Guidance

Declaration of Helsinki and Clinical Trial Regulations alignment

Updated 19 March 2026

Legal status of this guidance 

This guidance accompanies the Medicines for Human Use (Clinical Trials) Regulations 2004, as amended by the Medicines for Human Use (Clinical Trials) (Amendment) Regulations 2025.

These amendments come into force on 28 April 2026, and any reference to ‘the amended Clinical Trials Regulations’ in this guidance should be construed as referring to the amended version.

For assistance in determining whether a clinical trial is within the scope of these Regulations, refer to the Is it a clinical trial of a medicinal product? algorithm. 

Part 2 of Schedule 1 to the amended Clinical Trials Regulations requires that the investigator and sponsor have regard to all relevant guidance with respect to commencing and conducting a clinical trial.

Investigators and sponsors (and any individual or organisation that the sponsor delegates trial related activities to) must, therefore, ensure that they are fully aware of the information within this guidance and act accordingly to achieve and maintain regulatory compliance. 

Inclusion of the Declaration of Helsinki 

The Declaration of Helsinki (‘the Declaration’) sets internationally recognised ethical standards for medical research involving human participants. 

Part 2 of Schedule 1 to the amended Clinical Trials Regulations (‘Conditions and Principles which apply to all clinical trials’) requires that the principles of the Declaration of Helsinki must be complied with for all clinical trials except where it contravenes the requirements of the amended Clinical Trials Regulations. 

Reference to specific versions of the Declaration of Helsinki have been removed as compliance is expected with the principles of the Declaration rather than with a specific version. 

Areas of potential conflict 

Use of placebo or no intervention 

The Declaration expects that a new intervention is assessed against the best proven intervention. The 2024 version of the Declaration permits the use of placebos only under specific conditions: 

• if no proven intervention exists 
• if ‘compelling and sound methodological reasons’ for the use of any intervention other than the best proven one exist and that the use of placebo/no intervention does not increase the risk of serious or irreversible harm 

The amended Clinical Trials Regulations permit the use of placebos with a degree of flexibility, provided: 

• the trial is scientifically sound and ethically approved by a Research Ethics Committee  
• the risk-benefit ratio is favourable and does not compromise participant safety 
• the informed consent process informs the participant of the possibility of receiving placebo/no intervention 

Urgent safety measures 

The amended Clinical Trials Regulations permit sponsors to implement urgent safety measures without prior ethics approval in certain circumstances (for example, emergent risk to patient safety) which could conflict with the Declaration’s insistence on ethics committee oversight before changes to the trial being made.  

It would be expected that if a safety concern arises that requires the use of an urgent safety measure that the guidance regarding these is complied with. 

The licensing authority and research ethics committee will be notified but that formal approval will not be provided prior to implementation of the change. 

Post-trial provisions 

The Declaration requires arrangements for post-trial access to beneficial interventions, whereas the Regulations do not impose this as a statutory obligation. 

Expectations 

In practice, the principles of the Declaration and the amended Clinical Trials Regulations are aligned in regard to expectations.

Sponsors should aim to comply with both but where strict adherence to the Declaration would undermine UK statutory safeguards or operational feasibility, the MHRA expects sponsors to prioritise compliance with UK law while documenting the rationale for deviations.