Long-term outcomes following traumatic brain injury: a retrospective cohort study

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

Long-term outcomes following traumatic brain injury: a retrospective cohort study

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

This study addresses the long-term effects of traumatic brain injuries. A traumatic brain injury (TBI) is a head injury which results in symptoms of brain dysfunction. TBI can be classified according to the mechanism of injury in relation to the damage sustained by the skull. Closed TBI (CTBI) describes when external forces are transmitted through the skull to cause brain dysfunction without breaching the skull. Open TBI (OTBI) describes when brain dysfunction results from external forces and the skull is breached by a foreign body. In civilian populations, OTBI accounts for between 5–12% of all cases of TBI, and yet long- term outcomes after this type of brain injury remain unclear.

CTBI is associated with a long-term increase in mortality and reduced life expectancy. CTBI is also associated with an increased risk of developing a range of neurological and psychiatric conditions later in life, including dementia, stroke, epilepsy, depression, and sleep disorders. Because OTBI is less common and more often fatal than CTBI, the extent to which it is associated with other condition in the long-term is less clear. Patients with OTBI are at higher risk of medical complications following injury compared to those with CTBI, and often require expert intensive care. Given this, and the biological differences between OTBI and CTBI, it is plausible that OTBI is associated with greater risks to the health of long-term survivors; and yet, due to a lack of evidence, strategies for the prevention and mitigation of these risks do not form part of current TBI guidelines. More research is needed to understand why this is the case and what can be done to reduce these risks.

Recent studies have revealed important insights into the long-term effects of certain types of brain injuries, especially concussion. However, we still know very little about other types of brain injuries, including the most severe cases which involve direct damage to the brain caused by injuries that penetrate the skull. To address this, we will study a uniquely detailed collection of information gathered over the lifetime of three thousand veterans who were treated at the Military Hospital for Head Injuries (MHHI), established at St Hugh’s College in Oxford during World War II. This information describes physical and mental health outcomes (in the form of previously collected archived research records), which the University of Oxford propose to link with information describing life expectancy (mortality data from central registers). Through this study, the University of Oxford aim to answer the following question:

What are the long-term effects of penetrating brain injuries on physical health, mental health, and life expectancy?

This study is an update to an earlier epidemiological study which followed a standard historical cohort design. The cohort is already assembled, and no new study members will be recruited or registered. For the original study, recruitment took place between 1940-1954 and involved extracted information from archived research records that was linked with national registry data on mortality collected between 1940-2003. This study will update information on mortality by 21 years. The analyses will use standard epidemiological methodology.

The following NHS England Data will be accessed:

> Civil Registration Mortality – necessary to provide a status update on the cohort.

The level of the Data will be:

> Identifiable*

*Although the Data disseminated from NHS England to the University of Oxford under this Data Sharing Agreement is pseudonymised, the PhD student accessing the pseudonymised Data will also have access to the identifiers, and therefore, although there will be no attempt to re-identify participants, there is the technical means to do so.

The Data will be minimised as follows:

> Limited to a study cohort identified by the University of Oxford – the cohort consists of soldiers who showed evidence of brain dysfunction following a suspected head injury (cases), or peripheral nerve injuries (controls) during World War II and the Korean war and were subsequently treated at the Military Hospital for Head Injuries in St Hugh’s College, and formed the cohort of a previous study in 1998.

> Latest available data is required to update the study to a time when it is expected that almost all members of the cohort will be deceased.

The University of Oxford 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.

A member of staff from King's College London may provide support and guidance based on what the University of Oxford proposes, but the research team at the University of Oxford will be solely responsible for determining the purpose and means of the processing of personal data.

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;

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 of the potential impact of future results in understanding the long-term effect of different types of brain injuries, therefore rests on four key points: (1) Public interest and understanding future risk of traumatic brain injuries, (2) Need to utilise the uniqueness of the MHHI veteran cohort, (3) Efficient use of an assembled cohort, and (4) Increased statistical power and ability to address new questions.

The funding is provided by a Medical Research Council in the form of a PhD fellowship. The funding is for the PhD student and this project.

The funder will have no ability to suppress or otherwise limit the publication of findings.

Data will be accessed by:

> Substantive employees of the University of Oxford.

> A PhD Student enrolled with the University of Oxford. The individual has completed mandatory data protection and confidentiality training and is subject to the University of Oxford’s policies on data protection and confidentiality. The individual accessing the data will do so under the supervision of a substantive employee of the University of Oxford. The University of Oxford would be responsible and liable for any work carried out by the individual. The PhD student would only work on the data for the purposes described in this Data Sharing Agreement (DSA).

The University of Oxford have consulted with stakeholders representing the original study participants and veteran communities more broadly regarding this study and the proposed use of patient identifiable data without consent. As part of this consultation, the University of Oxford have engaged with a relative of a veteran in the study cohort. They were strongly supportive of the study, including specifically the use of personal data without consent as described in the protocol.

The Concussion Legacy Foundation (CLF) is a leading global charity addressing the effects of brain injuries on veterans. The University of Oxford have consulted with the UK branch of the CLF and provide their views regarding the acceptability of this project, which were also strongly supportive. In addition, researchers involved in the original study and related projects who met many of the original participants, have also offered their support.

The University of Oxford will transfer data to NHS England. The data will consist of identifying details (specifically name, sex, date of birth, NHS number, postcode and a unique person ID) for the cohort to be linked with NHS England data.

NHS England will provide the relevant records from the mortality dataset to the University of Oxford. The Data will contain no direct identifying data items but will contain a unique person ID which can be used to link the Data with other record level data already held by the recipient.

The Data will not be transferred to any other location.

The Data will be stored on servers at the University of Oxford.

The Data will be accessed by authorised personnel via remote access.

The Controller(s) must confirm and provide evidence upon audit by NHS England that access via any remote device complies with the data security obligations within this DSA and the Data Sharing Framework Contract.

For remote access:

- Remote access will only be from secure locations situated within the territory of use (as further restricted elsewhere within the DSA if so done) stated within this DSA;

- Access controls granting users the minimum level of access required are in place;

- Remote access is only via secure connections (e.g., VPNs or secure protocols) to protect data;

- Multifactor authentication (MFA) is required for remote access;

- Device security, including up-to-date software and operating systems, antivirus software, and enabled firewalls are utilised for the remote access;

- All remote access is undertaken within the scope of the organisation’s DSPT (or other security arrangements as per this DSA) and complies with the organisation’s remote access policy.

The above applies in addition to any condition set out elsewhere within the DSA (e.g. who may carry out processing, and for what purpose).

Remote processing will be from secure locations within England. The data will not leave England at any time.

Access is restricted to employees or PhD students at the University of Oxford who have authorisation from the Chief Investigator.

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

The Data will be linked at person record level using study IDs with pseudonymised mortality, exposure, and morbidity data obtained from index cards stored in St Hugh’s College Archive at the University of Oxford, which describe the date of injury/admission/discharge, nature of the injury, presenting characteristics, medical assessments, and responses to postal surveys describing neurological and psychiatric symptoms up to ten years after discharge from the MHHI. Pseudonymised mortality data will also be collected from death certificate index cards provided by the Office for National Statistics up to and including 2003, which are also stored in St Hugh’s College Archive.

The Data will not be linked with any other data.

The identifying details will be stored in a separate database to the linked dataset used for analysis. All analyses will use the pseudonymised dataset. There will be no requirement and no attempt to reidentify individuals when using the pseudonymised dataset.

Researchers from the University of Oxford will analyse the Data for the purposes described above.

The expected outputs of the processing will be:

> Submissions to peer reviewed journals, including at least one high-impact scientific paper

> Presentations at appropriate conferences, including at least one international conference presentation

> Findings will form part of the PhD student’s thesis

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

> Conferences

> Updates to the University of Oxford’s departmental webpages

> Social media

> St Hugh’s College webpage updates aimed at any surviving veterans and their relatives

> Newsletters aimed at any surviving veterans and their relatives

The target date for the above outputs to be achieved are throughout 2025 and 2026.

In 2022, the Brain Trauma Foundation emphasised the urgent need for more research into the long-term effects of OTBI. Opportunities to study long-term outcomes among people with OTBI are limited, and while prospective studies are underway, the study of existing cohorts can provide timely insights to inform brain injury management guidelines in the near term and inform the design of prospective studies in the longer term. The largest study of long-term outcomes after OTBI to date involved 1,221 veterans of the Vietnam War and spanned more than 40 years. Among the many insights gained from the Vietnam Head Injury Study (VHIS), it revealed a high burden of motor, visual, and memory impairment and an increased risk of epilepsy 15 years after injury among survivors of OTBI compared to uninjured controls. Thirty-five years after injury, OTBI survivors remained at higher risk of epilepsy and also cognitive impairment. Along with the VHIS, the MHHI cohort remains one of the largest and most detailed collections of data describing long-term outcomes among people with OTBI. The main benefit of this study is therefore that it will reveal lifelong effects of OTBI on mortality, supporting the anticipation and mitigation of adverse outcomes for this group of patients.

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 the need for, or effectiveness of, preventative health and care measures for particular populations or conditions.

> support knowledge creation or exploratory research (and the innovations and developments that might result from that exploratory work).

The University of Oxford hope to contribute towards improving the lives of people affected by traumatic brain injuries.

This study will be the largest of its kind ever performed. The results will be used to inform brain injury management guidelines, which currently do not provide guidance for people affected by penetrating brain injuries.

The University of Oxford aim to achieve these benefits in three main stages:

1) Reveal the lifelong effects of OTBI on mortality through analysis of the data provided (2025). Planned analyses to be conducted within the PhD include comparisons of age at death and frequency of neurological causes of death between open and closed TBI groups.

2) Publication and dissemination of these results will occur towards the end of the PhD and in the period immediately afterwards (2025-2026).

3) The University of Oxford foresee that applying these results to inform the development of TBI management guidelines is a longer-term goal (2026-2030). Practically, it is anticipated that the results of this study will be shared with the Brian Trauma Foundation, who produce authoritative guidelines on the management of TBI. The PhD student will be well-placed to sustain this effort, as an academic neurology trainee based in Oxford for at least the next five years.

Findings of this study will also be disseminated with any surviving veterans and their relatives, and veterans more broadly, through the Concussion Legacy Foundation (CLF). The CLF is a global leading brain injury charity who work closely with veteran communities, sharing the latest research through webinars, conferences, social media, and press engagement.

Yielded Benefits is not a requirement for new applications.