Clinical Trial Corner is a biweekly series from Dr. Vladimir Misik, founder of LongTaal and CSOFT’s VP of Global Clinical Strategy.

As I wrote in my introduction to this blog series, my aim here is to introduce and dissect one of the pertinent topics in the area of clinical trials as well as more broadly: pharmaceutical product development. The aim is not to provide a comprehensive review of each of the topics I will pick but to provide my own perspective on the selected topics. As in every good professional discourse, while I strive for objectivity, I would very much welcome alternative views on the selected topics.

While I would have preferred to start the series with a more uplifting topic, it would be remiss to ignore the subject of this post’s title not only because it has dominated in the media space ever since the war started in February 2022, but also because it has a significant adverse effect on global industry clinical trials (iCTs). Timely patient recruitment in clinical trials is one of the greatest challenges impacting the development of new products (I will dedicate a whole post to this topic in the coming weeks), and to date Russia and Ukraine have been providing a significant percentage of globally recruited patients into iCTs. Therefore, any significant disruption in these iCTs markets will inevitably send ripple waves through the industry.

The war launched by Russia in Ukraine has both an immediate and a long-term impact on iCTs not only in those countries but also globally, as the two contribute 3.6% of all global sites in clinical trials performed by innovative biopharma, and an estimated 5% of all global patients in these trials.

Previous articles have surveyed the iCTs landscape in Russia utilizing data by GlobalData, which outlined the possible pipeline consequences of the conflict both in Russia and globally. (1) (2) (3)  The conclusions were based on the number of impacted CTs by sponsor and therapeutic indication.

In our current paper on this topic, which I am using as the primary data source for this post, we went a step further by using LongTaal’s bespoke active sites methodology to provide a snapshot of iCTs at the time when Russia invaded Ukraine and also to project the likely impact not only on the two countries but also on global CTs, as well as outlining the broader socioeconomic consequences to both countries. (4)

Before I start using some new terms ((e.g., iCT market share, accessibility to iCTs, or county iCT reputation index) and start throwing around some numbers associated with those, let me refer you to our recent publication where these terms and the data sources and methodology we utilized in obtaining them are explained. (5)

First, let’s assess the impact of the war on both countries:

Impact on clinical trials in Russia:

On February 24, 2022, when Russia invaded Ukraine, there were 1,243 active CTs in Russia involving 10,158 sites. In 2021 Russia ranked 11th in terms of  global biopharma CT market share (2.44%). Oncology was the dominant therapeutic area.

Western international iCT sponsors contribute approximately of 90% of the iCT pipeline in Russia. While for ethical reasons the export of live-saving and pharmaceuticals does not fall under sanctions, all major pharmaceutical companies have vowed to stop new investments in Russia, including clinical trials (6) (7) (8), halted recruitment of new patients into on-going CTs, and pledged not to initiate new trials in Russia. As a result, over the next three years iCT activity is expected to see an almost 90% reduction from pre-war levels (or minus 2.2% of global iBPCT market share), resulting in a more US$ 1.2bn loss of annual economic value, the loss of almost 8,000 high-end jobs created by the iBPCT industry, and loss of access to cutting edge experimental therapies for over 30,000 patients annually.

Given the overwhelming share of western iCTs sponsors in the Russian CT market, it is unlikely that such market share loss can be compensated to an appreciable degree by Russian, Chinese, and Indian companies, the majority of which are producing generic compounds, which represent only a small fraction of total global biopharma R&D spend.

Impact on clinical trials in Ukraine:

Ukraine’s iCT market was approximately ½ of Russia’s. When the war started, there were 612 active studies conducted at 5015 sites in Ukraine. In 2021, Ukraine ranked 18th in terms of global biopharma CT market share, with 1.18% of global share. Oncology dominated among the leading therapeutic areas.

The short- and mid-term impact of the war will be similar in Ukraine to Russia: due to war disruptions (or anticipated war disruptions) most sponsors have halted recruitment of new patients into ongoing CTs and have paused initiation of new CTs. This situation is likely to continue as long as there are risks (real or perceived) of impact from the war on CTs. However, unlike in Russia, there is expected a swift rebound iCTs activities with the cessation of large-scale hostilities or upon reaching of some kind of peace deal. Lessons learned from the 2014 occupation of Crimea as well as parts of Luhansk and Donetsk regions show that biopharma and CROs are prepared to adapt quickly to a changed situation and place new trials in Ukraine, which has proven to be a reliable powerhouse in international iCTs.

In addition to the severe and immediate effect the war on iCTs in Russia and Ukraine, the global impact is being felt by every major pharma company, every large and mid-sized CRO, and other clinical trial services providers who have to secure delivery of the global industry pipeline with minimal disruptions, delays, or substantial budget overruns.

Impact on global clinical trials:

The global iCT industry needs to plan to reallocate almost 3.5% of global iCT sites and almost 5% of iCT (3) patients annually outside of Russia and Ukraine. We argue that countries in Central and Eastern Europe (Poland, Czech Republic, Hungary, Slovakia, Croatia, Serbia, Bulgaria, Romania, Latvia, Lithuania, Estonia) are best positioned to deliver all or a significant part of this industry pipeline, which is at risk from a unique combination of the proximity of logistical routes, comparable cost, site productivity, as well as underutilized clinical trial capacity.

If you would like to learn more, my in-extenso research paper on this topic is published in the September issue of the Clinical Leader. (4)

About Dr. Misik

Dr. Misik has 30+ years’ experience of working in biomedical R&D at the George Washington University, School of Medicine and at the National Cancer Institute in Bethesda, Maryland. In addition to holding several executive roles in multinational CROs, Dr. Misik founded LongTaal, a company that maintains up-to-date dashboards and visualizations of the global CT scene by introducing a range of tools, including a CT patient accessibility index and country CT reputation index.   

REFERENCES
  1. Castaneda R. Clinical trials in Russia: drug development pipeline at risk. Clinical Trials Arena, March 7, 2022, downloaded on May 26, 2022. [Online] https://www.clinicaltrialsarena.com/special-focus/ukraine-crisis/clinical-trials-in-russia-at-risk/.
  2. Castaneda R. Clinical trials in Russia: big pharma makesmoves but what’s the pipeline impact?; Clinical Trials Arena, March 24, 2022, dowloaded on May 26, 2022. [Online] https://www.clinicaltrialsarena.com/analysis/clinical-trials-in-russia-big-pharma-makes-moves/.
  3. Castaneda R; As Russia’s clinical trials sector falls, Ukraine rebuilds. Clinical Trials Arena; August 23, 2022. [Online] https://www.clinicaltrialsarena.com/special-focus/ukraine-crisis/russia-clinical-trials-fall-ukraine-rebuilds/.
  4. Misik V; The Impact Of The Russia-Ukraine War On Clinical Trials. Clinical Leader; September 7, 2022. [Online] https://www.clinicalleader.com/doc/the-impact-of-the-russia-ukraine-war-on-clinical-trials-0001.
  5. Misik V, Jarosz B, Beckowski L, Czarnecka M, Dabrowski T, Drake D, Milowska K, Ziecik P, Magielski P, Szczepannik W: REPORT: Industry Clinical Trials in Poland. Possibilities to increase number and scope of trials in Poland. Publishers: INFARMA and POLCRO. December 2021; pp 1-115. [Online] https://www.infarma.pl/raporty/raporty-infarmy/raport-%E2%80%9Ekomercyjne-badania-kliniczne-w-polsce.-mozliwo%C5%9Bc-zwiekszania-liczby-i-zakresu-badan-klinicznych-w-polsce/.
  6. Dyer O. BMJ 2022;326:o745. Essential medicines keep flowing to Russia, but sanctions could severely effect health. https://www.bmj.com/content/376/bmj.o745.full.
  7. GlobalData Healthcare. Sanctions hit Russian investors with limited impact on foreign innovator drugs. Pharmaceutical Technology 28 Mar 2022. https://www.pharmaceutical-technology.com/comment/sanctions-russia-foreign-innovator-drugs/.
  8. Mulero A. Ukraine-Russia war pushes big pharma into mixed response. HealthLeaders 23Mar2022 https://www.healthleadersmedia.com/pharma/ukraine-russia-war-pushes-big-pharma-mixed-response.