Soft Skills Critical To Clinical Trial Continuity In Ukraine
By Deborah Borfitz
May 24, 2022 | The importance of clinical trials as a care option in Ukraine, and the unthinkable bravery of its citizens since Russia launched the first bomb on Feb. 21, were predominant themes of a recent DIA webinar on the impact of the crisis on patients and clinical development. Moderated by Courtney Granville, global associate director of research and scientific programs for the association, the online event covered the situation on the ground and challenges to patient safety and the continuity of care and clinical research.
Before the war, Granville notes, between 200 and 500 trials were reportedly underway in Ukraine. Even now, ClinicalTrials.gov indicates the country has 250 active, ongoing phase 3 trials. But research entities, the government, and patient groups have all been relocating patients for their own safety and, as much as possible, to continue their treatment. Regulatory and governmental bodies in Europe, meanwhile, have stepped up with guidance documents on how to manage trials and participants in the war-torn nation.
In three regions of the country, Ukraine-based site management organization Pratia has 10 sites conducting trials, according to speaker Anna Titkova, M.D., Ph.D., a cardiologist and researcher who is the country head of the network. “Ukrainians have not been forgotten,” she says, noting the “participation of the whole world in our troubles.”
The trials being done by Pratia, “truly are real life and science working hand in hand,” Titkova says, alluding to Ukraine’s unique health system where general practitioners are contracted to care for the citizenry from birth to death. That network of doctors controls the flow of patients to specialists as well as clinical trials and can be the starting point for enrolling patients.
Many of the lessons learned from business continuity planning for COVID-19 applied to the war situation, including the focus on employee and patient safety, risk management, and clinical trial integrity, says speaker Teresa Lamantia, senior vice president of operational transformation and performance at IQVIA. The company has more than 82,000 employees worldwide and close to 400 in Ukraine.
Double Whammy
War or no war, for people with cancer “clinical trials are an important way to access treatment options,” says speaker Bettina Ryll, M.D., Ph.D., founder of the Melanoma Patient Network Europe (MPNE), a member of the first EU Cancer Mission Board, and a subject expert for personalized medicine for Vision Zero Cancer (financed by the Swedish innovation agency Vinnova). In 2012, when the MPNE started, melanoma treatment was accessible only through trials. Even with an approved chemotherapy drug now available, one out of two patients still die from the cancer, she notes.
Russia’s invasion of Ukraine—targeting civilians, hospitals, and clinics as well as soldiers—has been a double whammy for anyone with cancer, says Titkova. She reports that 246 hospitals in the country have been damaged, one-quarter of the population has been displaced, and five million people have fled to neighboring nations through April.
An estimated 139,000 people with a newly diagnosed cancer have left Ukraine, Ryll says. Both cancer treatment and survivorship care have been disrupted. In Kharkiv, Ukraine’s second largest city in the eastern part of the country, medical facilities have been bombarded nonstop.
She adds, “Right now there is only one main question: How are you?” The focus is on managing relocations, with three cancer patients successfully transported to Poland in April.
Patients continuing treatment are in despair, and sometimes without housing, “waiting for it all to end,” says Titkova. “They are heroes struggling through this battle,” referencing a popular Twitter post saying “I thought I knew what bravery was. And then I saw Ukraine.”
Regulatory amendments are why ongoing trials can continue, with patients being moved to other sites in or outside the country as necessary, Titkova says. The overriding needs are tolerance, compassion, and love, she adds.
Care Continuum
IQVIA has seen the strength and resilience of the Ukrainian people, says Lamantia. It’s important to know the personal impact, the “face of humanity here,” which includes people sleeping in bunkers unable to move for 36-hour periods.
General practitioners in Ukraine follow patients’ treatment in trials, which provides better access to care for those who require long or novel treatments, Lamantia says. People with chronic diseases may well be enrolled in several protocols.
Ukraine tends to be a high-recruitment country because clinical trials are in the care continuum, Lamania says. Despite the ongoing war, patients who had relocated to Romania or Poland are coming back into the country as they’re able to connect with investigators for treatment.
Clinical trials as a care option are much more accessible in Ukraine than what other countries aspire to, she continues. But that model requires strong regulatory oversight, as is the case throughout Eastern Europe.
Business Continuity Plan
Lamantia is response lead for IQVIA’s Russia-Ukraine War Business Continuity Plan team, and the position links to executive leadership, she says. Among the core workstreams are those for employee safety, patient safety, and clinical trial continuity. Team members include representatives from quality and regulatory affairs, finance, IT, and legal.
Risk planning is happening at the trial level, looking at the location of people, how they communicate, and their safety status, says Lamania. IQVIA is partnering on this front with UnitedHealthcare, which is helping with evacuations, and International SOS, which is providing geolocation services and helping at the borders. More than one-third of IQVIA employees have evacuated to neighboring countries, she reports, although individuals who are male or medically ill don’t have that option.
It remains necessary to halt enrollment and studies, she says, with many areas lacking the basics such as electricity and water. But customers, patients, and employees have been equipped with cell phones and internet connectivity across Ukraine and Russia for communication purposes.
New regulatory guidelines have been issued providing advice on protocol deviations, distribution of investigational medicinal products, and establishment of depots for the delivery of lab kits and working with central and local labs, Lamania reports. Most importantly, when it comes to trial continuity—be it during COVID, a tsunami, or war—is protocol monitoring, and that includes ensuring that participants get needed safety assessments.
Site management, she says, focuses on data integrity and the chain of custody. Site activations have ceased in Ukraine and Russia, and in the war-ravaged nation the associated risks to more than 100 clinical trials are being actively assessed and monitored.
Patient reassignment to other sites has been most challenging in Eastern Ukraine, says Lamania, although many investigators are purposefully situated in Western Ukraine. A call center has been established for patients, so they know where to go, what to do, and what kind of help is available.
In March, IQVIA’s clinical research associates had close to 3,600 contacts with investigators in Ukraine, she continues. “Regardless of the situation... what matters is the TLC you give to sites and site staff.”
That support “gives us hope, a willingness not to give up,” interjects Titkova, highlighting the resilience of the Ukrainian people.
Moving Forward
Recruitment of patients into oncology trials was strongly driven by the high cost of care before the war and that is even more so the case today, Ryll notes. Many people who used to be able to afford to pay for treatment are now out of a job, or the institution where they worked was bombed and no longer exists.
For men with cancer, leaving the country is possible but especially difficult, she adds. MPNE has been helping individuals access care, but the process of finding a specialist who can support patients is complicated. “Even to make a small difference with a single individual takes a lot of effort ... cancer is not a priority under war.”
On the other hand, says Ryll, an investigator in Kyiv was unwilling to leave the city when the bombing began until her patient could be transferred to a safer location. And in Odessa (in southwestern Ukraine) an investigator continues to provide treatments to patients and keeps in touch with them using MPNE-supplied digital devices.
More structured support would make efforts on the ground more effective, Ryll continues, noting delays in treatment translate into worse outcomes for people with cancer. The war has forced new ways of thinking about patients, data sharing, and the ability of a trial to continue even if individuals move and may literally be running. “Humanity is not entirely lost,” she concludes, referencing the many people who continue to offer support against a backdrop of evil.
Increased wartime collaboration among regulatory agencies around the world is an “opportunity to influence the clinical trial paradigm,” says Lamania. The DIA, the Association of Clinical Research Organizations, and the broader community of physicians and healthcare companies can help make that happen to ensure trial participants are supported “for the betterment of human health and humanity moving forward.”
Nationalism tends to emerge during disasters like war, but innovation results more from global-level collaboration, says Granville. She was responding to Titkova’s sentiment that site-based studies need to be more portable country to country so that they, like decentralized clinical trials, better accommodate patients of different nationalities.
