Case study: CLARITY IBD: Changing the way we do research
Designing and delivering research in a pandemic
CLARITY IBD is recognised in many countries as a triumph in clinical trial delivery. It recruited 7000 participants with inflammatory bowel disease in 12 weeks across 92 sites and rapidly answered key questions on the impact of immunomodulator and biologic therapies on COVID-19 immunity following infection and vaccination - and all that during a pandemic. Chief investigator, Dr Tariq Ahmad, reveals some of the secrets to the trial’s success.
When COVID-19 reached the shores of the UK in early 2020, Inflammatory Bowel Disease (IBD) patients receiving immunomodulating drugs were among those advised to shield. As the pandemic progressed, and vaccinations became available, the impact of these biologic therapies on antibody and T cell responses and the effectiveness of COVID-19 vaccines was unknown. CLARITY IBD is a pragmatic trial which was rapidly designed and delivered to fill this void. Chief investigator, Dr Ahmad, is a Consultant Gastroenterologist at the Royal Devon and Exeter NHS Foundation Trust and Honorary Associate Professor of Gastroenterology at the University of Exeter. He explains:
“The pandemic was a very worrying time for our patients with IBD. We needed answers quickly on whether or not vaccines would offer the same level of protection for patients treated with immunomodulator and biologic drugs. CLARITY IBD looks at the impact of two biologic medicines; infliximab and vedolizumab, on COVID-19 infection, vaccination and immune response in people with IBD conditions including Crohn’s disease and ulcerative colitis.”
But delivering a clinical trial quickly in the middle of a pandemic poses a few challenges. Dr Ahmad continues:
“We knew we had to make it as easy as possible for the patients to take part. And also for the research teams to deliver the study. We also knew we had to minimise clinician and patient contact time to reduce infection risk. So we designed the trial to be delivered during routine hospital infusion appointments, which occur approximately every 8 weeks.
“We needed to get conclusive results, and quickly. To achieve that we needed to recruit a lot of participants rapidly. We opened 92 sites, all within 5-6 weeks, and all 7000 participants were enrolled within a 12 week recruitment window. It was a phenomenal achievement.
“The rapid set up and recruitment of the trial was made possible by the NIHR research infrastructure in the UK. We have access to well established networks of research-active inflammatory bowel disease clinicians, many of whom we have worked with previously. So we were not starting from scratch. In addition, CLARITY IBD was given Urgent Public Health status which meant it was a priority study during the pandemic, again this was coordinated by the NIHR.”
But the success of CLARITY IBD wasn’t just down to the existing research infrastructure. Another key component of the study’s success was how it incorporated digital and decentralised delivery techniques to maximise engagement.
“We did a number of things differently with CLARITY”, says Dr Ahmad, “which will change the way we do research in future.
Evolving to communicate more effectively
“Firstly we communicated differently. In the past, when delivering multi-centre sites, the clinical trial coordinator would have communicated individually with participating sites via 1:1 phone calls. We would also have updates of study progress at national or regional meetings, maybe a few times a year, where we would share study progress including recruitment graphs illustrating how well each site was recruiting, or not, as the case may be.
“In contrast, for CLARITY IBD we held monthly video calls, for an hour, at lunch time. This proved popular and as many as 200 research nurses who were delivering the trial at the 92 sites would join. It was a really effective way to keep everyone motivated, engaged and updated. It also ensured everyone was getting the same messages at the same time. I think it was also a really positive thing that the other site personnel could see and talk to the team who were leading the trial.
“The way we communicated with participants also changed. We acquired permission to hold all participants' contact details in our REDcap database. This is a tried and tested secure system which allows different levels of access. So each recruiting site could see their own patients, but here in Exeter we had one master data controller with overall access.
“This was a game-changer as it enabled us to communicate directly with participants. We could electronically consent patients remotely, send letters and text messages, send links to video content about the study and - crucially for CLARITY IBD - it has allowed us to upload lab results which were then shared with the participants. We believe this is one of the reasons the study recruited so well. Participants really wanted to know about their antibody test results, and we were able to give them that information, it was mutually beneficial.”
Using this new, digital, direct approach patients were also able to submit data to the study team. Dr Ahmad’s was surprised at the dedication of the participants and the quality of their data:
“In previous studies I’ve conducted data was collected at clinic visits, recorded by the research nurses, then entered into case report forms and uploaded to the study database. However, in CLARITY IBD we issued study questionnaires directly to participants and let them collate the data. They did a really good job of it, we found. So the onus moved away from the research staff to the patients, this also further reduced the burden on the site teams delivering the study.”
Innovating to meet remote delivery needs
But half way through the study something happened that had the CLARITY IBD study team thinking on their feet once more, Dr Ahmad continues:
“As we have already said, the study was set up to recruit and monitor participants at their routine infusion appointments. However, while the study was underway, the companies that manufacture and provide infliximab and vedolizumab made these medicines available in a form that can be administered at home as a subcutaneous injection.
“Understandably, a significant number of participants were keen to avoid visiting the hospital to minimise their infection risk. We responded by quickly designing and testing a finger prick blood- testing kit that we could send to the participant’s homes. This meant that we could continue to collect blood samples for antibody and drug level monitoring from these participants, and retain them in the study. All they had to do was post the samples directly back to us in Exeter.
“This worked really well. In fact, we were able to publish a separate research paper relating specifically to this decentralised aspect, which is a really positive, yet unexpected, outcome of the trial.
CLARITY IBD is due to conclude in March by which time it will have run for 64 weeks in total. It has been recognised globally as a path-finding study with countries such as Canada, the USA and Australia citing CLARITY IBD findings in their clinical guidance around vaccine efficacy and immunosuppressive medications.
The size, scale and success of the study by far surpassed many similar studies in other countries and Dr Ahmad believes that the research infrastructure in the UK was a crucial component, “No other countries could achieve that level of participation in those timescales. CLARITY IBD was by far the most successful study in this area. NIHR support was a large factor in that success.”
He concludes by reflecting on how the new ways of working that have been tried and tested by CLARITY IBD will feature in future research delivery:
“There has been a lot of conversation about lessons learned from the pandemic. At a study level we will absolutely continue to use REDcap, Teams and other digital and decentralised tools and techniques - where appropriate - to encourage participation, maintain motivation, enhance engagement and strengthen communication.”
Listen to a related podcast: CLARITY IBD: Pragmatic pointers from a trial delivered in a pandemic
Professor Tariq Iqbal talks to Dr Tariq Ahmad about CLARITY IBD, the most important gastroenterology study undertaken during the recent COVID pandemic.
More about CLARITY IBD
- Read about the study on the CLARITY IBD website
- Watch an explainer video about the CLARITY IBD study on YouTube
- Watch the latest video on YouTube describing findings from CLARITY IBD.
View published findings from CLARITY IBD
- Covid-19 vaccine-induced antibodies are attenuated and decay rapidly in infliximab treated patients.
(publication pending - accepted Nature Communications)
- September 2021: Adalimumab and infliximab impair SARS-CoV-2 antibody responses: results from a therapeutic drug monitoring study in 11422 biologic-treated patients.
(J Crohns Colitis. 2021 Sep 2:jjab153)
- 21 July 2021: IntraCapillary pharmacoKinetic Sampling (fingerPRICKS) for therapeutic drug monitoring in patients with inflammatory bowel disease.
(J Crohns Colitis. 2021 Jul 21:jjab128)
- 26 April 2021: Infliximab is associated with attenuated immunogenicity to BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines in patients with IBD.
(Gut. 2021 Apr 26:gutjnl-2021-324789)
- 22 March 2021: Anti-SARS-CoV-2 antibody responses are attenuated in patients with IBD treated with infliximab.
First published March 22, 2021. Online issue publication April 07, 2021
(Gut. 2021 May;70(5):865-875)