Download AE-SAE Reporting Guidelines v2.0

AE/SAE Reporting Guidelines
Background
It is a legal requirement under clinical trial regulations, which implement the EU Clinical Trials
Directive 2001/20/EC into law, to record and report adverse events (AEs), Adverse Reactions
(ARs), Serious Adverse Events (SAEs), Serious Adverse Reactions (SARs) and Suspected
Unexpected Serious Adverse Reactions (SUSARs) that occur in patients participating in
Clinical Trials of Investigational Medicinal Products (CTIMPs).
Scope
These guidelines apply to the site Principal Investigator (PI) and all site staff who have been
delegated the task of recording and reporting AEs/SAEs.
Responsibilities of the Clinical Research Support Centre (CRSC)
The CRSC acting on behalf of the Sponsors have been delegated responsibility for
pharmacovigilance. The CRSC is responsible for keeping records of AEs and SAEs that
occur in trial patients as per the protocol and reporting SAEs and SUSARs to the Sponsors,
Ethics and Regulatory Agencies within the required timelines as per the regulatory
requirements. The CRSC will undertake a review of AE/SAE related documents at each site
during monitoring visits to ensure that all relevant documents are completed, filed and have
been reported as per the protocol and the regulatory requirements.
Responsibilities of the Principal Investigator (PI)
The PI may delegate AE and SAE recording and reporting responsibilities to medically
qualified persons who can cover in their absence. The delegation of tasks should be
documented in the Delegation Log (Doc No: TM01-RD04) which must be held in the
Investigator Site File (ISF). Delegation Logs should be faxed to the CRSC as any updates to
staff and tasks delegated occur. This will enable the CRSC to verify signatures on SAE forms
and check that only staff who have been delegated SAE reporting responsibilities have
completed the forms, and only those that have been delegated responsibility in the absence
of the PI signs SAE Forms.
The PI is responsible for keeping records of AEs and SAEs that occur in trial patients as per
the protocol and as outlined below.
Adverse Event Reporting

Assess each AE for seriousness, causality and expectedness (Appendix 1). The
following documents should be at hand when assessing any AE in the trial; Protocol
and Summary of Product Characteristics (SmPC).

Because HARP-2 is recruiting a population that is already in a life-threatening
situation, it is expected that many of the participants will experience AEs. Events that
are expected in this population (i.e. events that are in keeping with the patient’s
underlying medical condition) should not be reported.

An adverse reaction (AR) is an AE which is related to the administration of the study
drug. If any AEs are related to the study drug (i.e. are ARs) they must be reported.

The following are ARs which are expected and must be reported:
Creatinine Kinase > 10 times the upper limit of normal
Alanine Aminotransferase (ALT) > 8 times the upper limit of normal
Aspartate Aminotransferase (AST) > 8 times the upper limit of normal

The PI needs to enter the details relating to ARs in the medical records of the patient
and on the AE Form of the Case Report Form (CRF).

Submit the AE Form along with the other sections of the CRF to the CRSC as per the
CRF Submission Guidelines. ARs do not require expedited reporting. The data
manager will review the AE Form and raise queries for the site as deemed necessary,
eg. if an AR is not resolved at the time of reporting.
HARP-2
Page 1 of 3
AE/SAE Reporting Guidelines_v2.0 Final_ 29/03/12
AE/SAE Reporting Guidelines
Serious Adverse Event Reporting

Assess each AE for seriousness, causality and expectedness (Appendix 1). The
following documents should be at hand when assessing any AE in the trial; Protocol
and Summary of Product Characteristics (SmPC).

Because HARP-2 is recruiting a population that is already in a life-threatening
situation, it is expected that many of the participants will experience SAEs. Events
that are expected in this population (i.e. events that are in keeping with the patient’s
underlying medical condition) and that are collected as outcomes of the trial, including
death and organ failure should not be reported as SAEs. Other SAEs must be
reporte

A serious adverse reaction (SAR) is an SAE which is related to the administration of
the study drug. If any of the above are related to the study drug (i.e. are SARs) they
must be reported.

The following SAR is expected and must be reported:
Need for renal replacement therapy in patients with Creatinine Kinase > 10 times the
upper limit of normal.

The PI needs to enter the details relating to SAEs and SARs in the medical records of
the patient, the AE Form within the CRF, the Serious Adverse Event Log (Doc No:
TM02-RD05) and the SAE Form within the CRF.

SAEs require expedited reporting. Submit the SAE Form in the CRF to the CRSC
within 24 hours of first becoming aware of the event. The SAE Form should be faxed
to the CRSC along with a Notification of SAE form to:
Fax Number: 0044 (0)28 9063 3554
The SAE Form should be as complete as possible and must be signed and dated by
the PI or delegate as documented on the Delegation Log. For instances when both
the PI and delegate are absent in the first 24 hours, a partially completed SAE Form
should be submitted to the CRSC within 24 hours of becoming aware of the event.
The completed SAE form must subsequently be reviewed by the PI or delegate and
submitted to the CRSC as soon as possible.
If all the required information is not available at the time of reporting, the PI must
ensure that any missing information is provided as soon as this becomes available.
The PI should provide this information on the SAE Follow Up Form within the CRF
and fax this to the CRSC along with a Notification of SAE form. It should be indicated
on the report that this information is follow up information to a previously reported
event.
Following the submission of a SAE Form to the CRSC the Trial Manager/Trial Coordinator will confirm receipt within 2 business days. If confirmation of receipt is not
received, site staff should contact the CRSC.
All SAE reports to the CRSC should be retained in the ISF, along with the Notification
of SAE form and acknowledgement of receipt provided by the CRSC. The original
CRF (Sections 13 and 14) should be submitted along with all other sections of the
CRF within 3 months of randomisation.
NOTE: If the SAE is judged to be a SUSAR, the CRSC may require additional
information from the site to ensure all information required to be reported as per the
regulatory requirements is captured. The Trial Manager/Trial Co-ordinator will
contact the site to obtain further information as deemed necessary.
HARP-2
Page 2 of 3
AE/SAE Reporting Guidelines_v2.0 Final_ 29/03/12
AE/SAE Reporting Guidelines
Appendix 1 – Assessment of Adverse Events
These definitions are taken from the European Union Clinical Trials Directive 2001/20/EC.
Table 1
Term
Adverse Event (AE)
Adverse Reaction (AR)
Unexpected Adverse Reaction
(UAR)
Serious Adverse Event (SAE)
Serious Adverse Reaction
(SAR)
Suspected Unexpected
Serious Adverse Reaction
(SUSAR)
Definition
Any untoward medical occurrence in a patient or clinical
trial subject administered a medicinal product and
which does not necessarily have a causal relationship
with this treatment.
All untoward and unintended responses to an
investigational medicinal product related to any dose
administered
An adverse reaction, the nature or severity of which is
not consistent with the applicable product information
(e.g. investigator’s brochure for an unauthorised
investigational product or summary of product
characteristics for an authorised product).
Respectively, any adverse event, adverse reaction or
unexpected adverse reaction that:
a) results in death; b) is life-threatening; c) requires
hospitalisation
or
prolongation
of
existing
hospitalisation; d) results in persistent or significant
disability or incapacity; e) is a congenital anomaly or
birth defect; f) is any other important medical event(s)
that carries a real, not hypothetical, risk of one of the
outcomes above
Assessment of Seriousness
Each AE should be assessed for seriousness as per the definition of a SAE in Table 1 above.
Assessment of Causality
Each AE should be clinically assessed for causality, i.e. the relationship of the AE to the study
drug. For the purposes of this trial the causality should be assessed using the categories
presented below. Drug related AEs are defined as those considered by the PI to have a
possible, probable or definite relationship to the study drug.





Unrelated – clinical event with an incompatible time relationship to study drug
administration, and that could be explained by underlying disease, or other drugs or
chemicals
Unlikely – clinical event whose time relationship to study drug administration makes a
causal connection improbable, but that could plausibly be explained by underlying
disease or other drugs or chemicals
Possible – clinical event with reasonable time relationship to study drug
administration, but that could also be explained by concurrent disease or other drugs
or chemicals
Probable – clinical event with a reasonable time relationship to study drug
administration, and is unlikely to be attributed to concurrent disease or other drugs or
chemicals
Definite – clinical event with plausible time relationship to study drug administration,
and that cannot be explained by concurrent disease or other drugs or chemicals
Assessment of Expectedness
Each AE should be assessed as to whether it was expected or not. If an AE is judged to be
related to the study drug, the PI is required to make an assessment of expectedness based
on knowledge of the AR and any relevant product information as documented in the Summary
of Product Characteristics (SmPC).
HARP-2
Page 3 of 3
AE/SAE Reporting Guidelines_v2.0 Final_ 29/03/12