Lessons learned for Conducting Clinical Trials in Challenging Times

Clinical trials on many levels have been disrupted over the past year, and the current surge can cause further disruption as different regions and cities impose a fresh wave of mitigation measures. However, a number of biopharma companies in ophthalmology are fine-tuning workarounds they embraced earlier in the year to keep their clinical trials on track.

For Aerie Pharmaceuticals, that means adopting a hybrid model that tailors clinician and patient interactions to a trial site’s own mitigation practices. For Johnson & Johnson’s Janssen Pharmaceuticals unit, which expanded its ophthalmology franchise in the past year, that means gathering patients’ data without having to bring them into a clinical trial site. For Novartis, that means using technology to improve the accuracy of patient data gathering.

The numbers of new patients entering clinical trials have declined precipitously in the past months. Medidata, which tracks clinical trials globally, reports that numbers of new patients entering clinical trials in April had declined 59% globally and 45% in the US.1 The rates improved somewhat over the next three months, but shot up in August, the last month for which data are available, standing at 20% fewer new patients globally and 22% fewer in the US. But oncology trials are propping up those numbers; the number of new patients entering non-oncology trials is off about a third globally – 31% to be precise – through August, Medidata reports.

Aerie’s Hybrid Approach
Aerie has embraced what Michelle Senchyna, PhD, VP of Clinical Development and Medical Affairs, calls a hybrid model for executing the logistics of clinical trials. Aerie has embraced flexibility in how it approaches trials, Dr. Senchyna said. “I really challenged my team to think about every single site and even every subject as an individual customer,” she told OIS Weekly.

That means adapting if a site doesn’t allow on-site monitoring, limits the number of monitors allowed inside, or operates like it did before the pandemic. As Aerie is conducting multiple diverse studies, operations staff has been reorganized based partially on geography (“to allow more travel by car as opposed to airlines”) rather than study protocol. “It’s certainly a little bit more work up front because now instead of being a specialist in one protocol, you need to be very familiar with multiple protocols,” Dr. Senchyna explained.

“We’ve become very conscious of listening to our sites,” she continued. “Sites and investigators have always been critical variables to running successful studies, but now more than ever, it’s more than just having the right patients and the right equipment.”

That’s especially true in the current climate where restrictions in states and even counties can differ substantially, leading to not only legislative challenges but also differing sensitivities and fears for staff and subjects. Despite these challenges, Aerie has found that if the time and effort is taken to accommodate sites, studies can continue without compromising safety or data integrity.

For delivering investigational product to sites, Dr. Senchyna took a page out of the playbook of food delivery services, like Uber Eats. “It’s not that different from a drug-dispensing perspective when you think about it,” she said. Through partnering with a contract research organization, Aerie now provides options in certain studies to facilitate home delivery and site drive-through.

Dr. Senchyna also noted that in addition to minimizing site/subject burden and exposure, “the reminders subjects receive to schedule a delivery provide a great opportunity to give a little reminder about dosing compliance.”

She added, “I think we’ve done an incredibly good job of keeping the wheels turning and by the same token not interfering with the subjects’ safety or the site’s safety. Is it more work? Yes. Does it come with a little bit more expense? Yes. Was it all worth it? Absolutely. We met every one of our milestones this year [2020] and have set up 2021 for success.”

Janssen Stays Flexible
One of the lessons Janssen has learned about conducting trials during the pandemic is to not be so rigid in some protocols. “We work with regulators on the ability to have more flexibility in our clinical trials, to do more things in a site-less manner and/or to do things, when possible, where the patient doesn’t have to come into the site,” said James F. List, MD, PhD, global therapeutic head, cardiovascular and metabolism of Janssen Research and Development, the Janssen unit that oversees the ophthalmology franchise.

“Part of that is because our operations group has a tremendous ability to look at in a real-time basis feasibility and make sure our sites are open in the right places,” Dr. List said in an interview with OIS Weekly. Janssen has charged data scientists to track COVID-19 outbreaks in real time. “Those same tools are used in operations to make sure that we put the right resources in the right sites, and in the right countries,” he said.

Of course, Dr. List noted, by necessity some trials need to be slowed down because the patients themselves may be at risk – think of older patients with age-related macular degeneration or a patient with diabetes who also has diabetic eye disease – or the facility may be attached to a hospital that’s overwhelmed with COVID-19 patients. “But in all the other circumstances, we’ve actually generally done fairly well at keeping our trials running, again, with this sort of flexibility, without making any compromise in trial integrity or quality,” he added.

Leveraging Digital Initiatives
Over the past year Novartis has undertaken a series of digital initiatives, including one that uses analytics to interpret clinical data faster and more accurately. FocalView is an app that allows patients participating in clinical trials to self-record measurements. Not only does the app allow patients to avoid trips to research sites, but it also allows researchers to collect more data.

“You can take many more measurements and therefore you can start extracting data that previously you had no access to,” Nikos Tripodis, PhD, worldwide franchise head, ophthalmology, for Novartis, said in a previous OIS Weekly interview.

Novartis also launched a multi-year collaboration with RetinAI Medical, a Switzerland-based company that develops software for medical and pharma research, to support multiple projects in ophthalmology digital health. “We try to learn from all sides on how to use data and digital to enhance our knowledge, accelerate development, improve diagnosis, and help patients become more self-aware, compliant, and ultimately help improve their condition,” explained Dr. Tripodis.

1. COVID-19 and clinical trials: The Medidata Perspective, Release 9.0. Medidata Solutions Inc. Published September 21, 2020. Available at https://www.medidata.com/wp-content/uploads/2020/09/COVID19-Response9.0_Clinical-Trials_2020921_v2.pdf