Outcomes of Patients who survived Treatment on an Intensive Care unit for COVID-19 in England and Wales (OPTIC-19): a comparative retrospective cohort study

The University of Oxford requires access to NHS England data for the purpose of the following research project:

The OPTIC-19 Study: Outcomes of Patients who survived Treatment on an Intensive Care unit for COVID-19 in England and Wales

The following is a summary of the aims of the research project provided by the University of Oxford:

The OPTIC-19 Study is a comparative retrospective cohort study. This study is a collaboration between the Critical Care Research Group (University of Oxford) and Intensive Care National Audit and Research Centre (ICNARC).

It is not known how survivors’ severe COVID-19 infection, or the treatment they received on the ICU, will impact their long-term health. This retrospective cohort study aims to estimate the risk of adverse outcomes (death, emergency hospital readmission, heart attacks, strokes) in patients treated on an intensive care unit (ICU) with COVID-19 in England and Wales*, one year after discharge from hospital. The study team will compare these risks to patients treated in ICU for other conditions.

*For this Agreement, NHS England data is acknowledged to contain only those NHS Patients treated at secondary care sites in England only.

Since 2015, the Intensive Care National Audit and Research Centre (ICNARC) has collected audit data for all patients admitted to an ICU in England and Wales in their Case Mix Programme (CMP) data set. However, the CMP contains no information on patient outcomes after they are discharged from hospital. To investigate outcomes after discharge, this study proposes to link the data from the CMP with NHS England data to identify patients who have died in England and Wales.

Analysis of the linked data set will allow the study to provide novel insights into longer-term risks faced by survivors of severe COVID-19. The data requested will allow the study team to build a pseudonymised data set linking ICU data with longer term outcomes that results in death or require emergency hospitalisation. Using this large data set, the study can provide robust estimates of the risk of death and emergency hospital admission in the year after discharge from ICU faced by survivors of severe COVID-19.

The study will create a cohort of ICU admissions, containing data routinely collected in the Case Mix Programme. By linking these detailed ICU records with NHS long-term follow-up data (HES, ECDS, MSDS, Civil Registration) the study team can estimate the risk of death and emergency hospital admission in the year after discharge from ICU.

The following NHS England data will be accessed:

• Hospital Episode Statistics (HES)

o Admitted Patient Care (APC)

o Accident & Emergency (A&E)

o Outpatients (OP)

• Emergency Care Data Set (ECDS)

HES and ECDS data is necessary to allow the study to examine specific outcomes for which smaller studies suggest COVID-19 survivors could be at higher risk. These include respiratory infections (due to persistent lung damage) and strokes and pulmonary emboli (due to abnormalities in blood clotting).

• Civil Registration Mortality – necessary to allow the study to estimate the risk of death.

• Maternity Services Data Set (MSDS) v1.5 to v2.0 – necessary to permit analysis of a sub-group analysis of patients who were pregnant at the time of ICU admission. The aim of analysing pregnant patients is to obtain an understanding of whether long-term risks faced patients treated for COVID-19 while pregnant differ from age-matched controls. The Maternity Services Dataset is only required up until the end of the ‘treatment period’ which is 30th June 2022, since the main purpose of this dataset is to ascertain whether the patient was pregnant during their ICU admission. This is unlike the other datasets that are there to assess outcomes in the subsequent year.

• COVID-19 Vaccination Status – necessary to provide information on COVID-19 Vaccination status (including number and type of vaccinations) to account for effects of increasing vaccination rates over time, and the effect this had on long-term outcomes for patients surviving ICU.

The level of the data will be:

• Pseudonymised

The data will be minimised as follows:

• Limited to data for an estimated study cohort of 499,500 individuals identified by ICNARC. The cohort will include patients:

a. Aged ≥16 years

b. Admitted to an adult, general ICU in England or Wales as an emergency (unplanned)

c. Admitted to ICU for either:

i. confirmed COVID-19 between 1st January 2020 to 1st June 2022

ii. without confirmed COVID-19 between 1st July 2016 and 30th June 2022

The cohort will exclude patients who died in hospital after treatment on an ICU.

• Limited to data between 2011/12 – 2023/2024. The request for this number of years of data is based on a recruitment period between 1st July 2016 and 30th June 2022 and 5 years prior to the first admission; the study needs a minimum of 5 years of HES data prior to the incident admission to ICU to assess co-morbidities and risk factors. Including patients admitted to ICU before the emergence of COVID-19 in the study cohort allows the study to examine whether the risks faced survivors of COVID-19 differ from other critically unwell patients.

Patients who do not match to NHS England (due to the National opt out or for failure to match to the dataset) will be considered lost to follow-up. The study team will report simple summary statistics of those lost to follow-up to highlight any potential bias, but will not report any outcomes on these patients.

The University of Oxford and ICNARC are joint controllers as the organisations jointly responsible for ensuring that the data will only be processed for the purpose described above.

University of Oxford:

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

ICNARC:

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

> Article 6(1)(f) - the processing is necessary for your legitimate interests or the legitimate interests of a third party, unless there is a good reason to protect the individual’s personal data which overrides those legitimate interests. This research study is of legitimate interest to the patients who have survived critical illness, their families and the clinicians involved in their care. What happens to patients after they leave ICU and whether the study team can identify those at risk and potentially prevent it.

University of Oxford and ICNARC:

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.

COVID-19 caused a global pandemic with widespread health implications across the globe. It is in the public interest that it is understood what happens to these patients after they leave hospital and what can be learnt by comparing them to similar patients with other diseases.

The funding is provided by the University of Oxford’s COVID-19 Research Response Fund (Ref: 0009471). The funding is specifically for the project described.

Patient and Public Involvement and Engagement (PPIE) is planned to discuss the results and how best to report the findings to patients

The expected outputs of the processing will be:

• Submissions to peer reviewed journals; minimum of two submissions (e.g., British Medical Journal, Intensive Care Medicine and the Lancet) with a target year of 2025.

• Presentations at national and international conferences to experts in the field: For example, the UK Intensive Care Society State-of-the-Art annual conference and one of the European Society of Intensive Care Medicine’s bi-annual conferences.

• Publication on the University of Oxford’s Website: This is updated with a summary of latest findings - (https://www.ndcn.ox.ac.uk/research/critical-care-research-group-kadoorie-centre/research-studies/six-month-outcomes-after-surviving-treatment-for-covid-19-disease-on-an-intensive-care-unit-in-england-optic-19)

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: Promotion of results through the CCRG Twitter handle (@KadoorieCentre), which has over 1000 followers comprising of patients and health care professionals.

• Press/media engagement: All published output aim to be accompanied by a corresponding press releases including lay summaries of the findings and its applicability to patients. When major findings are published, the Departmental press office aims to assist with press releases, social media messages and interviews.

• Patient Groups: The study team aim to present their results to relevant patient groups and their families via the ICU charity “ICUsteps” (https://www.icusteps.org/). Progress is also hoped to be discussed with the Oxford ICU patient forum, whose members include former ICU patients and their relatives. The study team hope to specifically seek the advice of both groups on how best to present the study results to the wider public. The study team developed a patient notification strategy with input from the Oxford Research Ethics Committee (REC) and members of the Oxford ICU Forum (a group of previous ICU patients, families, and lay members).

• Engagement with senior critical care clinicians in Oxford and Thames Valley, should the results suggest how clinical follow-up of patients treated for COVID-19 on the Intensive Care Unit (ICU) might be improved.

The aim is to achieve these outputs by end of 2025.

Using the original dataset, the study found that patients who survived to hospital discharge following treatment on an ICU for COVID-19 during the first pandemic wave were less likely to die or be readmitted to hospital than critically ill patients prior to the pandemic, despite requiring more ICU-based care. The study conclude that irrespective of whether patients are admitted for COVID-19, patients require close follow-up after critical illness, as adverse outcomes are common. This work has been written up and will soon be published, and expect the information to inform treatment of patients.

More specifically, Oxford University expect that the study results will hopefully: reassure patients who have survived COVID-19 on the ICU about their longer-term risks; it will enable ICU follow-up clinicians (and other health professionals, such as GPs) to provide appropriate care to these patients.

Additionally, the results of this study will help inform the care of all ICU survivors (regardless of COVID-19 status). The study found that there is very little reliable literature on long-term events after ICU discharge, and therefore we expect the results of this study to be useful to patients and treating clinicians in their post-discharge care.

The University of Oxford requires access to NHS England data for the purpose of the following research project:

The OPTIC-19 Study: Outcomes of Patients who survived Treatment on an Intensive Care unit for COVID-19 in England and Wales

The following is a summary of the aims of the research project provided by the University of Oxford:

The OPTIC-19 Study is a comparative retrospective cohort study. This study is a collaboration between the Critical Care Research Group (University of Oxford) and Intensive Care National Audit and Research Centre (ICNARC).

It is not known how survivors’ severe COVID-19 infection, or the treatment they received on the ICU, will impact their long-term health. This retrospective cohort study aims to estimate the risk of adverse outcomes (death, emergency hospital readmission, heart attacks, strokes) in patients treated on an intensive care unit (ICU) with COVID-19 in England and Wales*, one year after discharge from hospital. The study team will compare these risks to patients treated in ICU for other conditions.

*For this Agreement, NHS England data is acknowledged to contain only those NHS Patients treated at secondary care sites in England only.

Since 2015, the Intensive Care National Audit and Research Centre (ICNARC) has collected audit data for all patients admitted to an ICU in England and Wales in their Case Mix Programme (CMP) data set. However, the CMP contains no information on patient outcomes after they are discharged from hospital. To investigate outcomes after discharge, this study proposes to link the data from the CMP with NHS England data to identify patients who have died in England and Wales.

Analysis of the linked data set will allow the study to provide novel insights into longer-term risks faced by survivors of severe COVID-19. The data requested will allow the study team to build a pseudonymised data set linking ICU data with longer term outcomes that results in death or require emergency hospitalisation. Using this large data set, the study can provide robust estimates of the risk of death and emergency hospital admission in the year after discharge from ICU faced by survivors of severe COVID-19.

The study will create a cohort of ICU admissions, containing data routinely collected in the Case Mix Programme. By linking these detailed ICU records with NHS long-term follow-up data (HES, ECDS, MSDS, Civil Registration, GPES Data), the study team can estimate the risk of death and emergency hospital admission in the year after discharge from ICU.

The following NHS England data will be accessed:

• Hospital Episode Statistics (HES)

o Admitted Patient Care (APC)

o Accident & Emergency (A&E)

o Outpatients (OP)

• Emergency Care Data Set (ECDS)

HES and ECDS data is necessary to allow the study to examine specific outcomes for which smaller studies suggest COVID-19 survivors could be at higher risk. These include respiratory infections (due to persistent lung damage) and strokes and pulmonary emboli (due to abnormalities in blood clotting).

• Civil Registration Mortality – necessary to allow the study to estimate the risk of death.

• Maternity Services Data Set (MSDS) v1.5 – necessary to permit analysis of a sub-group analysis of patients who were pregnant at the time of ICU admission. The aim of analysing pregnant patients is to obtain an understanding of whether long-term risks faced patients treated for COVID-19 while pregnant differ from age-matched controls.

• COVID-19 General Practice Extraction Service (GPES) Data for Pandemic Planning and Research (GDPPR) – necessary ensure comprehensive coverage of patients’ pre-existing comorbidities, which will be used to account for confounding factors in the study's risk estimates.

The level of the data will be:

• Pseudonymised

The data will be minimised as follows:

• Limited to data for a study cohort of 319,600 individuals identified by ICNARC. The cohort will include patients:

a. Aged ≥16 years

b. Admitted to an adult, general ICU in England or Wales as an emergency (unplanned)

c. Admitted to ICU for either:

i. confirmed COVID-19 between 1st January 2020 to 1st July 2020

ii. without confirmed COVID-19 between 1st July 2016 and 1st July 2020

The cohort will exclude patients who died in hospital after treatment on an ICU.

• Limited to data between 2011/12 – July 2021. The request for this number of years of data is based on a recruitment period starting in 2016 to 1st July 2020 and 5 years prior to the first admission; the study needs a minimum of 5 years of HES data prior to the incident admission to ICU to assess co-morbidities and risk factors. Including patients admitted to ICU before the emergence of COVID-19 in the study cohort allows the study to examine whether the risks faced survivors of COVID-19 differ from other critically unwell patients.

Patients who do not match to NHS England (due to the National opt out or for failure to match to the dataset) will be considered lost to follow-up. The study team will report simple summary statistics of those lost to follow-up to highlight any potential bias, but will not report any outcomes on these patients.

The University of Oxford and ICNARC are joint controllers as the organisations jointly responsible for ensuring that the data will only be processed for the purpose described above.

University of Oxford:

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

ICNARC:

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

> Article 6(1)(f) - the processing is necessary for your legitimate interests or the legitimate interests of a third party, unless there is a good reason to protect the individual’s personal data which overrides those legitimate interests. This research study is of legitimate interest to the patients who have survived critical illness, their families and the clinicians involved in their care. What happens to patients after they leave ICU and whether the study team can identify those at risk and potentially prevent it.

University of Oxford and ICNARC:

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.

COVID-19 caused a global pandemic with widespread health implications across the globe. It is in the public interest that it is understood what happens to these patients after they leave hospital and what can be learnt by comparing them to similar patients with other diseases.

The funding is provided by the University of Oxford’s COVID-19 Research Response Fund (Ref: 0009471). The funding is specifically for the project described.

Exponential-E Ltd provides IT hosting services to ICNARC and will store the data as contracted by ICNARC.

Patient and Public Involvement and Engagement (PPIE) is planned after results have been obtained to report back.

The expected outputs of the processing will be:

• Submissions to peer reviewed journals; minimum of two submissions (e.g., British Medical Journal, Intensive Care Medicine and the Lancet). The first article aims to report six month outcomes (target date: mid 2023) and the second aims to include one year outcomes (target date: mid-late 2023).

• Presentations at national and international conferences to experts in the field: For example, the UK Intensive Care Society State-of-the-Art annual conference and one of the European Society of Intensive Care Medicine’s bi-annual conferences.

• Publication on the University of Oxford’s Website: This is updated with a summary of latest findings - (https://www.ndcn.ox.ac.uk/research/critical-care-research-group-kadoorie-centre/research-studies/six-month-outcomes-after-surviving-treatment-for-covid-19-disease-on-an-intensive-care-unit-in-england-optic-19)

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: Promotion of results through the CCRG Twitter handle (@KadoorieCentre), which has over 1000 followers comprising of patients and health care professionals.

• Press/media engagement: All published output aim to be accompanied by a corresponding press releases including lay summaries of the findings and its applicability to patients. When major findings are published, the Departmental press office aims to assist with press releases, social media messages and interviews.

• Patient Groups: The study team aim to present their results to relevant patient groups and their families via the ICU charity “ICUsteps” (https://www.icusteps.org/). Progress is also hoped to be discussed with the Oxford ICU patient forum, whose members include former ICU patients and their relatives. The study team hope to specifically seek the advice of both groups on how best to present the study results to the wider public. The study team developed a patient notification strategy with input from the Oxford Research Ethics Committee (REC) and members of the Oxford ICU Forum (a group of previous ICU patients, families, and lay members).

• Engagement with senior critical care clinicians in Oxford and Thames Valley, should the results suggest how clinical follow-up of patients treated for COVID-19 on the Intensive Care Unit (ICU) might be improved.

The aim is to achieve these outputs by the end of 2023.

The University of Oxford requires access to NHS England data for the purpose of the following research project:

The OPTIC-19 Study: Outcomes of Patients who survived Treatment on an Intensive Care unit for COVID-19 in England and Wales

The following is a summary of the aims of the research project provided by the University of Oxford:

The OPTIC-19 Study is a comparative retrospective cohort study. This study is a collaboration between the Critical Care Research Group (University of Oxford) and Intensive Care National Audit and Research Centre (ICNARC).

It is not known how survivors’ severe COVID-19 infection, or the treatment they received on the ICU, will impact their long-term health. This retrospective cohort study aims to estimate the risk of adverse outcomes (death, emergency hospital readmission, heart attacks, strokes) in patients treated on an intensive care unit (ICU) with COVID-19 in England and Wales*, one year after discharge from hospital. The study team will compare these risks to patients treated in ICU for other conditions.

*For this Agreement, NHS England data is acknowledged to contain only those NHS Patients treated at secondary care sites in England only.

Since 2015, the Intensive Care National Audit and Research Centre (ICNARC) has collected audit data for all patients admitted to an ICU in England and Wales in their Case Mix Programme (CMP) data set. However, the CMP contains no information on patient outcomes after they are discharged from hospital. To investigate outcomes after discharge, this study proposes to link the data from the CMP with NHS England data to identify patients who have died in England and Wales.

Analysis of the linked data set will allow the study to provide novel insights into longer-term risks faced by survivors of severe COVID-19. The data requested will allow the study team to build a pseudonymised data set linking ICU data with longer term outcomes that results in death or require emergency hospitalisation. Using this large data set, the study can provide robust estimates of the risk of death and emergency hospital admission in the year after discharge from ICU faced by survivors of severe COVID-19.

The study will create a cohort of ICU admissions, containing data routinely collected in the Case Mix Programme. By linking these detailed ICU records with NHS long-term follow-up data (HES, ECDS, MSDS, Civil Registration, GPES Data), the study team can estimate the risk of death and emergency hospital admission in the year after discharge from ICU.

The following NHS England data will be accessed:

• Hospital Episode Statistics (HES)

o Admitted Patient Care (APC)

o Accident & Emergency (A&E)

o Outpatients (OP)

• Emergency Care Data Set (ECDS)

HES and ECDS data is necessary to allow the study to examine specific outcomes for which smaller studies suggest COVID-19 survivors could be at higher risk. These include respiratory infections (due to persistent lung damage) and strokes and pulmonary emboli (due to abnormalities in blood clotting).

• Civil Registration Mortality – necessary to allow the study to estimate the risk of death.

• Maternity Services Data Set (MSDS) v1.5 – necessary to permit analysis of a sub-group analysis of patients who were pregnant at the time of ICU admission. The aim of analysing pregnant patients is to obtain an understanding of whether long-term risks faced patients treated for COVID-19 while pregnant differ from age-matched controls.

• COVID-19 General Practice Extraction Service (GPES) Data for Pandemic Planning and Research (GDPPR) – necessary ensure comprehensive coverage of patients’ pre-existing comorbidities, which will be used to account for confounding factors in the study's risk estimates.

The level of the data will be:

• Pseudonymised

The data will be minimised as follows:

• Limited to data for a study cohort of 319,600 individuals identified by ICNARC. The cohort will include patients:

a. Aged ≥16 years

b. Admitted to an adult, general ICU in England or Wales as an emergency (unplanned)

c. Admitted to ICU for either:

i. confirmed COVID-19 between 1st January 2020 to 1st July 2020

ii. without confirmed COVID-19 between 1st July 2016 and 1st July 2020

The cohort will exclude patients who died in hospital after treatment on an ICU.

• Limited to data between 2011/12 – July 2021. The request for this number of years of data is based on a recruitment period starting in 2016 to 1st July 2020 and 5 years prior to the first admission; the study needs a minimum of 5 years of HES data prior to the incident admission to ICU to assess co-morbidities and risk factors. Including patients admitted to ICU before the emergence of COVID-19 in the study cohort allows the study to examine whether the risks faced survivors of COVID-19 differ from other critically unwell patients.

Patients who do not match to NHS England (due to the National opt out or for failure to match to the dataset) will be considered lost to follow-up. The study team will report simple summary statistics of those lost to follow-up to highlight any potential bias, but will not report any outcomes on these patients.

The University of Oxford and ICNARC are joint controllers as the organisations jointly responsible for ensuring that the data will only be processed for the purpose described above.

University of Oxford:

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

ICNARC:

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

> Article 6(1)(f) - the processing is necessary for your legitimate interests or the legitimate interests of a third party, unless there is a good reason to protect the individual’s personal data which overrides those legitimate interests. This research study is of legitimate interest to the patients who have survived critical illness, their families and the clinicians involved in their care. What happens to patients after they leave ICU and whether the study team can identify those at risk and potentially prevent it.

University of Oxford and ICNARC:

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.

COVID-19 caused a global pandemic with widespread health implications across the globe. It is in the public interest that it is understood what happens to these patients after they leave hospital and what can be learnt by comparing them to similar patients with other diseases.

The funding is provided by the University of Oxford’s COVID-19 Research Response Fund (Ref: 0009471). The funding is specifically for the project described.

Exponential-E Ltd provides IT hosting services to ICNARC and will store the data as contracted by ICNARC.

Patient and Public Involvement and Engagement (PPIE) is planned after results have been obtained to report back.

The expected outputs of the processing will be:

• Submissions to peer reviewed journals; minimum of two submissions (e.g., British Medical Journal, Intensive Care Medicine and the Lancet). The first article aims to report six month outcomes (target date: mid 2023) and the second aims to include one year outcomes (target date: mid-late 2023).

• Presentations at national and international conferences to experts in the field: For example, the UK Intensive Care Society State-of-the-Art annual conference and one of the European Society of Intensive Care Medicine’s bi-annual conferences.

• Publication on the University of Oxford’s Website: This is updated with a summary of latest findings - (https://www.ndcn.ox.ac.uk/research/critical-care-research-group-kadoorie-centre/research-studies/six-month-outcomes-after-surviving-treatment-for-covid-19-disease-on-an-intensive-care-unit-in-england-optic-19)

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: Promotion of results through the CCRG Twitter handle (@KadoorieCentre), which has over 1000 followers comprising of patients and health care professionals.

• Press/media engagement: All published output aim to be accompanied by a corresponding press releases including lay summaries of the findings and its applicability to patients. When major findings are published, the Departmental press office aims to assist with press releases, social media messages and interviews.

• Patient Groups: The study team aim to present their results to relevant patient groups and their families via the ICU charity “ICUsteps” (https://www.icusteps.org/). Progress is also hoped to be discussed with the Oxford ICU patient forum, whose members include former ICU patients and their relatives. The study team hope to specifically seek the advice of both groups on how best to present the study results to the wider public. The study team developed a patient notification strategy with input from the Oxford Research Ethics Committee (REC) and members of the Oxford ICU Forum (a group of previous ICU patients, families, and lay members).

• Engagement with senior critical care clinicians in Oxford and Thames Valley, should the results suggest how clinical follow-up of patients treated for COVID-19 on the Intensive Care Unit (ICU) might be improved.

The aim is to achieve these outputs by the end of 2023.

The OPTIC-19 Study: Outcomes of Patients who survived Treatment on an Intensive Care unit for COVID-19 in England and Wales is a comparative retrospective cohort study. This study is a collaboration between the Critical Care Research Group (University of Oxford) and Intensive Care National Audit and Research Centre (ICNARC).

This is a standalone research study funded by the University of Oxford’s COVID-19 Research Response Fund (Ref: 0009471)

This retrospective cohort study aims to estimate the risk of adverse outcomes (death, emergency hospital readmission, heart attacks, strokes) in patients treated on an intensive care unit (ICU) with COVID-19 in England and Wales*, one year after discharge from hospital. The study team will compare these risks to patients treated in ICU for other conditions.

*For this agreement, NHS Digital data is acknowledged to contain only those NHS Patients treated at secondary care sites in England only.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019. By July 2020 14 million people globally had been infected, of which over 600,000 died of coronavirus disease 2019 (COVID-19). In the UK, nearly 20% of patients hospitalised with COVID-19 were transferred to an intensive care unit (ICU) or high dependency ward. In total, over 10,000 patients have been treated for COVID-19 on an ICU in England and Wales. On average, 50% of these patients survived to hospital discharge, although survival rates appear to be increasing. It is not known how survivors’ severe COVID-19 infection, or the treatment they received on the ICU, will impact their long-term health.

Since 2015, the Intensive Care National Audit and Research Centre (ICNARC) has collected audit data for all patients admitted to an ICU in England and Wales in their Case Mix Programme (CMP) data set. However, the CMP contains no information on patient outcomes after they are discharged from hospital. To investigate outcomes after discharge, this study proposes to link the data from the CMP with Hospital Episode Statistics (HES) data (inpatients (also called Admitted Patient Care, or APC), outpatients (OP), emergency department (A&E or ECDS) and Civil Registrations (Deaths) data to identify patients who have died in England and Wales. Linkage to hospital admission data will allow the study to examine specific outcomes for which smaller studies suggest COVID-19 survivors could be at higher risk. These include respiratory infections (due to persistent lung damage) and strokes and pulmonary emboli (due to abnormalities in blood clotting). Including patients admitted to ICU before the emergence of COVID-19 in our study cohort, will allow the study to examine whether the risks faced survivors of COVID-19 differ from other critically unwell patients. Alongside HES data, linkage to the GPES Data for Pandemic Planning (GDPPR) will ensure comprehensive coverage of patients’ pre-existing comorbidities, which will be used to account for confounding factors in the study's risk estimates. The study team will also link to the Maternity Services Data Set (MSDS) to permit a sub-group analysis of patients who were pregnant at the time of ICU admission. The aim of analysing pregnant patients is to obtain an understanding of whether long-term risks faced patients treated for COVID-19 while pregnant differ from age-matched controls.

Analysis of the linked data set will allow the study to provide novel insights into longer-term risks faced by survivors of severe COVID-19. The data requested will allow the study team to build a pseudonymised data set linking ICU data with longer term outcomes that results in death or require emergency hospitalisation. Using this large data set, the study can provide robust estimates of the risk of death and emergency hospital admission in the year after discharge from ICU faced by survivors of severe COVID-19.

The study will create a cohort of ICU admissions, containing data routinely collected in the Case Mix Programme. By linking these detailed ICU records with NHS long-term follow-up data (HES, ECDS, MSDS, Civil Registration, GPES Data), the study team can estimate the risk of death and emergency hospital admission in the year after discharge from ICU. This cohort will include adult patients (16 years of age or old) admitted as an emergency to an ICU in England or Wales, who survived to hospital discharge.

The cohort will include patients:

a. Aged ≥16 years

b. Admitted to an adult, general ICU in England or Wales as an emergency (unplanned)

c. Admitted to ICU for either:

i. confirmed COVID-19 between 1st January to 1st July 2020

ii. without confirmed COVID-19 between 1st July 2016 and 1st July 2020

The cohort will exclude patients who died in hospital after treatment on an ICU.

Linkage to Civil Registrations will allow the study to estimate the risk of death. Linkage to hospital admission (HES) data will allow the study to examine specific outcomes for which smaller studies suggest COVID-19 survivors could be at higher risk. These include respiratory infections (due to persistent lung damage) and strokes and pulmonary emboli (due to abnormalities in blood clotting). Including HES and GDPPR data from the four years prior to ICU admission will allow the study to identify participants’ pre-existing comorbidities and reduce the effect of incomplete diagnostic coding. Including patients admitted to ICU before the emergence of COVID-19 in our study cohort, will allow the study to examine whether the risks faced survivors of COVID-19 differ from other critically unwell patients. The MSDS will allow the study team to undertake a sub-group analysis of patients who were pregnant at the time of ICU admission

Only pseudonymised data will be received by the coordinating site (Critical Care Research Group Oxford University) from NHS Digital. Only pseudonymised data will be retained and analysed by the study team. HES data is essential for the study as it provides diagnostic coding data required to assess our pre-defined secondary outcomes.

The applicants are unable to use the NHS Digital’s Trusted Research Environment (TRE) due to the fact that this data analysis tool does not yet support the upload of outside data (i.e. a cohort) and thus a data extract is required.

ICNARC (as a non NHS organisation) is not able to apply the National Data opt out to its data. NHS Digital will apply the National opt-out to the dataset. Patients who do not match to NHS Digital (due to the National opt out or for failure to match to the dataset) will be considered lost to follow-up (as the study team will not have any outcome data for them). The study team will report simple summary statistics of those lost to follow-up (to highlight any potential bias) but will not report any outcomes on these patients.

The study team has identified the minimal number of participants required to provide robust risk estimates for the primary (mortality) and secondary outcomes. Participants admitted to ICU with COVID-19 are determined by the study period.

The study needs a minimum of 5 years of HES data prior to the incident admission to ICU to assess co-morbidities and risk factors. The request for this number of years of data is therefore based on a recruitment period starting in 2016 to 1st July 2020 and 5 years prior to the first admission.

DATA CONTROLLERS AND PROCESSORS

The Critical Care Research Group based at the University of Oxford are Joint Data Controllers with the Intensive Care National Audit and Research Centre (ICNARC), who will also both be processing the data.

Exponential-E Ltd supply IT infrastructure for ICNARC where the data will be stored and host the server. They are therefore listed as a data processor. They supply support to the system, but do not access data. Therefore, any access to the data held under this agreement would be considered a breach of the agreement. This includes granting of access to the database[s] containing the data.

LEGAL BASIS

The lawful basis for processing data under GDPR has been reviewed and been assessed as acceptable. The University of Oxford process data under Article 6(1)(e): "processing is necessary for the performance of a task in the public interest or in the exercise of official authority vested in the controller" as they are a Public Authority.

ICNARC process data under Article 6(1)(f): “Legitimate interests: the processing is necessary for your legitimate interests or the legitimate interests of a third party, unless there is a good reason to protect the individual’s personal data which overrides those legitimate interests. (This cannot apply if you are a public authority processing data to perform your official tasks.)” This research study is of legitimate interest to the patients who have survived critical illness, their families and the clinicians involved in their care. What happens to patients after they leave ICU and whether the study team can identify those at risk and potentially prevent it.

Additionally, the University of Oxford and ICNARC process the Special Category Health Data under 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" as the data are required for research purposes in the public interest.

This study aims to publish at least two journal articles describing the risk faced by survivors of COVID-19 treated on an ICU. The first article aims to report six month outcomes (target date: 1st October 2021) and the second aims to include one year outcomes (target date: 1st December 2021).

The study team will be responsible for publishing outputs in high-impact open access peer-reviewed journals, such as the British Medical Journal, Intensive Care Medicine and the Lancet. All outputs will be aggregated with small number suppression applied as per the HES analysis guide. All published output aim to be accompanied by a corresponding press releases including lay summaries of the findings and its applicability to patients. When major findings are published, the Departmental press office aims to assist with press releases, social media messages and interviews.

The study hopes to also be promoted through the CCRG Twitter handle (@KadoorieCentre), which has over 1000 followers comprising of patients and health care professionals. Findings hope to be be presented at national and international conferences to experts in the field – for example, the UK Intensive Care Society State-of-the-Art annual conference and one of the European Society of Intensive Care Medicine’s bi-annual conferences.

The study team aim to present their results to relevant patient groups and their families via the ICU charity “ICUsteps” (https://www.icusteps.org/). They hope to also discuss their progress with the Oxford ICU patient forum, whose members include former ICU patients and their relatives. The study team hope to specifically seek the advice of both groups on how best to present the study results to the wider public. The study team developed a patient notification strategy with input from the Oxford Research Ethics Committee (REC) and members of the Oxford ICU Forum (a group of previous ICU patients, families, and lay members). The study will fully implement the National Data Opt-out and will therefore exclude any records related to patients who have notified the NHS of their wish for their data not to be used in research.

For a previous study, the study team were advised by the ethics committee that placing posters in the relative rooms or waiting areas of the participating ICUs to notify patients of the study, “was not practical and should not therefore be used”. All members of the Patient and Public Involvement (PPI) panel agreed with the ethics committee that displaying posters would not be appropriate. However, the PPI group advised that information should be available on a study website. The group advised that the website summary should be brief and accessible, with links to the detail (such as formal privacy policy) available. Members of the previous study PPI group were also consulted for this study (OPTIC-19) and were very clear in their support.

The aim is to achieve these outputs within the 15 month study period.

The study website (https://www.ndcn.ox.ac.uk/research/critical-care-research-group-kadoorie-centre/research-studies/six-month-outcomes-after-surviving-treatment-for-covid-19-disease-on-an-intensive-care-unit-in-england-optic-19) will be updated with all the details of the above.

The study team aim to engage with senior critical care clinicians in Oxford and Thames Valley should the results suggest how clinical follow-up of patients treated for COVID-19 on the Intensive Care Unit (ICU) might be improved.

Yielded Benefits is not a requirement for new applications.