Pharmacovigilance

Pharmacovigilance 

Pharmacovigilance (PV) is the science concerned with the detection, assessment, understanding and prevention of the adverse effects of medicines. For clinical trials, robust systems must be in place to identify, record, report, and analyse safety information so that emerging safety signals can be detected and addressed.

For Clinical Trials of Investigational Medicinal Products (CTIMPs), the sponsor's PV responsibilities are set out in Part 5 of the Clinical Trial Regulations (SI 2004/1031), and the Medicines and Healthcare products Regulatory Agency (MHRA) provides comprehensive guidance on the collection, verification, & reporting of safety events. The Health Research Authority (HRA) website outlines the procedures for safety reporting, which depend on whether or not the trial was submitted through the combined review process. 

To determine whether an adverse event qualifies as a Suspected Unexpected Serious Adverse Reaction (SUSAR), it must be assessed for seriousness, causality and expectedness. As the expectedness assessment is often misinterpreted, the MHRA has published a series of blogs to guide sponsors. An Adverse Event Flowchart (PDF, 180.98 KB) is also available. 

Reference Safety Information (RSI)

The status of the Investigational Medicinal Product (IMP) determines which RSI should be used. The RSI is usually the Investigator’s Brochure (IB) or the Summary of Product Characteristics (SmPC). In addition to the MHRA blogs, the Clinical Trial Facilitation Group (CTFG) has published a Q&A document (.PDF) on the RSI.

In non-commercial trials, an IB may be provided by the Marketing Authorisation Holder. If it cannot be obtained or if the IMP is being developed in-house, the sponsor is responsible for preparing the IB.

Investigator Site Preparation

Before the trial begins, investigators should inform all staff of the trial’s safety reporting requirements and ensure that systems are in place to detect, document, and report all protocol-required events (see Safety Reporting station). 

New Clinical Trials Regulations 

On 28 April 2026, the Medicines for Human Use (Clinical Trials) (Amendment) Regulations 2025 (SI 2025/538) will come into force. These changes to the Regulations include new PV requirements.

The MHRA has published guidance on the new Regulations setting out certain requirements that should be followed before 28 April 2026, and those that will take effect from 28 April 2026 onwards. The HRA has also published guidance to enable sponsors and researchers to prepare.

Further Reading

• ICH E19 (2023): Selective safety reporting in specific late-stage pre-approval or post-approval clinical trials.
• Safety Reporting station.