Quick Reference Guides and Updates for New Clinical Trials Regulations from 28 April 2026

As you are aware, the new UK Clinical Trials Regulations come into force at the end of April 2026.

Please read the below for an update on amendments (soon called modifications).

Please take a moment to read the information below - our SOPs will be updated accordingly.

The online Introduction to GCP Training is also being updated nationally to reflect the new regulations and should be finalised by the end of February. As soon as it’s available, we’ll let you know and ask all our staff involved in research delivery to plan time to complete the updated training. Sponsors will also begin asking for evidence of updated GCP, so we want everyone to be prepared as early as possible.

From 28 April 2026:

• All changes to an approved CTIMP will be called modifications, not amendments.
• Substantial amendments become Substantial Modifications.
• Non‑substantial amendments become Modifications of an Important Detail (small but regulated changes).
• Minor changes remain Minor Modifications.

The HRA confirmed that this terminology change applies to all studies under the new regulations: The approvals process for modifications (amendments) - Health Research Authority

The key reasons for this change are:

Before 28 April 2026

• Amendments are processed under old rules.
• MHRA had up to 35 days for substantial amendments.
• Process was slower and more fragmented.

From 28 April 2026

• Amendments become modifications.
• MHRA will use a new streamlined review process.
• The IRAS Modification Tool will be used instead of the Amendment Tool.
• Turnaround times are intended to be quicker and more consistent.

The old vs new rules: Amendments vs Modifications (from 28 April 2026) are summarised below as quick reference guide.

 

 

 

As part of the upcoming implementation of the new UK Clinical Trials Regulations at the end of April, we are sharing another key update that will impact how we deliver research across the Trust.

This update focuses on the new simplified consent provisions, which apply to specific lower‑risk CTIMPs.

Under the revised regulations, sponsors of eligible trials may use simplified arrangements for seeking and evidencing informed consent, replacing the default requirement for full written consent. These simplified arrangements are strictly limited to trials that:

• Use licensed medicines,
• Are given as part of routine NHS care, and
• Do not require any extra procedures, tests or treatments solely for research purposes.

Where simplified consent is used, REC approval is still required, and sponsors must provide clear justification in their protocol along with details of how participants will be informed and how consent will be recorded. Evidence of consent may be captured more flexibly (e.g., documentation in clinical notes rather than a signed consent form), but this must be agreed in advance.

SOPs and training materials will be updated to reflect this change.

For now, please familiarise yourselves with the changes summarised below:

• Not all studies qualify - this applies only to lower‑risk, authorised‑medicine trials delivered as part of routine care.
• Sponsors must tell us explicitly if simplified consent is being used.
• REC and MHRA remain responsible for approving its use.
• Staff will be trained in the agreed consent procedure for each study.
• Standard consent processes remain unchanged for all other studies.

 

Key links:

Simplified arrangements for consent in clinical trials - Health Research Authority

New report published on simplified arrangements for consent in clinical trials - Health Research Authority

 

 

Full MHRA & HRA guidance is still being finalised for this.

Under the current legislation, eligibility confirmation often has to be completed by a medically qualified investigator (e.g., doctor or dentist), unless the protocol explicitly allows another authorised clinical staff to do so.

Under the updated regulations, this changes. The definition of a qualified professional has been broadened: the term ‘authorised healthcare professional’ is being replaced with ‘UK registered healthcare professional’. This expanded definition includes a wider range of roles such as pharmacists, advanced practitioners, and other registered healthcare professionals, beyond the traditional medically‑qualified staff.

What this means for us:

• Under the new regulations, more roles can be delegated to confirm eligibility, including research nurses, advanced clinical practitioners, pharmacists, and other UK‑registered healthcare professionals (depending on protocol).
• Eligibility confirmation must still be:
  ✔ Delegated by the PI
  ✔ Performed by someone with appropriate registration, competence, and GCP + study‑specific training
• Clinical judgement elements must still be completed by someone professionally trained and competent to assess them.
• The PI retains overall responsibility for eligibility assessment.

The aim of this change is to make screening and set‑up more efficient and reduce dependency on medical availability, while continuing to ensure safe and appropriate decision‑making.

	OLD Rules (pre‑April 2026)	UPDATED Rules (from 28th April 2026)
Who could confirm eligibility?	Only medically qualified investigators (doctor, dentist) or a limited set of authorised health care professionals depending on protocol.	Can be completed by any UK registered health care professional, per new regulatory terminology. Broader list includes more professions such as pharmacists, some allied health professionals, advanced practitioners.
Definition of allowed staff	Narrow: doctor, dentist, or other clinician explicitly authorised.	Broader: ‘UK registered health care professional’ (new legal definition in updated regulations). Expands who can perform trial-related clinical tasks, including eligibility confirmation.
Competency requirements	Qualifications + GCP + protocol training; PI delegation required	Same requirements plus proportionate approach: competency, scope of practice, and delegation remain essential.
Delegation by PI	PI can only delegate eligibility confirmation to individuals allowed under old definition (doctor/nurse/pharmacist depending on local policy).	PI can delegate to a wider range of qualified healthcare professionals, as long as they are UK‑registered and trained for the task.
Documentation	Eligibility confirmation documented by medically qualified staff; protocol‑dependent.	Must still be clearly delegated and documented, but staff groups eligible to perform this task broaden.
Impact on research delivery	Limited flexibility; more pressure on medical staffing for screening and eligibility confirmation.	More flexible, enables research nurses, advanced practitioners, pharmacists, and other registered professionals to confirm eligibility where appropriate.
Clinical judgement requirement	Some criteria could be confirmed by non‑clinical staff, but clinical eligibility elements required a doctor/dentist.	Clinical judgement still required for clinical criteria, but performed by any appropriately registered clinician under expanded definition.
Overall effect	Tighter restrictions on who could confirm eligibility.	Broader workforce can confirm eligibility, improving speed and efficiency while maintaining safety.

 

While the regulatory terminology change has been confirmed, MHRA has not yet published full, detailed guidance on exactly how eligibility confirmation will be operationalised under the new rules.

We therefore expect:

• Further clarification from MHRA on scope of delegation
• Additional examples of which roles may perform clinical eligibility checks
• Updates to sit alongside the new GCP guidance and modification guidance already published

As soon as MHRA publishes the full guidance, we will review it and update our SOPs, training materials, and delegation processes accordingly.

In the meantime, please continue to follow:

• The current expectations and GCP requirements
• Protocol‑specific instructions
• PI’s delegation

This update is on changes to safety reporting requirements for CTIMPs.

 The updated legislation places stronger emphasis on risk‑proportionate safety oversight, efficient reporting, and removal of unnecessary duplication in expedited safety reporting:

-  Greater focus on Risk‑Proportionate Safety Oversight - Sponsors are now expected to embed a risk‑proportionate approach into safety management throughout the trial lifecycle, including ongoing review of safety signals identified during development and transparent documentation of how these signals are being managed

- Streamlining of SUSAR Reporting – the updated legislation specifically addresses duplication in SUSAR reporting. Sponsors remain responsible for expedited reporting but with clearer, leaner processes to reduce repeat or unnecessary submissions

-Clarified Roles and Responsibilities – the key responsibilities remain the same but are reinforced:

>Sponsors retain overall responsibility for participant safety, including benefit‑risk evaluation and all expedited/aggregate reporting obligations.

>Investigators remain responsible for the medical care and clinical decisions for participants.

>MHRA continues to oversee safety information to assess ongoing risk‑benefit.

 

Old vs. Updated Rules:

	OLD Rules (pre‑Apr 2026)	UPDATED Rules (from 28 Apr 2026)
Approach to safety management	Standard, often uniform requirements across trials	Strong focus on risk‑proportionate safety oversight
SUSAR reporting	Duplication in some reporting channels	Duplication reduced; more streamlined processes
Sponsor responsibility	Safety oversight + expedited/annual reporting	Same, but with enhanced expectations around risk‑signal review & documentation
Investigator role	Medical care & decision‑making	Unchanged, but reinforced
MHRA oversight	Review of safety info; AE/SUSAR regulation	Enhanced transparency and clearer processes under updated guidance
Safety guidance	Based on existing CTR framework	Updated MHRA guidance (2025/2026) aligned to amended Regulations

 

What this means for us:

• Our Sponsor Oversight SOPs, pharmacovigilance documentation, and reporting workflows will need updating to align with the revised requirements.
• Investigators and research teams must ensure continued compliance with current GCP, protocol requirements, and immediate reporting obligations while we transition to the updated processes.

As our R&I acts as both, study sponsor (Trust sponsored studies) and investigator sites (our own sponsored studies and hosted studies),below there is a split to make the updates clearer – please refer to the section that’s relevant toy your area of work:

• Section A – Responsibilities for the Trust as Sponsor
• Section B – Responsibilities for the Trust as Research Delivery Site

 

	Sponsor Responsibilities – please refer to section A below	Delivery Site Responsibilities – please refer to section B below
Risk‑proportionate safety oversight	Update safety management plans; monitor signals; document decisions	Follow updated Sponsor guidance and implement any revised processes
SUSAR reporting	Ensure streamlined, non‑duplicated SUSAR submission pathways	Provide timely causality/expectedness assessments to enable SUSAR reporting
AE/SAE reporting framework	Maintain RSI, safety records, annual reports, USM & breach submissions	Detect, document, and report AEs/SAEs per protocol and Sponsor timelines
Investigator responsibilities	Oversight of safety systems and compliance	PI responsible for participant care and clinical decisions
Documentation & training	Update Sponsor SOPs, templates & agreements	Adopt updated documents; complete updated training

 

Section A - Responsibilities for the Trust as Sponsor:

Key updates for Sponsor teams are:

1. Risk‑proportionate safety management - Sponsors must embed a risk‑proportionate approach throughout safety oversight by reviewing safety signals emerging during development and transparently and documenting how these are being managed in ongoing trials.

Implications for Sponsor teams:

• Update Sponsor-level risk assessments and safety management plans.
• Ensure safety signal detection and escalation processes are robust and documented.
• Review Pharmacovigilance responsibilities to ensure alignment with new requirements.

2. Streamlining SUSAR Reporting to remove duplication

Implications for Sponsor teams:

• Review SUSAR reporting workflows and determine where duplicate reporting steps can be removed.
• Ensure EudraVigilance/UK safety database processes are aligned with MHRA expectations.
• Update SOPs accordingly.

3. Sponsor Oversight of Safety Reporting

Sponsors remain responsible for:

• Oversight of all expedited and aggregate safety reporting.
• Maintaining RSI (Reference Safety Information) and ensuring it is aligned and version‑controlled.
• Submissions of annual safety reports, urgent safety measure notifications, and serious breach reports.

Sponsors must now prepare for:

• SOP updates to reflect revised definitions
• A more transparent record of safety signal review and decision‑making.
• Updated template agreements, reporting forms and Pharmacovigilance documentation once MHRA publishes additional guidance.

Updated MHRA Safety Reporting Guidance provides detailed expectations on the following:

• AE/SAE reporting
• MedDRA coding
• RSI (Reference Safety Information)
• SUSAR reporting procedures
• Annual safety reporting
• Serious breaches and urgent safety measures

Link to the guidance: Clinical trials for medicines: collection, verification and reporting of safety events - GOV.UK

• Section B – Responsibilities for the Trust as Research Delivery Site/ Research Delivery Teams:

While the Sponsors manages high‑level Pharmacovigilance oversight and regulatory reporting, the research delivery teams continue to hold responsibilities related to participant care, detecting/reporting AEs/SAEs, and implementing safety processes locally:

1. Investigator Responsibilities remain unchanged

Investigators are still responsible for:

• The medical care of participants and associated clinical decisions.
• Assessing seriousness, causality and expectedness in line with Sponsor guidance and protocol.
• Ensuring timely reporting of AEs/SAEs to the Sponsor.

2. Delivery Teams must continue Timely Safety Reporting to Sponsor

The updated MHRA guidance still requires:

• Prompt capture and reporting of AEs/SAEs.
• Use of correct safety reporting forms and adherence to protocol timelines.
• Ensuring safety documentation is complete, accurate and source‑verified.

3. Alignment with Updated Study Documents

Once Sponsor teams issue updated RSIs, reporting instructions or modified safety reporting sections of the protocol/SMPc:

• Delivery staff must transition to the updated materials immediately (via implementation of modifications procedure)
• All teams must complete any updated study‑specific or GCP‑linked safety training.

4. Responsibilities During Urgent Safety Measures or Serious Breaches

MHRA guidance re‑confirms processes for:

• Immediate implementation of urgent safety measures where necessary.
• Rapid notification to Sponsor for onward MHRA/HRA reporting.
• Delivery teams must ensure local procedures allow immediate escalation to CI/PI and Sponsor.

The MHRA is expected to release additional clarity as we approach implementation, including:

• Further explanation of risk‑proportionate safety expectations
• Updated templates and examples for SUSAR and annual safety reporting
• Additional operational guidance to accompany the new GCP (ICH‑GCP E6 (R3)) framework
  
  

In the meantime, please continue to follow:

• Current MHRA safety reporting requirements
• GCP principles and protocol‑specific safety instructions
• PI-led delegation and local reporting processes

This update is on the move to a proportionate and risk‑based framework through the UK’s implementation of the updated Good Clinical Practice guideline ICH E6 (R3).

The amended UK Clinical Trials Regulations apply to CTIMPs only - for CTIMPs, the UK will formally implement ICH E6(R3) from 28 April 2026, alongside the amended regulations.

For non‑CTIMPs, ICH E6(R3) is not being implemented as a legal requirement; however, HRA is introducing aligned processes (terminology, transparency and timelines) from April 2026 to improve overall UK consistency, and teams should continue to work to proportionate GCP principles as good practice for all research studies.

What is changing?

 ICH E6 (R3) puts stronger emphasis on proportionate, risk‑based delivery. It strengthens expectations around:

• Factors critical to safety and data reliability  - focus on what really matters and prioritise the parts of research projects that are most important for keeping participants safe and ensuring the data is accurate (these are called Critical‑to‑Quality factors - CtQ.)

 

• Flexible, fit‑for‑purpose approaches to study design and delivery - processes, tools and study designs should be appropriate for the level of risk and complexity, and not unnecessarily complicated.  

 

• Proportionate processes based on risk, complexity, and impact -oversight, monitoring and documentation should match the actual risk and impact, rather than using the same intensity for every study.

 

• Organisational responsibility and fit‑for‑purpose systems- teams and organisations must show they have clear delegation, good oversight, and systems that are fit‑for‑purpose to support safe, high‑quality research delivery.

 

This represents a strong shift away from one‑size‑fits‑all approach. For Research Delivery Teams this means:

 

1. More proportionate procedures, such as reduced routine SDV for low‑risk areas, leaner documentation focused on value and necessity and simpler, more scalable processes where risk is low.

 

2. Clearer expectations on risk assessment. For individual studies, Delivery Teams will need to have the understanding of:

-What is critical to safety and data reliability for the study

-Where oversight and resource should be focused for the study

-Where flexibility is appropriate for the study

 

3. For trial conduct and monitoring, Delivery Teams will see more targeted, risk‑based monitoring, fewer routine checks that don’t affect quality and more remote or centralised monitoring options.

 

4. Shift from amendments to modifications with more risk proportionate handling

 

5. Documentation should be relevant and proportionate. Documentation should focus on what is needed for safety, data quality and oversight - avoid creating paperwork just for the sake of it.

 

6. You’ll see more focus on using systems that are appropriate for the trial, ensuring clear delegation and oversight, and keeping local practice aligned with Sponsor expectations -especially for CTIMPs.

 

To support implementation of ICH E6(R3), updated NIHR GCP training is now live on NIHR Learn. By 28 April 2026, everyone involved in CTIMPs must have completed either the Intro or the Refresher to GCP.

 

• If you are new to research / never done NIHR GCP Intro: please complete Introduction to GCP E6(R3)
• If you’ve previously completed NIHR GCP Intro: please complete the GCP E6(R3) Refresher.

https://learn.nihr.ac.uk/course/view.php?id=1575

 

Old vs. Updated Rules

 

 

Formal Guidance is still to come:

 

MHRA has confirmed that further operational guidance supporting ICH E6(R3) will be published.
This is expected to include:

• Practical examples of proportionate approaches.
• Expectations for adaptive designs.
• Oversight and documentation expectations.
• How E6(R3) and E8(R1) will be operationalised in the UK.

We will update local SOPs as soon as guidance is released.

 

In the meantime, please continue to follow:

• Current GCP guidance and local processes
• PI and Sponsor delegation
• Existing study‑specific risk assessments
• Complete the updated GCP training