The Russian invasion has upended hundreds of clinical trials and interrupted the delivery of disease-fighting and life-saving treatments.
A little-known fact of the pharmaceutical business is that it increasingly has used Eastern European nations, and Russia and Ukraine in particular, for later phase clinical trials.
These Stage 3 clinical trials are critical to take a drug from the research bench to the bedside. They require larger populations of human volunteers – generally between 300 and 3,000 – than the first two stages, which test for safety in small groups, and may last for several years. Phase 3 includes volunteers from different regions and countries prior to approval by regulatory bodies. Phase four, is post-approval, longer-term safety screening.
Big pharma began investing in clinical trial sites in Ukraine and Russia for several reasons:
- The U.S. Food and Drug Administration requires that the application for approval of a new drug or treatment include studies conducted in sites with comparable race and ethnicity – something achieved more easily in Russia and Ukraine than in Asian countries.
- Clinical trial sites in Ukraine and Russia typically charge lower fees than the U.S.; always welcome for a research budget.
- With a centralized medical system in Ukraine, condition-specific hospitals and improved electronic medical record systems, the ability to conduct studies efficiently have made Ukraine increasingly popular for pharma.
- The medical journey for many Ukrainian patients, with fewer treatment options compared to North America or Europe, leads more quickly to enrollment in clinical trials. This is especially true for cancer patients who may have few other treatment options, especially those with late-stage cancers that are largely palliative.
Prior to the war, more than 60 per cent of the clinical trials in Ukraine involved oncology patients.
Prior to the war, more than 60 per cent of the clinical trials in Ukraine involved oncology patients, especially those with lung cancer, followed by central nervous system disorders, infectious disease, gastroenterology and cardiovascular diseases.
Research investigators in Ukraine are highly motivated and trusted by their patients, leading to low dropout rates and high recruitment, Vlad Bogin, founder of Cromos Pharma, a contract research organization with clinical trials in Ukraine and Russia told the Journal of the American Medical Association.
When Russia launched its invasion in February, there were 597 trials under way or actively recruiting in Ukraine, according to ClinicalTrials.gov, the global database of public and private funded studies. That number was 1,353 for Russia and, by comparison, 4,719 for Canada and 26,955 in the U.S.
The war’s impact on current trial patients in Ukraine and Russia is unclear. Status updates on clinical trial websites are often out-of-date and attempts to contact specific clinical trial site investigators across Ukraine have been unsuccessful. Patients and investigators alike may be displaced. Pharmaceutical companies like Roche report that they are still attempting to treat study patients in both Ukraine and Russia, even those displaced out of Ukraine.
Meanwhile, most large firms have said they will no longer use Russia for their trials but will continue to supply drugs to its health-care system. (Pfizer has said it would donate all its Russian profits “to causes that provide direct humanitarian support to the people of Ukraine.”)
Some cancer patients will be unable to receive life-prolonging or life-saving treatments, their last hope.
Big pharma’s Russian withdrawal may have been nudged by websites such as the Yale School of Management website that “grades” more than 1,200 companies since the invasion of Ukraine to promote withdrawal of companies from Russia. And according to this metric, it would appear that big pharma is doing the “right thing” by stopping enrollment in clinical trials; however, the majority of big pharma companies including Abbvie, Merck, Eli Lilly, Glaxosmithkline, Novartis, Pfizer, Sanofi and Roche get “Ds” for continuing “substantive business” while postponing future planned investment, development, marketing. In contrast, an “A” would mean complete cessation of Russian engagement or complete exit from Russia.
Suspension or premature cessation of clinical trials will have devastating consequences for some Ukrainians and Russians. Some cancer patients will be unable to receive life-prolonging or life-saving treatments, their last hope. Those with chronic diseases like Crohn’s will have reduced quality of life. From a science and patient point of view, the impact of missing data points on study results may slow down the successful testing of new treatments for people world-wide.
With the war still raging, the continued devastation of medical infrastructure in Ukraine, and sanctions against Russia, pharma may opt to resume these studies with new sites outside Ukraine and Russia. Planned clinical trial studies seem likely to exclude Russia and Ukraine for the foreseeable future.