Governance and Legislation

It is a requirement of the Department of Health's Research Governance Framework (RGF) that all NHS organisations carry out formal monitoring of research taking place on their premises, or involving their patients or staff.

There must also be Trust-level systems in place for on-going monitoring of research projects. These measures are in addition to the more detailed monitoring of studies by the research team and sponsor.

Study monitoring is carried out by the Trust's Quality Manager (QM) using a research governance tool known as 'MAJIK'. The tool consists of a checklist for determining compliance with the RGF and good clinical practice (GCP).

If you have any questions regarding the monitoring process please contact the Quality Manager, Dr George Gerogiou.

Clinical Trials of Investigational Medicinal Products

 

Which regulations apply to Clinical Trials of Investigational Medicinal Products (CTIMPs)?

CTIMPs conducted within the UK are subject to the certain regulations.

These are the Medicines for human use (Clinical Trials) regulations 2004, and the subsequent amendments of 2006 (1&2). These Regulations were introduced following the 2001 European Union Directive on Clinical Trials.

What is the scope of the regulations?

The Clinical Trials Regulations apply to every clinical trial of medicinal products whether sponsored by Industry, Government, Research Organisations, Charities or Universities.

• Establishment of ethics committees on a legal basis
• Licensing/Competent Authority (i.e. MHRA) procedures for trial commencement
• Manufacture, import and labelling of investigational medicinal products (IMPs)
• Establishment of inspection systems for Good Manufacturing Practice (GMP) and Good Clinical Practice (GCP)
• Safety monitoring of trial participants and sets procedures for reporting adverse drug reactions and events

What do the regulations describe?

The 2004 regulations take account of:

• Pre-trial authorisation - Research Ethics Committees and the MHRA should respond to a submission within 60 days
• Confidential database of trials - All trials must be registered on the European Clinical Trials Database (EudraCT)
• Research Ethics Committee approval - The scope and function of committees
• Protocol amendments - Defines significant amendments and approval
• Consent process - Subject protection and legal representatives
• Safety reporting - Includes definitions, reporting requirements and timelines
• Regulatory notification of trial end - Timelines for notification to the MHRA and Research Ethics Committee
• Trials supplies and manufacture of Investigational Medicinal Products (IMP)
• Trials involving vulnerable subjects

The 2006 amendments take account of:

• GCP
• Main principles of amendment regulations
• Sponsorship
• Investigator Brochure - Requires sponsor to annually review and update
• Non commercial trials - Provides definition and clarifies IMP issues

 

Medicines and Healthcare Products Regulatory Agency - MHRA

What is the MHRA?

The MHRA is the UK Competent Authority for the regulation of medicines and medical devices. It offers advice about the use of medicines and products in research, undertakes inspections of clinical trials and trial centres, and helps in the preparation of products used in them.

Research involving medicines (but not medical devices) is regulated under the Medicines for Human Use (Clinical Trials) Regulations 2004. All trials of new investigational medicinal products (IMPs) in humans must be authorised by MHRA. No clinical trial of an IMP can commence without a Clinical Trials Authorisation (CTA).

Clinical Trials Authorisations (CTA)

Clinical trials authorisations are provided by the MHRA.

After obtaining a EudraCT number, the trial sponsor (this is usually delegated to the Chief Investigator) completes the CTA application form via EudraCT: European Clinical Trials Database, or the Integrated Research Application System (IRAS). The application should be saved onto your computer as an XML file.

The application is designed to establish a number of criteria about the Investigational Medicinal Product and trial protocol. Further information on submitting a CTA to the MHRA is available in the guidance document, or visit the MHRA website (www.MHRA.gov.uk).

Information for Clinical Trial Investigators

Where can I get a general overview of clinical trials?

Is it a clinical trial?

Are there Trust Standard Operating Procedures?

 

Are there any template documents that the Trust can supply?

 

List of Trust SOPs

Reference Number     Title
RDSOP1                    Preparing and maintaining Trust-wide SOPs
RDSOP3                    Definition / Delegation of responsibilities
RDSOP4                    Research Approval Process (including amendments)
RDSOP5                    Study files and version control
RDSOP6                    Informed consent
RDSOP7A                  Informed consent in special circumstances - Paediatrics
RDSOP7B                  Informed consent in special circumstances - Incapacitated adults
RDSOP8A                  Pharmacovigilance - Trust-sponsored CTs
RDSOP8B                  Pharmacovigilance - non-Trust-sponsored CTs
RDSOP8C                  Adverse event reporting (non CTs)
RDSOP9                    End of study notification
RDSOP10                  Retention of data, archiving and destroying documents
RDSOP11                  Research Governance Monitoring
RDSOP12                  Research Passport - Honorary Research Contracts / Letters of Access
RDSOP13                  Contracts and Financial Management
RDSOP14                  Sponsorship
RDSOP15                  Preparing a GCP-compliant protocol - CTIMPs
RDSOP16                  Preparing a GCP-compliant protocol - non-CTIMPs
RDSOP17                  Research Data Security
RDSOP18                  Statistical Management
RDSOP19                  Financial Management of Clinical Trial

Safety reporting in clinical trials

UK Clinical Trials Regulations set out the legal requirements for pharmacovigilance in clinical trials that evaluate medicines.

The Regulations cover:

• Definitions of adverse events
• The responsibilities of investigators for recording adverse events and the notification of adverse events to sponsors
• The responsibilities of sponsors for reporting to regulatory authorities and Research Ethics Committees

Investigators must comply with Trust Standard Operating Procedures (SOPs) regarding pharmacovigilance and safety reporting in clinical trials.

Further guidance on can be found in:

• Clinical Trials Toolkit document on pharmacovigilance,
• The European Commission's ENTR/CT3: "Detailed guidance on the collection, verification and presentation of adverse reaction reports arising from clinical trials on medicinal products for human use", and
• The National Research Ethics Service's Safety Reporting (CTIMP) table

Definitions of Adverse Events:

Investigators must make themselves aware of the assessment and safety reporting requirements for the trials that they are involved with. These will be described explicitly in the study protocol or associated Standard Operating Procedure. If in doubt, contact the sponsor. In particular, SUSARs are subject to expedited reporting and must, by law, be notified to the sponsor at the earliest opportunity. The Research Office must also be informed of ALL SAEs and SUSARs occurring within the Trust as soon as possible. A list of Definitions can be downloaded here