Tim Williams, Head of Interventional Research for the Clinical Practice Research Datalink (CPRD) at the Medicines and Healthcare products Regulatory Agency (MHRA), discusses how pragmatic data-enabled, decentralised trials like DaRe2THINK are bringing in a new age of more efficient and secure clinical trial recruitment so patients can benefit from cutting-edge treatments when they need them most.
Clinical trials are an essential step in the development and testing of new treatments, medical devices and diagnostic techniques, evaluating both their safety and effectiveness/performance under real-world conditions.
For many people with rare diseases, especially those with no current cures, participating in clinical trials provides a potentially life-changing chance to receive experimental therapies they otherwise would not have access to.
Decentralised clinical trials are changing the way this research is carried out, using digital tools to minimise the impact of trials on patients’ day to day lives while maintaining high-quality data collection.
However, like any clinical trial, they can be difficult to recruit for, time-consuming for front-line staff to identify eligible participants, and can miss large swathes of the population. Not every person will be eligible to participate in every trial, with factors as diverse as age and prior treatments all having an impact on suitability.
Recruitment is usually a long, complex and expensive process, often failing to represent a truly diverse population and can take a long time to reach recruitment targets. For those patients who rely on clinical trials for new treatments, this delay can take time they simply do not have.
So how can we use data to speed up the recruitment process in a way that protects patients while supporting the development of new life-saving treatments? Can data improve the diversity of those recruited so that cohorts are more reflective of the population affected? And can digital tools reduce the impact of participation on patients without affecting the quality of the research?
Through our CPRD data services, we’ve been working with partners across the health and care sector to answer these questions.
With academics at the University of Birmingham, we’ve put an ambitious and innovative data-driven approach to clinical trial recruitment into practice in the DaRe2THINK NHS-embedded randomised trial.
DaRe2THINK uses data collected from Electronic Health Records in the NHS to facilitate recruitment and mortality data from the Office for National Statistics to track health outcomes for patients with a condition called atrial fibrillation (an irregular heartbeat).
Atrial fibrillation has been shown to increase the chance of blood clots, strokes and memory issues, and so this trial looks at whether giving patients under 75 a new class of blood-thinning drugs earlier will reduce their chances of strokes or dementia in later life.
This will answer a key question for 21st century healthcare relating to an increasingly common condition with a considerable burden on patient quality of life, the health of the nation and our economy.
Recruitment is blind to the CPRD so patient privacy is maintained. Our CPRD Aurum database covers the healthcare records of 13 million patients across a network of over 1,300 GPs and primary care centres. An algorithm automatically filters the records on GP systems to leave only those that match eligibility criteria, without anyone at CPRD or the academic researchers ever seeing who they are.
These records are given a flag that only your GP can see, who can then review, make sure that you are eligible and reach out to see if you would like to take part. At this point you can consent to share your data with the researchers. This runs weekly, to identify newly eligible patients on an ongoing basis, so recruitment isn’t limited to people available at the start of the trial.
“I am delighted that the pre-screening is done for us. Trawling through hundreds of patient records to find patients that are not eligible is the bane of my research role. DaRe2THINK should be the model for all research going forward.”
Dr Susanna Cary, General Practitioner, Pioneer Medical Group.
Using this recruitment method, researchers can target and reach a far larger and more diverse pool of patients who may not previously have been able to access relevant trials.
In fully decentralised trials, participant recruitment, delivery and administration of study medication, and acquisition of trial outcome data all proceed without involving in-person contact between the study team and the participant.
The DaRe2THINK trial fits this model and has been configured using a no-contact approach, with digital enrolment, remote e-consent and ‘no-visit’ follow-ups using regular patient-reported results. Patients haven’t had to set foot in a clinical trial centre and have been able to participate in their own time.
This patient-centric approach was developed by the University of Birmingham in close collaboration with patients, through their active Patient and Public Involvement group who helped to design and refine the system, so it focussed on the wants and needs of the patients themselves.
“DaRe2THINK ingeniously employs digital health technologies and the clinical information safeguarded by our vast network of GP practices – which form the backbone of the NHS – to meet the trial recruitment challenges of a post-COVID world. The result is a pragmatic clinical trial, the first of its kind to address the need for anticoagulation in patients with atrial fibrillation.”
Dr Asgher Champsi, Clinical Research Fellow, Cardiovascular Sciences, University of Birmingham
Over the course of this 10-year study, DaRe2THINK aims to show how this new class of blood thinning tablets could provide an effective way to prevent strokes, brain damage, and dementia in later life for a broader group of patients.
DaRe2THINK will recruit a total of 3000 patients with atrial fibrillation from 600 GP surgeries across the UK. To date, DaRe2THINK has recruited participants at a rate of 16% of invited patients using our data-driven approach, over 5 times higher than current recruitment methods, increasing the efficiency of clinical trial recruitment while reducing the burden of identifying participants on NHS staff.
This new approach could transform the way the NHS conducts clinical trials. Decentralised trials mean reduced impact on participants day to day lives, removing this barrier for recruitment and retention. While the use of health data already securely stored within the NHS can unlock huge potential for more automated and efficient clinical trial recruitment which is more representative of the patient population, while reducing the recruitment burden on NHS staff.