Quick links: Amendment processesAmendment categories / Urgent safety measuresPractice responsibilities / Updating files and paperwork / Agreeing to or rejecting an amendment / Amendment naming and numberingChanges not requiring an amendment / Glossary

How to guide: Amendments

When a study starts, the protocol and documents are all approved by the Health Research Authority (HRA) and research ethics committee (REC). If there are any changes to documents, processes or dates, these usually have to be notified to the HRA/REC and be reviewed again. A separate approval of this is then issued.

Key information you should be aware of:


See also

Full guide

Amendments are a necessary part of studies, as they allow the study to respond to emerging requirements and correct any errors.

Amendment processes

Template email for sponsors to share category A or B amendment documents with sites (regulatory approvals outstanding)
Template email for Category A or B amendment documents with sites – where regulatory approvals in place
Template email for sponsors to share category C amendment documents with sites
Template email for sponsors to confirm implementation of an amendment 

Amendment categories

Amendments are categorised to determine whether the site (practice) needs to review them before implementing them.

Urgent safety measures

Where patient safety is at risk, urgent changes may be implemented but these must be driven by the sponsor. If you feel the study is creating a risk, you must report it to the sponsor rather than making any changes.

The sponsor must inform all sites of the change. There will often be changes to documents following an urgent safety change – these should be submitted as usual as an amendment.

Practice responsibilities

The practice is responsible for delivering the study in accordance with the study protocol, including all amendments.

The study team is responsible for making any updates to the study documents, and securing all necessary approvals for these. The practice is responsible for replacing all documents with the latest versions in the site file, and only using the current document versions.

The Principal Investigator (PI) must ensure that all staff members are informed of any changes. The delegation log may need to be updated if staff take on new activities.

The sponsor will determine whether participants need to receive updated versions of documents. When the consent form is updated, the sponsor will determine whether participants who have already given consent, need to then sign a new consent form.

Updating files and paperwork

A site file must contain all study documents.

When a document is replaced with an updated version, the following process must be followed:

Amendment approvals should also be included in the site file.

Agreeing to or rejecting an amendment

Practices do not need to send a formal acceptance of an amendment, and the sponsor may implement the amendment (when approved) if the practice does not object or request more time to consider the amendment. They may implement category A or B amendments 35 days after they notify the site and may implement category C amendments as soon as they have notified the site. If the practice confirms to the sponsor that they accept the amendment, then it can be implemented sooner than 35 days.

Note that days means calendar days and not working days.

If your practice feels it cannot implement an amendment, it must raise an objection in writing to the sponsor as soon as possible. This must be within 35 days.

If your practice needs more time to consider an amendment, it must notify the sponsor (again, this must be within 35 days). However, it is best practice to progress amendments (or object) as quickly as possible.

Amendment naming and numbering

There is no standard way of naming and numbering amendments. Sometimes the terms ‘minor’ and ‘major’ are used, sometimes ‘substantial’ and ‘non-substantial’.

The definitions ‘minor’, ‘major’, ‘substantial’ and ‘non-substantial’ are simple descriptors – they all still need to be implemented.

Categories of amendment (A, B and C) are more relevant (see above) as they describe whether the amendment needs management or oversight from the site (practice).

Some studies prefer to number amendments starting at 1 and numbering each amendment chronologically; others number substantial amendments separately from non-substantial amendments. Others may use the date or a description rather than a number.

A practice may not always receive every amendment, as category B amendments are not necessarily relevant to all sites (for example if a new site is added to a study, or if a change is made to a different arm of the study). It is the sponsor’s responsibility to inform the practice of all amendments applicable to them.

Changes not requiring an amendment

If a study document contains a section designed to include local information or branding (see example below), or information that is not known at the time of the approval (for example a specific URL), then it does not require an amendment, if this is clear at the point of application.

Changes to an Organisation Information Document are a matter between the site and sponsor, so do not require an amendment.

When the study was approved, it will have specified a start and end date. If there are any changes to the study end date, particularly if they are substantial, they will usually be submitted as amendments.

In exceptional circumstances, there may be exemptions to requiring a study amendment. In recent years, the most important to be aware of are:

If you are not sure, then please contact or discuss with the study sponsor.

Glossary of Acronyms and Terms


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