UK Clinical Trials Enter a New Regulatory Era

Streamlined Approvals Process 

The combined review process, which enables a single coordinated application for both MHRA regulatory and Research Ethics Committee (the "REC") approval, has operated as an administrative process since its introduction, but was not previously enshrined in legislation. The New Rules now formally provide for combined review in legislation, making it the standard route for clinical trial applications. Combined reviews are submitted via the Integrated Research Application System (the "IRAS"), resulting in a single UK decision. Once validated (within seven days of submission), authorities must take all reasonable steps to issue a combined decision within 30 days beginning with the date on which any person responsible for the initiation, management and financing of the trial (the "Sponsor") is notified that the request is valid.

Where further information is requested, the Sponsor may submit a written response or amended request within 60 days beginning with the day the notice is given (or such extended period as may be allowed), and authorities must take all reasonable steps to give notice of its decision within 10 days of receipt of the amended request (subject to statutory extensions in specified cases) before issuing a final joint outcome.

Notifiable Trials

A particularly notable addition is the formalisation of a streamlined, risk-proportionate notification scheme for certain "notifiable trials". In broad terms, a trial will fall within this category where the investigational medicinal products ("IMP") are not being used for the first time in humans and where there are no significant safety concerns. Eligibility also depends on the status and prior regulatory history; for example where the IMP is UK-authorised and used within its authorisation (or in a way supported by established clinical practice), where a closely comparable UK trial was approved in the last two years, or where the trial has already been assessed and approved by a competent authority in the EU, an EEA State or the United States. The scheme is not available for certain higher-risk scenarios (including trials involving children, pregnant or breastfeeding participants, or advanced therapy medicinal products).

Notifiable trials are still submitted for combined review via IRAS. The practical advantage is that, once the application is validated, the MHRA will either confirm automatic authorisation or object within 14 calendar days (and, if it objects, the application moves into full assessment). The trial cannot start unless a combined decision is issued, so Sponsors should assume the overall timetable will still largely be driven by the combined review process (typically 30 calendar days from validation, subject to statutory extensions). Sponsors should assess notification eligibility early and keep a clear file note of the rationale and supporting evidence.

Modification Pathways

The New Rules set out a more clearly tiered, risk-based framework for handling postauthorisation changes. It is the Sponsor's responsibility to categorise the change correctly and maintain a clear audit trail.

At the top end, "substantial modifications" require approval from the licensing authority and the REC before implementation (subject to the urgent safety measures process). The New Rules distinguish between Route A substantial modifications, which are changes likely to have a substantial impact on participant safety or rights or on the reliability or robustness of trial data; and Route B substantial modifications, which are defined by reference to the "no new significant safety concerns" concept and specified conditions relating to (among other things) prior regulatory review. In practice, Route B is intended to support a more streamlined MHRA assessment, because the licensing authority may (if it considers it appropriate and without undertaking further assessment) rely on the Sponsor's Route B statement when reaching its decision; however, the modification still sits within combined review and will still require REC input where relevant. Substantial modification requests follow a formal statutory validation and decision process (including a mechanism to pause and resume review where further information is requested).

Alongside substantial modifications, the amended regime also introduces a distinct category of "modifications of an important detail". These are changes that do not significantly impact participant safety or rights but which the authorities should be aware of for administrative or oversight purposes. They must be notified and do not require prior approval. Other changes may fall within the category of "minor modifications", which can be implemented without notifying the MHRA or the REC at the point of implementation, provided the Sponsor keeps records and can supply them if requested, or on the next substantial modification submission. This is helpful flexibility, but makes disciplined internal change-control (and documentation) more important, particularly to avoid inadvertently treating a substantial modification as a minor change. Substantial modifications requests and notifications of important details are submitted through the online portal.

Notably, a request to modify a clinical trial approval received by the authorities after 28 April 2026 will be subject to the New Rules, regardless of whether the clinical trial was approved under the old rules.

Enhanced Transparency Requirements 

Under the previous framework, clinical trial transparency requirements were driven largely by research ethics conditions and policy guidance rather than express statutory obligations. Trial registration and results disclosure have been encouraged through the UK Policy Framework for Health and Social Care Research and the HRA's Make it Public strategy, but failures have not, in themselves, constituted criminal offences.

The New Rules represent a significant shift by placing transparency obligations on a statutory footing for the first time. Sponsors will be required to register a clinical trial in a public registry by the earlier of: (i) the date on which the first individual is recruited to be a participant; or (ii) 90 days after approval of the trial. Within 12 months of (global) trial completion, Sponsors must publish a summary of results in the same public registry and offer relevant persons a lay summary of the results. The amended framework also allows Sponsors to apply for a deferral or waiver (and Phase I trials may benefit from an automatic deferral, subject to registering minimum information by the relevant deadline).

Failure to comply with the registration or results publication requirements in the absence of an approved deferral or waiver will constitute an offence and may lead to enforcement action by the MHRA, which will take into account any outstanding failures when assessing future applications by the same Sponsor. Certain transitional exemptions may apply where clinical trial applications were submitted before 28 April 2026.

Simplified Consent Arrangements for Certain Lower-risk Trials

The New Rules introduce simplified arrangements for obtaining and evidencing consent in a defined category of lower-risk trials, where IMPs are authorised in the United Kingdom and used in accordance with their authorisation, administered as part of routine clinical care, and involve no additional medication, interventions or diagnostic procedures solely for trial purposes. Where a Sponsor intends to rely on simplified arrangements, the protocol must explain why simplified arrangements are being used, what information will be provided to participants and how, and how consent will be evidenced.

The New Rules' Explanatory Memorandum anticipates that simplified consent will be supported by detailed guidance. Sponsors should therefore expect this to be an area of ongoing focus for ethics review and should keep a close watch on emerging HRA principles and related materials when designing how consent will be obtained and evidenced in practice.

Good Clinical Practice

The New Rules make compliance with the ICH E6 GCP principles a legal requirement for all UK clinical trials of investigational medicinal products ("CTIMPs") from 28 April 2026. The New Rules also retain a UK-specific principle requiring Sponsors to have  regard to all relevant guidance when commencing and conducting a trial. This means that the MHRA's supporting guidance and the detailed materials in ICH E6(R3) (and ICH E8(R1)) will be key reference points for demonstrating compliance in practice.

Compared with the earlier version, the updated ICH E6(R3) guideline places greater emphasis on identifying factors critical to trial quality, embedding risk-based quality management across the trial life cycle, and adopting proportionate approaches to training, oversight and documentation. It also accommodates innovative trial designs, technological developments and decentralised trial models.

Safety Reporting and Pharmacovigilance

The New Rules introduce a streamlined and more proportionate safety reporting framework for UK CTIMPs. From 28 April 2026, all Suspected Unexpected Serious Adverse Reactions, or SUSARs, and annual safety reports must be submitted to the MHRA only, removing the previous requirement for parallel reporting to the REC. That said, RECs will continue to have an active role in trial oversight and will still be engaged, including in relation to urgent safety measures and substantial modifications.

Annual safety reports will no longer need to include detailed line listings of suspected serious adverse events and adverse reactions. Instead, Sponsors are expected to provide an aggregate assessment of safety across the reporting period, along with a coherent account of how safety data have been reviewed, interpreted and managed. This reflects the shift towards risk-proportionate oversight and a focus on meaningful safety signal evaluation over volume-driven reporting.

The timeframe for notifying urgent safety measures (the "USMs") has also been extended from three to seven calendar days. Under the new regime, the HRA will require an initial phone discussion for USMs, while REC phone calls are no longer required. Written notice must still be given to the licensing authority and the REC, but the pathway of reporting remains the same. Sponsors of ongoing trials may elect to remain temporarily under the previous safety reporting regime, subject to submitting a request to the MHRA within 60 calendar days beginning 29 April 2026. Otherwise, the new pharmacovigilance rules will apply from 28 April 2026. Information on how to make this type of request is available on the MHRA's transitional arrangements webpage.

Participant Recruitment Timeframes 

Where a clinical trial is submitted on or after 28 April 2026, approval will lapse at the end of 24 months beginning with the date of approval if no UK participant has been recruited within that period.

Extensions can be requested as part of the initial application or subsequently in writing before the initial two-year period expires. The authorities may grant an initial extension of up to 36 months (taking the total period to up to five years from approval) and a further extension of up to 24 months, provided the further extension is requested before the existing extension period expires.