Title: NIHR Global Health Research Group on Neurotrauma, University of Cambridge
Funder: Department of Health and Social Care

Abstract: D. PROPOSED PROGRAMME (a-c, e & f in the additional information section) Traumatic brain injury (TBI) is a leading cause of death & disability around the world with LMICs facing the greatest burden of disease. We are well positioned to be leading the application for a Global Neurotrauma Research Group due to the track record of the neurotrauma programme in academic excellence, national leadership in systems engineering and public health. We have experience of working with partners in LMICs in delivering multicentre randomised trials (RESCUEicp & RESCUE-ASDH NIHR-funded trials) and have been selected as the first centre for global neurotrauma training by the World Federation of Neurosurgical Societies. We have established collaborations with partners in Colombia, Ethiopia, India, Indonesia, Malaysia, Myanmar, South Africa, and Tanzania. The delivery of neurotrauma care is complex, involving different teams, equipment, infrastructure, culture, political will, legal frameworks, and finance. The need to address this complexity is well recognised. The WHO have called for robust systems approaches to the development of care, particularly in LMICs, following a recognition that improving care and performing research flounders without an understanding of the multiple factors involved. While some groups have sought to apply ‘systems thinking’ to improving care in LMICs, this has largely been in isolation from established systems engineering researchers. Our intention is to work with our partners in LMICs in order to improve TBI clinical care and research leveraging our expertise in neurotrauma care and research, and systems engineering across four themes: •THEME 1 - Mapping TBI Clinical Care: Volume, case mix, and current practice This theme aims to map the current landscape of TBI care provision in 8 partner countries. This is a priority for our LMIC partner organisations and a strategic priority for the World Federation of Neurosurgical Societies (WFNS; President elect Franco Servadei; co-applicant). Additionally, the establishment and maintenance of robust data collection mechanisms is a key target in the Global Surgery 2030 roadmap (3). Hence, we are proposing the establishment of a WFNS-endorsed neurotrauma registry in the partner institutions prior to wider dissemination. The web-based registry will map the pre-hospital, acute in-hospital (imaging, neurosurgery, intensive care), and post-acute care (access to rehabilitation) of TBI patients and will be used for defining the contemporary case mix and outcomes of TBI patients. We will also map the available resources and define the current status of measures used in terms of primary prevention (compared to HICs). This registry will aim to leverage the experience of Cambridge (neuro-informatics ORION unit), which is currently hosting similar registries in the UK on behalf of the Society of British Neurological Surgeons. The establishment of a registry as part of the 3-year project is a critical element of the long-term sustainability of Global Neurotrauma efforts, as it will be used by LMICs collaborators in quality improvement (including methods for safe management of head injuries by non-neurosurgeons in rural environments) and research in future phases of the long-term programme. •THEME 2 - Understanding TBI care: Frameworks, stakeholders and critical issues This theme aims to develop an in-depth understanding of the challenges associated with improving TBI care, using a Systems Modelling approach. Initially, we intend to perform the majority of this work in Myanmar, a major recipient of UK Aid. Cambridge has an institutional health partnership with Yangon General Hospital (YGH) funded by the Tropical Health Education Trust (THET). This aims to improve systems of trauma care within YGH through educational activities, mentoring, academic research, and clinical exchange. As a result of the success of this partnership, we have been invited by the Myanmar Ministry of Health to perform a national survey of trauma intensive care facilities in Myanmar, and to advise on appropriate interventions to improve this service. We aim to develop a process to perform this level of inquiry within a systems approach, based upon a Design Research Methodology (DRM) - the accepted standard in other systems-based industries with an academic pedigree spanning over a decade. We will apply an iterative approach in which a set of criteria for success are established, followed by an initial descriptive study, or reference model of the current state of affairs. This will be followed by a prescriptive study, which can be thought of as an impact model, or proposed state of affairs. Finally, a second descriptive study will be performed to explore whether the new model fulfils the criteria defined at the outset. The supporting diagram (uploads section) provides further details. •THEME 3 - Generating & implementing innovation This theme will build on the outputs of Themes 1 & 2 to develop and implement innovation aimed at improved clinical care of TBI, both in terms of systems and individual intervention in partner LMICs. The systems level intervention that we will test will emerge from Theme 2, while specific interventions will address phases of the care pathway in other partner LMICs. These will be prioritised based on the analysis undertaken in Themes 1 & 2. However, following initial literature search and discussion with LMIC partners we have already nominated four exemplar projects that will allow us to hit the ground running -Sub-theme A: System refinement for better and more cost-effective outcomes Subsequent to mapping the pathway of TBI management (theme 1) we will look at ways in which the system can be refined in terms of pre-hospital care, acute and on-going hospital care and rehabilitation. In the UK progress has been made at each of these pathway stages and it is now appropriate to translate this approach to LMICs. In addition, we recognise the importance of primary prevention and will explore means by which this can be improved in the LMICs (e.g. motorcycle helmets, road design). -Sub-theme B: Patient triage and risk stratification *Index project 1* - Cost-effective non-invasive monitoring of intracranial pressure (ICP). Intracranial pressure is routinely monitored in HICs but ICP monitoring is not routinely available in most LMICs. Prospective research will focus on initiating pilot projects on the utility of non-invasive measures of ICP [optic nerve sheath diameter (ONSD)] to aid management decisions (4). This pilot project will aim to leverage the potential for downsizing of relevant technology to enhance access to these technologies (i.e. with the use of ultrasound probes with smartphones). *Index project 2* - Infrascanner for early detection of traumatic mass lesions. Timely access to CT imaging is already recognised as a major issue in LMICs. The Infrascanner is a hand-held, brain haematoma detection device for TBI assessment based on Near-Infrared (NIR) technology (5). It can be applied in the pre-hospital and hospital setting (6). It has been used in HICs but we will explore its application in terms of sensitivity, specificity and aid to decision making in the partner LMICs. -Sub-theme C: Surgical interventions for TBI The institutions from partner LMICs will become involved in an existing relevant randomised trial (RESCUE-ASDH, an NIHR-funded randomised controlled trial of craniotomy versus craniectomy for acute subdural haematomas) (7). In parallel, working closely with partners in LMICs, we intend to design new trials addressing needs in low-resource settings. Early discussions indicate that priorities are: a trial of early surgical evacuation of intraparenchymal lesions and a trial of different decompression techniques [e.g. craniectomy (bone flap left out necessitating later replacement with second procedure) vs hinge-craniotomy (bone flap is left in but can float in order to accommodate evolving brain swelling)] (8). -Sub-theme D: Collection of long-term outcomes To facilitate the establishment of registries and conduct of clinical trials, the collection of long-term outcomes needs to be improved. Through the involvement of patients and healthcare professionals, we will develop and validate novel methods of collecting long-term outcome data in low-resource settings using SMS, smartphone and web-based applications. •THEME 4 - Quantifying & nurturing research capacity This theme will leverage a mixed methods approach in order to define the contemporary TBI research output and map the current resources available for conducting clinical research in partner LMICs. A research output analysis will be conducted but we are also particularly interested in research output published in non-traditional platforms (e.g. social media, video sharing websites etc). Focus groups and interviews will be undertaken with relevant stakeholders in the partner LMICs in order to map current resources and understand challenges. We will explore the initiation of an in-depth analysis of the challenges in one of the participating LMICs leveraging a systems approach after the aforementioned systems engineering project in Myanmar is consolidated. Our plans to develop research skills entail research methodology courses in partnership with the BMJ (RtoP programme, academic editor Trish Groves). The clinical research fellows, who will be involved in the individual projects, will have access to the research training offered in Cambridge and the research training offered in local partner universities. We will establish PhD student exchange programmes involving the participating institutions in order to train academic leaders in global TBI research. In the long-term, this will lead to the establishment of networks of research-competent clinicians & networks of trial-competent centres. Please see diagram for delivery targets

Lay abstract: According to the WHO, more than 5 million people die every year (14,000 every day) as a result of trauma, accounting for 9% of the world’s deaths. Trauma also results in millions of non-fatal injuries leading to life-long disability. Of all the types of injuries, those to the brain are the most likely to result in death or permanent disability (1). About 90% of injury-related deaths occur in low and middle income (LMIC) countries. The WHO recognises that “improving the organization, planning and access to trauma care systems, including prehospital and hospital-based care, can help reduce the effects of injuries” (1). In addition, it has called for an increased focus on systems thinking for strengthening health systems in LMICs (2). We have made considerable progress in the treatment of traumatic brain injury (TBI) in the UK and other high income countries (HICs) and it now essential that we translate this to LMICs. The NIHR Global Health Research Group on Neurotrauma is working closely with partners in Colombia, Ethiopia, India, Indonesia, Malaysia, Myanmar, Nigeria, Pakistan, South Africa, Tanzania and Zambia with the aim of improving the care of patients with traumatic brain injury (TBI). We work along 4 themes to the project: i. THEME 1 – MAPPING TBI CARE. We aim to define the current landscape of TBI care in LMICs (provision of pre-hospital care, acute hospital care and post-acute care). We will map resources and establish neurotrauma registries of patient demography, treatment and outcome. ii. THEME 2 – UNDERSTANDING TBI CARE. We are using a systems engineering approach to develop an in-depth understanding of the challenges associated with improving TBI care in terms of frameworks, stakeholders and critical issues. iii. THEME 3 – GENERATING AND IMPLEMENTING INNOVATION IN TBI. Following data collection and modelling from themes 1 and 2, we will implement strategies to refine the TBI management pathways and apply novel approaches tailored to the LMICs. These will be prioritised based on the analysis undertaken in Themes 1 & 2. However, following discussion with LMIC partners we have already nominated four exemplar projects. These will include improved methods of investigation (early detection of blood clots, measurement of brain pressure and swelling), treatment (including refinements in surgery) and outcome data collection (long-term follow-up by SMS, smartphone). iv. THEME 4 – MEASURING AND NURTURING RESEARCH CAPACITY. We will determine the types of research output from LMICs and resources available for research, and nurture capacity by various mechanisms including research methods courses in partnership with the BMJ (Research to Publication programme). The 3-year project will create a platform that will attract further funding for pursuing a long-term (15-year) global neurotrauma programme. The Group comprises health care professionals from high, middle and low income countries, partner organisations (including the World Federation of Neurological Societies) and service user representation including charities. The NIHR Global Health Research Group on Neurotrauma’s goal is to increase the understanding of the challenges around the management of TBI in LMICs and to implement changes in practice to save lives, reduce disability and improve quality of life for patients and their families.

Research activity codes: 8.5 RESOURCES AND INFRASTRUCTURE (HEALTH SERVICES)
Health categories: INJURIES AND ACCIDENTS