Kharkiv National Medical University
Pratia Clinic Ukraine
n February 24, 2022, many aspects of life in Ukraine were profoundly changed or altogether stopped. This included the clinical research industry: On this very day, the approximately 600 clinical trials in Ukraine were stopped. Subsequently, the State Expert Center of the Ministry of Health of Ukraine, the primary regulator of clinical research in the country, received 132 letters of premature clinical trial termination: 108 due to the invasion and 24 due to financial, safety, and efficacy issues. The State Expert Center also received 223 letters from sponsors and CROs regarding the transfer of clinical trial patients to other Ukrainian clinical trial sites or sites in other countries. Most of these were oncologic, neurologic, rheumatologic, gastroenterologic, or cardiologic patients.
Here is the story of one of those patients.
From March to September 2020, Anastasiya received six courses of BEACOPP-14 (a chemotherapy combination that includes bleomycin sulfate, etoposide phosphate, doxorubicin hydrochloride, cyclophosphamide, vincristine sulfate, procarbazine hydrochloride, and prednisone), resulting in 70% regression of major pathologic indicators. In October 2020, she received remote gamma therapy of the mediastinum (40 Gy) and cervical-supraclavicular zone (38 Gy).
In January 2021, Anastasiya relapsed. She received two courses of ICE (a chemotherapy combination used to treat lymphomas that do not respond to other treatments and includes isofamide, carboplatin, and etoposide phosphate) between March and April 2021 with no results. Between June and September 2021, she received three courses of adcetris, but her disease continued to progress.
After her doctors told her that there may be no other options (with approved drugs) available to help her in Ukraine, Anastasiya signed an informed consent form (ICF) to participate in a clinical trial for treatment with pembrolizumab. Significant disease regression was documented after two dosages.
After her last infusion in March 2022, Anastasiya was informed that it was impossible for her to continue in the clinical trial because there would be no reliable delivery of the IMP (Investigational Medicinal Product) to Ukraine for the foreseeable future. However, by April 2022, several international organizations had helped develop recommendations for procedures to transfer patients to safer locations in response to this conflict, and Anastasiya was offered and accepted the opportunity to transfer her treatment to an affiliated research site in Krakow, Poland. This option appeared to be her last chance for survival.
After confirmation of her acceptance from the site in Poland, Anastasiya was transferred there from the Ukrainian site. The original Ukrainian site was responsible for and executed all necessary notifications and documentation submitted to the MoH and the Local Ethical Committee (LEC). Anastasiya was evacuated by train to Lviv and then by bus to Krakow. At the Krakow site, Anastasiya signed a new ICF, her medical documentation was translated from Ukrainian to Polish, and a Ukrainian-speaking doctor accompanied her to help navigate language translation issues.
Anastasiya now lives in Poland, has found employment in Warsaw, continues to participate in this trial, and is in stable condition.
Regulatory, Ethical, and Patient Safety Steps Along the Way
Anastasiya was one of 14 patients who were transferred from our research sites in Ukraine to continue treatment at sites in Poland during the first half of 2022. Our various challenges in arranging transportation, coordinating languages, and relocating patients and documentation included:
- Documentation
- Study-specific patient identification numbers remained unchanged.
- eCRF data was transferred from sites in Ukraine to sites in Poland.
- Source documents, including all imaging tests and associated descriptions, were electronically scanned and sent by study doctors in Ukraine to study doctors in Poland.
- Study investigators performed all required document language translations.
- Informed Consent: Transferred patients signed new ICFs in both Polish and Ukrainian at the same time in the presence of a bilingual investigator at the new (Polish) site. This center had a Ukrainian doctor who speaks fluent Ukrainian, Polish, and Russian, which proved significantly important in this transfer process.
- Regulatory and Legislative Support
- The MoH State Expert Center issued recommendations for local ethics committees, study sponsors, clinical research organizations (CROs), and patients designed to help patients continue participating in clinical trials during the conflict such as remote or telephone visits, home visits, using digital documents and signatures, using local laboratories, delivering IMP directly to the patient, 24/7 stakeholder communication, and so on.
- The time for regulatory approval of clinical trial materials was reduced from 47 to 30 days (Amendments to the Order of the Ministry of Health of Ukraine #690, 23.09.2009).
- Rules for transporting medical products were simplified: Transportation can be done by public transport and in postal or luggage shipments as long as temperature and storage conditions are properly observed and maintained.
- Requirements for import and distribution of medicines and medical devices in Ukraine were simplified.
- Packaging and shelf-life requirements for the import and distribution of medical devices that can be used as benchmarks in Ukraine were simplified.
- New exceptions were allowed for storage of medical devices: Licensed companies can use new storage premises without submitting the new location for state review and approval.
Conclusions and Calls to Action
The aggravating factor of the conflict introduces many other ethical questions and preconceived notions about how to do the right thing, what to do in certain situations, how to continue the patient’s participation in the study, and so on. But the main principle of our work—patient access to innovative treatment and medical care—remains the same in peace or war and guides our effort regardless of the circumstances or obstacles.
Anastasiya’s example demonstrates that when patients need access to clinical research and care, obstacles and challenges like a shortage of facilities or medicines can be overcome with enough creativity, community care, and support. It is a good reminder that the scientific, clinical, logistical, regulatory, ethical, digital, or other aspects of clinical research can quickly and profoundly change, and that such creativity, community care, and support can be just as important as subsequent medical interventions.