The PRINCIPLE Trial developed novel and highly effective approaches for conducting robust and rapid clinical trial evaluations among people who represent the diversity of the UK population. Its findings that inhaled budesonide, which is widely available, safe and relatively inexpensive, is effective at reducing the severity of symptoms and speeding the recovery of COVID-19 in patients over 50 in the community was a major advance in the UK and worldwide. The importance of PRINCIPLE was recognised when it was highly commended in the HDR UK Impact of the Year Award.
Finding scalable, safe and effective treatments for COVID-19 patients in the community who are older and with pre-existing conditions, was a high national priority. This section of the population is amongst the most prone to infection and serious complications – leading to increased risk of hospitalisation and death. Reducing the severity of their illness at an early stage would not only save lives but relieve pressure on hospitals.
Carrying out the work would require the rapid assembling of a skilled team and the recruitment of a large cohort of appropriate volunteers that reflected the UK’s morbidities, ethnic diversity, gender balance, deprivation level and demography. It would also be essential to have access to, and make secure use of, large amounts of patient data.
The PRINCIPLE Trial, co-led by Oxford University Nuffield Department or Primary Care Health Sciences Professor of Primary Care, Chris Butler, collaborated closely with organisations including HDR UK and NHS Digital to provide a solution. This involved pioneering ways of contacting patients who had positive test results – for example through social media, via1,000 participating GP surgeries and a range of other NHS bodies – to ask if they would like to participate. Prof. Butler said those contacted were “almost universally” happy to take part.
Access to Summary Care records allowed the team to more quickly identify whether a drug they were testing was safe for a particular patient. Drugs were sent to patients’ homes, rather than them going to a clinical site. The trial was designed to allow more participants to receive treatments that appeared to have greater benefit.
Impact and outcomes
Prof. Butler says that: “connecting directly with a person unwell with the condition was a step-change in our trial delivery, it’s a huge innovation internationally. The result was a truly UK-wide, democratic trial, where we now can take research directly to the patient.”
The finding that inhaled budesonide was an effective treatment has brought benefits worldwide. Equally, the findings that two commonly prescribed drugs, azithromycin and doxycycline, did not work helped avoid ineffective treatment and will reduce unnecessary antibiotic use and antibiotic resistance.
PRINCIPLE has demonstrated new and effective ways of designing and conducting large-scale trials that can yield results at great speed. The infrastructure and expertise that is now in place can potentially be applied to other infectious illnesses such as flu, and to future pandemics.
Prof. Butler can be contacted at email@example.com
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