Originally published in the October 2025 edition of DIA’s Global Forum magazine, this article — authored by Mandy Budwal-Jagait, Kingyin Lee, Maria Urdaneta-Abate, Hedwig Ganguly, Rachel Mead, and Louisa Obillo of the UK Medicines and Healthcare products Regulatory Agency (MHRA), together with Catherine Blewett of the Health Research Authority (HRA) — outlines how upcoming revisions to the UK’s clinical trials legislation will reshape safety reporting. The authors explain the new risk-proportionate framework, harmonised timelines, and streamlined reporting pathways designed to enhance participant safety while reducing administrative burden for sponsors.

 

As part of the revision to the UK clinical trials legislation coming into force on 28 April 2026, the Medicines and Healthcare products Regulatory Agency (MHRA) undertook a review of requirements and timelines associated with safety management and reporting. As a regulator, we support a pragmatic and risk-proportionate approach, and the revised legislation encourages sponsors to embed risk proportionality within their operations. In today’s context of evolving clinical trials, technology, and innovative products, this revision places emphasis on the sponsor to review safety signals identified during product development and transparently describe to the regulator how these are being managed in the context of their ongoing clinical trials. Efforts have also been made to remove duplication in the reporting of Suspected Unexpected Serious Adverse Reactions (SUSARs). While a risk-proportionate approach is encouraged throughout this regulatory reform, participant safety remains paramount. This article describes these changes, why they have been made, and what stakeholders can do to prepare.

 

Roles and Responsibilities

Within both the current and future UK clinical trials regulations, the sponsor remains responsible for overall safety of participants in the clinical trial through ongoing review of the benefit-risk profile of the product(s) and trial and complying with all safety requirements in the regulations, including expedited and aggregate reporting of safety events. The investigator retains responsibility for the medical care and decisions made on behalf of their participants. The MHRA has oversight of safety information received in relation to a clinical trial to review the ongoing risk-benefit of the trial.

Robust pharmacovigilance processes are essential for all parties to act promptly, ensure participant safety, and report safety events transparently. Since clinical trial participants face risks without the certainty of benefit, clearly communicating safety information to participants and investigators is crucial for informed consent, and for building trust in research participation. Following the clinical trial, transparently reporting safety information informs decisions on Marketing Authorisation applications or prescribing practice and can deepen scientific knowledge which can inspire further development or research.

 

Modifications and Pre-market Pharmacovigilance

The revised clinical trial legislation will introduce the term “modifications” to replace “amendments” used to denote an update or change to a clinical trial approval.

There will be two categories of substantial modifications:

– “Route A” is where the MHRA assessment is required because of a likely substantial impact on participant safety or to address new safety concerns, the rights of participants, or the data integrity.

– “Route B” is an automatic approval route without the MHRA assessment, as explained in the MHRA website guidance Clinical trials for medicines: modifying a clinical trial approval.

The categorization of substantial modifications (Route A or Route B) is not applicable to reviews conducted by the Research Ethics Committee (REC). All substantial modifications pertinent to the REC shall undergo the standard review and approval process.

Safety-related modifications which have an impact on the benefit-risk of the Investigational Medicinal Product (IMP) or trial will continue to be assessed to uphold the MHRA’s commitment to ensuring safety of UK clinical trial participants.

 

Read the full original article on the DIA Global Forum website