Rehabilitation Exercise and psycholoGical support After covid-19 InfectioN (REGAIN)

University Hospitals Coventry and Warwickshire NHS Trust (UHCW) and University of Warwick, as joint data controllers, are requesting NHS Digital data under the current COPI Notice that will allow potentially eligible participants to be identified and invited to take part in the REGAIN (Rehabilitation Exercise and psycholoGical support After covid-19 InfectioN) study. The REGAIN study is a UK multi-centre, two-arm, randomised controlled trial funded by the National Institute for Health Research (NIHR) COVID-19 Recovery and Learning Programme (NIHR 132046).

THE AIM OF THE TRIAL

The trial aims to find out if an eight-week programme of online, home based exercise rehabilitation with behavioural, motivational and mental health support is beneficial compared to a single online session of advice and support, in adults with ongoing COVID-19 sequelae (a condition which is the consequence of having Covid-19) more than three months after hospital discharge (long Covid).

It is to be noted that the definition of long Covid used in this trial and agreement is not a universally agreed definition at this present time, but one that has been created for the specific use within this study.

Several hundred thousand people in the UK have been discharged from hospital by the NHS after treatment for COVID-19. Many will return relatively quickly to good health and a normal life. However, a proportion will have ongoing health problems. These problems are multi-systemic including motor, cognitive, neurological, musculoskeletal, respiratory and cardiovascular as well as depression, anxiety, and post-traumatic stress disorder (PTSD). In April 2020, the NHS predicted that 45% of people discharged from hospital would need some ongoing support from health and/or social care. The most recent ONS data indicates that at least 1 in 10 people discharged from hospital will continue to suffer with COVID-19 related problems (Long-Covid) for a period of more than 12 weeks post-discharge. The scale of the pandemic means that many thousands of people in the UK will require long-term multi-disciplinary support and rehabilitation.

There are limited rehabilitation or structured support programmes for COVID-19 survivors with long-extending conditions beyond 12 weeks after hospital discharge. Where programmes exist, their potential benefit/harm is unproven. Research is needed now to find out how best to treat people with Long-Covid. Multi-disciplinary physical and psychological rehabilitation may be beneficial in improving people’s quality of life. However, the size of the problem requires the testing of approaches to multi-disciplinary rehabilitation that can be delivered at scale.

Due to the nature of the Pandemic, this clinical trial was created as an online study, limiting face to face contact. The study team are aware that the online nature of the trial may mean a digitally able population are more likely to join the study than those who do not have access to the online participant facing platform. Where possible, a participant may engage the assistance of a family member or friend with the technical aspects of the study, in which instance the participant would still be able to participate in the trial.

The REGAIN trial is not investigating or tracking any specific Covid-19 variant or investigating Long-Covid (following a hospital stay) resulting from any specific Covid-19 variant, however the study team may as part of this clinical trial, review dates of participant hospitalisation to relate participants to particular Covid waves over the course of the Pandemic.

BACKGROUND TO RECRUITMENT

Since recruitment started in January 2021, the REGAIN study recruited 210 participants of a target 535 participants primarily from secondary care Trusts. The study team has fallen short of the originally intended timeline for completion of recruitment (Aug 2021) due to the significant strains on capacity experienced at all UK NHS Trusts due to the pandemic. Trusts have not had the necessary capacity to undertake the limited screening and mailout work for the study, often declining participation immediately. Recruiting Trusts often paused activity for significant periods of time as they juggled conflicting work pressures. As such, potentially eligible patients are missing out on the opportunity to be invited to the study. This agreement is specifically to support the recruitment to this trial, and aims to recruit to target in 2022 and answer the crucial research question and thus inform long-term care for COVID-19 survivors with Long-Covid following a hospital stay and potentially benefitting patients and society.

STUDY TEAM

Any reference to "the study team" in this agreement refers to members staff employed by University Hospitals Coventry and Warwickshire NHS Trust (UHCW) and University of Warwick directly working on the REGAIN study.

PATIENT AND PUBLIC INVOLVEMENT (PPI)

The study team engaged with an active PPI group, consisting of 6-8 people who had been hospitalised with COVID-19 and had symptoms of long COVID. This PPI group were instrumental in co-creating the REGAIN intervention, attending weekly intervention development meetings. The group extensively piloted live online physical activity sessions, were filmed as participants for on-demand sessions, and tested the online trial outcomes database. The group provided iterative feedback on the participant information leaflet, study flyer, workbooks and outcomes questionnaire. The group includes people with lived experience of long COVID who strongly advocate for rehabilitation. Their recovery trajectory has been slow, and they have received only limited support. They have identified that formal and targeted support is required to help improve the condition and their ability to work and socialise. Their experiences of protracted recovery and diverse symptom profiles have informed the REGAIN intervention and trial design. The study team met regularly with long COVID and chronic fatigue groups to refine the processes and intervention based on lived experience. Lay partners are part of the Trial Management Group (TMG) and Trial Steering Committee (TSG) where they have voting rights in each. TMG and TSG members will be included as co-authors on publications and given the opportunity to engage in trial publicity and dissemination.

LEGAL BASIS FOR COMMON LAW

The UK health and social care system is taking action to manage and mitigate the spread and impact of the Covid-19 pandemic. Action to be taken will require the sharing of confidential patient information amongst health organisations and other appropriate bodies for the purposes of protecting public health, providing healthcare services to the public and monitoring and managing the outbreak. The Secretary of State for Health and Social Care has issued NHS Digital with a Notice under Regulation 3(4) of the Health Service (Control of Patient Information) Regulations 2002 (COPI) to require NHS Digital to share confidential patient information with organisations entitled to process this under COPI for COVID-19 purposes.

The purpose of the COPI Notice (expires on 30 June 2022) is to provide NHS Digital with the necessary statutory power to disseminate confidential patient information to organisations permitted to process confidential patient information under Regulation 3(3) of COPI for the purposes set out in Regulation 3(1) of COPI to support the Secretary of State’s response to Covid-19 (Covid-19 Purpose). This Notice is necessary so that NHS Digital can lawfully and efficiently disseminate confidential patient information to those organisations set out in Regulation 3(3) of COPI being persons employed or engaged for the purposes of the health service or other persons employed or engaged by a Government Department or other public authority in communicable disease surveillance in connection with the health and social care system’s management of the response to Covid-19.

The study team envisage the recruitment to have completed by 30/06/2022 and therefore no alternative legal basis is being pursued post expiry of COPI.

The aim of this application is to request, under the COPI Notice, information from NHS Digital that will allow potentially eligible people to be identified and invited to take part in the REGAIN study. This information will be used by NHS DigiTrials' sub-processor, APS Group, to send postal invites to around 20,000 potential participants, over two mailings with the aim to recruit a further 325 participants to the trial. Following the mail-outs, should the study team fail to meet the recruitment target a further mailout(s) may be undertaken until the recruitment target is met within the COPI notice period (to expire on 30 June 2022). The information will not be shared with the University of Warwick or University Hospitals Coventry and Warwickshire NHS Trust who act as joint data controllers for the study. After receipt of the postal invitation, interested people will contact the study team at University of Warwick directly via the study website suitability checker and provide contact details allowing the team to contact them by telephone to conform eligibility. This will be the first time the REGAIN team views any confidential information.

GDPR LEGAL BASIS FOR PROCESSING

Both University Hospitals Coventry and Warwickshire NHS Trust and University of Warwick rely on GDPR Article 6(1)(e) of the General Data Protection Regulation (GDPR) to process personal data where processing is necessary for a task carried out in the public interest. In this instance the public interest task is research. The data are required for research purposes in the public interest- meeting the conditions in the DPA 2018 Schedule 1 Part 1 (4) - which GDPR Recital 52(2) determines is an appropriate derogation from the prohibition on processing special categories of personal data. The ways in which the processing of data will be of benefit to the public – thereby demonstrating that the processing is in the public interest – are described in section ‘5d. ii. Expected Measurable Benefits to Health and/or Social Care Including Target Date’.

- In accordance with GDPR Article 89(1) processing is subject to appropriate safeguards. These include:

i. The data recipient’s technical and organisational measures to safeguard the data have been assessed and meet NHS Digital’s acceptance criteria (see sections 2 and 5b of this application for further details) although it should be noted that neither University of Warwick and University Hospitals Coventry and Warwickshire NHS Trust will be receiving data from NHS Digital in this agreement;

ii. The requested data has been assessed as proportionate to the aim pursued (see section 5a of this application for further details);

iii. Controls, data retention and processing activities have been assessed to ensure respect to the essence of the right to data protection;

iv. Measures to protect the rights and freedoms of data subjects have been assessed including transparency (fair processing) publishing subject’s rights.

Both Controllers also rely on Article 9(2)(j) of the GDPR to process special category data (in this case health data) where processing is necessary for scientific research purposes. This study will use scientific research in order to identify rehabilitation solutions for people with Long-Covid following a hospital stay. The data minimisation process is being followed and only data that is required specifically for the purposes of this study has been requested, to protect the rights of the data subjects.

INCLUSION AND EXCLUSION CRITERIA

The trial will be conducted throughout the UK and the aim is to recruit a further 325 participants.

Inclusion criteria:

• 18 years or older,*

• Treated in hospital with COVID-19,

• Discharged from hospital at least 3 months ago,

• Alive

Exclusion criteria:

• Potential participants from NHS Trusts in England that have already undertaken REGAIN invitation mailouts as Primary Identification Centre sites (PIC sites). This will ensure the likelihood of contacting patients who have already been invited is minimal and therefore reduces patient burden.

* Children (17 years or younger) have not been included in this clinical trial as the logic model applied to the development of this intervention for Long-Covid has been based on a previously developed adult intervention which was not designed for use by children.

ORGANISATION’S ROLES AND RESPONSIBILITIES:

UHCW and University of Warwick are the applicant and joint data controllers. They are responsible for the trial and overseeing the work carried out to aid recruitment into the trial. They are also responsible for providing the core eligibility criteria for participants.

UHCW and University of Warwick are joint data controllers and are responsible for:

1. Generating the invitation request(s) and sending to NHS Digital.

2. Monitoring uptake by invitees (i.e. numbers of invitees consenting to participate in the trial)

4. Monitoring scope of the population booking appointments and entering the study

NHS Digital are acting as a data processor on behalf of UHCW and University of Warwick and are responsible for:

1. Applying the inclusion and exclusion criteria from the invitation request to the datasets to generate a list of invitees

2. Feeding back to UHCW and University of Warwick the number of invitees actually fulfilled out of the total target population (if less than 20,000 target)

3. Removing objections or opt outs

4. Sending the list of invitees on to their third-party provider (Allied Publicity Services (APS) Group) for generating the invitation letters and mailing these out

5. Agreeing with UHCW and University of Warwick key processing timelines, including

a. Time from submission to APS Group to mailout

b. Date of the mail outs

6. Overseeing performance of APS Group and alerting performance issue to UHCW and University of Warwick.

7. Feeding back to UHCW and University of Warwick performance in relation to KPIs of APS and NHS Digital

8. Where the number of invitees is less than the population available, invoking a system to choose invitees at random

9. Maintaining a record of people invited and ensuring they are excluded from second rounds of invitations.

Allied Publicity Service (APS) are acting as a sub-processor of NHS Digital. Their responsibility is to receive the lists of invitees from NHS Digital and mail out to them accordingly.

The Trial Management Group (TMG) and Trial Steering Committee (TSG) - Both groups contain members of the study team and other external collaborators from other academic institutions who are likely leads in the field of respiratory health or clinical trials. The groups are responsible for monitoring all aspects of the conduct and progress of the study, to ensure that the protocol is adhered to and to take appropriate actions to safeguard participants and the quality of the study itself. These members do not making decisions on the design of the study and the purpose and means of processing the data and are therefore not considered Data Controllers. External collaborators have no access to NHS Digital data and are therefore not considered Data Processors either.

The National Institute for Health Research (NIHR) funds this clinical trial but does not make any decisions determining the purposes and means of the processing, nor the way the study is conducted and is therefore not considered a Data Controller.

While UHCW and University of Warwick are joint data controllers for this trial, neither will have access to the patient-level identifiable data provided by NHS Digital to APS Group.

As joint data controller, UHCW and University of Warwick will provide the core eligibility criteria for those potential participants who will receive invitations. UHCW and University of Warwick, refine the population that receive these invitations based on NHS Trusts (as a proxy for location), making adjustments as required to ensure adequate representation of target populations. NHS Digital would be using an established contract with a mailing provider (APS Group) to fulfil the communications. The APS Group are also used by NHS England and NHS Improvement as a marketing service group that is a recognised and trusted provider of NHS Services. They are used frequently to co-ordinate mail outs for NHS Bodies. APS Group will use REC-approved template invitation letters and would add address details onto the letters prior to mailing it out. All identifiable data provided to APS Group by NHS Digital will be done so under the legal basis of COPI Regulations.

Data processing is carried out by substantive employees of NHS Digital who have been appropriately trained in data protection and confidentiality. NHS Digital will access records allowing them to gather the following information needed to determine suitability for invitation to the REGAIN study.

COHORT IDENTIFICATION:

• Using the inclusion and exclusion criteria as specified by UHCW and University of Warwick, NHS Digital will interrogate the Patient Demographics Service (PDS) dataset and extract all those potential participants who meet the criteria within the latest specification as provided by UHCW and University of Warwick.

• Of the potential participants, for the first 2 mailouts, 20,000 records (approximately 10,000 per mail out) will have their relevant contact details (Forename, Surname, Address, Postcode,) extracted ready for despatch to APS Group. (Should any further mailouts be required, the number of records required will be ascertained based on the current uptake percentage and the number of participants yet to be recruited to the trial at that time. No potential participant will be contacted more than once for this trial)

• NHS Digital will then remove any records where a national Data opt-out has been registered, as well as special categories of people for whom the data should not be disseminated. The purpose of the restriction is to ensure that patient information that might imply a location is protected.

• NHS Digital will also provide APS Group with a generic Screening ID to include within the mailing (in the format NHS0001). This screening ID will allow UHCW and University of Warwick study team to know that the patient received a postal invite following the mailout from NHS Digital. UHCW and University of Warwick would not be able to use this screening ID to identify any individual member of the cohort.

COHORT DISSEMINATION AND MAILOUT:

• NHS Digital will create an extract of potential participant records which will be added to a mailing list cohort dataset (approximately 10,000 per mail out for the initial 2 mailings. Extract number to be determined should any future mailing be required to meet recruitment target)

• NHS Digital will provide APS Group with Forename, Surname, Address, Postcode, and screening ID via Secure Electronic File Transfer (SEFT.)

• APS will then mail out to individuals as required.

• All potential participants will receive an invitation letter containing their Name, Address and Postcode, and Screening ID. The screening ID provided on the postal invitation letter for all patients may be entered by interested patients on the REGAIN study website when registering their interest in the study. This screening ID will allow the REGAIN team to know that the patient received a postal invite following the mailout (as opposed to a PIC site mailout).

• APS will destroy all data received from NHS Digital one week after mailing as instructed by NHS Digital.

No patient data will flow from University of Warwick and UHCW to NHS Digital and vice versa.

Patients will receive one postal invitation; there will be no attempts to remind or re-approach patients who do not respond to the postal invitation. In the unlikely event an invitation letter is sent to a person who has not had COVID-19, the invitation letter/flyer will explicitly state that they should ignore/destroy the letter/flyer.

The data from NHS Digital will not be used for any other purpose other than that outlined in this Agreement. The data from NHS Digital will not be linked to any other data other than those outlined in this Agreement.

As a result of this recruitment agreement with NHS DigiTrials, the REGAIN study team are hoping to recruit to target having posted out adequate numbers of invitations to potentially eligible participants. The completion of this trial in a timely fashion would be in jeopardy without the adoption of this recruitment approach and the use of data in this way is now critical to the success of the trial.

Results for this trial are time sensitive and should the trial continue to recruit at its previous rate, results will be less relevant in a post-pandemic environment. Timely completion of the trial is in the interests of both NHS providers and people with Long-Covid after a hospital stay, and the study team will aim to report on both clinical and cost-effectiveness.

The results of the REGAIN study have the potential to influence rehabilitation practices UK wide, therefore, the study team aim to submit trial results for publication and dissemination as quickly as possible. All outputs and publications will contain only aggregated data.

Identifiable health data requested from NHS Digital will only be used to identify and invite potential participants. NHS Digital record Level Identifiable data will not be reported, and participants will be anonymised in all outputs and publications.

This is an NIHR funded study, and all outputs of the trial will therefore be reported to the NIHR. It is anticipated that the NIHR will publish a report of the REGAIN study on its website. The trial will be reported in accordance with the Consolidated Standards of Reporting Trials (CONSORT) guidelines.

Specific anticipated outputs include:

• The final NIHR Health Technology Assessment (HTA) Mongraph; due to be published in 2023.

• Peer reviewed publications submitted mid-late 2022 and published early 2023.

• Main trial findings summarised on the Warwick Clinical Trials Unit main website.

• Findings to be disseminated via social media, including the Warwick Clinical Trials Twitter page (@WarwickCTU) and the REGAIN study Twitter page (@RegainStudy)

The study findings hope to be widely promoted on Twitter and usual scientific routes, thus via national and international academic conferences and peer-reviewed publications. There are patient representatives within the research team who it is expected will also be involved with preparing materials for wider dissemination. Findings should feedback to patient groups who provided input to the early development phases of the trial.

The University of Warwick are planning to work with their Marketing and Communication team to develop a strategy for communication with the media (television, radio, newspaper etc) to enhance communication of the trial results to patients / participants.

The University of Warwick also intend to produce a lay summary of the trial results with their public and patient involvement partners that include the trials management group (monthly meeting) and the independent trial steering committee that meets on a bi-annual basis. All groups have lay representation and participants from variety of backgrounds. This is anticipated to be disseminated to participants of the trial who indicated they wanted to know the results.

Due to the specific exclusion and inclusion criteria of this study, it should be noted that the outputs of the study are based on those hospitalised with Long-Covid, and will not include any participants who may meet other diagnostic criteria for Long-Covid but were not hospitalised.

There is a need to deliver the REGAIN study rapidly to inform care for COVID-19 survivors with Long-Covid after a hospital stay and to achieve the greatest benefit for patients and society.

Use of data from NHS Digital for a REGAIN invitation mailout aims to ensure 20,000 patient invites are sent out over the duration of one month which is much higher than current rate of recruitment. To date NHS Trusts have sent out an estimated 8000 invites over 13 months. The use of data from NHS Digital should allow for more timely recruitment into the REGAIN study and remove the significant capacity constraints suffered by NHS Trusts which have impaired recruitment to date and would have seen recruitment end in 2024.

The aim of this agreement is to allow the study to reach its recruitment target within 2022, answer important research questions, and disseminate results with maximum impact at a time where the answer is still relevant and sought after. The study team anticipate that the impact of this study will be sufficient to influence rehabilitation policy for people with Long-Covid.

Completion of the study benefits healthcare provision by addressing the rehabilitation challenge the UK is now facing as a result of the large number of people with Long-Covid (after a hospital stay) over a short time frame. This has physical, psychological and economic consequences at individual and societal levels. While acute interventional research has rapidly developed, the REGAIN intervention has the potential to guide recovery and re-entry to economic productivity for those living with the longer-term consequences of COVID-19. It should again be noted that due to the specific exclusion and inclusion criteria of this study, the expected benefits of the study are therefore focused on those hospitalised with Long-Covid.

Long-term rehabilitation interventions are not routinely offered to people with Long-Covid. The study team are under the understanding that there are no rehabilitation interventions currently being tested in the UK for people who have not fully recovered from COVID-19 more than three months after hospital discharge. This group are likely to require intensive support as they are at high risk of chronic physical and mental health problems.

If either of the interventions tested in this trial are found to be effective, the study team will have an intervention suitable for immediate implementation nationally and internationally. Implementation of a successful programme has the potential to substantially reduce the chronic burden of COVID-19 in a large number of survivors, who, in the current unique pandemic environment, may not have access to normal social and primary/community care support. Apart from the direct benefits for those concerned, improving the general health of survivors has the potential to reduce demand on health and social services more widely and improve economic productivity.

The immediate benefit of using information from NHS Digital for a REGAIN mailout will be comprehensively and accurately measured by the number of patients expressing an interest via the study website after receiving the postal invitation. The study team intend to observe trial uptake during the time when mailout work will be undertaken, in line with the end of the current COPI Notice (30 June 2022). The REGAIN team are suitably equipped and staffed to manage the predicted upturn in participants following a mailout using NHS Digital.

Yielded Benefits is not a requirement for new applications.