Substantial amendments involve significant changes to the design and methodology of a research project.  A substantial amendment is defined as an amendment to the terms of the application, or to the protocol or any other supporting documentation, that is likely to affect to a significant degree:

• the safety or physical or mental integrity of the subjects of the study;
• the scientific value of the study;
• the conduct or management of the study; or
• the quality or safety of any investigational medicinal product used in the trial.

They should be submitted to the relevant review bodies for approval before the changes can be implemented unless there is an urgent safety issue.

Non-substantial amendments do not involve significant changes to the design and methodology of a research project. This may include correcting typographical errors in documents, changes to documentation used by the research team to record trial data, or changes to funding arrangements. It is the responsibility of the Sponsor to submit all amendments (including non-substantial) to the Health Research Authority (HRA) for categorisation and, if necessary, assessment. There are no requirements for sponsors to submit non-substantial amendments to the Ethics Review Body although it is considered good practice to notify them of the amendment and the rationale for classifying it as non-substantial.

As part of the Health Research Authority (HRA) review process, amendments will be further categorised –

• Category A amendments affect all sites in the study and require local Research & Development (R&D) approval.
• Category B amendments will only affect certain research sites and will only require local approval if they affect NuTH as a site e.g. Change of PI at NuTH.
• Category C amendments do not require local R&D approval however they should still be sent to R&D for audit purposes. An example could be new sites being added that do not affect NuTH or protocol amendments that only involve a typographical error.

Sponsors

All amendments

• If the study is sponsored by NuTH, Chief Investigators or their delegated representatives should submit all planned amendments to R&D (via nuth.amendments@nhs.net) for review prior to submission to the regulatory authorities.

• External sponsors should submit the amendment ‘pack’ to the Principle Investigator and copy in their contacts in the Research Delivery Team and the R&D Team using the email address given above.

Research Delivery Teams

Category A or B amendments (where NuTH is affected as a site) –

• The amendment should be submitted to R&D for local approval using the email address above.  You should include the Amendment Capability Form (either NuTH sponsored or Hosted) and include all relevant documents as outlined on the relevant R&D Amendment Checklist.

Category B amendments (where NuTH is not affected as a site) and all Category C amendments –

• The amendment should be forwarded to R&D for information purposes only and the changes can be introduced straightaway.