Prophylaxis for patients at risk of COVID-19 infection (PROTECT-V)

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Objective for processing

University of Cambridge (UoC) and Cambridge University Hospitals NHS Foundation Trust (CUH) requires access to NHS England data for the purpose of the following clinical trial: Prophylaxis for patients at risk of COVID-19 infection (PROTECT-V) [2 paragraphs unchanged] The drug tested in the PROTECT-V trial is niclosamide, a common safe [63 words unchanged] COVID-19 infection usually first takes hold. This formulation of the drug is unlicensed, unlicensed but has been shown to be safe and well tolerated in a [35 words unchanged] dose than the single 2000mg tablet which is taken for tapeworm infections. ORGANISATIONAL ROLES The trial is now complete. The Medicines for Human Use (Clinical Trials) Regulations (2004) stipulates that clinical trial data needs to be retained for at least 5 years. The PROTECT-V trial has been ethically approved to allow data to be retained for 15 years post trial. UoC and CUH would like to retain this Data to ensure reconstruction of the trial analysis is possible if required. Cambridge University Hospitals NHS Foundation Trust (CUH) and The University of Cambridge (UoC) are the Sponsors for this clinical trial based in the UK. In the context of a clinical trial, “Sponsor” means the organisation(s) ultimately responsible for the conduct of the trial and thus under this agreement Cambridge University Hospitals NHS Foundation Trust and The University of Cambridge are Data Controllers. Both organisations are also Data Processors as they have substantively employed individuals involved in the PROTECT-V Trial Team. There is an overarching Research Governance Framework agreement between CUH and UoC regarding their responsibilities related to the research. No additional data will be requested from NHS England. FUNDING This Data Sharing Agreement (DSA) permits processing of the Data for the purpose of secure storage and back up. PROTECT-V is funded by LifeArc (a UK life science medical research charity), Addenbrookes Charitable Trust (ACT), Kidney Research UK, and UNION Therapeutics (a Denmark-based pharmaceutical company). UNION Therapeutics will also provide packaged study medication (Niclosamide) for the study. None of these funders will have access to record-level NHS England data. None of the funders determines what data is collected, how this data is collected and for which purpose in this trial, and are therefore not considered Data Controllers in this agreement. This DSA does not permit any further processing that involves analysis or linkage other than for the purpose of verifying findings in line with the original objectives of the study by repeating previous analyses described in this DSA. PATIENT AND PUBLIC INVOLVEMENT AND ENGAGEMENT (PPIE) Following publication of the study findings, it is possible that the findings will be questioned or challenged by third parties through direct contact with UoC and CUH, contact via the publishing journal or an open letter. In such circumstances, UoC and CUH may repeat the previously analyses undertaken to verify that the published results were accurate and may write a response to be issued directly to the challenger or published. Prior to its start, the study was submitted and received feedback from the Cambridge University Hospitals NHS Foundation Trust Patient and Public Involvement (PPI) panel, which is coordinated by the NIHR Cambridge BRC PPI team. The trial was viewed positively and panel comments and suggestions were worked into the resulting consent materials. UoC and CUH may not undertake different analyses to those undertaken during the original analysis. COHORT This DSA does not permit any onward sharing of the Data with the exception that the Data may be viewed for the purpose of an audit by a regulator such as the Medicines and Healthcare products Regulatory Agency (MHRA). The MHRA maintains a list of all clinical trials registered with them and reserve the right to audit the trial at any point from when the trial is opened to 5-year post trial closure. The PROTECT-V study has multiple arms of study, investigating Niclosamide, Ciclesonide, and Sotrovimab. This application refers only to the Niclosamide arm of the study. The first participant was recruited on the 19-Feb-2021 and the last UK participant recruited was the 22-Nov-2022. The trial closed to recruitment on the 28-Nov-2022. All participants have consented to follow-up data from NHS England for up to 9 months following the Date of Randomisation. A sponsoring organisation and/or the controller itself may also exercise the right to audit. DATA REQUESTED This DSA permits the necessary processing of the Data for the purposes of permanently destroying, deleting or erasing the Data once it is no longer required for the purpose for which it was collected. Once destroyed/deleted or erased, UoC and CUH must confirm destruction to NHS England. The University of Cambridge and Cambridge University Hospitals NHS Foundation Trust to obtain a one-off drop of record-level data linked to a cohort of approximately 1,200 individuals for Civil Registrations (Deaths) data. Data fields have been limited to only those required to undertake a sensitive analysis of the data for Primary Outcomes measures. If any further data processing is required in addition to the above purposes or if the Data needs to be moved to a different location/organisation UoC and CUH must submit an Amendment request to NHS England before Data is accessed. Civil Registrations (Deaths) data is required for the study to undertake calculation for time to COVID-19 infection by 9 months. For participants without COVID-19 infection by 9 months, they will be censored at the date of death (if the date of death is less than 9 months) or at 9 months (no death). Data from the following NHS England Data will be retained: The primary outcome is the time to COVID-19 infection. If patients pass away before having gotten to the end of the time in the trial, their data will be censored at the time of death. Otherwise the study would have to assume the individual got to 9 months without infection (which they would not have - for example, a patient could pass away after 3 months, so their timeframe without COVID-19 would actually be 90 days as opposed to 270 days). Without the death data to calculate this timeframe the study would be introducing a significant bias to the time to COVID-19 infection analysis (the primary outcome for the trial) and this would significantly affect the reliability of the trial results. • Civil Registration of Deaths COMMON LAW The level of the Data being retained will be: NHS England have satisfied themselves that the consent materials supplied to participants are compatible with consent (reasonable expectations) and that this request is appropriate, necessary and proportionate for the performance of the task described in the Purpose statement and that there is no other reasonable means for the data processor to achieve their purpose that is less intrusive to the data subjects. • Pseudonymised COMMERCIAL PURPOSE The data was minimised as follows: In the interests of Transparency, the study acknowledge that whilst the aim of PROTECT-V is to investigate the effectiveness of specific treatments (for the purposes of this agreement, Niclosamide) on patients on dialysis or receiving immunosuppressive medications in preventing the spread of COVID-19 - if proven safe and effective - UNION Therapeutics will benefit from the potential increased use of Niclosamide. • Limited to data for a study cohort identified by UoC and CUH – approximately 1200 individuals, with data limited to up to 9 months after date of randomisation. This an investigator initiated trial with a purpose of investigating the effectiveness of specific treatments on patients on dialysis or receiving immunosuppressive medications in preventing the spread of COVID-19. UNION Therapeutics will also provide packaged study medication (Niclosamide) for the study. If the results show that Niclosamide is safe and effective this will be used to evidence their licencing application of Niclosamide and therefore could also increase revenue for the manufacturer and funder UNION Therapeutics (as the manufacturer of the drug). However this is not the primary purpose of PROTECT-V. UoC and CUH are joint sponsors and are responsible for ensuring that the Data will only be processed for the purpose described above. Whilst not directly relevant to this data sharing agreement, it is noted here in the interests of transparency that GSK PLC are funding a separate drug arm of the overarching PROTECT-V study for a drug called Sotrovimab. Should Sotrovimab be shown to be effective, data from that arm of the trial may be used to support GSK’s licencing application for Sotrovimab as a prophylactic agent and therefore could also increase revenue for GSK PLC (as the manufacturer of the drug). UK GDPR does not apply to data solely relating to deceased individuals. The data received by Cambridge University Hospitals NHS Foundation Trust (CUH) and The University of Cambridge (UoC) will not be used for any purpose other than to meet objectives as stated in this Data Sharing Agreement and will not be shared with any other third party, funder or organisation not already stated within this agreement unless first aggregated with small number suppression applied as per the relevant data set disclosure rules. The funding is provided by LifeArc (a UK life science medical research charity), Addenbrookes Charitable Trust (ACT), Kidney Research UK, and UNION Therapeutics (a Denmark-based pharmaceutical company). The funders will have no ability to suppress or otherwise limit the publication of findings.

Processing activities

Under this agreement, one extract of Civil Registrations (Deaths) data linked to the PROTECT-V cohort of participants (approximately 1,200 individuals) will be requested from NHS England. The cohort will include all participants from the Niclosamide arm of the PROTECT-V study, randomised in England/Wales. No data will flow to NHS England for the purposes of this Data Sharing Agreement (DSA). The cohort identifiers for linkage purposes will include PROTECT-V study number (Pseudonymised Study ID), NHS Number, First name, Surname, Date of Birth, Post Code and Date of Randomisation. The Civil Registrations (Deaths) dataset will be minimised by the NHS England Data Production team using the Date of Randomisation to produce an extract of data for those cohort members who have sadly died within 9 months of the Date of Randomisation. UoC and CUH holds the relevant records from the Civil Registration of Deaths dataset. The Data will: After receipt of the cohort details and respective linkage, NHS England will provide a linked record-level extract of the Civil Registrations (Deaths) dataset on a one-off basis as soon as possible. • contain no direct identifying data items, but will contain a unique person ID which can be used to link the Data with other record level data already held by the recipient. The data file will be transferred via NHS England's Secure Electronic File Transfer System (SEFT). No additional data will be disseminated by NHS England for the purposes of this DSA. All data processing will be carried out by authorised members of the PROTECT-V study team who are substantive employees of the University of Cambridge and/or Cambridge University Hospitals NHS Foundation Trust. All investigators and trial site staff involved in this trial must comply with the requirements of the Data Protection Act 2018 and Trust Policy with regards to the collection, storage, processing and disclosure of personal information, have received appropriate training in data protection and confidentiality. This DSA does not permit any onward sharing of the Data with the exception that the Data may be viewed for the purpose of an audit by a regulator such as the Medicines and Healthcare products Regulatory Agency (MHRA). Personal identifiable data (PID) will be stored separately from pseudonymised study data on a secure server hosted within University of Cambridge School of Clinical Medicine Secure Data Hosting Service. PID will be accessible to the PROTECT-V trial team within the Cambridge Clinical Trials Unit, monitors, auditors and inspectors as required. It is necessary to: The Data will be stored on servers at UoC. 1) perform validation of NHS Numbers and linkage to routinely collected datasets, and This DSA is required for the following reason: 2) to generate datasets with participant details for mail merge creation of questionnaires, and is therefore imperative to the conduct of the study. Clinical trial data needs to be retained and accessible for 15 years after trial completion as per ethical approvals. This requirement would be subject to further data extension requests – no data will be retained without a DSA being in place. Statistical data analysis will be carried out via devices owned and managed by the University of Cambridge by connecting to internal networks where the data are stored securely, either directly in person or remotely inline with NHS England's remote access policy, using an appropriate statistical package. To remotely access the devices requires a secure 2-factor authenticator (VPN) and users are then able to securely access the secure server on the University’s IT framework. All data analysis will be conducted within the confines of the University’s secure server, and will not be downloaded to remote devices for storage or processing. By signing the Data Sharing Agreement, all organisations party to this agreement must comply with the Data Sharing Framework Contract, including requirements on the use (and purposes of that use) by "Personnel" (as defined within the Data Sharing Framework Contract i.e.: employees, agents and contractors of the Data Recipient who may have access to that data). The Data Controller should ensure appropriate data processing agreements are in place with all data processors contracted to undertaking work referenced within this agreement. Upon instruction from NHS England, a Certificate of Data Destruction must be completed by the Data Controller confirming the data has been appropriately disposed of following use. [1 paragraph unchanged]

Benefits reported

Yielded Benefits is not a requirement for new applications. If demonstrated, use of Niclosamide acting as a prophylactic treatment of COVID-19 would significantly benefit those immunocompromised individuals that have been shown to have a poor vaccine response. There are no drugs proven to prevent COVID-19 or to reduce the severity of illness if given as particularly in immunocompromised individuals for whom vaccine responses may be suboptimal. The results of the trial aim to be provided to the Department of Health and Social Care (DHSC). It is hoped that, using the results of this trial, they will be able to influence policy guidelines and other guidelines regarding the clinical practice within the patient population. The findings of this research study are expected to contribute to evidence-based decision-making for policy-makers, local decision-makers such as doctors, and patients to inform best practice to improve the care, treatment and experience of health care users relevant to the subject matter of the study. It is hoped that through publication of findings in appropriate media (publications, conferences and other media communication i.e. PR releases, news interviews etc.), the findings of this research will add to the body of evidence that is considered by the bodies, organisations and individual care practitioners charged with making policy decisions for or within the NHS or treatment decisions in relation to specific patients. As the trial has closed to recruitment the final data analysis aims to be completed this year (2023) and could have significant impact on clinical practice. One of the trial funders is the Kidney Research UK (KRUK). The KRUK will be provided results of the trial and will directly support the patients in these immunocompromised populations.

Unchanged: Expected output, Expected measurable benefits.