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In early April, ClinicalTrials.gov listed nearly 400 ongoing studies with sites in Ukraine. The country has attracted pharmaceutical companies from around the globe that want to conduct clinical trials of their products. However, as a result of the Russian invasion of Ukraine, “the clinical research has been temporarily stuck at the moment,” Lucy Lu, MA, chief financial officer of Suzhou, China–based Kintor Pharmaceutical, said in an interview.
The fighting in Ukraine and sanctions against Russia have forced drug manufacturers to stop recruiting patients to existing trials and put the launch of new trials on hold.
The war “has affected the scientific side of medicine in our country, particularly clinical trials,” surgeon Slava Kopetskiy, MD, and third-year surgical resident Inesa Huivaniuk, MD, both of the Ukraine National Cancer Institute in Kyiv, the site of many inpatient and outpatient clinical trials, wrote in an email. “We had a number of medical facilities taking part in international medical trials and providing essential data for medical science.”
No more, they wrote. “In such terrible circumstances, it is impossible to keep providing medical services and work on clinical trials,” Kopetskiy, who has written the protocols for a couple of surgical trials, and Huivaniuk wrote. “Sometimes it is unsafe to stay inside the building,” let alone process patient data from clinical trials.
Before the Russian invasion, Ukraine was a desirable destination for companies scouting clinical trial sites.
“The infrastructure, hospitals, and principal investigators make Ukraine important” for clinical trials, Lu said. “They have professionalism and efficiency,” as well as patients willing to enroll in trials, she said.
Vlad Bogin, MD, founded Cromos Pharma, a contract research organization based in Portland, Oregon, in 2004 to take advantage of the factors that made Eastern and Central Europe so attractive for clinical trials. Born in Moscow, Bogin came to the US in the 1990s to train in medicine at Yale University and the University of Rochester.
His company, which runs clinical trials of a wide range of investigational drugs for small and midsize pharmaceutical and biotechnology companies, conducted about 40% of its business in Ukraine and Russia before the war began. “It’s been a really good run up to this,” Bogin, Cromos’ chief executive officer, said in an interview.
He cited several factors that have made Ukraine conducive for clinical trials.
For one, “the recruitment is very robust,” Bogin said, noting that sites in Ukraine typically have enrolled participants 3 to 7 times more quickly than sites in Western Europe or North America. In fact, he said, when pharma and biotech companies first began conducting trials in Ukraine, they sometimes halted enrollment because they couldn’t believe that all the patients who signed up so quickly were real.
It helped that Ukraine has a highly centralized health care system in which patients are referred to condition-specific institutions such as cardiology and cancer hospitals with 3000 to 5000 beds each, Bogin said. The patients recognize that clinical trials provide first-rate medical care and trust their physicians’ advice, resulting in significantly lower dropout rates compared with most countries, Bogin said.
In addition, “the investigators are highly motivated,” he said. They get paid for each patient they enrolled, a welcome addition to their incomes, and they are eager to collaborate with their peers in other countries on cutting-edge research, Bogin said.
An Unexpected Turn
If someone had told him as recently as late February that his company and others would be scrambling to salvage clinical trials in Ukraine, Bogin said, he wouldn’t have believed them.
Cromos ended some nonessential trials but is still at least maintaining about 80% of patients in cancer therapy trials, Bogin said. “We’re trying to really be creative about relocating patients from Ukraine.”
The path of least resistance is moving them to established Cromos trial sites in countries such as Poland and Georgia that have already given regulatory approval for the investigational treatment being studied, he said.
“Another issue is the logistics of the drug supply,” Bogin said. “How do you deliver those drugs to those cities?”
One Cromos partner in Ukraine is a company called COREX, which supplies active treatments and placebos for clinical trials. Bogin said its Ukraine warehouse is located near the Kyiv airport. In a March 25 update, however, COREX noted that “[d]espite the current conditions, the Ukrainian COREX warehouse is operating without interruption. Almost the entire COREX Ukraine team left Kyiv. Everyone is in a safe place. We keep in touch with each employee and provide the necessary assistance.”
Meanwhile, lessons learned from the pandemic have proved to be useful during wartime, Bogin said. “COVID taught us how to run remote trials and do remote monitoring,” he explained.
By late March, Kintor had suspended enrollment at all 7 Ukraine sites—and shelved plans to open an eighth site in the country, Lu said—for its phase 3 placebo-controlled trial studying the effectiveness of proxalutamide, an androgen receptor antagonist, for the treatment of hospitalized patients with COVID-19.
Kintor is continuing to monitor proxalutamide’s safety in the Ukraine patients who had completed treatment and has added additional trial sites in China and the Philippines to compensate for the suspension of enrollment at the Ukraine sites, Lu said.
In a statement, a Merck spokeswoman said that “[i]n light of the invasion of Ukraine, we have determined the need to adapt our approach to clinical studies in Ukraine and Russia. Screening and enrollment in ongoing clinical trials and planning for new studies in these regions have been paused until further notice.”
Merck operates clinical trial sites in 50 countries, so they can pick up the work that had been allocated to Ukraine and Russia, the spokeswoman said. “We are continuing to treat patients already enrolled and collecting data from these studies in both Ukraine and Russia and are working hard to ensure that no patient is left behind.”
The vast majority of staff members from medical facilities in large eastern and northern cities that have been the site of heavy fighting, such as Kharkiv, Sumy, and Chernihiv, have fled, as have many of their patients, Kopetskiy and Huivaniuk wrote. “As a result, east Ukrainian hospitals that were not damaged are empty, and west Ukrainian hospitals are overloaded with patients.”
The fighting forced hospitals to suspend work on clinical trials; some resumed a few weeks after the war started, “but not like before,” Kopetskiy and Huivaniuk said. “A lot of these clinics’ resources are used to provide emergent and general medical help for civilians and combatants,” they explained. “This is one of the major reasons new patients are not included in trials.”
About 1.5% of the active patient population in Roche clinical trials worldwide were enrolled in Ukraine, where sites for 33 studies were located, spokesman Karsten Kleine of Roche Group Media Relations in Basel, Switzerland, said in an email.
“We have set up a task force and are currently assessing the impact of the situation on our clinical trials in Ukraine,” Kleine said. “We are actively working on solutions to ensure continued access to treatment for these patients, including if they have left Ukraine and moved to other countries.”
GSK recently announced it wouldn’t be launching any new trials in Ukraine, where it employs 400 people, and would stop enrolling patients into existing trials. And a Pfizer representative confirmed via email that the company has paused recruitment of new patients for clinical trials in Ukraine and Russia and won’t initiate new trials in the latter.
Some Cromos employees in Ukraine who are male physicians have been called up to provide care to wounded soldiers, Bogin said. “I’m checking every day to make sure everyone is alive.”
Read the full JAMA Medical News & Perspectives article here.
Full link: https://jamanetwork.com/journals/jama/fullarticle/2790980