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Making changes to a research study to manage the impact of COVID-19

Last updated on 3 Jun 2020

Version 3, 28 May 2020

This guidance is for sponsors, sites and researchers who need to make changes to an existing study to manage the impact of COVID-19. The arrangements described are designed to ensure that changes (known as amendments) can be made quickly whilst subject to the appropriate oversight to protect the interests of participants.

MHRA has published information for CTIMPs and for Medical Devices on its website.

A fast-track review process is available for studies relating to COVID-19 where there are public health grounds for rapid review. The fast-track review process is for new COVID-19 studies and existing studies that are adding elements to understand, diagnose or treat COVID-19.

This guidance covers:



Arrangements for handling all amendments 

There are a number of scenarios where an existing study may need to be rapidly amended due to the wider impact of COVID-19 on NHS staffing, restrictions on movement of people or in response to Government advice. Guidance is given for each scenario below. 


All amendments that need to be submitted to a review body should be submitted in the usual way. Please follow the information below relating to categorisation and assessment. Any amendments that do not require assessment based on the guidance below do not need to be sent to HRA or HCRW but should be provided to sites as above.


Any type of amendment to a research study to manage the impact of COVID-19 should be sent to participating sites in accordance with existing guidance. To support site implementation, you should make sure that the changes and local implications are clear, and any changes to documentation are provided in tracked changes as well as clean versions.


For multi-centre studies in Scotland or Northern Ireland, amendments should be provided to the national coordinating functions for dissemination to the participating R&D offices as usual. Sponsors should continue to share with the Principal Investigator (PI)/delivery teams. For single centre studies all correspondence to sites should be copied to R&D/I department and the PI/delivery teams.

In England and Wales all correspondence to sites should be copied to R&D/I department and the PI/delivery teams.


Safety of patients of course remains a priority. If the safety of a participant is at risk because they cannot complete key safety checks, then the local research team should consider withdrawing that participant from the study. Where necessary, urgent safety measures may be implemented first and notified subsequently.


The MHRA provides more detailed guidance on handling of particular scenarios for clinical trials and clinical investigations involving medical devices.


Re-opening studies or sites that have been paused 

Where a CI or sponsor wishes to re-open a study, it is expected that this will be discussed between the sponsor, Principal Investigators at sites, R&D offices and NIHR (where relevant), before re-opening. The NIHR has issued guidance on considerations for re-starting studies, and the devolved administrations are providing similar advice. 

Where the pause was communicated to sites in a non-substantial amendment, any re-opening can also be communicated to sites in a non-substantial amendment. This does not require HRA/HCRW Approval. The site will need to confirm to the sponsor when it is able to re-open.

For studies that remained open in some places, individual sites that were paused should undertake a risk assessment before restarting and agree arrangements with the sponsor.

Please see the guidance below for managing any arrangements that need to be put in place for research to restart.


Reversing arrangements put in place during COVID-19

Any return to pre-COVID-19 arrangements that were previously approved does not need to be approved when re-instated, if the changes made for COVID-19 were classified as a non-substantial amendment that did not need to be approved. Any new changes should be handled in accordance with the guidance below.

Similarly, if some arrangements revert to previously approved arrangements and other elements remain for an interim or long-term period, these do not need HRA and HCRW Approval. 


Clear communication to sites should be provided with clarity about the versions of documents that should be followed. Sites will need to confirm that they can adopt any re-instated arrangements.


Changes to site monitoring arrangements or changes to administrative arrangements to reduce burden or physical contact with sites 

Any changes to monitoring or administration of studies should not increase the burden on NHS sites. 


In most cases, monitoring of studies by sponsors will need to be undertaken remotely. Remote monitoring and source data verification must not result in confidential patient information being sent to the sponsor or stored by the sponsor if this has not already been addressed in the participant information sheet. For example, unredacted copies of medical notes, from which individuals may be identified, should not be emailed or posted to the sponsor. Source data verification may be done remotely by electronic means if the necessary security arrangements can be put in place, for example by using video calls or via access to electronic health records, but sponsors must not retain screenshots.  


Changing from on-site to remote source data verification does not require an amendment to the participant information sheet if this guidance is followed and the participant information sheet does not specifically refer to source data verification occurring exclusively within the physical premises of the site. Such changes to remote monitoring are a non-substantial amendment that does not require HRA/HCRW Approval or R&D agreement. For studies involving the NHS/HSC, changing to remote monitoring should be marked by the sponsor as category C and not requiring assessment, and sent directly to sites following the instructions above. These should be implemented at sites on the date specified by the sponsor.


Sponsors should consider what monitoring needs to be done in real time, and what checks can be undertaken later, taking a risk-based approach. Where it is necessary for the sponsor to physically receive and/or store confidential patient information in order to undertake immediate source document verification for reasons of participant safety and data integrity, (for example, for phase I dose escalation), the participant information sheet and consent form should be revised and submitted as a substantial amendment, along with the risk assessment justifying the changes to access to confidential patient information. Such amendments will be categorised and assessed according to existing guidance, but the process will be expedited. They should be sent to sites following the instructions above. These should be implemented at sites on the date specified by the sponsor.


Changes to how or when patients are seen to avoid exposing them to COVID-19 or to reduce the burden on clinical services 

In some cases, changes will be deemed by the sponsor to reduce the risk of potential exposure to COVID-19 by participants (for example, changing participant site visits to phone calls or postal questionnaires). Sponsors must not make any such changes that would create additional burden to NHS staff or resources. These changes should be handled as a non-substantial amendment that does not require HRA and HCRW Approval or R&D agreement. For studies involving the NHS/HSC, these should be marked by the sponsor as category C and not requiring assessment and sent directly to sites following the instructions above. These should be implemented at sites on the date specified by the sponsor.


In other cases, changes will be deemed by the sponsor to potentially increase risk to participants (for example, less frequent participant checks). Sponsors must not make any such changes that would create additional burden to NHS staff or resources. These should be handled as a substantial amendment. Such amendments will be categorised and assessed according to existing guidance, but the process will be expedited. They should be sent to sites following the instructions above. These should be implemented at sites on the date specified by the sponsor.


Changes to how treatment or an investigational medicinal product is provided to participants 

Where changes to how treatment or an investigational medicinal product is provided to participants need to be made, sponsors must assess the risks relating to the product and consider any shipping and storage arrangements. Where a participant is self-isolating or in quarantine, arrangements for a nominated person to collect the product may be implemented with the participant’s verbal consent. Where a product is being sent directly to a participant’s home, the participant must consent verbally to providing contact details for shipping purposes. Any such temporary arrangements should be handled as a non-substantial amendment that does not require HRA and HCRW Approval or R&D agreement. For studies involving the NHS/HSC, these should be marked by the sponsor as category C and not requiring assessment and sent directly to sites following the instructions above. These should be implemented at sites on the date specified by the sponsor.

Implementing a temporary halt to all or some of the study

Sponsors must decide when they need to implement a formal temporary halt. The MHRA provides advice for CTIMPs and clinical investigations involving medical devices. For non-CTIMPs consider reporting a formal halt if there are safety considerations for existing participants, or actions that sites need to take. 


Simply pausing recruitment does not need to be reported as a temporary halt, although sponsors should record such decisions for their records. 


For CTIMPs, in the scenarios where MHRA has advised that this would be substantial amendment, such amendments will be categorised and assessed according to existing guidance, but the process will be expedited. They should be sent to sites following the instructions above. These should be implemented at sites on the date specified by the sponsor.


For non-CTIMPs where a formal halt is required, this should be handled as a non-substantial amendment that does not require HRA and HCRW Approval or R&D agreement. For studies involving the NHS/HSC, these should be marked by the sponsor as category C and not requiring assessment and sent directly to sites following the instructions above. These should be implemented at sites on the date specified by the sponsor


Closing a study 

For any studies not involving provision of treatment to participants, where a study is terminated early due to COVID-19, a notification to the REC or national coordinating function (for non-REC studies) should be provided, and an end of study report should subsequently be provided. 


For any studies involving provision of treatment to participants, careful consideration should be given to post-study care. If this cannot be in line with the information provided in the participant information sheet, a substantial amendment should be submitted to amend the participant information sheet. Such amendments will be categorised and assessed according to existing guidance, but the process will be expedited. They should be sent to sites following the instructions above. These should be implemented at sites on the date specified by the sponsor. Whether or not the participant information needs to be amended, early termination of a study due to COVID-19 should be notified to the REC or national coordinating function (for non-REC studies), and an end of study report should subsequently be provided. If a clinical trial has been terminated early for safety reasons it should be registered with immediate effect even if a registration deferral has been allowed by the HRA.


Changes instigated by individual sites due to clinical requirements 

Sites may need to make rapid changes to manage clinical situations. The priority should be the safety of patients. For CTIMPs, the MHRA expects any protocol deviations to be documented.

Studies where sites need to suspend recruitment at any stage 

Sites must raise such issues with the sponsor as early as possible if this is likely to occur. No further action by sites is required except where instructed by sponsors.


It is for the sponsor to decide whether or not to temporarily halt or close a study (seeImplementing a temporary halt to all or some of the study and Closing a study)


Studies where sites need to move participant visits

Sites must raise such issues with the sponsor as early as possible if this is likely to occur.


Where possible such arrangements should be handled prospectively and, where required, submitted as an amendment. In cases where there is no time to arrange for such review, changes should be implementedas urgent safety measures and reported retrospectively. In any such situation the impact on participants should be considered and arrangements made to cover this (for example, by providing additional transport).


Where participant visits can be done remotely rather than face to face, this does not need to be reported as an amendment, although it may be appropriate to record this if it might affect the study data (for example, subjective interview responses).


Where individual sites need to arrange to courier treatments to patients, this does not need to be reported as an amendment but should be agreed with the sponsor and a risk assessment documented.


If patient visit locations need to be moved, the options are to: 

  • set up as a sub-contracted location of the existing site if oversight can be maintained by the existing site, or
  • set up new sites, or 
  • implement direct home care arrangements by the sponsor, with the sponsor acting as a site.


For study types where the addition of new sites is a substantial amendment, existing guidance for submitting a substantial amendment for new sites should be followed. In all other cases, existing guidance for non-substantial amendments and addition of new sites should be followed.


Establishing subsidiary locations for an existing site is a non-substantial amendment. These should be handled as a non-substantial amendment that does not require HRA/HCRW Approval or R&D agreement. For studies involving the NHS/HSC, these should be marked by the sponsor as category C and not requiring assessment and sent directly to sites and subsidiary locations following the instructions above. These should be implemented at sites on the date specified by the sponsor.


When patients participating in a study are moved for clinical reasons to other hospitals, the options are to: 

  • move the patient to a site already participating in the study, or 
  • set up the new location as a site, or 
  • retain the participant under the oversight of the original site, with the new hospital as a subsidiary location.

Studies were sites need to withdraw participants 

Sites must raise such issues with the sponsor as early as possible if this is likely to occur.


For any studies involving provision of treatment to participants, careful consideration should be given to post-study care. If this cannot be in line with the information provided in the participant-information sheet, a substantial amendment should be submitted. Such amendments will be categorised and assessed according to existing guidance, but the process will be expedited. They should be sent to sites following the instructions above.


Studies where a Principal Investigator is removed 

If the absence will be greater than one month, the REC should be notified. If the Principal Investigator will be absent for greater than three months, alternative arrangements should be put in place.


General considerations for all studies due to physical distancing

Electronic vs ink signatures in research approval documents 

When setting up any new study, there is no requirement for ink signatures on any research approval documents. In relation to NHS site set-up, use of time-efficient methods of exchange of contracts and agreements, including exchange of confirmation by email, is encouraged. This guidance has been in place for many years.


The MHRA has issued guidance on amending your operating procedures if your own current processes still require the use of ink signatures.  


Seeking consent

It may not be feasible at present to seek written consent on paper forms from a participant. Sponsors should consider alternative approaches to seeking consent in line with published guidance on proportionate consent and e-consent. 


For sites, if it is no longer feasible to seek consent as described in the protocol, consider alternative approaches such as e-consent or witnessed verbal consent, and document in the patient record. Changes to physical arrangements for consent using the same text such as providing text on a tablet, or as witnessed verbal or phone consent, should be agreed with the sponsor and documented at site but is not a substantial amendment. 


For further queries please contact: 

Version number Date Changes made since previous version
1 12 March 2020
1.1 13 March 2020 Correction of error at 3.1.4 (inserting word 'non' before 'CTIMPs' at the start of the second paragraph)
2 17 March 2020 Section 2 – clarification about arrangements for provision of amendments. Section 3 – includes link to MHRA blog. Section 3.1.1 – additional information on monitoring. Section 3.1.4 – clarification on when a sponsor should report a formal temporary halt. Section 3.2.1 – clarification of distinction between site temporary halt and sponsor temporary halt. Section 3.2.2 – additional scenarios included
2.1 20 March 2020 Link to MHRA guidance updated following new MHRA guidance. Section 2 - clarification about non-substantial amendment form. Section 3.1.4 - wording clarified. Section 3.2 - additional information about protocol deviations.
2.2 26 March 2020 To add a new link to the NIHR's guidance on public health emergency research, as approved by the Chief Medical Officer
2.3 21 April 2020 To add a link in the opening paragraph that directs to the wider COVID-19 research section.
3 28 May 2020 Link to MHRA guidance on Devices added following new MHRA guidance. Guidance on re-starting studies and reverting to previous arrangements added. Substantial reordering of text, with no change to principles.
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