Uob-QMS-QCD-001

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 -
o For new trials identified prior to any grant application, follow the processes from ‘Idea’ onwards.
o For trials in the phase of grant application, follow the processes from ‘Award receipt and distribution’ onwards, and follow any previous processes as far as possible.
o 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.
o 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-May-2016

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Document code: / UoB-CLN-CTM-SOP-001 / Print Date: / 12-Apr-16
Version no: / 5.0 / Page: / 1 of 18

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.

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

o 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

o 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.

Procedure summary

Pre-award clinical research governance check

UoB procedures – award receipt and distribution

UoB procedures – towards account set up

Trial set up

Site initiation to archiving

Amendments

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/mds-rkto/governance/Clinical-Trials-QMS.aspx:

o 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

o Set up and maintain a Trial Master File and Investigator Site Files; see UoB-CLN-ESD-SOP-001 Essential Documents development and maintenance

o Develop Case Report Forms; see UoB-CLN-ESD-SOP-001 Essential Documents development and maintenance

o Set up data management and tracking systems; see UoB-CLN-TSM-SOP-001 Trial Systems development and management

o 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-TQM-SOP-001 Trial Quality Management

o 24 hour emergency coverage procedures (site/coordinating centre); see UoB-CLN-CTM-SOP-002 Randomisation and Blinding

o For blinded trials, procedures relating to blinding and (emergency) unblinding; see UoB-CLN-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

o 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

o Provide training to trial staff; see UoB-GEN-TRN-SOP-001 Training

o Provide training to site staff; see UoB-CLN-SMA-SOP-0001 Site Management

o Maintain all essential documents in the Trial Master File; see UoB-CLN-ESD-SOP-001 Essential Documents development and maintenance

o Adverse Event monitoring and reporting, ensuring the required timelines are met; see UoB-CLN-AES-SOP-001 Adverse Event reporting

o 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

o Protocol defined statistical analysis

o Vendor Management; see UoB-CLN-VEN-SOP-001 Vendor Management

o End of Trial Processes; see UoB-CLN-EOT-SOP-001 End of Trial management

o Archiving; see UoB-CLN-ARC-SOP-001 Archiving

References:

o University of Birmingham Finance Office teams:

o Research Governance Team: https://intranet.birmingham.ac.uk/finance/accounting/Research-Support-Group/Research-Governance/index.aspx

o Research Ethics Team: https://intranet.birmingham.ac.uk/finance/accounting/Research-Support-Group/Research-Ethics/Ethical-Review-of-Research.aspx

o Research Contracts Team: https://intranet.birmingham.ac.uk/finance/accounting/Research-Support-Group/Contracts/contracts.aspx

o Research Finance Office: https://intranet.birmingham.ac.uk/finance/accounting/Research-Support-Group/Research-Finance/research-finance.aspx

o Birmingham Region Research and Training Collaborative. (2013). Research Training. Retrieved November 9th, 2015, from Birmingham Region Research and Training Collaborative: http://brtc.org.uk/

o 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

o 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_4122427.pdf

o 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

o 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/vol-1/dir_2003_94/dir_2003_94_en.pdf

o 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

o HRA approval process (2016, March): http://www.hra.nhs.uk/about-the-hra/our-plans-and-projects/assessment-approval/

o 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/research-development/index.aspx

o 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

o MHRA. (2011, July 11). How we regulate devices. Retrieved November 9th, 2015 , from MHRA: https://www.gov.uk/topic/medicines-medical-devices-blood/medical-devices-regulation-safety /

o National Institute for Health Research. (2013). Pharmacovigilance. Retrieved November 9th, 2015, from Clinical Trials Toolkit: http://www.ct-toolkit.ac.uk/routemap/pharmacovigilance

o National Institute for Health Research. (2013). Trial Management & Monitoring . Retrieved November 9th, 2015, from Clinical Trials Toolkit: http://www.ct-toolkit.ac.uk/routemap/trial-management-and-monitoring

o 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

o 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

o 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.

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.