ACCORD SOP Number: CR012v1.

0
NHS Lothian R&D and
The University of Edinburgh Effective Date: 14/SEP/2011

IDENTIFYING, RECORDING AND REPORTING ADVERSE

EVENTS FOR CLINICAL INVESTIGATIONS OF MEDICAL
DEVICES

SOP NUMBER: CR012

VERSION NUMBER: 1.0

EFFECTIVE DATE: 14/September/2011

RELEASE DATE: 31/August/2011

Signature Date

30th August
AUTHOR: Louisa Wilson, Senior Clinical Trials Monitor, ACCORD 2011

APPROVED BY (1): Marise Buçuko lu, University of Edinburgh, Head 31st August
of Research Governance 2011

31st August
APPROVED BY (2): Paul Dearie, QA Manager, ACCORD 2011

REVIEWED BY:
Gareth Thomas, Lynn Morrice, Dawn Lyster

Parties using this SOP must visit www.accord.ed.ac.uk to guarantee adherence to the
latest version

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ACCORD SOP Number: CR012v1.0
NHS Lothian R&D and
The University of Edinburgh Effective Date: 14/SEP/2011

1. INTRODUCTION

Adverse Device Effects (ADEs) and other safety event identification, recording and
reporting procedures will comply with the requirements of the Medical Device
Regulations 2002/618 and Good Clinical Practice (GCP).

The Investigator will be responsible for identifying and reporting ADEs and other
safety events as detailed in this procedure.

ACCORD will be responsible for medical device vigilance for Clinical Investigations of
Medical Devices (CIMDs) that are sponsored by NHS Lothian and/or the University of
Edinburgh (UoE). This responsibility may not be delegated to the Investigator.

Where NHS Lothian and/or UoE agrees to co-sponsor a CIMD with another
organisation the responsibility for medical device vigilance must be agreed between
both organisations before the trial commences and should be clearly documented in
a clinical trial agreement or equivalent.

2. PURPOSE

To describe the procedure for identifying, recording and reporting AEs and other
safety events occurring in CIMDs that are sponsored by NHS Lothian and/or the
UoE.

3. SCOPE

This SOP applies to clinical researchers participating in CIMDs sponsored by NHS

Lothian and/or the University of Edinburgh (UoE). This SOP is also applicable to
ACCORD members of staff responsible for medical device vigilance.

4. REFERENCES

The Medical Device Regulations (SI: 2002/618) as amended

5. PROCEDURE

5.1 Definitions

Adverse Device Effect (ADE)

Adverse event related to the use of an investigational medical device.
NOTE 1- This includes any adverse event resulting from insufficiencies or
inadequacies in the instructions for use, the deployment, the implantation, the
installation, the operation, or any malfunction of the investigational medical device.
NOTE 2- This includes any event that is a result of a use error or intentional misuse.

Adverse Event (AE)

Any untoward medical occurrence, unintended disease or injury or any untoward
clinical signs (including an abnormal laboratory finding) in subjects, users or other
persons whether or not related to the investigational medical device.
NOTE 1: This includes events related to the investigational device or the comparator.
NOTE 2: This includes events related to the procedures involved (any procedure in
the clinical investigation plan).
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ACCORD SOP Number: CR012v1.0
NHS Lothian R&D and
The University of Edinburgh Effective Date: 14/SEP/2011

NOTE 3: For users or other persons this is restricted to events related to the
investigational medical device.

Serious Adverse Event (SAE)

Adverse event that:
a) led to a death,
b) led to a serious deterioration in health that either:
1) resulted in a life-threatening illness or injury,
or
2) resulted in a permanent impairment of a body structure or a body function,
or
3) required in-patient hospitalization or prolongation of existing hospitalization,
or
4) resulted in medical or surgical intervention to prevent life threatening illness
or injury or permanent impairment to a body structure or a body function.
c) led to fetal distress, fetal death or a congenital abnormality or birth defect.
NOTE 1: This includes device deficiencies that might have led to a serious adverse
event if a) suitable action had not been taken or b) intervention had not been made or
c) if circumstances had been less fortunate. These are handled under the SAE
reporting system.
NOTE 2: A planned hospitalization for pre-existing condition, or a procedure required
by the Clinical Investigation Plan, without a serious deterioration in health, is not
considered to be a serious adverse event.

Serious Adverse Device Effect (SADE)

Any ADE that:
• results in death of the clinical investigation participant
• is life-threatening*
• requires inpatient hospitalisation^ or prolongation of existing inpatient
hospitalisation
• results in persistent or significant disability or incapacity
• consists of a congenital anomaly or birth defect

* Life-threatening in the definition of an SADE refers to an event where

the participant 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.

^Any hospitalisation that was planned prior to randomisation will not meet SADE
criteria. Any hospitalisation that is planned post randomisation, will meet the SADE
criteria.

Unanticipated Serious Adverse Device Effect (USADE)

Serious adverse device effect which by its nature, incidence, severity or outcome has
not been identified in the current version of the risk analysis report.

Device Deficiency
Inadequacy of a medical device with respect to its identity, quality, durability,
reliability, safety or performance. Device deficiencies include malfunctions, use errors
and inadequate labelling.

5.2 Identifying AEs

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NHS Lothian R&D and
The University of Edinburgh Effective Date: 14/SEP/2011

5.2.1 The decision on what AE data to record will be the result of an assessment of
the risk associated with the research, before the clinical investigation is undertaken.
The protocol should define what AEs are to be recorded, notified and reported. AEs
should be recorded from the time the participant signs the consent form to take part
in the trial, unless otherwise defined in the protocol.

5.2.2 The protocol will also define how AEs will be identified. Unless otherwise stated
in the protocol, the Investigator(s) (or a member of the research team with delegated
responsibility to do so – such delegation must be captured in the study site
delegation log) will ask research participants at each trial visit about any
hospitalisations, consultations with other medical practitioners, disability or incapacity
or whether any other adverse events have occurred. AEs may also be identified by
support departments, for example, clinical biochemistry, haematology, radiology.
Where notification of such abnormal values or measurements would not occur as
standard clinical practice, the procedure for notifying the Investigator of such adverse
events must be clearly documented in the protocol or trial specific procedures.

5.3 Recording AEs, SAEs and Device Deficiencies

5.3.1 The protocol will define exactly what adverse event data points will be recorded
and the AE and SAE pages of the Case Report Forms (CRFs) or equivalent can be
designed accordingly. AE and SAE data will be recorded by the Investigator(s) (or a
member of the research team with delegated responsibility to do so) on CRFs.

5.3.2 Unless otherwise stated in the protocol AEs and SAEs will be followed up until
resolution or death of the trial participant.

5.4 Assessment of ADEs

5.4.1 Each AE must be assessed for seriousness, causality, severity and

expectedness by the Principle Investigator or another suitably qualified physician in
the research team who is trained in recording and reporting AEs and who has been
delegated this role. For randomised double blind studies, AEs will be assessed as
though the research participant was subjected to the device.

5.4.2 The Investigator will make an assessment of seriousness (as defined in section
5.1). The Investigator will also make an assessment of whether the ADE is likely to
be related to the device according to the following definitions:

Unrelated: where an event is not considered to be related to the device.

Possibly Related: The nature of the event, the underlying medical condition,
concomitant medication or temporal relationship make it possible that the AE has a
causal relationship to the device.

5.4.3 Assessment of Severity

The Investigator will make an assessment of severity for each AE and this should be
recorded on the CRF according to the following categories:

Mild: an event that is easily tolerated by the research participant, causing minimal
discomfort and not interfering with every day activities.

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ACCORD SOP Number: CR012v1.0
NHS Lothian R&D and
The University of Edinburgh Effective Date: 14/SEP/2011

Moderate: an event that is sufficiently discomforting to interfere with normal everyday

activities.

Severe: an event that prevents normal everyday activities.

The term ‘severe’ used to describe the intensity of an event should not be confused
with the term ‘serious’, as defined in section 5.1, which is a regulatory definition
based on trial participant/event outcome action criteria. For example, a headache
may be severe but not serious, while a minor stroke may be serious but is not
severe.

5.4.4 Assessment of Expectedness

If the AE is judged to be related to the device, the Investigator will make an
assessment of expectedness based on knowledge of the reaction and any relevant
product information as documented the risk analysis report. The event will be classed
as either;

Expected: the reaction is consistent with the effects of the device listed in the risk
analysis report.

Unexpected: the reaction is not consistent with the effects listed in the risk analysis
report.

5.5 Reporting SAEs/SADEs/USADEs and device deficiencies to the sponsor

5.5.1 The protocol will define and justify which SAEs will not be subject to expedited
reporting to the Sponsor. SAEs, including SADEs, USADEs and device deficiencies
are subject to expedited reporting requirements. Post-study USADEs that occur after
the trial participant has completed a clinical trial and are also notified by the
investigator to the sponsor. SAEs (SADEs) and USADEs will be documented on
CR012-T01 Medical Device Vigilance Report. Device deficiencies will be
documented on CR012-T02 Medical Device Deficiency Report.

5.5.2 SAEs (SADEs), USADEs and device deficiency reports will be faxed to the
ACCORD office on +44 (0)131 242 9447 using the appropriate template report
(CR012-T01 or CR012-T02) and the Fax Cover Sheet and Return Receipt (CR012-
F01). In the absence of a functioning fax machine, a verbal report may be given to an
ACCORD Clinical Trials Monitor, or designee, in person or by telephoning ACCORD
on +44 (0)131 242 9430 or +44 (0)131 242 6639. Leaving a voice message will not
suffice as a verbal report. All verbal reports must be followed up as soon as
possible with a signed report from the Investigator. SAE (SADE), USADE and device
deficiency reports must provide an assessment of causality at the time of initial
reporting to ACCORD. SAE (SADE), USADE and device deficiency reporting to
ACCORD should maintain the blind unless it is considered necessary to break the
blind in the interest of research participant safety. Initial reports will be submitted
within 24 hours of the investigator becoming aware of the event.

5.5.3 To ensure patient confidentiality, SAE (SADE), USADE and device deficiency
reports will detail the trial participant number only. If reports are received by
ACCORD with identifiable data, the data will immediately be scored through with a
black marker by the individual receiving the fax. It is then the responsibility of the
individual receiving the fax to inform the sender of this breach in confidentiality and
that they must take steps to ensure that this does not reoccur.
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ACCORD SOP Number: CR012v1.0
NHS Lothian R&D and
The University of Edinburgh Effective Date: 14/SEP/2011

5.5.4 The Senior Clinical Trials Monitor, or designee, will send complete and return
the Fax Cover Sheet and Return Receipt (CR012-F01) to confirm receipt of the SAE
(SADE), USADE or device deficiency report within 1 working day by completing the
Fax Cover Sheet and Return Receipt (CR012-F01). If this fax is not received within 1
working day of sending the report to the ACCORD office, the Investigator must
telephone the ACCORD office on +44 (0)131 242 9430 or +44 (0)131 242 6639 to
check that the report has been received by ACCORD.

5.5.5 On receipt of device deficiency reports, the Senior Clinical Trials Monitor, or
designee, will assess the report to ensure the correct assessment has been made. In
the case of the event meeting SAE (SADE) or USADE criteria, the Senior Clinical
Trials Monitor, or designee will ensure that all the correct reporting procedures have
been followed. Once confirmed as complete, the device deficiency reports will be
filed to the TMF and/or sponsor files.

5.5.6 Once an SAE (SADE) or USADE report is received by ACCORD it will be

entered onto the ACCORD vigilance database by the Clinical Research Administrator
or individual designated by the Clinical Research Facilitator. If all the required
information is not available at the time of reporting, the Investigator must ensure that
any missing information is faxed to the ACCORD office as soon as this becomes
available. It should be indicated on the report that this information is follow-up
information of a previously reported event.

5.5.7 Where missing information has not been sent to the ACCORD office after an
initial report, the ACCORD office will contact the Investigator and request the missing
information. If it is not possible to supply any further detail this will be recorded on the
database. All SAE (SADE), USADE and device deficiency reports faxed to the
ACCORD office and any follow-up information will be kept by the Investigator in the
Investigator Site File (ISF) and by the Sponsor in the Trial Master File (TMF).

5.6 Expedited Reporting of SADEs, USADEs and device deficiencies to the

Research Ethics Committee and the Licensing Authority

5.6.1 ACCORD is responsible for reporting SAEs (SADEs) and USADEs reports
received from Investigators to the Licensing Authority(ies) and the Research Ethics
Committee (REC).

5.6.2 Any SAEs (SADEs)/USADEs - which indicate an imminent risk of death,

serious injury or serious illness and that requires prompt remedial action for other
subject/users or other persons - will be reported within 2 calendar days of awareness
by the sponsor(s). Any other SAEs (SADEs)/USADEs will be reported within 7
calendar days of the sponsor becoming aware. The report must be provided to all
Licensing Authorities relevant to all states in which the clinical investigation is taking
place. The report will be made using the reporting form (appendix) found here
http://ec.europa.eu/health/medical-devices/files/meddev/2_7_3_en.pdf.

For blinded studies the blind will be broken before USADEs are reported to the REC
and Licensing Authority. The Senior Clinical Trials Monitor, or designee, or another
individual not involved in the everyday running of the study, will be responsible for
breaking the blind to ensure that the blind design of the trial is maintained.

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ACCORD SOP Number: CR012v1.0
NHS Lothian R&D and
The University of Edinburgh Effective Date: 14/SEP/2011

Guidance, in regards to reporting to the REC can be found here:

http://www.nres.npsa.nhs.uk/applicants/after-ethical-review/safetyreports/safety-
reports-for-ctimps/

5.7 Other Reporting Requirements

5.7.1 In multi-centre studies the ACCORD office is responsible for informing

Investigators at all participating sites of any reported USADEs and any other arising
safety information. This can be delegated to a coordinating unit/group/individual.
Reports sent directly to the Investigator regarding USADEs from other studies of the
same IMP must be reviewed by the Investigator and acted upon if appropriate. All
copies of such USADE reports must be kept in the ISF and copies sent to the
ACCORD office for the TMF.

5.7.2 External Contracting of SAE (SADE) and USADE Reporting

Expedited reporting may be contracted to an external facility for individual studies.
The facility will perform these tasks without contradiction to this SOP. The facility will
report all SAE (SADE) and USADEs received from Investigators to the ACCORD
office as soon as the facility is first aware of the event. Furthermore, all relevant
follow-up information should be submitted to the ACCORD office.

6. RELATED DOCUMENTS

• CR012-T01 Medical Device Vigilance Report

• CR012-T02 Medical Device Deficiency Report
• CR012-F01 Fax Cover Sheet and Return Receipt

7. DOCUMENT HISTORY

Version Effective Reason(s) for change(s):

Number: Date:
N/A N/A N/A – new procedure

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