Title: NIHR Global Health Research Unit on Global Surgery, University of Birmingham
Funder: Department of Health and Social Care

Abstract: BACKGROUND Existing Network (Fig 1): GlobalSurg (www.globalsurg.org, Twitter: @globalsurg) is a collaboration of frontline surgeons, spanning 230 hospitals from 43 LMIC countries, working to address the unmet need for research in global surgery. It was founded in 2013, joining surgeons from LMICs with researchers from the Universities of Birmingham (UoB), Edinburgh (UoE) and Warwick (UoW). Together, we are applying to form a Global Surgery Research Unit. GlobalSurg has established a secure, worldwide data collection platform and completed two prospective cohort studies including 27,000 patients. Our first paper on emergency abdominal surgery [1] is ranked in the top 1% of Altmetric research outputs. In 2016, GlobalSurg prioritised a research question (surgical site infection) and finalised a trial protocol (RCT-1) to be delivered through five GlobalSurg research ‘Hubs’ reaching into 40 GlobalSurg ‘Spoke’ research hospitals. Institutional Strategies: The strategies of GlobalSurg and the UK consortium are aligned with those of the United Nation’s Sustainable Development Goals and the Government’s UK Aid manifesto, detailed in our ODA compliance statement. UoB, UoE and UoW have high-level strategic objectives focused around partnerships and international research impact, bringing complementary expertise, detailed in Team expertise and Research capacity. VISION The Global Surgery Research Unit will create a sustainable platform of frontline clinicians, prioritising and delivering research that will challenge and change surgical care relevant to patients in low and middle income countries (LMICs). The Unit will build on the success of the pre-operative WHO Surgical Safety Checklist [2], by evaluating and standardising intra-operative practice. Our pre-application phase has identified prevention of abdominal wound infection as our first research priority. Results from clinical research will be transformed into guidelines and cost-effective policy through our Global Surgery Policy Consortium (GSPC, see Collaborations), which will work across our 230-centre network to deliver sustainable global change. CAPACITY BUILDING (Fig 2) Five core-funded regional Hubs (West Africa, Southern Africa, Central and East Africa, Central America, South Asia) will support 40 surgeon-investigator “Spokes”. These represent central and district hospitals in LMICs, and will recruit into randomised trials. Hubs have local senior surgeon-leaders, who have secured high-level administrative support at each of their institutions (Supporting Letters). We have finalised the protocol for RCT-1 (see Additional Information), which will be piloted in the Hubs (Yr1) and then rolled out into a full trial to develop the Spoke infrastructure. This will deliver evidence to change practice within the funding envelope, and enable further interventional trials across the platform. With the first three Hubs, we will create a toolkit to streamline site set up. Our surgeon-investigators are already establishing ethical approval processes, research contracts, and Good Clinical Practice certification. Bespoke training packages will move Hub staff towards autonomy within the 4yr funding envelope. SCIENTIFIC STRATEGY Strategy is centred around Prioritisation Cycles (PCs, Fig 3). These will be initiated through GlobalSurg and led by LMIC Hubs at an annual workshop and delivered through 4 stages: 1. Workshops, 1-week long, including bespoke workshop training 2. Information Gathering, including feasibility studies 3. Evidence Generation, through trials, cohort studies, service delivery evaluation 4. Sustainability and Output, generating competitive external funding applications, and influencing global clinical policy 1. WORKSHOPS Annual Workshops will be hosted by Hubs, and will use two functions to drive the PCs. Firstly, to select new research priorities (as shortlisted by Hubs/Spokes). Secondly, to share experience in set up and training, Spoke development and running trials. Each host will invite its Spoke hospitals, other Hub leads, UK management, and GSPC representation (below). Responsiveness: The PCs allow the network to address emerging research priorities not only across the network, but also as set by the NIHR, WHO, or Department of Health. Future examples include: i. Topics of unmet clinical need: standardising staging and surgical treatment of cancer appropriate to low income settings; safety and effectiveness of low cost devices (e.g. sterilised mosquito nets for hernia repair [3]). ii. Health services delivery research: Surgical outcomes depend on service innovations (e.g. surgical checklist) and training, as well as clinical innovations. When service delivery/training topics are prioritised within Workshops, we will engage with cognate disciplines (e.g. psychology/education) in developing protocols for leverage funding. 2. INFORMATION GATHERING Data Science: Our secure online data collection and analysis platform has been refined through the GlobalSurg-1/-2 studies, exploiting expertise in UoE and the Farr Institute. The data phases of the PCs will allow training of Hubs members in data science, with projects developing mobile technology applications, seeking global scale-up of cloud-based infrastructure under Hub control. High quality data will be central to PCs, measuring outcomes in both feasibility and interventional studies. The cohort studies will be flexible to the needs of PCs, in some cases directly answering prioritised research questions (e.g. epidemiology of surgical diseases [4]). 3. EVIDENCE GENERATION Trials: We aspire to launch one RCT annually, designed with feasibility data from a prioritised topic. Trial design will be flexible to match the research question. Our first PC has created a protocol for RCT-1 (See Additional Information), during which Hubs will expand the inclusion criteria to include gynaecological surgery and caesarean section, efficiently exploiting the Hub infrastructure. Future research topics will efficiently work across specialties, thereby widening impact and reach. Within this coordinated framework, Hubs will develop feasibility studies and roll out interventional trials to Spokes, whilst retaining flexibility to run additional studies (e.g. as part of responsiveness). Health Economics: We will embed health economics at the design, execution and analysis stages of surgical trials with a focus on feasible and pragmatic objectives. We will ensure appropriate and essential resource identification and measurement, and the application of locally relevant unit costs. Appropriate outcome measurement will be undertaken and models developed to facilitate generalising results to other settings where costs, resources and outcomes may differ. Sensitivity analysis will test robustness of results to changes in assumptions or setting; scenario analysis can explore the impact of alternative hypotheses not directly tested, but with implications for local policy makers. Patient and Public Involvement (PPI, Fig 4): We have started training a Rwandan patient representative, who with our paired UK patient representative (co-applicants) contributed to the first PC and design of RCT-1. Our UK representative is developing a PPI network across Europe with the European Society of Coloproctology, crossing languages and cultures. This experience will be exploited across our global surgery platform. The research aims are to blend PPI with the PC to: - Create a simple, flexible toolkit for identifying and implementing PPI for other countries, with customisable options from a global bundle. - Enable each Hub to integrate trained PPI into their PCs through their Workshop. - Use this PPI network to develop culturally sensitive patient information/consent material. - Identify simple Patient Reported Outcome Measures related to surgery, translate into local languages, explore suitability for LMICs, and test in hospital and community settings. 4. SUSTAINABILITY + OUTPUTS This 4yr funding will enable GlobalSurg leadership to be transferred from UK HEIs into a sustainable LMIC led structure. We will create long-term sustainability through: >A renewable funding strategy: Externally competitive research applications from PCs, strengthened by feasibility work in Hubs. >Research Training Plan (Fig 5), creating (i) a network of emerging research savvy clinicians across LMIC Hubs and Spokes, including LMIC surgeon-leaders; (ii) the next generation of LMIC and UK-based Global Surgery leaders. >Wider infrastructure beyond the Unit. Our partnerships will develop deeper links with: (i) Global Surgery Policy Consortium (GSPC, see Collaborations and Partnerships) including National Surgical Associations, NGOs, and KPMG to influence guidelines, policy, expansion, and longer-term funding; (ii) Industry partners, to support supply chains and testing of emerging technologies. KEY OBJECTIVES AND OUTPUTS (Fig 2) Short-term (yr1-2) - Set-up and train 3 Hubs - Recruit first patients into RCT-1 by month 6 (funding through Hub set-up) - Deliver 2 annual workshops (rotating through hubs) - Prioritise 2nd round of research topics - Launch 2 feasibility studies encompassing the second observational cohort study - Launch RCT 2 pilot - 40 GCP-trained surgeon-investigators, 5 Hub-UK fellowships initiated - Design and setup PPI toolkit - Establish health economic analysis platform Medium-term (yr3-4) These represent the ‘minimum ambition’, as funding applications from feasibility work will be generated: - Complete set-up of 2 further Hubs (five total) - Complete recruitment of RCT-1 - Complete RCT-2 pilot; external funding for main trial - Complete 3 feasibility studies (Unit-funded) - Develop at least 1 service research application - 80 GCP-trained surgeon-investigators, 15 Hub-UK fellowships initiated - Complete and report PPI projects - Prioritise 3rd topic and develop protocol(RCT-3)

Lay abstract: NEED FOR RESEARCH: Surgery remains under-prioritised in low and middle countries (LMICs) in terms of provision, training, research, and quality. Where surgery is available , patients are three times more likely to die after operation than in high-income countries. A sustainable global research platform can start addressing these challenges. WORK TO DATE: We formed GlobalSurg (www.globalsurg.org) in 2013 and have connected 230 hospitals in 43 LMICs, and have completed two worldwide studies, documenting outcomes in 27,000 surgery patients. We now wish to empower our international surgical colleagues to lead practice-developing research projects. At our first prioritisation meeting in Birmingham (November 2016), 22 surgeons from 16 LMICs attended to finalise their protocol for a first randomised trial, aimed at reducing wound infection after abdominal surgery. OBJECTIVES: To create a sustainable platform where patients and surgeons from LMICs can identify priority areas, perform studies to find solutions, and find ways to bring these solutions to their patients. This will initially focus on surgery of the abdomen, but will cross over into other neglected areas of surgery, including women’s health and cancer treatment, within the 4yr period. CAPACITY BUILDING: At the heart of our Unit will be five research ‘Hubs’, across three continents: West Africa, Southern Africa, Central and East Africa, Central America, South Asia. Three UK Universities (Birmingham, Edinburgh, Warwick) will provide support for network development initially in a leadership role, but shifting activity and ownership to LMIC partners through the 4yrs. The Hubs will be provided with training and funding to build local support structures and reach into surrounding rural hospitals (‘Spokes’). A bespoke training programme of Hub-UK exchanges and online modules will train clinical staff to perform high quality research, building future leaders. This will create a network of 5 research Hubs with at least 40 research ‘Spokes’, that will generate clinical evidence and create guidance for 230 engaged LMIC network centres and beyond. RESEARCH PLAN: We have created a ‘Prioritisation ‘Cycle’ where LMIC surgeons can identify a research priority and deliver a study to develop practice. We have already started a Cycle which has finalised the protocol for our first randomised research trial, aimed at reducing wound infections after surgery. This trial will strengthen the network and also generate evidence to change international policy within the funding envelope. Applying the Cycle annually will enable sustainable development. OUTPUTS AND SUSTAINABILITY: We will create sustainability beyond this 4yrs by (i) generating competitive external funding applications, (ii) training the next generation of Global Surgery researchers, and (iii) working with national surgical associations and governments to develop guidance suitable for constrained budgets. BENEFITS TO PATIENTS: Our model is patient-facing with direct patient-benefit at its core. It allows patients, surgeons, and health organisations to identify and address pressing LMIC needs and to generate evidence-based, cost-effective solutions. Patient and Public Involvement is central to priority setting but is virtually non-existent in many LMIC settings; we have trained and included Rwanda’s first surgical patient representative in this proposal. We will expand this experience to create a flexible PPI toolkit for others to use.

Research activity codes: 8.5 RESOURCES AND INFRASTRUCTURE (HEALTH SERVICES)
Health categories: GENERIC HEALTH RELEVANCE