Guidance on Good Clinical Practice for PET Imaging Centres

This guide is intended as a brief introduction to the principles of good clinical practice and how this relates to PET centres imaging patients as part of clinical trials. It is not intended as a replacement for existing guidance or as a substitute for GCP training. References to the regulations and further resources can be found here:

• The Medicines and Healthcare Products Regulatory Agency (MHRA) Good Clinical Practice for Clinical Trials Guidance provides advice on how to show the MHRA you are meeting good clinical practice (GCP) standards and what to expect from an inspection.
• The National Institute for Health Research (NIHR) Clinical Trials Toolkit provides practical advice to researchers in designing and conducting publicly funded clinical trials in the UK.
• The Medical Research Council (MRC) Good Research Practice webpages set out the MRC's expectations for MRC funded researchers and facilities.

What is Good Clinical Practice (GCP)?

Good Clinical Practice (GCP) is an ethical and scientific standard covering all aspects of the design, conduct and reporting of clinical trials involving humans. The purpose of the standard is to ensure that the rights, integrity and confidentiality of trial subjects are protected and to provide assurance that the data and reported results are credible and accurate.

Scope

All clinical trials involving investigational medicinal products (CTIMPS) are covered by the UK Clinical Trials Regulations which require compliance with the conditions and principles of GCP. Staff involved in the conduct of clinical trials need to be appropriately trained so that all members of the investigating team know what is expected of them in relation to trial procedures, and in order to ensure that the conditions and principles of GCP can be applied to any trial in a proportionate manner. Further details can be found in the Joint Statement on the Application of Good Clinical Practice to Training for Researchers.

The Clinical Trials Regulations do not encompass non-CTIMPS, however the UK Policy Framework for Health and Social Care Research does require ALL research to be conducted using the principles of GCP.

Responsibilities

Responsibility for compliance with GCP and the conduct of clinical trials falls with the Sponsor. Sponsors may formally delegate specific aspects of the clinical trial to individuals or organisations who act on behalf of the Sponsor, for example the Chief Investigator (CI) or the clinical trials unit, but overall responsibility still lies with the Sponsor. The full definition of the Sponsor's functions and responsibilities can be found in the Clinical Trials Regulations and the Research Governance Framework. For clinical trials with multiple participating sites a Principal Investigator is assigned who will have responsibility for the trial at that specific site.

Sponsors should ensure the delegation of functions and responsibilities is clearly documented (usually with a delegation and training log and through site agreements). Any individuals who have delegated functions are responsible for knowing and following the law and principles of GCP. Therefore the Sponsor must ensure all staff involved in research undergo GCP training.

Conditions and Principles of GCP

In UK law the principles of GCP are defined in The Medicines for Human Use (Clinical Trials) Amendment regulations 2006. The NIHR Clinical Trials Toolkit provides a summary document here.

Trial Master File and Site File

To comply with the Clinical Trials Regulations all CTIMPS must have a 'Trial Master File' containing all essential documents and authorisations relating to a trial. In addition to this for multi-site trials, each site must also have an 'Investigator Site File' which contains copies of the documentation relevant to the site. The Trial Master File and Investigator Site File are not compulsory for non-CTIMPS, however maintaining these will ensure compliance with GCP and will help towards the smooth running of the trial.

The Trial Master File and Investigator Site File should be set up at the start of a trial and maintained throughout the duration of the trial. These are subject to inspection and should be readily available for the Sponsor or external regulator to review. The previous versions of documents should be retained alongside the latest versions and a record of amendments e.g. the trial protocol or patient information sheet. Any amendments will require ethics approval and the sponsor should also be made aware of the changes. For amendments involving PET radiation doses the Administration of Radioactive Substances Advisory Committee (ARSAC) should be made aware of the variation. Updated ethics approval letters will be issued and should be retained in the file.

The Trial Master File is normally kept at the Chief Investigators institution and the Investigator Site File is kept at participating sites. Both should be stored in a locked cabinet or room in a secure area with access restricted to authorised trial personnel only. Depending on the type of trial, complexity of the PET procedures and the management team setup, Investigator Site Files may be stored within the PET department and designated PET staff will be responsible for maintaining them. Even if the PET department is not responsible for maintaining the site files, they must provide records and essential documentation relevant to the PET procedures / staff for the Investigator Site File.