
p.000004: In case the contracting authority is a non-profit organization, a clinical trial may be conducted with products that
p.000004: not provided by the contracting authority, with the explicit consent of the individual / legal entity financing
p.000004: the treatment.
p.000004: In the case of a non-interventional study, the study may be conducted with products not provided by
p.000004: the contracting authority.
p.000004: 5.14.2. The contracting entity does not deliver the investigational medicinal product to the investigator until they are available
p.000004: all necessary documents (ie positive opinion of Ethics Committee and Regulators).
p.000004: 5.14.3. The contracting entity shall ensure that the researcher is provided with written procedures including instructions,
p.000004: which he is obliged to follow when handling and storing the investigational medicinal product; and
p.000004: the documentation to it. Procedures include adequate and safe receipt, handling, storage, dispensing,
p.000004: collecting unused quantities from patients and returning the unused quantities to the client
p.000004: the investigational medicinal product (or destruction or otherwise absorption, if authorized by
p.000004: the contracting authority and complies with the applicable regulatory requirements).
p.000004: 5.14.4. The contracting authority:
p.000004: 5.14.4.1. guarantee the timely delivery of the investigational medicinal product to the investigators;
p.000004: 5.14.4.2. keeps records documenting the sending, receiving, distribution,
p.000004: the return and destruction of the tested medicinal product in accordance with item 8;
p.000004: 5.14.4.3. maintains a system for recovering and documenting tested medicinal products
p.000004: reimbursement (ie for insufficient return of the medicinal product, return upon completion of
p.000004: clinical trial, expiry date);
p.000004: 5.14.4.4. maintains a system for destroying / transmitting to other persons unused quantities and documentation thereof
p.000004: destruction / transmission.
p.000004: 5.14.5. The contracting authority:
p.000004: 5.14.5.1. ensure that the medicinal product is stable throughout its use;
p.000004: 5.14.5.2. stores sufficient quantities of the investigational medicinal product used during the clinical trial
p.000004: testing to confirm the specifications if necessary and keep records of
p.000004: analysis and characteristics of the test batch;
p.000004: 5.14.5.3. store the samples to the extent that stability allows, until the analyzes of the data from the
p.000004: the clinical trial or for a longer period if required by other applicable regulatory requirements.
p.000004: 5.15. Access to documentation
p.000004: 5.15.1. The contracting entity shall document in the record or other written agreement that the principal investigator / institution,
p.000004: the study center will provide direct access to clinical data sources / documents
p.000004: testing for monitoring, verification, review by the ethics committee and inspection by the regulatory authorities.
p.000004: 5.15.2. The Contracting Authority verifies that all participants have given their written consent for direct access to theirs
p.000004: original medical records for conducting clinical-related monitoring, inspections,
p.000004: review by ethics and inspection committee of
p.000004: regulatory authorities.
p.000004: 5.16. Safety information
p.000004: 5.16.1. The contracting authority is responsible for the continuous safety assessment of the investigational medicinal product
p.000004: product.
p.000004: 5.16.2. The sponsor shall inform the BDA, the Ethics Committee and the researchers of any new information that
p.000004: may pose a threat to the health and well - being of patients, affecting the course of
p.000004: study or change the BDA's authorization to conduct the study and / or change the positive
p.000004: opinion of the ethics committee to continue the clinical trial.
p.000004: 5.16.3. The contracting authority shall keep detailed records of all reports of suspected adverse events that have occurred
p.000004: when using the investigational medicinal product for which it has been informed by the investigator or from another source
p.000004: of information.
p.000004: 5.16.4. The assignor evaluates the adverse events in terms of severity, expectation and
p.000004: causal connection. The contracting authority shall develop and implement procedures for evaluating adverse events for
p.000004: severity, expectation and cause and effect in accordance with published International Guidelines
p.000004: harmonization conference, the European Commission and the European Medicines Agency.
p.000004: 5.16.5. The contracting authority shall actively collect any additional information that is necessary to evaluate the
p.000004: individual reports of adverse events.
p.000004: 5.1.6.6. All adverse events rated by the researcher or assignor as least likely to be related
p.000004: with the test product, are treated and reported as adverse reactions.
p.000004: 5.17. Reporting side effects
p.000004: 5.17.1. Reports of suspected serious and unexpected adverse reactions under Art. 138 LPPM are submitted by
p.000004: the sponsor of the clinical trial.
p.000004: The contracting authority is responsible for reporting serious adverse reactions, including when
p.000004: reactions are to an authorized test medicinal product used in the test as a product for
p.000004: a comparison for which the contracting authority does not hold the marketing authorization. In these cases the contracting authority
p.000004: inform the marketing authorization holder of the product for the territory of Bulgaria of the reaction and of the submission of the product
p.000004: information to the BDA.
p.000004: Where the investigational medicinal product is not authorized, the sponsor shall notify the BDA and
p.000004: the Ethics Committee, in addition to the communications under Art. 138, para. 1 and 3 of ZLPHM and for all suspects
p.000004: serious and unexpected side effects when using the test drug regardless of origin
p.000004: them.
p.000004: Serious and unexpected adverse reaction reports are submitted to the Medicines Executive Agency and
p.000004: the ethics committee immediately and no later than 15 days after receipt of information on their occurrence. At
p.000004: explicit written consent of the Ethics Committee reports of suspected serious and unexpected undesirable
p.000004: reactions may be reported at larger intervals, but not less than once every six months.
p.000004: The contracting authority is responsible for submitting reports to all interested researchers,
p.000004: ethics and regulatory authorities for any side effects that are serious and unexpected.
p.000004: 5.17.2. Serious and unexpected adverse reaction reports should comply with applicable regulatory requirements
p.000004: requirements and guidance of the International Harmonization Conference on the processing of safety data
p.000004: Clinical Trials - "Definitions and Standards for Emergency Reporting" (ICH Guideline for Clinical Safety Data
p.000004: Management: Definitions and Standards for Expedited Reporting).
p.000004: 5.17.3. The contracting authority shall submit to the regulatory authorities all updates of
p.000004: safety data and periodic reports. The contracting authority shall provide the Executive Agency once a year
p.000004: medicines and ethics committee list all suspected serious side effects that are
p.000004: occurred during the previous period, and a safety report of the test participants.
p.000004: 5.17.4. The annual safety report contains a summary of the safety of the tested medicinal product for
p.000004: the last one-year period from the date of the first authorization to conduct a clinical trial with
p.000004: test product in the territory of the European Union.
p.000004: The contracting authority submits the annual safety report to the BDA and the Ethics Committee within 60 calendar days
p.000004: after the end of the period covered by the report.
p.000004: For clinical trials of less than one year duration, an annual safety report shall be submitted to
p.000004: term up to 90 days after the end of the test with the notification under art. 142, para. 2 CLPM.
p.000004: When conducting more than one clinical trial with the same test product, the contracting authority shall submit a total annual
p.000004: safety report. In such cases, the report shall contain data on the safety profile of the product tested and annual
p.000004: safety reports on each of the clinical trials conducted in Bulgaria.
p.000004: 5.17.5. The contracting authority shall provide an annual safety report beyond the deadline requested by the BDA and / or
p.000004: the ethics committee.
p.000004: 5.18. Monitoring
p.000004: 5.18.1. The purpose of monitoring is to verify that the rights and well-being of
p.000004: people; the reported data are accurate, complete and consistent with the original documents; conducting the clinical
p.000004: testing is in accordance with the approved plan and changes, DCT and applicable regulatory requirements.
p.000004: 5.18.2. Selection and qualification of monitoring entities
p.000004: 5.18.2.1. The persons conducting the monitoring are appointed by the contracting authority.
p.000004: 5.18.2.2. The monitoring personnel are trained and have the necessary scientific and / or medical knowledge,
p.000004: to properly monitor the clinical trial. Qualification of the practitioners
p.000004: monitoring, is documented.
p.000004: 5.18.2.3. Monitoring persons should be fully aware of the drug tested
p.000004: the product, the minutes, the written informed consent form and any other written information to be provided
p.000004: of the participants, the SOP of the contracting authority, the CPT and the applicable regulatory requirements.
p.000004: 5.18.3. Scope and nature of monitoring
p.000004: The contracting entity shall ensure that the tests are properly monitored. The contracting authority is obliged to
p.000004: determine the scope and manner of monitoring, taking into account the purpose, design, complexity, blinding, size
p.000004: and clinical trial endpoints. On-site monitoring is generally performed before, during and
p.000004: after the clinical trial. By way of exception, the contracting authority may determine that central monitoring,
p.000004: involving procedures such as training and meetings of researchers and the use of advanced written manuals,
p.000004: Ensure that the clinical trial is conducted in accordance with DCT. Acceptable method for selecting verification data
p.000004: is the method of statistically controlled samples.
p.000004: 5.18.4. Obligations of monitoring persons
p.000004: In accordance with the requirements of the contracting entity, the monitoring entity shall ensure that the clinical
p.000004: the test shall be conducted and properly documented by performing the following:
p.000004: 5.18.4.1. acts as the main link for correspondence between the sponsor and the researcher;
p.000004: 5.18.4.2. determine whether the researcher has the relevant qualifications and resources,
p.000004: which will remain appropriate throughout the test that the conditions including the laboratory, equipment and
p.000004: staff, are appropriate and will remain so throughout the clinical trial for his or her own
p.000004: safe and proper conduct;
p.000004: 5.18.4.3. establishes that with regard to the investigational medicinal product:
p.000004: 5.18.4.3.1. storage time and conditions are appropriate and deliveries are sufficient for the whole test;
p.000004: 5.18.4.3.2. the test drug is only delivered to participants who are eligible for the preparation
p.000004: his dose, as determined by the protocol;
p.000004: 5.18.4.3.3. members of the research team are provided with the necessary instructions for proper use, handling,
p.000004: storage and return of the test medicinal product;
p.000004: 5.18.4.3.4. the receipt, use and return of the test medicinal product at the venues of
p.000004: the clinical trial is properly controlled and documented;
p.000004: 5.18.4.3.5. handling unused quantities of the tested medicinal product is relevant
p.000004: regulatory requirements and agreed with the contracting authority;
p.000004: 5.18.4.4. determine whether the researcher follows the approved protocol and any approved changes, if any;
p.000004: 5.18.4.5. determine whether informed consent has been obtained from each participant prior to its inclusion in the clinical setting
p.000004: testing;
p.000004: 5.18.4.6. ensure that the researcher receives the researcher 's current brochure, all documents and
p.000004: all clinical trial supplies necessary for its proper conduct and in accordance with
p.000004: applicable regulatory requirements;
p.000004: 5.18.4.7. ensure that the researcher and his or her team are sufficiently familiar with the clinical trial;
p.000004: 5.18.4.8. verifies that the researcher and his or her team perform the identified clinical activities
p.000004: testing in accordance with the protocol and all other written contracts between the sponsor and the researcher and that
p.000004: have not transferred these activities to other unauthorized persons;
p.000004: 5.18.4.9. checks that the researcher includes only suitable persons;
p.000004: 5.18.4.10. report the status of involvement of participants;
p.000004: 5.18.4.11. verifies that the original documents and other clinical trial documents are accurate,
p.000004: complete and up-to-date and stored;
p.000004: 5.18.4.12. checks that the researcher provides all required reports, notifications and requests and
p.000004: whether these documents are accurate, complete, timely, legible, dated and identify the study;
p.000004: 5.18.4.13. verifies and compares the accuracy and completeness of the patient's clinical record data,
p.000004: original documents and other clinical trial related documents; the person performing the
p.000004: monitoring, must check whether:
p.000004: 5.18.4.13.1. the data required by the protocol is accurately reported to the CCP and is in accordance with the original documents;
p.000004: 5.18.4.13.2. any dose modification and / or treatment for each individual participant is well documented;
p.000004: 5.18.4.13.3. adverse events, concomitant treatment, and additional illnesses are
p.000004: reported to the CCP in accordance with the protocol;
p.000004: 5.18.4.13.4. visits that participants could not make and studies that were not made clear
p.000004: reported as such in the CCP;
p.000004: 5.18.4.13.5. all dropped and excluded participants in the clinical trial were reported and explained to the CCP;
p.000004: 5.18.4.14. notifies the researcher of any incorrect CCP replacements, omissions or illegibility; the person performing the
p.000004: monitoring, ensure that adjustments, additions or
p.000004: deletions are made with date and explained (if necessary) and with initials set by the researcher
p.000004: or by a member of the researcher's team who is authorized to place their initials on
p.000004: changes to the CCP for the researcher; the power of attorney is documented;
p.000004: 5.18.4.15. determine whether all adverse events have been reported within the time limits required by the DCP,
p.000004: the protocol and the applicable regulatory requirements;
p.000004: 5.18.4.16. determine whether the researcher keeps the basic documents;
p.000004: 5.18.4.17. draws the researcher's attention to protocol deviations, SOPs, DCTs and applicable regulatory requirements
p.000004: and shall take the necessary measures to prevent any such deviations.
p.000004: 5.18.5. Monitoring procedures
p.000004: In order to monitor the specific test, the person performing the monitoring shall comply with those established by the contracting authority
p.000004: written SOPs, as well as those procedures that are specified by the client for the specific clinical trial.
p.000004: 5.18.6. Monitoring report
p.000004: 5.18.6.1. The monitoring person shall submit a written report to the contracting authority after each visit to the contracting authority
p.000004: the center of the clinical trial and after any communication related to the clinical trial.
p.000004: 5.18.6.2. The reports shall include the date, the name of the center, the name of the monitoring person, the name of
p.000004: the researcher or other persons he has contacted.
p.000004: 5.18.6.3. The reports should include a summary of what the reviewer has reviewed
p.000004: monitoring, and its views on important facts, deviations and incompletions, conclusions and actions,
p.000004: that have been or will be undertaken and / or recommended compliance actions.
p.000004: 5.18.6.4. The review and follow-up of actions following a monitoring report by the contracting entity shall be documented
p.000004: by a person authorized by the contracting authority.
p.000004: 5.19. Checking
p.000004: When examining as part of the quality assurance, the contracting entity is obliged to consider the following:
p.000004: 5.19.1. Purpose
p.000004: The purpose of the verification of the contracting entity, which is independent and separate from the routine functions of the executing entity
p.000004: monitoring or quality control functions should be an assessment of the conduct of the clinical trial and
p.000004: compliance with the protocol, SOP, DCT and applicable regulatory requirements.
p.000004: 5.19.2. Selection and qualifications of examiners
p.000004: 5.19.2.1. The contracting authority appoints persons who are independent of the clinical trials / systems to carry out the checks.
p.000004: 5.19.2.2. The contracting authority must ensure that the examiners are qualified in training and training
p.000004: an attempt to properly conduct checks. The qualifications of the examiners are documented.
p.000004: 5.19.3. Verification procedures
p.000004: 5.19.3.1. The sponsor shall ensure that the verification of clinical trials / systems is carried out in accordance with
p.000004: written procedures of the contracting authority as to what and how to check, frequency of inspection, form and
p.000004: the content of the inspection reports.
p.000004: 5.19.3.2. The plan and procedures for verifying a clinical trial by the sponsor are guided by the importance
p.000004: the clinical trial, the number of participants in the clinical trial, the type and complexity of the clinical trial
p.000004: testing, the degree of risk to participants and any problems identified.
p.000004: 5.19.3.3. The examiner's observations and findings shall be documented.
p.000004: 5.19.3.4. Regulatory authorities may require access to an audit report for each
p.000004: a particular case where there is evidence of a serious non-compliance with the DCT or in administrative or
p.000004: court proceedings.
p.000004: 5.19.3.5. When required by applicable law or regulation, the contracting authority shall submit a certificate of inspection.
p.000004: 5.20. Violation
p.000004: 5.20.1. In the event of a breach by the researcher or by the research member (s)
p.000004: the contracting authority shall take immediate action on the protocol, SOP, DCP and / or applicable regulatory requirements
p.000004: intervention to maintain compliance.
p.000004: 5.20.2. If, during monitoring and / or inspection, it is found that a material breach of
p.000004: the fault of the researcher, the contracting authority shall terminate his participation in the clinical trial and shall inform in due time
p.000004: regulatory authorities where the breach results in termination of the investigator's involvement.
p.000004: 5.21. Premature termination or termination of testing
p.000004: If a test is prematurely terminated or discontinued, the contracting authority shall be bound
p.000004: inform the investigator and the regulatory authorities in a timely manner of termination or termination and the reasons
p.000004: for that. The researcher or the contracting authority shall, in due time, comply with the applicable regulatory requirements
p.000004: inform the Ethics Committee, giving the reasons for termination or termination.
p.000004: 5.22. Clinical trial / study reports
p.000004: If a test is completed or prematurely terminated or discontinued, the contracting authority
p.000004: ensure that the reports and ethics reports are prepared and presented to the regulatory authorities and the Ethics Committee
p.000004: the clinical trial in accordance with applicable regulatory requirements. The contracting authority also guarantees compliance
p.000004: of the test reports annexed to the application for authorization with the standards set out in
p.000004: the guidance of the International Harmonization Conference on the structure and content of
p.000004: clinical trial reports.
p.000004: 5.23. Multicenter tests
p.000004: In the case of multi-center tests, the contracting entity shall ensure that:
p.000004: 5.23.1. All researchers carry out the clinical trial in strict accordance with the approved by the client
p.000004: minutes and after a favorable opinion from the Ethics Committee, if required by the regulatory authorities.
p.000004: 5.23.2. Patients' clinical records are compiled to capture data from all centers
p.000004: of the multicenter test. Those researchers who collect additional data are sourced
p.000004: with additional CCPs designed to capture this additional data.
p.000004: 5.23.3. The responsibilities of the coordinating researcher and the participating researchers are documented directly
p.000004: before starting the clinical trial.
p.000004: 5.23.4. All researchers were instructed to follow the protocol to comply with
p.000004: standards set by the contracting authority for the evaluation of clinical and laboratory findings and for completing the clinical
p.000004: map of the patient.
p.000004: 5.23.5. Communication between researchers is facilitated.
p.000004: 6. Clinical trial protocol and protocol changes
p.000004: The clinical trial protocol should mainly contain the listed data. The specific information that
p.000004: applicable only to individual clinical trial centers, may be included on a single page / pages
p.000004: or be included in a separate agreement. Some of the information listed below may be contained in others,
p.000004: protocol related documents such as the researcher's brochure.
p.000004: 6.1. General information
p.000004: 6.1.1. Protocol title, identification code and date. Each change / changes includes a number and a date.
p.000004: 6.1.2. Name and address of the contracting entity and the monitoring entity and the contracting research organization, if any
p.000004: included in the clinical trial.
p.000004: 6.1.3. Name and position of the person (s) authorized to sign the protocol and its amendment (s)
p.000004: the name of the contracting authority.
p.000004: 6.1.4. Name, position, address and telephone number (s) of the medical examiner by the client (or dentist)
p.000004: medicine) for the clinical trial.
p.000004: 6.1.5. Name and position of the investigator (s) responsible for conducting the clinical trial,
p.000004: as well as the addresses and telephone numbers of the clinical trial center (s).
p.000004: 6.1.6. Name, position, address and telephone number (s) of the physician or dentist who is
p.000004: responsible for any clinical (or dental) decision-making (if different) from the clinical trial
p.000004: researcher).
p.000004: 6.1.7. Name (s) and address (es) of the clinical laboratory (s) and other health and / or technical departments and / or institutions,
p.000004: included in the clinical trial.
p.000004: 6.2. Basic information
p.000004: 6.2.1. Name and description of the product (s) tested.
p.000004: 6.2.2. Summary of non - clinical trial data of clinical relevance and of
p.000004: clinical trials related to the present.
p.000004: 6.2.3. Summary of identified and potential risks and benefits, if any, to humans.
p.000004: 6.2.4. Description and rationale for route of administration, dose, dosage regimen and treatment
p.000004: period.
p.000004: 6.2.5. The view that the clinical trial will be conducted in accordance with the protocol,
p.000004: DCT and applicable regulatory requirements.
p.000004: 6.2.6. Description of the category of persons to be tested.
p.000004: 6.2.7. Used literature and data that are relevant to the clinical trial and provide the basis for
p.000004: the clinical trial.
p.000004: 6.3. Tasks and purpose
p.000004: A detailed description of the tasks and purpose of the clinical trial.
p.000004: 6.4. Test design
p.000004: The scientific value of the clinical trial and the reliability of the data depend significantly on the design of the clinical trial
p.000004: the clinical trial. The design description includes:
...
p.000004: and be able to make a personal judgment as to the purpose of the proposed test to be accurate with respect to
p.000004: risk - benefit. A medical person is involved in the publication of the researcher's booklet
p.000004: qualification, and approval of the content is done by specialists in the relevant medical
p.000004: majors who compiled the data described.
p.000004: The type and amount of information may vary depending on the stage of development of the product being tested. When
p.000004: the test product is authorized and doctors are widely aware of its pharmacology, it is not
p.000004: a detailed booklet of the researcher is required. Alternatively, a basic brochure may be presented
p.000004: product information or a summary of the product, stating that they contain a contemporary, complete and
p.000004: detailed information on all aspects of the product under test and may be relevant to
p.000004: the researcher. If a new application (eg a new indication) is tested for a product authorized to
p.000004: use, a booklet for the researcher specific to this new use is prepared. Researcher's brochure
p.000004: it shall be reviewed once a year and modified, where necessary, in accordance with the contracting entity's written procedures.
p.000004: More frequent changes can be made depending on the stage of product development and the type of new product
p.000004: information. Relevant new information, in line with good clinical practice, may be such
p.000004: the importance of discussing it with researchers and, if possible, in the Ethics Committee
p.000004: and / or regulatory authorities before being included in a researcher's brochure.
p.000004: The contracting authority is responsible for ensuring that researchers are aware of the updated brochure
p.000004: and researchers are required to submit a new booklet to the researcher
p.000004: the relevant ethics committees. In the case of a test commissioned by a researcher, the contracting authority is
p.000004: obliged to provide assurance that the manufacturer's brochure may be obtained from the manufacturer. If
p.000004: the test product is manufactured by the researcher, he is obliged to provide the necessary information
p.000004: in front of the test team. In case the preparation of an official booklet of the researcher is impossible,
p.000004: as a substitute, the contracting authority shall provide in the protocol a detailed basic information section containing
p.000004: a minimum of up-to-date data described in this Annex.
p.000004: 7.2. Basic considerations
p.000004: The researcher's brochure includes:
p.000004: 7.2.1. Home page
p.000004: It includes: name of the contracting authority, characteristic of each product tested, ie. research code, chemical
p.000004: or an approved generic name and trade name (if any), date of issue, edition number and reference number
p.000004: and the release date it replaces. Sample:
p.000004: HOME PAGE
p.000004: NAME OF THE CONTRACTING AUTHORITY
p.000004: Medicine:
p.000004: Test number:
p.000004: Name (s): Chemical, INN (if approved): Trade name
p.000004: Researcher's brochure Edition number:
p.000004: Release Date:
p.000004: Replaces previous edition number: Date:
p.000004: 7.2.2. Privacy Statement
p.000004: The contracting authority may include an opinion giving instructions to
p.000004: the researcher / recipients to accept the researcher's brochure as confidential throughout
p.000004: information and use by the researcher team and the ethics / regulatory committee.
p.000004: 7.3. Content of the researcher's brochure
p.000004: The researcher's booklet contains the following sections, each of which, if possible, has one
p.000004: literary reference:
p.000004: 7.3.1. Table of Contents:
p.000004: Privacy Statement Signature Page
p.000004: 1. Content
p.000004: 2. Summary
p.000004: 3. Introduction
p.000004: 4. Physical, chemical and pharmaceutical properties and formula
p.000004: 5. Non-clinical trials
p.000004: 5.1. Non-clinical pharmacology
p.000004: 5.2. Pharmacokinetics and metabolism of the product in animals
p.000004: 5.3. Toxicology
p.000004: 6. Effects in humans
p.000004: 6.1. Pharmacokinetics and metabolism of the product in humans
p.000004: 6.2. Safety and efficiency
p.000004: 6.3. Experience after marketing authorization
p.000004: 7. Summary of data and recommendations to the researcher
p.000004: 1. Publications
p.000004: 2. Reports
p.000004: Applications (if any)
p.000004: 7.3.2. Summary
p.000004: A brief summary (not exceeding two pages) is given indicating an important physical, chemical,
p.000004: pharmaceutical, pharmacological, toxicological, pharmacokinetic, metabolic and clinical information that
p.000004: corresponds to the stage of clinical development of the test product.
p.000004: 7.3.3. Introduction
p.000004: A brief introductory description containing the chemical name (as well as the generic and trade name) is included
p.000004: name, when approved) of the product (s) tested, all active ingredients, pharmacological class and
...
p.000004: pharmacological and toxicological findings in animal species.
p.000004: 7.3.5.3. Toxicology
p.000004: A summary of the toxicological effects found in relevant studies conducted on different subjects shall be provided
p.000004: animal species, including the following: single dose toxicity; repeated dose toxicity
p.000004: dosing; carcinogenicity; special tests (eg irritability and sensitivity); reproductive toxicity;
p.000004: genotoxicity (mutagenicity).
p.000004: 7.3.6. Effects in humans
p.000004: A full description of the known effects of the tested product (s) on humans, including information on
p.000004: pharmacokinetics, metabolism, pharmacodynamics, dose response, safety, efficacy and other pharmacological
p.000004: actions. Whenever possible, a summary of each completed clinical trial as well as
p.000004: information regarding the results of any use of the test medicinal product to be tested
p.000004: different from clinical trials (eg post-market experience).
p.000004: 7.3.6.1. Pharmacokinetics and metabolism of the product in humans
p.000004: A summary of the pharmacokinetics of the investigational medicinal product shall be provided,
p.000004: which, if possible, includes the following: pharmacokinetics (including metabolism and absorption, binding to
p.000004: plasma proteins, distribution and elimination); bioavailability (where possible absolute and / or relative),
p.000004: using a dosage form for comparison; subgroups of the population (eg gender, age and impaired function)
p.000004: to an authority); interactions (eg product-product interactions or food effects); others
p.000004: pharmacokinetic data (eg, results from population-based studies conducted in clinical trials).
p.000004: 7.3.6.2. Safety and efficiency
p.000004: A summary of information obtained from previous human clinical trials (healthy volunteers) is provided
p.000004: and / or patients) for the safety, pharmacodynamics, efficacy and dose response of the product (s) tested
p.000004: (and their metabolites where appropriate). The conclusions of this information are commented. Where they are
p.000004: completed a large number of clinical trials, the use of safety and efficacy summaries of
p.000004: multiple sub-group indication tests may be representative of the data. Summaries can
p.000004: also be presented in tabular form for adverse reactions for all clinical trials (incl.
p.000004: those for all testimony tested). Important differences in trends / incidence of
p.000004: side effects against indications or subgroups.
p.000004: A description of the potential risks and undesirable effects is provided
p.000004: reactions based on direct experience with the study drug
p.000004: product and related products, as well as precautions or special observations that
p.000004: to be carried out during the tested use of the medicinal product (s).
p.000004: 7.3.6.3. Experience after authorization for use
p.000004: Indicate the countries in which the test medicinal product is authorized. Commented
p.000004: any relevant information obtained from use after authorization (eg formulas, doses, routes of administration or administration)
p.000004: side effects). The countries in which the test medicinal product has not been authorized shall also be indicated
p.000004: for use or has been withdrawn from the market.
p.000004: 7.3.7. Summary of data and recommendations to the researcher
p.000004: This section shall, as far as possible, provide a comprehensive commentary on non - clinical and non - clinical settings
p.000004: clinical data and summarizes information from different sources on different aspects of the product tested.
p.000004: In this way, the researcher may be familiar with the most informative interpretation of the available data and
p.000004: assessing the conclusions of the information for future clinical trials.
p.000004: Commented on published reports of relevant medicinal products to help the researcher
p.000004: predicted side effects or other problems in clinical trials.
p.000004: The main purpose of this section is to provide the researcher with a clear understanding of the possible risks,
p.000004: side effects and specific tests, observations and precautions that may be required to
p.000004: clinical trial. This understanding needs to be based on accessible physical, chemical,
p.000004: pharmaceutical, pharmacological, toxicological and clinical information on the study (s) medicinal product (s).
p.000004: A guide is also provided to the investigating physician to identify and treat possible overdose
p.000004: adverse reaction based on previous human experience and pharmacology of the studies
p.000004: medicine.
p.000004: 8. Basic documents for conducting a clinical trial
p.000004: 8.1. Introduction
p.000004: Core documents are those documents that individually and collectively allow for an assessment of the conduct of one
p.000004: testing and the quality of the data obtained and constitute the main dossier of the clinical trial. These
p.000004: the documents serve to demonstrate compliance by the researcher, the contracting authority and the person performing the work
p.000004: monitoring, the standards of Good Clinical Practice and all applicable regulatory requirements.
p.000004: The basic documents also serve several other important purposes. Completion of the main documents in a timely manner
p.000004: at the center of the researcher and the contracting authority can significantly contribute to the successful completion of a test
p.000004: by the researcher, the contracting entity and the monitoring person. These documents are subject to independent review
p.000004: (audit) by the contracting authority's independent auditor and inspected by regulatory authorities as part of the process
p.000004: to confirm the validity of the test and the completeness of the data obtained.
p.000004: The list of minimum set of basic documents is set out below. The various documents are grouped into three
p.000004: divided according to the stage of the clinical trial, during which they are usually drawn up: 1. before
p.000004: initiation of the clinical phase of the clinical trial; 2. during the course of the clinical trial,
p.000004: and 3. upon completion or termination of the clinical trial. A description of each is provided
p.000004: document and where it needs to be stored - with the researcher, with the sponsor, or both.
p.000004: It is acceptable to combine some of the documents in such a way that the individual elements can be easily
p.000004: recognize.
p.000004: A basic clinical trial dossier should be compiled at the beginning of the clinical trial as
p.000004: at the center of the researcher and at the office of the contracting authority. The final completion of a clinical
p.000004: the test shall only take place when the monitoring body has examined the main test file of
p.000004: the investigator and the principal dossier of the contracting entity's examination and found that all necessary documents were available
p.000004: in the relevant files.
p.000004: Some or all of the documents described may be subject to review by the contracting authority and
p.000004: inspection by regulatory authorities, which should be accessible for that purpose.
p.000004: 8.2. Before starting the clinical phase of the clinical trial
p.000004: During the planning of this stage and before the formal start of the clinical trial, it is necessary to
p.000004: draw up and keep the following documents:
p.000004: Document Purpose Stored
p.000004: in the documentation of the assigning researcher
p.000004: 1 2 3
p.000004: 4
p.000004: 8.2.1. Researcher's Brochure Document that X
p.000004: X
p.000004: the corresponding and ac-
p.000004: complete scientific test information
p.000004: the product is presented to the researcher.
p.000004: 8.2.2. Minutes signed and changes Documented X
p.000004: X
p.000004: the contract between
p.000004: (if any) and a sample from the clinician and sponsor for
p.000004: protocol /
p.000004: The patient's card changes and CCP.
p.000004: 8.2.3.
p.000004: 8.2.3.1.
p.000004: 8.2.3.1.
p.000004: 8.2.3.2.
p.000004: 8.2.4.
p.000004: 8.2.5.
p.000004: Information given to subjects in the clinical trial
p.000004: Informed consent form (incl. Applicable translations)
p.000004: Any other written information
p.000004: Recruitment ad (if any)
p.000004: Financial aspects of the clinical trial
p.000004: Insurance policy
p.000004: Document X X informed compliance
p.000004: participant lassi.
p.000004: Document that the X X participants will
p.000004: be presented
p.000004: relevant information (such as content and style).
p.000004: Document that X 0
p.000004: recruitment measures-
p.000004: not patients
p.000004: appropriate and involuntary.
p.000004: Document X X
p.000004: financial contracts-
p.000004: between the researcher and the assignor
p.000004: for the clinical trial.
p.000004: Document that in X X
p.000004: case of contact
p.000004: but with the clinical trial the disability will be compensated.
p.000004: 8.2.6. Signed contract between the parties To be documented
p.000004: contracts.
p.000004: participants
p.000004: 8.2.6.1.
p.000004: 8.2.6.2.
p.000004: 8.2.6.3.
p.000004: 8.2.7.
p.000004: 8.2.7.1.
p.000004: 8.2.7.2.
p.000004: 8.2.7.3.
p.000004: 8.2.7.4.
p.000004: 8.2.7.5.
p.000004: 8.2.7.6.
p.000004: 8.2.7.7.
p.000004: 8.2.8.
p.000004: 8.2.9.
p.000004: 8.2.10.
p.000004: between the researcher and the contracting authority / contracting research organization;
p.000004: between the client and the medical center - the center of the study; between contracting authority and contract research
p.000004: organization
p.000004: Dated, documented permission / affirmative opinion of
p.000004: CE for the following:
p.000004: Protocol and amendments to the CCP
p.000004: Informed Consent Form Any other information provided to participants
p.000004: Recruitment announcement (if used)
p.000004: Participant compensation All other documents subject to approval / opinion
p.000004: Composition of the Ethics Committee / Appointment Order
p.000004: Authorization / notification of regulatory authorities
p.000004: CV and / or other document
p.000004: ment proving the qualifications of the principal investigator and
p.000004: X
p.000004: X 0
p.000004: Document that the X clinical exam-
p.000004: This was considered by a committee on
p.000004: ethics and has received
p.000004: positively-
p.000004: will. To identify the number and date-
p.000004: and the version of the documents.
p.000004: Document that the X Ethics Committee
p.000004: It is compiled in accordance with the DCT.
p.000004: Document that X permission is
p.000004: received / the notice period expired before the clinical start
p.000004: testing and in accordance with
p.000004: you have regulatory requirements.
p.000004: Document the X qualifications and
p.000004: reliability for
p.000004: conducting the clinical trial and / or for
p.000004: X
p.000004: X X
p.000004: X
p.000004: (If required)
p.000004: X
p.000004: X
p.000004: rendering me-
p.000004: Researchers' child monitoring of participants.
...
p.000004: 8.3.11 Additional correspondence, Document all
p.000004: agreements
p.000004: other than visits to valuable or meaningful comments on
p.000004: regarding of
p.000004: : letters, meeting reports, administration, minutes,
p.000004: violations,
p.000004: notes from telephone conversations conducting clinical
p.000004: testing and
p.000004: reporting of adverse events.
p.000004: 8.3.12 Signed forms of information- Document that
p.000004: consent is semi-
p.000004: early consent in accordance with the DCP and the Plan and is
p.000004: dated just before participation
p.000004: for each participant in the clinical exam-
p.000004: bath. Document permission as well
p.000004: for direct access (8.2.3).
p.000004: 8.3.13 Background documents Document the existence of
p.000004: and confirm the completeness of the semi-
p.000004: data. Include original
p.000004: documents related to the clinical exam-
p.000004: bath, medical treatment and history
p.000004: of the disease.
p.000004: 8.3.14 Signed, dated and completed - Document that
p.000004: the researcher or
p.000004: their clinical records of a patient-authorized team member
p.000004: confirms
p.000004: Entities (CCP) recorded observations.
p.000004: 8.3.15 Documenting Adjustments Document all
p.000004: changes / until-
p.000004: in the CCP, additions or corrections made to the CCP
p.000004: after filling in
p.000004: initial data.
p.000000: 0
p.000000: 0
p.000000: X
p.000000: X
p.000000: X
p.000000: X
p.000000: (copy)
p.000000: X
p.000000: (copy)
p.000000: X
p.000000: X
p.000000: X
p.000000: 0
p.000000: 0
p.000000: X
p.000000: (originals)
p.000000: X
p.000000: (originals)
p.000000: 8.3.16 Notice to the Contracting Authority Notification to the Contracting Authority X X by
p.000000: research-
p.000000: from the explorer for serious waders for serious unwanted
p.000000: events and
p.000000: adverse events and relevant relevant reports in
p.000000: in accordance with items 4, 11.
p.000000: reports
p.000000: 8.3.17 Notification by the Contracting Authority Notification by the Contracting Authority
p.000000: and / or from
p.000000: and / or by the investigator's investigator, where applicable
p.000000: applicable, to re-
p.000000: the regulatory bodies and the commission the regulatory bodies and the commission
p.000000: ethics for
p.000000: ethics for the unexpected and the unexpected and serious
p.000000: unwanted doctor-
p.000000: Risk side effects in accordance
p.000000: with item 5.17 and
p.000000: reactions and other information 4.11.1 and other information
p.000000: for safety-
p.000000: for safety in accordance with 5.16.2 and 4.11.2.
p.000000: 8.3.18 Notification by the Contracting Authority Notification by the Contracting Authority
p.000000: on research-
p.000000: of the researcher for the informant for information on
p.000000: safety
p.000000: in accordance with paragraph 5.16.2.
p.000000: 8.3.19 Temporary or annual reports - Temporary or annual
p.000000: comic reports
p.000000: to the Ethics Committee and the Ethics Committee accordingly
p.000000: with item 4.10 and
p.000000: the authorities the authorities in accordance with p.
p.000000: 5.17.3.
p.000000: 8.3.20 Screened persons documented
p.000000: the identity of
p.000000: who have undergone screening before
p.000000: the clinical trial.
p.000000: 8.3.21 List of recognition codes- Document that
p.000000: the researcher /
p.000000: not the persons of the institution kept confidential
p.000000: a list of the names of all participants,
p.000000: which are indicated by the numbers on
p.000000: in the clinical trial.
p.000000: 8.3.22 Documentation table for inclusion
p.000000: turn on and mark
p.000000: persons with the clinical trial number-
p.000000: of the participants in the
p.000000: 0 X
p.000000: X X
p.000000: X X
p.000000: X When required
p.000000: X 0
p.000000: X 0
p.000000: chronological order.
p.000000: 8.3.23 Test reporting It should be documented that X
p.000000: X
p.000000: the test pro-
p.000000: product in the center duct was implemented in accordance with the plan.
p.000000: 8.3.24 Signature sheet Document the signatures X
p.000000: X
p.000000: and initiative-
p.000000: all persons authorized to
p.000000: complete and make adjustments to the CCP.
p.000000: 8.3.25 Sample Document Document X
p.000000: X
p.000000: the location and
p.000000: human fluids and tissues identification of
p.000000: the saved samples,
p.000000: (if any) if additional analyzes are needed.
p.000000: 8.4. After completion of the clinical trial
p.000000: Upon completion or termination of the clinical trial, all documents listed in sections 8.2 and 8.3 shall be
p.000000: need to be stored together by adding the following:
p.000000: Document Purpose Stored
p.000000: in the documentation of the assigning researcher
p.000000: 8.4.1 Test Reporting - Document that tests
p.000000: pro-
p.000000: duct in the center duct was implemented in accordance with the plan.
p.000000: Document the final pre-
p.000000: counting the product tested which
p.000000: was received at the center distributed to
p.000000: participants returned from persons and returned
p.000000: to the PRINCIPAL.
p.000000: 8.4.2 Documents for destruction Documented
p.000000: the destruction of non-
p.000000: of the test product the quantity used
p.000000: tests
p.000000: product from the contracting authority or in the center
p.000000: 8.4.3 Completed code list for To be possible
p.000000: recognition of
p.000000: face recognition all involved in the clinical
p.000000: experience-
p.000000: not persons, if necessary
p.000000: tracking. The list should be kept-
p.000000: is not confidential and within the agreed period.
p.000000: X X
p.000000: X X
p.000000: If destroyed in the center
p.000000: X 0
p.000000: 8.4.4 Certificate of verification To document that it is 0
p.000000: X
p.000000: done
p.000000: (if available) check.
p.000000: 8.4.5 Final report by the person,
p.000000: monitoring for
p.000000: To document that they are
p.000000: 0 X performed
p.000000: all necessary closing activities-
p.000000: closing the center net center and that copies of
p.000000: basic-
p.000000: these documents are stored in accordance with
p.000000: documentation.
p.000000: 8.4.6 Treatment allocation and
p.000000: To document that X X has been returned to
p.000000: documents for decoding the contracting authority, if any
p.000000: has arisen
p.000000: (when treating-
p.000000: some decoding. this is known to the research team)
p.000000: 8.4.7 Final research report
p.000000: to the Ethics Committee
p.000000: and regulators, in the
p.000000: tea that this is required
p.000000: To document X 0
p.000000: completion of
p.000000: the clinical trial.
p.000000: 8.4.8 Clinical report To document 0
p.000000: X
p.000000: results and in-
p.000000: trial interpretation of the clinical trial.
p.000000: Annex No. 2 to Art. 10, para. 1
p.000000: Content and format of the dossier of the tested medicinal product
p.000000: 1. Introduction
p.000000: 2. Product details
p.000000: 2.1. Chemical-pharmaceutical data
p.000000: 2.1.1. Details of the substance
p.000000: 2.1.1.1. General information
p.000000: 2.1.1.1.1. Nomenclature
p.000000: 2.1.1.1.2. Structure
p.000000: 2.1.1.1.3. General properties
p.000000: 2.1.1.2. Production
p.000000: 2.1.1.2.1. Manufacturer (s)
p.000000: 2.1.1.2.2. Description of production process and control
p.000000: 2.1.1.2.3. Control of raw materials
p.000000: 2.1.1.2.4. Control of critical and intermediate stages
p.000000: 2.1.1.2.5. Validation and evaluation of production processes
p.000000: 2.1.1.2.6. Development of the production process
p.000000: 2.1.1.3. Characterization
p.000000: 2.1.1.3.1. Methods for determining the structure and other characteristics
p.000000: 2.1.1.3.2. Impurities
p.000000: 2.1.1.3.3. Control of the drug substance
p.000000: 2.1.1.3.4. Specification
p.000000: 2.1.1.3.5. Analytical procedures
p.000000: 2.1.1.3.6. Validation of analytical procedures
p.000000: 2.1.1.3.7. Batch analysis
p.000000: 2.1.1.3.8. Validation of specifications
...
General/Other / participants in a control group
Searching for indicator placebo:
(return to top)
p.000004: the contracting authority for each individual participant.
p.000004: 1.11. Clinical trial / study
p.000004: Clinical trial of a medicinal product is any human study designed to
p.000004: the clinical, pharmacological and / or other pharmacodynamic effects of one or
p.000004: more tested medicinal products, and / or to identify adverse reactions to one or more tested
p.000004: medicinal products, and / or to study the absorption, distribution, metabolism and excretion of one or
p.000004: more medicinal products tested in order to ascertain their safety and / or efficacy.
p.000004: The definitions of clinical trial and clinical trial are synonymous.
p.000004: Non-interventional study is a study in which the medicinal product (s) is prescribed as usual
p.000004: in accordance with the conditions laid down in the Marketing Authorization. The appointment of the patient to
p.000004: a specific therapeutic strategy is not predefined by a test protocol, but falls within
p.000004: the established practice and the decision to prescribe the medicinal product is clearly distinguished from the decision to
p.000004: included the patient in the trial. No additional treatment should be applied to patients
p.000004: diagnostic or monitoring procedures and epidemiological methods are used to analyze the data collected.
p.000004: 1.12. Clinical trial / study report
p.000004: Written description of each trial / study of a therapeutic, prophylactic or diagnostic tool,
p.000004: applied to humans, which includes full clinical and statistical results, descriptions and
p.000004: analyzes integrated into a single report.
p.000004: 1.13. Medicinal product for comparison
p.000004: Tested or authorized medicinal product (aka active control) or placebo used for
p.000004: comparison during a clinical trial.
p.000004: 1.14. Conformity (as regards test)
p.000004: Compliance with all requirements - related to the test, the requirements of the DCT and the applicable ones
p.000004: regulations.
p.000004: 1.15. Confidentiality
p.000004: Preventing the disclosure by persons other than authorized persons of information belonging to
p.000004: the contracting authority or the identity of the participants.
p.000004: 1.16. Contract
p.000004: A written, dated and signed agreement between two or more parties setting out all the measures under
p.000004: assignment, assignment of tasks and responsibilities and, if applicable, financial matters. The protocol may
p.000004: to serve as the basis of a contract.
p.000004: 1.17. Coordinating committee
p.000004: Commissioner-designate committee to coordinate multicenter activities
p.000004: clinical trials.
p.000004: 1.18. Coordinating researcher
p.000004: Researcher appointed to coordinate researchers from the various multicenter centers
p.000004: testing.
p.000004: 1.19. Contract Research Organization (DIO)
p.000004: A natural or legal person or scientific organization that has contracted with the contracting authority to perform one or
p.000004: more than the test-related functions and duties of the contracting authority.
p.000004: 1.20. Direct access
p.000004: Permission to examine, analyze, verify and reproduce all records and reports that are relevant for evaluation
p.000004: of one clinical trial after authorization. Each country (e.g., local or foreign regulatory authorities,
...
p.000004: assessment of whether the researchers, the conditions, the methods for conducting the test are appropriate.
p.000004: 1.28. An informed consent
p.000004: Informed consent is a statement of will that must be written, personally dated and signed in order to participate in
p.000004: a clinical trial taken completely free after being duly informed of its nature,
p.000004: significance, consequences and risks and appropriately documented by any person who is able to give
p.000004: his consent, or when the person is unable to give his consent, from his legal representative.
p.000004: 1.29. Inspection
p.000004: Official inspection of the inspection bodies for documents, conditions, records and any other data sources provided
p.000004: are considered by them to be related to the clinical trial and may be stored at the clinical venue
p.000004: testing, the office of the contracting authority / DIO or other places deemed appropriate by these inspection bodies.
p.000004: 1.30. Institution (medical)
p.000004: Medical establishments where clinical trials are conducted.
p.000004: 1.31. Interim clinical trial report
p.000004: Report on the provisional results of the study and their evaluation based on analyzes made during the
p.000004: conducting the clinical trial.
p.000004: 1.32. Tested medicinal product
p.000004: Test drug is a formulation of an active substance or a placebo,
p.000004: which is being tested or used as a comparison in a clinical trial, including products for which it has been issued
p.000004: marketing authorization, but are used for unauthorized use or for the purpose of obtaining an additional one
p.000004: information on the authorized form, or supplied (in dosage form or packaged) in a way other than
p.000004: the authorized form.
p.000004: 1.33. Principal Investigator
p.000004: The principal investigator is the physician or dental practitioner designated by the contracting authority who is in charge
p.000004: the complete conduct of the clinical trial at the center in accordance with the approved protocol and
p.000004: the DCM manual and is responsible for the work of the researchers.
p.000004: 1.34. Explorer
p.000004: The researcher is the doctor or dentist designated by the sponsor and the principal investigator who
p.000004: practically conducts the clinical trial under the direction of the principal investigator according to the approved protocol and
p.000004: the DCT manual at the clinical trial research center. If the clinical
p.000004: testing is conducted by a team, the researcher is the team leader responsible for the team and is called the principal
p.000004: Explorer.
p.000004: 1.35. Researcher's brochure
p.000004: Document containing all clinical and non-clinical trial data (s) for medicinal product (s)
p.000004: refer to the administration of the tested medicinal products to humans.
p.000004: 1.36. Legal representative
p.000004: An individual who, under applicable law, is a legal representative and can agree to participate
p.000004: of the future participant in the clinical trial on his behalf.
p.000004: 1.37. Monitoring
p.000004: Action to monitor the development of the clinical trial and ensure that it is conducted, recorded and reported
...
p.000004: some aspect of the clinical trial (eg protocol modification, informed consent form, and
p.000004: any other information that will be provided to the participants and / or other procedures) shall be provided by the contracting authority
p.000004: a copy of the modification made by the researcher and the date of issue of a favorable opinion by the
p.000004: ethics.
p.000004: 5.11.3. The contracting authority shall provide the researcher with documents and dates for any new positive opinions
p.000004: for changes, and any withdrawal or termination of a favorable opinion.
p.000004: 5.12. Information on the investigational medicinal product
p.000004: 5.12.1. When planning a clinical trial, the contracting authority shall ensure that sufficient data are available,
p.000004: demonstrating the safety and efficacy of non-clinical and / or clinical trials of the product in support
p.000004: of its administration to humans by route, dosage, duration and test group of patients to be
p.000004: study.
p.000004: 5.12.2. The contracting authority shall update the researcher's brochure when new and relevant information becomes available.
p.000004: 5.13. Production, packaging, labeling and coding of the test drug
p.000004: product
p.000004: 5.13.1. The sponsor shall ensure that the investigational medicinal product (including
p.000004: comparator and placebo medicinal product, if used) is characterized in accordance with the development stage of
p.000004: a medicinal product that is manufactured in accordance with the applicable GMP and is coded and labeled in a manner that preserves
p.000004: blinding, if any. The contracting entity shall prepare a labeling of the tested medicinal product in accordance
p.000004: with the requirements of Good Manufacturing Practice rules for medicinal products under development and
p.000004: study and applicable regulatory requirements.
p.000004: 5.13.2. The contracting authority determines the storage temperature and conditions (eg light protection), storage time,
p.000004: dissolution fluids and procedures, as well as infusion products, if any.
p.000004: The sponsor notifies all parties involved in the clinical trial (i.e., monitoring, investigators,
p.000004: pharmacists, storage officers) for certain conditions.
p.000004: 5.13.3. It is necessary to protect the packaging of the tested medicinal product from contamination and unacceptable
p.000004: degradation of quality during transport and storage.
p.000004: 5.13.4. In blind trials, the coding system for the investigational medicinal product must be included
p.000004: mechanism for immediate disclosure of the medicinal product in case of emergency, but not allowing for imperceptible detection
p.000004: on the code.
p.000004: 5.13.5. If significant changes are made to the composition of the trials during the clinical trial
p.000004: medicinal product or medicinal product comparison, the results of any additional
p.000004: tests on medicinal products with a new composition (ie stability test, solubility profile,
...
p.000004: 6.1.6. Name, position, address and telephone number (s) of the physician or dentist who is
p.000004: responsible for any clinical (or dental) decision-making (if different) from the clinical trial
p.000004: researcher).
p.000004: 6.1.7. Name (s) and address (es) of the clinical laboratory (s) and other health and / or technical departments and / or institutions,
p.000004: included in the clinical trial.
p.000004: 6.2. Basic information
p.000004: 6.2.1. Name and description of the product (s) tested.
p.000004: 6.2.2. Summary of non - clinical trial data of clinical relevance and of
p.000004: clinical trials related to the present.
p.000004: 6.2.3. Summary of identified and potential risks and benefits, if any, to humans.
p.000004: 6.2.4. Description and rationale for route of administration, dose, dosage regimen and treatment
p.000004: period.
p.000004: 6.2.5. The view that the clinical trial will be conducted in accordance with the protocol,
p.000004: DCT and applicable regulatory requirements.
p.000004: 6.2.6. Description of the category of persons to be tested.
p.000004: 6.2.7. Used literature and data that are relevant to the clinical trial and provide the basis for
p.000004: the clinical trial.
p.000004: 6.3. Tasks and purpose
p.000004: A detailed description of the tasks and purpose of the clinical trial.
p.000004: 6.4. Test design
p.000004: The scientific value of the clinical trial and the reliability of the data depend significantly on the design of the clinical trial
p.000004: the clinical trial. The design description includes:
p.000004: 6.4.1. Explicit indication of primary and secondary endpoints to be used as indicators for
p.000004: efficacy and safety to be evaluated during the clinical trial.
p.000004: 6.4.2. Description of the type / design of the clinical trial to be conducted (e.g., double-blind,
p.000004: placebo-controlled, parallel design) and schematic diagram of clinical design, procedures, and steps
p.000004: testing.
p.000004: 6.4.3. Description of measures taken to reduce / avoid deviations, incl. randomization and
p.000004: blinding.
p.000004: 6.4.4. Description of study treatment (s), dose and dosage regimen of test drug; includes
p.000004: a description of the dosage form, packaging and labeling of the test product.
p.000004: 6.4.5. The expected length of participation of the persons as well as a description of the sequence
p.000004: and the duration of all clinical trial periods, including follow-up, if any.
p.000004: 6.4.6. Description of the "stopping rules" and "removal criteria" for specific individuals in clinical stages
p.000004: test and throughout the test.
p.000004: 6.4.7. Reporting procedures for the test product, including placebo and the medicinal product for
p.000004: comparison, if any.
p.000004: 6.4.8. Retention of randomization codes and procedures for revealing treatment codes in
p.000004: the clinical trial.
p.000004: 6.4.9. Indication of all data that will be directly recorded in the CCP (ie without direct written information
p.000004: or electronic recording) and which are considered original data.
p.000004: 6.5. Selection and removal of participants
p.000004: 6.5.1. Eligibility criteria for participants.
p.000004: 6.5.2. Exclusion criteria for participants.
p.000004: 6.5.3. Exclusion criteria for participants (ie termination of treatment with trials
p.000004: product / treatment tested) and procedures specifying:
p.000004: 6.5.3.1. when and how participants will be excluded from the trial / treatment with the test product;
p.000004: 6.5.3.2. the type of data and the period for which the data on the removed participants will be collected;
p.000004: 6.5.3.3. whether and how the dropped participants will be replaced;
p.000004: 6.5.3.4. follow-up of drop-outs from test treatment / treatment with test product.
p.000004: 6.6. Treatment of participants
p.000004: 6.6.1. The treatment (s) prescribed, including the names of all products, dose (s), dosage regimens, routes / routes
p.000004: of administration, treatment periods, including follow-up periods for participants for each treatment / treatment period tested
p.000004: test product, clinical trial arm / arm.
p.000004: 6.6.2. Authorized medicinal product (s) / treatment (s) (including life-saving ones), as well as unauthorized before and / or
p.000004: time of the clinical trial.
p.000004: 6.6.3. Procedures to monitor participants' assistance with treatment.
p.000004: 6.7. Evaluation of efficacy
p.000004: 6.7.1. Definition of efficacy parameters.
p.000004: 6.7.2. Methods and time for evaluating, recording and analyzing performance parameters.
p.000004: 6.8. Safety assessment
...
Orphaned Trigger Words
Appendix
Indicator List
| Indicator | Vulnerability |
|---|
| access | Access to Social Goods |
| age | Age |
| authority | Relationship to Authority |
| child | Child |
| children | Child |
| coerce | Presence of Coercion |
| dependent | Dependent |
| disability | Mentally Disabled |
| drug | Drug Usage |
| education | education |
| embryo | embryo |
| emergencies | patients in emergency situations |
| emergency | Public Emergency |
| ethnic | Ethnicity |
| fetus | Fetus/Neonate |
| gender | gender |
| healthy volunteers | Healthy People |
| home | Property Ownership |
| illness | Physically Disabled |
| impaired | Cognitive Impairment |
| impairment | Cognitive Impairment |
| infant | Infant |
| influence | Drug Usage |
| job | Occupation |
| language | Linguistic Proficiency |
| liberty | Incarcerated |
| military | Soldier |
| minority | Racial Minority |
| opinion | philosophical differences/differences of opinion |
| party | political affiliation |
| placebo | participants in a control group |
| research staff | Laboratory Staff |
| single | Marital Status |
| substance | Drug Usage |
| threat | Threat of Stigma |
| unemployed | Unemployment |
| union | Trade Union Membership |
| volunteers | Healthy People |
| vulnerable | vulnerable |
Indicator Peers (Indicators in Same Vulnerability)
| Indicator | Peers |
|---|
| child | ['children'] |
| children | ['child'] |
| drug | ['influence', 'substance'] |
| healthy volunteers | ['volunteers'] |
| impaired | ['impairment'] |
| impairment | ['impaired'] |
| influence | ['drug', 'substance'] |
| substance | ['drug', 'influence'] |
| volunteers | ['healthyXvolunteers'] |
Trigger Words
consent
ethics
protect
protection
risk
volunteer
Applicable Type / Vulnerability / Indicator Overlay for this Input