Far-reaching impact of the Russian invasion of Ukraine on global cancer research

Clinical research is crucial for national cancer control plans. Prior to the Russian invasion on 24th Feb 2022 both Russia and Ukraine were signiﬁcant contributors to global clinical trials and cancer research. In this short analysis we describe this and the impact that the conﬂict has had with wider consideration for the global cancer research ecosystems ª 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

The Russian invasion of Ukraine on February 24 2022 has set in motion a series of catastrophic events.For the aggressor Russia, economic sanctions, including reduced imports of pharmaceuticals, will directly impact the health of the country's most vulnerable [1].For Ukraine, population displacement within and across national boundaries, destruction of healthcare facilities, displacement of healthcare workforce and damage to healthcare logistics will have serious long-term consequences that will only be mitigated by an end to the conflict and reconstruction of Ukraine's health system.Overall, around 1100 medical facilities were damaged, 144 among those were completely destroyed.Hospitals and clinics in 17 regions of Ukraine suffered from shelling and air strikes.Most affected regions are as follows: Kharkivska oblast e 249 medical facilities, Donetska oblast e 210, Mykolaivska oblast e 148 and Kyivska oblast e 121.Life in Ukraine changes on an almost daily basis as Ukrainian citizens move to safer places or return homes.Nevertheless, figures show that about 7.5 million Ukrainians have left the country and approximately 3.0 million returned.Almost 7 million citizens are considered internally displaced.It is hard to say the exact number because Ukrainian counterattacks, liberation of captured cities and winter conditions constantly change patients place of residence, particularly in the Eastern Oblasts (see Table 1).
The impact of Ukrainian refugees in Europe will also create new challenges for health systems capacity, especially for Central and Eastern European countries, particularly for non-communicable diseases.While there has been substantial discourse on this already [2,3], what has gone relatively unnoticed is the profound impact the war is having on cancer clinical research.Both Russia (upper middle-income) and Ukraine (lower middleincome) are unusual in their global cancer research activities.Both are two of the largest contributors to clinical cancer research, especially to industry-sponsored randomised clinical trials (RCTs).
Ukrainian clinical cancer research, in particular, has enjoyed a long history.Between 2014 and 2017, a total of 636 cancer RCTs were published.Ukraine contributed to 39 of these, one of the highest lower middleincome contributors, placing it only just behind India, a country over thirty times its size.Moreover the quality of RCT remains high; Ukraine is the only one post-Soviet country which is represented in the "Clarivate Analytics" ranking (2022) among the 19 leading countries of the world with highly cited publications in clinical oncology.For upper middle income countries, Russia was by far the largest contributor to 115 cancer RCT over this period.At the start of the war, an analysis of ClinicalTrials.Gov on February 24 2022 indicated that Ukraine had n Z 245 active pharmaceutical cancer clinical trials, of which 127 were actively recruiting.Corresponding figures for Russia were n Z 667 and 352, respectively.
Beyond the numbers, clinical cancer research finds itself in unchartered territory.The loss of centres which are such major recruiters to global RCTs will have significant impact worldwide.It has taken many years for Ukraine to develop it's strong cancer clinical trials ecosystem including research ethics processes, contract research organisations and high public trust.Such developments have been put at grave risk by the ongoing conflict.The loss of the opportunity to participate in RCT is a significant loss for Ukrainian patients who thereby lose access to innovative cancer treatment.In addition, since the start of the war, Ukraine has lost a large number of clinical research specialists.Human capital that will need to be rebuilt in the post-conflict era.
Many major clinical trials will be delayed as new centres elsewhere are brought online and some will undoubtedly fail to recruit.Pharmaceutical companies are struggling to balance ethical duties to patients with broader security and geopolitical realities.Even if the legal, ethical and security issues can be surmounted, the war has created massive logistical barriers to supplying basic standard-of-care cancer medicines.Sponsors are also grappling with serious moral issues, for example, do they have an obligation to continue ongoing cancer clinical trials in conflict settings?
As the extent of Russian violations against international humanitarian law has become apparent, multinational corporations have come under increasing pressure to withdraw all engagement with Russia.Additional pressure has been applied to these companies through the so-called Yale List [4], which has illuminated which companies have/have not withdrawn from Russia.Many of the major pharmaceutical companies on the Yale (AstraZeneca, Pfizer, Glaxo Smith Kline (GSK) et al) have taken the position to stop new investment and new clinical trials but to continue both preexisting trial recruitments and supplying standard cancer medicines as per contractual arrangements.
The situation in Ukraine is very different.While many cancer centres in Kyiv and the more Western and Central Oblasts are still functioning at time of writing, many centres in the East and South have been destroyed/occupied by Russian forces or rendered unsafe by proximity of the fighting [5].The massive displacement of the Ukrainian population, coupled to hospitals having to orientate themselves to a war footing, has meant that many cancer trials have had to be suspended, although anecdotal reports reflect attempts by many cancer centres still operating in Kyiv and Western, Central Ukrainian Oblasts and even those

Table 1
Top 5 country-level participation in global randomised clinical trials (RCTs) published 2014e2017 by United Nations income category compared to their total cancer research outputs over same period.