Procedure for Adverse Events (AE) reporting in TasP Trial

Africa Centre Standard Operating Procedure: ACRO CR51
Version: 1.0
Issue Date: 30 th November, 2011
Procedures for Adverse Events (AE)
Reporting in TasP trial
Author: Collins Iwuji Signature: ………………………………..
Approved by: Head of Research Operations Signature:
1. PURPOSE
This SOP describes the procedures for evaluation and reporting of serious adverse events
(SAE) including timeline for completing tasks.
2. SCOPE
This SOP applies to the evaluation and reporting of SAE’s in the TasP study
3. POLICY AND PROCEDURE
3.1. The research nurse will collect information on adverse events at every visit including
enrolment and follow up.
3.2. The medical management of patients experiencing grade 3 and 4 adverse events is the
responsibility of the trial physician/investigator who must be informed about this by the
research nurse.
3.3. All adverse events must be documented in CRF and followed until resolution.
3.4. Safety reporting definitions
Term
Definition
Adverse Event (AE) Any untoward medical occurrence in a patient or clinical
trial subject to whom a medicinal product has been
administered including occurrences which are not
necessarily caused by or related to that product.
Adverse Reaction (AR) Any untoward and unintended response to an
investigational medicinal product related to any dose
Postal: PO Box 198, Mtubatuba 3935, South Africa
Physical: Africa Centre, R618 en route to Hlabisa, Somkhele
Tel.: +27 (0)35 550 7500
Fax: +27 (0)35 550 7565
Email: info@africacentre.ac.za
Web: www.africacentre.com

Africa Centre Standard Operating Procedure: ACRO CR51
Adverse Event (AE) Reporting in TasP Trial
Unexpected Adverse
Reaction (UAR
Serious Adverse Event
(SAE) or Serious Adverse
Reaction (SAR) or
Suspected Unexpected
Serious Adverse Reaction
(SUSAR)
administered
An adverse reaction, the nature or severity of which is not
consistent with the information about the medicinal
product in question set out in the Summary of Product
Characteristics (or Investigator Brochure) for that product.
Respectively any adverse event, adverse reaction or
unexpected adverse reaction that:
results in death
is life-threatening*
requires hospitalisation or prolongation of existing
hospitalisation**
results in persistent or significant disability or
incapacity
consists of a congenital anomaly or birth defect
requires medical intervention intended to prevent
one of the outcomes listed above in the definition
of SAE
is estimated by the investigator as potentially
serious
3.4.1. Clarifications
3.4.1.1. The term ‘life-threatening’in the definition of serious’refers to an event in
which the patient was at risk of death at the time of the event; it does not refer
to an event which hypothetically might have caused death if it were more
severe.
3.4.1.2. Hospitalisation is defined as an inpatient admission, regardless of length of stay,
even if the hospitalisation is a precautionary measure for continued observation.
Hospitalisations for a pre-existing condition (including elective procedures that
have not worsened) do not constitute an SAE.
3.4.2. Within the frame of this trial SAE also includes
3.4.2.1. Grade 4 clinical and biological events
3.4.2.2. Acute renal failure or Fanconi’s syndrome
3.5. Characterisation of an adverse event
3.5.1. Severity
3.5.1.1. Apart from its seriousness, adverse events are also described based on its
severity; which is established based on gradation tables of clinical and
biological events (appendix 1). ANRS Serious Quotation Table for the
adverse events in Adults—version no 6 dated 9 September 2003 in Frenchversion
no 1 dated 4 November 2008 in English.
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Africa Centre Standard Operating Procedure: ACRO CR51
Adverse Event (AE) Reporting in TasP Trial
3.5.1.2. The severity of an adverse event is not synonymous with seriousness: severity
refers to the intensity of a given event while seriousness refers to the impact
of an event on the vital or functional prognosis of a subject.
3.5.2. Causality
3.5.2.1. This assesses the relationship between the adverse event and the study
drugs, associated drug(s) or with the conduct of the research itself.
3.5.2.2. The study physician/investigator assesses the relationship between the
event and the study and or associated drugs on the initial and
complementary notification forms.
3.5.2.3. The sponsor (pharmacovigilance team of ANRS) also determines the
relationship between the event and the study and or associated drugs or the
research. The opinion of the sponsor is given by the pharmacovigilance team.
3.5.2.4. The final causality of the events with respect to the study and or associated
drugs or the research shall be either the causality established by the
investigator or the sponsor’s. However the causal relationship given by the
investigator shall not be modified: if the sponsor does not agree with the
conclusions of the investigator, both divergent conclusions shall be
mentioned in the report.
3.5.3. ANRS causality assessment
3.5.3.1. All adverse events are to be assessed for the relationship to the study drug by
the trial physician based on the following definitions:
3.5.3.1.1. Not related: The event is clearly related to other causes, such as the
clinical event of the patient or a concomitant treatment without any
pharmacological interaction with the experimental drug.
3.5.3.1.2. Possibly related: Clinical or biological event with a compatible
chronological, aetiological and semilogical relation.
3.5.3.1.3. Relationship impossible to determine: A potential causal relation
between the experimental drugs and the event may exist; it may neither be
affirmed nor excluded at the time of the declaration through a lack of
clinical elements.
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Africa Centre Standard Operating Procedure: ACRO CR51
Adverse Event (AE) Reporting in TasP Trial
3.5.4. Expectedness
3.5.4.1. The expectedness of an event is assessed by the trial physician and is based
on information listed in the package insert or summary of product
characteristics.
3.5.4.2. If a SAR is assessed as being unexpected it becomes a SUSAR
3.5.5. SAE reporting
3.5.5.1. The SAE should be reported by the trial physician if they occur from the date of
the informed consent signature for ART (even if no drugs were administered).
3.5.5.2. During the entire duration of the trial.
3.5.5.3. Up to one month after the end of the trial if the event is suspected to be related
to the trial.
3.5.5.4. And any time after the completion of the trial if the event is suspected to be
related to ART.
3.5.6. SAE notification
3.5.6.1. The trial coordinator/HIV phsyician will notify each SAE to the trial investigator
at the Africa Centre as soon as he is aware of the event.
3.5.6.2. The trial coordinator/HIV physician will complete the trial specific “Initial
Serious Adverse Event Notification” form.
3.5.6.3. This initial reporting form will include:
3.5.6.3.1. Study ID of participant.
3.5.6.3.2. Date of SAE.
3.5.6.3.3. Detailed description of the SAE.
3.5.6.3.4. Drug history
3.5.6.3.5. Name and signature of the investigator notifying the SAE
3.5.6.4. The trial investigator at the Africa Centre will send the notification to the
ANRS pharmacovigilance unit within two working days of being notified of
the event.
ANRS pharmacovigilance unit
Fax: +33 1 53 94 60 02
Mail: pharmacovigilance@anrs.fr
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Africa Centre Standard Operating Procedure: ACRO CR51
Adverse Event (AE) Reporting in TasP Trial
3.5.6.5. Complementary notification
3.5.6.5.1. The investigator or the trial physicians are responsible for the Clinical,
therapeutic and biological follow-up of each SAE until resolution or
stabilization.
3.5.6.5.2. The investigators/trial physician have to report each SAE evolution
(resolution, aggravation, death, final status at the end of the trial) using a
“Complementary SAE Notification Form”.
3.5.6.5.3. Complementary information has to be reported in the following cases:
3.5.6.5.3.1. systematically within 8 days in case of death and life-threatening
event to clarify any relevant complementary information
3.5.6.5.3.2. to report new information on the SAE diagnosis, its evolution, or the
causal relationship to the study drug
3.5.6.5.3.3. to answer any complementary information requested by ANRS
pharmacovigilance unit
3.5.6.6. All SAE will be reported to the UKZN Biomedical Research Ethics Committee,
the trial DMSB, Study Steering group and the KwaZulu-Natal Department of
Health.
4. REFERENCES
4.1. Management of Serious Adverse Events occurring in ANRS sponsored trials and cohorts in
developing countries.
4.2. The ANRS 12249 TasP (Treatment as Prevention) trial, Protocol version 1.2; 1 September
2011
4.3. ICH Topic E 6 (R1) Guideline for Good Clinical Practice- CPMP/ICH/135/95 (Step 5, July
2002)
4.4. Clinical safety data management: Definition and standards for expedited reporting-ICH
guidance E2A-CPMP/ICH/377/95.
4.5. EudraLex - Volume 10 Clinical trials guidelines
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Africa Centre Standard Operating Procedure: ACRO CR51
Adverse Event (AE) Reporting in TasP Trial
5. Attachments and Appendices
5.1. Appendix 1: ANRS scale to grade the severity of adverse events in adults
5.2. Appendix 2: Initial Severe Adverse events notification form
5.3. Complementary Severe Adverse event notification form
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