Creating clarity in a time of uncertainty The Nuffield DepartmentEnter of Population Health’s contribution to the COVID-19 response 2020 → “The University of Oxford has responded swiftly and effectively to the COVID-19 pandemic, with colleagues across the Medical Sciences Division delivering major breakthroughs in the research response. NDPH focuses on providing reliable evidence on the causes, treatment and prevention of diseases that affect millions of people across the world. It has drawn on its multi-disciplinary expertise and the strengths of partners within and beyond the University to answer some of the most important research questions and respond at speed to a challenge unlike any other we have experienced.” Professor Sir John Bell, Regius Professor of Medicine, University of Oxford The Nuffield Department of underlying infrastructure, and → Our perinatal team is improving Population Health (NDPH) is uniquely longstanding partnerships to the care and treatment of babies placed to make a major contribution respond to the pandemic. and pregnant women directly and to the response to COVID-19 because indirectly affected by COVID-19. For example, our two registered it covers all aspects of population clinical trials units have longstanding → The Wolfson Laboratory team health and works at scale to provide experience in developing bespoke established the laboratory clarity about the most important research systems and delivering process for the biggest of the questions affecting human health. innovative, streamlined clinical Lighthouse laboratories. Introduction The department delivers randomised trials; we combined this experience → Our ethics expertise made trials, observational studies, ethics, with expertise in emerging viral a critical contribution to the Professor health economics and health infections in the Nuffield Department development and introduction services research, and is supported of Medicine (NDM) to deliver of mobile phone applications. Sir Rory Collins by dedicated laboratory, IT, the first major breakthrough Head of Department communications and administrative in the COVID-19 response. → We are shining a light on the wider staff. NDPH is a key partner in the impacts of COVID-19 for patients The department is working with Big Data Institute (BDI), a cross- with other diseases, such as heart partners in the UK and across department initiative that focuses disease and bowel cancer. the world to help solve the on the analysis of large, complex, problems that are having the This report provides an overview of heterogeneous data sets. greatest impact. For example: the work we have undertaken in 2020 We have built on our track record to support the COVID-19 effort. → In 2020, the RECOVERY trial of success in large-scale and delivered results on four potential global work and capitalised on COVID-19 treatments, changing our multi-disciplinary approach, clinical practice globally. The important questions and our contribution What are the How can What are How can we risk factors diagnostic testing the levels of design effective and effective be delivered infection and containment treatments? effectively? immunity? strategies? What are the How is COVID-19 How can longer term impacting wider we inform effects of SARS- public health and decision-making? CoV-2 infection? services? Testing treatments in the biggest in 2020 randomised trial of COVID-19 therapies 176 3 At the start of the COVID-19 pandemic, hospitals major results in 100 days nobody knew which treatments would be effective. The RECOVERY trial is a large, randomised controlled trial of possible treatments for patients admitted to hospital with COVID-19. 23340 9 participants days to set up The trial is focusing on testing treatments that are already used for other conditions. The trial is led by Professor Peter Horby in NDM 828000 website visitors 15203 items of media coverage which has world-leading expertise in infectious diseases, and by Professor Martin Landray in NDPH which has Diagnostic testing Surveillance Infection control Longer-term effects Wider impacts Public debate pioneered novel approaches to in global practice three times. treatments can be tested through delivering effective and streamlined It showed that two drugs used RECOVERY+, including treatments randomised clinical trials. to treat hospitalised COVID-19 tested in Phase II (smaller) and Phase patients throughout the world, III studies. The team are now preparing Over 23,000 patients were hydroxychloroquine and lopinavir- to deliver RECOVERY internationally, randomised to nine treatment arms, ritonavir, do not improve survival, with new sites being set up in or no additional treatment, in 176 “The UK has done really whilst one drug that was not Indonesia and Nepal. hospital sites across the UK between recommended, dexamethasone, saves March-December 2020. well on the therapeutics The trial is the best performing trial lives. The use of dexamethasone side… largely because anywhere for COVID-19 and is being The trial was set up at unprecedented following the RECOVERY trial of the huge success held up as the way forward for drug speed; it took just nine days from results is estimated to have saved trials. Academics from across the conception to launch. Over 10,000 of the Phase III trials approximately 12,000 lives in the UK world are drawing lessons from the patients were recruited in just two and particularly the and many more worldwide. pioneering design of the trial which months, making it the fastest ever RECOVERY study.” RECOVERY also found that there is minimises the impact on frontline teams recruiting individually randomised no benefit from use of the antibiotic, by integrating the research with clinical controlled trial. The trial is deliberately Sir Patrick Vallance, azithromycin, in patients hospitalised care and making best use of national inclusive: the youngest participant was UK Government Chief with COVID-19. The trial is continuing data sources. less than six months old and the oldest Scientific Adviser to test other treatments, including over 100 years, one-third are women, The trial is also generating wider Regeneron’s antibody cocktail. and one-sixth are of Black, Asian or understanding of the importance Minority Ethnic (BAME) background. Given the success of the Phase III of clinical trials in providing reliable RECOVERY trial, the UK Government evidence, and has been described as a In 100 days, the RECOVERY trial has increased investment so that new ‘beacon of excellence’. provided results enabling change Diagnostic testing Surveillance Infection control Longer-term effects Wider impacts Public debate This innovative approach paved (WHO). Both trials minimised the impact Streamlining the way for other successful trials on frontline staff by using simple online clinical trials designed and delivered by NDPH and enrolment, randomisation and follow- directly informed the design of the up forms, and embedding the research to provide RECOVERY trial and of SOLIDARITY, the in clinical practice. international COVID-19 treatment trial reliable evidence The SOLIDARITY protocol developed led by the World Health Organization “More than a third of trials rapidly by Professor Sir Richard Peto, enabled over 400 hospitals in have been too small to Professor Sir Richard Peto (NDPH) and over 30 countries to randomise provide conclusive answers. Professor Sir Rory Collins pioneered over 11,000 patients (from March- You have to do things at the concept of large simple trials for October 2020) to quickly and scale as RECOVERY and the International Studies of Infarct reliably answer critical questions. SOLIDARITY have done.” Survival (ISIS), a series of randomised The RECOVERY and SOLIDARITY “The SOLIDARITY trial Sir Jeremy Farrar, trials that assessed the effects of trials have demonstrated that provides simplified widely usable treatments on survival hydroxychloroquine, lopinavir (with Director of Wellcome following a heart attack. Around procedures to enable or without) ritonavir, azithromycin, 140,000 patients participated even hospitals that have interferon beta-1a and remdesivir Drawing on their NDPH research, worldwide between 1985 and 1993. been overloaded to have little or no effect on mortality or Professor Peto and Professor To recruit as many participants participate.” other important clinical outcomes. In Hongchao Pan worked closely with as possible, the studies involved June, the RECOVERY trial announced the WHO principal investigator on integrating the trials with clinical Dr Tedros Adhanom that dexamethasone, a low-cost governance and study conduct, and practice, simplifying the recruitment Ghebreyesus, and widely available corticosteroid made a major contribution to analysis, and data entry processes, and using WHO Director-General regimen, saves the lives of those with interpretation and presentation of government records for follow-up. severe COVID-19. SOLIDARITY trial datasets. Diagnostic testing Surveillance Infection control Longer-term effects Wider impacts Public debate on clinical outcomes to COVID-19 Co-development Panel have worked The COVID-19 in Pregnancy study Enabling the researchers, the team, led by Professor closely with the NHS DigiTrials team is investigating the incidence of provision Martin Landray, quickly refocused to ensure that patient and public COVID-19 infection, and answering efforts on linking trial cohorts to NHS feedback has been included in the these critical questions: of outcome data data sources, so that researchers design of