As the COVID-19 pandemic impacted many clinical trials, sponsors were forced to quickly re-evaluate potential solutions to mitigate risks and keep trial participants safe. Continuing trials in Idiopathic Pulmonary Fibrosis (IPF) research was especially difficult as patients living with chronic lung diseases may face a greater likelihood of complications if infected with SARS-CoV-2.
To help sponsors understand the strategies for ensuring research continuity, protecting patients and “future-proofing” upcoming studies from similar unanticipated disruptions, Veerle Van De Velde, Senior Medical Director, Infectious Disease & General Medicine (iiGM) and Mark Dowling, Senior Director, Strategy & Planning, iiGM, shared their recent experiences in a presentation at the 4th Annual IPF Summit in 2020.
Challenging the Protocol Design
Evaluating a sponsor’s proposed protocol design is a practice that was in place before the pandemic, but it proved especially helpful to address the challenges of COVID-19. During the RFP (request for proposal) stage, our team evaluates sponsors’ protocols and makes recommendations for adjusting the eligibility criteria and protocol design.
“With IPF, specifically, several eligibility criteria like ECG parameters, Hepatitis B infection screening and creatinine clearance often lead to a high screen failure rate because we work with an older population,” explained Veerle.
“We also determine what should be done in terms of COVID-19 testing. Currently, a lot of sites ask for the test to be part of the protocol or at least part of potential procedures so they can be reimbursed.”
Vendor set up is another area where our team offers recommendations to sponsors on spirometry and imaging requirements and how that could be performed most efficiently. The team also examines the potential burden on sites and patients to determine where it could be possible to reduce the number of procedures, make use of tele-visits or use site- or patient-based applications as part of a decentralized approach.
“A sponsor with a 52-week study, for example, may want the patient to come in every four weeks for a six-minute walk test (6MWT), but it doesn’t necessarily need to be that frequent,” said Veerle. “The sponsor could consider implementation of actigraphy, a wearable medical device, as an endpoint. This is the kind of feedback that our team can give, which has been even more relevant in the era of a pandemic.”
“A lot of decentralized clinical trial [DCT] technologies have been in use for quite a while now, but these are now part of a complete and connected ecosystem,” added Mark. “At a high level, we look at ways to incorporate DCT elements into a protocol to maximize data collection and minimize the burden on the site and patient.”
Protecting the Primary Endpoint for Studies in Maintenance
For trials that were underway before the pandemic, continuing under lockdown conditions required several different solutions. Our Infectious Disease & General Medicine (iiGM) team shared one case study that involved a mid-size pharmaceutical company in a multi-country Phase II trial with 69 patients.
“When the pandemic hit in March, we had 26 of the 69 subjects completed and 11 patients that discontinued participation,” explained Veerle. “We still needed final endpoint data for approximately half of the patients but did not have home spirometry in this trial. Many of the sites had restricted access because the clinical trial staff were quarantined or there were travel restrictions and they couldn’t leave their houses.”
Without the patients’ forced vital capacity (FVC) data, which was the primary endpoint as in many IPF trials, the study faced risk of failure. The study team put a protocol amendment in place to extend the treatment period, hoping to bridge the worst of the pandemic once sites could reopen for study subjects. IMP was shipped directly to patients to ensure daily oral dosing continued and visits to local providers supported data collection for labs, vital signs and ECG.
The team also continually evaluated when the sites would again be able to accommodate patient visits and implemented COVID-19 testing on-demand when the sites or the patients requested it.
With all the mitigation strategies in place, the study completed successfully. At the end of the study, only two subjects had missing endpoint data due to the pandemic and none of the subjects were infected by COVID-19. A total of 54 subjects were able to complete the study and 15 discontinued it; two of those discontinued subjects dropped out because their family did not want them interacting with the clinical trial staff due to exposure concerns.
Applying Decentralized Clinical Trial (DCT) Approaches to Mitigate Operational Delivery Risks
As the pandemic continues to cause additional disruptions, DCT approaches have been invaluable for salvaging endpoints in ongoing trials. Newly starting IPF trials should also evaluate the potential cost benefits and reduction of site/patient burden with DCT approaches. For example, trials that rely on spirometry data can make use of home-based spirometry where a combined device includes the e-Diary and spirometer.
“We know that spirometry in the clinic is considered the gold standard,” said Mark, “but we’ve also seen that you can maintain study integrity with these connected devices that allow patients to perform assessments remotely. Sites can monitor these spirometry data and schedule telehealth visits with home health nursing teams to provide patient education and coaching.”
“Another advantage of home spirometry in the COVID-19 environment is that each patient has their own device,” added Veerle. “We’ve seen that clinical trial participants can be worried about contracting COVID-19 at the site, even though we know the filters on the spirometers protect the patient from getting infected and clinical sites have a lot of precautions in place.”
When DCT approaches are part of a study’s ecosystem, a patient-centric study can also become more attractive to potential participants, promoting increased recruitment and retention rates in a highly competitive space like respiratory studies.
“The DCT approach can provide more resilience in a trial to handle unforeseen circumstances,” said Mark. “We’ve seen how sponsors are still able to gather key pieces of data when they have DCT mechanisms in place from the outset, allowing them to capture information from both the clinic and a remote setting.”
“Sponsors are starting to embrace the elements of DCT as the “new” normal since these changes were imposed on us by COVID. I think adoption of some of these technologies, like remote spirometry, will not happen overnight, but sponsors are witnessing how COVID can stop a study in its tracks. When they consider a DCT from the start, it does make for a more streamlined study that is designed with flexibility in mind.”
Learn more about IPF Drug Development.