Work Instruction Title: Adverse Event Reporting
Work Instruction Number: 20
Version Number: V2
Effective Date: 24 January 2011
Author
Name: Heather Leishman
Title: PCRN-EoE Network Co-ordinator
Date: 7 February 2010
Approved by
Name: Helen Macdonald
Title: Research Delivery Manager
Date: 8 October 2014
Review date: 8 October 2016
Review History
Version No.
V1
V2
date
amendments
01/07.13 Minor change: Removal of PCT reference
24.9.14
Minor changes plus participant responsibilities
when consenting to a study in relation to safety
reporting. HL
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1. Introduction, Background and Purpose
Pharmacovigilance is the continuous process of monitoring, evaluating and
improving the safety of medicines, which is ongoing throughout the period of drug
development, from animal testing through to post-marketing surveys.
In order to assess the safety of an investigational product it is important to:
 Collect baseline information on the health status of trial participants
 Be aware of and record all concomitant medications
 Ask about these, and about the subjects health status at every visit
 Record all untoward medical occurrences (AEs) as specified in the protocol
 Report AEs within the specified timeframes
 Collect all data as accurately as possible
An Adverse Event ( AE) is defined by ICH GCP (Glossary 1.2) as: ‘Any untoward
medical occurrence in a patient or clinical investigation subject administered a
pharmaceutical product and which does not necessarily have a causal relationship
with this treatment. An Adverse Event (AE) can therefore be any unfavourable or
unintended sign (including an abnormal laboratory finding), symptom or disease
temporally associated with the use of a medicinal (investigational) product, whether
or not related to the medicinal (investigational) product.’



Elective hospitalisations for pre-trial conditions are not adverse events
An Unexpected Adverse Reaction (UAR) is said to have occurred when the
nature or severity of the reaction is not consistent with the applicable product
information (e.g. Investigator Brochure or an unauthorised investigational
product, or Summary of Product Characteristics for an authorised product)
All Adverse Events occurring during the study should be recorded in the
participant case report form and the medical notes.
An Adverse Reaction (AR) is defined as: Any untoward or unintended response to
an investigational medicinal product (IMP) at any dose administered. This includes
all adverse events judged by either the Principal Investigator or the Sponsor as
having a reasonable causal relationship to the IMP.
EudraVigilance is a data processing network and management system for reporting
and evaluating suspected adverse reactions during the development and following
the marketing authorisation of medicinal products in the European Economic Area
(EEA). eudravigilance.ema.europa.eu
All interventional research (involving drugs or devices - whether or not licensed)
should have safety reporting procedures in place. These procedures should form
part of the study protocol and be approved by the Research Ethics and Research
Governance Departments. This document complies with the legal requirements of
the EU Clinical Trials Directive (2001/20/EC) and the standards set out in the
Research Governance Framework for Health and Social Care (second edition 2005).
This Work Instruction (WI) relates to SOP 05 Safety Reporting and describes the
procedure for Adverse Event Reporting. This does not include Serious Adverse
Event/ Reaction (SAE/R), Suspected Serious Adverse Reaction (SSAR) or
Suspected Unexpected Serious Adverse Reactions (SUSAR) reporting, which are
covered in WI 21.
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2. Abbreviations
See Reference Document: CRN Glossary of Terms and Abbreviations.
3. Scope
This WI affects all CRN staff working on NIHR adopted studies. It should be read
and applied in conjunction with relevant local policies and approved study protocols.
4. Responsibilities
The overall responsibility for the accurate and timely reporting of Adverse Events and
Adverse Reactions lies with the Principal Investigator for the site where the study
visits are being carried out. The Principal Investigator may ask a delegated team
member (as set out in the authorised delegation log) to undertake these duties.
5. Procedures
The safety reporting procedures follow a general pattern but are study specific. The
study protocol should be followed closely and any uncertainties raised with the study
Sponsor or representative. The Sponsor will state at what point in the trial Adverse
Event Reporting will start. It is essential to collect and complete accurate baseline
data on the health status of trial participants to ensure that changes to health status
will be detected.
Planning
When considering the hosting of a Clinical Trial of Investigational Medicinal Products
(CTIMP) study the Principal Investigator and study nurse should take time to
consider the study protocol, the Summary of Product Characteristics or the
Investigator’s Brochure with respect to the safety reporting elements. An
assessment of the exact reporting requirements should be made in relation to the
time and space capacity that may be required to undertake the reporting procedures
properly before accepting such as research project. Safety reporting requirements
for an interventional study are subject to change as a result of an amendment
5.2 Reporting
After initiation of the study treatment (this may not include run- in medication),
participants receiving study drugs should be closely monitored for their clinical safety.
They should be questioned about their health status at every visit.
The study protocol should state clearly what Adverse Events needs to be reported
and how this should be done. A study protocol may ask for symptoms and signs to
be reported separately (i.e. 1 “sore throat” 2. ”sneezing” 3. “pyrexia”) or the protocol
may ask for the adverse report to be reported as a diagnosis (“common cold”).
Reporting of symptoms is generally more useful to the study sponsors but is more
time consuming for the study staff to report.
Each Adverse Event must be evaluated for seriousness, causality and expectedness,
along with the action taken, including concomitant medications, and outcome. All
adverse events judged by the Principal Investigator as having a reasonable causal
relationship to the IMP will be classified as Adverse Reactions. See Appendix 1:
Example of AE Reporting Form.
Staff reporting Adverse Events must be aware of the more serious categories of
adverse events which require expedited reporting. SAE’s and SUSARs are covered
in WI 21 Serious Adverse Event Reporting.
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5.3 Informed Consent
As part of the informed consent procedure (see SOP 01 Informed Consent) the
potential study participant should be told in detail about the safety reporting
requirements for the study. The potential participant, by consenting to take part in a
study is also consenting to comply by the safety reporting procedures, which may
include carrying a card and also informing family and friends of participation in a trial
and keeping the contact details of the study team easily accessible.
5.4
Patient Diary
Some studies supply the participants with REC approved study diaries to help them
to record when they experience a new or recurring sign or symptom. Participants will
be asked to record the event including start and end dates (these are often missed).
The diary should be reviewed with the participant at a study visit and the information
from the participant diary should be reported in line with the study protocol on the
appropriate and approved reporting forms.
Participant diaries must always be kept in the trial file. It is prudent to ensure that the
participants ID number is used on the diary plus the date of the diary. The diary will
be used in most cases as the source documentation for Adverse Events in the case
of Source Data Verification (SDV). The study sponsor may ask for the diary to be
scanned into the clinical notes or that the entries are transcribed into the clinical
notes.
Where a study diary is not supplied for a study, check with the sponsor prior to the
study starting regarding how they wish the participants to record adverse events
between visits and whether documents such as the participant’s own clinical records
should be copied for SDV purposes.
5.5 Emergency Contact Details
The participants who have given their consent to be part of an interventional study
should always be given the contact information of the Principal Investigator or
delegated study team member. This may be given on the emergency contact card,
(See Appendix 2). This is particularly important for the period following
randomisation when the participant may need help and guidance with any signs and
symptoms they may experience (which may or may not be related to the study drug).
5.6 Follow up
Prior to the next participant study visit, “open” Adverse Events (where the participant
did not give an end date at the last visit) should be reviewed and followed up at the
upcoming study visit. This is because the participant diary would have been handed
in at the last visit and the participant would not have had the opportunity to report an
end date within that diary.
5.7 Special Categories
Some study protocols have special categories of reporting such as “Medically
Attended Adverse Events”. In this case it may be possible that the study Sponsor
only wishes you to report Adverse Events where participants consult a clinician.
It is important that the study team in this case do not rely solely on attendances
reported in the participant’s clinical record, but must always ask the participant if they
have attended a clinician since the last visit in case the participant attended a
clinician outside the practice/usual clinical service.
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6. Related SOPs, Work Instructions and Reference Documents
6.1 SOPs
SOP 01 Informed consent
SOP 05 Safety reporting
6.2 Work Instructions
WI 21 Serious Adverse Event reporting
6.3 Reference Documents
ICH Good Clinical Practice (GCP)
EU Clinical Trials Directive (EUCTD)
CRN Glossary of Terms and Abbreviations
7. Appendices
Appendix 1: Example of Adverse Event report form
Appendix 2: Example of an emergency contact card
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APPENDIX 1 ADVERSE EVENT CASE REPORT FORM
STUDY NAME:_____________________________________
SITE …………………………………………………………………………
PT INITIALS……………..…….
PRINCIPAL INVESTIGATOR ……………………………………………..
PT STUDY No. …………….…
AE Description
1 = Mild
2 = Moderate
3 = Severe
4 = Life threatening
or disabling*
5 = Fatal*
Submitted
As On SAE
Causality
1 = Unrelated
2 = Unlikely
3 = Possible
4 = Probable
5 = Definite
1 = Expected
2=
Unexpected
Severity
Action Taken
1 = None
2 = Medication
Therapy
3 = Procedure
4 = Hospitalization*
5 = Other
1 = No
2 = Yes
Outcome
1 = Recovered
2 = Improved
3 = Ongoing
4 = Death*
5 = Unknown
Date of AE Onset and Resolution
(mm-dd-yyyy)
Check box “on-going”
if the AE is on-going at the time of report
 On-going (X or √)
Start Date:
_____ - _____ - 20_____
Resolution Date:
1
_____ - _____ - 20 _____
 On-going
Start Date:
_____ - _____ - 20_____
Resolution Date:
2
_____ - _____ - 20 _____
 On-going
Start Date:
_____ - _____ - 20_____
Resolution Date:
3
_____ - _____ - 20 _____
 On-going
Comments:
Investigator Signature:
Date: ____ - ____ - 20____ (mm-dd-yyyy)
* If AE is life threatening, disabling or fatal please submit details to the sponsor within 24 hrs of becoming aware of the event
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Appendix 2 Example of wording on Emergency Contact Card:

Patient Name: ……………………

Patient Number:…………………..

GP Name:……………………………….

GP Number…………………………..
WARNING

This patient is taking part in a clinical trial, and may be on xxx (name of
drug)

To discuss obtaining a code-break, treating doctors should contact:

Tel no: xxx (needs to be 24/7)
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