Published: 12 April 2021
Balancing trial design with patient experience
Irritable bowel syndrome (IBS) is a common, long-term condition that affects approximately 5% of the population, one-third of whom have diarrhoea predominant IBS (IBS-D). The symptoms of IBS-D can be difficult to live with, impacting patients’ personal and professional lives. IBS-D also has a significant financial impact, costing the UK an estimated £200 million per year, which includes a £45.6 million cost to the NHS, and time off work for patients.
IBS-D is most commonly managed by lifestyle and dietary changes with symptoms being treated with over the counter drugs. As the condition is so disruptive to patients’ daily lives, a new treatment for IBS-D is welcomed. The RELIEVE IBS-D trial, conducted collaboratively by Enteromed and the NIHR, is testing a new drug-free intestinal adsorbent oral gel to help relieve the symptoms of IBS-D.
Due to the nature of IBS-D, both the sponsor company, Enteromed, and the chief investigator, Professor Yan Yiannakou, knew they had to ensure the trial was as accessible as possible for participants. To achieve this they collaborated with patients on the trial design which resulted in a number of improvements to the proposed trial design. For example, patient activity as part of the trial was reduced to a short daily diary available online through daily text reminders. Following the initial face to face consent process, clinical visits were kept to a minimal three sessions from the outset. The reduction in face-to-face contact was made possible by shipping the treatment to patients, which later proved pivotal in adapting the trial to a fully virtual model. Patients were also keen to try the new treatment, so an open-label phase was included after the double-blind phase of the trial to ensure those participants receiving the placebo also had an opportunity to try the new treatment.
This transparency combined with the patient-centric design of the trial led to a good recruitment response when the trial opened. However, IBS patients often receive excellent treatment in primary care settings, which means that they may not come into contact with specialist clinics in hospitals. The result is that, although IBS is a common condition, it can prove difficult to recruit patients to trials as, traditionally, the clinical trials have tended to focus their recruitment strategies on hospital sites.
RELIEVE IBS-D overcame this, in part, by selecting a mix of primary care (general practice) and secondary care (hospital) sites to contribute to the study, and also by allowing the secondary care sites to use up to five Patient Identification Centres (PIC) sites to support recruitment. The PIC approach is a common hub and spoke model which spans primary and secondary care. The general practices (spokes) identify and refer suitable patients to take part in a study at the hospital site (hub). In addition, the team based at PRC: Newcastle implemented a further recruitment strategy to raise awareness of RELIEVE IBS-D beyond primary and secondary care.
Innovation in research delivery
Using multiple advertising techniques, including digital advertising on social media, they were able to reach into the community to encourage IBS-D patients (who would not typically come into contact with clinical trials) to sign-up to an online database called ContactMe IBS. On signing up, patients give their permission to be contacted about research that is relevant to them. Condition-specific registries like ContactMe IBS are becoming a popular strategy for recruitment because, as well as providing an excellent way for researchers to engage patients, they also empower the public to proactively volunteer to take part in research. By combining innovative digital marketing with the ContactMe registry, the PRC: Newcastle team was able to reach out to a large number of potential participants for the RELIEVE IBS-D trial.
As a result, the RELIEVE IBS-D trial recruited reasonably well with 28 sites in England enrolling 253 participants in 18 months. This was in part due to its patient-friendly design. However, when COVID-19 lockdown restrictions were implemented in March 2020, the trial was paused at these sites, along with many other studies, as part of the infection control measures.
This triggered the need for a different approach and a new, virtual solution was championed by Professor Yiannakou, who is also Clinical Director of PRC: Newcastle. Working with NHS Digital, the NIHR, and with input from research ethics committees, the team in Newcastle was able to create a fully compliant electronic consent process, an online waiver form and virtual screening consultations to enable the trial to be conducted completely online. Carol Howell, Research Director at Enteromed, attributed the ability to shift to a virtual model to the flexibility and expertise of the PRC: Newcastle team:
“Without the NIHR’s involvement, there was a real risk that we wouldn’t have been able to continue the trial without the sites being open. Working closely with Professor Yiannakou and the PRC team at Newcastle meant that we had the expertise and the forward-thinking approach to support the design and development of a virtual trial. It is because of the dedication of the whole team at PRC: Newcastle that this was made possible. Being able to adapt to a virtual trial meant we were able to generate valuable clinical data, while also protecting patients.”
The team at PRC: Newcastle again collaborated with Enteromed and their local Patient and Public Involvement (PPI) service to design effective digital processes to recruit and screen vast numbers of potential participants remotely. The screening aspect was crucial as the virtual model opened up the trial to patients that did not have an existing patient-clinician relationship with the study site, meaning there was no clinical insight on who was suitable for the trial. To help overcome this challenge, the Digital Informatics Team at Newcastle Hospital developed an online pre-screening questionnaire to help identify eligible patients and keep screening failure rates to a minimum.
When it opened to recruitment on 16 September 2020, the information about the virtual version of the trial was cascaded through the ContactMe IBS registry. The response was positive and rapid. In 24 hours over 150 potential participants had indicated an interest in being screened to take part.
This virtual approach resulted in rapid recruitment, with the 50th participant being randomised within just two months. Using this as a benchmark, it demonstrates that the virtual version of the trial has significantly out-performed the site-based version of the trial: a single site using a virtual approach recruited 67% faster than 28 sites using a traditional approach.
Carol Howell, Research Director at Enteromed, reflected on this early success and how it had been achieved:
“We are really proud of being part of the first interventional virtual trial in the UK and it’s been an amazing achievement in such a short space of time. Recruitment closes at the end of April and we have been recruiting really well since September, with only 35 more patients needed to reach our target. We have been able to promote the trial through NIHR resources as well as the ContactMe IBS registry, the Research+Me registry and through active advertising. It’s been amazing how many patients have responded and been screened.”
UK virtual capabilities
This success was made possible by one of the UK’s greatest assets; the National Health Service (NHS) providing both primary and secondary care countrywide. Add to that the NIHR Clinical Research Network and you have a fully integrated research system covering the whole of England with links to the rest of the UK. The integrated nature of the NHS, and its ability to share patient data both safely and securely, was a key factor that facilitated the move to a fully virtual model. Carol Howell agrees:
“The virtual trial was also made possible because of the way the NHS works. We were able to recruit external patients - patients that were not under the care of Newcastle upon Tyne Hospitals NHS Foundation Trust - into the study, and we were able to then approach their GP to get all of their patient permissions and medical notes so that these patients could participate in the trial at home safely.”
From a commercial perspective, this enabled participants to be processed through one study site, regardless of where they were based in the UK. Eradicating the need to set up multiple study sites is an attractive prospect as it offers both time and resource savings for the study sponsor. The virtual approach also supports efficient study delivery by removing geographical barriers and consequently increasing the pool of available candidates. Professor Yiannakou explains:
“When we cascaded information about the original, site-based RELIEVE IBS study to the ContactMe IBS registry, we had over 200 potential participants who passed the screening questionnaire and who were keen to take part. However, the majority of those people, in fact 95% of them, lived too far away from any of the 28 study sites to make participation feasible. When we shifted to a virtual model, we were able to offer the study to those people who had previously been excluded due to their location. Participants have now enrolled in the study from as far away as Penzance.”
Due to the nature of IBS-D, many patients are reluctant to travel long distances to take part in research. Moving to a fully virtual model also enables patients to participate from the comfort of their own homes. This makes the study even more attractive to potential participants, explains Carly, who joined the virtual trial from Yeovil in the South West of England:
“I found the virtual aspect of the study fantastic. Being able to participate in something virtually without having to go anywhere has been really positive for me as I live so far away from the hospital. If this trial had not been not virtual, it probably wouldn’t have been possible for me to get involved as there’s no way I would have been able to travel back and forth to take part.
“The regular video calls have been really useful and the text messages that come through each night to remind me to do my diary have been really good. Without them I wouldn’t have completed my diary as well as I have, which is a key part of the study. It has had a massive positive impact on me and the team have been great in providing guidance through the whole process.”
As well as overcoming geographical barriers, virtual trials increase accessibility to trials in other ways, for example by addressing barriers such as mobility, working hours and caring responsibilities. Expanding access to the population at large can create opportunities for the collection of real-world data - another attractive prospect for a potential sponsor company. Capturing real-world data ensures that study findings are a good representation of, and can be applied to, the entire patient population.
But not all studies are suitable for virtual delivery. The virtual version of RELIEVE IBS-D was made possible, in part, due to the nature of the treatment and the initial design of the trial. Enterosgel is a safe treatment, so patients are able to take it at home and self-monitor. No clinical tests or blood work are required, meaning clinical visits could be easily replaced by virtual consultations. Additionally, the initial trial design had already established logistical processes to deliver the treatment to patients, helping to quickly adapt the trial to a virtual model. Now that these systems are in place, they could potentially be replicated in other trials across a range of medical conditions. This sentiment was echoed by Carol who said:
“Moving forward, hopefully, our initial steps in this virtual trial world will help other studies feel that they can also do it.”
On 5 May 2021 the RELIEVE IBS-D trial reached its recruitment target and in June 2022 results form the trial were published.
- Listen to a related podcast: The power of virtual trials: Overcoming geographical boundaries
- Find out what studies are being delivered at PRC: Newcastle by visiting the Participate in a study at PRC: Newcastle web page
- News: Virtual trial discovers all-in-one treatment for IBS with diarrhoea
- News: Virtual trial recruits 67% faster led by NIHR Patient Recruitment Centre in Newcastle in collaboration with Enteromed
- News: Newcastle Hospitals to run the first Virtual Clinical Trial in the North East