Andy Studna

Jane Myles, Vice President, Clinical Trial Innovation at Curebase, discusses her current role, what led her there, and challenges their clients face with DCTs.

Podcasts

The Key To Innovation In Clinical Research? Listening.

Chief Science Officer at Unlearn.AI, Dave Miller, discusses digital twins, their pros and cons for the industry, and developments in Bayesian design and adaptive trials for CDER and CBER.

The Ins and Outs of Digital Twins

When Russian forces invaded Ukraine in late February of 2022, the world was searching for answers. Many industries and their respective markets were flipped completely upside down in a matter of weeks. Included is the clinical trials ecosystem in Ukraine—which has had a significant impact on trials globally as well.

 on the state of clinical trials in Ukraine. It reported that: “The field of clinical trials in Ukraine is currently suffering significant losses…hundreds of clinical trials have been disrupted.” The article also features research from GlobalData, which at the time, reported 502 trials were underway in the country.

Contract research organizations (CROs) and sponsors were now suddenly placed at the frontlines of a battle for clinical trials. Difficult logistical challenges rapidly unfolded, some of the most notable being the transport of critical supplies, communication with stakeholders outside of Ukraine, and most importantly, the safety of clinical research associates (CRAs) and patients.

In the face of adversity, one of the many organizations that stepped up to address these challenges was G1 Therapeutics. G1 is a biopharma company headquartered in Research Triangle Park, NC, that specializes in developing small-molecule therapies to address significant unmet needs in oncology. At the time of the invasion, G1 was executing trials in metastatic colorectal, bladder, and triple-negative breast cancers in Ukraine. The company was working with CROs IQVIA, Arensia, and Parexel on the trials. With the help of their CRO partners, G1 orchestrated the relocation of 12 patients to Poland, Moldova, Georgia, and Spain, where they are now continuing to receive cancer therapies.

Efforts to accommodate the patients began almost immediately after the war broke out. “We lost contact with our sites and with the CRA in the study,” says Anna Leblond, G1 clinical study lead. “We immediately had to make some critical decisions.”

One of those first decisions was getting therapies to the patients. With martial law having been instituted, couriers could not ship drugs to the sites from G1’s depot in Ukraine. Even if the drugs were needed right next door, it was impossible to ship due to strict regulations requiring controlled transfer. Several sites received shipments just prior to the invasion, but most did not. “Most of [the sites] ran out fairly quickly,” says Leblond. “[Around] April and May, we had a lot of sites that were using partial drug regimens or just not treating patients and hoping that they would be able to receive drug shipments soon.”

In addition to the immediate supply chain challenges, the violence unfolding around patients, sites, and CRAs quickly became a cause for concern. “We received reports from our CRO partners who had CRAs choosing to stay in the country and trying to text their sites from bomb shelters,” Jenn Warneke, SVP of clinical operations for G1, tells 

“Our first response was not about the trials; it was about the patients themselves. I think at that point, trial participation becomes incidental to safety. After that settled a bit, we started to think about, ‘okay, what does this mean relative to the clinical trial? How do we alleviate burden from the sites and how do we keep getting treatment to patients?’”

Warneke was impressed with the way the CROs handled the immediate chaos. Using their available local resources, the CROs were able to quickly mobilize their internal staff to help them get necessary supplies. There were CRAs who even elected to stay in Ukraine at the sites; some of them had to stay because of constraints relative to age, gender, and a potential call up to military duty, but others stayed because they wanted to help. “The people of Ukraine are incredibly resilient and determined,” says Warneke.

When it came to physically moving the patients out of Ukraine, the first step was finding sites in nearby countries that could accommodate them. Poland and Moldova were among the surrounding countries in which G1 had existing site relationships. The initial stages of planning came during a time when communication was almost impossible; it was mostly conducted through individual CRAs, as G1 had lost direct contact with sites. Leblond even recalls communicating via text message with a CRA who was in a bomb shelter for updates. Despite hurdles in communication, G1 made it clear to patients and investigators they had the option of leaving Ukraine, as they could not guarantee the shipment of therapies. According to Warneke, it couldn’t have happened without their CRO partners.

“CROs have incredibly broad reach, with local people in every country,” says Warneke. “It was remarkable how quickly CROs mobilized their internal staff and got them what they needed; the way they were able to communicate from the ground up.”

The language barrier was another significant area of concern for patients and sites alike. In the event patients had an adverse effect from treatment, they needed to be able to communicate that clearly. There were also different regulations and documentation required by other countries for clinical trials. Despite these initial challenges, the surrounding countries were able accommodate them. “Luckily, [the countries] were very understanding of the situation,” says Leblond. “It did take a lot of planning and getting documentation in place, but once that was secured, it was pretty straightforward. Everyone had the same goal of keeping patients safe and getting them access to the treatment they needed.”

While G1 paid for patients’ travel and, in many cases, their lodging, some logistical challenges—such as who they were going to stay with and how they were going to get across Ukrainian borders—were mostly out of their hands. Warneke recalls this as one of the scariest times in the process considering the uncertainty. “Every single time you heard that a patient made it, and they had connected with another clinic, we were really happy,” she tells 

. “We were constantly wondering, ‘Are they going to make it? Are they going to be able to get across [the border]? We don’t know what it was like; we only saw what was on the news and what we were hearing from our partners.”

Once the patients were safely situated, there were still challenges affecting the study and data collection. Due to patients missing doses, lapses in treatment, and site closures, G1 had to evaluate enrollment numbers and accelerate recruitment in surrounding countries to ensure quality data. However, data is still being tracked for patients who chose to relocate out of the Ukraine, and that helped reduce data gaps. “There was an impact, but we’ve been able to pivot enough to continue and follow through on these studies and meet our timelines and our objectives as needed for the study,” says Leblond.

Warneke shares the same sentiment that, once the logistical challenges were overcome, business was running as normally as it could considering the circumstances. “Once we got through the obstacles of the physical patient transfer, and then the logistics surrounding their journey to a new site for continued care, it really has been business as usual,” says Warneke. “Very few patients were lost to follow-up during this period of time.”

While the pandemic and the war in Ukraine have been unprecedented challenges for global trials, they have served to strengthen the industry’s approach to clinical research and patient care. From virtual site visits to remote monitoring to wearable devices, trials have rapidly adopted new technology to bring studies to patients, rather than patients to sites. Likewise, companies are recruiting more diverse individuals to ensure that study data accurately reflect the populations their drugs will treat. Countries like Ukraine are welcoming these opportunities, and they have ample staff to accommodate them—until recently.

“There are always more considerations when initiating global trials due to cultural, regulatory, procedural, and language differences,” says Leblond. “We were willing to take the risk, knowing what we knew. “[But] if we knew this was going to happen, absolutely not. Everybody lost money, time, data, and—most importantly—patients were in danger and temporarily lost access to critical drugs.”

Looking forward, there are lessons to be learned from this experience. “One of the biggest things during a debrief after a crisis or challenge is to try and anticipate and mitigate risks for future protocols and study start-ups,” says Warneke. “This teaches us to build in mitigations maybe a little bit sooner, and to assess the global landscape so we’re prepared to pivot more quickly.”

Warneke also hopes that G1’s work serves as a beacon of hope for industry in difficult times. “It makes me realize that we’re really a lot smaller globally than we think we are,” she says. “When we need to come together, we do. It renews my faith. It adds another foundational brick that, in my sense, in this industry we are all out to do good. We create a solution, no matter what situation we find ourselves in.”

is Associate Editor of Applied Clinical Trials. He can be reached at

Articles

Ukraine invasion tests the resiliency and quick action of CROs and sponsors.

Mobilizing and Maintaining Clinical Trials in Midst of War

Susan Wood, president and CEO of VIDA Diagnostics, discusses her journey into healthcare from an engineering path, changes in the field of imaging, virtual control arms, and much more

Advantages of Precision Endpoints

Todd Luckritz, Associate Director, Patient Solutions at Myonex, recently left Mayo Clinic as the lead pharmacist for its clinical research programs. In this podcast, Luckritz discusses his journey “bringing protocols to life,” the joy of interacting with patients, and the frustrations with sourcing that led him to make a difference at Myonex.

sign up for their on-demand webcast about eliminating the site burden of comparator sourcing.

A Passion For Sourcing

Paula Brown Stafford, CEO of Novan, came to her role via increasing clinical development role responsibilities with Quintiles, now IQVIA. In this podcast, she reflects on her professional experiences, her achievements and her advice for clinical trials professionals.