The PANORAMIC study of COVID-19 treatments in primary care: a review and learning exercise

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NIHR Clinical Research Network The PANORAMIC study of COVID-19 treatments in primary care: a review and learning exercise Evans P, Tonner E, Williamson J D, Dolman M, Chambers E, Crawshaw S E and Yu L-M. Study IRAS Number: 1004274 August 2024 Foreword Ever since the start of the COVID-19 pandemic in early 2020, primary care and primary care research have been undergoing unprecedented and rapid change. The Platform Adaptive trial of NOvel antiviRals for eArly treatMent of COVID-19 In the Community (PANORAMIC), the fastest recruiting and the largest trial of a therapeutic agent for COVID-19 ever in primary care, has just closed to recruitment. It is therefore opportune to review and reflect on the lessons learned from the delivery of this major UK-wide trial that is informing care and guidelines in the NHS and world-wide. The many contributors from different professional backgrounds and the wide range of topics highlighted in this report illustrate the collaborative nature of research, which was demonstrated powerfully during the pandemic. When, despite adverse conditions in the public, professional and private lives of health and research professionals, colleagues stood up to deliver urgent public health studies, and PANORAMIC, against the odds. In many cases going ‘above and beyond’. This report is therefore a collection of contributions from all concerned in the design and delivery of the trial. However, it is primarily written from the perspective of research delivery through the National Institute of Health and Care Research Clinical Research Network (NIHR CRN) in England and the analogous networks in Wales, Scotland and Northern Ireland. It includes reflections about the delivery of the study across the four UK nations, talking in detail to those involved, and is therefore probably the first of its kind. It includes considerations of both the successes but also the challenges of conducting a study such as this in the pandemic environment. It inevitably touches on aspects of research design, but is predominantly about research delivery. It is hoped that readers of this report, both now and in the future, will be able to reflect on our collective experience of primary care research in the COVID-19 pandemic and that this report will have a positive influence on the design and delivery of future studies. The main thrust of this report is to inform future studies conducted in primary care, both within and without a pandemic. But the broad principles derived from the delivery of this trial will apply to other studies in primary care, secondary care and across the health and social care research ecosystem. I’m grateful to the NIHR CRN team and to the study team for constructing this report over the last year and strongly commend it to you. Professor Philip Evans, Deputy Medical Director NIHR CRN, and NIHR CRN Clinical Link for PANORAMIC Executive Summary The ‘Platform Adaptive trial of NOvel antiviRals for eArly treatMent of COVID-19 In the Community’ or PANORAMIC study, led by Professor Chris Butler and colleagues at the University of Oxford, was one of the flagship primary care trials in the COVID-19 pandemic. Its sister trial, PRINCIPLE, tested the clinical effectiveness of repurposed drugs in patients with mild to moderate COVID-19 in the community. While PANORAMIC evaluated the clinical and cost-effectiveness of novel oral antivirals, i.e. molnupiravir (Lagevrio) and nirmatrelvir-ritonavir (Paxlovid) in a platform trial delivered in primary care. The trial was delivered in collaboration with the NIHR Clinical Research Network (CRN) in England and partner networks across Northern Ireland, Scotland and Wales. The NIHR funds, enables and delivers world-leading health and social care research that improves people's health and wellbeing and promotes economic growth. The NIHR Clinical Research Network (CRN) is a national research network in England that coordinates and supports the delivery of high-quality clinical research across health and social care. As of April 2024 the NIHR Clinical Research Network transitioned into the NIHR Research Delivery Network (RDN), and in October 2024 the LCRNs will be transitioned into the new Regional Research Delivery Networks (RRDNs). PANORAMIC is to our knowledge the largest randomised trial of COVID-19 therapeutics in primary care in the world. At the height of recruitment in early 2022, it was also the fastest-ever recruiting primary care Clinical Trial of an Investigational Medicinal Product (CTIMP) delivered through the NIHR CRN. PANORAMIC recruited just under 30,000 participants into a randomised platform trial using innovative methods of recruitment that had not previously been tested in a primary care setting. This was made possible by the four nation UK-wide approach to the delivery of the trial and digitally supported delivery and outcome assessment. Given the unique and historic nature of the trial, and the many innovations that were rapidly implemented, some more successful than others, it is essential that we reflect and learn from its remarkable achievements. The NIHR CRN team led this learning work along with members of the study team, and convened a series of meetings specifically asking key stakeholders for their reflections and learnings. These covered many diverse aspects of the delivery of such a complex trial drawing out important innovations but also key challenges. This report also forms an output of the NIHR CRN Primary care Research Programme. The details of the delivery of this trial are well documented in this report, both for clarification of precise delivery methods but also as an historical record of what is potentially an undertaking of global significance. There has been international interest in the delivery of this trial from other countries, some of whom were unable to adequately deliver COVID-19 research in a primary care setting. This report, therefore, will be of interest both to international academics but also to commercial trial sponsors beyond the UK. The trial itself has significant implications for the future delivery of both pandemic and non-pandemic primary care studies, and this report outlines the collective learnings from key stakeholders across all four nations. This report also includes wide-ranging recommendations to further enhance the delivery of primary care research trials, both in a pandemic but also in a non-pandemic situation and has demonstrated the potential impact of this large decentralised and remotely delivered trial to clinical research in the UK and beyond. Background to the PANORAMIC Trial At the onset of the COVID-19 pandemic in 2020, caused by the SARS-CoV-2 virus, the Department of Health and Social Care (DHSC) instituted the Urgent Public Health (UPH) Group in response to the urgent need for research in a pandemic setting. The UPH Group was convened by the National Institute for Health and Care Research (NIHR) Clinical Research Network (CRN), was chaired by the NIHR CRN Medical Director, and aimed to prioritise COVID-19 research studies to be delivered through the NIHR CRN. As part of the initial COVID-19 pandemic response, it was recognised that there was a need for primary care research in less severely ill patients in the community, and to evaluate both diagnostics and therapeutics in a community setting. In view of this, the RAPTOR study (PI Richard Hobbs) was designed to test new diagnostics in this setting, and opened to recruitment in October 2020. To test therapeutics in a primary care setting the PRINCIPLE study was set up and opened to recruitment in April 2020, led by CIs Professors Chris Butler and Richard Hobbs with colleagues from the Primary Care Clinical Trials Unit (CTU), Nuffield Department of Primary Care Health Sciences, University of Oxford. PRINCIPLE studied repurposed medications for COVID-19 in patients who had mild to moderate COVID-19 in the community and who had not been admitted to hospital and became one of seven pub

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