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

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 need to be submitted in the usual way using the amendment tool and online submission. Any non-substantial amendments that also do not require assessment based on the guidance below will receive an automated confirmation of receipt on submission. This should then be provided to sites as described in the tool.

During the pandemic changes to legislation and government guidance are likely to be made frequently and may be introduced at short notice.

Wherever possible, we recommend that information about requirements or consequences of new evidence, government guidance or legislation relating to COVID-19 are provided to participants or potential participants as generic, rather than study-specific information. For studies taking place in the NHS, there will often be local organisational information relating to COVID-19 that will also be relevant to research participants.

Where a government requirement will apply because of a study-specific activity e.g. the inclusion of COVID-19 testing, the sponsor should ensure that participants or potential participants are made aware of the requirements. Implications of the amended Health Protection (Notification) Regulations 2010 to research projects should be described to participants or potential participants in generic non-research documents, since the requirement for reporting and the flows of personal data involved are distinct and separate from those for the research.

For existing projects, the introduction of any such generic information alongside a research study would not constitute an amendment to the study.

For any research involving consent, assent or advice from representatives, it should be normal practice to review ongoing participation in a research study with participants and/or representatives. This is particularly important in the context of rapidly changing circumstances and information during the pandemic.

Please contact the HRA via fast.track@hra.nhs.uk if you have any questions, before implementing changes across all studies due to national reporting or other national requirements.

For amendments relating to COVID-19 studies that meet the current criteria for fast-track, please submit the amendment in the usual way. Once submitted, please notify the fast-track team providing, IRAS number, amendment reference number, and REC (if applicable).

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. Templates are available to support provision of information.

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. Do not complete or submit the amendment tool in this situation.

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 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 avoid increasing 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. There is also the possibility of the site uploading electronic copies of source documents into a portal provided by the sponsor. In these cases, there must be redaction to ensure anonymity and only the participant trial identification number should be used. These records should be promptly deleted after the monitor has completed monitoring activity. 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. The MHRA has produced detailed guidance on requirements for access to electronic health records.

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. For studies involving the NHS/HSC, changing to remote monitoring should be submitted via online submission using the amendment tool.

The following options in the tool should be selected:

The study must be a CTIMP.

Area of Change: CTIMP Safety

Specific Change: Study oversight - Temporary change in arrangements for monitoring (e.g. remote instead of on-site) where the arrangements will not contradict those previously described to the participant and the necessary security arrangements will be in place.

These will be classified by the tool as category C, not requiring further study wide review. Once submitted following the instructions within the tool these should be 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, using the amendment tool, 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.

If changes are being made to the participant information as a result of the monitoring, the following options in the tool should be selected:

The study must be a CTIMP.

Area of Change: CTIMP Safety

Specific Change: Study oversight - Change in arrangements for monitoring (e.g. remote instead of on-site) where the new arrangements need to be described in updated information for the participant.

This will result in a category A or B amendment, depending on whether the change affects some or all sites.

The HRA information leaflet on research transparency has been updated to reflect remote monitoring. All participant information sheets should link to this page, which should be offered to patients as a paper copy.

The MHRA have published detailed guidance on considerations for monitoring.

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 UK study wide review or R&D agreement. The sponsor should complete the amendment tool and submit via online submission.

The following options in the tool should be selected:

Area of Change: Participant Procedures

Specific Change: Participant procedures - minor change that can be implemented within existing resource at participating organisations - please specify in the free text below.

These will be classified as a category C not requiring further study wide review. Once submitted the sponsor should send directly to sites following the instructions above. These should be implemented at sites on the date specified by the sponsor.

The 'Participant Procedures' Area of Change in the amendment tool also includes Specific Change options for where the changes are deemed by the sponsor to be significant (for example, less frequent participant checks), and/or where the changes will have additional resource implications for participating organisations. Carefully select the option applicable to the situation; the amendment will be categorised and processed 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 UK Study wide review or R&D agreement. The sponsor should complete the amendment tool and submit via online submission. These should be implemented at sites on the date specified by the sponsor.

The following options in the tool should be selected:

The study must be a CTIMP

Area of Change: CTIMP IMP

Specific Change: Temporary alternative arrangements to provide participants with IMP (e.g. delivery directly by courier) where there is no increased risk to the participant

These will be classified as a category C, non-notifiable amendment that can be sent directly to sites.

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.

The following options in the tool should be selected:

The study must be a CTIMP.

Area of Change: Stop or Restart

Specific Change: Temporary halt of CTIMP

For non-CTIMPs where a formal halt is required, this should be handled as a non-substantial amendment. The sponsor should complete the amendment tool and submit in accordance with the submission guidance via online submission. Once submitted the amendment should be sent directly to sites following the instructions above. These should be implemented at sites on the date specified by the sponsor.

For non-CTIMPs the following options in the tool should be selected:

Area of change: Stop or Restart

Specific Change: Temporary halt of non-CTIMP due to COVID-19

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 discussed with the sponsor and 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 where 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.

The following options in the tool should be selected:

Area of change: participant procedures

Specific change other. Provide in the text this relates to one site (naming site)

This will result in a category A or B amendment, depending on whether the change affects some or all sites.

Studies where a Principal Investigator is removed 

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

The following options in the tool should be selected:

Area of change: Researchers

Specific Change: PI - New PI, or temporary arrangements to cover the absence of a PI

Select change only impacts Some sites.

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: 

• HRA Queries: queries@hra.nhs.uk
• MHRA Clinical Trials Unit Helpline: clinicaltrialhelpline@mhra.gov.uk or 020 3080 6456.