Special Section: Clinical Research in Ukraine
From COVID-19 Pandemic to War: Clinical Trial Industry Powers On Under Extreme Conditions
Anina Adelfio
Association of Clinical Research Organizations (ACRO)
@ACROhealth
T

he years 2020 and 2021 shaped how clinical trials are currently operationalized. When the COVID-19 pandemic began in early 2020, sponsors and Clinical Research Organizations (CROs) were up against unforeseen changes, including site closures and a shift to remote monitoring of source data. Sponsors and CROs set up business continuity teams to keep trials running despite the site closures they were seeing and unprecedented circumstances they were up against, and were able to deploy remote technologies while prioritizing patient safety and data integrity.

Remote Trial Operations During the COVID-19 Pandemic

In 2020 and 2021, as a result of the COVID-19 pandemic, clinical trials were utilizing more remote components. This was already spreading across the clinical trial industry because of the increase in the speed, quality, and availability of the technology and the regulatory and clinical flexibility to use centralized monitoring and remote monitoring. But the response to COVID-19 really brought it to the next level.

A landscape survey conducted by ACRO of approximately 5,000 clinical trials shows that centralized monitoring increased by 119% between 2020 and 2021 and off-site or remote monitoring increased by 72% in the same timeframe. When you look back at 2019, you also see off-site or remote monitoring increase by 150% in 2020. This shows the dramatic shift made by CROs and sponsors during the COVID-19 pandemic. This same landscape report shows a slowing of the uptick of these components in new studies started in 2021 as on-site visits resumed, and we see the normalization of COVID-19 and fewer site shutdowns. The data reported on new study starts illustrates how remote approaches might impact post-pandemic clinical trial operations.

Regulatory Guidance

Global regulators reacted quickly when the COVID-19 pandemic hit. The stakes were high, and industry needed guidance on how to continue operations despite the difficult and unprecedented circumstances they were facing. The US FDA, the EMA, and the MHRA (UK) were just some of the regulators who rapidly released guidance documents and continued to update these guidance documents as the pandemic progressed.

This quick response from regulators was instrumental in supporting efforts to respond to the pandemic. Sponsors and CROs maintained compliance with good clinical practice (GCP) principles while minimizing risks to trials and to data integrity during the pandemic.

Business Continuity in More Extreme Circumstances

At the start of 2022, clinical trial operations had finally settled down after the COVID-19 pandemic. On February 24, 2022, the world witnessed the start of a war in Ukraine. Similar to when COVID-19 started, we had no idea at the start how long this would last. Two weeks of uncertainty? Two years of uncertainty? February 2023 marked one year since this invasion and we still do not know how long this war will persist.

To facilitate the continuity of clinical trials when the war started, sponsor companies and CROs worked to support their staff and patients in and around Ukraine. Shipping services were immediately halted and supplies including the investigational medicinal product (IMP) sequestered. In the first four months of the conflict, an increase in remote monitoring visits was observed as travel to some clinical trial sites was extremely tenuous. Clinical trial participants and clinical staff members were thrown into a war zone. As they were relocating, either within Ukraine or to different countries, sponsors and CROs persevered so that their clinical trials could continue.

Ukraine is a country with significant clinical trial activity and substantial contributions to the medical community. According to the Ukrainian Ministry of Health’s State Expert Center (SEC), 794 clinical trials had been either approved or were in the process of being conducted at various stages within Ukraine when the war began. The war brought profound and tragic impact on the lives of most Ukrainian clinical trial participants. Many moved out of the country, but many were also still able to receive the care they needed due to the actions taken by sponsors, CROs, and investigators on the ground. The Ukrainian SEC reported that in the first four months of the war, 115 patients were approved to be transferred to other clinical trial sites within Ukraine, while 196 patients were transferred to trial sites in other countries. Most of these patients transferred to Poland, but some moved farther into Europe, to Germany, France, Spain, and Italy.

The SEC also reported receiving a total of 386 substantial amendments to clinical trials in this same timeframe. Many of the same operational and regulatory innovations are in place because the pandemic had helped industry prepare to operate under extreme conditions such as the war in Ukraine.

How have some CROs responded to the challenges of ensuring continuity for patients?

  • Business continuity teams, armed with the experience of navigating through COVID-19, were established for studies under way in Ukraine.
  • Solutions were developed to provide continuity: provision of transportation for participants to sites; complementary alternate, remote monitoring; and direct-to-patient delivery of IMP were deployed on trials that were not previously utilizing these approaches.
  • CROs and sponsors coordinated new supply chain solutions for delivery of IMP and other supplies, including provision of routine care.
  • Staff and investigators were supported: first to assure their return home if away on business at the start of the war and continuing during the exodus, especially of women and children, from Ukraine.
  • Individualized solutions were developed for study sponsors, including serving as a local connection to remote sites and as a source of information on the local environment, sourcing power generators, etc.
  • The safety of site staff was prioritized, including facilitating relocation (temporarily or permanently) upon their request.
  • Solutions for laboratory testing were identified when expedited shipping became impossible.

Regulatory Guidance During the War

When the war in Ukraine started, many regulators pointed to the same guidance documents they had developed during the pandemic to provide insights on how to conduct clinical trials in the wake of any disruption, be it a global pandemic or a regional war. For example, the Ukrainian health authority, the State Expert Center (SEC) of the Ministry of Health (MoH), released recommendations for sponsors of clinical trials/representatives of sponsors, researchers, managers of enterprises, institutions, and organizations involved in conducting clinical trials.

In addition, national authorities in Poland, Moldova, the Czech Republic, and Austria issued their own recommendations on how to accept patients from Ukraine; and the European Medicines Agency (EMA) released specific Points to consider on the impact of the war in Ukraine on methodological aspects of ongoing clinical trials, which explicitly refers sponsors to their pandemic-related guidance. This response provided a framework for how to overcome uncertainty and support the continuity of clinical trials, especially for those patients whose participation in a research study provided critical care to them.

“Industry sponsors and CROs are using the experience gained during the COVID-19 pandemic to apply the approaches and flexible practices outlined in regulatory guidance to adapt ongoing studies. Ultimately, this helps patients avoid dropping out of trials,” explained Silvia Garcia of the European Federation of Pharmaceutical Industries and Associations. “Participation in a clinical trial is an important element of healthcare, especially for patients with life-threatening and/or rare diseases for whom a medicinal product under investigation might be the only therapeutic option.” To further support cross-border access to clinical trials in Europe, EFPIA and the European Forum for Good Clinical Practice (EFGCP) kicked off the EU-X-CT initiative in January 2023.

Moving Forward, Not Backward

Regulatory guidance put into place rapidly during the pandemic is being followed to this day. As we’ve seen, regulators pointed to, and industry relied on, these same guidance documents when the war in Ukraine started. It is imperative that we build on this and keep these provisions in place despite the fact that guidances issued in response to COVID-19 were originally intended to be temporary.

In the US, for example, the FDA’s COVID-19 regulatory guidance will be in effect as long as the public health emergency, which has been renewed continuously every 90 days since early 2020, remains in place. In January 2023, President Biden announced that the public health emergency status will end on May 11. To move lessons learned through the global pandemic forward, these pandemic-related guidance documents should not go to waste when this public health emergency comes to a close. They can be repurposed to provide direction for industry in all disruptions and times of uncertainty. We can learn one important lesson from these unusual circumstances and implement remote and hybrid strategies, instead of reverting back to how trials were operationalized before the pandemic.

The unexpected events of 2022 taught us that the uncertainty is likely to continue, whether in conflict zones, in a pandemic, or (often on a smaller scale) in natural disasters. Throughout 2022, regulators, sponsors, and CROs wanted to keep the clinical trial enterprise up and running for sound ethical and scientific reasons: The moral commitment is to keep patients in trials, especially when their participation is incredibly important to their health and safety, such as, for example, the compelling need to focus on continuity of care within cancer treatment trials. Ensuring that patients continue to receive life-saving treatments and are also able to contribute to the development of medicines that benefit the global medical and patient community is imperative.

References are available upon request.

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