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Clinical Trials Quality Manual

Purpose:The purpose of this Clinical Trials Quality Manual is to explain the framework in which any clinical trials are to be conducted within the University of Birmingham. By reading this manual, anybody considering clinical trials should be aware of what is expected of them.

Scope:This Quality Manual applies to all staff members and others within the University of Birmingham who are actively involved in clinical trials.

Implementation Plan:This Quality Manual will be implemented directly after its implementation date.

Date of implementation: 02-Feb-2015

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Document code: Clinical Trials Quality Manual Print Date: 18-May-23Version no: 1.0 (EAv1.0) Page: 1 of 18


Table of Contents

Summary............................................................................................................................................ 3

1. Abbreviations and Definitions.................................................................................................4

2. Introduction............................................................................................................................ 7

3. Policy on clinical trials governance framework.......................................................................7

4. Policy on quality management and compliance.....................................................................8

5. Policy on Chief Investigators, UoB Leads and grant holders.................................................9

The Chief Investigator...............................................................................................................9

The University of Birmingham Lead...........................................................................................9

The Grant Holder(s)................................................................................................................... 9

6. Policy on University of Birmingham approval of clinical trials.................................................9

The University of Birmingham as the Sponsor...........................................................................9

Internal Chief Investigator....................................................................................................9

External Chief Investigator................................................................................................10

The University of Birmingham as a Co-Sponsor......................................................................10

The University of Birmingham as Coordinating Centre............................................................10

The University of Birmingham Clinical Trials Unit as host........................................................11

7. Policy on Sponsor oversight.................................................................................................11

Birmingham Centre for Clinical Trials................................................................................11

Clinical Trials Oversight Committee...................................................................................11

Research Governance and Ethics Team...........................................................................11

Clinical Research Compliance Team.................................................................................11

Research Facilitators.........................................................................................................12

Internal Audit Service........................................................................................................12

8. Organogram of the University of Birmingham oversight in clinical trials...............................13

9. Policy of UoB as support for a host site...............................................................................14

10. Policy on training.................................................................................................................. 14

11. Policy on pharmacovigilance................................................................................................14

12. Policy on IT.......................................................................................................................... 14

13. Policy on document storage and archiving...........................................................................14

14. Related procedures/checklists:............................................................................................15

15. References:.......................................................................................................................... 15



SummaryThis Clinical Trials Quality Manual lists the University of Birmingham policies on specific topics relating to clinical trials:

Clinical trials governance framework; detailing all the regulations and standards that are applicable to clinical trials and must be adhered to

University of Birmingham approval of clinical trials

Chief Investigators, University of Birmingham Leads and grant holders

Quality management and compliance

Sponsor oversight

Pharmacovigilance

IT

Document storage and archiving

All staff members within the University of Birmingham involved in clinical trials must adhere to these policies.



1. Abbreviations and DefinitionsTerm DescriptionBCCT See: Birmingham Centre for Clinical Trials

Birmingham Centre for Clinical Trials

An overarching centre set up to further improve the links between stakeholders involved in clinical trials within the University of Birmingham.

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.

CI See ‘Chief Investigator’

Coordinating Centre A term commonly used to refer to the team responsible for the overall management of the trial and their physical location. A Coordinating Centre may be based in a Clinical Trials Unit, and may also be referred to as a Trials Office. There may be more Coordinating Centres involved in a trial, e.g. for international trials the international and national Coordinating Centre, and for trials managed regionally the central and local Coordinating Centre.

CRCT Clinical Research Compliance Team; forms part of the College of Medical and Dental Sciences Research and Knowledge Transfer Office, and is responsible for developing an infrastructure for researchers involved in clinical studies. In addition, the team takes on responsibilities relating to Sponsor oversight such as audits and quality checks.

CTIMP A Clinical Trial of an Investigational Medicinal Product(s)

CTOC Clinical Trials Oversight Committee

CTU Clinical Trials Unit

CTU hosted study A trial for which the CTU undertakes some individual tasks related to the conduct of the trial, but for which the CTU has not been delegated the overall task of managing the entire trial on behalf of the Sponsor. Examples, though not exhaustive, would be acting as or supporting the investigator site, and/or undertaking one or more individual tasks such as Monitoring, Pharmacovigilance, IMP Supply, Data Management, Statistics. Where the CTU undertakes such specific tasks, the CTU is responsible for ensuring those tasks are conducted as expected and in line with the relevant QMS. Where all or the majority of the functions listed above are being carried out, it may be appropriate to regard the trial as CTU managed.

CTU managed study A trial for which the overall trial management or the majority of trial 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.

GCP Good Clinical Practice guidelines

ICH International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use; commonly referred to as ‘International Conference on Harmonisation’

ICH GCP International Conference on Harmonisation Good Clinical Practice Guidelines; this is an international ethical and scientific quality standard for designing, conducting, recording and reporting trials that involve the participation of human subjects. ICH GCP is also referred to as ‘GCP’.

IMP See ‘Investigational Medicinal Product’

Investigational Medicinal Product

A pharmaceutical form of an active substance or placebo being tested or used as a reference in a clinical trial, including products already with a marketing authorisation but used or assembled (formulated or packaged) in a way different from the authorised form, or when used for an unauthorised indication, or when used to gain further information about the authorised form

MDS The College of Medical and Dental Sciences

MHRA Medicines and Healthcare products Regulatory Agency; the Competent Authority in the UK

NIHR CRN National Institute for Health Research Clinical Research Network

Non-CTIMP Any clinical trial which is not a CTIMP

PI See ‘Principal Investigator’

Policies Policies are developed to describe the approach of the UoB on areas that are heavily regulated. Policies may also be developed when there is ambiguity in how regulatory requirements should be implemented in the QMS or when procedures to be captured in the QMS address areas controversial within the UoB at the time of implementation. Policies explain why the UoB has its procedures. Policies should be read in conjunction with the relevant SOP. Policies that are not part of a Quality Manual are coded up as ‘POL’.

Principal Investigator The investigator is responsible for the conduct of a clinical trial at a trial site. If a trial is conducted by a team of individuals at a trial site, the investigator is the leader responsible for the team and may be called the Principal Investigator.

QCD See ‘Quality Control Documents’

QMS See ‘Quality Management System’

Quality Control Quality Control Documents can be instructions, forms, templates



Documents or checklists. They are developed to share best practices, promote standardisation to guarantee quality standards are maintained and reduce resources otherwise needed to develop similar documents. Unless indicated otherwise in the relevant SOP, QCDs are not mandatory and are designed to be an optional aid to UoB staff.

Quality Management System

A Quality Management System (QMS) is a system that includes procedures and policies to describe how certain tasks should be performed and that encapsulate any standards and/or regulatory requirements that may apply to those tasks. By adhering to the Quality Management System, the user and the UoB will be assured that applicable regulations are adhered to.

R&KT Research and Knowledge Transfer

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. Research Facilitators work closely with Head of School to ensure compliance with the UoB Code of Practice for research and other regulations especially with regard to more junior researchers or those working outside of a Clinical Trials Unit. Different Colleges may use different job titles for the same role.

RG&ET Research Governance and Ethics Team, consisting of the Research Governance Team and the Research Ethics Team.

RGF Research Governance Framework

SOP See ‘Standard Operating Procedure’

Sponsor Individual, organisation or group taking on responsibility for securing the arrangements to initiate, manage and finance a clinical study.

Standard Operating Procedures

Standard Operating Procedures are detailed written instructions to achieve uniformity of the performance of a specific function. They define tasks, allocate responsibilities, detail processes, indicate documents and templates to be used and cross-reference to other work instructions and guidance or policy documents. They are standards to which the UoB may be audited or inspected.

SUSAR Suspected Unexpected Serious Adverse Reaction

TMF Trial Master File

Trials Office A term commonly used to refer to the team responsible for the overall management of the trial, and their physical location. A Trials Office may be based in a Clinical Trials Unit, and may also be referred to as Coordinating Centre.

UKCRC UK Clinical Research Collaboration



UoB University of Birmingham

UoB CTU One of the three UKCRC 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.

2. IntroductionThe University of Birmingham (UoB) is one of the leading centres for clinical research in the United Kingdom. It is committed to supporting clinical trials, and it aims for clinical trials to be conducted to a high quality standard. For this purpose it has set up a Quality Management System (QMS) of which this Quality Manual forms part. The QMS reflects the legislative and any other applicable requirements. By adhering to the QMS any staff member working in clinical trials and the UoB as an institution can be assured that the rights and wellbeing of the subjects participating in clinical trials are protected and the trial data is credible, and that the trial is conducted in compliance with the approved protocol/amendment(s), the applicable regulatory requirements and Good Clinical Practice (GCP), an international ethical and scientific quality standard for designing, conducting, recording and reporting trials that involve the participation of human subjects.

3. Policy on clinical trials governance framework Clinical trials are governed by regulatory requirements, internationally accepted standards and governance frameworks, all with the ultimate aim to ensure subject safety and data quality. Any UoB staff member involved in clinical trials must familiarise themselves with and adhere to any applicable regulations, standards and governance frameworks.

The World Medical Association has developed a statement of ethical principles for physicians and other participants in medical research involving human subjects; this is the Declaration of Helsinki. Any medical researcher is expected to follow the principles captured in this Declaration of Helsinki (World Medical Association, 2008).

The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use have developed a set of international guidelines designed to protect human subjects involved in clinical trials; these are referred to as ‘ICH Guidelines’ (ICH, 2012). Some of the guidelines have been adopted into European and UK law, in particular, the guidelines on the principles of Good Clinical Practice (‘ICH-GCP’) are now seen as an international standard for both commercial and non-commercial clinical trials.

In 2004 the European Union Clinical Trials Directive became effective, which applies to all clinical trials using an ‘Investigational Medicinal Product’ or IMP; these clinical trials are referred to as ‘CTIMPs’. An IMP is defined as ‘a pharmaceutical form of an active substance or placebo being tested or used as a reference in a clinical trial, including products already with a marketing authorisation but used or assembled (formulated or packaged) in a way different from the authorised form, or when used for an unauthorised indication, or when used to gain further information about the authorised form’. The Clinical Trials Directive and any other related directives and guidelines can be found in Eudralex Volume 10 (European Committee, 2012).

In the UK, the Clinical Trials Directive is embedded in national law via the ‘The Medicines for Human Use (Clinical Trials) Regulations 2004’ (SI 1031) and subsequent amendments (HM Government, 2004).

Up to recently, clinical trials in the paediatric setting lagged behind in numbers compared to the adult setting given the vulnerability of children. As a result, medication was used off label, and without


http://www.legislation.gov.uk/uksi/2004/1031/pdfs/uksi_20041031_en.pdf

http://www.legislation.gov.uk/uksi/2004/1031/pdfs/uksi_20041031_en.pdf

http://www.wma.net/en/30publications/10policies/b3/


supporting evidence. The EU has put in place the regulation on medicinal products for paediatric use (European Union, 2006) that makes it mandatory for manufacturers to develop a ‘Paediatric Investigation Plan’ as part of their application for Marketing Authorisation. Manufacturers must undertake studies in children, covering all age groups and using appropriate formulations for each age group.

Similarly, in the UK the Mental Capacity Act (HM Government, 2005) has been set up to help facilitate clinical trials involving adults lacking mental capacity. Mental capacity is the ability to make a decision, and people lacking capacity are unable to make decisions themselves. The Mental Capacity Act is to improve the knowledge of what causes a person to lack or lose capacity, and the diagnosis, treatment, care and needs of people who lack capacity.

Where the clinical trial involves the use of a non-CE marked medical device, then the provisions of the Medical Devices Regulations 2002 (HM Government, 2002), and any subsequent amendments thereof, apply.

In addition, in England the Research Governance Framework (RGF) version 2 (Department of Health, 2005) must be adhered to for any research concerned with the protection and promotion of public health, research undertaken in or by the Department of Health, its non-Departmental Public Bodies and the NHS, and research undertaken by or within social care agencies. Equivalent Frameworks are in effect in Scotland, Wales and Northern Ireland. It includes clinical and nonclinical research, research undertaken by NHS or social care staff using the resources of health and social care organisations, and any research undertaken by industry, charities, research councils and universities within the health and social care systems that might have an impact on the quality of those services. The RGF requires any research to have a designated Sponsor, this being defined as the Individual or Organisation taking responsibility for the initiation and conduct of research. The University of Birmingham is registered with the Department of Health as a Sponsor under the RGF.

When working in clinical trials, other guidelines and laws have to be adhered to, for example the Data Protection Act, Equality Act, Freedom of Information Act, Human Tissue Act, legislation specific to children and vulnerable adults, any other professional codes of conducts and local Trust policies.

4. Policy on quality management and complianceAs described in the UoB Research Quality Manual, researchers are expected to develop their own system to ensure compliance to any international standards, guidelines, regulations, local policies or Standard Operating Procedures (SOPs). This may include quality checks.In addition, the UoB Clinical Research Compliance Team (CRCT; see section 7) will develop a Clinical Trials QMS (labelled as ‘UoB-CLN-’) covering key processes that must be followed when conducting clinical trials. Any policies and SOPs within this QMS will be approved by the Clinical Trials Oversight Committee (CTOC; see also section 7). The UoB Clinical Trials QMS must be used in conjunction with the overarching UoB QMS (labelled as ‘UoB-GEN-’).The three UKCRC registered UoB Clinical Trials Units (referred to as ‘UoB CTUs’) have their own QMS set up covering the same key processes; this is required for their UKCRC registration, and includes further instructions relating to local management and oversight. It is anticipated that in some cases research teams working outside a UoB CTU may also have their own QMS. In both cases, the minimum standards as set out in the UoB SOPs will still need to be adhered to, but it would suffice for a local staff member to cross-check their local QMS against the UoB QMS to ensure the contents of the UoB QMS is covered in their local QMS, to document this process, and to continue to adhere to their local QMS. Where the UoB (co-)sponsors a trial that is to be (partially) managed outside the UoB (e.g. international trials or trials managed by a UKCRC registered CTU), their QMS must be reviewed against the UoB QMS to ensure those aspects that ensure compliance with regulations and GCP are appropriately covered. This review must be conducted by the CI or their team, in collaboration with the CRCT.The UoB CRCT will review the compliance of researchers and/or CTUs with any international standards, guidelines, regulations, local policies or SOPs relating to clinical trials.


http://ec.europa.eu/health/files/eudralex/vol-1/reg_2006_1901/reg_2006_1901_en.pdf

http://ec.europa.eu/health/files/eudralex/vol-1/reg_2006_1901/reg_2006_1901_en.pdf


5. Policy on Chief Investigators, UoB Leads and grant holdersThe Chief Investigator Any researcher who has a contract with the UoB can take on the role of CI for a clinical trial that is not a CTIMP (‘non-CTIMP’). By doing so, they take on responsibilities as assigned to the CI in the RGF. For CTIMPs, the CI must be an authorised health care professional (doctor, dentist, nurse or pharmacist), and the CI takes on the CI responsibilities as described in the RGF and the Medicines for Human Use (Clinical Trials) Regulations. The Research Governance and Ethics Team (RG&ET, see also section 7) have developed a ‘CI Declaration Form’ which summarises these responsibilities. The CI will be asked to sign this declaration, thereby confirming they will take on the responsibilities assigned to them.Where the trial is externally sponsored, the CI will also have to inform the Insurance Office of their role in the clinical trial so appropriate insurance cover for the CI can be put in place.

The University of Birmingham LeadFor trials where the CI is located outside the UoB, there is a need for a 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 UoB CTU.

The Grant Holder(s)Normally, the principal grant holder for a study will be expected to act as CI. However, where the principal grant holder is not appropriately qualified to act as CI on a clinical trial (e.g. is a statistician or other member of the clinical trials team who is not clinically qualified) then an appropriately qualified individual must be identified to act as CI. The grant holder may take on the role of UoB Lead, where this is required.

6. Policy on University of Birmingham approval of clinical trialsGiven the complexity of clinical trials, the UoB as an institution is involved in the review and approval of clinical trials that are either (co-) sponsored by the UoB or where one of the 3 UoB CTUs takes on the trial management for the trial.

The University of Birmingham as the SponsorInternal Chief InvestigatorThe UoB is strongly supportive of clinical trials and is prepared to act as Sponsor for clinical trials under the RGF and the Medicines for Human Use (Clinical Trials) Regulations, provided that the criteria listed in the document named ‘UoB Pre-Award Sponsorship Checks for Clinical Trials’ (available from the Research Governance and Ethics Team) are met. The RG&ET (Research Governance and Ethics Team) makes the initial decision on Sponsorship. The RG&ET will liaise with the CI if any of the criteria listed are not met, with the aim to resolve any hurdles. The RG&ET may refer any issues to other experts, e.g. the CRCT and the CTOC.Where the UoB accepts the role as Sponsor, the RG&ET will ask the CI to confirm their acceptance of CI responsibilities and Sponsor duties delegated to the CI via the CI Declaration Form. Where a UoB CTU takes on the trial management of the trial, it is expected that CI responsibilities and Sponsor duties delegated to the CI will be further delegated to staff members in the CTU, as described in the CTU’s QMS. Where an external UKCRC registered CTU takes on the trial management of the trial, it is expected that the contractual agreement between the UoB and the external UKCRC registered CTU will clearly explain the following -

A clear description of the division of responsibilities and duties between the CI and the CTU

A clear agreement as to what QMS are going to be adhered to. Where the CTU’s QMS is to be used, the CI and their team must review the CTU’s QMS against the UoB QMS. Where these are consistent with each other, the check should be documented and kept on file in Sponsor file. Where differences are noted, these must be discussed with the CRCT.



The CI and their team are responsible for overseeing that the terms in the contractual agreement are met.

External Chief InvestigatorWhere the UoB is sponsoring and managing a clinical trial preferably within one of its UoB CTUs, but where the CI is employed elsewhere, arrangements must be put in place with the CI and the CI’s employing Institution covering the CI’s duties. This may take the form of a formal Co-Sponsorship arrangement as discussed above. However, it may in many cases be more appropriate for the UoB to act as sole Sponsor, to ensure clarity of trial management functions, and to enter into a separate “Chief Investigator Agreement” with the CI and his/her employers. The UoB Trials Office should discuss with the RG&ET which arrangement is most suitable for any individual clinical trial.

The University of Birmingham as a Co-SponsorThe UoB may share the Sponsor responsibilities with another institution, where the UoB and the Co-Sponsor each take responsibilities for certain aspects of a clinical trial. In this case a Co-Sponsorship arrangement will be put in place specifying the responsibilities for each Co-Sponsor. Situations where Co-Sponsorship may be considered are:

The design of the study has been carried out by one party, but coordination will be by the other

A collaborating partner is better resourced to conduct a specific aspect of a trial, such as trial statistics

The CI is based at another institution (see below)Where the UoB acts as a co-Sponsor the RG&ET will initiate regular contacts with the external co-Sponsor to ensure appropriate oversight is maintained.The UoB will not take on a Joint Sponsorship role, as there is no clear division of responsibilities.

The University of Birmingham as Coordinating Centre The three UoB CTUs have expertise in the design, management and conduct of clinical trials. The UoB recognises that the expertise and experience of its CTUs should be available to support medical research generally by working in collaboration with other members of the clinical trials community, and in particular by managing or hosting clinical trials on behalf of an external, non-commercial Sponsor.However, the UoB will not normally permit a research team operating outside the three UoB CTUs to act as a Coordinating Centre, unless the clinical trial is non-interventional.In the context of international trials sponsored by another institution, the UoB may take on the role of the UK National Coordinating Centre for the clinical trial.In order to undertake the role of a Coordinating Centre for an externally sponsored clinical trial there must be:

A clear definition of the delegated duties to be carried out by the UoB

A clear agreement as to what QMS are going to be adhered to; typically this will be the UoB and UoB CTU’s QMS. Where an external Sponsor’s QMS is to be used, the UoB CTU must review the external Sponsor’s QMS against the UoB QMS. Where these are consistent with each other, the check should be documented and kept on file in the UoB CTU. Where differences are noted, these must be discussed with the CRCT.

A clearly identified UoB Principal Investigator (referred to as ‘UoB Lead’), taking responsibility for the activities of the UoB CTU acting as a Coordinating Centre. This may be a clinical investigator or a senior member of the CTU management team.

Adequate resources within the UoB CTU to carry out the delegated duties.

A clear definition of the level of support to be provided by the Sponsor, especially in terms of information and documentation required to register and conduct the clinical trial, the sourcing and supply of any IMPs, pharmacovigilance assessment, pharmacovigilance reporting, and financial support for the costs of providing the activities of the Coordinating Centre.



An appropriate contractual agreement governing the above and a procedure to oversee the terms in the contractual agreement are met.

The University of Birmingham Clinical Trials Unit as host In certain cases, the UoB CTU may take on the role as “CTU hosted”. This means that the CTU undertakes some individual tasks related to the conduct of the trial, but the UoB CTU has not been delegated the overall task of managing the entire trial on behalf of the Sponsor. Examples, though not exhaustive, would be acting as or supporting the investigator site, and/or undertaking one or more individual tasks such as monitoring, pharmacovigilance, IMP supply, data management and statistical input. Where the CTU undertakes such specific tasks, the CTU is responsible for ensuring those tasks are conducted as expected and in line with the relevant QMS. It is also expected that clear documentation is put in place at the start of the trial to describe what tasks are delegated to the CTU. Where all or the majority of the functions listed above are being carried out, it may be appropriate to regard the trial as UoB CTU managed.

7. Policy on Sponsor oversightThe UoB in its role as Sponsor for clinical trials has set up an infrastructure for maintaining appropriate Sponsor oversight and uses a number of committees, groups and teams that are fully committed to clinical trials.

Birmingham Centre for Clinical TrialsThe Birmingham Centre for Clinical Trials (BCCT) is the overarching structure bringing together the clinical trial expertise from across the UoB and in particular the three UoB CTUs.

Clinical Trials Oversight CommitteeThe CTOC is the main operational arm of the BCCT. The CTOC reports directly to both the Pro-Vice Chancellor and Head of College of Medical and Dental Sciences (MDS) through the MDS Research and Knowledge Transfer Executive Committee and the Pro-Vice Chancellor for Research & Knowledge Transfer through the University Research Governance and Ethics Group. The CTOC has two responsibilities; firstly to advise the RG&ET whether or not a trial to be managed outside the CTU should receive UoB sponsorship and secondly for ensuring Sponsor oversight. For the latter, the CTOC reviews and approves clinical trial related policies and SOPs within UoB Clinical Trials Quality Management System. In addition, it reviews any reports relating to compliance review activities. Where required, the CTOC will take action to ensure issues are appropriately dealt with, which includes escalation to senior members of staff within UoB. The CTOC may provide advice on future conduct, appoint a “mentor” to oversee conduct of the clinical trial, or, exceptionally, to advise the RG&ET to suspend the clinical trial on grounds of patient safety or futility, or to withdraw Sponsorship. The CTOC is responsible for overseeing all clinical trials activity involving the UoB.

Research Governance and Ethics Team The Research Governance and Ethics Team (RG&ET) is located within the UoB Research Support Group and is responsible for the process by which the UoB sponsors research and establishes sound governing arrangements for the research that the UoB sponsors. The RG&ET also maintains oversight of the projects that are sponsored or co-sponsored by the UoB and manages the ethical review process at the UoB. The RG&ET makes the initial decision on Sponsorship, referring to the CTOC as required. Where Sponsorship has been agreed, the RG&ET provides support to a clinical trial as the Sponsor representative, via site agreement development and by managing the process of insurance referrals. It will direct researchers to e.g. the CRCT and the UoB Advanced Therapies Facility Director as appropriate.

Clinical Research Compliance TeamThe CRCT was set up within the MDS R&KT Office to further improve the compliance of the MDS based clinical researchers with the applicable guidelines, standards and regulations. Its remit is clinical research conducted under the Research Governance Framework where the UoB is Sponsor. For clinical trials its main focus is to manage the Clinical Trials Quality Management System, including


http://www.birmingham.ac.uk/research/activity/mds/mds-rkto/index.aspx

http://www.birmingham.ac.uk/research/support/research.aspx

http://www.birmingham.ac.uk/research/support/research.aspx

http://www.rcs.bham.ac.uk/governance/index.shtml


the development and management of clinical trial related policies and SOPs. In addition, the team reviews compliance of UoB staff involved in clinical trials with these policies and SOPs. The CRCT also plays a central role in clarifying any training needs and identifying relevant training for staff working outside a UoB CTU, alongside facilitating the provision of in-house training. The CRCT works closely together with the RG&ET to ensure new trials are set up as per UoB policies and SOPs. For Independent CI managed CTIMPs the CRCT will perform on-site monitoring as per the trial specific Monitoring Plan. The CRCT reports to the CTOC and liaises with UoB staff where issues are noted to ensure a proper corrective and preventative action plan has been put in place.

Research FacilitatorsThe Research Facilitator acts as the central contact point in project development, helping initially with development of early-stage ideas and identifying relevant funding streams, then initiating correspondence with the relevant contacts in Finance, Estates, RSG, peer review and any other internal or external bodies which may be able to assist. They then make sure that development is progressing in a timely and efficient manner and will meet appropriate deadlines, as well as monitoring the costings and clinical governance processes to ensure that high risk projects are identified and the School/College is fully aware of potential problems, and that these are addressed as far as possible. Research Facilitators work closely with Head of School and Administration Managers to provide live metrics, as well as with School-based thematic leads in order to help monitor, develop and support clusters of research activity, especially with regard to more junior researchers.Within MDS, the Research Facilitators may also be called on to support clinical trials compliance review throughout the duration of the trial.

Internal Audit ServiceThe UoB Internal Audit Service is responsible for performing audits across the UoB, focussing on the controls that departments have put in place to ensure appropriate governance, risk management, quality and adherence to regulations, policies and processes. In the case of clinical trials, the Internal Audit Office will focus on assessment of compliance with the QMS, including assessment of the adequacy and effectiveness of the quality checks and audits undertaken within the CTUs and the Sponsor oversight processes.



8. Organogram of the University of Birmingham oversight in clinical trials



9. Policy of UoB as support for a host siteThe UoB may provide site management support (via one of its three UoB CTUs) to a local NHS (Foundation) Trust that is set up as a trial site. The Principal Investigator and the Trust are responsible for the conduct of the trial at that Trust, but may delegate some of the site duties to one of the three UoB CTUs. In these situations, it is appropriate to put in place a short agreement or sub-contract defining the support that the UoB CTU is providing. In all cases the site’s Principal Investigator is responsible for ensuring their staff members are appropriately trained.

10. Policy on trainingAny staff involved in clinical trials must be appropriately qualified to take on their respective task(s) in the clinical trial. Any relevant training or education must be documented, and readily available e.g. for quality review. Staff members who are involved in the day to day (site) management of a clinical trial (e.g. Chief Investigator, Research Nurse, Trial Coordinator) are required to have completed NIHR GCP training. In addition, staff members have to ensure (and be able to evidence) they stay up to date with their knowledge of GCP and applicable regulations, for example through attending NIHR GCP refresher courses every 3 years. The UoB is a collaborator of the Birmingham region Research Training Collaborative that provides training throughout the region; see http://www.brtc.westmidlands.nhs.uk/ for further details.

11. Policy on pharmacovigilanceAll UoB staff involved in clinical trials are expected to adhere to the applicable regulations and guidance documents. For CTIMPs, the UoB as Sponsor via its RG&ET will take on the role of ensuring any Suspected Unexpected Serious Adverse Reactions (SUSARs) and major safety issues relating to a specific Investigational Medicinal Product are reported to any other trial team of a UoB sponsored trial using the same IMP.

12. Policy on ITAll UoB staff are expected to ensure that all clinical trial data is stored appropriately for their trial. The data should be secure and protected from inadvertent use. The data should also be resilient and backed up to prevent loss in the event of a disaster. For further information on the University’s IT Services policies see https://intranet.birmingham.ac.uk/it/governance/policy/index.aspxAll staff members will have access to their College file servers where they can store a fixed amount of data; the exact amount can be obtained via the IT Service Desk. This data is backed up on a daily basis. Retention periods differ depending on the type of data and the College storing it. Full details can be obtained from the local IT Support Team via the IT Service Desk.If a staff member or research group are expecting to store more than the allocated amount of data, they can arrange for their quota to be increased. This can be arranged via raising a call with the IT Service Desk. Costs may be incurred for arranging additional storage space; the IT Service Desk can be asked for further advice.

13. Policy on document storage and archivingFor any clinical trial there will be a body of “Essential Documents” which individually and collectively permit evaluation of the conduct of a trial and the quality of the data produced. These documents serve to demonstrate the compliance of the Investigator and Sponsor with the standards of GCP and with all applicable regulatory requirements. These documents need to be stored in such a way that their physical integrity is maintained and also in a way that protects the confidential information held within them. It should be available for prompt retrieval and stored in a secure facility with appropriate environmental control and adequate protection from fire, flood and unauthorised access. The storage of the documentation may be transferred to a subcontractor but the ultimate responsibility for the quality, integrity, confidentiality and retrievability of the documents resides with the Sponsor.This policy will apply to all material relevant to clinical trials and for which the UoB has been delegated the Sponsor responsibility for archive; this may include sections of the Sponsor’s Trial Master File (TMF). Note it does not include the Investigator Site File. The ultimate responsibility for the documents


https://intranet.birmingham.ac.uk/it/governance/policy/index.aspx

http://www.brtc.westmidlands.nhs.uk/


to be retained by the Investigator/Institution resides with the Investigator/Institution, typically a clinician based in a NHS Trust. Arrangements for archiving of the Investigator Site File should be agreed between the Principal Investigator, the Trust and the Sponsor at the trial set-up stage. On occasion the UoB may arrange for long term storage or archiving of the trial documentation on behalf of the Trust/Principal Investigator; this must be detailed in the subcontract between the Trust and the UoB.The TMF should be retained for a minimum of 5 years after trial completion. In addition, where the documentation relates to a CTIMP and the trial results are planned to be used for registration purposes in Europe, the documentation is required to be archived for at least 15 years after completion or discontinuation of the trial, or for at least 2 years after the last Marketing Authorisation has been granted, or for at least 2 years after formal discontinuation of clinical development of the IMP. For children, the Records Management: NHS Code of Practice (Department of Health, 2009) states that all information must be retained until the patient’s 25th birthday or 26th if young person was 17 at conclusion of treatment, or 8 years after death. If the illness or death could have potential relevance to adult conditions or have genetic implications, the advice of clinicians should be sought as to whether to retain the records for a longer period of time. In addition, the UoB Code of Practice for Research explains that -

The Research Finance Office will archive their documentation including contracts for 7 years following closure of the relevant account; if the documentation needs to be archived for a longer period it is the responsibility of the CI or their delegate to inform the Research Finance Office as soon as possible.

Human Resources will maintain any staff related documentation electronically ad infinitum. The Insurance Office will maintain any insurance policies and related certificates ad infinitum. The RG&ET will maintain any trial specific documentation for at least the same period of time that the TMF will need to be maintained for.

Note that the TMF would include e-mails and any trial specific databases; systems must be set up to guarantee access to the data throughout the retention period, taking into account possible software system upgrades, change in storage devices and incompatibilities leading on from such changes. With regards to e-mail archiving - all staff University e-mail is hosted on Microsoft Exchange Server. All staff members have their own mailbox but also have the option of having a personal archive which provides them with an alternative storage location in which to store historical messaging data. A personal archive is an additional mailbox (called an archive mailbox) which can be enabled upon request via the IT Service Desk. This is typically done if a user’s existing mailbox is exceeding the agreed limit.For electronic document retention other than e-mails, liaise with the local IT Support Team via the IT Service Desk.

14. Related procedures/checklists: UoB-CLN-CTM-SOP-001: Clinical Trial Management

UoB-CLN-CTM-QCD-001: Glossary of Terms

The UoB CTM QMS related documents and any related guidelines are available on http://www.birmingham.ac.uk/research/activity/mds/mds-rkto/governance/index.aspx and can also be requested from members of the CRCT.

15. References: Department of Health, 2005. Research governance framework for health and social care: Second

edition. [Online] Available at: http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_4108962[Accessed 20 February 2012].


http://www.birmingham.ac.uk/research/activity/mds/mds-rkto/governance/index.aspx


Department of Health, 2009. Records Management: NHS Code of Practice. [Online] Available at: http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/documents/digitalasset/dh_093024.pdf[Accessed 10 October 2012].

European Committee, 2012. Reference documents - EudraLex - Volume 10 Clinical trials guidelines | Public health , European Commission. [Online] Available at: http://ec.europa.eu/health/documents/eudralex/vol-10/[Accessed 20 February 2012].

European Union, 2006. EC regulation No 1901/2006 on medicinal products for paediatric use. [Online] Available at: http://ec.europa.eu/health/files/eudralex/vol-1/reg_2006_1901/reg_2006_1901_en.pdf[Accessed 07 June 2012].

HM Government, 1998. Data Protection Act 1998. [Online] Available at: http://www.legislation.gov.uk/ukpga/1998/29/data.pdf[Accessed 21 February 2012].

HM Government, 2002. The Medial Devices Regulations 2002. [Online] Available at: http://www.legislation.gov.uk/uksi/2002/618/pdfs/uksi_20020618_en.pdf[Accessed 07 June 2012].

HM Government, 2004. The Medicines for Human Use (Clinical Trials) Regulations 2004. [Online]

Available at: http://www.legislation.gov.uk/uksi/2004/1031/pdfs/uksi_20041031_en.pdf[Accessed 21 February 2012].

HM Government, 2005. Mental Capacity Act 2005. [Online] Available at: http://www.legislation.gov.uk/ukpga/2005/9/pdfs/ukpga_20050009_en.pdf[Accessed 07 June 2012].

ICH, 2012. ICH official website. [Online] Available at: http://www.ich.org/[Accessed 20 February 2012].

MHRA, 2011. Risk-adapted Approaches to the Management of Clinical Trials of Investigational Medicinal Products. [Online] Available at: http://www.mhra.gov.uk/home/groups/l-ctu/documents/websiteresources/con111784.pdf[Accessed 21 February 2012].

University of Birmingham, 2014-2015. Code of Practice for Research. [Online] Available at: http://www.birmingham.ac.uk/Documents/university/legal/research.pdf[Accessed 06 November 2014].

World Medical Association, 2008. Declaration of Helsinki. [Online] Available at: http://www.wma.net/en/30publications/10policies/b3/[Accessed 07 June 2012].



Development summary:Author:Name: Wilma van Riel Signature: See original copy

Function: Clinical Trials Quality Assurance Manager

Date: See original copy

Reviewed by: This document has received extensive review to include review by CTU QA Managers, Clinical Trials Oversight Committee, the Research Governance and Ethics Group and topic experts.

Authorised by:Name: Prof. Pam Kearns Signature: See original copy

Function: Chair of Clinical Trials Oversight Committee

Date: See original copy

Issue date: 19-Jan-2015

Supersedes: N/A

Reason for update:N/A

Review of final version:Date: Reviewed by: Signature: Outcome:

N/A

Editorial Amendments Tick box if not applicable

Reason for update:Administrative update: links and layout updated

Date of amendment:27-Jan-15

Supersedes:Clinical Trials Quality Manual v1.0 dd 20-Jan-15



Editor:Name: Conor McGoldrick Signature: See original copy

Function: Clinical Trials Compliance Officer

Date: 27-Jan-15

Authoriser:Name: Wilma van Riel Signature: See original copy

Function: Clinical Trials Quality Assurance Manager

Date:


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