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© 2022 HDR UK2022 “The treatment for COVID-19 today is better than the treatment was a year ago or 2 years ago and it's only because patients took part in the clinical trial”, says Martin Landray about the RECOVERY trial, the largest randomised trial of COVID-19 treatments, which he co-leads. Landray is Professor of Medicine and Epidemiology at the Nuffield Department of Population Health, Oxford University, UK, and Chief Executive Officer of Protas, a not-for-profit trials organisation. RECOVERY is built into usual NHS practice and, since its launch in 2020, it has shown multiple anti-inflammatory drugs can be used in combination to lower COVID-19 mortality. Writing the protocol with co-chief investigator Peter Horby, Landray recalls: “We knew it had to be straightforward for the patients, who were going to be breathless, really sick, often elderly, always alone” and “practical for the doctors and nurses who were going to be in PPE and be completely overwhelmed in terms of time and emotional stress.” They also knew they could link to routine NHS data to “get vast amounts of useful information”. RECOVERY is now in “an era of looking at antiviral treatments both individually and in combination. As we’ve seen in HIV and many other infections…it's often necessary to use combinations, sometimes to produce greater efficacy and sometimes to guard against resistance”, he says. The trial is also being extended globally for science and public health reasons and “for capacity building reasons, because we need to be able to take the lessons of what's worked well in the NHS and help deliver that in other parts of the world”.

ce greater efficacy and sometimes to guard against resistance”, he says. The trial is also being extended globally for science and public health reasons and “for capacity building reasons, because we need to be able to take the lessons of what's worked well in the NHS and help deliver that in other parts of the world”. Prescribing and the power of large clinical trials to change practice and save lives influenced Landray early on. While studying medicine at Birmingham University, UK, he was inspired by clinical pharmacology lecturer Martin Kendall and by the ISIS-2 trial, led by Rory Collins and Richard Peto, which “completely changed practice for cardiology almost overnight”, he says. In 1996, he became a lecturer in Clinical Pharmacology and Therapeutics at Birmingham University and completed a PhD on the cardiovascular complications of kidney disease. After joining Oxford University's Clinical Trials Service Unit (CTSU) in 2000 as Clinical Research Fellow, he worked with Colin Baigent on a large trial of cholesterol lowering treatments to prevent cardiovascular disease (CVD) in people with kidney disease. There, he learned “the fundamentals of doing trials” first-hand from Collins and Peto.

ersity's Clinical Trials Service Unit (CTSU) in 2000 as Clinical Research Fellow, he worked with Colin Baigent on a large trial of cholesterol lowering treatments to prevent cardiovascular disease (CVD) in people with kidney disease. There, he learned “the fundamentals of doing trials” first-hand from Collins and Peto. At CTSU, he has helped design and run large randomised controlled trials (RCTs), mainly on cholesterol lowering treatments in CVD and kidney disease, working with Jane Armitage, Louise Bowman, and Richard Haynes. By randomisation and going to scale, you can “actually get the science right”, he says. An example is niacin, which had been recommended to lower cholesterol and reduce heart disease risk. “We did a trial of niacin in 25 000 patients and found that it didn’t have a meaningful impact on CVD; worse, it increased the risk of being admitted to hospital with serious bleeding or serious infection—hazards that had not been recognised despite 50 years of clinical use…It's not used anymore.”

e heart disease risk. “We did a trial of niacin in 25 000 patients and found that it didn’t have a meaningful impact on CVD; worse, it increased the risk of being admitted to hospital with serious bleeding or serious infection—hazards that had not been recognised despite 50 years of clinical use…It's not used anymore.” Landray, who still sees patients in a weekly cardiology clinic, wants to share successful trial methods. As Director of NHS DigiTrials from 2019 to 2021, he worked with NHS Digital to develop the approach used by his team of harnessing data from hospital records to invite and recruit large numbers of people into trials. Improving the regulations and guidance for trials is a key part of his work. “These are often framed as so-called Good Clinical Practice guidelines…The reality is they don’t focus on the principles of what makes a good randomised trial, instead focusing on what's easy to check. Too often they hinder the use of new approaches that would enhance the experience for trial participants, generate more informative results for future clinical decision making, and reduce the costs of drug development”, he comments. In 2011, his work with many colleagues on the Clinical Trial Transformation Initiative led to recommendations on risk-based monitoring and quality-by-design for trials, resulting in updated guidance from regulators around the world. “In other words, you put the emphasis on the issues that matter to the overall quality of the trial—those that make a material difference to the participants in the trial and the results that will impact the care of future patients”, he says. Since 2019, Landray has led the Good Clinical Trials Collaborative, which has developed guidance to enable better RCTs globally.

that matter to the overall quality of the trial—those that make a material difference to the participants in the trial and the results that will impact the care of future patients”, he says. Since 2019, Landray has led the Good Clinical Trials Collaborative, which has developed guidance to enable better RCTs globally. Janet Woodcock, the US Food and Drug Administration's Principal Deputy Commissioner, commends Landray's focus on the “generation of actionable information” and describes the “early RECOVERY trial result on the usefulness of corticosteroids for hospitalised patients with severe COVID-19” as “a huge step forward”. It is one example of “the approach to clinical evidence generation that he has helped forge…His goal has always been to find out what we should do to improve health outcomes”. At the newly formed Protas, Landray wants to help develop robust trials for common diseases. The aim is to “take the innovation, imagination, and rigour that comes from academia, combine that with the scale and efficiency you can get from business, and partner with the clinicians and patients who have to deal with the consequences of ill health”, he explains. “We have to create not just exemplars; RECOVERY is, methodologically at least, an exemplar, but we have to systematise that. Protas is a way to do that and to allow more good trials to happen.” Because, he says, “We don’t just need more trials; we need more good trials.”