The GCP & Serious Breach Reporting station follows the Ongoing Management & Monitoring station and precedes the MHRA Inspection station. This process occurs in parallel with Safety Reporting, Progress Reporting, and Ongoing Management & Monitoring. It also has the potential to occur simultaneously with an MHRA Inspection, Audit, Substantial Amendments, Addition of New Sites & Investigators, Urgent Safety Measures, Temporary Halt, and Early Termination. GCP & Serious Breach Reporting is a legal requirement which is relevant to all trials. This station is part of the ‘recruitment phase’ group of stations.
The Clinical Trials Regulations require all clinical trials of investigational medicinal products (CTIMPs) to be run to the conditions and principles of Good Clinical Practice (GCP). The Regulations define GCP as:
“.... a set of internationally recognised ethical and scientific quality requirements which must be observed for designing, conducting, recording, and reporting clinical trials that involve the participation of human subjects.”
Compliance with GCP provides assurance that the rights, safety, and well-being of subjects are protected and that trial results are credible.
For CTIMPs, the conditions and principles of GCP are set out in Part 2 of the Medicines for Human Use (Clinical Trials) Amendment Regulations 2006 and can be accessed here. The MHRA and HRA advocate a proportionate approach to the application of GCP to the conduct of clinical trials. These flexibilities are described in a joint statement.
The MHRA Inspectorate has published the Good Clinical Practice Guide, which provides information and practical examples of how to apply the conditions and principles of the GCP in a risk-based way.
Non-CTIMP research, should be conducted in a manner that provides public assurance that the rights, safety, and wellbeing of research participants are protected, and that research data are reliable.
Participating Sites Responsibilities:
For a multi-site trial, the person with overall responsibility for the trial at each site is defined as the Principal Investigator. Guidelines for GCP, from the perspective of the Principal Investigator, are detailed in Section 4 of ICH GCP E6 (R2).
The sponsor should ensure that each site is aware of all regulations and quality standards that apply to CTIMPs by:
- Specifying the standards that must be adhered to in any site agreements
- Ensuring that site staff have received GCP and Clinical Trials Regulation training commensurate to their role.
Serious Breach of GCP/Protocol:
The Clinical Trials Regulations require the reporting of serious breaches of GCP or the protocol (regulation 29A of S12004-1031 as amended). Guidance on the definition and reporting requirements can be found on the MHRA web pages: Serious Breach and Good Clinical Practice Reporting. In the UK, serious breaches should also be reported to the relevant ethics committee at the same time as the report to the MHRA, in accordance with Research Ethics Committee Standard Operating Procedures.
Sponsors of CTIMPs should ensure the requirement to report serious breaches to the MHRA and the ethics committee is incorporated into their standard operating procedures to ensure all relevant staff are aware of this legal requirement. This should include detail of how site staff are made aware of requirements (via training or protocol procedures). Host organisations and other parties working with the trial sponsor may also need to consider their own mechanisms for reporting serious breaches (including arrangements for reporting serious breaches directly to the MHRA if the sponsor is in breach).
For non-CTIMP research, serious breaches of GCP or the protocol should be reported to the relevant ethics committee in accordance with the Research Ethics Committee Standard Operating Procedures.
- Ongoing Management & Monitoring station
- Conditions and Principles of Good Clinical Practice Summary Document
- The MHRA Good Clinical Practice Guide
- WMA Declaration of Helsinki - Ethical Principles for Medical Research Involving Human Subjects