0A4F4F9BD490A749D5437F821CF06DF1
Manual of Adverse Event Notification and Safety Monitoring in Clinical Trials Involving Drugs (2016)
http://portal.anvisa.gov.br/documents/33836/2492465/Manual+para+Notifica%C3%A7%C3%A3o+de+Eventos+Adversos+e+Monitoramento+de+Seguran%C3%A7a+em+Ensaios+Cl%C3%ADnicos+-+1%C2%AA+Edi%C3%A7%C3%A3o/04a68574-8aac-43c9-b0b2-7b7cd80831c4
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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
Health / Drug Usage
Searching for indicator drug:
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p.000003: SECURITY MONITORING IN CLINICAL TRIALS
p.000003: SUMMARY
p.000003: 1. SIGLARY
p.000005: 5
p.000005: 2. INTRODUCTION
p.000005: 5
p.000005: 3. LEGAL BASIS
p.000005: 5
p.000005: 4. OBJECTIVE
p.000005: 5
p.000005: 5. ADVERSE EVENT MONITORING (EA)
p.000006: 6
p.000006: 6. NOTIFICATION OF EAGs (FORMSUS)
p.000006: 6
p.000006: 6.1 TRACEABILITY
p.000007: 7
p.000007: 7. SUBMISSION OF OTHER EAs (SECURITY UPDATE REPORT) 8
p.000007: 8. WHEN NOT TO NOTIFY THE ADVERSE EVENT TO ANVISA 9
p.000007: 9. TERMINOLOGY
p.000009: 9
p.000009: 10. QUALIFYING INTENSITY GRADING FOR HEALTH CONDITIONS (WHO) 9
p.000009: 11. INDEPENDENT DATA MONITORING AND SECURITY COMMITTEE 10
p.000009: 12. GLOSSARY
p.000011: 11
p.000011: 13. BIBLIOGRAPHIC REFERENCES
p.000012: 12
p.000012: 14. PROCESS FLOWCHART
p.000014: 14
p.000014: 14.1 ADVERSE EVENTS NOTIFICATION FLOWCHART IN CLINICAL TRIALS 14
p.000014: 15. ANNEXES
p.000015: 15
p.000015: 15. 1 WHO-UMC SYSTEM FOR STANDARDIZED CAUSALITY ASSESSMENT 15
p.000015: 16. CHANGE HISTORY
p.000018: 18
p.000004: 4
p.000004: MANUAL FOR NOTIFICATION OF ADVERSE EVENTS AND
p.000004: SECURITY MONITORING IN CLINICAL TRIALS
p.000004: 1. SIGLARY
p.000004: EA - Adverse Event
p.000004: EAG - Severe EC Adverse Event - Clinical Trial
p.000004: WHO - World Health Organization DRC - Collegiate Board Resolution
p.000004: SUSAR - Suspected Unexpected Serious Adverse Reaction
p.000004: WHO - World Health Organization
p.000004: WHOART - The WHO Adverse Reactions Terminology
p.000004: WHO-UMC - The WHO Uppsala Monitoring Center
p.000004: 2. INTRODUCTION
p.000004: The publication of regulations on Clinical Trials with medicines in Brazil brings notification of
p.000004: adverse events as one of the forms of security monitoring that the sponsor should
p.000004: perform during the development of the experimental drug. This manual is intended to
p.000004: provide guidance for the Sponsor, Independent Security Monitoring Committee, Investigator
p.000004: or Legal Representatives, when applicable, do security monitoring and notification of
p.000004: adverse events in clinical trials appropriately.
p.000004: This is a non-binding regulatory measure adopted as a complement to legislation
p.000004: health, with the educational purpose of providing guidance on routines and procedures for compliance with
p.000004: legislation, not intended to expand or restrict established technical or administrative requirements.
p.000004: 3. LEGAL BASIS
p.000004: Anvisa Resolution - RDC nº 9, of February 20, 2015, which provides for the regulation for the
p.000004: conducting clinical trials with medicines in Brazil.
p.000004: 4. OBJECTIVE
p.000004: Without prejudice to the existing provisions in the legal provisions, this manual aims to guide the
p.000004: security monitoring and notifications of adverse events, as described in chapter VI of the DRC nº
p.000004: 09/2015. We recommend that the format be standardized in terms of order and content to facilitate evaluation.
p.000005: 5
p.000005: MANUAL FOR NOTIFICATION OF ADVERSE EVENTS AND
p.000005: SECURITY MONITORING IN CLINICAL TRIALS
p.000005: 5. ADVERSE EVENT MONITORING (EA)
p.000005: It is the sponsor's responsibility to collect and monitor all adverse events, including non-serious ones,
p.000005: classifying them according to Chart 2 of the WHO-UMC System for standardized assessment of causality (Annex I). The
p.000005: Late adverse events should have a monitoring plan in place.
p.000005: All adverse events must be treated and the affected participants accompanied by the
p.000005: principal investigator and his team until resolution or stabilization.
...
p.000006: • In case of any difficulty or doubt, whether in relation to the correct way of filling in the data
p.000006: notification or information technology issue, contact Anvisa through the
p.000006: official communication. Specify that the questioning refers to “notification of adverse events in trials
p.000006: clinical data ”or enter this information in the application data.
p.000006: 6.1 TRACEABILITY
p.000006: All updates regarding the evolution and other data must be made in the initial notification, changing the field
p.000006: side dish.
p.000006: • To access the EA notification, access: Anvisa's Electronic Portal> Medicines>
p.000006: Clinical Research> Adverse Events> Serious Adverse Events Notification Form in
p.000006: Clinical Trials - Notivisa EC> Amends File.
p.000007: 7
p.000007: MANUAL FOR NOTIFICATION OF ADVERSE EVENTS AND
p.000007: SECURITY MONITORING IN CLINICAL TRIALS
p.000007: • Enter the notification protocol to retrieve it and update the information.
p.000007: 7. SUBMISSION OF OTHER EAs (SECURITY UPDATE REPORT)
p.000007: The aggregated data for all other adverse events that are not categorized as serious and unexpected, whose
p.000007: relationship with the product under investigation is not possible, probable or defined must be
p.000007: systematically assessed by the sponsor or the Independent Security Monitoring Committee
p.000007: and the results of this assessment must be submitted to Anvisa in the Security Update Report of
p.000007: Development of Experimental Medicine.
p.000007: The security update report is intended to understand, review and evaluate information annually
p.000007: safety data collected during the investigation period of the experimental drug, commercialized or not.
p.000007: a) For regulatory submission purposes, these reports must be secondary electronic petitions
p.000007: linked to the DDCM case number.
p.000007: b) The linking of secondary petitions to the corresponding processes is fundamental for the
p.000007: analysis and traceability of them in Anvisa electronic systems.
p.000007: c) The subject of petition 10825 - CLINICAL TRIALS - Update Report should be used
p.000007: Security of Experimental Drug Development;
p.000007: d) All modifications of the DDCM not considered substantial must be submitted to ANVISA as part of the
p.000007: safety update report on experimental drug development;
p.000007: e) It is recommended that the Development Security Update Reports for the
p.000007: Experimental Medicines are presented in the ICH Development Safety Update Report (DSUR), Guideline
p.000007: E2F Step 5;
p.000007: f) The sponsor must send Anvisa Safety Development Update Reports annually to Anvisa.
p.000007: Experimental Medication, filed within a maximum period of 60 (sixty) consecutive days having as reference
p.000008: 8
p.000008: MANUAL FOR NOTIFICATION OF ADVERSE EVENTS AND
p.000008: SECURITY MONITORING IN CLINICAL TRIALS
p.000008: annuality the date of approval of the DDCM by ANVISA or the date determined in international development.
p.000008: 8. WHEN NOT TO NOTIFY THE ADVERSE EVENT TO ANVISA
p.000008: The adverse event does not need to be notified to Anvisa when it occurs outside the national territory and
p.000008: when the adverse event was defined in the clinical trial protocol as a primary or secondary outcome.
p.000008: 9. TERMINOLOGY
p.000008: Adverse event reporting should be done using the terminology of “The WHO Adverse Reactions Terminology”
p.000008: (WHOART) to specify the adverse event.
p.000008: The term serious should be translated as “serious” in Portuguese and Spanish, according to “WHO Collaborating
p.000008: Center for International Drug Monitoring. Safety Monitoring of Medicinal Products: Guidelines for
p.000008: setting up and running a Pharmacovigilance Center. ”
p.000008: 10. QUALIFICATION INTENSITY GRADING FOR HEALTH CONDITIONS (WHO)
p.000008: Light
p.000008: A problem is present less than 25% of the time, with an intensity that a person can tolerate and that rarely
p.000008: happens in the last 30 days.
p.000008: Moderate
p.000008: It means that a problem that is present less than 50% of the time, with an intensity, that is
p.000008: interfering in people's day-to-day lives and which happens occasionally in the last 30 days.
p.000009: 9
p.000009: MANUAL FOR NOTIFICATION OF ADVERSE EVENTS AND
p.000009: SECURITY MONITORING IN CLINICAL TRIALS
p.000009: Severe
p.000009: It means that a problem that is present more than 50% of the time, with an intensity that changes
p.000009: partly the day-to-day lives of people and which often happens in the last 30 days.
p.000009: Complete commitment
p.000009: It means that a problem that is present more than 95% of the time, with an intensity that changes
p.000009: completely the day-to-day of the person and that occurs every day for the last 30 days.
p.000009: Not specified
p.000009: It means that there is not enough information to specify the intensity.
p.000009: Not applicable
p.000009: It means that it is inappropriate to use a gradation (eg menstrual functions).
p.000009: 11. INDEPENDENT DATA MONITORING AND SECURITY COMMITTEE
p.000009: In the case of the development of a phase III clinical trial, monitoring must be accompanied by Committees
p.000009: Security Monitoring Independents and their recommendations must be reported to Anvisa by the sponsor.
p.000009: In cases where there is no constitution of a safety monitoring committee, its absence must be justified,
p.000009: according to RDC 09/2015
p.000009: The constitution of the committee, bylaws and functioning, members, conflict of interest, meetings,
p.000009: communications and recommendations must follow the Operational Guidelines for the Establishment and
p.000009: o Operation of Data and Security Monitoring Committees / Ministry of Health, Organization
p.000009: World Health Organization. - Brasília: Ministry of Health, 2008. 44 p. - (Series A. Standards and Technical Manuals).
p.000010: 10
p.000010: MANUAL FOR NOTIFICATION OF ADVERSE EVENTS AND
p.000010: SECURITY MONITORING IN CLINICAL TRIALS
p.000010: 12. GLOSSARY
p.000010: I - Clinical trial - research conducted in humans with the aim of discovering or confirming the effects
p.000010: clinical and / or pharmacological and / or any other pharmacodynamic effects of the experimental medicine and / or
p.000010: identify any adverse reaction to the experimental drug and / or study absorption,
p.000010: distribution, metabolism and excretion of the experimental drug to verify its safety and / or effectiveness;
p.000010: II - Adverse Event - any adverse medical event in a patient or trial participant
p.000010: to whom a pharmaceutical product has been administered and which does not necessarily have a causal relationship to
p.000010: treatment. As a result, an EA can be any unfavorable and unintended sign, symptom, or disease (including
p.000010: results outside the reference range), associated with the use of a product under investigation, whether
p.000010: related to it or not;
p.000010: III - Serious Adverse Event - one that results in any adverse experience with medicines, biological products
p.000010: or devices, occurring at any dose and resulting in any of the following outcomes:
p.000010: a) death;
p.000010: b) threat to life;
p.000010: c) persistent or significant disability / disability;
p.000010: d) requires hospitalization or prolongs hospitalization;
p.000010: e) congenital anomaly or birth defect;
p.000010: f) any suspicion of transmission of an infectious agent by means of a drug or;
p.000010: g) clinically significant event.
p.000010: IV - Unexpected Adverse Event - event not described as an adverse reaction in the medicine brochure
p.000010: experimental or on the label.
p.000010: V - Experimental medicine - pharmaceutical product under test, object of DDCM, to be used in the clinical trial,
p.000010: for the purpose of obtaining information for your registration or post-registration;
p.000010: VI - Product under investigation - experimental drug, placebo, active comparator or any other product to be
p.000010: used in the clinical trial;
p.000010: VII - Clinical Trial Protocol - document that describes the objectives, design, methodology,
p.000010: statistical considerations and trial organization. It also provides the context and rationale for the essay
p.000010: clinical;
p.000011: 11
p.000011: MANUAL FOR NOTIFICATION OF ADVERSE EVENTS AND
p.000011: SECURITY MONITORING IN CLINICAL TRIALS
p.000011: 13. BIBLIOGRAPHIC REFERENCES
p.000011: 1. ACKER JE 3rd, Pancioli AM, Crocco TJ, et al. Implementation strategies for emergency medical
p.000011: services within stroke systems of care: a policy statement from the American Heart Association / American Stroke
p.000011: Association Expert Panel on Emergency Medical Services Systems and the Stroke Council. Stroke 2007; 38: 3097–3115.
p.000011: 2. BASTOS, Alessandra Soler et al. Time of arrival of the patient with acute myocardial infarction in a
p.000011: emergency. Rev Bras Cir Cardiovasc, São José do Rio Preto, v. 27, n. 3, Sept. 2012. Available at:
p.000011: accessed on: 19 ago. 2014
p.000011: http://dx.doi.org/10.5935/1678-9741.20120070.
p.000011: 3. BRAZIL. National Health Surveillance Agency. RDC Resolution 09 of February 20, 2015. This
p.000011: Resolution aims to define the procedures and requirements for conducting clinical trials
p.000011: medications, including submitting the Clinical Drug Development Dossier (DDCM) to
p.000011: be approved by Anvisa. Available in:
p.000011: p.000011: Subject + of + Interest / Research + clinic / Resolution + of + Board + Board + RDC + n + 9 + of + 20 + of + February + of + 2015> Access in:
p.000011: 25 jan. 2016.
p.000011: 4. DSUR ICH E2F Step 5. Available at
p.000011: accessed on: 31
p.000011: ago. 2016.
p.000011: 5. EUROPEAN STROKE ORGANIZATION (ESO) Executive Committee; ESO Writing Committee. Guidelines for
p.000011: management of ischaemic stroke and transient ischaemic attack 2008. Cerebrovasc Dis 2008; 25: 457–507.
p.000011: 6. LEES KR, Bluhmki E, von Kummer R, et al. Time to treatment with intravenous alteplase and outcome
p.000011: in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet 2010;
p.000011: 375: 1695–1703.
p.000011: 7. MINISTRY OF HEALTH, WORLD HEALTH ORGANIZATION. Operational Guidelines for the
p.000011: Establishment and Operation of Data and Security Monitoring Committees. Series
p.000011: A. Standards and Technical Manuals Available at:
p.000011: Accessed on June 3. 2014.
p.000011: 8. MINNERUP, J., Wersching, H., Unrath, M. and Berger, K. (2014), Effects of emergency medical
p.000011: service transport on acute stroke care. European Journal of Neurology. doi: 10.1111 / ene.12367
p.000012: 12
p.000012: MANUAL FOR NOTIFICATION OF ADVERSE EVENTS AND
p.000012: SECURITY MONITORING IN CLINICAL TRIALS
p.000012: 9. SHERMAN R B et al. New FDA regulation to improve safety reporting in clinical trials. The New England journal of
p.000012: medicine. 365 (1): 3-5. 2011
p.000012: 10. THE UPPSALA MONITORING CENTER. WHO Collaborating Center for International Drug Monitoring. Glossary of
p.000012: Terms in Pharmacovigilance. Available in:
p.000012: . Accessed on Jun. 3 2014.
p.000012: 11. THE UPPSALA MONITORING CENTER. WHO Collaborating Center for International Drug Monitoring. WHO-UMC Causality
p.000012: Assessment. Available at: . Accessed on Jun. 3 2014.
p.000012: 12. WORLD HEALTH ORGANIZATION. ICF CHECKLIST Version 2.1a, Clinician Form for International Classification of
p.000012: Functioning, Disability and Health. Available in:
p.000012: Accessed on June 3. 2014.
p.000012: 13. WORLD HEALTH ORGANIZATION. WHO Collaborating Center for International Drug Monitoring. Safety Monitoring of
p.000012: Medicinal Products: Guidelines for setting up and running a Pharmacovigilance Center. Geneva, World
p.000012: Health Organization, 2000. Available at: Accessed on June 3. 2014.
p.000013: 13
p.000013: MANUAL FOR NOTIFICATION OF ADVERSE EVENTS AND
p.000013: SECURITY MONITORING IN CLINICAL TRIALS
p.000013: 14. PROCESS FLOWCHART
p.000013: 14.1 ADVERSE EVENT NOTIFICATION FLOWCHART FOR CLINICAL TRIALS
p.000013: Adverse events occurred in clinical trial participants and detected by the Investigator
p.000013: Adverse events
p.000013: SERIOUS
p.000013: Adverse events
p.000013: NOT SERIOUS
p.000013: 24h
p.000013: Sponsor
p.000013: INDEPENDENT SECURITY MONITORING COMMITTEE
p.000013: Recommendations
p.000013: SERIOUS Adverse Events
p.000013: NON SERIOUS Adverse Events
p.000013: UNEXPECTED SERIOUS Adverse Events
p.000013: EXPECTED SERIOUS Adverse Events
p.000013: Electronic notification to ANVISA - Security update report on the development of the experimental drug.
p.000013: Standardized causality assessment of the WHO-UMC system
p.000013: Improbable, conditional / unclassified, inaccessible / unclassifiable EAGs
p.000013: Unexpected, possible, probable or defined EAGs
p.000013: 7 calendar days: fatal or life-threatening EAGs; 15 calendar days: others.
p.000013: Electronic Notification to ANVISA -
p.000013: FORMSUS
p.000014: 14
p.000014: MANUAL FOR NOTIFICATION OF ADVERSE EVENTS AND
p.000014: SECURITY MONITORING IN CLINICAL TRIALS
p.000014: 15. ANNEXES
p.000014: 15. 1 WHO-UMC SYSTEM FOR STANDARDIZED CAUSALITY ASSESSMENT
p.000014: 15.1.1 Table 1. Advances and limitations of the system for standardized causality assessment
p.000014: What can causality assessment do?
p.000014: What can't the causality assessment do?
p.000014: Decrease disagreement between evaluators
p.000014: Provide accurate quantitative measure of the probability ratio
p.000014: Classify probability relation Distinguish between valid and invalid cases
p.000014: Mark reports individually To prove the relationship between the medication and the
p.000014: event
p.000014: Improve scientific, educational assessment
p.000014: Quantify the drug's contribution to the development of an adverse event
p.000014: Changing uncertainties to certainties
p.000015: 15
p.000015: MANUAL FOR NOTIFICATION OF ADVERSE EVENTS AND
p.000015: SECURITY MONITORING IN CLINICAL TRIALS
p.000015: 15.1.2 Box 2. WHO-UMC Causal categories
p.000015: Categories + Criteria in the assessment of causality ++
p.000015: • Event or change (abnormal) in laboratory exam with plausible temporal relation in relation to
p.000015: administration of the intervention;
p.000015: • Cannot be explained by illness or other intervention, medication;
p.000015: Right / Defined
p.000015: • Response to plausible interruption or withdrawal (pharmacologically, pathologically);
p.000015: • Pharmacologically or phenomenologically defined event (i.e. an objective disorder
p.000015: and specific or a pharmacologically recognized phenomenon);
p.000015: • Satisfactory restocking, if necessary.
p.000015: Likely
p.000015: • Event or alteration (abnormal) in laboratory exam with reasonable temporal relation in relation to
p.000015: administration of the intervention;
p.000015: • Unlikely to be attributed to a disease or other intervention, medication;
p.000015: • Response to clinically reasonable interruption or withdrawal;
p.000015: • Reexposure not required.
p.000015: Possible
p.000015: • Event or alteration (abnormal) in laboratory exam with reasonable temporal relation in relation to
p.000015: administration of the intervention;
p.000015: • It can also be explained by illness or other interventions, drugs;
p.000015: • Information about withdrawing or stopping treatment may be missing or unclear.
p.000015: Unlikely
p.000015: • Event or alteration (abnormal) in laboratory examination that in relation to the time of administration
...
Health / Mentally Disabled
Searching for indicator disability:
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p.000009: communications and recommendations must follow the Operational Guidelines for the Establishment and
p.000009: o Operation of Data and Security Monitoring Committees / Ministry of Health, Organization
p.000009: World Health Organization. - Brasília: Ministry of Health, 2008. 44 p. - (Series A. Standards and Technical Manuals).
p.000010: 10
p.000010: MANUAL FOR NOTIFICATION OF ADVERSE EVENTS AND
p.000010: SECURITY MONITORING IN CLINICAL TRIALS
p.000010: 12. GLOSSARY
p.000010: I - Clinical trial - research conducted in humans with the aim of discovering or confirming the effects
p.000010: clinical and / or pharmacological and / or any other pharmacodynamic effects of the experimental medicine and / or
p.000010: identify any adverse reaction to the experimental drug and / or study absorption,
p.000010: distribution, metabolism and excretion of the experimental drug to verify its safety and / or effectiveness;
p.000010: II - Adverse Event - any adverse medical event in a patient or trial participant
p.000010: to whom a pharmaceutical product has been administered and which does not necessarily have a causal relationship to
p.000010: treatment. As a result, an EA can be any unfavorable and unintended sign, symptom, or disease (including
p.000010: results outside the reference range), associated with the use of a product under investigation, whether
p.000010: related to it or not;
p.000010: III - Serious Adverse Event - one that results in any adverse experience with medicines, biological products
p.000010: or devices, occurring at any dose and resulting in any of the following outcomes:
p.000010: a) death;
p.000010: b) threat to life;
p.000010: c) persistent or significant disability / disability;
p.000010: d) requires hospitalization or prolongs hospitalization;
p.000010: e) congenital anomaly or birth defect;
p.000010: f) any suspicion of transmission of an infectious agent by means of a drug or;
p.000010: g) clinically significant event.
p.000010: IV - Unexpected Adverse Event - event not described as an adverse reaction in the medicine brochure
p.000010: experimental or on the label.
p.000010: V - Experimental medicine - pharmaceutical product under test, object of DDCM, to be used in the clinical trial,
p.000010: for the purpose of obtaining information for your registration or post-registration;
p.000010: VI - Product under investigation - experimental drug, placebo, active comparator or any other product to be
p.000010: used in the clinical trial;
p.000010: VII - Clinical Trial Protocol - document that describes the objectives, design, methodology,
p.000010: statistical considerations and trial organization. It also provides the context and rationale for the essay
p.000010: clinical;
p.000011: 11
p.000011: MANUAL FOR NOTIFICATION OF ADVERSE EVENTS AND
p.000011: SECURITY MONITORING IN CLINICAL TRIALS
p.000011: 13. BIBLIOGRAPHIC REFERENCES
p.000011: 1. ACKER JE 3rd, Pancioli AM, Crocco TJ, et al. Implementation strategies for emergency medical
p.000011: services within stroke systems of care: a policy statement from the American Heart Association / American Stroke
p.000011: Association Expert Panel on Emergency Medical Services Systems and the Stroke Council. Stroke 2007; 38: 3097–3115.
p.000011: 2. BASTOS, Alessandra Soler et al. Time of arrival of the patient with acute myocardial infarction in a
...
p.000011: in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet 2010;
p.000011: 375: 1695–1703.
p.000011: 7. MINISTRY OF HEALTH, WORLD HEALTH ORGANIZATION. Operational Guidelines for the
p.000011: Establishment and Operation of Data and Security Monitoring Committees. Series
p.000011: A. Standards and Technical Manuals Available at:
p.000011: Accessed on June 3. 2014.
p.000011: 8. MINNERUP, J., Wersching, H., Unrath, M. and Berger, K. (2014), Effects of emergency medical
p.000011: service transport on acute stroke care. European Journal of Neurology. doi: 10.1111 / ene.12367
p.000012: 12
p.000012: MANUAL FOR NOTIFICATION OF ADVERSE EVENTS AND
p.000012: SECURITY MONITORING IN CLINICAL TRIALS
p.000012: 9. SHERMAN R B et al. New FDA regulation to improve safety reporting in clinical trials. The New England journal of
p.000012: medicine. 365 (1): 3-5. 2011
p.000012: 10. THE UPPSALA MONITORING CENTER. WHO Collaborating Center for International Drug Monitoring. Glossary of
p.000012: Terms in Pharmacovigilance. Available in:
p.000012: . Accessed on Jun. 3 2014.
p.000012: 11. THE UPPSALA MONITORING CENTER. WHO Collaborating Center for International Drug Monitoring. WHO-UMC Causality
p.000012: Assessment. Available at: . Accessed on Jun. 3 2014.
p.000012: 12. WORLD HEALTH ORGANIZATION. ICF CHECKLIST Version 2.1a, Clinician Form for International Classification of
p.000012: Functioning, Disability and Health. Available in:
p.000012: Accessed on June 3. 2014.
p.000012: 13. WORLD HEALTH ORGANIZATION. WHO Collaborating Center for International Drug Monitoring. Safety Monitoring of
p.000012: Medicinal Products: Guidelines for setting up and running a Pharmacovigilance Center. Geneva, World
p.000012: Health Organization, 2000. Available at: Accessed on June 3. 2014.
p.000013: 13
p.000013: MANUAL FOR NOTIFICATION OF ADVERSE EVENTS AND
p.000013: SECURITY MONITORING IN CLINICAL TRIALS
p.000013: 14. PROCESS FLOWCHART
p.000013: 14.1 ADVERSE EVENT NOTIFICATION FLOWCHART FOR CLINICAL TRIALS
p.000013: Adverse events occurred in clinical trial participants and detected by the Investigator
p.000013: Adverse events
p.000013: SERIOUS
p.000013: Adverse events
p.000013: NOT SERIOUS
p.000013: 24h
p.000013: Sponsor
p.000013: INDEPENDENT SECURITY MONITORING COMMITTEE
p.000013: Recommendations
p.000013: SERIOUS Adverse Events
p.000013: NON SERIOUS Adverse Events
p.000013: UNEXPECTED SERIOUS Adverse Events
p.000013: EXPECTED SERIOUS Adverse Events
p.000013: Electronic notification to ANVISA - Security update report on the development of the experimental drug.
p.000013: Standardized causality assessment of the WHO-UMC system
p.000013: Improbable, conditional / unclassified, inaccessible / unclassifiable EAGs
p.000013: Unexpected, possible, probable or defined EAGs
p.000013: 7 calendar days: fatal or life-threatening EAGs; 15 calendar days: others.
p.000013: Electronic Notification to ANVISA -
p.000013: FORMSUS
p.000014: 14
p.000014: MANUAL FOR NOTIFICATION OF ADVERSE EVENTS AND
p.000014: SECURITY MONITORING IN CLINICAL TRIALS
p.000014: 15. ANNEXES
...
Health / Physically Disabled
Searching for indicator illness:
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p.000013: Standardized causality assessment of the WHO-UMC system
p.000013: Improbable, conditional / unclassified, inaccessible / unclassifiable EAGs
p.000013: Unexpected, possible, probable or defined EAGs
p.000013: 7 calendar days: fatal or life-threatening EAGs; 15 calendar days: others.
p.000013: Electronic Notification to ANVISA -
p.000013: FORMSUS
p.000014: 14
p.000014: MANUAL FOR NOTIFICATION OF ADVERSE EVENTS AND
p.000014: SECURITY MONITORING IN CLINICAL TRIALS
p.000014: 15. ANNEXES
p.000014: 15. 1 WHO-UMC SYSTEM FOR STANDARDIZED CAUSALITY ASSESSMENT
p.000014: 15.1.1 Table 1. Advances and limitations of the system for standardized causality assessment
p.000014: What can causality assessment do?
p.000014: What can't the causality assessment do?
p.000014: Decrease disagreement between evaluators
p.000014: Provide accurate quantitative measure of the probability ratio
p.000014: Classify probability relation Distinguish between valid and invalid cases
p.000014: Mark reports individually To prove the relationship between the medication and the
p.000014: event
p.000014: Improve scientific, educational assessment
p.000014: Quantify the drug's contribution to the development of an adverse event
p.000014: Changing uncertainties to certainties
p.000015: 15
p.000015: MANUAL FOR NOTIFICATION OF ADVERSE EVENTS AND
p.000015: SECURITY MONITORING IN CLINICAL TRIALS
p.000015: 15.1.2 Box 2. WHO-UMC Causal categories
p.000015: Categories + Criteria in the assessment of causality ++
p.000015: • Event or change (abnormal) in laboratory exam with plausible temporal relation in relation to
p.000015: administration of the intervention;
p.000015: • Cannot be explained by illness or other intervention, medication;
p.000015: Right / Defined
p.000015: • Response to plausible interruption or withdrawal (pharmacologically, pathologically);
p.000015: • Pharmacologically or phenomenologically defined event (i.e. an objective disorder
p.000015: and specific or a pharmacologically recognized phenomenon);
p.000015: • Satisfactory restocking, if necessary.
p.000015: Likely
p.000015: • Event or alteration (abnormal) in laboratory exam with reasonable temporal relation in relation to
p.000015: administration of the intervention;
p.000015: • Unlikely to be attributed to a disease or other intervention, medication;
p.000015: • Response to clinically reasonable interruption or withdrawal;
p.000015: • Reexposure not required.
p.000015: Possible
p.000015: • Event or alteration (abnormal) in laboratory exam with reasonable temporal relation in relation to
p.000015: administration of the intervention;
p.000015: • It can also be explained by illness or other interventions, drugs;
p.000015: • Information about withdrawing or stopping treatment may be missing or unclear.
p.000015: Unlikely
p.000015: • Event or alteration (abnormal) in laboratory examination that in relation to the time of administration
p.000015: of the intervention makes an unlikely (but not impossible) relationship;
p.000015: • Illness or other treatments support plausible explanations.
p.000015: Conditional / Unclassified
p.000015: • Event or alteration (abnormal) in laboratory examination;
p.000015: • More data is needed for an appropriate assessment, or;
p.000015: • Additional data under investigation.
p.000016: 16
p.000016: MANUAL FOR NOTIFICATION OF ADVERSE EVENTS AND
p.000016: SECURITY MONITORING IN CLINICAL TRIALS
p.000016: Inaccessible / Unclassifiable
p.000016: • The narrative of the report suggests an adverse reaction;
p.000016: • It cannot be classified because the information is insufficient or contradictory;
p.000016: • Data cannot be supplemented or verified.
p.000016: + Terms for the relationship
p.000016: ++ To classify the relationship using one of the terms, the aspects observed must be reasonably within the
p.000016: criteria presented.
p.000017: 17
p.000017: MANUAL FOR NOTIFICATION OF ADVERSE EVENTS AND
p.000017: SECURITY MONITORING IN CLINICAL TRIALS
p.000017: 16. CHANGE HISTORY
p.000017: Version
p.000017: Changes made
p.000017: Explanation and Justification
p.000017: 1st edition
p.000017: Initial release
...
Social / Access to Social Goods
Searching for indicator access:
(return to top)
p.000005: b) Other methods can be used for categorization as long as correspondence with the
p.000005: WHO-UMC system;
p.000005: c) The Suspected Unexpected Serious Adverse Reaction (SUSAR) is included in the criteria for notification of
p.000005: serious adverse event and must be notified, however, the criteria listed in the DRC are not limited to it only.
p.000005: d) Notifications must be made exclusively through the electronic form “Notification of
p.000005: EAGs in Clinical Trials with Medicines or Biological Products - Notivisa EC ”, available on the Electronic Portal
p.000005: da Anvisa> Medicamentos> Clinical Research> Adverse Events> Form for Notification of
p.000005: Serious Adverse Events in Clinical Trials - Notivisa EC.
p.000006: 6
p.000006: MANUAL FOR NOTIFICATION OF ADVERSE EVENTS AND
p.000006: SECURITY MONITORING IN CLINICAL TRIALS
p.000006: • Some pages of the form may take a long time to load, please wait;
p.000006: • To notify adverse events it is not necessary to log in;
p.000006: • After completing the last page, a protocol number and a mirror of the notification will be generated. Save this
p.000006: number to update your notification;
p.000006: • If the system is temporarily unavailable, the notification must be sent as soon as the system returns;
p.000006: • In case of any difficulty or doubt, whether in relation to the correct way of filling in the data
p.000006: notification or information technology issue, contact Anvisa through the
p.000006: official communication. Specify that the questioning refers to “notification of adverse events in trials
p.000006: clinical data ”or enter this information in the application data.
p.000006: 6.1 TRACEABILITY
p.000006: All updates regarding the evolution and other data must be made in the initial notification, changing the field
p.000006: side dish.
p.000006: • To access the EA notification, access: Anvisa's Electronic Portal> Medicines>
p.000006: Clinical Research> Adverse Events> Serious Adverse Events Notification Form in
p.000006: Clinical Trials - Notivisa EC> Amends File.
p.000007: 7
p.000007: MANUAL FOR NOTIFICATION OF ADVERSE EVENTS AND
p.000007: SECURITY MONITORING IN CLINICAL TRIALS
p.000007: • Enter the notification protocol to retrieve it and update the information.
p.000007: 7. SUBMISSION OF OTHER EAs (SECURITY UPDATE REPORT)
p.000007: The aggregated data for all other adverse events that are not categorized as serious and unexpected, whose
p.000007: relationship with the product under investigation is not possible, probable or defined must be
p.000007: systematically assessed by the sponsor or the Independent Security Monitoring Committee
p.000007: and the results of this assessment must be submitted to Anvisa in the Security Update Report of
p.000007: Development of Experimental Medicine.
p.000007: The security update report is intended to understand, review and evaluate information annually
p.000007: safety data collected during the investigation period of the experimental drug, commercialized or not.
p.000007: a) For regulatory submission purposes, these reports must be secondary electronic petitions
p.000007: linked to the DDCM case number.
p.000007: b) The linking of secondary petitions to the corresponding processes is fundamental for the
p.000007: analysis and traceability of them in Anvisa electronic systems.
p.000007: c) The subject of petition 10825 - CLINICAL TRIALS - Update Report should be used
p.000007: Security of Experimental Drug Development;
p.000007: d) All modifications of the DDCM not considered substantial must be submitted to ANVISA as part of the
...
p.000010: statistical considerations and trial organization. It also provides the context and rationale for the essay
p.000010: clinical;
p.000011: 11
p.000011: MANUAL FOR NOTIFICATION OF ADVERSE EVENTS AND
p.000011: SECURITY MONITORING IN CLINICAL TRIALS
p.000011: 13. BIBLIOGRAPHIC REFERENCES
p.000011: 1. ACKER JE 3rd, Pancioli AM, Crocco TJ, et al. Implementation strategies for emergency medical
p.000011: services within stroke systems of care: a policy statement from the American Heart Association / American Stroke
p.000011: Association Expert Panel on Emergency Medical Services Systems and the Stroke Council. Stroke 2007; 38: 3097–3115.
p.000011: 2. BASTOS, Alessandra Soler et al. Time of arrival of the patient with acute myocardial infarction in a
p.000011: emergency. Rev Bras Cir Cardiovasc, São José do Rio Preto, v. 27, n. 3, Sept. 2012. Available at:
p.000011: accessed on: 19 ago. 2014
p.000011: http://dx.doi.org/10.5935/1678-9741.20120070.
p.000011: 3. BRAZIL. National Health Surveillance Agency. RDC Resolution 09 of February 20, 2015. This
p.000011: Resolution aims to define the procedures and requirements for conducting clinical trials
p.000011: medications, including submitting the Clinical Drug Development Dossier (DDCM) to
p.000011: be approved by Anvisa. Available in:
p.000011: p.000011: Subject + of + Interest / Research + clinic / Resolution + of + Board + Board + RDC + n + 9 + of + 20 + of + February + of + 2015> Access in:
p.000011: 25 jan. 2016.
p.000011: 4. DSUR ICH E2F Step 5. Available at
p.000011: accessed on: 31
p.000011: ago. 2016.
p.000011: 5. EUROPEAN STROKE ORGANIZATION (ESO) Executive Committee; ESO Writing Committee. Guidelines for
p.000011: management of ischaemic stroke and transient ischaemic attack 2008. Cerebrovasc Dis 2008; 25: 457–507.
p.000011: 6. LEES KR, Bluhmki E, von Kummer R, et al. Time to treatment with intravenous alteplase and outcome
p.000011: in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet 2010;
p.000011: 375: 1695–1703.
p.000011: 7. MINISTRY OF HEALTH, WORLD HEALTH ORGANIZATION. Operational Guidelines for the
p.000011: Establishment and Operation of Data and Security Monitoring Committees. Series
p.000011: A. Standards and Technical Manuals Available at:
p.000011: Accessed on June 3. 2014.
p.000011: 8. MINNERUP, J., Wersching, H., Unrath, M. and Berger, K. (2014), Effects of emergency medical
p.000011: service transport on acute stroke care. European Journal of Neurology. doi: 10.1111 / ene.12367
p.000012: 12
p.000012: MANUAL FOR NOTIFICATION OF ADVERSE EVENTS AND
p.000012: SECURITY MONITORING IN CLINICAL TRIALS
p.000012: 9. SHERMAN R B et al. New FDA regulation to improve safety reporting in clinical trials. The New England journal of
p.000012: medicine. 365 (1): 3-5. 2011
p.000012: 10. THE UPPSALA MONITORING CENTER. WHO Collaborating Center for International Drug Monitoring. Glossary of
p.000012: Terms in Pharmacovigilance. Available in:
p.000012: . Accessed on Jun. 3 2014.
...
Social / Threat of Stigma
Searching for indicator threat:
(return to top)
p.000009: The constitution of the committee, bylaws and functioning, members, conflict of interest, meetings,
p.000009: communications and recommendations must follow the Operational Guidelines for the Establishment and
p.000009: o Operation of Data and Security Monitoring Committees / Ministry of Health, Organization
p.000009: World Health Organization. - Brasília: Ministry of Health, 2008. 44 p. - (Series A. Standards and Technical Manuals).
p.000010: 10
p.000010: MANUAL FOR NOTIFICATION OF ADVERSE EVENTS AND
p.000010: SECURITY MONITORING IN CLINICAL TRIALS
p.000010: 12. GLOSSARY
p.000010: I - Clinical trial - research conducted in humans with the aim of discovering or confirming the effects
p.000010: clinical and / or pharmacological and / or any other pharmacodynamic effects of the experimental medicine and / or
p.000010: identify any adverse reaction to the experimental drug and / or study absorption,
p.000010: distribution, metabolism and excretion of the experimental drug to verify its safety and / or effectiveness;
p.000010: II - Adverse Event - any adverse medical event in a patient or trial participant
p.000010: to whom a pharmaceutical product has been administered and which does not necessarily have a causal relationship to
p.000010: treatment. As a result, an EA can be any unfavorable and unintended sign, symptom, or disease (including
p.000010: results outside the reference range), associated with the use of a product under investigation, whether
p.000010: related to it or not;
p.000010: III - Serious Adverse Event - one that results in any adverse experience with medicines, biological products
p.000010: or devices, occurring at any dose and resulting in any of the following outcomes:
p.000010: a) death;
p.000010: b) threat to life;
p.000010: c) persistent or significant disability / disability;
p.000010: d) requires hospitalization or prolongs hospitalization;
p.000010: e) congenital anomaly or birth defect;
p.000010: f) any suspicion of transmission of an infectious agent by means of a drug or;
p.000010: g) clinically significant event.
p.000010: IV - Unexpected Adverse Event - event not described as an adverse reaction in the medicine brochure
p.000010: experimental or on the label.
p.000010: V - Experimental medicine - pharmaceutical product under test, object of DDCM, to be used in the clinical trial,
p.000010: for the purpose of obtaining information for your registration or post-registration;
p.000010: VI - Product under investigation - experimental drug, placebo, active comparator or any other product to be
p.000010: used in the clinical trial;
p.000010: VII - Clinical Trial Protocol - document that describes the objectives, design, methodology,
p.000010: statistical considerations and trial organization. It also provides the context and rationale for the essay
p.000010: clinical;
p.000011: 11
p.000011: MANUAL FOR NOTIFICATION OF ADVERSE EVENTS AND
p.000011: SECURITY MONITORING IN CLINICAL TRIALS
p.000011: 13. BIBLIOGRAPHIC REFERENCES
p.000011: 1. ACKER JE 3rd, Pancioli AM, Crocco TJ, et al. Implementation strategies for emergency medical
p.000011: services within stroke systems of care: a policy statement from the American Heart Association / American Stroke
...
Social / education
Searching for indicator educational:
(return to top)
p.000007: 8. WHEN NOT TO NOTIFY THE ADVERSE EVENT TO ANVISA 9
p.000007: 9. TERMINOLOGY
p.000009: 9
p.000009: 10. QUALIFYING INTENSITY GRADING FOR HEALTH CONDITIONS (WHO) 9
p.000009: 11. INDEPENDENT DATA MONITORING AND SECURITY COMMITTEE 10
p.000009: 12. GLOSSARY
p.000011: 11
p.000011: 13. BIBLIOGRAPHIC REFERENCES
p.000012: 12
p.000012: 14. PROCESS FLOWCHART
p.000014: 14
p.000014: 14.1 ADVERSE EVENTS NOTIFICATION FLOWCHART IN CLINICAL TRIALS 14
p.000014: 15. ANNEXES
p.000015: 15
p.000015: 15. 1 WHO-UMC SYSTEM FOR STANDARDIZED CAUSALITY ASSESSMENT 15
p.000015: 16. CHANGE HISTORY
p.000018: 18
p.000004: 4
p.000004: MANUAL FOR NOTIFICATION OF ADVERSE EVENTS AND
p.000004: SECURITY MONITORING IN CLINICAL TRIALS
p.000004: 1. SIGLARY
p.000004: EA - Adverse Event
p.000004: EAG - Severe EC Adverse Event - Clinical Trial
p.000004: WHO - World Health Organization DRC - Collegiate Board Resolution
p.000004: SUSAR - Suspected Unexpected Serious Adverse Reaction
p.000004: WHO - World Health Organization
p.000004: WHOART - The WHO Adverse Reactions Terminology
p.000004: WHO-UMC - The WHO Uppsala Monitoring Center
p.000004: 2. INTRODUCTION
p.000004: The publication of regulations on Clinical Trials with medicines in Brazil brings notification of
p.000004: adverse events as one of the forms of security monitoring that the sponsor should
p.000004: perform during the development of the experimental drug. This manual is intended to
p.000004: provide guidance for the Sponsor, Independent Security Monitoring Committee, Investigator
p.000004: or Legal Representatives, when applicable, do security monitoring and notification of
p.000004: adverse events in clinical trials appropriately.
p.000004: This is a non-binding regulatory measure adopted as a complement to legislation
p.000004: health, with the educational purpose of providing guidance on routines and procedures for compliance with
p.000004: legislation, not intended to expand or restrict established technical or administrative requirements.
p.000004: 3. LEGAL BASIS
p.000004: Anvisa Resolution - RDC nº 9, of February 20, 2015, which provides for the regulation for the
p.000004: conducting clinical trials with medicines in Brazil.
p.000004: 4. OBJECTIVE
p.000004: Without prejudice to the existing provisions in the legal provisions, this manual aims to guide the
p.000004: security monitoring and notifications of adverse events, as described in chapter VI of the DRC nº
p.000004: 09/2015. We recommend that the format be standardized in terms of order and content to facilitate evaluation.
p.000005: 5
p.000005: MANUAL FOR NOTIFICATION OF ADVERSE EVENTS AND
p.000005: SECURITY MONITORING IN CLINICAL TRIALS
p.000005: 5. ADVERSE EVENT MONITORING (EA)
p.000005: It is the sponsor's responsibility to collect and monitor all adverse events, including non-serious ones,
p.000005: classifying them according to Chart 2 of the WHO-UMC System for standardized assessment of causality (Annex I). The
p.000005: Late adverse events should have a monitoring plan in place.
p.000005: All adverse events must be treated and the affected participants accompanied by the
p.000005: principal investigator and his team until resolution or stabilization.
p.000005: In the event of a serious adverse event, the sponsor and the investigator must take immediate
p.000005: safety to protect clinical trial participants from any imminent risk and the sponsor
p.000005: must notify Anvisa and describe the measures adopted from item 79 of the Notification Form
p.000005: of Serious Adverse Events in Clinical Trials available on the Anvisa website> Medicamentos>
...
p.000013: 14. PROCESS FLOWCHART
p.000013: 14.1 ADVERSE EVENT NOTIFICATION FLOWCHART FOR CLINICAL TRIALS
p.000013: Adverse events occurred in clinical trial participants and detected by the Investigator
p.000013: Adverse events
p.000013: SERIOUS
p.000013: Adverse events
p.000013: NOT SERIOUS
p.000013: 24h
p.000013: Sponsor
p.000013: INDEPENDENT SECURITY MONITORING COMMITTEE
p.000013: Recommendations
p.000013: SERIOUS Adverse Events
p.000013: NON SERIOUS Adverse Events
p.000013: UNEXPECTED SERIOUS Adverse Events
p.000013: EXPECTED SERIOUS Adverse Events
p.000013: Electronic notification to ANVISA - Security update report on the development of the experimental drug.
p.000013: Standardized causality assessment of the WHO-UMC system
p.000013: Improbable, conditional / unclassified, inaccessible / unclassifiable EAGs
p.000013: Unexpected, possible, probable or defined EAGs
p.000013: 7 calendar days: fatal or life-threatening EAGs; 15 calendar days: others.
p.000013: Electronic Notification to ANVISA -
p.000013: FORMSUS
p.000014: 14
p.000014: MANUAL FOR NOTIFICATION OF ADVERSE EVENTS AND
p.000014: SECURITY MONITORING IN CLINICAL TRIALS
p.000014: 15. ANNEXES
p.000014: 15. 1 WHO-UMC SYSTEM FOR STANDARDIZED CAUSALITY ASSESSMENT
p.000014: 15.1.1 Table 1. Advances and limitations of the system for standardized causality assessment
p.000014: What can causality assessment do?
p.000014: What can't the causality assessment do?
p.000014: Decrease disagreement between evaluators
p.000014: Provide accurate quantitative measure of the probability ratio
p.000014: Classify probability relation Distinguish between valid and invalid cases
p.000014: Mark reports individually To prove the relationship between the medication and the
p.000014: event
p.000014: Improve scientific, educational assessment
p.000014: Quantify the drug's contribution to the development of an adverse event
p.000014: Changing uncertainties to certainties
p.000015: 15
p.000015: MANUAL FOR NOTIFICATION OF ADVERSE EVENTS AND
p.000015: SECURITY MONITORING IN CLINICAL TRIALS
p.000015: 15.1.2 Box 2. WHO-UMC Causal categories
p.000015: Categories + Criteria in the assessment of causality ++
p.000015: • Event or change (abnormal) in laboratory exam with plausible temporal relation in relation to
p.000015: administration of the intervention;
p.000015: • Cannot be explained by illness or other intervention, medication;
p.000015: Right / Defined
p.000015: • Response to plausible interruption or withdrawal (pharmacologically, pathologically);
p.000015: • Pharmacologically or phenomenologically defined event (i.e. an objective disorder
p.000015: and specific or a pharmacologically recognized phenomenon);
p.000015: • Satisfactory restocking, if necessary.
p.000015: Likely
p.000015: • Event or alteration (abnormal) in laboratory exam with reasonable temporal relation in relation to
p.000015: administration of the intervention;
p.000015: • Unlikely to be attributed to a disease or other intervention, medication;
p.000015: • Response to clinically reasonable interruption or withdrawal;
p.000015: • Reexposure not required.
p.000015: Possible
p.000015: • Event or alteration (abnormal) in laboratory exam with reasonable temporal relation in relation to
p.000015: administration of the intervention;
p.000015: • It can also be explained by illness or other interventions, drugs;
p.000015: • Information about withdrawing or stopping treatment may be missing or unclear.
p.000015: Unlikely
...
General/Other / Public Emergency
Searching for indicator emergency:
(return to top)
p.000010: or devices, occurring at any dose and resulting in any of the following outcomes:
p.000010: a) death;
p.000010: b) threat to life;
p.000010: c) persistent or significant disability / disability;
p.000010: d) requires hospitalization or prolongs hospitalization;
p.000010: e) congenital anomaly or birth defect;
p.000010: f) any suspicion of transmission of an infectious agent by means of a drug or;
p.000010: g) clinically significant event.
p.000010: IV - Unexpected Adverse Event - event not described as an adverse reaction in the medicine brochure
p.000010: experimental or on the label.
p.000010: V - Experimental medicine - pharmaceutical product under test, object of DDCM, to be used in the clinical trial,
p.000010: for the purpose of obtaining information for your registration or post-registration;
p.000010: VI - Product under investigation - experimental drug, placebo, active comparator or any other product to be
p.000010: used in the clinical trial;
p.000010: VII - Clinical Trial Protocol - document that describes the objectives, design, methodology,
p.000010: statistical considerations and trial organization. It also provides the context and rationale for the essay
p.000010: clinical;
p.000011: 11
p.000011: MANUAL FOR NOTIFICATION OF ADVERSE EVENTS AND
p.000011: SECURITY MONITORING IN CLINICAL TRIALS
p.000011: 13. BIBLIOGRAPHIC REFERENCES
p.000011: 1. ACKER JE 3rd, Pancioli AM, Crocco TJ, et al. Implementation strategies for emergency medical
p.000011: services within stroke systems of care: a policy statement from the American Heart Association / American Stroke
p.000011: Association Expert Panel on Emergency Medical Services Systems and the Stroke Council. Stroke 2007; 38: 3097–3115.
p.000011: 2. BASTOS, Alessandra Soler et al. Time of arrival of the patient with acute myocardial infarction in a
p.000011: emergency. Rev Bras Cir Cardiovasc, São José do Rio Preto, v. 27, n. 3, Sept. 2012. Available at:
p.000011: accessed on: 19 ago. 2014
p.000011: http://dx.doi.org/10.5935/1678-9741.20120070.
p.000011: 3. BRAZIL. National Health Surveillance Agency. RDC Resolution 09 of February 20, 2015. This
p.000011: Resolution aims to define the procedures and requirements for conducting clinical trials
p.000011: medications, including submitting the Clinical Drug Development Dossier (DDCM) to
p.000011: be approved by Anvisa. Available in:
p.000011: p.000011: Subject + of + Interest / Research + clinic / Resolution + of + Board + Board + RDC + n + 9 + of + 20 + of + February + of + 2015> Access in:
p.000011: 25 jan. 2016.
p.000011: 4. DSUR ICH E2F Step 5. Available at
p.000011: accessed on: 31
p.000011: ago. 2016.
p.000011: 5. EUROPEAN STROKE ORGANIZATION (ESO) Executive Committee; ESO Writing Committee. Guidelines for
p.000011: management of ischaemic stroke and transient ischaemic attack 2008. Cerebrovasc Dis 2008; 25: 457–507.
p.000011: 6. LEES KR, Bluhmki E, von Kummer R, et al. Time to treatment with intravenous alteplase and outcome
p.000011: in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet 2010;
p.000011: 375: 1695–1703.
p.000011: 7. MINISTRY OF HEALTH, WORLD HEALTH ORGANIZATION. Operational Guidelines for the
p.000011: Establishment and Operation of Data and Security Monitoring Committees. Series
p.000011: A. Standards and Technical Manuals Available at:
p.000011: Accessed on June 3. 2014.
p.000011: 8. MINNERUP, J., Wersching, H., Unrath, M. and Berger, K. (2014), Effects of emergency medical
p.000011: service transport on acute stroke care. European Journal of Neurology. doi: 10.1111 / ene.12367
p.000012: 12
p.000012: MANUAL FOR NOTIFICATION OF ADVERSE EVENTS AND
p.000012: SECURITY MONITORING IN CLINICAL TRIALS
p.000012: 9. SHERMAN R B et al. New FDA regulation to improve safety reporting in clinical trials. The New England journal of
p.000012: medicine. 365 (1): 3-5. 2011
p.000012: 10. THE UPPSALA MONITORING CENTER. WHO Collaborating Center for International Drug Monitoring. Glossary of
p.000012: Terms in Pharmacovigilance. Available in:
p.000012: . Accessed on Jun. 3 2014.
p.000012: 11. THE UPPSALA MONITORING CENTER. WHO Collaborating Center for International Drug Monitoring. WHO-UMC Causality
p.000012: Assessment. Available at: . Accessed on Jun. 3 2014.
p.000012: 12. WORLD HEALTH ORGANIZATION. ICF CHECKLIST Version 2.1a, Clinician Form for International Classification of
p.000012: Functioning, Disability and Health. Available in:
p.000012: Accessed on June 3. 2014.
p.000012: 13. WORLD HEALTH ORGANIZATION. WHO Collaborating Center for International Drug Monitoring. Safety Monitoring of
p.000012: Medicinal Products: Guidelines for setting up and running a Pharmacovigilance Center. Geneva, World
p.000012: Health Organization, 2000. Available at: Accessed on June 3. 2014.
p.000013: 13
p.000013: MANUAL FOR NOTIFICATION OF ADVERSE EVENTS AND
p.000013: SECURITY MONITORING IN CLINICAL TRIALS
p.000013: 14. PROCESS FLOWCHART
...
General/Other / participants in a control group
Searching for indicator placebo:
(return to top)
p.000010: II - Adverse Event - any adverse medical event in a patient or trial participant
p.000010: to whom a pharmaceutical product has been administered and which does not necessarily have a causal relationship to
p.000010: treatment. As a result, an EA can be any unfavorable and unintended sign, symptom, or disease (including
p.000010: results outside the reference range), associated with the use of a product under investigation, whether
p.000010: related to it or not;
p.000010: III - Serious Adverse Event - one that results in any adverse experience with medicines, biological products
p.000010: or devices, occurring at any dose and resulting in any of the following outcomes:
p.000010: a) death;
p.000010: b) threat to life;
p.000010: c) persistent or significant disability / disability;
p.000010: d) requires hospitalization or prolongs hospitalization;
p.000010: e) congenital anomaly or birth defect;
p.000010: f) any suspicion of transmission of an infectious agent by means of a drug or;
p.000010: g) clinically significant event.
p.000010: IV - Unexpected Adverse Event - event not described as an adverse reaction in the medicine brochure
p.000010: experimental or on the label.
p.000010: V - Experimental medicine - pharmaceutical product under test, object of DDCM, to be used in the clinical trial,
p.000010: for the purpose of obtaining information for your registration or post-registration;
p.000010: VI - Product under investigation - experimental drug, placebo, active comparator or any other product to be
p.000010: used in the clinical trial;
p.000010: VII - Clinical Trial Protocol - document that describes the objectives, design, methodology,
p.000010: statistical considerations and trial organization. It also provides the context and rationale for the essay
p.000010: clinical;
p.000011: 11
p.000011: MANUAL FOR NOTIFICATION OF ADVERSE EVENTS AND
p.000011: SECURITY MONITORING IN CLINICAL TRIALS
p.000011: 13. BIBLIOGRAPHIC REFERENCES
p.000011: 1. ACKER JE 3rd, Pancioli AM, Crocco TJ, et al. Implementation strategies for emergency medical
p.000011: services within stroke systems of care: a policy statement from the American Heart Association / American Stroke
p.000011: Association Expert Panel on Emergency Medical Services Systems and the Stroke Council. Stroke 2007; 38: 3097–3115.
p.000011: 2. BASTOS, Alessandra Soler et al. Time of arrival of the patient with acute myocardial infarction in a
p.000011: emergency. Rev Bras Cir Cardiovasc, São José do Rio Preto, v. 27, n. 3, Sept. 2012. Available at:
p.000011: accessed on: 19 ago. 2014
p.000011: http://dx.doi.org/10.5935/1678-9741.20120070.
p.000011: 3. BRAZIL. National Health Surveillance Agency. RDC Resolution 09 of February 20, 2015. This
p.000011: Resolution aims to define the procedures and requirements for conducting clinical trials
p.000011: medications, including submitting the Clinical Drug Development Dossier (DDCM) to
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p.000011:
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Orphaned Trigger Words
Appendix
Indicator List
| Indicator | Vulnerability |
|---|
| access | Access to Social Goods |
| disability | Mentally Disabled |
| drug | Drug Usage |
| educational | education |
| emergency | Public Emergency |
| illness | Physically Disabled |
| placebo | participants in a control group |
| threat | Threat of Stigma |
Indicator Peers (Indicators in Same Vulnerability)
Trigger Words
protect
risk
Applicable Type / Vulnerability / Indicator Overlay for this Input