Clinical Trial Management
UoB QMS reference number: UoB-CLN-CTM-SOP-001
Purpose:
The purpose of this document is to explain how clinical trials should be conducted within the
University of Birmingham (UoB). It maps out all aspects of clinical trial management, and explains
how different departments within the UoB work together.
Scope:
All UoB staff members involved in clinical trials sponsored and managed by the UoB have to follow
this procedure, focussing on those aspects of this procedure that cover their day to day work. Where
clinical trials are (co-)sponsored and/or (partially) managed by another institution, this procedure
should be followed as far as possible.
Implementation plan:
The implementation period is 2 weeks after the completion date to allow for the procedure to be
embedded in local structures.
Thereafter  For new trials identified prior to any grant application, follow the processes from ‘Idea’
onwards.
 For trials in the phase of grant application, follow the processes from ‘Award receipt &
distribution’ onwards, and follow any previous processes as far as possible.
 For trials in their set up phase, ensure any regulatory requirements are met, follow the
processes ‘Site initiation to archiving’ and onwards, and follow any previous processes as far
as possible.
 For ongoing trials and trials in the closure phase, ensure any regulatory requirements are met,
follow the process ‘Amendments’, and supply information to Sponsor as requested on the
process map ‘Site initiation to archiving’.
Date of implementation:
01-Jan-2016
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Document code:
UoB-CLN-CTM-SOP-001
Version no:
4.0
Print Date:
16-Mar-16
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Clinical Trial Management
Responsibilities:
Given the complexity of this procedure, a colour coding has been used to identify individuals/teams
and their role in the procedure. Below is a summary of their responsibilities and the colour coding
used for the individual/team. In addition, where an individual/team other than the CI is to undertake an
activity, this will be written in italics, and the relevant individual/team is mentioned in the actual text.
Chief Investigator or delegate
The Chief Investigator (CI) is responsible for the initiation, conduct and completion of the clinical trial.
They may however delegate tasks. Delegates may include trial team members, who may be based in
a Clinical Trials Unit (CTU). Where the CI does not hold a contract with the UoB and the UoB takes on
trial management, it would be expected the CI works together with a UoB Lead, who may also be
delegated certain tasks.
Specific tasks are indicated in the procedure in black text.
Research Support Partner, Research Facilitator, Research Administrator
Each College within the UoB has a Research Support Partner, who works closely together with the
College’s Director of Research and Knowledge Transfer, contributing to the College’s Research and
Knowledge Transfer strategy and dealing with associated matters. The Research Support Partner
may take on the role of Research Facilitator and/or may manage a team to include Research
Facilitators. The team supports research in the College by functioning as the first point of contact,
both internally and externally, for advice and assistance with all research-related issues. The team
also provides information to their researchers regarding research funding, and provides an essential
interface with relevant corporate services.
In the College of Medical and Dental Sciences (MDS), the team includes a Research Administrator (a
central administrative post). In the College of Life and Environmental Sciences (LES) the post of
Research Administrator is covered by the Research Support Partner.
Specific tasks are indicated in the procedure in green text.
Clinical Research Compliance Team
The Clinical Research Compliance Team forms part of the MDS Research and Knowledge Transfer
(R&KT) Office, and is responsible for developing an infrastructure for researchers involved in clinical
research, helping to ensure clinical research projects and in particular clinical trials are conducted in
line with any applicable regulations, international standards and University standards. This is done
through the development of the Quality Management System (QMS), monitoring, and responsibilities
relating to Sponsor oversight such as audits and quality checks.
Specific tasks are indicated in the procedure in red text.
Research Governance Team
The Research Governance Team (RGT) is responsible for Sponsorship decisions and confirmation of
Sponsorship on behalf of the UoB, signing-off any applications for approval/authorisation as Sponsor
representative, issuing Trial Specific Template Site Agreements, and for maintaining Sponsor
oversight. The Research Governance Team is also responsible for processing any requests for
clinical trial insurance via their Research Insurance Administrator.
Specific tasks are indicated in the procedure in light blue text.
Research Finance Office
The Research Finance Office is responsible for providing staff costs and advice on funder rules for
research applications, setting up trial accounts, and all other pre- and post-award financial
administration.
Specific tasks are indicated in the procedure in purple text.
Research Ethics Team
The Research Ethics team is responsible for the operation of the University’s internal ethical review
processes, including the administration of the UoB Ethical Review of Research Self Assessment Form
(SAF) and the co-ordination of applications requiring further review by an internal ethical review
committee.
Specific tasks are indicated in the procedure in dark blue text.
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Clinical Trial Management
Research Contracts Team
The Research Contracts team is responsible for drafting, reviewing and negotiating contracts with
funders and other collaborating parties, ensuring that the University and individual researchers are
protected from contractual risks and liabilities. The team is also responsible for approving the final
agreement for signing by an authorised signatory (usually the Deputy Director of Finance or Head of
Research Support Group).
Specific tasks are indicated in the procedure in orange text.
Procedure:
Explanatory notes
 The procedure consists of several flowcharts. The first flowchart is a summary; with each
coloured box being detailed further in subsequent flowcharts:
o The ‘Pre-award clinical research governance check’ flowchart and links are highlighted in
pink
o The ‘UoB procedures – award receipt and distribution’ and ‘UoB procedures – towards
account set up’ flowcharts and links are highlighted in orange
o The ‘Trial set up’ flowchart and links are highlighted in green
o The ‘Site initiation to archiving’ flowchart and links are highlighted in blue
o The ‘Amendments’ flowchart and links are highlighted in yellow
 Within the UoB different teams/offices are responsible for undertaking specific tasks relating
to clinical trials. Average timelines have been added to the flowcharts to create clarity to the
CI and their team as to when they can expect results, and when it would be appropriate for
them to check on the progress with the relevant team/office.
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Clinical Trial Management
Procedure summary
Across the duration of the trial:
o Adhere to the applicable
regulations, standards and
guidelines (see references)
o Follow the Research Quality
Manual and the UoB Quality
Management System for
Clinical Trials; documents can
be found on the Clinical
Research Compliance Team
webpage (see references
below)
o Ensure appropriate levels of
staffing are in place
o Ensure staff are appropriately
qualified and trained including
training on GCP and that
qualification and training is
documented using UoB-GENTRN-SOP-001 Training SOP,
and see also the BRTC
website for training
information.
o When suspecting fraud, follow
the UoB Code of Practice for
Research; see references for
additional information
o Ensure appropriate version
control, tracking and
maintenance is applied to
essential documents; see
UoB-CLN-ESD-SOP-001
Essential Documents for more
information
Idea worked up in
grant proposal
Pre award clinical research
governance check
(See flowchart ‘Pre-award clinical
research governance check’)
Grant award
received
Trial set up
(See flowchart
‘Trial set up’)
UoB procedures
(See flowcharts ‘UoB procedures
– award receipt and distribution’
and ‘UoB procedures – towards
account set up’)
Site setup and initiation
(See flowcharts ‘Trial set up’
and ‘Site initiation to
archiving’)
Amend the project
(See flowchart
‘Amendments’)
YES
Recruitment start
(See flowchart ‘Site
initiation to
archiving’)
Trial completion
(See flowchart ‘Site
initiation to
archiving’)
Document code:
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Any
amendments to
project?
NO
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Clinical Trial Management
Pre-award clinical research governance check
o
o
o
o
Work up idea to grant proposal
Ensure all required costs are worked up in the final costs, including excess treatment costs
Where a CTU is to be involved, ensure their processes relating to new business are followed
For MDS trials, complete the ‘College of Medical and Dental Sciences Application for Research Grants and
Contracts Approval Form’ (Pink Form); see ‘related documents’ below
For MDS trials, see for further guidance the MDS R&KT Office website (link below)
As part of grant proposal review on College level, the Research Support Partner will review
proposal against questions as listed on the Pre-award Research Governance Checklist (see
‘related documents’ below). The checklist will prompt the need for further review of the RGT to
ensure the ability of the UoB to Sponsor and/or insure the project. The Research Support Partner
will maintain proof that the review was conducted.
Note that for MDS this process is part of the Pink Form review process.
Is further
review by the RGT
required?
NO
YES
YES
Continue grant submission
process following College
specific procedures; for
MDS see for further
guidance the R&KT Office
website (link below).
When awarded, see ‘UoB
procedures-award receipt
and distribution’
Research Support Partner will forward to
RGT via E-mail
researchgovernance@contacts.bham.ac.uk:
· Relevant trial information e.g. grant
proposal
· Issues identified
Research Support Partner
will inform Chief Investigator
of need for referral and
possible inability of UoB to
insure and/or provide
sponsorship and thus to
accept any awards. Chief
Investigator can submit or
delay until issues are
clarified.
RGT will assess UoB’s ability to sponsor
using pre-defined Sponsorship Review
Criteria and/or provide insurance.
See also related documents below.
Sponsorship
and/or insurance cover
possible?
YES
YES, with proviso
NO
RGT will inform Chief
Investigator and
Research Support
Partner of outcome
RGT will inform Chief
Investigator and
Research Support
Partner of outcome
Submit grant
When awarded, see ‘UoB
procedures-award receipt
and distribution’
End of project
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Clinical Trial Management
UoB procedures – award receipt and distribution
Award contract
received by CI
Award offer received
Check award offer and conditions, and where applicable
identify aspects where negotiation is required
NO:
Negotiate award
offer with funder
Award offer
accepted?
YES
o
o
o
o
Award letter, or contract as applicable, sent by CI to Research Finance Office
For LES trials, forward the award letter to the LES Research Support Partner
Ensure the information as captured on the Pre-award Research Governance
Checklist is up to date, and inform the MDS Research Administrator/LES
Research Support Partner accordingly (note that in MDS the information is
embedded in the Pink Form)
For trials that are to be externally sponsored, confirm to the MDS Research
Administrator/LES Research Support Partner as to who will take on external
sponsorship
For MDS trials only:
Upon receipt of the award letter or award contract as applicable, the Research Finance
Office will send an E-mail to the MDS Research Administrator typically within two
working days with a copy to the CI (if UoB employee) or UoB Lead and the Research
Facilitator:
o
Informing of the grant being awarded
o
Requesting if a governance referral is required
o
If required, reminding the CI/UoB Lead to complete the UoB Ethical Review of
Research Self Assessment Form (SAF)
o
Including the Pink Form reference number
Typically within 5 working days of receipt of the E-mail from the CI/UoB Lead or
delegate confirming the information as captured on the Pre-award Research
Governance Checklist is up to date, and for MDS an E-mail receipt of the Research
Finance Office and for LES receipt of the award letter, the MDS Research
Administrator responds to email confirming if a governance referral is required and
forwards the confirmation from the UoB CTU/UoB Lead as to who will take on
sponsorship, copying in RGT.
o
For MDS trials they will forward the Pink Form to include the up to date
information as captured in the Pre-award Research Governance Checklist
o
For LES trials, where not yet done so, they will send an up to date completed Preaward Research Governance Checklist together with the grant application form
o
For LES trials only, they will remind the CI/UoB Lead to complete the SAF
RGT conducts governance
referral if required and sends
confirmation to Research
Finance Office, copying in
MDS Research Administrator
o
o
o
o
CI completes Request for Contract Services form and
sends draft/new contract to Research Contracts Team,
copying in the Research Finance Office
Research Contract Team reviews draft/new contract,
negotiates and resolves any issues as applicable and
confirms to Research Finance Office.
Continue project set up:
(see also flowchart ‘Trial set up’)
Consider arranging a meeting/meetings with key
personnel within the UoB (including UoB Procurement if
required) to discuss the project in more detail with the aim
to create clarity for all parties of what is expected of them.
Examples include:
o
Trials with complex 3rd party(ies) set up – liaise with
representative of the Research Contracts Team, the
RGT and (for contracts/agreements with a financial
aspect) the Research Finance Office
o
Complex trials, e.g. international trials or trials where
the Investigational Medicinal Product is
manufactured locally – liaise with a representative of
the RGT and the Clinical Research Compliance
Team or delegate
Start trial set-up (see also flowchart ‘Trial set up’):
Obtain and agree any further required contracts and sub-contracts
Initiate any required procurement processes; this applies to any purchase on an individual basis being
equal to or more than £10,000.00 ex VAT (for Approved Suppliers) or £501 ex VAT if there is no
Approved Supplier – see References for link to UoB Procurement processes
Book existing estates and facilities
Work up any new vacancies with Human Resources; the Research Finance Office will sign off any
vacancies at least to advert upon receipt of the award letter.
Research Finance Office will set up an account typically within 5 working days from receipt of a fully signed contract or in case there is no contract:
o
Award letter and award breakdown
o
Confirmation that either no governance referral is required, or that RGT have completed a governance referral and is satisfied
o
Notification of completed Self Assessment Form and Ethics Registration Number and
o
Confirmation that insurance can be obtained
They will send out a Research Activation (RA1) form to the CI and/or UoB Lead, Trial Coordinator, MDS Research Administrator or LES Research
Support Partner, Research Facilitator, Head of School and relevant administrative staff to inform them of the account number within 5 working days of
account being set up.
Note that when other awards are received for the same project, the Research Finance Office can link these awards. In this case ensure to inform the
Research Finance Office at the moment the grant is awarded as they need the 5 digit project number.
See Flowchart ‘UoB Procedures – towards account set up’
Document code:
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Clinical Trial Management
UoB procedures – towards account set up
Continue from previous flowchart
UoB Ethics review
Complete UoB SAF. Note that where CI does not have a UoB contract, the UoB Lead completes the SAF, otherwise the CI completes the SAF. (Note:
for clinical trials a Trial Coordinator may complete the SAF for the CI/UoB Lead, provided the CI/UoB Lead is listed as the CI/UoB Lead on the actual
SAF).
If you do not already have Sponsorship then the completion and signing of the SAF constitutes the sponsorship application form.
The Research Ethics Team will create an Ethics Registration Number (ERN), and will inform the applicant (and any other contacts added in the E-mail
box), the Research Finance Office and RGT typically within 3 working days.
Arrange for sponsorship and assess if insurance/indemnity cover can be obtained:
o
Where working with an external (co-)Sponsor, follow their local procedures and ensure it will be clearly documented what duties are taken on by
UoB staff, e.g. via contract, protocol, delegation of duties log and ensure this information is sent to the RGT when available
o
For UoB (co-)Sponsored trials the process for arranging sponsorship starts up automatically upon receipt of the project information (via MDS
Pink Form or grant application form) and the up to date information as captured in the Pre-award Research Governance Checklist (for MDS
embedded in the Pink Form).
o
Download the CI declaration form as directed by the SAF.
The RGT will ascertain if (co-)Sponsorship can be provided using the Sponsorship Review Criteria (see ‘related documents’ below). Note this may be
the second time the RGT reviews the trial; where this is the case the RGT will refer to the previous review and assess any changes in the trial since
the previous review.
Where (co-)Sponsorship cannot be provided, the RGT will liaise with the CI/UoB Lead to resolve any issues. If sponsorship can be provided, they will:
o
Confirm insurance cover can be obtained and arrange for a valid quote if the previous quote has expired.
o
Assign a Research Governance (RG) number to the project (if not already assigned)
o
Send an E-mail to the CI, UoB Lead, Trial Coordinator, Research Administrator, Research Finance Office and Research Facilitator typically
within 3 working days, quoting the RG number
Arrange for funding related contracts/agreements to be put in place
Complete a ‘Request for contract services’ form as far as possible, including for external Sponsors requesting a Delegation of Sponsor Duties
Agreement and for external CIs a CI agreement, and forward to the Research Contracts Team via newcontracts@contacts.bham.ac.uk; see also the
Research and Commercial Services website. For funding related contracts/ agreements initiated by third parties, ensure to progress them until receipt,
and upon receipt, forward these to the Research Contracts Team, ensuring that the UoB Procurement processes have been followed (see References
for link)
The Research Contracts Team will develop the required contracts and agreements in consultation with the RGT where required; a first draft is sent
typically within 12 working days of receiving the completed ‘Request for contract services’ form. Upon agreement by the external party, the Research
Contracts Team will forward the funding related contracts/agreements to the Research Finance Office.
The Research Finance Office will arrange for sign off of the funding related contracts/agreements upon receipt of:
o
Award breakdown
o
Confirmation that governance issues have been resolved
o
Notification of completed SAF and ERN
The Research Finance Office will forward the electronic version of the funding related contract typically within 2 working days of receipt to the CI and/
or UoB lead, Trial Coordinator, Research Facilitator, Research Contracts Officer and RGT
Note that a template Site Agreement will be developed by the RGT and forwarded to the CI at the time of Sponsorship confirmation; see further.
Where a UoB CTU is involved, the UoB CTU may take on the development of the template Site Agreement, whereby the RGT takes on the role of
reviewer.
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Clinical Trial Management
Trial set up
Receipt of award letter by
CI/UoB Lead (continued)
Arrange for peer review of the trial where this was not part
of the review process of the funding body
o
o
Start risk assessment process
For gene therapy trials ensure a gene therapy specific risk assessment is performed, including liaising with
the Biological Safety Officer
For Clinical Trials using Investigational Medicinal Products (CTIMPs), refer to the MHRA Risk-adapted
Approaches to the Management of CTIMPS; see references
Develop documents required for favourable opinion/authorisation:
o
For CTIMPS, obtain EudraCT number
o
Register trial on public registry
o
Documents to be handed out to subjects, e.g. Quality of Life questionnaires and diaries
o
Protocol
o
Patient Information Sheet, Informed Consent Form, GP Letter
Refer to UoB-CLN-ESD-SOP-001 Essential Documents development and maintenance
Ensure sponsorship and insurance cover is confirmed
For external Sponsor, follow their local processes; note the UoB still needs to ensure appropriate insurance cover is in place. UoB
staff may be able to sign as Sponsor representative; this has to be formally documented e.g. in a Delegation of Sponsor Duties
agreement
o
Forward the following to the RGT:
·
The completed Clinical Trials Task Delegation Log; see UoB-CLN-CTM-QCD-002 Clinical Trials Task Delegation Log
·
The completed Risk Assessment and Monitoring Plan; see UoB-CLN-TQM-SOP-001 Trial Quality Management
·
Any finalised Information Sheets/ Consent Forms and Protocols for insurance purposes; see UoB-CLN-ESD-SOP-001
Essential Documents development and maintenance
·
For trials managed outside a UKCRN registered CTU, any other documents that are to be submitted to Research Ethics
Committee (REC), Competent Authority (CA), R&D department etceteras; see UoB-CLN-ESD-SOP-001 Essential Documents
development and maintenance
·
The expected recruitment start date and trial completion date
·
A clarification as to whether or not the UoB only takes on a Coordinating Centre role, and if so, who is the Sponsor
·
A fully signed CI declaration
o
When using the Integrated Research Application System (IRAS) for obtaining favourable opinions/approvals/authorisations,
submit the forms for authorisation by the RGT
For UoB Sponsored trials, the RGT will typically within 10 working days of receiving the above mentioned information:
o
Perform a review of the project, including the Clinical Trials Task Delegation Log, the Risk Assessment and the Monitoring Plan,
and sign or respond to the application forms as UoB Sponsor representatives via the Integrated Research Application System
(IRAS); where further updates are required, these will be reviewed typically within 3 working days of receipt of the updates.
o
Send the Sponsorship confirmation letter and insurance confirmation letter via E-mail to the CI, UoB Lead, Trial Coordinator,
Research Administrator, Research Finance Office and the Research Facilitator
The Research Insurance Administrator will liaise with the UoB Insurers to formalise insurance cover.
o
o
o
o
o
o
o
o
o
o
o
o
o
o
o
o
Trial set up
Ensure all processes detailed below ‘Procedures through from trial set up to archiving’ are followed
Engage the NIHR Coordinated Network Support Service (see references for contact details); note this can be done prior to portfolio
adoption
Set up human tissue collection procedures where applicable; see references for further guidance
Where primary or secondary endpoints are to be assessed in research labs, consider the need for the research laboratory to work in line
with the MHRA guidance for Good Clinical Practice in the laboratory; see references
Finalise procurement processes as required
Finalise booking of Estates and Facilities as required
Where UoB substantive post holders perform clinical management roles in a trust, ensure that appropriate trust honorary attachments are
in place
Site selection and initial training; see UoB-CLN-SMA-SOP-001 Site Management
Obtain favourable opinions/authorisation:
Apply for UK National Institute for Health Research (NIHR) portfolio adoption using the portfolio adoption form. If accepted apply for approvals
using the Coordinated System for gaining NHS Permission (NIHR CSP)
Clinical Trial Authorisation for CTIMPs
REC favourable opinion
NHS permission; consider obtaining NHS permissions in a phased approach to facilitate the NIHR networks being able to obtain the set target of
having the first patient in the trial 30 days after obtaining NHS permission
Consider Administration of Radioactive Substances Advisory Committee (ARSAC) / The Ionising Radiation (Medical Exposure) Regulations
2000 (IRMER) requirements
Site set up
Including finalising the Clinical Trial Agreement(s), also known as ‘Clinical Study Site Agreement’ or ‘Site PI Agreement’
Provide training to site staff, including informing the sites of serious breach reporting requirements; see UoB-CLN-SMA-SOP-001 Site Management
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Clinical Trial Management
Site initiation to archiving
Site initiation
See UoB-CLN-SMA-SOP-001
Site Management
Subject registration /
randomisation
o Where the actual
registration/randomisation
is expected to be earlier
than the date listed in the
IRAS form, ensure the
insurance cover start date
is amended accordingly
by liaising with the RGT
Research Insurance
Administrator.
o Inform the RGT of the
date that the first subject
was enrolled in the trial
See UoB-CLN-CTM-SOP-002
Randomisation and Blinding
for further information
Data Management
see UoB-CLN-DMA-SOP-001
Data Management
Procedures ongoing from site initiation to trial closure:
Ensure all processes detailed below ‘Procedures through from trial set up to archiving’ are
followed
o Supply information to Sponsor as requested.
·
For UoB (co-)sponsored trials send a copy of the following reports at the time of reporting to
the REC/CA:
§ Any major safety issues, e.g. urgent safety measures; send a copy to the RGT
§ Any Suspected Unexpected Serious Adverse Reactions (SUSARs; for CTIMP) or
Unexpected and Related Serious Adverse Events (non-CTIMPs); send a copy with a
note from the CI explaining how this case impacts the safety profile of the study to the
RGT
§ Annual Safety Report (for non-CTIMPs), DSURs (for CTIMPs) and Annual Progress
Report; send a copy to the RGT
§ Any Serious Breaches; send a copy to the Clinical Research Compliance Team. Note
that where these affect patient safety these will be forwarded to the Research Insurance
Administrator
§ MHRA Compliance Report as completed by UoB CTU; send a copy to the RGT
·
Any other information sent to and from the REC and/or MHRA, with confirmation that any
conditions as set out by the REC or MHRA have been met
·
Confirmation of the correctness of the Clinical Trials Task Delegation Log, on an annual
basis
·
Forward Audit/Inspection reports to the Clinical Research Compliance Team within 3
working days of receipt of the report, and subsequent response reports within 3 working
days of completing these reports
§ For UoB CTUs- only send copies of audit/inspection reports where UoB CTU as
coordinating centre has been audited/inspected
§ For independent CIs – send any audit/inspection report relating to the trial (either at site
or at coordinating centre)
Where the UoB is ( co-) Sponsoring the trial, the UoB will maintain Sponsor oversight via activities
executed by the Clinical Research Compliance Team (e.g. Via Sponsor Support Visits and Audits)
and Research Facilitators and the RGT; for CTIMPs activities will be reported to the CTOC. Further
information may be requested from the CI and their team to allow for appropriate oversight.
o
Review the quality of the trial on a regular basis
For Serious Breach reporting
refer to UoB-CLN-SBR-SOP001 Serious Breach reporting
Continue trial
as planned
NO
Following
review of the quality of
the trial, were there any
issues noted?
YES
Follow up on issues until resolution, including:
o Consider need for changes in trial design (see flow ‘Amendments’)
o Consider need for changes in the systems that may be set up to review the trial quality
o Consider need for changes in resource allocation
Site closure
Trial Closure
Inform the RGT of the date the last subject completed trial treatment
For CTIMPs submit a “declaration of end of a clinical trial” form within the required timelines and provide a copy to the RGT
For non-CTIMPs submit a “NRES declaration of the end of a study” form within the required timelines and provide a copy to the
RGT
The Research Insurance Administrator will liaise with the UoB Insurers to ensure the insurance cover end date is amended accordingly.
See UoB-CLN-EOT-SOP-001 End of Trial
o
o
o
o
o
Trial Reports
Send a clinical trial summary report to the REC and for CTIMPs to CA within the required
timelines and provide a copy to the RGT
Inform Principal Investigators and participants of trial results
Archiving
See UoB-CLN-ARC-SOP-001 Archiving
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Clinical Trial Management
Amendments
Changes in the trial or
its organisation
Review the Risk Assessment and
update where required
Consider how the changes in the trial will impact on previously agreed
resources, roles and procedures
o
Sponsorship, e.g. change of external Sponsor or UK CI location
o
Insurance and Indemnity cover
o
Contracts and agreements
o
Trial supplies and labelling procedures
o
Human tissue collection procedures
o
Primary/secondary endpoint assessments performed in a research laboratory
If required, update funding and finance:
o
Perform Costing as covered in flowchart ‘full application’
o
Note that for additional funding requests in MDS a copy of the original Pink Form can be used
o
Note that when other awards are received for the same project, the Research Finance Office can link these awards; in this case inform the
Research Finance Office accordingly.
If required, update documents required for REC favourable opinion/CA authorisation/NHS permission and obtain favourable opinion/
authorisation/NHS permission, e.g.:
o
Protocol
o
Information Sheet and Consent Form
o
GP Letter
o
Documents handed out to patients, e.g. Quality of Life questionnaires and diaries
If required, update information on the following topics either in trial specific guidelines or in the protocol:
o
Plan for statistical analysis
o
Management of trial quality, including monitoring, quality checks, ...
o
24 hour emergency coverage procedures (site/coordinating centre)
o
Unblinding procedures
o
Registration/Randomisation procedures
If required, update data collection tools:
o
Case Report Form
o
Trial Master File and Investigator Site File
o
Serious Adverse Event form
o
Registration/Randomisation procedures
If required, update trial delegation documentation:
o
Clinical Trials Task Delegation Log
o
Site Signature and Delegation Log
If required, update/archive/add any contracts/agreements as appropriate, including the Clinical Trial Agreement (also known as ‘Clinical Study Site
Agreement’ or ‘Site PI Agreement’.
o
o
o
Ensure relevant parties are informed as required, including but not limited to:
Sites, e.g. Following protocol amendment, amendment to Information Sheet and Consent Form,
changes to the Case Report Form
Sponsor, e.g. protocol amendment or changes to the Clinical Trials Task Delegation Log. For UoB
Sponsored trials, the RGT will perform a review of the project and sign or respond to any
amendment forms as UoB Sponsor representatives typically within 5 working days of receiving the
application via IRAS.
UoB Research Insurance Administrator following:
§
Change in number of patients to be recruited
§
Changes to treatment and/or treatment schedule
§
Expansion to other (newly identified) countries
§
Expansion of the eligibility criteria now to include pregnant women
§
Expansion of the eligibility criteria now to include under 5 year olds
Note that changes in the trial may impact the fees for the insurance cover. Obtain confirmation of
the Research Insurance Administrator following any relevant changes as this will ensure
appropriate cover is still in place.
Document code:
UoB-CLN-CTM-SOP-001
Version no:
4.0
Provide additional training:
o
Staff
o
Site staff
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Procedures required from trial set up through to archiving:
Ensure the following procedures are followed throughout the trial, from trial set up to archiving; SOPs
referenced are available at: http://www.birmingham.ac.uk/research/activity/mds/mdsrkto/governance/Clinical-Trials-QMS.aspx:
 Set up and maintain a Data Monitoring Committee and other committees as appropriate, e.g.
Trial Steering Committee, Trial Management Group; see UoB-CLN-TQM-SOP-001 Trial
Quality Management
 Set up and maintain a Trial Master File and Investigator Site Files; see UoB-CLN-ESD-SOP001 Essential Documents development and maintenance
 Develop Case Report Forms; see UoB-CLN-ESD-SOP-001 Essential Documents
development and maintenance
 Set up data management and tracking systems; see UoB-CLN-TSM-SOP-001 Trial Systems
development and management
 Ensure the following topics are covered either in SOPs, trial specific guidelines or in the
protocol:
o Plan for statistical analysis where applicable; see UoB-CLN-STA-SOP-001 Statistics
o Management of trial quality, including monitoring and quality checks; see UoB-CLN-TQMSOP-001 Trial Quality Management
o 24 hour emergency coverage procedures (site/coordinating centre); see UoB-CLN-CTMSOP-002 Randomisation and Blinding
o For blinded trials, procedures relating to blinding and (emergency) unblinding; see UoBCLN-CTM-SOP-002 Randomisation and Blinding
o Registration/Randomisation procedures; see UoB-CLN-CTM-SOP-002 Randomisation
and Blinding
o Pharmacovigilance procedures; see UoB-CLN-AES-SOP-001 Adverse Event reporting
o Ongoing review of trial supplies management, for CTIMPs including IMP management;
see UoB-CLN-IMP-SOP-001 Investigational Medicinal Product Management
o Regular review of the trial risk assessment; see UoB-CLN-TQM-SOP-001 Trial Quality
Management
o Financial and resource management
 External review of (aspects of the) trial, including funding bodies, Data Monitoring Committee,
REC and CA review; ensure any required reports for such review are generated within the
expected timeframe, for example the Annual Progress Report and the Development Safety
Update Report (DSUR); also see UoB-CLN-AES-SOP-001 Adverse Event reporting
 Provide training to trial staff; see UoB-GEN-TRN-SOP-001 Training
 Provide training to site staff; see UoB-CLN-SMA-SOP-0001 Site Management
 Maintain all essential documents in the Trial Master File; see UoB-CLN-ESD-SOP-001
Essential Documents development and maintenance
 Adverse Event monitoring and reporting, ensuring the required timelines are met; see UoBCLN-AES-SOP-001 Adverse Event reporting
 Process any suspected Serious Breaches within the required timelines and as per REC
guidelines and for CTIMPs as per MHRA guidelines; see UoB-CLN-SBR-SOP-001 Serious
Breach reporting
 Protocol defined statistical analysis
 Vendor Management; see UoB-CLN-VEN-SOP-001 Vendor Management
 End of Trial Processes; see UoB-CLN-EOT-SOP-001 End of Trial management
 Archiving; see UoB-CLN-ARC-SOP-001 Archiving
Document code:
UoB-CLN-CTM-SOP-001
Version no:
4.0
Print Date:
16-Mar-16
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Related documents:
Links below were correct at time of writing:
 Pre-award Research Governance Checklist: available from Research Governance Team
 College of Medical and Dental Sciences Application for Research Grants and Contracts
Approval Form (Pink Form): http://mymds.bham.ac.uk/portal/staff/researchgrants/
 Clinical Trials Oversight Committee Terms of Reference: available from the Clinical Research
Compliance Team
 Sponsorship Review Criteria: available from the Research Governance Team
 Sponsorship Application Form (PF2 and PF3) and the CI Declaration Form:
https://intranet.birmingham.ac.uk/finance/accounting/Research-Support-Group/ResearchGovernance/UoB-Sponsorship.aspx
 UoB SAF: https://intranet.birmingham.ac.uk/finance/accounting/Research-SupportGroup/Research-Ethics/Ethical-Review-Forms.aspx
 Insurance Questionnaire: https://intranet.birmingham.ac.uk/finance/insurance/ClinicalTrials.aspx
 Request for Contract Services.
https://intranet.birmingham.ac.uk/finance/accounting/Research-SupportGroup/Contracts/Request-a-Contract.aspx
 MHRA Instructions and Template for Serious Breach reporting
http://www.mhra.gov.uk/Howweregulate/Medicines/Inspectionandstandards/GoodClinicalPract
ice/SeriousBreachesReporting/index.htm
 Annual Progress Report (of NRES). http://www.nres.nhs.uk/applications/after-ethicalreview/annual-progress-reports/
 Declaration of end of a Clinical Trial Form. http://www.nres.nhs.uk/applications/after-ethicalreview/endofstudy/
 NRES Declaration of the end of a Clinical Study Form.
http://www.nres.nhs.uk/applications/after-ethical-review/endofstudy/ (National Institute for
Health Research, 2013)
 University of Birmingham Quality Management System (QMS) Standard Operating
Procedures, available at: http://www.birmingham.ac.uk/research/activity/mds/mdsrkto/governance/index.aspx
o Clinical Trials Quality Manual
o UoB-CLN-CTM-QCD-002
Clinical Trials Task Delegation Log
o UoB-CLN-CTM-SOP-002
Randomisation and Blinding
o UoB-CLN-TQM-SOP-001
Trial Quality Management
o UoB-CLN-ESD-SOP-001
Essential Documents development and maintenance
o UoB-CLN-DMA-SOP-001
Data Management
o UoB-CLN-IMP-SOP-001
Investigational Medicinal Product Management
o UoB-CLN-TSM-SOP-001
Trial Systems development and management
o UoB-CLN-SMA-SOP-001
Site Management
o UoB-CLN-AES-SOP-001
Adverse Event Reporting
o UoB-CLN-AES-QCD-004
DSUR Template
o UoB-CLN-STA-SOP-001
Statistics
o UoB-CLN-SBR-SOP-001
Serious Breach reporting
o UoB-CLN-ARC-SOP-001
Archiving
o UoB-CLN-EOT-SOP-001
End of Trial management
o UoB-CLN-VEN-SOP-001
Vendor Management
Document code:
UoB-CLN-CTM-SOP-001
Version no:
4.0
Print Date:
16-Mar-16
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References:
 Birmingham Region Research and Training Collaborative. (2013). Research Training.
Retrieved November 9th, 2015, from Birmingham Region Research and Training
Collaborative: http://brtc.org.uk/
 Clinical Research Compliance Team. (2013). Clinical research, clinical trials and governance.
Retrieved November 9th, 2015, from University of Birmingham:
http://www.birmingham.ac.uk/research/activity/mds/mds-rkto/governance/index.aspx
 Department of Health. (2005, April). GOV.UK. November 9th, 2015, from Research
Governance Framework for health and social care: second edition:
https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/139565/dh_412
2427.pdf
 European Committee. (2011). ‘Detailed guidance on the collection, verification and
presentation of adverse event/reaction reports arising from clinical trials on medicinal products
for human use. Retrieved November 9th, 2015, from Eudralex Volume 10:
http://ec.europa.eu/health/files/eudralex/vol-10/2011_c172_01/2011_c172_01_en.pdf
 European Committee. (2003, October 14). Comission Directive 2003/94/EC laying down the
principles and guidelines of good manufacturing practice in respect of medicinal products for
human use and investigational medicinal products for human use. Retrieved November 9th,
2015, from Eudralex Volume 10: http://ec.europa.eu/health/files/eudralex/vol1/dir_2003_94/dir_2003_94_en.pdf
 European Committee. (2006, July). Recommendation of the content of the Trial Master File
and Archiving. Retrieved November 9th, 2015 from
http://ec.europa.eu/health/files/eudralex/vol-10/v10_chap5_en.pdf
 MDS Research and Knowledge Transfer Office. (2013). Research Development and
Contracts. Retrieved November 9th, 2015, from MDS Reseach and Knowledge Transfer
Office: http://www.birmingham.ac.uk/research/activity/mds/mds-rkto/researchdevelopment/index.aspx
 MHRA. (2010, June 14). Clinical trials for medicines: Legislation. Retrieved November 9th,
2015, from MHRA: https://www.gov.uk/guidance/good-clinical-practice-for-clinical-trials
 MHRA. (2011, July 11). How we regulate devices. Retrieved November 9th, 2015 , from
MHRA: https://www.gov.uk/topic/medicines-medical-devices-blood/medical-devicesregulation-safety /
 National Institute for Health Research. (2013). Pharmacovigilance. Retrieved November 9th,
2015, from Clinical Trials Toolkit: http://www.ct-toolkit.ac.uk/routemap/pharmacovigilance
 National Institute for Health Research. (2013). Trial Management & Monitoring . Retrieved
November 9th, 2015, from Clinical Trials Toolkit: http://www.ct-toolkit.ac.uk/routemap/trialmanagement-and-monitoring
 National Institute for Health Research. (2013). Trial Supplies. Retrieved November 9th, 2015,
from Clinical Trials Toolkit: http://www.ct-toolkit.ac.uk/routemap/trial-supplies
 University of Birmingham. (2012-2013). Code of Practice for Research. Retrieved November
9th, 2015, from http://www.birmingham.ac.uk/Documents/university/legal/research.pdf
 University of Birmingham Procurement process. Retrieved November 9th, 2015:
https://intranet.birmingham.ac.uk/finance/procurement/Procurement-Services.aspx
Note the Clinical Trials Toolkit contains references to any applicable regulations and (inter)national
guidance relating to clinical trials. These are reiterated in the UoB Clinical Trials Quality Manual.
Document code:
UoB-CLN-CTM-SOP-001
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Abbreviations and Definitions:
Term
Description
ARSAC
Administration of Radioactive Substances Advisory Committee
BRTC
Birmingham region Research Training Collaborative
The BRTC supports the delivery of high quality clinical research in its
member organisations by providing access to research related training
activities and a communication forum whereby learning resources and local
events can be shared.
Chief Investigator
The person who takes overall responsibility for the design, conduct and
reporting of a study if it is at one site; or if the study involves researchers at
more than one site, the person who takes primary responsibility for the
design, conduct and reporting of the study, whether or not that person is an
investigator at any particular site.
Note that for CTIMPs the Chief Investigator must be an authorised health
professional.
CA
Competent Authority
CI
See ‘Chief Investigator’
Clinical research
Any health related research on humans.
Clinical study
Any health related research study on humans. This includes:
·
·
·
·
Clinical trial
Study administering questionnaires/interviews for quantitative analysis, or
using mixed quantitative/qualitative methodology
Study involving qualitative methods only
Study limited to working with human tissue samples (or other human
biological samples) and data (specific project only)
Study limited to working with data (specific project only)
For clinical trials using an Investigational Medicinal Product:
Any investigation in human subjects intended to discover or verify the clinical,
pharmacological and/or other pharmacodynamic effects of one or more
investigational medicinal product(s), and/or to identify any adverse reactions
to one or more investigational medicinal product(s) and/or to study
absorption, distribution, metabolism and excretion of one or more
investigational medicinal product(s) with the object of ascertaining its (their)
safety and/or efficacy.
For all other clinical trials:
Prospective biomedical research on human subjects that are conducted to
allow safety (or more specifically, information about adverse drug reactions
and adverse effects of other treatments) and efficacy data to be collected for
health interventions. Examples include devices, surgery and radiotherapy
trials.
Clinical Trial Task
Delegation Log
A UoB document that defines all Clinical Trials tasks and how these are
delegated between CI and CTU
Clinical Trials
Oversight
Committee
The Clinical Trials Oversight Committee (CTOC) provides sponsor oversight
of UoB’s portfolio of Clinical Trials of Investigational Medicinal Products
(CTIMPs). The CTOC also provides a means for the Research Governance
Team to obtain expert advice relating to non-CTIMPs. The CTOC reports to
the Pro-Vice Chancellor for Research & Knowledge Transfer through the
University Research Governance and Ethics Group, and to the University of
Document code:
UoB-CLN-CTM-SOP-001
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4.0
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Birmingham Internal Audit Office.
CTIMP
A Clinical Trial of an Investigational Medicinal Product
CTOC
See: ‘Clinical Trials Oversight Committee’
CTU
Clinical Trials Unit
CTU managed study A study for which the overall study management or the majority of study
management duties has been delegated to the CTU on behalf of a Sponsor.
Examples include all or most of the activities of Registration, Site Initiation,
Monitoring, IMP supply, Pharmacovigilance, Data Management and
Statistical Analysis.
DSUR
Development Safety Update Report
ERN
Ethics Registration Number; an internal number assigned to a project
following completion of a UoB Ethical Review of Research Self Assessment
Form
IRAS
Integrated Research Application System; set up to streamline the research
application process in the UK
IRMER
The Ionising Radiation (Medical Exposure) Regulations 2000
LES
College of Life and Environmental Sciences
MDS
College of Medical and Dental Sciences
MHRA
Medicines and Healthcare products Regulatory Agency; the Competent
Authority in the UK
NIHR
National Institute for Health Research
NIHR CSP
NIHR Coordinated System for gaining NHS Permission
Pink Form
College of Medical and Dental Sciences Application for Research Grants and
Contracts Approval Form; this is a college specific form that facilitates the
review, approval and tracking of any new grant proposals and is commonly
known as ‘Pink Form’.
R&KT Office
Research & Knowledge Transfer Office
RA1 Form
Research Activation Form used by the Research Finance Office to document
that an account has been set up and listing the account code.
REC
Research Ethics Committee
RG Number
Research Governance Number; the number that the Research Governance
Team will assign to any project put forward for UoB Sponsorship
RGT
See: ‘Research Governance Team’
Research
Facilitator
The Research Facilitator acts as the central contact point in project
development, initiation and conduct. The Research Facilitator liaises with
relevant contacts e.g. Finance Office, peer review and any other internal or
external bodies which may be able to assist. Different Colleges may use
different job titles for the same role.
Research Support
Partner
The Research Support Partner is responsible for ensuring research in the
College is supported by providing the first point of contact, both internally and
externally, for advice and assistance with all research-related issues, by
providing up to date information regarding research funding. Different
Colleges may use different job titles for the same role.
Document code:
UoB-CLN-CTM-SOP-001
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SAE
Serious Adverse Event
SAF
UoB Ethical Review of Research Self Assessment Form
SUSAR
Suspected Unexpected Serious Adverse Reaction
UKCRN
UK Clinical Research Network
UoB
University of Birmingham
UoB CTU
One of the three UKCRN fully registered University of Birmingham Clinical
Trials Units, i.e. Cancer Research UK Clinical Trials Unit (CRCTU),
Birmingham Clinical Trials Unit (BCTU) or the Primary Care Clinical Research
and Trials Unit (PC-CRTU).
UoB Lead
The UoB Lead is a (senior) person in the UoB who takes responsibility for the
conduct and delivery of those parts of the study which are either carried out
at or managed/overseen by the UoB. Normally this would be an academic
researcher, but in some cases it may be a senior member of a UKCRC
registered UoB CTU.
See also Glossary of Terms.
Document code:
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Development summary:
Author:
Name:
Conor McGoldrick
Signature:
Function:
Clinical Trials Compliance Officer
Date:
See original copy
Reviewed by:
Clinical Trials Oversight Committee
Craig Maskell, Senior Research Facilitator, College of Medical and Dental Sciences
Tamara Jordan, Research Finance Team Leader, Finance Office
David Law, Head of Research Support Group, Finance Office
Katie Stant, Clinical Trials Compliance Officer
Prof. Julian Bion, Chair of Clinical Trials Oversight Committee
See original copy
Authorised by:
Name:
Prof. Julian Bion on behalf of CTOC
Signature:
Function:
Chair of the Clinical Trials Oversight Committee
Date:
See original copy
Name:
Wilma van Riel
Function:
Clinical Trials Quality Assurance Manager
Date:
See original copy
Issue date:
08-Dec-2015
Signature:
See original copy
See original copy
Supersedes:
UoB-CLN-CTM-SOP-001, Clinical Trial Management v. 3.0 (EAv2.0)
Reason for update:
Update following recommendations from MHRA inspection 2015, to include the introduction of the
Clinical Trials Task Delegation Log and annual review thereof, the review of the Risk Assessment and
Monitoring Plan by the Sponsor, confirmation of correspondence between REC and/or MHRA and
conditions set being met, and explaining UoB Procurement processes.
Review of final version:
Date:
Reviewed by:
Signature:
Outcome:
N/A
Document code:
UoB-CLN-CTM-SOP-001
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Editorial Amendments
Tick box if not applicable
Reason for update:
Date of amendment:
Supersedes:
Editor:
Name:
Signature:
Function:
Date:
Authoriser:
Name:
Signature:
Function:
Date:
Document code:
UoB-CLN-CTM-SOP-001
Version no:
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