Sarah Pountain - Stroke Oxygen Study · Research and Development Department North Staffordshire Combined Healthcare h'l:fj ... Reporting of SAEs and SUSARs: Researchers (R&D-FC-SOS-001)

Research and Development Department North Staffordshire Combined Healthcare h'l:fj NHS Trust

Safety Reporting in the Stroke Oxygen Study

R&D-SOP-SOS-001SOP Reference ,

Final Version 1.1Version Number

19111 February 2010 Effective Date

Review Date 18th February 2012

Author Karen Hampson

Position Research and Development Manager

Amended by Sarah Pountain

Approved by Christine Roffe

Position Chief Investigator/R & D Committee Member

gin April 2010 Approval Date -~~~-~~~-~

SOP Research Template 1.0 Template

Previous

Version

Current

Version

Amended by Amendment

IDate

1.0 Sarah Pountain 19m

1.1 February

2010

Reason for amendment

Update of contact details

R&D-SOP-SOS-001 Page 1 of 21 Final Version 1.1 (19-Feb-10)

© North Staffordshire Combined Healthcare NHS Trust

Research and Development Department North Staffordshire Combined Healthcare '~l:bj NHS Trust

Contents

Section Description Page

1 Background 4

2 Purpose 4

3 Definitions 4

3.1 Adverse Incident 4

3.2 Adverse Event 4

3.2.1 Adverse Reaction 5

3.2.2 Unexpected Adverse Reaction 5

3.3 Serious Adverse Event (SAE) 5

3.3.1 Serious Adverse Reaction 5

3.3.2 Suspected Unexpected Serious Adverse Reaction (SUSAR) 5

3.4 Urgent Safety Measure (USM) 6

3.5 Abbreviations 6

4 Scope and Responsibilities 6

4.1 Sponsor 6

4.2 Organisation Providing Care 7

4.3 Chief Investigator 7

4.4 Principal Investigator 8

5 Procedures for Reporting Adverse Events, Serious Adverse Events and SUSARs 8

5.1 Adverse Events, Adverse Reactions and any Unexpected Adverse Reactions (excluding 8 Adverse Incidents)

5.2 Serious Adverse Events (SAEs) 9

5.2.1 Serious Adverse Event reporting - All Researchers 9

5.2.2 Serious Adverse Event reporting - Chief Investigator 10

5.3 Suspected Unexpected Serious Adverse Reactions (SUSARs) 10

5.3.1 SUSAR reporting - All Researchers 10

5.3.2 SUSAR reporting - Chief Investigator 11

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Research and Development Department North Staffordshire Combined Healthcare rill:b1 NHS Trust

6 Assessment of Adverse Events 12

6.1 Intensity 12

6.2 Causality 12

6.3 Expectedness 13

7 Procedures for reporting Urgent Safety Measures (USMs) 14

7.1 USM reporting - All Researchers 14

7.2 USM reporting - Chief Investigator 14

8 Safety Reports 15

9 References 15

10 Related SOPs 16

11 Approval signature 16

Appendices

1 Contact details: Chief Investigator, Study Manager, Sponsor 17

2 Summary table of reporting guidelines for researchers 18

3 Flowchart - Reporting of SAEs and SUSARs: Researchers (R&D-FC-SOS-001) 19

4 Flowchart - Reporting of SAEs and SUSARs: Chief Investigator (R&D-FC-SOS-002) 20

5 Annual Safety Report requirements 21

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Research and Development Department North Staffordshire Combined Healthcare 'ct:fj NHS Trust

1 Background

Safety reporting is an essential part of pharmacovigalence and is necessary to comply with the Research Governance

Framework for Health and Social Care 2nd edition (2005) and the Medicines for Human Use (Clinical Trials) Regulations

(2004). It is also an essential part of Good Clinical Practice, described in the ICH Topic E 6 (R1) Guideline for Good

Clinical Practice Step 5.

Stroke is a complex and severe condition which is often accompanied by serious complications which can be Iife

threatening or lead to death, prolonged hospital stay, or long-term disability. In the context of clinical trials these are

termed Serious Adverse Events (SAEs). Trials in acute stroke typically record SAE rates of up to 50% showing how

frequent these may be. SAEs are expected to occur in both actively treated patients and controls in any large stroke trial.

If an SAE is considered as having a 'reasonable' causal relationship with the trial intervention then it is a Serious

Adverse Reaction (SAR). SARs can be expected to occur in any large stroke trial.

However. some events will be uncommon and therefore unexpected. If they can reasonably be attributed to the trial

intervention rather than to the stroke itself then they are called Suspected Unexpected Serious Adverse Reactions

(SUSARs). In the context of the S02S trial a SUSAR is an SAE which is unexpected in patients with acute stroke and

could reasonably be attributed to oxygen supplementation.

Investigators must check for Adverse Events at every patient contact and report any SAE or SUSAR to the Chief

Investigator or deputy within 24 hours of becoming aware of the event. The Chief Investigator or deputy must adjudicate

whether the reported event is a SUSAR or not. It is essential for this SOP to be followed. Failure to report, or failure

to report them in the correct way could put research participants at risk. This is unacceptable and could result in

the trial being terminated at a particular trial site.

2 Purpose

This SOP describes the process for safety reporting during the Stroke Oxygen Study. sponsored by North Staffordshire

Combined Healthcare NHS Trust.

3 Definitions

3.1 Adverse incident

An incident (Clinical, non-clinical and near misses) which occurs and does not fall into the Adverse Event. Serious

Adverse Event or Suspected Unexpected Serious Adverse Reaction categories. Adverse Incidents should be reported to

the relevant NHS trust using local guidelines.

3.2 Adverse Event

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. If the event was not an untoward medical

occurrence then it is an Adverse Incident and needs to be reported using the local reporting policies.

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Research and Development Department North Staffordshire Combined Healthcare h'l:bj NHS Trust

3.2.1 Adverse Reaction

Any untoward and unintended response in a subject to an investigational medicinal product which is related to any dose

administered to that subject.

3.2.2 Unexpected Adverse Reaction

An Adverse Reaction, the nature and severity of which is not consistent with the information about the medicinal product

in question (in the case of a product with a marketing authorization this refers to the summary of product characteristics

for that product, in the case of any other investigational medicinal product this refers to the information in the

investigator's brochure relating to the trial in question).

3.3 Serious Adverse Event

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 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, or

(e) consists of a congenital anomaly or birth defect

3.3.1 Serious Adverse Reaction

Any untoward and unintended response in a subject to an investigational medicinal product which is related to any dose

administered to that subject; that:



(c) requires hospitalisation or prolongation of existing hospitalisation,



3.3.2 Suspected Unexpected Serious Adverse Reaction (SUSAR):

An Adverse Reaction, the nature and severity of which is not consistent with the information about the medicinal product

in question (in the case of a product with a marketing authorization this refers to the summary of product characteristics

for that product, in the case of any other investigational medicinal product this refers to the information in the

investigator's brochure relating to the trial in question) that:



(c) requires hospitalisation or prolongation of existing hospitalisation,





Research and Development Department North Staffordshire Combined Healthcare b'!/:bl NHS Trust

3.4 Urgent Safety Measure (USM)

Any deviation from the approved version of the protocol necessary to ensure the safety of the research participant.

3.5 Abbreviations

SAE Serious Adverse Event

SUSAR Suspected Unexpected Serious Adverse Reaction

USM Urgent Safety Measure

4 Scope and Responsibilities

This SOP is to be used by all personnel involved in the Stoke Oxygen Study.

4.1 Sponsor

• Arrangements are in place to ensure that all Adverse Events possibly related to the investigational medicinal

product are recorded and records maintained, and they are reported to the relevant NHS Trust if necessary.

• Adverse Events are reviewed by a medical assessor, and a summary of Adverse Events is sent to the

appropriate committee for the monitoring of trial safety on a regular basis.

• Arrangements are in place to ensure that specific SAEs (see 5.2.2 for detailS) are reported to the regulatory

authorities and relevant ethics committee within the required timelines and the relevant NHS Trust.

• Arrangements are in place to ensure that SAEs are reviewed by an appropriate committee for the monitoring of

trial safety.

• Arrangements are in place to ensure that SAEs are recorded and records maintained.

• Arrangements are in place to ensure that SUSARs are identified and reported to the regulatory authorities and

relevant ethics committee within the required timelines and the relevant NHS Trust.

• Arrangements are in place to ensure that all investigators are aware of any SUSARs in relation to the

investigational medicinal product.

• Arrangements are in place to ensure that annual safety reports are submitted to the regulatory authorities and

relevant ethics committee within the required timelines.

• Arrangements are in place to ensure the ongoing safety evaluation of the investigational medicinal product

including trend analyses.

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Research and Development Department North Staffordshire Combined Healthcare 'rl:bj NHS Trust

• Arrangements are in place to ensure that all investigators are made aware of findings which could affect

adversely the safety of the subjects.

• Arrangements are in place to ensure that USMs are reported to the regulatory authorities and relevant ethics

committee within the required timelines.

4.2 Organisation Providing Care

• Ensure that Adverse Events, including SAEs and SUSARs in the context of research are reported to the National

Patient Safety Agency in line with the standard procedures of the organisation; or to the systems for reporting

adverse events in social care.

4.3 Chief Investigator

• All Adverse Events possibly related to the investigational medicinal product are reported to the Sponsor.

• Specific SAEs (see 5.2.2 for details) are reported to the regulatory authorities and relevant ethics committee

within the required timelines and reported immediately to the Sponsor. Arrangements are in place to ensure the

relevant NHS Trust is informed.

• SAEs are reviewed by an appropriate committee for the monitoring of trial safety.

• SAEs are recorded and records maintained.

• SUSARs are identified and reported to the regulatory authorities and relevant ethics committee within the

required timelines and reported immediately to the Sponsor. Arrangements are in place to ensure the relevant

NHS Trust is informed.

• All investigators are aware of any SUSARs in relation to the investigational medicinal product.

• Annual safety reports are submitted to the regulatory authorities and relevant ethics committee within the required

timelines.

• All SAEs are evaluated by the Chief Investigator.

• All investigators are made aware of findings which could affect adversely the safety of the subjects.

• USMs are reported to the regulatory authorities and relevant ethics committee within the required timelines and

the sponsor is alerted immediately. Arrangements are in place to ensure the relevant NHS Trust is informed of

the event.



Research and Development Department North Staffordshire Combined Healthcare h'l:kj NHS Trust

4.4 Principal Investigator

• Investigators must check for Adverse Events at every patient contact and report any SAE or SUSAR to the Chief

Investigator within 24 hours of becoming aware of the event.

• All non-serious adverse events (excluding Adverse Incidents) are recorded and records maintained.

• All non-serious adverse events (excluding Adverse Incidents) possibly related to the investigational medicinal

product are reported to the Sponsor within 14 days and if necessary the relevant NHS Trust (using local

guidelines).

• All SAEs are recorded and records maintained.

• All investigators are aware of any SUSARs in relation to the investigational medicinal product.

• All investigators are made aware of findings which could affect adversely the safety of the subjects.

5 Procedures for Reporting Adverse Events

5.1 Adverse Events, Adverse Reactions and any Unexpected Adverse Reactions (excluding Adverse

Incidents)

NB If the adverse events, adverse reactions and any unexpected adverse reactions are not classed as serious and are

unrelated or unlikely to be related to the investigational medicinal product the relevant NHS Trust local guidelines should

be consulted and the event should be reported using these guidelines.

If the Adverse Events, Adverse Reactions and any Unexpected Adverse Reactions are not classed as serious and are

possibly related, probably related or definitely related to the investigational medicinal product, or the causality is unknown.

the incident needs to be reported using the following procedure:

1J Complete 'Adverse Event (non-serious) reporting form (R&D-RF-SOS-001), available from the SOS website. The event

should be assessed to determine the intenSity. causality and expected ness using the guidelines set out in sections 6.1

6.3.

2J Send completed form to the Sponsor by fax 01782 441624 within 14 days.

3] The relevant NHS Trust local guidelines should also be consulted and the event should be reported using these

guidelines.



Research and Development Department North Staffordshire Combined Healthcare h"l:f1 NHS Trust

A record of all adverse events should be maintained and a copy of the completed 'Adverse Event (non-serious) reporting

form' needs to be placed in the Investigator Site File.

The Sponsor will monitor these events, which will be reviewed by a medical assessor. A summary table of all these

events will be submitted to the trial Data Monitoring and Safety committee for review.

This is outlined in the flow chart 'Reporting of SAEs and SUSARs: Researchers (R&D-FC-SOS-001)' in appendix 3.

5.2 Serious Adverse Events (SAEs)

5.2.1 Serious Adverse Event reporting - All Researchers

NB. If the event is a SUSAR it should be reported following the guidelines in section 5.3.1 (SUSAR Reporting - All

Researchers)

All SAEs should be reported using the following procedure:

1] You must notify the SOS study centre immediately by either telephoning 0300 1230891 (office hours) 07740 372852

(out of hours) 07734 068408 (back up out of hours number); sending a fax to 0300 123 894 (office hours) or sending an

email to [email protected] (Chief Investigator) AND [email protected] (SOS Study

Manager).

2] Report this event using the Serious Adverse Event Notification form (Assessment Form 4) which is available in the

CRF, or on the SOS website. The event should be assessed to determine the intensity, causality and expected ness using

the guidelines set out in sections 6.1 - 6.3. The completed form must be faxed to 0300 1230894 as soon as possible

within 24 hours of becoming aware of the event. Copies of these forms also need to be sent to the Sponsor within 24

hours by faxing to 01782 441624.

3J The relevant NHS Trust local guidelines should also be consulted and the event should be reported using these

guidelines.

A record of all SAEs should be maintained and a copy of the completed Serious Adverse Event Notification form

(Assessment Form 4) form needs to be placed in the Investigator Site File.

This is outlined in the flow chart 'Reporting of SAEs and SUSARs: Researchers (R&D-FC-SOS-001)' in appendix 3.



mailto:[email protected]


Research and Development Department North Staffordshire Combined Healthcare '~/:fj NHS Trust

5.2.2 Serious Adverse Event reporting - Chief Investigator

NB. If the event is a SUSAR it should be reported following the guidelines in section 5.3.2 (SUSAR Reporting - Chief

Investigator).

Is the SAE any of the following:

a) an increase in the rate of occurrence or a qualitative change of an expected serious adverse reaction, which is judged

to be clinically important

b) post-study SUSARs that occur after the patient has completed a trial and are reported by the investigator to the

sponsor

c) a new event, related to the conduct of the trial or the development of the Investigational Medicinal Product, that is likely

to affect the safety of subjects, such as:

a serious adverse event which could be associated with the trial procedures and which could modify the conduct

of the trial (for example a SAE occurring during the run-in period)

a significant hazard to the subject population such as lack of efficacy of an IMP used for the treatment of a life

threatening disease

a major safety finding from a newly completed animal study (such as carcinogenicity).

any anticipated end or temporary halt of a trial for safety reasons where the trial is conducted with the same IMP

by the same sponsor in another country.

(d) the conclusions or recommendations of a data monitoring committee, where relevant for the safety of subjects.

If the answer is yes the European Commission guidance recommends that reports on these occurrences should also be

sent to the main REC according to the same timelines as SUSARs (see 5.3.2 SUSAR Reporting - Chief Investigator).

If the answer is no a copy of the completed form needs to be sent to the Sponsor using the contact details listed in

appendix 1 and the completed Serious Adverse Event Notification form (Assessment Form 4) needs to be placed in the

Trial Master File. The Serious Adverse Event Notification form (Assessment Form 4) also needs to be submitted to the

trial safety committee for review and trend analysis needs to be carried out where appropriate.

This is outlined in the flow chart 'Reporting of SAEs and SUSARs: Chief Investigator (R&D-FC-SOS-002)' in appendix 4.

5.3 Suspected Unexpected Serious Adverse Reactions (SUSARs)

5.3.1 SUSAR reporting - All Researchers

All SUSARS, including post-study SUSARs that occur after the patient has completed a trial, should be reported using the

following procedure:


(out of hours) 07734 068408 (back up out of hours number); sending a fax to 0300 1230894 (office hours) or sending an



Research and Development Department North Staffordshire Combined Healthcare ' ..l:fj NHS Trust


Manager).

2] Report this event using the Serious Adverse Event Notification form (Assessment Form 4) which is available in the

CRF, or on the SOS website. The event should be assessed to determine the intensity, causality and expected ness using

the guidelines set out in sections 6.1 - 6.3. The completed form must be faxed to 0300 123 0894 as soon as possible

within 24 hours of becoming aware of the event. Copies of these forms also need to be sent to the Sponsor within 24

!!2.Yr!. by faxing to 01782 441624.


guidelines.

A record of all SUSARS should be maintained and a copy of the completed Serious Adverse Event Notification form

(Assessment Form 4) form needs to be placed in the Investigator Site File.

This is outlined in the flow chart 'Reporting of SAEs and SUSARs: Researchers (R&D-FC-SOS-001), in appendix 3.

5.3.2 SUSAR reporting - Chief Investigator

The Chief Investigator has to assess all SUSARS: Is the SUSAR fatal or life-threatening?

If the answer is yes the Chief Investigator must notify the following authorities within 7 days:

MHRA

Main Research Ethics Committee

If the answer is no the Chief Investigator must notify the following authorities within 15 days:

MHRA

Main Research Ethics Committee

Reporting to MHRA

Reports can be scanned as PDF documents and [email protected]. clearly stating that the

attachment is a UK clinical trial SUSAR.

Paper UK clinical trial SUSAR reports should be sent to the centralised scanning facility in Gloucester:

MHRA

PO Box 20

Mitcheldean

GL170WQ





6


Reporting to ethics

The Report should be accompanied by the 'Clinical trials of investigational medicinal products safety report to main

research ethics committee' submission form (available from the NRES website:

http://www.nres.npsa.nhs. uk/applicants/after -ethical-review/safetyreports/safety-reports-for -ctimps/#s ubmiss ionofreports)

A copy of the completed form needs to be sent to the Sponsor using the contact details listed in appendix 1 and the

completed Serious Adverse Event Notification form (Assessment Form 4) needs to be placed in the Trial Master File. The

Serious Adverse Event Notification form (Assessment Form 4) also needs to be submitted to the trial safety committee for

review and trend analysis needs to be carried out where appropriate.

This is outlined in the flow chart 'Reporting of SAEs and SUSARs: Chief Investigator (R&D-FC-SOS-002)' in appendix 4.

Assessment of adverse events:

6.1 IntenSity

To assess the intenSity of the Adverse Event the following definitions should be used, along with the investigator's clinical

judgement:

1] Mild

This describes an event that causes minimal discomfort to the patient and/or does not interfere with everyday activities

2] Moderate

This describes an event which is moderately discomforting and/or interferes with normal everyday activities.

3] Severe**

This describes a event which is discomforting and/or prevents normal everyday activities.

**The term severe which describes the intenSity of an adverse event is not the same as an event being classed as

'serious', which is based on patient/event outcome or action criteria. A 'serious' event refers to an event which:

resulted in death,

is life-threatening,

requires hospitalisation or prolongation of existing hospitalisation,

results in persistent or significant disability or incapacity, or

consists of a congenital anomaly or birth defect

6.2 Causality

The relationship between the Adverse Event and the administered investigational medicinal product needs to be

assessed using the investigator's clinical judgement and the definitions listed below. To aid in the causality the

investigator should also refer to the protocol, product information and the investigator brochure.



http://www.nres.npsa.nhs

Research and Development Department North Staffordshire Combined Healthcare ,.!f:fj NHS Trust

1] Unrelated

There is no evidence of any causal relationship between the investigational medicinal product and the Adverse Event.

2] Unlikely

There is little evidence to suggest there is a causal relationship between the investigational medicinal product and the

Adverse Event and there is another reasonable explanation which may explain the occurrence of the event for the event

(e.g. the patient's clinical condition, other concomitant treatment).

3] Possibly related*

There is some evidence to suggest a causal between the investigational medicinal product and the Adverse Event and

there is another reasonable explanation which may can explain the occurrence of the event (e.g. the patient's clinical

condition, other concomitant treatment).

4] Probably related*

There is evidence to suggest a causal relationship between the investigational medicinal product and the Adverse Event

and the influence of other factors is unlikely. As such the event is more likely to be related to the investigational medicinal

product.

5] Definitely related*

There is clear evidence to suggest a causal relationship and there are no other possible contributing factors.

6] Unknown

There is insufficient or incomplete evidence to make a clinical judgement of the causal relationship.

*these events are described as adverse reactions

6.3 Expectedness

The relationship between the Adverse Event and the administered investigational medicinal product needs to be

assessed using the investigator's clinical judgement and the definitions listed below to assess if the reaction was

expected or unexpected. To aid in the this the investigator should also refer to the protocol, product information or

investigator brochure.

1] Expected

The nature or severity of the Adverse Reaction is consistent with the applicable product information.

2] Unexpected

The nature or severity of the Adverse Reaction is not consistent with the applicable product information.



Research and Development Department North Staffordshire Combined Healthcare "'/:k1 NHS Trust

7 Procedures for reporting Urgent Safety Measures (USMs)

7.1 USM Reporting - All Researchers

All USMs should be reported using the following procedure:


(out of hours) 07734 068408 (back up out of hours number); sending a fax to 0300 123 894 (office hours) or sending an


Manager) marking the email/fax with 'URGENT SAFETY MEASURE'.

2] Report the USM using the SOS ' Urgent Safety Measure Reporting Form (R&D-RF-SOS-002)' available on the SOS

website ASAP within 24 hours of becoming aware of the event. This form can then be emailed to

[email protected] (Chief Investigator) AND [email protected] (SOS Study Manager) or

faxed to 0300 123 0894 (office hours). Copies of these forms also need to be sent to the Sponsor immediately by

em ailing to [email protected] or faxing to 01782 441624.


guidelines.

7.2 USM Reporting - Chief Investigator

The USM should be reported using the following procedure:

1] The Chief Investigator should phone the Clinical Trial Unit at the MHRA and discuss the issue with a medical assessor

immediately and should phone the main REC and discuss the issue immediately.

2] The Chief Investigator must notify the MHRA and the main research ethics committee, in writing, of the measures taken

and the reason for the measures within 3 days by submitting a substantial amendment. The sUbstantial amendment

should include a covering letter detailing the measures taken, the reason for them and the medical assessor contacted; a

Notification of Amendment form (available from the Eudract website http://eudract.emea.eufopa.eu/document.html#forms); and

supporting documentation. The substantial amendment should be:

Faxed to the Clinical Trials Unit on 020 7084 2443 or

[email protected] marked 'Urgent Safety Measure'

Sent to the main REC marked 'Urgent Safety Measure'

3] The MHRA must also be notified of a Serious Breach, as described in the SOP 'Breach of protocol or GCP (R&D-SOP

SOS-002) within 7 days of the Chief Investigator being made aware of the breach.



http://eudract.emea.eufopa.eu/document.html#forms






Research and Development Department North Staffordshire Combined Healthcare 'rl:bj NHS Trust

4] The substantial amendment must also be sent as PDF documents on disk to:

Information Processing Unit,

Area 6,

Medicines and Healthcare products Regulatory Agency,

Market Towers,

1 Nine Elms Lane,

London.

SW85NQ

A copy of the completed report needs to be sent to the Sponsor using the contact details listed in appendix 1 and the

completed report needs to be placed in the Trial Master File. The report also needs to be submitted to the trial safety

committee for review and trend analysis needs to be carried out where appropriate.

8 Safety Reports

The Chief Investigator is responsible for producing Annual Safety reports, These should be provided at yearly intervals

from the date of the original exemption, for trials ongoing on 1 May 2004, or the date of the CT A approval for trials starting

after 1 May. For trials with marketed products, the date is the first marketing authorisation granted in the EU. These

should be sent to the MHRA and main ethics committee. Guidance on what the annual safety report should include can

be found in appendix 5.

NB. For short term trials a safety report should be submitted within 90 days of the end of the trial along with the end of

trial notification.

The Chief Investigator is also responsible for providing reports to the Sponsor on the conclusions or recommendations of

the Data and Safety Monitoring Committee.

9 References

The Medicines for Human Use (Clinical Trials) Regulations 2004

Research Governance Framework for Health and Social Care 2nd edition (2005)

Detailed guidance on the collection, verification and presentation of adverse reaction reports arising from clinical trials on medicinal products for human use (April 2006) http://ec.europa. eu/enterprise/pharmaceuticals/eudralexlvol-1 0121 susar rev2 2006 04 11. pdf

National Research Ethics Service guidance on safety reporting for clinical trials with investigational medicinal products http://www.nres.npsa.nhs.uklapplicants/after-ethical-review/safetyreportslsafetv-reports-for-ctimpsl

MHRA guidance on clinical trial authorisations: Safety reporting - SUSARS and ASRs http://www.mhra.qov.uklHowweregulate/Medicines/Licensingofmedicines/Clinicaltrials/SafetyreportingSUSARSandASRs/index.htm



http://www.mhra.qov.uklHowweregulate/Medicines/Licensingofmedicines/Clinicaltrials/Safetyreporting

http://www.nres.npsa.nhs.uklapplicants/after-ethical-review/safetyreportslsafetv-reports-for-ctimpsl

http://ec.europa

Research and Development Department North Staffordshire Combined Healthcare 'cl:fj NHS Trust

ICH Topic E 6 (R1) Guideline for Good Clinical Practice Step 5 NOTE FOR GUIDANCE ON GOOD CLINICAL PRACTICE (CPMP/ICH/135/95) http://www.emea.europa.eu/pdfs/human/ich/013595en.pdf

Standard Operating Procedures for Research Ethics Committees in the United Kingdom ('SOPs') v 3.5 May 2008 http://www.nres.npsa.nhs. uklnews-and-publications/pu blications/standard-operating-proced uresl

10 Related SOPs

Serious breach of protocol or GCP (R&D-SOP-SOS-002)

11 Approval signature: Do not use this SOP unless it has been signed below

As a member of the R&D Committee I authorise the use of this SOP.

SOP Reference: R&D-SOP-SOS-001

Version Number: Final version 1.1 (19-Feb-10)

Name Prof. Christine Roffe Position Chief Investigator

ISigned Date C( Cr" f iJ



http://www.nres.npsa.nhs

http://www.emea.europa.eu/pdfs/human/ich/013595en.pdf

Research and Development Department North Staffordshire Combined Healthcare 'rl:fj NHS Trust

Appendix 1: Contact details

Contact address

Contact email

Contact phone number

Contact fax number

Prof. Christine Roffe - Chief Investigator

SOS Study, Stroke Research Office, North Staffs. Combined Healthcare NHS Trust, Holly Lodge, 62 Queens Road, Stoke-onTrent, ST 4 7LH

[email protected]

0300 1230891 (office hours) 07740 372852 (out of hours) 07734 068408 (back up out of hours number)

0300 1230894 (office hours)

Contact name

Contact address

Contact email


Dr Sarah Pountain - SOS Study Manager

SOS Study, Stroke Research Office, North Staffs. Combined Healthcare NHS Trust, Holly Lodge, 62 Queens Road, Stokeon-Trent, ST4 7LH

[email protected]

0300 1230891 (office hours) 07740 372852 (out of hours) 07734 068408 (back up out of hours number)

0300 1230894 (office hours)

Contact name Laurie Wrench - Research and Development Manager

I Contact address Research and Development Dept, Academic Suite, Harplands Hospital, Hilton Road, Harpfields, Stoke-on"Trent, ST46TH

i

I Contact email [email protected]


01782441624 (office hours)

Contact fax number

01782441624 (office hours; same number as phone number)

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Research and Development Department North Staffordshire Combined Healthcare rifl:bj NHS Trust

Appendix 2: Summary table of reporting guidelines for researchers

EVENT

Adverse Incident

Adverse Event (nonserious) - not related to IMP

Adverse Event (nonserious) - possibly related to IMP

REPORT TO

Relevant NHS Trust using local policies and guidelines

Relevant NHS Trust using local policies and guidelines

Sponsor

Local NHS Trust

TIME FRAME

Consult relevant NHS Trust local policies and guidelines


Within 14 days

Consult relevant NHS Trust local pOlicies and guidelines

FORMS TO USE



Adverse Event (non-serious) reporting form (R&D-RF-SOS001)


!

i

SAE

Chief Investigator, Study Manager and Sponsor

Local NHS Trust

Within 24 hours


Serious Adverse Event Notification form (Assessment Form 4)


SUSAR

Chief Investigator, Study Manager and Sponsor

Local NHS Trust

Within 24 hours

Consult relevant NHS I Trust local policies and I guidelines

Serious Adverse Event Notification form (Assessment Form 4)

IConsutt relevant NHS Trust local policies and guidelines

I

Urgent Safety Measure

, Chief Investigator, Study I Manager and Sponsor

Local NHS Trust

I

Within 24 hours


Urgent Safety Measure (USM) reporting form ( R&D-RF-SOS002)




Research and Development Department North Staffordshire Combined Healthcare '~l:kj NHS Trust

Appendix 3: Flowchart - Reporting of SAEs and SUSARs: Researchers (R&D-FC-SOS-001)

Stroke Oxygen Study Eudract number: 2006-003479-11 Reporting of SAEs and SUSARs: Researchers

Researchers: Is the answer YES to any of the following:

Did the event result in death? Is/was the event life threatening? Did /does the event lead to hospitalization or prolonged hospitalization? Did/does the event result in persistent or significant disability/incapacity? Did/does the event result in congenital anomalylbirth defect/carcinogenesis? Does the investigator consider the event a serious adverse event for other reasons? Is it a SUSAR?

/ This is a SAEISUSAR

1] Inform the SOS study centre immediately 2] Report within 24 hours using the Serious Adverse Event Notification form (assessment form 4) and sending by fax 3] Send copy to sponsor by fax 4] Report to relevant NHS trust using local guide lines 5] Place a copy of form in Investigator site file

This is a non-serious adverse event

Is the non-serious adverse event possibly related, probably related or definitely related to the IMP or is the causality unknown?

1 ] Record this incident using the Adverse Event (non-serious) reporting form 2] Fax form to Sponsor within 14 days 3] Report to relevant NHS trust using local guidelines 4] Place a copy ofform in Investigator site file

1] No further action needs to be taken in relation to the clinical trial 2] Report to relevant NHS trust using local guidelines




Appendix 4: Flowchart - Reporting of SAEs and SUSARs: Chief Investigator (R&D-FC-SOS-002)

Stroke Oxygen Study Eudract number: 2006-003479-11 Reporting ofSAEs and SUSARs: Chief Investigator

ChiefInvestigator: Is the SAE a SUSAR?

Is the SUSAR fatal or Ii fe-threatening?

1] Send the report form and safety report cover letter to the MHRA and the main REC within 7 days 2] Send completed report furm to Sponsor 3] Place a copy of form in Trial Master file 4] Ensure event is reviewed by Trial Safety Committee

1] Send the report furm and safety report cover letter to the MHRA and the main REC within 15 days 2] Send completed report form to Sponsor 3J Place a copy of form in Trial Master file 4] Ensure event is reviewed by Trial Safety Committee

Is the SAE any of the following: a) an increase in the rate ofoccurrence or a qualitative change of an expected serious adverse reaction, which is judged to be clinically important b) post-study SUSARs that occur after the patient has completed a trial and are reported by the investigator to the sponsor c) a new event, related to the conduct of the trial or the development of the IMP, that is likely to affect the safety of subjects, such as:

a serious adverse event which could be associated with the trial procedures and which could modifY the conduct of the trial (for example a SAE occurring during the run-in period) a significant hazard to the subject population such as lack of efficacy ofan IMP used for the treatment ofa life threatening disease a major safety finding from a newly completed animal study (such as carcinogenicity). any anticipated end or temporary halt of a trial for safety reasons where the trial is conducted with the same IMP by the same sponsor in another country.

(d) the conclusions or recommendations ofa data monitoring committee, where relevant for the safety of subj ects.

Report using procedures described for a SUSAR 1] Send completed report form to Sponsor 2] Place a copy of form in Trial Master file 3] Ensure event is reviewed by Trial Safety Committee



r.'I:kjNational Patient Safety Agency

National Research Ethics Service Appendix 5: Annual Safety Report requirements

What should the Annual Safety Report (ASR) include? The aim of the Annual Safety Report is to describe concisely all new safety information relevant for one or several clinical trial(s) and to assess the safety of subjects included in these studies. The Annual Safety Report of a clinical trial should have three parts: Part 1: Analysis of the subjects' safety in the concerned clinical trial(s) with an appraisal of its ongoing risk: benefit.

Part 2: A line listing of all suspected serious adverse reactions (including all SUSARs) that occurred in the concerned trial(s), including all serious adverse reactions from third countries.

Part 3: An aggregate summary tabulation of suspected serious adverse reactions that occurred in the concerned trial(s). Full details of what to include in an Annual Safety Report can be found in Section 5.2 of Detailed guidance on the collection, verification and presentation of adverse reaction reports arising from clinical trials on medicinal products for human use - April 2006 European Commission document, http://ec.europa.eu/enterprise/pharmaceuticals/eudralexlvoI10_en.htm

Where to send the Annual Safety Report (ASR)

Annual safety reports should be provided as electronic documents on disk and be sent to: Information ProceSSing Unit, Area 6, Medicines & Healthcare products Regulatory Agency, Market Towers, 1 Nine Elms Lane, Vauxhall, London SW8 5NQ.

Annual safety reports should also be sent to the main REC responsible for a trial of the IMP

Safety reportfarm (eTlMP), version 4.0, April 2007 R&D-SOP-SOS-001 Final Version 1.0 (9-0ct-08)


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http://ec.europa.eu/enterprise/pharmaceuticals/eudralexlvoI10_en.htm

Documents

Sarah Pountain - Stroke Oxygen Study · Research and Development Department North Staffordshire Combined Healthcare h'l:fj ... Reporting of SAEs and SUSARs: Researchers (R&D-FC-SOS-001)