Pneumococcal Vaccination to Accelerate Immune Recovery in Sepsis Survivors (VACIRiSS)

Guy’s and St Thomas’ NHS Foundation Trust requires access to NHS England data for the purpose of the following Clinical Trial: Vaccination for immune recovery following sepsis Trial” (VACIRiSS).

The following is a summary of the aims of the Clinical Trial provided by Guy’s and St Thomas’ NHS Foundation Trust:

“This Clinical Trial aims to find out if a safe and widely used vaccine (a Pneumoccocal vaccine) can help in preventing new infections for patients who survive an Intensive Care Unit (ICU) admission with sepsis. The Trial will also explore if the vaccine would help those who do get new infections to recover more quickly.

“214 adult patients have been recruited to be part of the study; 183 of these were recruited from sites in England and Wales. All patients are registered with a GP and the reason for admission to intensive care unit or high dependence unit was sepsis. They were put into one of two groups. This was decided by chance. One group received a single injection of Pneumococcal vaccine. One group received a dummy vaccine that contained no active ingredients. There was an equal chance of receiving the vaccine or the dummy injection. Neither the patient or the doctors and nurses knew which group participants were in. This type of study is called a “double-blind, placebo controlled, randomised trial” and it ensures that the treatment is tested fairly.

“Participants of this study are followed up for one year after their first admission with sepsis to determine whether vaccination reduces infection rate and severity during this time. Blood samples were also taken to determine the ways by which vaccination might work .”

The following NHS England data will be accessed:

• Hospital Episode Statistics Admitted Patient Care – necessary to (i) identify patients readmitted to hospital and whether that readmission was due to an infection; and (ii) understand the hospital costs of such readmissions. Hospital costs will be estimated by using the Healthcare Resource Group code provided from the HES Admitted Patient Care dataset to assign a cost per bed-day taken from published reference costs.

• Demographics data - necessary to provide Date of Death used to calculate duration of survival (a required endpoint) by counting the days from the date of randomisation.

The level of the data will be identifiable - necessary to enable linkage of the data with data collected from the participants themselves and other information collected by the Trial sites including medical records and GP records.

The data will be minimised as follows:

• Limited to a cohort of 183 adults recruited from 9 NHS critical care units in England and Wales between 18 August 2018 to 20 April 2022.

Participants are recruited under informed patient consent where possible. In the circumstance the participant was not able to consent for themselves, a legal representative of the participant was approached and consent was obtained via the legal representative. The study holds ethical approval and this method of recruitment comes under Medicine for Human Use (Clinical Trials) Regulations 2004. Should the participant regain capacity during the study, informed patient consent would be sought.

Guy’s and St Thomas’ NHS Foundation Trust is the research sponsor and the controller as the organisation responsible for ensuring that the data will only be processed for the purpose described above.

The lawful basis for processing personal data under the UK GDPR is:

Article 6(1)(e) - processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller;

This study would be in the public interest to explore if administering a commonly available vaccine could reduce infection related hospitalisation in sepsis survivors. The results of the trial could potentially have an effect on policy making decisions, and health care pathway.

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.

This processing is in the public interest because the aim is to explore if administering a commonly available vaccine could reduce infection related hospitalisation in sepsis survivors. The results of the trial could potentially have an effect on policy making decisions, and health care pathway. The funding is provided by the National Institute for Health Research (NIHR), through a NIHR Clinical Scientist Award. The funding is specifically for the VACIRiSS Trial described . Funding is in place until completion of the trial publication.

The Intensive Care National Audit and Research Centre (ICNARC) is a processor acting under the instructions of Guy’s and St Thomas’s NHS Foundation Trust. ICNARC’s role is limited to processing the data according to the agreed protocol and statistical analysis plan.

Exponential-E Ltd is a processor providing IT back up services to ICNARC and will store copies of the data as contracted by ICNARC.

Babble Cloud (SUI) Limited will provide external desktop and network managed services and will provide remote access to ICNARC servers hosted by Exponential-E Ltd.

As part of NIHR Funding requirements, the trial was overseen by a Trial Steering committee and a Data Monitoring committee to ensure best practice of research governance. Both these committees for the VACIRiSS trial consisted of a number of health care professionals, providing independent advice to the Chief Investigator.

The statistician at ICNARC will be the only person accessing the record level data. The Chief Investigator who is a substantive employee of University of Edinburgh working under an Honorary contract with Guy’s and St Thomas’ NHS Foundation Trust and other trial investigators will receive output data which is aggregated derived data. This will be amalgamated summary data from all four home nations and it will not be possible for a recipient to determine the country or trial site of any individual from the data. The reports may included unsuppressed small numbers as permitted by the HES Analysis Guide given the national level of the data.

Patient and Public Involvement and Engagement activity was conducted during the idea development, design, planning, and conduct of the VACIRiSS trial. The engagement was to explore whether patients would be interested in participating in such a trial. This engagement led to further development of the information sheet.

The expected outputs of the processing will be:

• A report of findings to NIHR

• Submissions to peer reviewed journals [The primary manuscript will be submitted within 6-8 weeks of linkage data availability. This will include completed follow up data, primary, secondary, and exploratory biological outcomes.

• Presentations at appropriate conferences, which may include the European or UK Societies of Intensive Care Medicine or similar

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

• Social media

• Public events such as conferences highlighted above

• Reports to the funder including a lay summary

• VACIRiSS Study website and posts on ICNARCs social media accounts (e.g. ICNARC has more than 7,000 followers on Twitter, https://twitter.com/icnarc?lang=en)

It is difficult to predict target dates, as it is dependent on data linkage, analysis, manuscript write up, submission to journal, peer review, manuscript revisions, and finally acceptance of publication. The average time from submission to acceptance is around 3-4 months.

There are no yielded benefits to date. This amendment is to correct an error in the original application so that usable data can be shared.

Guy’s and St Thomas’ NHS Foundation Trust requires access to NHS England data for the purpose of the following Clinical Trial: Vaccination for immune recovery following sepsis Trial” (VACIRiSS).

The following is a summary of the aims of the Clinical Trial provided by Guy’s and St Thomas’ NHS Foundation Trust:

“This Clinical Trial aims to find out if a safe and widely used vaccine (a Pneumoccocal vaccine) can help in preventing new infections for patients who survive an Intensive Care Unit (ICU) admission with sepsis. The Trial will also explore if the vaccine would help those who do get new infections to recover more quickly.

“214 adult patients have been recruited to be part of the study; 183 of these were recruited from sites in England and Wales. All patients are registered with a GP and the reason for admission to intensive care unit or high dependence unit was sepsis. They were put into one of two groups. This was decided by chance. One group received a single injection of Pneumococcal vaccine. One group received a dummy vaccine that contained no active ingredients. There was an equal chance of receiving the vaccine or the dummy injection. Neither the patient or the doctors and nurses knew which group participants were in. This type of study is called a “double-blind, placebo controlled, randomised trial” and it ensures that the treatment is tested fairly.

“Participants of this study are followed up for one year after their first admission with sepsis to determine whether vaccination reduces infection rate and severity during this time. Blood samples were also taken to determine the ways by which vaccination might work .”

The following NHS England data will be accessed:

• Hospital Episode Statistics Admitted Patient Care – necessary to (i) identify patients readmitted to hospital and whether that readmission was due to an infection; and (ii) understand the hospital costs of such readmissions. Hospital costs will be estimated by using the Healthcare Resource Group code provided from the HES Admitted Patient Care dataset to assign a cost per bed-day taken from published reference costs.

• Demographics data - necessary to provide Date of Death used to calculate duration of survival (a required endpoint) by counting the days from the date of randomisation.

The level of the data will be identifiable - necessary to enable linkage of the data with data collected from the participants themselves and other information collected by the Trial sites including medical records and GP records.

The data will be minimised as follows:

• Limited to a cohort of 183 adults recruited from 9 NHS critical care units in England and Wales between 18 August 2018 to 20 April 2022.

Participants are recruited under informed patient consent where possible. In the circumstance the participant was not able to consent for themselves, a legal representative of the participant was approached and consent was obtained via the legal representative. The study holds ethical approval and this method of recruitment comes under Medicine for Human Use (Clinical Trials) Regulations 2004. Should the participant regain capacity during the study, informed patient consent would be sought.

Guy’s and St Thomas’ NHS Foundation Trust is the research sponsor and the controller as the organisation responsible for ensuring that the data will only be processed for the purpose described above.

The lawful basis for processing personal data under the UK GDPR is:

Article 6(1)(e) - processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller;

This study would be in the public interest to explore if administering a commonly available vaccine could reduce infection related hospitalisation in sepsis survivors. The results of the trial could potentially have an effect on policy making decisions, and health care pathway.

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.

This processing is in the public interest because the aim is to explore if administering a commonly available vaccine could reduce infection related hospitalisation in sepsis survivors. The results of the trial could potentially have an effect on policy making decisions, and health care pathway. The funding is provided by the National Institute for Health Research (NIHR), through a NIHR Clinical Scientist Award. The funding is specifically for the VACIRiSS Trial described . Funding is in place until completion of the trial publication.

The Intensive Care National Audit and Research Centre (ICNARC) is a processor acting under the instructions of Guy’s and St Thomas’s NHS Foundation Trust. ICNARC’s role is limited to processing the data according to the agreed protocol and statistical analysis plan.

Exponential-E Ltd is a processor providing IT back up services to ICNARC and will store copies of the data as contracted by ICNARC.

Babble Cloud (SUI) Limited will provide external desktop and network managed services and will provide remote access to ICNARC servers hosted by Exponential-E Ltd.

As part of NIHR Funding requirements, the trial was overseen by a Trial Steering committee and a Data Monitoring committee to ensure best practice of research governance. Both these committees for the VACIRiSS trial consisted of a number of health care professionals, providing independent advice to the Chief Investigator.

The statistician at ICNARC will be the only person accessing the record level data. The Chief Investigator who is a substantive employee of University of Edinburgh working under an Honorary contract with Guy’s and St Thomas’ NHS Foundation Trust and other trial investigators will receive output data which is aggregated derived data. This will be amalgamated summary data from all four home nations and it will not be possible for a recipient to determine the country or trial site of any individual from the data. The reports may included unsuppressed small numbers as permitted by the HES Analysis Guide given the national level of the data.

Patient and Public Involvement and Engagement activity was conducted during the idea development, design, planning, and conduct of the VACIRiSS trial. The engagement was to explore whether patients would be interested in participating in such a trial. This engagement led to further development of the information sheet.

The expected outputs of the processing will be:

• A report of findings to NIHR

• Submissions to peer reviewed journals [The primary manuscript will be submitted within 6-8 weeks of linkage data availability. This will include completed follow up data, primary, secondary, and exploratory biological outcomes.

• Presentations at appropriate conferences, which may include the European or UK Societies of Intensive Care Medicine or similar

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

• Social media

• Public events such as conferences highlighted above

• Reports to the funder including a lay summary

• VACIRiSS Study website and posts on ICNARCs social media accounts (e.g. ICNARC has more than 7,000 followers on Twitter, https://twitter.com/icnarc?lang=en)

It is difficult to predict target dates, as it is dependent on data linkage, analysis, manuscript write up, submission to journal, peer review, manuscript revisions, and finally acceptance of publication. The average time from submission to acceptance is around 3-4 months.

Yielded Benefits is not a requirement for new applications.