As Professor of Primary Care in the Nuffield Department of Primary Care Health Sciences at the University of Oxford, UK, and a practising general practitioner in south Wales, Chris Butler has a bird's eye view of the potential impact of primary care research on clinical practice. Unsurprisingly, COVID-19 research is a priority, with Butler co-leading the PRINCIPLE trial to try and identify treatments for the alleviation of COVID-19 symptoms in community settings. “I am hopeful that our innovations in research methods will identify effective early treatment for the disease”, he says.
The PRINCIPLE trial uses a platform, response-adaptive design that builds on the approach used by Butler and colleagues in an EU-funded trial that investigated the effect of oseltamivir for seasonal influenza. It is pragmatic and open label, “mirroring the reality of primary care. Crucially, this kind of trial design relies on Bayesian statistics, and interim analyses can efficiently identify success, futility, or the need for more data for treatments as the trial progresses”, he explains. The trial has so far recruited about 4500 participants, and is currently investigating the efficacy of the inhaled corticosteroid budesonide and the anti-inflammatory colchicine. Results of the arm that investigated azithromycin for community treatment of suspected COVID-19 in people at increased risk of an adverse clinical course in the UK are published in The Lancet and show azithromycin is not a sufficiently effective treatment to justify its routine use for COVID-19 treatment.
His career began in South Africa. After an undergraduate degree in English literature from Rhodes University, Butler studied medicine at the University of Cape Town (UCT). “Appreciating the importance of setting up the research question in a clear, intriguing way, how evidence is gathered, and communicating what it all means, where every word has to count, has been invaluable in the way I have approached my clinical research journey”, he says. Reflecting on his time at medical school, Butler recalls: “It was the early 1980s, the appalling era of apartheid, where we had to deal with a lot of trauma and infectious disease medicine, although the clinical experience and teaching at UCT were outstanding”. Initially working in paediatrics, he left South Africa to avoid compulsory military service. “I was told that if I didn't present myself at a specified military base, I would be arrested.” Butler went to Canada, working as a family doctor in rural Saskatchewan for 3 months in early 1989, the moment he recalls as “defining my future career in primary care medicine”.
Butler was drawn back to South Africa briefly to work in internal medicine at the Cecilia Makiwane Hospital in the township of Mdantsane, near East London, where he witnessed the power of antibiotics. “Patients often close to death would literally get up and walk after treatment”, he recalls. He moved to the UK in 1990, spending a year working in psychiatry, before completing general practice training. At the University of Wales College of Medicine in Cardiff, Butler found an ideal professional home, where he could combine general practice with primary care research. “Cardiff in the early 1990s was the place to be if you were interested in the emerging field of academic general practice”, he says.
Butler broadened his research and academic credentials back in Canada around the turn of the millennium, studying clinical epidemiology at the University of Toronto; later, as Associate Professor at McMaster University in Hamilton, he combined academic primary care research with family medicine practice, before returning to the UK in 2002 and becoming Professor of Primary Care at Cardiff University. “Opportunities for primary care research at that time were generally small scale and local, but far-sighted EU funding opened up Europe-wide collaborations for large-scale, international, but locally relevant studies, especially in the areas of greatest interest to me, such as in the use of antibiotics in respiratory care”, he says.
In 2013, Butler joined the University of Oxford's Nuffield Department of Primary Care Health Sciences. Since 2015, he has been Clinical Director of the university's Primary Care Clinical Trials Unit, which oversees the PRINCIPLE trial. “It is the UK's only dedicated primary care trials unit. In normal circumstances, our team of 80 staff would be working on around 40 research projects across three key themes: infections and acute care; cardiovascular and metabolic diseases; and in health behaviours. It is a remarkable resource for enhancing the evidence base for delivering high-quality primary care in the UK and worldwide”, he says.
Stephen Rollnick, Honorary Distinguished Professor in the School of Medicine at Cardiff University, worked with Butler for more than two decades and comments: “Chris's determination to make a difference through research was evident from our first meeting. His prolific output on common conditions, antibiotic resistance, and improving the consultation reflects an all but unique ability to travel with ease across the fields of biomedicine, clinical care, and public health. Primary care, worldwide, has been the beneficiary”, he says. And while Butler may have spent the latter part of his career focused on primary care research, at heart he remains a clinician. He still works as a general practitioner in the south Wales practice of Mountain Ash that he joined back in 2004. “Being a hands-on clinician connects me with the important clinical questions, creating a synergy with my research mission, and, above all, enables me to lead research that is both useful and achievable within the hurly burly of busy primary care”, he says.