Compliance with the regulations | Good Clinical Practice

Good Clinical Practice

What is Good Clinical Practice?

Good Clinical Practice is a term used to identify the components of Schedules 1 and 2 of the Medicines for Human Use (Clinical Trials) Regulations 2004. Schedule 2 describes 13 principles and 3 conditions which define lawful conduct when carrying out research into medicinal products. GCP is a major part of the overall Research Governance Framework for Health and Social Care.

GCP principles

Clinical trials shall be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki, and that are consistent with good clinical practice and the requirements of these regulations.
Before the trial is initiated, foreseeable risks and inconveniences have been weighed against the anticipated benefit for the individual trail subject and other present and future patients. A trial should be initiated and continued only if the anticipated benefits justify the risks.
The rights, safety and well-being of the trial subjects are the most important considerations and shall prevail over interests of science and society.
The available non-clinical and clinical information on an investigational medicinal product shall be adequate to support the clinical trial.
Clinical trials shall be scientifically sound, and described in a clear, detailed protocol.
A trial shall be conducted in compliance with the protocol and has a favourable opinion from an ethics committee.
The medical care given to, and medical decisions made on behalf of, subjects shall always be the responsibility of an appropriately qualified doctor or, when appropriate, of an qualified dentist.
Each individual involved in conducting a trial shall be qualified by education, training, and experience to perform his or her respective task(s).
Subject to the other provisions of this schedule relating to consent, freely given informed consent shall be obtained from every subject prior to clinical trial participation.
All clinical trail information shall be recorded, handled, and stored in a way that allows its accurate reporting, interpretation and verification.
The confidentiality of records that could identify subjects shall be protected, respecting the privacy and confidentiality rules in accordance with the requirements of the Data Protection Act 1998 and the law relating to confidentiality.
Investigational medicinal products used in the trial shall be
a) manufactured or imported, and handled and stored, in accordance with the principles and guidelines of good manufacturing practice, and
b) used in accordance with the approved protocol.
Systems with procedures that assure the quality of every aspect of the trial shall be implemented.

Conditions

A trial shall be initiated only if an ethics committee and the licensing authority comes to the conclusion that the anticipated therapeutic and public health benefits justify the risks and may be continued only if compliance with this requirement is permanently monitored.

The rights of each subject to physical and mental integrity, to privacy and to the protection of the data concerning him in accordance with the Data Protection Act 1998 are safeguarded.

Provision has been made for insurance or indemnity to cover the liability of the investigator and sponsor which may arise in relation to the clinical trial.

Associated requirements

Ethics

Ethics committees are recognised as key gatekeepers in determining the quality and appropriateness of research. However, their mode of operation is not universally efficient. The Regulations therefore also includes standards for relevant local REC's and main REC's which mainly focus on ensuring that proposals are dealt with within a specific time frame. This will be 60 days from the date of receipt of a properly completed application. Download details of the research governance framework for REC's (GAfREC) below.

Download Governance Arrangements for NHS Research Ethics Committees (GAfREC).

Data Protection

The Data Protection Act (1998) was developed to protect the confidentiality of personal data stored on living individuals. Personal data is defined as data which relates to a living individual who can be identified from those data. It is a legal duty to abide by the Data Protection Act. Its eight defining principles are that data should be

Fairly and Lawfully processed
Processed for specified purposes
Adequate, relevant and not excessive
Accurate
Not kept for longer that necessary
Processed in accordance with the data subjects rights
Secure from unauthorised access or alteration
Not transferred to countries without adequate data protection controls.

The Medicines and Healthcare products Regulatory Agency (MHRA)

The Medicines and Healthcare products Regulatory Agency (MHRA) website has information on it about the standards and the basis of inspections and a FAQ. This can be found at http://www.mhra.gov.uk/Howweregulate/Medicines/Inspectionandstandards/GoodClinicalPractice/index.htm

To whom does GCP apply?

Any organisation which develops, hosts or sponsors clinical trials involving a medicinal products intended for use in humans is covered by GCP requirements.

The role of the research sponsor

Under the Regulations, the research sponsor is identified as, 'The organisation responsible for the initiation, management and/or financing a trial'.

In most cases this will be the company/other body paying for the trial. However, some trials take place which have no funding attached, or the funder is unable to take on the responsibility. As sponsorship is linked to the initiation of a study, the Trust or Queen Mary University of London may find themselves in the position of being a GCP sponsor. This will be decided on a case by case basis and is dependant on an all parties agreement relating to roles and responsibilities.

The sponsor is responsible for ensuring all legal standards and processes have been adhered to prior to, and during, the clinical trial. An ethics committee will not consider a study without a sponsor being identified so it is imperative that this consideration is handled early in the approval process. More information about arranging sponsorship for your trial>>

How GCP compliance is monitored

Monitoring is carried out by the MHRA, who have statutory rights of access and can make planned or unannounced visits. Capacity in the inspection team is limited, but it is not unreasonable for either the Medical School or the Trust to expect to be inspected in the first 2-3 years.

A system of internal research audit is in place within the Trust which follows similar lines to the MHRA audit process. This is to ensure that research being conducted is in compliance to regulation and allows for the development of clear lines of accountability and support throughout the organisation.

Ensuring researchers are compliant

Staff working with commercial companies should be able to call on the advice of company representatives or those working for contract research organisations. Most CROs have their own auditors on hand to ensure that GCP processes are followed and documentation is up to scratch.

For those working on non-commercial studies at the London, the Research Governance & GCP Managers can give advice on GCP issues. They will visit departments and units where trials are being undertaken, check what the degree of compliance is and advise investigators on any corrective action they should take.

Training

In addition the Joint Research Management Office offers a training programme on GCP targeted at two different groups of staff:

Chief/Principal Investigators
trial staff providing day to day support for research: eg pharmacists, trials co-ordinators, research nurses, fellows etc

It is compulsory for any Investigator wishing to have the Trust or University as sponsor, to have been through this training, or to have certificated evidence of attendance on other, external GCP courses.

See here for more information on training for GCP, Research Governance and Regulations

As GCP is a legal requirement anyone involved in trials must make sure that they have at least a basic knowledge of the standards.

Further information

The JRMO has produced a leaflet with further guidance on the Clinical Trials Regulations and some practical advice.

Download Clinical trials regulations leaflet.

For any GCP related queries, please contact Research Governance & GCP Managers

You can also get advice from the MHRA website http://www.mhra.gov.uk/ or contact the MHRA's Clinical Trials Unita:

GCP Inspectorate, MHRA, 151 Buckingham Palace Road, Victoria, London SW1W 9SZ - Tel: 020 3080 6606
GCP Inspectorate, MHRA, 2 Falcon Way, Shire Park, Welwyn Garden City, Hertfordshire, AL7 1TW - Tel: 01707299130, Fax: 01707 376649
GCP Inspectorate, MHRA, 2a Hunter House, 57 Goodramgate, York, YO1 7FX - Tel: 01904 610556, Fax: 01904 625430

Email: info@mhra.gsi.gov.uk or clintrialhelpline@mhra.gsi.gov.uk

The MHRA's offices are staffed from 9am to 5pm. Outside these hours a voice mail system is in operation.