Clinical Arms

Pre-2022, the Russian Federation was among the top 10 destinations for clinical development, according to trial data analytics specialist Phesi. Up until its invasion of Ukraine, Russia’s number of actively recruiting clinical investigation sites ran almost parallel with that of Poland – peaking at 3,519 in March 2022. By March 2023, however, that number had dropped to 1,239, representing a decrease of almost two thirds, whilst numbers increased in Poland to 3,889 at its peak in November 2022, broadening the gulf in active research between the two Eastern European neighbors.

Actively recruiting clinical investigation sites have also shown a dramatic decrease in numbers in Ukraine during the same period as a result of the ongoing conflict. Similarly, the decrease is again by around two thirds from 1,846 in March 2022 to just 670 in March 2023.

These trends are not surprising, but the data do strongly highlight the huge loss of development – to the detriment of patients. Here, Phesi CEO Gen Li discusses the effects of the conflict on clinical trials.

What impact could the reduction of trials in Russia and Ukraine have on new drug approvals?
 

The reduction in clinical trial sites is unlikely to have a direct impact on new drug approvals, but it will affect trials that are ongoing, delaying them from getting to the approval stage. As recruiting sites close and patients are relocated, trials will be slowed down as they go off-plan.  

Certain disease indications are particularly affected. In early 2022, more than a quarter (26 percent) of schizophrenia trials took place in Ukraine and Russia, as well as a high proportion of gastrointestinal disease studies – including ulcerative colitis (14 percent) and Crohn’s Disease (10 percent). These disease indications have been disproportionately impacted in related development programs.

Another issue that I am concerned about is that geopolitical events continue to shrink the map for clinical development. Conflict and other political events can make it more difficult to diversify in terms of patient participation, reducing the size of the population that innovative medicines can benefit.

What challenges do sponsors face in acquiring, analyzing, verifying, and publishing such data in extreme circumstances?
 

Acquiring data is going to be the main challenge here. As clinical development activities in Russia, Ukraine, and Belarus have been put on hold, clinicians have had to redirect their time and attention to more urgent needs while patients have been directed to sites in neighboring countries. This leads to a fall in recruitment as reallocation puts additional burden on patients who must travel further. It also poses questions around data integrity and continuity as data is transferred between sites and clinicians. As ever, protecting the wellbeing of patients in this and similar situations should be at the center of all actions.

What can researchers do to mitigate the effects of conflict in clinical trials?
 

Researchers should not be asked to bear the sole responsibility of adapting clinical trial protocols when disruption occurs. It is the responsibility of sponsors and trial planners to prepare for conflict, assess potential risk, and prepare risk mitigation plans. Intelligent application of clinical data science has proven effective at facilitating these important steps. And that means using data from previous clinical trials to generate deeper insights into trial protocol design, target patient populations, and eliminate unnecessary and dated practices, such as placebo arms. Such an approach allows sponsors to be flexible when unexpected events and disruption occur – with minimal impact on patients.

Companies should also explore how data and AI technologies can be applied to simulate trials and predict outcomes, using scenario modeling to bolster protocols against disruption. Moreover, insights from existing data can supplement disrupted studies to get trials over the finish line. For many trials in the later stages, there may already be enough data available to create digital twins that can replace comparator arms, helping urgently needed treatments reach patients faster.

Is there a case for increased uptake of decentralized clinical trials in such extreme circumstances?
 

Decentralization was applied to many trials at speed during the pandemic and brought many benefits, including widening participation among hard-to-reach populations and reducing the burden of travel and attendance on patients. But beyond times of crisis, decentralized trials should not be seen as a wholesale replacement for in-person studies, which are also highly valuable. For the best chance of success, trials will increasingly need to deliver a mix of in-person, decentralized, and even digital trial arms, depending on the indication under study.