Title: Improving the delivery of randomised controlled trials in surgery in low- and middle-income countries.
Funder: Department of Health and Social Care

Abstract: BACKGROUND When patients in low- and middle-income countries (LMICs) undergo surgery, they are three times more likely to suffer a surgical site infection (SSI) and twice as likely to die than in a high-income country; up to 4-million people per year die following surgery. Perioperative oxygeN therapy and surGical oUtcomes in high-risk abdomiNal surgery (PENGUIN trial) will evaluate whether liberal versus restrictive oxygen therapy given intraoperatively impacts the rate of SSI and death after midline laparotomy. An already-funded, external pilot study will launch in early 2019 to inform the design of the main, phase III trial. The major challenge to study delivery will be following-up patients; a sample size of 10,000 patients is anticipated. AIMS > Research aim: To improve the delivery of future global surgery trials through identifying and evaluating methods to improve follow-up and use these to improve the design of the phase III PENGUIN trial. > Training aim: To develop a skillset in the design and delivery of high-quality pragmatic randomised surgical trials using the training platform of the PENGUIN pilot. WORK PACKAGES (WP) WP1: Could in-hospital outcome assessment replace 30-day follow-up? > Method: Use of existing data to evaluate consistency of in-hospital assessment of SSI and mortality as a surrogate for 30-day follow-up. WP2: Can telephone-based wound assessment replace in-person follow-up at 30-days? > Method: Cognitive debriefing to adapt a patient-reported Wound Healing Questionnaire (WHQ) for use in one middle and one low income country. > Method: Study Within A Trial testing the feasibility and validity of telephone WHQ administration in the detection of SSI. WP3: What methods can be used to optimise completion of follow-up assessments? > Method: Semi-structured interviews to explore barriers to trial retention. > Method: Focus groups to explore incentives to reduce loss to follow-up. WP4: Can I engage LMIC Public and Patient Involvement in Research (PPIR) to enhance outcome assessment? > Method: Systematic review of published PPIR toolkits and mapping of components. > Method: Delphi consensus process to prioritise components and content for an LMIC PPIR toolkit. > Method: Use of the PPIR toolkit to determine culturally-specific methods for telephone-based mortality assessment after discharge. PATIENT AND PUBLIC REPRESENTATION Patients have been built into the heart of this proposal. Working with established UK patient representatives I have trained and embedded a Rwandan patient into my research design, and have formed an international surgical patient forum. Members of this group will be involved in all aspects of study management and design of a PPIR toolkit to support researchers working across resource-limited settings. IMPACT My fellowship aims to improve the efficiency and quality of randomised trials in global surgery, allowing greater benefit for a greater number of patients. My research will create generalisable methods for follow-up within future trials both internationally and within the NHS. I will disseminate my findings to researchers across low- and high-income settings through publication, conferences, online training modules, social media, and across collaborative networks. This will position me to leverage funding to lead international trials in my postdoctoral career.

Lay abstract: BACKGROUND The importance of research in global surgery When patients in low- and middle-income countries (LMICs) undergo surgery, they have a higher risk of a poor outcome, being twice as likely to experience a wound infection and three times more likely to die than in a high-income country. Training of new 'Global Surgery' research leaders is needed, working with surgeons and anaesthetists around the world to improve health outcomes through practice-changing research. Patients undergoing surgery in the NHS stand to benefit through shared learning with other health services. Learning platform The NIHR Unit on Global Surgery is delivering international trials that will include thousands of patients undergoing surgery over the next decade. Perioperative oxygeN therapy and surGical oUtcomes in high risk abdomiNal surgery (PENGUIN) will examine whether we can test high versus low dose of oxygen in patients undergoing general anaesthesia (a 'pilot' trial). The main trial plans to include 10,000 patients. Following up these patients for research assessment (seeing them again in outpatient clinic after surgery) poses a major challenge; waiting times for clinics are already long and patients often live a distance from the hospital, incurring travel costs and loss of earnings. AIMS This research will test ways of improving research follow-up that be used within the main PENGUIN trial. From this fellowship, I hope to learn the skills to design and deliver trials that improve care for patients undergoing surgery around the world. OBJECTIVES 1. Determine whether recording a wound infection or death before a patient leaves hospital could be used for research instead of following them up after discharge. 2. Test whether a telephone questionnaire could be used to assess a patient's wound and how accurate this assessment is. 3. Explore why patients choose to leave studies and what methods could encourage people to stay involved in research. 4. Explore whether current ways of involving patients with research design can be adapted for resource limited settings. WORK PACKAGES (WP) WP1. Using existing data, I will explore using statistical techniques whether testing outcomes in-hospital could avoid the need for follow-up after discharge. WP2. Within a pilot trial (PENGUIN), I will test a patient questionnaire performed over the telephone to see how it compares to assessment in-person by a trained surgeon. WP3. I will interview patients, doctors and research staff about the reasons that patients leave studies and review these discussions to find common themes. I will explore ways of encouraging people living in low-income countries to stay involved in research. WP4. I will assess 'toolkits' that support patient involvement in research and adapt these for patients in low-income countries. I will use the adapted toolkit to determine the best way to telephone patients and their families to check whether they have survived following surgery. PATIENT & PUBLIC INVOLVEMENT Patients have been directly involved in designing this research. Worries about research follow-up have grown from discussion with our UK and Rwandan representatives (Azmina and Emmy). Working with Emmy, I have set up a discussion forum for surgical patients across several LMICs. This group will help me to design, carry out and interpret my research. A 'toolkit' for international patient involvement will be made available to other researchers, learning from these experiences. IMPACT & DISSEMINATION My research will improve the way that we design future global surgical trials. Ways of making follow-up more efficient and accurate will benefit patients, researchers, and hospitals both in low resource countries and within the NHS. This fellowship will train me to lead future international research, and improve a large trial that will answer an important question about oxygen therapy during surgery.

Research activity codes: 6.4 SURGERY
Health categories: GENERIC HEALTH RELEVANCE