Mass evaluation of lateral flow immunoassays for the detection of SARS-CoV-2 antibody responses in immunosuppressed people (MELODY)

This agreement is to support the Mass evaluation of lateral flow immunoassays (test of the immune system) for the detection of SARS-CoV-2 antibody responses in immunosuppressed people (MELODY) Study, being conducted by Imperial College London (sponsor and data controller), and being funded by the Medical Research Council.

MELODY aims to determine:

1. The proportion of immunosuppressed people who have detectable SARS-CoV-2 antibodies following a primary vaccine course (3 doses), and the demographic, disease, and treatment characteristics that influence antibody status.

2. If the detection of antibodies inversely correlates with subsequent risk of SARS-CoV-2 infection and/or severity of disease in immunosuppressed people.

The MELODY study includes two parallel arms: one where a cohort of people who are immunosuppressed due to autoimmune diseases and cancers are identified by the National Disease Registration Service (NDRS), and another parallel arm and methodologically similar arm where a cohort of people who are immunosuppressed due to solid organ transplants are included through NHS Blood and Transplant. This application relates only to the arm involving NDRS and the patients with autoimmune diseases and cancers. The arm involving NHS Blood and Transplant does not involve NHS Digital.

Imperial College is leading this research, but other organisations are also involved. Imperial College have engaged Ipsos MORI, an independent research organisation, as data processor, to send out invitations to people who are eligible for the MELODY study, to conduct the survey, and post out the home antibody testing kits to participants. The National Disease Registration Service (NDRS) are supplying the cohort of patients to invite to the autoimmune disease and cancer arm of the study, and NDRS will receive the study data once the survey and antibody tests are complete to perform the study analysis, and for those participants who consent to data linkage with process it further as part of the NDRS record. NHS Blood and Transplant are supplying the cohort of patients to invite to the transplant arm of the study and will receive the study data relating to the transplant cohort once the survey and antibody tests are complete to perform the study analysis. Other organisations (University of Nottingham, University of Cambridge, University of Southampton) employ people who are clinical experts and form part of the study team but are not involved in data flows.

The study team are undertaking a rapid study set up in order to capture this participant cohort in line with the current roll out of 3rd doses of COVID 19 vaccinations for people who are immunosuppressed, which was announced on 1 September 2021. The study team need to collect antibody test results within 90 days of people's 3rd dose of COVID 19 vaccination.

The MELODY study will invite up to 80,000 immunosuppressed people with either a autoimmune disease or haematological malignancy aiming to recruit 24,000. (An additional 12,000 people immunosuppressed following solid organ transplantation will also take part in the MELODY study, but the process of inviting them falls outside this DARS application.) The patient demographic service (PDS) data requested from NHS Digital is restricted to this cohort, for the sole purpose of sending them letters of invitation asking them if they wish to consent to take part in the study and confirming their identity if they register on the study web portal or contact the Ipsos MORI helpline. Those eligible will be immunosuppressed people aged ≥18 years of age who have received 3 doses of a COVID-19 vaccine.

The near patient antibody testing kits (also called Lateral Flow Immunoassay, or LFIA kits) used in the MELODY study are licensed by the Medicines and Healthcare products Regulatory Agency (MHRA) only for use in people aged 18 or over. Therefore the MELODY study is being limited to participants aged 18 and over at the present time in order to start the MELODY study without delay. The MELODY study team are planning to apply to the MHRA to use the LFIA kits in people aged 12-18, and if this is granted apply for an amendment to include participants aged 12+ (the age group who have been offered vaccination at the time of writing); but the MELODY study team do not wish to delay the start of the study while awaiting the outcome of this application process.

There will also be two online or telephone questionnaires to complete. There are no invasive procedures, although finger prick may cause some short-lived discomfort.

The processing of data for this study is a task of public interest. Imperial College London is data controller and processes data under the legal basis of Article 6(1)(e) and Article 9(2)(j) ‘processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes …’ as the data are required for research purposes in the public interest and judged subject to the appropriate safeguards. The research will provide a measure of the national seroprevalence (percentage of people in the population who have antibodies in their blood) for these vulnerable populations, and also describe the real-world effectiveness of 3 COVID-19 vaccinations against COVID-19 infection, hospitalisation and death. Furthermore, it may identify a cohort of people who have not developed measurable antibodies following 3 doses of COVID-19 vaccination and who may be targeted for further studies or interventions, for example of prophylactic monoclonal antibody treatments to prevent COVID-19 infection.

The legal basis for the patient identifiable data from NDRS to flow from NHS Digital to Ipsos MORI for the purpose of Ipsos MORI inviting them is Health Research Authority (HRA) Confidentiality Advisory Group (CAG) Section 251 approval (NHS Act 2006).

The survey will involve processing special category data in relation to the health and ethnicity of individuals taking part. The results will be used to help provide stratified advice to specific patient groups, rather than classify all immunosuppressed patients at risk. This information could also help estimate and/or identify the number of patients who may benefit from additional or alternative methods of prophylaxis (treatments to prevent disease), such as monoclonal antibody therapy (A type of protein that is made in the laboratory and can bind to certain targets in the body, such as antigens).

While the legal basis is public interest the research has had ethical approval from the London Central Research Ethics Committee (REC) and Health Regulator Authority (HRA) dated 30 November 2021.

The cohort will be selected from the National Disease Registration Service (NDRS), comprising the National Congenital Anomaly and Rare Disease Registration Service (NCARDRS) and the National Cancer Registration and Analysis Service (NCRAS).

The data required is demographic information from the NHS Digital Patient Demographic Service, to allow individuals aged 18+ from the cohort selected above to be contacted for the purpose of undertaking a survey of seroprevalence using self-administered lateral flow assays (test). The data requested (name, address, postcode, mobile telephone number, and date of birth) are the minimum required to send letters of invitation to a random cohort of suitable participants, and confirm their identity on registration or when they contact the helpline.

Ipsos MORI will use the names and addresses to post letters of invitation to potential participants, and mobile telephone numbers to send text message reminders. They will use the name and date of birth to check the identity of each person who registers (to ensure they are the invited person). Each potential participant will also be assigned a unique invitation ID so that so that issues with specific records can be communicated between Ipsos MORI and NDRS, such as if an invitee wishes to opt out. Personal identifiable information such as names, addresses and mobile telephone numbers will be kept separately from the study data and used only for the purpose of contacting invitees and confirming their identity as described in the protocol. It will be destroyed by Ipsos MORI after all invitations have been issued, which is estimated to be at the end of March 2022.

The data extracts requested from NHS Digital will be used in order to contact a nationally representative cohort of adults to take part in the testing. There is no other national register of the population that would allow contact with a named and representative cohort of those with a rare autoimmune disease or with lymphoid malignancies. Data will not be made available to any third parties, other than those specified in this agreement, except in the form of aggregated outputs with small numbers suppressed in line with the suppression rules stated in the HES analysis guide.

When the survey and antibody results have been collected they will be collated by Ipsos MORI, and securely transferred to NDRS for analysis. Participants will be identified by their unique invitation ID (not name, address and mobile phone number). MELODY is an approved NDRS analytical project. Data may be used to complete or correct NCRAS or NCARDRS records.

Data controllers:

• Imperial College London (sponsor)

Data processors:

• Ipsos MORI – who are working with the following suppliers to deliver the project:

• Formara Limited – Print and despatch

• Txtlocal Ltd - Text message reminders

• Tivian GmbH - Online front-end data collection platform

accessed by Ipsos Germany

The data will be requested in one drop: NHS Digital to provide the identifiable data extract (approx. 80,000), including demographic and contact details, to Ipsos MORI. Imperial have a Data Processing Agreement with Ipsos Mori, that has the provisions for sharing data outside of the UK for example standard contractual clauses within their Data Processing Agreement.

The contact details will be used to contact up to 80,000 people to ask them to register and consent to complete the test - stopping when 24,000 have consented to do this. In order to do this each person will be sent a letter by an approved print supplier (Formara Ltd). If they agree they will register online which will then trigger a test being sent to their address by Formara Limited. The test is then self-administered and the participant is asked to take part in a short online or telephone survey including information on demographic variables, household composition and their medical condition.

Tivian GmbH is responsible for the technical implementation of the online registration/ survey and data collection platform. While Ipsos Germany programme the questionnaires using the Tivian GmbH platform and therefore have access to sample data, Tivian GmbH actually hold the sample data on their servers.

Name and address information is held securely and separately from the survey data, for example, there is controlled and restricted access to the computer system where this information is stored at Ipsos MORI.

The personal data is only used for the purpose of inviting people to take part in the research, and confirming the identities of people who register for the study or contact the helpline. No identifiable data is shared outside the research team (unless they consent to data linkage) and it is not possible to identify individuals in the published results.

No linkage will be done without consent from patients. If participants do not consent to data linkage they will be withdrawn from the second part of the study (aim 2: If the detection of antibodies inversely correlates with subsequent risk of SARS-CoV-2 infection and/or severity of disease in immunosuppressed people) as outcome measures for the second part require linkage to other datasets within NDRS at NHS Digital.

The identifiable patient level data is used to invite patients to register to take part in the research.

Data resulting from the study will be incorporated into patients’ records per Section 3.4 of the Requirements Specification for the National Disease Registries Directions 2021: National Congenital Anomaly and Rare Disease Registration Service.

All employees involved in the processing are appropriately trained in data protection and confidentiality. Ipsos MORI is certified to ISO 27001 the international standard for Information Security and ISO 20252 the international standard for market research, as well as an MRS Company partner. All employees sign contracts that include appropriate confidentiality clauses, requiring them to comply with relevant data protection policies and procedures. Information Security and acceptable use policies and procedures include clauses that clearly define unauthorised use and/or deliberate misuse, disclosure, loss or destruction as misconduct, with appropriate links to disciplinary procedures. Policies and procedures also include clear warnings that such actions may also lead to legal action against those involved.

All suppliers (for printing and online survey delivery) are approved suppliers (also certified to ISO 9001 and ISO 27001) and Article 28 compliant agreements are in place.

All personal data held in delivering this survey will be subject to appropriate security measures to ensure it is kept secure from accidental or deliberate loss, destruction or disclosure. All organisations handling personal data are accredited to the international standard for information security (ISO 27001), which requires an information security policy documenting their approach.

In terms of technical measures, all users have their own login and password, and access controls are based on user accounts with rights automatically controlled by ‘Active Directory’ group security policy objects.

Access to patient identifiable data will be restricted to the minimum number of personnel; all of whom have undergone training in data protection law, their duty of confidentiality under contract and in the care and handling of personal data. Any locations containing patient identifiable information would have restricted access to a limited number of project team members, with access rights regularly reviewed.

The NHS Digital data will not be used for any other purposes or combined with any other datasets other than those detailed in this Agreement.

The outputs will be a report for the Department of Health and Social Care (DHSC) to inform health policy, and papers in the peer-reviewed medical literature to make the results available for the benefit of all. Target date for report of antibody prevalence in people who are immunosuppressed - Jan/Feb 2022; target date for full study results publication in the medical literature - up to and including Oct 2022.

It is anticipated that the data may help the study to:

1) Quantification of the proportion of immunosuppressed patients who have detectable SARS-CoV-2 antibodies following a primary vaccine course (3 doses). It is hoped that this will inform patients, clinicians and those who devise health policy of the numbers of immunosuppressed people in the UK who have not responded to the SARS-CoV-2 by developing antibodies. It is hoped that this will pave the way to protect them in other ways, for example by additional targeted protection with prophylactic monoclonal antibody treatments – target date February 2022.

2) Description of and the demographic, disease, and treatment characteristics that influence antibody status. It is hoped that this will allow stratification of the whole group of people who are immunosuppressed into groups at different risks of having no detectable antibodies to SARS-CoV-2 following their 3rd primary vaccination. It is hoped that this will inform which groups may benefit from targeted strategies such as prophylactic monoclonal antibodies. Target date March 2022.

3) Understanding if the detection of antibodies inversely correlates with subsequent risk of SARS-CoV2 infection and/or severity of disease in immunosuppressed individuals. It is hoped that this will further inform the potential need for additional measures targeted towards these individuals. Target date – July 2022.

Yielded Benefits is not a requirement for new applications.