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Research Department

STANDARD OPERATING PROCEDURE

STH Researcher

Recording, Management & Reporting of

Adverse Events for STH sponsored studies

SOP History
SOP Number A123
Created STH Research Department (AL)
STH Research Department (AD)
Superseded 2.4
Version 2.5
Date 02 June 2009
Review Date June 2010
Related SOPs A102 Sponsorship
A116 Study Site File
A101 Study Set-up
C111 Urgent Safety Measures
Approved by Senior Research Manager

A123 SOP Version 2.5

Recording, Management & Reporting of Adverse Events for STH sponsored studies
02 June 2009
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Standard Operating Procedure

Recording, Management & Reporting of Adverse Events for STH sponsored studies

This SOP has been produced in accordance with the Medicines for Human Use (Clinical Trials)
Regulations 2004, Medicines for Human Use (Clinical Trials) Amendment Regulations 2006 and the
Research Governance Framework 2005. This SOP will outline the procedure for the recording,
management and reporting of
• Adverse Events (AE),
• Adverse Reactions (AR),
• Serious Adverse Events (SAE),
• Suspected Serious Adverse Reactions (SSAR)
• Suspected Unexpected Serious Adverse Reactions (SUSAR)
for clinical trials that are sponsored by Sheffield Teaching Hospitals NHS Foundation Trust (Glossary-
Appendix 1).

Background

To comply with the Medicines for Human Use (Clinical Trials) Regulations 2004, the sponsor and
Chief Investigator must have systems in place for pharmacovigilance: recording, management and
reporting.

Definition

This SOP focuses on the recording, management and reporting of all AE, AR, SAE, SSAR and
SUSAR that occur in trial participants and that require reporting in accordance with the Medicines for
Human Use (Clinical Trials) Regulations 2004 when STH accepts sponsorship for the trial. This
document outlines the responsibilities of the Investigator (Chief or Principal1). Any delegation of duties
must be agreed in writing (Project Delegation Log in the Investigator Site File).

The CI/PI’s responsibilities are:

a. Providing the Sponsor with details of all AE and AR identified as critical to the evaluation of
safety within the agreed timeframes.
b. Assessing each event for causality.
c. Reporting of SAE, SSAR and SUSAR to the Sponsor (STH Research Department) within
agreed timeframes.
d. Submitting a detailed follow up report of the event to the Sponsor.
e. Supplying the Sponsor and the Research Ethics Committee (REC) with any supplementary
information requested.

Procedure for recording events prior to study start.

1. The Chief Investigator (CI) decides how to record events in the Case Report Form (CRF – as
approved by the sponsor), source document (patient notes) and Investigator Site File. The CI
documents these in the study protocol.
2. The CI decides if any events classed as serious should be excluded from immediate reporting
for this disease area (e.g. hospital admittance for ascetic drainage in ovarian cancer) and
documents these in the study protocol.
3. The CI documents delegated responsibilities of event reporting in the Investigator Site File.

1
The investigator who takes primary responsibility for the overall conduct of a trial is the Chief
Investigator. The investigator who takes responsibility for the conduct of a clinical trial at an individual
site is the Principal Investigator. In relation to a clinical trial conducted at a single site the investigator
is may be referred to as both Chief and Principal Investigator.
A123 SOP Version 2.5
Recording, Management & Reporting of Adverse Events for STH sponsored studies
02 June 2009
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Procedure for management and reporting events

1. The PI or delegate enquires with the participant at each study visit as to whether there have
been any adverse events and records all details in full in the Case Report Form (CRF) and
source document (patient notes).
2. The PI or delegate uses the Adverse Event Flowchart (Appendix 2) to determine the
appropriate procedure for each event as it occurs.
3. The PI or delegate assesses the event for seriousness.
4. If the event is not serious (AE or AR):
4.1 The PI documents the event in the CRF and source document (e.g. patient notes). No
additional recording is required.
5. If the event is not classed as serious, but is seen as critical to evaluation of safety (a notable
event, or increased frequency or severity of a particular AE); the PI should inform the Sponsor
who will report this to the MHRA following the same procedure as for reporting a SUSAR.
6. If the event is serious:
6.1 The PI documents the event in the CRF and source document.
6.2 The PI completes the STH Serious Adverse Event Report Form assessing
seriousness, frequency, intensity, relationship to study drug, action and outcome.
6.3 The PI faxes the completed, signed SAE Report Form to the Research Department within
24 hours of discovery of the event on 0114 22 65937.
6.4 The SAE Report Form is faxed without a PI signature if it is not possible to complete
before the 24 hour timeframe. The form is re-sent when the signature for the PI is added.
6.5 The PI provides further information on the event when it becomes available, using an
additional SAE Report Form and marking these as follow up reports, until the event is
resolved.
6.6 The Sponsor assesses the event to determine the category (SAE, SSAR, or SUSAR).
6.7 If the event is an SAE:
6.7.1 The PI provides additional, related information of the event as requested by the
Sponsor.
6.8 If the event is a SSAR:
6.8.1 The PI provides additional, related information of the event as requested by the
Sponsor.
6.8.2 The Sponsor reports all SSAR relating to the study to the MHRA on the
anniversary of the CTA issued.
6.9 If the event is a SUSAR:
6.9.1 The PI provides additional, related information of the event as requested by the
Sponsor.
6.9.2 The Sponsor reports (to the MHRA and the REC by using the CIOMS form
along with a copy of the STH SAE Report Form) all life threatening or fatal
SUSAR within 7 days and all non life threatening SUSAR within 15 days, where
day 0 is the day that the Sponsor receives the SAE Report Form from the PI.
6.9.3 The Director of Research and Development on behalf of the Sponsor assesses
the SUSAR and makes a decision as to if the study should be terminated based
on the risk.
6.9.3.1 If the study is terminated:
6.9.3.1.1 The Sponsor informs the MHRA and the REC of the closing
of the study using the Declaration of End of Clinical Trial
form within 15 days of the study closure.
6.9.3.1.2 The Sponsor informs all sites and PIs of the study closure.
6.9.4 The Sponsor ensures that all PIs using the suspect IMP are informed of
SUSARs related to it including those PIs using the IMP in other studies for
which the sponsor is responsible. This information will be sent to the PI by their
preferred method of contact, i.e. fax or email with a request for confirmation of
receipt.
6.9.5 The Sponsor ensures that the manufacturer of the IMP is notified of the
SUSAR.
6.10 The PI files all SAE report forms and correspondence in the Investigator Site File.

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1. Pregnancy
The study protocol should include information regarding how to deal with pregnancy of a participant or
their partner during a clinical trial, including follow up procedures to identify any congenital disorders
caused by the IMP.

If a research participant or their partner becomes pregnant during the study, this should be notified by
the PI to the Sponsor as an SAE unless pregnancy is noted within the protocol as being an event that
does not require reporting, for example in the case of studies where pregnancy is the primary
outcome of the study.

2. Urgent Safety Measures

If the severity of an SAE requires that an immediate change in the study procedures or a temporary
halt to the study is required in order to protect clinical trial subjects from any immediate hazard to their
health and safety, the SOP C111 Urgent Safety Measures should be followed.

3. Reporting SUSARs during periods of Sponsor Representative extended leave

During periods of extended leave within the Research Department, for example over the Christmas
period, the responsibility of reporting SUSARs to the MHRA and REC may be delegated to the PI
(See SOP C112 - Reporting SUSARs during periods of Sponsor Representative extended leave). The
Research Department will provide the PI with instructions should this be required.

4. SUSARs arising from the comparator drug or study procedure

In the case of a SUSAR arising from a comparator drug or study procedure, the PI should notify the
Sponsor who is also obliged to report to the MHRA and REC. In addition, the Sponsor must inform the
marketing authorisation holder of the comparator drug and informs them of the notification to the
MHRA.

Events associated with the placebo will usually not satisfy the criteria for an Adverse Reaction and
therefore will not be subject to expedited reporting. However, where SUSARs are associated with
placebo, the PI must notify the Sponsor who will report this to the MHRA and REC.

5. Notable events
If the event is not classed as serious, but is seen as a “notable event” (critical to evaluation of safety
or increased frequency or severity of a particular AE); the PI must inform the Sponsor who will report
this to the MHRA following the same procedure as for reporting a SUSAR.

6. Blinded studies
In the case of a blinded study, it is advantageous to retain the blind for all participants prior to the
analysis of the study results. However, when an SAE may potentially be an Adverse Reaction,
expected or judged reportable on an expedited basis for any other reason, the Investigator must break
the blind for that specific participant only.

The event is assessed for seriousness, expectedness and causal relationship assuming that the IMP
has caused the event. If the event appears to be a SUSAR, then the blind should be broken by the
responsible party, as detailed in the protocol, for the participant prior to reporting.

Where possible the blind should be maintained for those researchers who are responsible for data
analysis and interpretation of the results at the end of the study.

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02 June 2009
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Appendix 1

Glossary2

Adverse Event (AE)

Any untoward medical occurrence in a 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 in a subject to an investigational medicinal product which is
related to any dose administered to that subject.

Serious Adverse Event (SAE)

Any adverse event or adverse reaction that
a. results in death
b. is life threatening3
c. requires hospitalisation or prolongation of existing hospitalisation
d. results in persistent or significant disability or incapacity
e. consists of a congenital anomaly or birth defect.

Suspected Serious Adverse Reaction (SSAR)

Any adverse reaction that is classed in nature as serious and which is consistent with the information
about the medicinal product in question set out
a. In the case of a licensed product, the summary of product characteristics (SmPC) for that
product
b. In the case of any other investigational medicinal product, the Investigator’s Brochure (IB)
relating to the trial in question.

Suspected Unexpected Serious Adverse Reaction (SUSAR)

Any adverse reaction that is classed in nature as serious and which is not consistent with the
information about the medicinal product in question set out
a. In the case of a licensed product, the summary of product characteristics (SmPC) for that
product
b. In the case of any other investigational medicinal product, the Investigator’s Brochure (IB)
relating to the trial in question.

2
Glossary taken from Medicines for Human Use (Clinical Trials) Regulations 2004
3
Life-threatening in the definition of an SAE or SAR refers to an event in which the subject 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
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Appendix 2
Adverse Event Flowchart

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Appendix 3

Associated Documents

Document Research Department network location Website Database Created by

1 STH Serious Adverse S:\General\Research Yes No AL/AD
Event report form Governance\Pharmacovigilance\Adverse
events
2 Declaration of End of Trial http://eudract.emea.europa.eu/docs/declarati No No EMEA
Form (notification to onoftheendoftrialform170805withfields.doc
MHRA and REC)

3 CIOMS form for reporting S:\General\Research No No Council For

SUSARs to MHRA and Governance\Pharmacovigilance\Adverse International
REC events Organizations
Of Medical
Sciences
4 Delegation of study duties S:\General\Research Governance\Project No No PC
log Authorisation\Templates\Site file documents

A123 SOP Version 2.5

Recording, Management & Reporting of Adverse Events for STH sponsored studies
02 June 2009
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A123 SOP Version 2.3

Recording, Management & Reporting of Adverse Events for STH sponsored studies
05 February 2008
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