Running clinical trials in the UK

Understanding CTIMP authorisation

Clinical trials authorisation overview

Overview of MHRA authorisation requirements for clinical trials of investigational medicinal products

A Clinical Trial of an Investigational Medicinal Product (CTIMP) is a study involving investigational medicines to test safety, efficacy, or other properties. No CTIMP can be started, recruit participants, or advertise for recruitment until the MHRA authorises it via a Clinical Trial Authorisation (CTA).

It is a legal requirement to have a sponsor for every CTIMP. Sponsors have legal obligations and must have corporate systems to manage these responsibilities.

Primary legislation: Medicines for Human Use (Clinical Trials) Regulations 2004 (SI 2004/1031)
Major reform: Amendment Regulations 2025 - most changes effective 28 April 2026
Combined review start: 1 January 2022 - single application via IRAS

MHRA clinical trials authorisation guidance

Is your study a CTIMP?

Yes, if:

Testing a new investigational medicinal product
Testing a licensed medicine for a new indication
Comparing licensed medicines in a new way
Using a placebo as comparator

Probably not a CTIMP:

Observational studies of routine prescribing
Non-interventional studies
Medical device trials (separate regulations)

Trial classification and timelines

Your trial's risk classification determines the approval timeline.

Clinical trial type classifications

Trial classification system affecting review pathways and approval timelines

Clinical trials are classified by risk level, which determines review timelines:

Type A trials: Lower-risk trials where sponsor considers risk to participants from IMP is no greater than standard care
Type B trials: Intermediate risk trials
Type C trials: Higher-risk trials including first-in-human studies

Type A approval timeline: 14 days from notification if no objections (Clinical Trial Notification Scheme)
Type B/C initial response: 30 days (average 14 days for Phase 1 healthy volunteer studies)
Advanced therapy products: 90 days for gene therapy/advanced therapy products

HRA CTIMPs guidance

Clinical trial phases

Definition of Phase I, II, III, and IV clinical trials

Clinical trials progress through distinct phases:

Phase I: First-in-human and early-stage trials (may qualify for expedited assessment)
Phase II: Proof of concept, dose-finding, dose-response studies
Phase III: Efficacy and safety evaluation, typically 300+ participants, multicentre, comparing against placebo or standard care
Phase IV: Post-marketing surveillance trials of licensed medicines

Phase IV notification fee: £0 (no fee)
Annual clinical trials fee: None charged by MHRA
MHRA fee schedule period: April 2025 to March 2027

Choosing the right pathway

The Type A/B/C risk classification was the legacy risk-proportionate approach. Since 28 April 2026, the statutory notification scheme replaces it for eligible lower-risk trials: the trial is authorised automatically on notification to the MHRA, though REC approval is still required. The scheme suits:

Trials of licensed medicines used within licence terms
Low-risk comparisons of standard treatments
Studies where IMP risk is no greater than standard care

Full applications (combined MHRA and REC review) are needed for higher-risk trials including first-in-human studies and novel compounds.

Good Clinical Practice

All CTIMPs must comply with GCP principles.

Good Clinical Practice requirements

GCP compliance requirements for clinical trials

All CTIMPs must comply with the conditions and principles of Good Clinical Practice (GCP) set out in UK Clinical Trials Regulations. The current standard is ICH E6(R2), with ICH E6(R3) becoming a legal requirement from 28 April 2026.

GCP training is required for all researchers conducting CTIMPs to protect participant rights, safety, and wellbeing. Refresher training is recommended every 2-3 years.

Current ICH GCP version: ICH E6(R2) - effective since 14 June 2017
New ICH GCP version: ICH E6(R3) - legal requirement from 28 April 2026
GCP principles (R3): 11 detailed principles (reduced from 13 in R2)

ICH GCP guidelines

GCP training requirements

All site staff must complete GCP training before site activation
Chief Investigator responsible for ensuring training completed
Refresher training recommended every 2-3 years
Training must reflect ICH E6(R3), which applies under the 2026 framework

Safety reporting (SUSARs)

Sponsors must report safety events within strict timelines.

SUSAR reporting requirements

Safety reporting timelines for suspected unexpected serious adverse reactions

Sponsors must report Suspected Unexpected Serious Adverse Reactions (SUSARs) to MHRA within strict timelines:

Fatal/life-threatening SUSARs: Report within 7 days, supplementary information by day 8
Non-fatal/non-life-threatening SUSARs: Report within 15 days
Urgent safety measures: Phone MHRA within 3 days, followed by written notification

Annual Development Safety Update Reports (DSURs) covering patient safety analysis must also be submitted.

Fatal SUSAR deadline: 7 days from awareness (supplementary by day 8)
Non-fatal SUSAR deadline: 15 days from awareness
Urgent safety phone: 020 3080 6456 (within 3 days)
2026 change: SUSARs reported only to MHRA (not RECs) from 28 April 2026

MHRA safety reporting guidance

Setting up safety reporting

Register with MHRA ICSR Submissions platform or MHRA Gateway
Establish 24/7 process for identifying urgent safety issues
Create templates for SUSAR reports
Train investigators on adverse event identification
Schedule annual DSUR preparation

Informed consent

Participants must give informed consent before any trial-specific activity.

Informed consent requirements

Requirements for obtaining and documenting informed consent from trial participants

Trial participants must give informed consent before entering a trial (before first trial-specific activity). Consent must be:

Recorded in writing - signed consent form
If unable to write (e.g., disability): oral consent in presence of at least one witness
Electronic consent permitted per HRA and MHRA joint statement

From April 2026: Simplified consent available for lower-risk trials - prescribers can document consent in participant's medical record.

Current requirement: Written consent before first trial-specific activity
Simplified consent (from 2026): Medical record documentation for lower-risk trials
Ongoing duty: Must provide new information that might affect willingness to participate

HRA informed consent guidance

Trial registration

Trials must be registered on a public registry.

Clinical trial registration requirements

Public registry requirements for clinical trials

Clinical trials must be registered on a WHO-recognised public registry. Currently, favourable REC opinion is conditional on registration before first participant recruitment or within 6 weeks.

From 28 April 2026: Legal requirement to register before recruitment of first participant or within 90 days of approval (whichever is sooner).

HRA automatically registers CTIMPs approved through combined review with the ISRCTN registry since 1 January 2022.

Approved registries: ISRCTN or ClinicalTrials.gov (both feed into Be Part of Research)
ISRCTN registration fee: £226 + VAT (ClinicalTrials.gov is free)
2026 legal deadline: Before first participant or within 90 days of approval

HRA research registration guidance

Record retention and archiving

Retention requirements changed significantly for trials applied for on or after 28 April 2026.

Clinical trial record retention

Document archiving and retention requirements for clinical trials

Sponsors must archive Trial Master Files and all essential documents at trial completion. Key requirements:

Appoint named individuals for archiving responsibility
Establish secure archive facilities with environmental control
Documents must be readily accessible to competent authorities on request

Major change from April 2026: Minimum retention period increases from 5 years to 25 years.

Current minimum retention: 5 years (industry standard 10-15 years)
New retention from April 2026: 25 years mandatory minimum
Archive responsibility: Remains with sponsor even if using commercial archive

The 2026 framework (in force since 28 April 2026)

The Medicines for Human Use (Clinical Trials) (Amendment) Regulations 2025 came into force on 28 April 2026.

2026 clinical trials regulatory reform

Key changes coming into force 28 April 2026 under Amendment Regulations 2025

The Medicines for Human Use (Clinical Trials) (Amendment) Regulations 2025 bring the most significant reform of UK clinical trials regulation in 20+ years. Key changes effective 28 April 2026:

Results publication: Legal requirement to publish summary within 12 months of trial end
Participant summary: Must offer to share results in accessible language
Recruitment deadline: First participant within 2 years of approval (extensions available)
Terminology changes: 'amendment' → 'modification', 'subject' → 'participant', 'trial site' → 'trial location'

Results publication deadline: 12 months from end of trial
Recruitment deadline: 2 years from approval (approval lapses otherwise)
REC minimum members: 5 members (with collective qualifications)

HRA clinical trials regulations reform

What the framework requires

Results publication: Publish results within 12 months of trial end
Participant summaries: Provide lay summaries of results
Recruitment timelines: First participant within 2 years or approval lapses
GCP training: Aligned to ICH E6(R3)
Archiving: 25-year retention for trials applied for on or after 28 April 2026

Running clinical trials in the UK

MHRA authorisation for medicines and medical devices

Medicines and controlled drugs compliance

MHRA licensing for medicines and medical devices

Run a retail pharmacy or optical business

Start a clinical laboratory service

Understanding CTIMP authorisation

Is your study a CTIMP?

Trial classification and timelines

Choosing the right pathway

Good Clinical Practice

GCP training requirements

Safety reporting (SUSARs)

Setting up safety reporting

Informed consent

Trial registration

Record retention and archiving

The 2026 framework (in force since 28 April 2026)

What the framework requires

Related guides in Professional Bodies

Understanding CTIMP authorisation

Is your study a CTIMP?

Trial classification and timelines

Choosing the right pathway

Good Clinical Practice

GCP training requirements

Safety reporting (SUSARs)

Setting up safety reporting

Informed consent

Trial registration

Record retention and archiving

The 2026 framework (in force since 28 April 2026)

What the framework requires