War zone or not, Ukraine seeks to reclaim its role as a hub for clinical trials

In the years leading up to Russia’s invasion, Ukraine had become a burgeoning hub of clinical trials, particularly in oncology. The war put a hold on the vast majority of those studies.

But as the country marks two years this week since the invasion — and as the war has dragged on without a clear end in sight — Ukrainian researchers and executives are increasingly urging companies to restart clinical trials, insisting that the advantages that lured drugmakers in the first place still make the country a desirable one in which to run studies.

They acknowledge the obvious — that the ongoing war is not exactly a selling point. After all, trial sponsors worry about the fighting interrupting a study and losing precious patient data. Some companies also have policies that restrict running trials in countries with war zones.

But Ukrainian investigators argue that much of the country, away from the battlefield, has adapted to the new reality, with economic activity and daily life long resumed — though, they admit, with the occasional air raid siren.

They also stress they’ve managed to sustain the studies that were being run in the country. They’ve rerouted shipping networks to guarantee the quick transport of supplies. Hospitals have generators and Starlink terminals, allowing them to avoid fretting about power outages or severed internet connections. Just as important, there are a host of investigators and patients on the lookout for trials.

“Clinical research is alive. We’ve proved we are robust, we are trustable,” said Ivan Vyshnyvetskyy, the head of the Ukrainian Association for Clinical Research.

And yet, Vyshnyvetskyy said, while Ukraine was authorizing some 200 trials in the years leading up to the war — even reaching around 300 in 2021 — only about 40 new clinical trials started last year.

Ukraine became a key center of clinical trials for a number of reasons. It has an organized and digitized health system, yet running trials there was comparatively cheap compared to Western Europe.

Ukrainians have also been eager to participate. Trials enabled patients an opportunity to try treatments that otherwise wouldn’t be available in the country. They’re a desirable population for companies as well, because with fewer medications available, patients haven’t tried as many other lines of treatment as their counterparts in Western Europe or the United States. It can be simpler to show a drug’s benefit by testing it in such patients.

For doctors, the studies provided another source of income. Trials also boosted revenue for health systems, and there are now a host of researchers experienced in running sites for international drug trials. (Before the war, Russia was also a major site of clinical trials.)

As a result, Ukraine was second only to India — a country with about 30 times its population — among lower middle-income countries in terms of the number of oncology clinical trials participated in, according to a 2022 study. Of the oncology trials with sites in Eastern Europe, Ukraine was included in 42% of them, according to a report from a European pharmaceutical trade group. Many of the studies were late-stage trials.

Much of that went out the window with the invasion on Feb. 24, 2022, according to investigators and businesses that work on clinical trials. Trials that were set to start in Ukraine were halted, and new inquiries plummeted.

But after the first few hectic weeks of the war, as it became clear that Russia wasn’t going to sweep through Ukraine, clinical trial organizers and others found paths forward to ensure that trials that had started could continue. Some sites in occupied territory or near the fighting were cut off, but researchers were often able to find new clinics for patients who fled to other parts of the country.

“Before the war, we couldn’t have imagined how it was possible to continue our usual working tasks,” said Yuriy Lebed, the CEO of the contract research organization Pharmaxi. “Now we are adjusted, we are adapted to this.”

Shipments of trial supplies resumed within months, though with the civil aviation system down, they were instead flown into other countries — mainly Poland — and driven into Ukraine, said Olga Vizgalova, a managing director at Oximio, a clinical trials logistics company. The company has been able to secure its depots and ensure supplies could be kept at the necessary cold temperatures during transport. Throughout the war, Oximio has also been updating its map of the country showing what’s accessible and what’s off-limits.

“Despite all the challenges, despite the brutal war, despite the limitations,” the company helped complete the trials that didn’t stop, Vizgalova said.

What’s helped to an extent is that the war is not the first challenge the industry has faced. During the 2014 conflict with Russia, some Ukrainian trial sites had to cease operations and patients had to be transferred to other clinics. Then, during the Covid-19 pandemic, trials had to incorporate more remote monitoring and telemedicine to track patients, shifts that have enabled researchers to keep up with patients during the war as well.

In recent months, trial investigators say they’ve seen some companies coming back to Ukraine, often smaller firms with limited budgets looking to run quick studies. As they’ve pitched the country as a home for trials, Ukrainian boosters have highlighted in particular the speed of enrollment there.

For a Phase 3 study of its ulcerative colitis drug, the Swedish company InDex Pharmaceuticals had included sites in Ukraine when the trial launched at the end of 2021, after running part of its Phase 2 study there. The company paused the Ukrainian work when Russia invaded, but as the situation stabilized, it decided to restart its trial sites in Ukraine in September 2022.

Eva Arlander, the company’s chief development officer, noted at an event last year about clinical research in Ukraine that it was not a simple study. The drug was shipped patient by patient, and investigators had to conduct endoscopies. When the study’s Ukrainian arm resumed, the sites had mitigation plans that included being prepared to evacuate patients to other sites.

But, Arlander said at the conference, “we have had no interruptions.”

“Of course in Ukraine there are some challenges now and then, but that happens in all countries when you work with a complex study like this,” she said.

In western Ukraine, at Central City Clinical Hospital of Ivano-Frankivsk City Council, investigators have recently started studies in COPD and among hospitalized Covid patients, said Roman Fishchuk, the head of the hospital’s clinical trials unit. Companies have been visiting the hospital as they look for potential sites.

But, Fishchuk said, the number of trials is “nothing compared to what we used to have.”

“We feel as a team helpless — we know these trials are out there, we know these treatments are out there,” he said.

Indeed, at Dnipro State Medical University, there hasn’t been a new cancer drug trial started since the war, said Igor Bondarenko, the head of the oncology and medical radiology department. Cancer studies typically last longer than some other trials, so companies might be more worried about the risk of being disrupted.

But, Bondarenko said, the vast majority of trial staff has remained in Ukraine and are ready for the studies to restart. Of the patients who left Ukraine when the war started — some of whom the team was able to link to other sites in countries like Germany, Spain, and Italy — most have returned, he said.

“Now that the war is ongoing for two years, you can imagine how many patients didn’t get access to the trials,” he said.

At some point, when the war ends, many experts see drugmakers flocking back to Ukraine, given the factors that built up the trial infrastructure in the first place.

“Pharma is going to be running around like crazy looking for anyone to run their trials if they have patients,” said Richard Sullivan, the co-director of the Centre for Conflict and Health Research at King’s College London, who has written about the war’s impact on cancer research in Ukraine.

The bigger question that the industry will face is the labor force, some experts said. Running clinical trials requires specialized expertise, and the scientific community in Ukraine has taken a hit. A study published in December estimated that nearly one in five Ukrainian scientists had left the country by the fall of 2022. (Some of the researchers who left in the first months of the war have since returned, the study’s authors said.)

To mark the one-year anniversary of the invasion last year, Nataliya Shulga, a molecular biologist and the CEO of the Ukrainian Science Club, wrote in the journal Science about rebuilding the country’s research community after the war. As the second year of the war concludes, she said she thought scientists would return if the country showed it was committed to them.

“Human capital — if you lose it, it takes decades to replenish, to rebuild,” she said. “But if you create the jobs, if you create the field for people to work, they will come back.”