Published: 06 May 2021
The NIHR research infrastructure, embedded in the NHS, supports the delivery of complex and innovative clinical trials.
The PD-STAT trial investigated the effectiveness of a common cholesterol-lowering statin, simvastatin, as a disease-modifying treatment for Parkinson’s disease (PD). It concluded in June 2020 and, although the trial found that simvastatin holds no promise as a neuroprotective treatment for PD, it generated robust data and best practice processes which can now be analysed and implemented for use in future research. The trial is also an exemplar of innovation and remote research delivery, and demonstrates the UK’s agile response to delivering research during the COVID-19 pandemic.
Parkinson’s disease (PD) is a progressive neurodegenerative condition that affects approximately 145,000 people in the UK. At present, no drugs have been shown to slow or reverse PD. Current treatments aim to relieve symptoms but are limited in their effectiveness due to progressive neuronal loss.
Read an accessible transcript for the video: Paving the way for the future of remote trial delivery.
The PD-STAT trial is one of the first academic, multicentre studies of a neuroprotective treatment for PD, and the largest of its kind to run in the UK - running at 23 sites. The trial was led by a study team at University of Plymouth. Dr Camille Carroll is the chief investigator; she knew a study of this size would be challenging to deliver and recognises the role that the NIHR played:
“The NIHR Clinical Research Network (CRN) was instrumental in supporting the successful delivery of the trial from the outset. The Network initially assisted in identifying suitable sites for the trial and supported the feasibility assessments for each site. As a number of the sites serve rural catchment areas and communities, the feasibility assessments were important to ensure that the selected sites were able to successfully deliver the trial.”
The NIHR Neurodegenerative Diseases Speciality Group also supported the trial by promoting it locally and helping to ensure it maintained its recruiting momentum across the 23 sites. The study opened to recruitment in February 2016 and, by April 2018, the trial had exceeded its recruitment target of 198, successfully recruiting a total of 235 patients.
One of the stand out features of PD-STAT was its use of digital technology, which was considered quite advanced when the study was designed. Dr Carroll is a strong advocate for exploring the opportunities of using digital technology in trials:
“The PD-STAT trial has embraced technology from the outset. When the trial first opened in 2016, its use of digital tools to monitor patient symptoms was considered quite novel and forward-thinking. For example, part of the assessment of patients during clinical visits was an internet-based measure of tapping speed and a sensor worn on the digits which could provide more detailed and granular data about the patient’s movement. In fact, the challenges and benefits of utilising digital technology in this way is currently being analysed by the team with a view to sharing the learning that has taken place on the trial.”
Once enrolled, patients were required to take part in PD-STAT for 26 months. The long duration of the trial combined with the degenerative nature of PD, meant that patient retention was challenging, but also crucial to the success of the study. Therefore, from its inception, the trial was designed to be as easy as possible for staff to deliver, and for patients to participate.
A number of aspects of the trial design and delivery supported good patient retention. Firstly, the trial was adapted to include home visits rather than clinic visits, for example for participants in rural areas, or those who were less willing or able to frequently travel to a study site. This immediately improved accessibility to the trial.
Secondly, the expertise of the teams supporting the trial at the 23 sites also had a positive impact on retention. Dr Carroll is also the Clinical Research Network National Specialty Lead for Neurodegenerative Diseases, therefore she knew the study was in good hands:
“We certainly benefited from the expertise that was available at the different sites due to the support infrastructure provided by the NIHR. I think without having the infrastructure support in place, we would have really struggled to deliver the study. It provided a stable staff base, which meant that, on the whole, the same nurses were able to support patients throughout the two years of being on the study, which was really important for patients. And of course, for a neuroprotective trial, particularly one of that duration, patient retention is really important to ensure that we're able to meet our primary outcome. So I think without the support of the NIHR Clinical Research Network, this study would not have been possible to deliver.”
The final retention challenge came in March 2020 when the COVID-19 pandemic reached the UK.
Swtiching to remote delivery
At this time the study was no longer seeking new participants, however, a significant proportion of participants were still visiting their clinics for ongoing study monitoring and assessments. Yet country-wide, for safety reasons, study visits to hospitals were no longer viable and many clinical research studies had to be paused as a result of the pandemic.
With PD-STAT on the final stretch, the study team was determined to ensure the trial could continue. Again with NIHR support, the team was able to quickly gain regulatory approval to switch to a virtual approach. This enabled all remaining assessments to be completed remotely via video consultations with mitigations in place for patients for whom this was not an option. For example, teleconsultations and questionnaires were also offered to ensure that robust data was collected from the remaining participants.
As the impact of the pandemic on the NHS increased, frontline staff who had supported PD-STAT at the 23 sites were redeployed to either assist with frontline healthcare, or to deliver nationally prioritised Urgent Public Health COVID-19 trials. With a remote model now in place, the PD-STAT team was able to quickly adapt and implement a cross-organisational approach to deliver the final participant assessments.
This was facilitated by NIHR Clinical Research Network teams at all NHS sites which helped ensure the relevant data sharing processes were in place between NHS trusts, and the correct consents were obtained. This enabled the contact details of the remaining participants to be shared safely with the study team leading the trial from University Hospitals Plymouth (UHP) NHS Trust. Specialist nurses based in Plymouth were then able to offer remote assessments for those participants across the country.
The forward-thinking design of the PD-STAT trial undoubtedly contributed to its success in the wake of the COVID-19 pandemic. However, a cross-organisational, remote approach like this is quite unique to the UK, made possible by our single National Health Service and the NIHR research infrastructure embedded within. Dr Carroll said:
“I think the UK response to the COVID-19 pandemic has really exemplified what can be achieved within the UK in terms of delivering clinical research. We now have the opportunity to build on that and ensure that what we've developed becomes truly embedded in new care pathways and a new way of delivering research, which is better for teams, better for patients and better for sponsors.”
Dr Carroll is also the chair of the UK Remote Trial Working Group, which has been established to collate and share learning and best practice in remote trial delivery. This group’s recommendations and guidance for robust quality assurance processes will ensure that future trials share the same scientific rigour and validity of data as traditional site-based trials. Reflecting on her own experiences Dr Carroll feels the UK has all the right ingredients to become a world leader in remote trial delivery:
“I think the UK will be a great place for those studies to be based in the future. We have all of the individual component parts, working together, facilitated by the NIHR, with really good communication and dissemination processes and infrastructure in place, which allow for best practice to be shared, problems to be mitigated, and challenges to be identified, in a way that is rapid, flexible and adaptable.”
- Listen to our podcast 'Harnessing the power of digital technology in clinical trials' to hear Dr Camille Carroll describe the advantages of using digital technology in clinical trials such as sensors and wearables. She explains the concept of ecological validity and how these innovations can help researchers to overcome obstacles such as bias, recall error and human error to achieve accurate and objective results.
- Read a report from the NIHR UK working group on remote trial delivery for the COVID-19 pandemic and beyond (published 11 December 2021)
- Visit our 'Delivering complex and innovative trials' web page to learn more about NIHR support and read more case studies.