Good TREs work

Evidera Ltd projects

35 data files in total were disseminated unsafely (information about files used safely is missing for TRE/"system access" projects).

VidPrevtyn Beta® Vaccine Effectiveness against hospitalisation due to SARS-CoV-2 infection in the UK study — DARS-NIC-717485-F8L6H

Type of data: information not disclosed for TRE projects

Opt outs honoured: Anonymised - ICO Code Compliant (Does not include the flow of confidential data)

Legal basis: Health and Social Care Act 2012 – s261(2)(a)

Purposes: Yes (Research)

Sensitive: Sensitive, and Non-Sensitive

When:DSA runs 2024-10-11 — 2025-10-10 2024.11 — 2024.11.

Access method: System Access
(System access exclusively means data was not disseminated, but was accessed under supervision on NHS Digital's systems)

Data-controller type: SANOFI PASTEUR

Sublicensing allowed: No

Datasets:

  1. Civil Registrations of Death
  2. COVID-19 General Practice Extraction Service (GPES) Data for Pandemic Planning and Research (GDPPR)
  3. COVID-19 SGSS First Positives (Second Generation Surveillance System)
  4. COVID-19 Vaccination Status
  5. Hospital Episode Statistics Admitted Patient Care (HES APC)
  6. Hospital Episode Statistics Critical Care (HES Critical Care)
  7. Hospital Episode Statistics Outpatients (HES OP)
  8. Uncurated Low Latency Hospital Data Sets - Emergency Care

Objectives:

Sanofi Pasteur requires access to NHS England data for the purpose of the following research project:
VidPrevtyn Beta® Vaccine Effectiveness against hospitalisation due to SARS-CoV-2 infection - a secondary database study in the UK

The following is a summary of the aims of the research project provided by Sanofi Pasteur:

Specific populations are still at a high risk for severe COVID-19 outcomes including hospitalization and death following a SARS-CoV-2 infection. Vaccines effectiveness wanes over time and new variants of SARS-CoV-2 can result in some vaccines to be more or less effective than others. Thus, effective booster doses are required to protect at risk populations. In England, the vaccination guidelines as set out by the Joint Committee on Vaccination and Immunisation (JCVI) as of 27 January 2023 state that:
• Adults over 75+ years, residents in care homes and individuals aged 5 years and over who are immunocompromised will be offered a spring 2023 booster dose.
• Some people, including those aged 50 years or over, those at higher risk or who are pregnant, and frontline health and social care workers, will be offered a seasonal booster.

VidPrevtyn Beta® was approved by the Medicines and Healthcare products Regulatory Agency (MHRA) on the 20th of December 2022 for use in seasonal booster programmes. Regulatory and health assessment agencies (e.g., MHRA and European Medicines Agency EMA) require additional real-world evidence to supplement and augment trial data. This additional information will help relevant agencies (e.g., The Joint Committee on Vaccination and Immunisation) inform decisions on priorities among these populations, anticipating health expenditure, and providing guidance on VidPrevtyn Beta® usage.

Research on the effectiveness of the VidPrevtyn Beta® booster in seasonal booster campaigns is needed to understand how well specific populations are protected with this booster.

Sanofi Pasteur and GSK (GlaxoSmithKline) co-created one of the COVID-19 vaccines that was widely deployed during the COVID-19 pandemic, and Sanofi Pasteur is the sponsor and holder of the marketing authorization for VidPrevtyn Beta®, a booster vaccine against COVID-19. GSK (GlaxoSmithKline) may be asked to comment on the protocol, but they will not have any authority over the protocol design and finalization. Aggregated summary statistics will be shared with GSK.

The overall purpose of this study is to assess the real-world vaccine effectiveness of VidPrevtyn Beta® as a booster vaccine against severe COVID-19 outcomes. This study will utilize the requested data to provide commercial services to Sanofi Pasteur, the creator of VidPrevtyn Beta®. Sanofi Pasteur will use the outputs and insights generated from this study to work collaboratively with NHS organisations to promote health and improve the wellbeing of patients. The use of the data supports the development of innovative solutions and service improvement, to track outcomes and provide the real-world evidence as required by the EMA and MHRA, the aim of which is to improve patient care and support enhanced access to improved services and innovative solutions. In addition, Sanofi Pasteur will utilize the findings of this study to provide supporting information required by the EMA and MHRA for business cases, epidemiological research, pathway analysis, burden of disease analysis, health economic research, and quality and outcome analysis. The outputs of this study will be shared directly with the EMA and MHRA to support improvements in patient care.

The Primary Study Objective is to:
1. Estimate the vaccine effectiveness of VidPrevtyn Beta® against hospitalisation due to COVID-19 with laboratory-confirmed SARS-CoV-2 infection in patients who have received at least one dose of VidPrevtyn Beta® as their last booster, compared with patients who have not received a booster dose within the same vaccination campaign period (between 3 April 2023 – 30 June 2023).

The Secondary Study Objectives are to:
1. Estimate the vaccine effectiveness of VidPrevtyn Beta® against death due to COVID-19 in patients who have received at least one dose of VidPrevtyn Beta® as their last booster, compared with patients who have not received a booster dose within the same campaign period (between 3 April 2023 – 30 June 2023).
2. Estimate the relative vaccine effectiveness of VidPrevtyn Beta® against hospitalisation due to COVID-19 with laboratory-confirmed SARS-CoV-2 infection in patients who have received at least one dose of VidPrevtyn Beta® as their last booster, compared with patients who have received an mRNA booster as their last dose within the same campaign period.

The Exploratory Study Objective is to:
1. Estimate the vaccine effectiveness of VidPrevtyn Beta® against hospitalisation due to COVID-19 with laboratory-confirmed SARS-CoV-2 infection in patients who have received at least one additional dose of VidPrevtyn Beta® as their last dose, compared with patients who have not received a booster dose within the same campaign period, stratified by:
• Age groups
• Gender
• COVID-19 vaccination history
• Subgroups defined by comorbidities (for example, immunocompromised patients, Charlson comorbidity scores).

For the Primary Objective, Secondary Objective 1, and Exploratory Objective, individuals in the VidPrevtyn Boosted Cohort will be based on individuals in the Un-Boosted Cohort. For Secondary Objective 2 individuals in the VidPrevtyn Boosted Cohort will be based on those in the mRNA Boosted Cohort. For all objectives, there will be two study periods; baseline and follow-up.

The commercial interests of Sanofi Pasteur in this project are to better understand the effectiveness of VidPrevtyn Beta® against severe COVID-19 outcomes, as well as to provide evidence requested by health authorities for the assessment of VidPrevtyn Beta® in a real-world setting. Potential benefits of the project to Sanofi Pasteur might include: a) if there is a reduction of the number of severe COVID-19 outcomes in the VidPrevtyn Beta® cohort, this will fulfill regulatory requirements which may result in the vaccine staying on the market; b) if there is a difference in effectiveness in favor of VidPrevtyn over other vaccines, regulatory agencies may be more likely to recommend VidPrevtyn over other vaccines and payors more likely to reimburse for the vaccine c) Evidera will benefit since they will deepen their knowledge of COVID-19 observational research and therefore additional clients might be more likely to approach them based on their experience in this field.

The following NHS England Data will be accessed:
> Hospital Episode Statistics Admitted Patient Care (HES APC), HES Critical Care (CC), HES Outpatients (OP) and Uncurated Low Latency Hospital Data Sets Emergency Care – necessary to identify COVID-19 diagnoses and hospitalizations, as well as risk factors for severe COVID-19 outcomes.
> Civil Registration Mortality – necessary to help define COVID-19 deaths. The date of death will be used to censor follow-up period and as part of the definition of a COVID-19 death.
> COVID-19 SGSS First Positives (Second Generation Surveillance System) – necessary because test results from Pillar 1 and Pillar 2 will be used to identify patients who have a laboratory diagnosis of COVID-19.
> COVID-19 Vaccination Status – necessary to provide information on patient vaccination status, dose, date of injection, and product, which will be used to identify if patients received VidPrevtyn Beta®, another vaccine, or were not boosted during the vaccination campaign. This dataset will also be used to determine how many vaccines a patient has received and the time from the last vaccine.
> COVID-19 General Practice Extraction Service (GPES) Data for Pandemic Planning and Research (GDPPR) – necessary to identify positive SARS-CoV-2 results, risk factors for severe COVD-19 Outcomes including immunosuppressive medication, and other demographic information. Some conditions (e.g., asthma) are routinely managed by primary care professionals and may not require care provided by specialists or consultants; while other conditions are more commonly managed by specialists (e.g., cancer) rather than general practitioners (GP). Therefore, primary and secondary care data sets are required to identify patient groups of interest that are at risk of severe covid-19 outcomes.

The level of the Data will be:
> Pseudonymised

The Data will be minimised as follows:
> Limited to data provided by NHS England to cover all individuals within England aged 18 or over as of 3rd of April 2023 who received a primary vaccination series (i.e., at least 2 doses of any COVID-19 vaccine prior to 3 April 2023). The COVID-19 vaccination status dataset will be used to identify patient’s vaccination status. All patients 18 and older in England who meet the above criteria are requested to ensure patients from each cohort can be properly matched.
> For vaccine estimates to be reliable, patients from each sub-cohort listed below will be matched on several criteria, including age, sex, and comorbidities (using data from HES and GDPPR). This matching will be conducted by Evidera Ltd. Patients who did not receive a booster during the spring campaign period may be younger and healthier than those boosted. A sample of these un-boosted patients may result in the exclusion of patients who may be a better match to the boosted patients. Therefore, all patients who meet the eligibility criteria above are requested for optimal matching that will reduce bias and increase the reliability of the results. Subject to them meeting the above criteria, three cohorts will be constituted:
• VidPrevtyn Boosted Cohort: Patients who received VidPrevtyn Beta® during the campaign
• mRNA Boosted Cohort: Patients who received an mRNA COVID-19 vaccine during the campaign
• Un-Boosted Cohort: Patients who did not receive any vaccine during the campaign and have no record of a primary vaccination.
> Limited to data to include the period between 3rd April 2018 and 31st December 2023. The baseline period will begin five years prior to the index date and end the day before the index date and is requested to ensure important chronic conditions are captured that could affect a patients’ risk of a severe COVID-19 outcomes. Some conditions such as solid organ transplants can place a patient at higher risk even 5 years after the transplant took place. The observation period has been minimised to end after the spring and autumn vaccine campaigns but only as much data that is needed for 6 months of follow-up after the autumn campaign begins (31st December 2023). The follow-up period will begin on the index date and end at the earliest of death, new vaccine, outcome of interest, or 6-months after the index date. The index date for the VidPrevtyn Boosted Cohort and for the Boosted Cohort will be 14 days after receiving the vaccine. The index date for the Un-Boosted Cohort will be the same date as their matched VidPrevtyn Boosted counterpart.

Sanofi Pasteur is the sponsor and controller as the organisation responsible for ensuring that the Data will only be processed for the purpose described above.

Sanofi Pasteur works under the larger 'Sanofi' trading name. Sanofi is not a legal entity and do not determine the means or purpose for data processing.

The lawful basis for processing personal data under the UK GDPR is:
Article 6(1)(f) - processing is necessary for the purposes of the legitimate interests pursued by the controller or by a third party.

Sanofi Pasteur has determined the processing is necessary for its legitimate interests in relation to the ongoing risk of severe COVID-19 in at risk NHS populations. Regulators need to have access to evidence to inform recommendations for booster campaigns and to ensure high risk populations receive the most effective vaccine.

The lawful basis for processing special category data under the UK GDPR is:
Article 9(2)(j) - processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject.

There is public interest to this research as it will help inform the effectiveness of the VidPrevtyn Beta® as a booster vaccine against severe COVID-19 related outcomes. If the vaccine is not as effective as shown in clinical trials agencies and clinicians may not want to offer the vaccine in future campaigns. If it is more effective than other vaccines, they may prefer to offer this vaccine. Additionally, subgroups of individuals at higher risk of sever outcomes regardless of booster dose may be identified. These patients may want to take additional precautions to prevent exposure to SARS-CoV-2.

The funding is provided by Sanofi Pasteur.

Evidera Ltd is a processor acting under the instructions of Sanofi Pasteur. Evidera Ltd's role is limited to accessing available data sources for executing this study.

Commerical purposes explanation:

Evidera is a business within Pharmaceutical Product Development LLC (PPD), a leading global contract research organisation. Evidera has been contracted by and received funding from Sanofi Pasteur to conduct the current research project. The contracted services include drafting the study protocol and statistical analysis plan and finalising these according to the review comments received from Sanofi Pasteur, data preparation, data analysis, results reporting and dissemination. There are no other known conflicts of interest.

Sanofi Pasteur co-created VidPrevtyn Beta® COVID-19 vaccine which is being used in the spring 2023 booster campaign. This study fulfils a requirement by the EMA and MHRA to assess the real-world vaccine effectiveness of VidPrevtyn Beta®. Benefits of this study might include:
• If the study identifies high vaccine effectiveness, Sanofi and GSK may benefit from this research which may in turn demonstrate the benefits of VidPrevtyn Beta®.
• If the study identifies there is a greater vaccine effectiveness in VidPrevtyn Beta® than other vaccines, than NICE or other regulatory agencies might be more likely to approve VidPrevtyn Beta® for prevention of COVID-19 over other vaccine options. NICE assesses whether the approval of new therapies should be used in the NHS
• Evidera will benefit from this research since it will deepen its knowledge of COVID-19 observational research and therefore other clients (i.e., pharmaceutical companies) will be more likely to approach them for this type of research. It is also benefitting from the study since Sanofi Pasteur is paying Evidera to conduct the research on its behalf.

The primary focus of this study is to understand the vaccine effectiveness of VidPrevtyn Beta® in preventing severe COVID-19 outcomes and to inform regulatory agencies (EMA, MHRA) of the results so that these agencies can update recommendations and approval if needed. Results of the studies may identify the unmet needs of the current COVID-19 vaccines being delivered, and specific populations that may benefit more from additional boosters or other treatments. The commercial interests of Sanofi in this project are to better understand the effectiveness of VidPrevtyn Beta® in preventing severe COVID-19 outcomes. The potential public benefits to healthcare in England are considered to outweigh the potential commercial benefit (i.e., the effectiveness of the vaccine inform regulatory agencies, clinicians, and the public on how well protected patients will be if given the booster and if current recommendations need to change to best protect those at a high risk of COVID-19).

Expected Benefits:

Benefits from this study are expected to include the following:

1. Benefits for regulators (e.g., EMA, MHRA): the findings from this study will provide evidence to help with the EMA and MHRA’s evaluation of VidPrevtyn Beta® vaccine effectiveness in real-world setting and inform their decisions for future COVID-19 vaccine booster campaigns, such as updating their recommendations and approval if needed. The findings from this study will also allow for a contemporaneous comparative effectiveness assessment, following the administration of sufficient doses.

2. It is anticipated that there will be benefits for the UK Department of Health and Social Care, clinicians, and healthcare providers: The wide-spread vaccination of the British population has significantly improved the impact of COVID-19 on healthcare systems, thus reducing its pressure on the limited healthcare resources and allowing healthcare providers to plan and act proactively (as opposed to acting reactively when the pandemic first started). To appropriately plan for the management and administration of resources, healthcare agencies will benefit from understanding the effectiveness of vaccines in reducing the risk of severe COVID-19, especially as the SARS-CoV-2 virus continues to evolve. By understanding and monitoring the effectiveness of VidPrevtyn Beta®, healthcare agencies will also be able to provide accurate information to the public to improve vaccine uptake, thus further reduces future impact of COVID-19. In addition, clinicians will have increased knowledge about the effectiveness of VidPrevtyn Beta® on all patients and specific patient subgroups to recommend the best types of vaccines for those who are more vulnerable to the disease.

3. It is anticipated that there will be benefits for patients and the public: Patients and the public benefit from improved healthcare provision. By making the study results available in the public domain, the public can benefit from more accurate assessment of the effectiveness of VidPrevtyn Beta® and make informed health decisions (e.g., taking up vaccine boosters or seek advice on other treatments).

4. If the study identifies an increasing incidence of severe COVID-19 outcomes in specific groups, governments might make the decision to administer booster vaccinations in other populations as part of their booster programme or administer boosters more regularly in some groups.

The use of the data could:
> help the system to better understand the health and care needs of populations.
> lead to the identification or improvement of treatments or interventions, or health and care system design to improve health and care outcomes or experience.
> advance understanding of regional and national trends in health and social care needs.
> advance understanding of the need for, or effectiveness of, preventative health and care measures for particular populations or conditions such as obesity and diabetes.
> inform planning health services and programmes, for example to improve equity of access and outcomes.
> inform decisions on how to effectively allocate and evaluate funding according to health needs.
> support knowledge creation or exploratory research (and the innovations and developments that might result from that exploratory work).

Sanofi Pasteur will use utilize the findings of this study to provide supporting information required by the EMA and MHRA for business cases, epidemiological research, pathway analysis, burden of disease analysis, health economic research, and quality and outcome analysis. The outputs of this study will be shared directly with the EMA and MHRA to support improvements in patient care.

Outputs:

The expected outputs of the processing will be:
> A report of findings to Sanofi at the end of the study.
> A report of final results will be submitted to the EMA and MHRA to demonstrate the benefit of the vaccine in a real-world setting.
> Submissions to peer reviewed journals [expected 1-2 abstract submissions in 2024 and 1-2 manuscript submissions in 2024 or early 2025]. High impact respiratory/infectious disease journals will be targeted, such as British Medical Journal (BMJ), New England Journal of Medicine and Lancet Infectious Disease.
> Presentations at appropriate conferences, such as European Congress of Clinical Microbiology and Infectious Disease (ECCMID), International Society for Pharmacoeconomics and Outcomes Research (ISPOR). High impact respiratory/infectious disease conferences will be targeted.

The outputs will not contain NHS England Data and will only contain aggregated information with small numbers suppressed as appropriate in line with the relevant disclosure rules for the dataset(s) from which the information was derived.

Sanofi Pasteur will not suppress findings or receive exclusive access to findings.

The outputs will be communicated to relevant recipients through the following dissemination channels:
> Journals
> Conferences
> Reports aimed at Sanofi Pasteur
> Reports aimed at the EMA and MHRA
> Webinars to Physicians using key Sanofi Pasteur Medical Science staff to communicate results

The initial results for this study are expected within 6 months following access to the NHS England-linked datasets. Once study report has been drafted, manuscripts will be prepared for submission to peer-reviewed journals and abstracts for conference presentation in Q4 2024/Q1 2025.

Processing:

No data will flow to NHS England for the purposes of this Data Sharing Agreement (DSA).

NHS England will grant access to the Data via the Secure Data Environment (SDE). The SDE is a secure data and research analysis platform. It allows approved researchers with approved projects access to pseudonymised data and industry-leading analytics tools.

NHS England will provide access to the relevant records from the HES, Emergency Care, Deaths, COVID-19 SGSS, COVID-19 Vaccination Status and GDPPR datasets to Evidera Ltd via NHS England Secure Data Environment (SDE). The Data will contain no direct identifying data items. The Data will be pseudonymised and individuals cannot be reidentified through linkage with other data in the possession of the recipient.

The Data will not be transferred to any other location.

SDE users can request exportation of aggregated analysis results (suppressed and summarised according to the NHSE SDE Disclosure Control rules) subject to review and approval by the NHS England SDE Output Checking team. The SDE Output Checking team will ensure that no output contains information which could be used either on its own or in conjunction with other data to breach an individual's privacy.

Users must identify themselves via a multi-factor authentication mechanism and are only able to access the datasets detailed within this DSA. The access and use of the system is fully auditable, and all users must comply with the use of the Data as specified in this DSA.

Users are only authorised to access the Data specified in this DSA and can utilise a variety of analytical tools available within the SDE platform. Users are not permitted to export record-level data from the SDE.

The Data will be stored on servers at NHS England.

Remote processing will be from secure locations within the UK.

The Data will not leave the UK at any time.

Access is restricted to employees of Evidera Ltd who have authorisation from the Senior Investigator.

All personnel accessing the Data have been appropriately trained in data protection and confidentiality.

The Data will not be linked with any other data.

Only analysts employed by Evidera Ltd will analyse the Data for the purposes described above.

Descriptive Epidemiology, Treatment Patterns, and Outcomes of Patients with Renal Cell Carcinoma in England: A Retrospective Cohort Study Using SACT Data and Cancer Registry (DORCES) ( ODR2021_055 ) — DARS-NIC-656879-L3Y5Z

Type of data: information not disclosed for TRE projects

Opt outs honoured: Anonymised - ICO Code Compliant (Does not include the flow of confidential data)

Legal basis: Health and Social Care Act 2012 – s261(2)(a)

Purposes: No (Research)

Sensitive: Sensitive

When:DSA runs 2024-03-29 — 2024-08-31

Access method: One-Off

Data-controller type: EVIDERA LTD

Sublicensing allowed: No

Datasets:

  1. Hospital Episode Statistics Admitted Patient Care (HES APC)
  2. Hospital Episode Statistics Outpatients (HES OP)
  3. NDRS Cancer Registrations
  4. NDRS Systemic Anti-Cancer Therapy Dataset (SACT)

Objectives:

Evidera Ltd are requesting an extension to retain the data provided under DARS-NIC-656879 for a few months longer. Evidera Ltd are currently working on preparing a manuscript to disseminate results of the study. Therefore, Evidera Ltd are requesting that the data sharing agreement is extended in case Evidera Ltd are required to go back to the data due to queries raised in manuscript review. Evidera Ltd are not requesting any new data and use of the data remains for the same purpose/objectives as the original application.
Evidera Ltd utilised existing Cancer Registration data from Public Health England (PHE) to assess the trends in treatment patterns and survival outcomes of patients with kidney cancer (renal cell carcinoma [RCC]) in England, and how the trends vary by stage at diagnosis, disease histology, line of therapy, year of diagnosis and receipt of nephrectomy (surgical removal of the kidney). Specifically, Evidera Ltd analysed the data to describe patient characteristics. Evidera Ltd also calculated a measured called “overall survival”, which is an estimate of the length of time between a defined time point, such as the date of diagnosis of a condition, and the date of death.
The Cancer Registration dataset includes data on demographics, characteristics of the tumour, patients’ vital status and basic information regarding the treatment received. Evidera Ltd utilized the Systemic Anti-Cancer Therapy dataset, which contained information on systemic treatment received by patients in the cancer registry. This was linked to another dataset, Hospital Episode Statistics, which contains information on all hospital visits, admissions and procedures in England.


The following NHS England data will be accessed:
• BAU Hospital Episode Statistics Admitted Patient Care (HESAPC)
• BAU Hospital Episode Statistics Outpatient Patient (HESOP)
• NDRS Cancer Registration
• NDRS Systemic Anti-Cancer Therapy (SACT)
The level of the data will be pseudonymised.


The data will be minimised as follows:
• Limited to patients diagnosed with malignant neoplasm of kidney, except renal pelvis (ICD-10 code: C64x) between 01 April 2014 to 31 December 2018
• Limited to the following geographic areas England
• Limited to patients above the age of 18


Evidera Ltd is the data controller as the organisation responsible for ensuring that the data will only be processed for the purpose described above.

Although BMS UK is the research sponsor, BMS UK will not carry out any data controllership activities.


The lawful basis for processing personal data under the UK GDPR is:
Article 6(1)(f) - processing is necessary for the purposes of the legitimate interests pursued by the controller or by a third party, except where such interests are overridden by the interests or fundamental rights and freedoms of the data subject which require protection of personal data, in particular where the data subject is a child.
Evidera have legitimate interest in processing the data as part of a client agreement with BMS to study the treatment and outcomes in patients with renal cell carcinoma.

The lawful basis for processing special category data under the UK GDPR is:
Article 9(2)(j) - processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject.
There is public interest in the processing of this data as it is scientific research regarding treatment and outcomes of patients with renal cell carcinoma in England. Evidera anticipate several potential public health benefits for their analysis. It is necessary to determine any trends in treatment patterns and outcomes in patients with RCC to better understand the evolving treatment landscape in the UK. The dataset contains variables that are not commonly available in UK primary or secondary care data sources, such as cancer stage. This allows for a more granular description of mortality trends within subgroups known to have very different survival experiences. SACT data contain detailed information on cancer treatments received during follow-up. The Cancer Registration data from PHE covers the entire English population, and results are therefore generalisable to the population of England. Evidera have already presented findings at two scientific conferences and are in the process of preparing a manuscript for journal submission.


The funding is provided by BMS UK. The funding is specifically for the study described. Funding is in place until completion of the agreed study. The funder will have no ability to suppress or otherwise limit the publication of findings.


Evidera Ltd is the sole data controller and the data processor.

Yielded Benefits:

Two conference posters containing aggregate results have been presented at ASCO Genitourinary Cancers symposium 2023, and the International Kidney Cancer Symposium, Europe, 2023

Expected Benefits:

Evidera Ltd anticipate several potential public health benefits for the analysis and dissemination. It is necessary to determine any trends in treatment patterns and outcomes in patients with RCC to better understand the evolving treatment landscape in the UK. The dataset previously received contained variables that are not commonly available in UK primary or secondary care data sources, such as cancer stage. This allowed for a more granular description of mortality trends within subgroups known to have very different survival experiences. SACT data contained detailed information on cancer treatments received during follow-up. The cancer registration data from PHE (called PHE at the time of receiving the data) covered the entire English population, and results will therefore be generalisable to the population of England.


The information generated from this study provides insight on characteristics of patients with RCC, and it highlights populations with potentially unmet needs regarding treatment persistence and survival. This information available to healthcare professionals will indirectly impact patient care.


Based on the information published from this study, healthcare professionals will be able to further understand the characteristics of patients with RCC and their treatment patterns using real-world evidence.

Outputs:

The expected outputs of the processing will be:
• An internal report
• Presentations to various conferences in the form of posters in 2023
• Submissions to peer reviewed journals at the end of the study in late 2023


The outputs will not contain NHS England data and will only contain aggregated information with small numbers suppressed as appropriate in line with the relevant disclosure rules for the dataset(s) from which the information was derived.


The outputs will be communicated to relevant recipients through the following dissemination channels:
• Journals
• Posters displayed at ASCO Genitourinary Cancers symposium 2023, and the International Kidney Cancer Symposium, Europe, 2023.


The target dates for submission of the manuscript is by the end of 2023.

Processing:

No data will flow to NHS England for the purposes of this Agreement.


NHS England data have provided the relevant records from the NDRS HESAPC, NDRS HESOP, NDRS SACT and NDRS Cancer Registration datasets to Evidera Ltd. The data contains no direct identifying data items but will contain a unique person ID which can be used to link the datasets together.


The data will not be transferred to any other location.


The data will be stored and backed-up on servers at Evidera Ltd.


The data will be accessed by authorised personnel via remote access . The data will remain on the servers at Evidera Ltd at all times.
Personnel are prohibited from downloading or copying data to local devices.


The data will not leave England/Wales at any time.


Access is restricted to employees or agents of Evidera Ltd who have authorisation from the Principal Investigator .


BMS UK is not permitted to access the data.


All personnel accessing the data have been appropriately trained in data protection and confidentiality.


The data will not be linked with any other data outside the scope of this agreement.


There will be no requirement and no attempt to reidentify individuals when using the data. As in the previous agreement, Evidera Ltd do not have access to identifiable information such as a patient’s name, NHS number, geographic location or date of birth. This study did not use identifiable personal data. Publications will only summarize aggregate level data void of any personal identifying information. Small numbers will be anonymised.


Analysts from Evidera Ltd will analyse the data for the purposes described above.

Health Burden of COVID-19 and Healthcare Resource Utilisation in England — DARS-NIC-561357-X0F3N

Type of data: information not disclosed for TRE projects

Opt outs honoured: Anonymised - ICO Code Compliant (Does not include the flow of confidential data)

Legal basis: Health and Social Care Act 2012 - s261(5)(d), Health and Social Care Act 2012 – s261(2)(a)

Purposes: Yes (Research)

Sensitive: Sensitive, and Non-Sensitive

When:DSA runs 2022-11-18 — 2023-11-17 2022.12 — 2024.11.

Access method: System Access, One-Off, Ongoing
(System access exclusively means data was not disseminated, but was accessed under supervision on NHS Digital's systems)

Data-controller type: ASTRAZENECA UK LIMITED, HEALTH & SOCIAL CARE INFORMATION CENTRE, ASTRAZENECA UK LIMITED, NHS ENGLAND - X26, ASTRAZENECA UK LIMITED

Sublicensing allowed: No

Datasets:

  1. Civil Registration - Deaths
  2. COVID-19 Second Generation Surveillance System
  3. COVID-19 Vaccination Status
  4. GPES Data for Pandemic Planning and Research (COVID-19)
  5. Hospital Episode Statistics Accident and Emergency
  6. Hospital Episode Statistics Admitted Patient Care
  7. Hospital Episode Statistics Critical Care
  8. Hospital Episode Statistics Outpatients
  9. Medicines dispensed in Primary Care (NHSBSA data)
  10. Uncurated Low Latency Hospital Data Sets - Admitted Patient Care
  11. Uncurated Low Latency Hospital Data Sets - Critical Care
  12. Uncurated Low Latency Hospital Data Sets - Emergency Care
  13. Uncurated Low Latency Hospital Data Sets - Outpatient
  14. Civil Registrations of Death
  15. COVID-19 General Practice Extraction Service (GPES) Data for Pandemic Planning and Research (GDPPR)
  16. COVID-19 Second Generation Surveillance System (SGSS)
  17. Hospital Episode Statistics Accident and Emergency (HES A and E)
  18. Hospital Episode Statistics Admitted Patient Care (HES APC)
  19. Hospital Episode Statistics Critical Care (HES Critical Care)
  20. Hospital Episode Statistics Outpatients (HES OP)
  21. COVID-19 SGSS First Positives (Second Generation Surveillance System)
  22. COVID-19 Electronic Prescribing and Medicines Administration (ePMA) in Secondary Care
  23. NDRS Cancer Consolidated Data Set

Expected Benefits:

Benefits from this study are expected to include the following
1. Benefits for regulators (e.g., MHRA): the findings from this study are hoped will support MHRA’s review of EVUSHELD for the use among patients who are immunocompromised and other vulnerable populations to supplement the trial evidence, based on which the Conditional Marketing Authorisation in PrEP (pre-exposure prophylaxis) was granted. Furthermore, the results of this study will provide a baseline against which to benchmark the overall impact of the use of EVUSHELD, until data accrual and maturity allow for a contemporaneous comparative effectiveness and safety assessment, following the administration of sufficient doses. Additionally, should the respective clinical trials confirm EVUSHELD’s safety and efficacy in outpatient and inpatient treatment indications, the results of this study will serve as foundation for the development of the submission dossier to ascertain the most accurate characterisation of the source population in England.

2. Its is anticipated that there will be benefits for Health Technology Assessment and endorsement bodies such as NICE and the Scottish Medicines Consortium (SMC): During the early scientific advice procedure in which AstraZeneca engaged, NICE requested more accurate information on the expected number of patients that would be eligible for EVUSHELD use. NICE also recommended that AstraZeneca conduct an observational study to continue identifying which populations do not respond to vaccinations, beyond patients who are immunocompromised, and expressed concern for the dynamic landscape due to the emergence of new variants, which should also be monitored. Lastly, NICE requested that the health-economic model be populated with efficacy data from the phase III trial PROVENT (NCT04625725, please see - https://clinicaltrials.gov/ct2/show/NCT04625725) but the baseline characteristics be adjusted to more accurately reflect the population in England as well as account for the substantial heterogeneity likely to exist in the target population (e.g., in terms of comorbidities, resource use, risk of severe COVID-19). These are the exact research questions that guided the design of the current study. The results from objectives 2 and 3 will be used to adjust the population characteristics for the cost-effectiveness model. Additionally, the patterns of HCRU and costs associated with an episode of COVID-19 will be an important input for the cost-effectiveness model. The accurate count of patients at risk from objective 1 will also be used in the budget impact model. The exploratory objectives to identify and quantify risk profiles with high unmet clinical need will be the basis for sensitivity analyses in both health-economic models. Furthermore, as the pandemic becomes endemic, regulators and policy makers will also benefit from country-specific estimates on the burden of long-COVID-19 to patients and to the healthcare system to be factored in policy decisions.

3. It is anticipated that there will be benefits for the UK Department of Health and Social Care, clinicians, and healthcare providers: The wide-spread vaccination of the British population has significantly improved the epidemiological situation, thus reducing its pressure on the limited healthcare resources and allowing to plan and act proactively (as opposed to reactively, like during the worst moments of the pandemic). To appropriately plan for the management and administration of resources all agents in the continuum of the healthcare provision will benefit from understanding the nature and magnitude of the outstanding unmet needs in the prevention and treatment of COVID-19. This study will provide these insights. Furthermore, the supply of EVUSHELD to address some of these needs is limited and it is expected that doses will become available in consecutive batches, which means that priorities will need to be established based on formal criteria. This study will also provide the evidence to inform those decisions.

4. It is anticipated that there will be benefits for payers (i.e., NHS and taxpayers in the UK): A thorough and evidence-based understanding of the health and economic burden of COVID-19 across different vulnerable populations enables effective planning and efficient resource allocation. Thus, the benefits described for NICE, healthcare providers, and patients may ultimately translate in cost savings or even costs being averted.

5. It is anticipated that there will be benefits for patients and the general public: Patients and the general public benefit from improved healthcare provision. By making the study results available in the public domain (see Section 5c), the general public can benefit from more accurate assessment of their risk of contracting COVID-19 and developing long-COVID-19 and make informed health decisions (e.g., taking up vaccine boosters or seek advice on eligibility for prophylaxis or treatment).

Outputs:

The initial results for this study are expected within a year following the access to the NHS Digital-linked datasets.

Evidera will be conducting all of the data processing and the analysis. They will send aggregated results that will be in the format of excel tables to AZ for review. The tables that they will send will include patient attrition cells (number of patients excluded during the patient selection process), baseline descriptive results of the study populations (i.e., number and percentage of patient demographics and clinical characteristics identified at baseline), the number and percentage of patients identified as ineligible for COVID-19 vaccine (different row will be provided for each ineligibility criteria), the number and percentage of patients at risk of COVID-19 infection (different row will be provided for each risk factor), the number of new COVID-19 infections and incidence of COVID-19 overall and in each time period of interest, the number of new long COVID-19 infections and incidence of long COVID-19, the rate of resource utilisation per patient and per-patient per COVID-19 episode. Only aggregated data with secondary suppression of cells will be send to AZ. At no point will the patient level data be transferred from Evidera to AZ. The results will also be presented in a study report and sent to AZ for review.

The planned study outputs include a study report, manuscripts in submission to peer-reviewed journals and presentations at scientific conferences. Only aggregated data with secondary suppression of cells will be presented in the planned study outputs. It is anticipated that high impact respiratory/infectious disease conferences/journals will be targeted. These include BMJ, New England Journal of Medicine, Lancet Infectious Disease and BMC Infectious Disease. Where possible, results will be published via the open access route to ensure that all clinicians, policy makers and members of the public can access the results freely. It is also anticipated that the results will be disseminated via presentations at key conferences (e.g., European Congress of Clinical Microbiology and Infectious Disease (ECCMID), International Society for Pharmacoeconomics and Outcomes Research (ISPOR)), webinars to Physicians using key AZ Medical Science staff to communicate results.

In addition, active engagement with charity organisations including the research communities (King’s College London, COVID Symptom Study Team) for topics like Long COVID is planned. AZ intend to work with Long-COVID clinics in the country to identify suitable interested patient groups to disseminate results in the form of presentation, newsletters or sharing of publication summaries. AZ will also be engaging immunocompromised patients, who are considered to not been adequately protected by COVID-19 vaccines due to their body unable to generate an optimal level of antibodies, to provide feedback on the current and future studies. Patients will provide input during study analysis planning, first results readout and publications.

PPIE
AZ will also be engaging immunocompromised patients, who are considered to not been adequately protected by COVID-19 vaccines due to their body unable to generate an optimal level of antibodies, to provide feedback on the current and future studies. Patients will provide input during study analysis planning, first results readout and publications.

Based on an assumed data delivery date in Nov 2022, Evidera estimates to complete data analysis in Jan 2023 and study report in August/September 2023. Once study report has been drafted, manuscripts will be prepared for submission to peer-reviewed journals and abstracts for conference presentation in Q3/Q4 2023.

These planned outputs will be designed with the intention of including sufficient information on methods to ensure research transparency and reproducibility. All types of results, including those sometimes seemed as unfavourable, will be published along with key code list used for case definition. The code lists refer to the SNOMED (https://termbrowser.nhs.uk/) and ICD-10 (https://icd.who.int/browse10/2019/en#/ ) diagnosis codes for identifying patients with COVID or long-COVID. The case definition refers to how cases (i.e., COVID and long COVID-19) are defined and identified from the requested datasets. The proposed study is descriptive in nature, e.g., estimating the size of populations that are not protected by COVID-19 vaccines. The incidence of COVID-19 and long COVID-19, and COVID-19-related healthcare service use, as opposed to estimating the effectiveness of certain treatments/vaccines. The aim is to understand the current health and economic burden of COVID-19. The plan is to publish results regardless of whether the estimates are high or low. With that said, given the data published on COVID dashboard (https://coronavirus.data.gov.uk/), it is unlikely to be low/unfavourable. COVID-19 research results need to and will be interpreted in the wider context, e.g., social restrictions and movement, infection rate, vaccination/booster roll-out and availability of an-viral treatments.

This study is also exploring whether machine learning based methods can help with identifying risk profiles of vaccinated patients who experienced a composite outcome of COVID-19 hospitalisation or COVID-19-related death. As previously mentioned, machine learning methods will first identify all patients that have a COVID-19 hospitalisation or COVID-19 related death after 14 days of a COVID-19 vaccination (i.e., break through infections). Then clustering methods and supervised learning with nested cross-validation will be used to classify these patients into k clusters with similar characteristics. These results, details on the development of algorithms and lessons learned are also planned to be disseminated.