As Russian soldiers advanced toward a suburb not far from Bucha, Ukraine, where a Russian military massacre left hundreds of civilians dead, the damage from missiles and drones piled up near Aleksei Zhmuro’s home.
The fighting inched closer until one day, missile shrapnel tore through his house like “a knife cutting through butter.”
No one was home, but the near miss prompted Zhmuro — like many Ukrainians — to flee. Zhmuro, the head of clinical operations, global monitoring and Ukraine country director at Parexel, relocated his family to Germany. Before long, however, he began traveling to Ukraine to resume work. Despite the fighting, Zhmuro said work at Parexel’s Kyiv office never stopped.
Over two years in, the war in Ukraine shows few signs of abating. Tens of thousands of Russian troops still occupy large swaths of territory in eastern and southern Ukraine and intense fighting continues.
In addition to the death toll — more than 10,000 civilians have been killed according to the United Nations — the war has ravaged Ukraine’s infrastructure, power supply and key sectors of its economy, including drug research.
Before the war, Ukraine was becoming pharma’s “darling” of clinical trials, said Andreas Muehler, chief medical officer of Immunic Therapeutics, a U.S. and German biotechnology company currently running four multiple sclerosis trials in the country.
Clinical studies surged from a yearly average of about 500 active trials to nearly 800 in 2021, according to Ivan Vyshnyvetskyy, head of the Ukrainian Association for Clinical Research. Merck & Co. and Roche were sponsoring about 100 trials in the country and UACR estimates the drug research industry was pumping about $650 million dollars into its economy.
But after Russia’s invasion, clinical work sputtered or ground to a halt. One California biotech said Ukrainian investigators were initially able to keep its study on track, but when shipping depots closed, drug supplies got pinched.
“Ultimately, we were no longer able to get drug to trial sites and [closed] new enrollment at sites across Ukraine and Russia,” the company, which asked to remain anonymous, told PharmaVoice.
Trial starts plummeted to fewer than 30 in 2022, UACR estimated, and by the beginning of 2023, sponsors from 40 ongoing multinational trials in Ukraine reported disruptions related to the war.
The disruptions added new misery for patients who rely on drug studies to access cutting-edge medications. They also created a sudden roadblock in pharma’s global trials network, sending companies scrambling for new sites around the globe.
Even as missiles continue to fly, Ukraine hopes to reclaim its position as a hub of biotech and pharma research. Regulators have sped up trial approvals and and, despite ongoing logistical challenges, companies like Immunic are finding ways to make it work.
“With the tightness of resources in Ukraine, these clinical trials are very important for hospitals and patients,” Muehler said. “And we are very happy with how they’ve performed.”
How Ukraine became a clinical trial hub
Middle-income countries around the world are attractive to drugmakers due to the lower cost of clinical work. Ukraine, which has a well-educated population and an industry adept at digital medical solutions, provided an ideal location for trial sponsors.
“Studies conducted in Ukraine cover a wide range of medical fields,” said Deb Tatton, president of global clinical and data operations at Parexel, a multinational contract research organization that’s currently running about 15 studies in Ukraine. “We have a variety of studies in hematology, ophthalmology, rheumatology, GI, psychiatry … the full gamut. However, oncology has been the largest category.”
Between 2014 and 2017, Ukraine sponsored 46% of the randomized clinical trials for cancer held in lower middle-income countries, according to an August 2022 analysis published in JAMA.
In particular, Ukraine has built a reputation for achieving high patient enrollment and retention while providing reliable data.
Last June, at a Ukrainian clinical trials industry event organized by UACR and the country’s health regulators, an infectious disease researcher named Jens Lundgren described his experience in the country. While recruiting patients for a far-reaching multinational academic consortium called STRIVE, Lundgren said patient enrollment in Ukraine was outpacing Georgia — which Tatton called a “world champion” in patient enrollment — by a factor of six.
Ukraine is a “dominant enrolling country in this academic collaboration,” Lundgren said of the studies that span over 30 countries on six continents.
While Ukraine provides free healthcare to its citizens, the coverage often doesn’t extend to the most advanced therapies, which helps drive patients into clinical studies.
“For patients there, clinical trials are the best option for access to innovative medicines,” Zhmuro said.
Maintaining that access is part of why the country has boasted high retention rates, even as the war rages on.
“For some patients, it is life or death,” Zhmuro said. “For others, it’s about quality of life. But it’s always better to continue being in the study.”
With so much on the line, reestablishing the country as a clinical trials destination has become a top focus for the industry.
“Ukrainians are very proud people and they want to show the world they can conduct [trials] in a time of war,” Muehler said. “[Clinical staff] have said over and over again … [they] continue to operate normally, react to questions, allow monitoring at sites … they want to show us there’s not a difference now than before.”
Adapting research in a time of war
Although the country went through what Zhmuro described as a “period of shock” during the first few months of the war, Ukrainians not living in combat zones adapted to a new normal. Those in the clinical trials industry also made adjustments to keep studies on track.
The first concern, Tatton said, was ensuring patients and trial staff were safe. Using Everbridge, an emergency management platform, Parexel received safety updates and trial status reports around the clock. An in-house task force helped the company keep tabs on developments in Ukraine, as did sources on the ground, Tatton and Muehler said.
In instances when trial participants were forced from their homes and clinical studies, Tatton said Parexel worked to keep them in the study by finding new sites they could join.
“Once a patient is on an investigational drug, the [clinical research organization] and/or trial sponsor is responsible for them,” Tatton said.
The company also helped dozens of clinical trial employees in Ukraine relocate to nearby countries and has provided support, including mental health resources, to those who’ve remained, Tatton said.
And as the CRO developed workarounds to the emerging logistical challenges, lessons learned during the COVID-19 pandemic proved useful again. COVID-era adjustments paved the way for remote clinical work, for example.
“COVID helped with remote monitoring, and although many countries don’t allow direct access to [electronic medical record] data, they will allow some form of remote monitoring to ensure patient safety and protocol adherence,” Tatton said.
While Ukraine’s clinical trials industry has adapted, the transport of biosamples remains a hurdle. With civil aviation grounded, samples are moved by land to airports in nearby countries, Zhmuro said, which can lengthen travel time. Drivers are also difficult to find for border crossings, due to customs control and restrictions on Ukrainian men between 18 and 60 years old leaving the country. As a result, Immunic tries to do as much work with samples inside Ukraine as it can, Muehler said.
According to UACR’s Vyshnyvetskyy, “the rest of the logistical challenges have been resolved. Everything works.”
Still, it’s not clear whether Ukraine would have enough clinical trial professionals to support a return to pre-war activity. Vyshnyvetskyy said the ratio is currently “balanced,” but admitted that if the number of trials increased suddenly, staffing could be a “challenge.”
“But in my personal communications with many clinical professionals … they are sitting in nearby countries waiting,” he said. “As soon as we have more studies [many of them] will come back home.”
Will pharma return?
For many pharma companies, Ukraine is still off the map. Tatton said Parexel is still seeing “hesitance” to start new studies in Ukraine due to uncertainty related to the war. Instead, companies have been looking to nearby countries like Poland, Bulgaria, Bosnia, Turkey and Georgia.
Companies that do choose Ukraine benefit from having relationships with local staff, said Muehler. “A company might usually do site visits themselves, but all of this is off,” he added. “This has to be done by local staff you trust. You need a good partner there.”
In a country where “the hospital could get bombed or may lose electricity,” Muehler said flexibility is also crucial.
For example, in other trials, Immunic never had to secure source documents at sites. In Ukraine, the company has been able to secure documents in the cloud so they wouldn’t be vulnerable to potential destruction.
“You have to pay attention to [all of these details in Ukraine], and sometimes bigger companies are not willing to do this,” he said.
In response to the drop in trial starts, Ukrainian regulators have sped study approvals to a 35-day turnaround to get them off the ground quickly, Vyshnyvetskyy said.
“Our minister of health changed its attitude,” Vyshnyvetskyy explained. “Before the war, it was purely a regulator. Now, it is also a supportive partner of the industry.”
Muehler echoed the sentiment, explaining that Ukraine is a “very quick country.”
“Regulators have implemented a system where everything can be submitted electronically because they want companies to do trials there,” he said.
Although Parexel recently signed a contract with a large pharma to start a new trial in Ukraine, Tatton predicted 2024 will remain a “year of reflection” on how studies are going. Trial starts could pick up more quickly next year, particularly if a large company finds success.
To help lure companies back, Vyshnyvetskyy has been getting the word out that “not only are clinical trials needed in Ukraine, but Ukraine is needed for the industry.”
Vyshnyvetskyy said he isn’t sure how receptive pharma companies have been to his advocacy, though. UACR recently identified about 50 pharma companies looking to start studies around the world and reached out with an email providing information about Ukraine. So far, none of the companies have followed up.
“We need to clearly demonstrate that during these two years of war, Ukrainian investigators and clinical professionals showed not only resilience but robust results. This is a huge and important message,” he said.