Joint Research Office
Office Location:
1st Floor Maple House
149 Tottenham Court Road
London W1T 7DN
Postal Address:
UCL,
Gower Street
London WC1E 6BT
Tel: 020 3447 5193 Fax: 020 3447 9937
Website: www.uclh.nhs.uk; www.ucl.ac.uk; www.ucl.ac.uk/jro
JRO RMG RSS SOP11
Standard Operating Procedure (SOP) for
Audit of Research Studies
SOP ID Number
Version
Number
Effective Date
Review Date
15 November 2012
15 November 2014
JRO/RM&G/RSS SOP-11
V3.0
Author:
Name and Job Title
Emma Clark, Research Network Co-ordinator
Susan Kerrison, Head of Risk & Regulation
Patricia Galligan, Senior RM&G/QA Co-ordinator
Approved by
Date:
15 November 2012
Target Trusts
University College London Hospitals NHS Foundation Trust
Royal Free London NHS Foundation Trust
Target Audience
Joint Research Office
Related SOPs
JRO RMG RSS SOP 15 Study Oversight
SOP e-Document kept: G: \RM&G Team\NIHR RMG RSS SOPs\ Final;
S:RMG\NIHR RSS SOP
Director UCL SLMS Research Support Centre, Director R&D UCLH – Professor Monty Mythen
Managing Director UCL SLMS Research Support Centre – Dr Nick McNally
JRO/RM&G RSS /SOP- 11
Audit of Research Studies version 3.0
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Revision Chronology
Previous SOP ID Number
Version 1.0 and 2.0
Effective
Date
Reasons for Change
Draft
30/08/2012
Inclusion of comments from QA
Version 3.0
JRO RMG RSS SOP 11
Audit of Research Studies version 3.0
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Author
Emma Clark
& Susan
Kerrison
Patricia
Galligan
Joint Research Office
1. SUMMARY
This SOP describes the internal procedures that must be followed by members of staff at
the Joint Research Office (JRO) when auditing research studies. The SOP covers:
•
•
•
UCL sponsored non-CTIMPs (clinical trial of an investigational medicinal product)
All research sponsored by UCLH and Royal Free
Studies hosted at UCLH or Royal Free
Hosted CTIMPs will not be audited by JRO but sponsors will be requested to supply copies
of any audit reports of hosted studies. This process is outlined in the JRO RMG RSS SOP
15 Study Oversight.
For studies which are audited a risk based sampling frame will be used.
2. DEFINITIONS
Audit
A systematic, independent and documented process for obtaining
audit evidence and evaluating it objectively to determine the extent to
which the audit criteria are fulfilled.
ISO19011
Joint Research
Office (JRO)
The JRO is a partnership between University College London, UCL
Hospitals NHS Foundation Trust and the Royal Free London NHS
Foundation Trust.
Quality
Assurance
Refers to the planned and systematic activities implemented in a
quality system so that quality requirements for a product or service
will be fulfilled. It is the systematic measurement, comparison with a
standard, monitoring of processes and an associated feedback loop
that confers error prevention. This can be contrasted with Quality
"Control", which is focused on process outputs.
Sponsor
Individual, organisation or group taking on responsibility for securing
the arrangements to initiate, manage and finance a study. (A group of
individuals and/or organisations may take on sponsorship
responsibilities and distribute them by agreement among the
members of the group, provided that, collectively, they make
arrangements to allocate all the responsibilities in this research
governance framework that are relevant to the study.)
Standard
Operating
Procedure
(SOP)
Established procedure to be followed in carrying out a given
operation or in a given situation
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“Simple” or “Complex”
Any study where the following boxes are selected for screening question 2 on the NHS R&D
and NHS REC form should be deemed a “simple” study. Any other studies should be treated
as "complex".
•
Study administering questionnaires/ interviews for quantitative analysis, or using
mixed quantitative/qualitative methodology
Study involving qualitative methods only
Study limited to working with human tissues samples (or other biological samples)
and data
Study limited to working with data
•
•
•
3. PURPOSE and SCOPE
This SOP provides part of the study oversight required by the National Institute for Health
Research (NIHR) Research Support Services (RSS) Framework:
http://www.nihr.ac.uk/systems/Pages/RSS_Documents.aspx
It describes the internal procedures that must be followed by members of staff at the JRO
when auditing research studies. The SOP primarily covers the RM&G portfolio:
•
•
•
UCL sponsored non-CTIMPs
All research sponsored by UCLH and Royal Free
Studies hosted at UCLH or Royal Free
UCL sponsored CTIMPs including monitoring and audit are governed by a separate set of
SOPs. A list of published UCL sponsored CTIMP SOPs are available at:
http://www.ucl.ac.uk/jro/standingoperatingprocedures/.
Audits of the RM&G portfolio will consist of the following types of audit:
•
•
Routine audits
For-cause audit
The purpose of study audit within the scope of this SOP is to verify that systems are in
place to ensure:
a. The rights and well-being of human subjects are protected
b. The reported study data is accurate, complete, and verifiable from source
documents
c. The conduct of the study is in compliance with the approved study
protocol/amendments, with Research Governance Framework and with the
applicable regulatory requirements.
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4. RELATED SOPs
•
•
•
JRO RMG RSS SOP 2
JRO RMG RSS SOP 3
JRO RMG RSS SOP 6
•
•
•
•
•
•
JRO RMG RSS SOP 7
JRO RMG RSS SOP 8
JRO RMG RSS SOP 9
JRO RMG RSS SOP 12
JRO RMG RSS SOP 13
JRO RMG RSS SOP 15
Categorisation and Sponsorship of “simple” studies
UCL Sponsorship of “complex” studies
Setting up and controlling External Agreements for
Hosted Studies
Administration of the Research Passport Scheme
Reporting Amendments / Changes in Studies
Reporting Incidents and Events
Study Close Down and Archiving
Preparation of Site File
Study Oversight
5. JOINT RESEARCH OFFICE (JRO) POLICY
All SOPs produced from the JRO must be used in conjunction with local NHS Trust and UCL
policies and procedures. Where applicable there is also a requirement to include stakeholder
engagement as appropriately identified.
The JRO represents UCL, UCLH or Royal Free as the Sponsor and UCLH and Royal Free
as Participating Sites, depending on the type of research study. The JRO is responsible to
ensure that appropriate research management and governance processes are in place. The
RM&G SOPs will provide a quality assurance system for these requirements.
6. BACKGROUND
This SOP complies with:
•
•
•
Research Governance Framework for Health and Social Care 2005 (2nd Edition),
NIHR RSS framework
Principles of Good Clinical Practice (GCP)
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7. RESPONSIBLE PERSONNEL AND THEIR DUTIES
Personnel
Duties
•
1 Auditor
•
•
•
•
•
•
•
•
•
2 Chief Investigator
Principal Investigator (as
applicable)
•
Research Staff
•
3 Senior RM&G/QA Co-ordinator
•
•
•
•
4 Auditor
Senior RM&G/QA Co-ordinator
Head of Risk and Regulation
•
•
•
Assist with audits in developing tools,
conducting audits and drafting audit reports.
Using the risk assessment of “Complex” studies
as outlined in Appendix 1, select a sample of
studies, stratified as in section 8.1.1 Table 1
Prepares audit plan using the template
(Appendix 2) and checklist
Undertake audit visits arranged using the
agenda template (Appendix 3)
Produce individual audit reports for each study
using the template (Appendix 4) or modified as
necessary to suit the audit activities.
Corrective and preventive actions (CAPAs) will
need to be included within the audit report as
agreed by the CI/PI (as applicable).
Escalate any serious issues or risk highlighted
through audit
Prepares and presents audit reports using the
template (Appendix 5) and summaries to Risk
and Regulation Group
Inform of future audit activities for future
improvements
Comply with any audit visits and make available
any documentation requested.
Review the audit report to highlight any
corrective and preventative actions which
needed to be taken to improve compliance.
Address any corrective and preventive actions
in a timely manner.
Outline the audit programme for RM&G portfolio
i.e. non UCL sponsored CTIMPs.
Maintain a log of audit activity
Develop audit tools and templates
Allocation of audit work
Prepares summaries of audit reports and
reports of audits for discussion by Risk and
Regulation Group
Prepares summaries of audit reports for the
Sponsor Oversight Committee (SOC) and
Clinical Research Governance Committee
(CRGC)
Escalate any issues arising from audits to the
Risk & Regulation Group, Managing Director of
Research Support Centre/Director or Research
& Development through SOC or CRGC as
required
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5 Risk and Regulation Group
Reviews summaries of audit reports and audits.
6 Sponsor Oversight
Committee/Clinical Research
Governance Committee
Receives and reviews audit summary reports.
8. PROCEDURE
8.1
Routine Audits
8.1.1
Sampling frame
1. CTIMPs that are externally sponsored will not be included within the programme of
routine audit, unless there are particular audit/inspection findings in relation to quality
management systems that warrant it. For all externally sponsored non CTIMPs, a
10% sample may be included in routine audits.
2. Audits of sponsored studies will follow a risk-based approach. During the
sponsorship process, studies will be risk assessed according to JRO RMG RSS SOP
2 and JRO RMG RSS SOP 3. Studies are categories as “simple” or “complex”.
Within the “complex” category, studies are risk assessed according to Appendix 1
and divided into 4 categories:
Category 4 very high risk
Category 3 high risk
Category 2 medium risk
Category 1 low risk
Routine audits will be performed to prioritise with studies within category 4, followed
by 3, 2 and 1.
A ReDA report will be run to establish the sample to be audited. The sample will
consist of approved studies which are sponsored by UCL, UCLH, or Royal Free and
hosted non CTIMPs which are externally sponsored. The following will excluded:
•
•
•
Studies closed to recruitment
Studies in set up
Studies that have recently been audited or inspected
The sample should be stratified according to Table 1 below.
Table 1 Audit Sampling for Non-CTIMP Studies
Category
Sponsor
Study
Type
Audit %
1
External
NonCTIMP
10
Simple
5
10
2
3
UCL, UCLH and Royal Free
“Complex” Studies
10
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25
4
100
8.1.2
Audit Preparation
8.1.2.1 The auditor will draft an audit plan using the template (see Appendix 2) and develop
audit tools (questionnaire and checklist) according to the aim of the audit.
8.1.2.2 The study documentation contained within the R&D study file and ReDA will be
reviewed ahead of the audit to ensure events have been reported to the JRO. Where
possible the local annual progress report or REC Annual Progress Report will be
reviewed to ensure that amendments, adverse events, serious breaches of protocol
and other relevant events have been notified to the JRO. If any issues are highlighted
from this review these should discussed with the research team at the audit meeting.
8.1.2.3 For all study visits, the auditor should contact the CI/PI (as applicable) to notify of the
audit, provide an agenda using the template (see Appendix 3) and arrange a
mutually agreeable meeting time. The agenda will outline a list of the study
documentation which should be available for the visit. This should include the
documentation required in JRO RMG RSS SOP 13 “Site File”. Some of the key
documents contained within the investigator site file/study file are (but not limited to):
•
•
•
•
•
•
Recruitment log(s)
Consent Forms
Delegation Log(s)
Agreements
Honorary contracts
Any study specific additional requirements e.g. regulatory approvals
8.1.2.4 Where the study has been risk assessed as in “Complex “, Cat 3 or 4, the audit
preparation should include a review of the regulatory requirements. If any potential
regulatory issues have been identified during preparation these too should be
discussed with the research team at the audit meeting.
8.1.3
Audit Activities
8.1.3.1 The auditor will need to meet the appropriate members of the research team (the
auditees stated on the agenda) by way of an opening meeting to inform them of the
remit of the audit and also to ask any relevant questions within the questionnaire to
address the audit aim.
8.1.3.2 The auditor should review the study documentation and complete the audit checklist,
according to the audit remit as outlined in the agenda. The review should consist of
(but not exclusive to):
• review of the investigator site file/study file
• review of consent process
• adherence to protocol e.g. inclusion/exclusion criteria
• research team – delegation log, training, honorary contracts
• event reporting (amendments, adverse events, serious breaches of protocol)
• progress with recruitment
8.1.3.3 At the end of the visit the auditor should meet with the CI/PI (as applicable) and
research team and provide feedback on their findings. The auditor should provide
guidance (as necessary) and agree on specific corrective and preventive actions
(CAPAs) provided by the CI/PI. These CAPAs are to be completed within an agreed
timeframe to resolve any issues or risks highlighted during the visit.
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8.1.4
Reporting
8.1.4.1 After the visit, the auditor should prepare a report and action plan. A copy of this
report should be sent to the CI/PI (as applicable) within 2 weeks. This should be
reviewed and agreed by the investigator.
8.1.4.2 The auditor should ensure that the agreed actions have been completed by the CI/PI
(as applicable). The CI/PI should be given a minimum of 6 weeks to complete any
actions. An audit certificate should be issued to be stored in the investigator site
file/study file to confirm that an audit took place.
8.1.4.3 The auditor should record the agreed actions on the database and a copy of the audit
report should be filed both electronic and as paper record in the R&D study file.
8.1.5
Follow up/Escalation
8.1.5.1 The auditor should follow up with the CI/PI (as applicable) to ensure the actions have
been completed in the agreed timescales. Once the actions have been completed
this should be updated on the audit database.
8.1.5.2 Failure to complete CAPAs within the agreed timescales, after numerous reminders,
will be considered as misconduct and will need to be escalated through the Risk and
Regulation Group, Sponsor Oversight Committee (SOC), appropriate R&D
Committee and Clinical Research Governance Committee (CRGC) as required.
8.1.5.3 A summary of the audits and key findings should be presented to the Risk and
Regulation Group and SOC. Any findings of concern that require escalation should
be brought to the Risk & Regulation Group, Managing Director of Research Support
Centre/Director or Research & Development through SOC or CRGC as required.
8.1.5.4 If any serious breaches are highlighted through any audit activities, these are
reported on Datix in line with JRO RMG RSS SOP 9 Reporting Incidents and Events.
8.2
For-Cause Audit
8.2.1
Where there are concerns in relation to the conduct of a study a for-cause audit may
be required as part of an investigation to better understand the root of the concern(s).
Incidents, serious breaches of GCP, internal/external audits or inspections may also
prompt for-cause audits of other studies within the investigator’s portfolio of research.
Findings from the for-cause audit may help to establish the extent of the concern.
8.2.2
The process outlined in sections 8.1.2 Audit Preparation, 8.1.3 Audit Activities, 8.1.4
Reporting and 8.1.5 Follow up/Escalation as above should be followed.
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9. IMPLEMENTATION & TRAINING
This SOP will be implemented according the procedure agreed by the Approvals
Development Group. Training on the SOP can be provided as necessary by the Senior
RM&G/QA Co-ordinator.
10. PUBLICATION & COMMUNICATION
This SOP is published on the JRO website: http://www.ucl.ac.uk/jro and can also be
found on the UCL S: drive, UCLH G drive and Royal Free Z drive.
The fully approved and signed master copy is also stored in a designated binder within the
JRO. Any further changes to the SOP after this point will have to be undertaken through the
Document Control System.
11. REVIEW
SOPs will be reviewed every 2 years unless an earlier review is required.
12. REFERENCES
JRO Website
http://www.ucl.ac.uk/jro
Research Governance Framework 2005 (2nd Edition)
http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/@dh/@en/documents/digital
asset/dh_4122427.pdf
NIHR RSS Framework (including Appendix 1 – Glossary of Terms and Acronyms)
http://www.nihr.ac.uk/systems/Pages/RSS_Documents.aspx
13. APPENDICES
Appendix 1 – Risk Assessment of “Complex” Studies
Appendix 2 - Audit Plan Template
Appendix 3 – Audit Agenda Template
Appendix 4 – Individual Audit Report Template
Appendix 5 – Audit Report Template
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14. SIGNATURE
URE PAGE
Author:
Name / Job Title
Patricia Galligan, Senior RM&G/QA Co-ordinator
Signature /
Date:
Reviewed by:
Name / Job Title
Susan Kerrison, Head of Risk & Regulation
Signature /
Date:
Authorised by:
Name / Job Title
Rajinder Sidhu, Deputy Director of Research Support Centre
Signature /
Date:
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Appendix 1 - Risk assessment of “complex” studies
CATEGORY:
Intervention
Medical device
1
2
Limited checks action required before
sponsorship agreed
Standard intervention
Slight deviation from
used in routine practise
normal practice or a
deviation that has been
used before.
Medical device that is CE
marked and used within its
product indication.
Medical device that would
be unlikely to cause any
consequences as a direct
result of not being
operated correctly or
failing to operate e.g. tens.
No training required or self
training. Research team
are trained and
experienced in using the
device as part of clinical
care.
CE mark outside the
product indication.
Medical device that would
have a significant impact
on patient care or cause
temporary adverse health
consequences should they
not be operated correctly
or fail in operations e.g.
vital signs monitoring
equipment .
Self training by user
suitable training can be
sought from product
instruction and self
assessment from the use.
3
4
Full set up procedure before sponsorship agreed
Clinical intervention that is
a significantly different to
routine practice. Inclusion
of a combination of
interventions
Non CE marked device
Novel intervention that is
highly invasive or
combination of
interventions that have not
been previously been
used within the disease
group before.
No CE marked device
Medical devices that have
the potential to cause
serious adverse
consequences or death
should they not be
operated correctly or fail in
operation.
Combination of medicinal
product and medical
device.
Competency assess
training (competency
based training with either
the trust or the
manufacturer associated
with some form of
assessment in practice or
Specialist course (rigorous
training with competency
based assessment )
Clinical Directors are
responsible for ensuring
that the confirmation of
training is provided by all
staff and that this notified
to the medical device
training co-ordinators in
the dept of medical
physics and
bioengineering
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Team using the device
have no training in the use
of the device as is novel.
Appendix 2 - Audit Plan Template
Draft audit plan Sampling Draft audit tools and email 4 send email to Chief Investigator/Principal Investigator (as applicable) 6 Arrange meeting with investigators to explain the aims and procedures of the audit Prior document review 7 opening meeting with investigator and/or research team investigator site file review 8 9 Reporting Audit preparation 1 2 3 5 10 11 12 13 14 Scope Milestones Responsibility Timeframe Audit Activities close out meeting with investigator and research team write up findings resolution of responses by all parties final report Prepare paper for appropriate Committee Review and oversight of actions and responses to ensure they are resolved Aim Method JRO RMG RSS SOP 11
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Appendix 3 – Audit Agenda Template
Joint Research Office
<Insert Audit Title>
Aim
Scope
Criteria
nd
Research Governance Framework 2005 (2 Edition)
Conditions outlined within the notice of favourable ethical opinion letter
Standard Operating Procedure
Principles of Good Clinical Practice
SI 2006:1928
SI 2004:1031
ISO19011
Auditees
Auditors
Date of audit
Reporting
Timeframe
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Appendix 4 – Individual Audit Report Template
Joint Research Office
<Insert audit title>
Audit Report 2012
Audit Details
Auditor:
Date Conducted: <Insert Date> 2012
Auditee(s):
Trial Information
Sponsor:
Chief Investigator:
Principal Investigator:
R&D ID:
UKCRN ID:
EudraCT number:
REC Reference:
Title:
Executive Summary
Summary of observations and findings.
The most noteworthy finding(s) was/were as follows:
Finding 1:
Finding 2:
Finding 3:
Classification of findings
e.g. Compliance or non-compliance with GCP,
Conformity or Non-Conformity to SOP
e.g. Critical, Major or Minor according to MHRA guidelines
Source: GCP Report Template Effective 15 November 2010 and SOP C006/07 “Reporting of GCP Inspections”
http://www.mhra.gov.uk/home/groups/is-insp/documents/websiteresources/con2033551.pdf
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Introduction
Summary of the purpose of the audit, specifics about the audit conduct and any
relevant background or supplemental information.
Observations and findings
Include observations and findings including responses, as appropriate (these may be
presented by level of classification).
Finding 1:
Response 1:
Corrective Actions 1
Date
Name of person
Preventative Actions 1
Date
Name of person
Corrective Actions 2
Date
Name of person
Preventative Actions 2
Date
Name of person
C1.1
C1.2
P1
Finding 2:
Response 2:
C2.1
C2.2
P2
Finding 3:
Response 3:
Corrective Actions 3
Date
Name of person
Preventative Actions 3
Date
Name of person
C3.1
C3.2
P3
Authorisation Signatures
<insert auditor name>
Name:
Title:
Name:
Title:
Date:
Signature:
Date:
Signature:
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Appendix 5 – Audit Report Template
Joint Research Office
<Insert Audit Title>
Audit Report
Template version 1 April 2012
<insert Author>
Contents
Page
1.
2.
3.
4.
5.
6.
7.
8.
9.
2
Executive Summary
Background
Aims
Method
Findings
Summary of Findings
Recommendations
References
Appendices
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1. Executive Summary
2. Background
3. Aims
4. Method
5. Findings
6. Summary of Findings
7. Recommendations
8. References
9. Appendices
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