Under the new clinical trials regulations, the Research Ethics Committee (REC) and the Medicines and Healthcare products Regulatory Agency (MHRA) can request that sponsors modify their clinical trials.
This differs to an urgent safety measure (USM) where a sponsor or investigator takes appropriate urgent safety measures to protect participants against any immediate hazard to their health or safety, without prior authorisation from a regulatory body.
When the REC or MHRA can request a modification
These requests will be made in cases where the MHRA or REC is made aware of the following concerns:
- the clinical trial does not comply with the conditions and principles of good clinical practice
- the safety of the clinical trial
- the scientific validity of the clinical trial
If the REC receives concerns raised by a third party about an ongoing trial, they'll initially contact the sponsor to notify them of the concerns and begin a discussion regarding the validity of the concerns raised.
If the REC determines that a modification needs to be made, they’ll issue a request to the sponsor.
How the REC will make a request for a modification
The REC will issue a request for a modification by emailing the individuals they have listed as points of contact for the trial (named sponsor representatives and the chief investigator for the trial).
The request will specify what modification needs to be made, the reason it’s needed, and when it should be implemented. Requests for a modification will be sent at least 7 calendar days before the date the sponsor is expected to implement the change.
The number of days the REC will give for a change to be implemented will be proportionate to the complexity and scale of the proposed changes. If the sponsor has no objections to the modifications, or the timeframe in which they should be implemented, the sponsors should implement them in line with the instructions in the correspondence.
It will be the responsibility of the sponsor to communicate the changes to the locations involved in the trial so they can confirm capacity and capability to support and implement the changes within the given timeframe.
If a modification meets the criteria of being a substantial modification, the sponsor will need to submit a substantial modification request. This will need to be submitted and approved before the sponsor implements the modification.
In these cases, the REC will issue an outcome as soon as possible. The substantial modification submission will need to specify if the modification was requested by the MHRA or REC as well as the changes that were requested and made.
Making a written representation against a request for modification
If the sponsor disagrees with the request for a modification (either the changes requested or the timeframe to implement them) they can make a written representation. The sponsor can submit a written representation if they disagree with making the changes requested and/or the timeframe given by the MHRA or the REC to implement the changes.
The sponsor must submit a representation in writing to the MHRA or REC (whichever body issued the request for the modification) within 7 calendar days of receiving the request. In the representation, the sponsor should explain why they oppose the modification and what they plan to do next.
The MHRA or REC will confirm that they've received the written representation. They will then consider the points made in the representation and, if necessary, let the sponsor know if they should delay implementing the change so that the MHRA or REC can consider it further.
Once a decision is reached, they'll inform the sponsor of the outcome as quickly as possible. If it's determined that the proposed modification does not need to be made, or if a different timeframe for implementing it should be followed, the sponsor will be notified and they will be given instructions on how they should proceed.
If, after reviewing the written representation from the sponsor, the MHRA or REC decides that the proposed modification is needed, the sponsor will be expected to implement it by a given date. The sponsor should then inform the sites of the modification that is being made and work with them to implement them within the given timeframe. If the modification meets the criteria of being a substantial modification, the sponsor will need to submit a substantial modification request. This can be done by following the same process for submitting modifications outlined in our approvals process for modifications guidance page. This substantial modification would need to be submitted and approved before the sponsor implements the modification.
In these cases, the REC will issue an outcome as soon as possible. The modification submitted by the sponsor should specify that it relates to a modification requested by the MHRA or REC and should be consistent with the changes requested by the MHRA or REC.
Appealing a request for modification from the MHRA or REC
If the MHRA or REC agree that the modification should still be made after reviewing a written representation, the sponsor can appeal this decision.
The sponsor should contact us at appeals@hra.nhs.uk within 28 calendar days of receiving the email from the MHRA or REC informing them they should continue to implement the modification. In their email to us, the sponsor should confirm their intent to appeal the decision. We’ll then contact the sponsor to discuss the next stages of the appeal process.