How To Transfer Clinical Trial Participants From Ukraine To EU Sites
Executive Summary
An EU expert group and a number of member state agencies have published advice on the practicalities of safely moving Ukrainian clinical trial subjects to sites in EU and European Economic Area countries.
The EU’s Clinical Trials Coordination Group (CTCG) has issued guidance on how to manage the transfer of patients from Ukrainian trial centers to sites in the EU within a multinational clinical trial as the conflict in Ukraine continues.
Among other things the group says that it is up to the trial sponsor to decide whether to transfer patients, pointing out that the benefit to trial subjects “needs to be carefully considered in each case.”
The guidance follows the publication of advice last month by the European Commission, the European Medicines Agency and the EU Heads of Medicines Agencies (HMA) on how to deal with the inevitable trial protocol deviations resulting from the Russian invasion of Ukraine. (Also see "EU Advises Use Of Pandemic Flexibilities For Trials In Ukraine" - Pink Sheet, 31 Mar, 2022.)
A number of EU member state regulators have also published their own guidance on the transfer of trial subjects, taking into account national specificities such as language requirements and local clinical trial insurance arrangements. They include Hungary, Poland and Slovakia, which have borders with Ukraine, as well as the Czech Republic and Austria.
Links to these national documents are provided in the guidance published by the CTGC, which is an expert working group of the HMA that works on the classification, assessment and oversight of clinical trials in EU member states.
“Sponsors are encouraged to make necessary arrangements to allow transfer of refugees to study sites in the EU/EEA” – CTCG guidance
In general, the CTCG guidance says, “the primary objective of ensuring further participation of clinical trial participants is that they have continuous access to the investigational treatment that they are likely to benefit from.” In such situations, sponsors are “encouraged to make necessary arrangements to allow transfer of refugees to study sites in the EU/EEA.”
Where possible, sponsors should inform the Ukrainian sites that participants could be moved to an EU/EEA trial site, and should provide a list of all such sites and their recruitment status. They also need to determine whether the EU/EEA sites have the capacity to assume responsibility for additional trialists, and whether any changes to the clinical trial agreement with the investigator or institution are needed.
Sponsors should assess the availability of interpreters for the EU/EEA site as well as in the ongoing medical care setting, and the trialist should confirm in writing that they agree to the transfer. Relevant documents including questionnaires, where ,applicable should also be in a language understood by the participant.
“Trial participants might have their trial participant number available” to “allow the sponsor to provide the treatment as initiated in Ukraine,” says the guidance. Case report forms in electronic versions should allow EU/EEA centers to gain access to data already collected for an individual trial participant.
The regulatory provisions for the transfer of patients from Ukraine to an EU/EEA center could include accelerated approval procedures and a post-transfer notification process, according to the guidance. It says that where substantial modifications to the trial are needed, EU/EEA member states have “indicated their willingness to offer accelerated procedures for applications clearly indicating to be in relation to the war in Ukraine.”
Other aspects to consider include reimbursement of the EU/EEA centers for any additional medical care provided, travel assistance, and local insurance conditions.
Hungarian Guidance
The Hungarian National Institute of Pharmacy and Nutrition said that with any transfer of trial subjects to an ongoing trial in Hungary, patient safety and wellbeing were the main responsibility of the trial sponsor.
It said that patient information and proper communication between sites and patients should be provided throughout the clinical trial, for example with the help of an interpreter, a relative, a friend or an acquaintance. The sponsor should also ensure the timely translation of the patient diary (if applicable), as the investigator will need this to make decisions related to the patient’s treatment.
A risk assessment should be carried out regarding the further use of data on patients who started their trial participation in Ukraine and continued it in Hungary. “The sponsor needs to bear in mind that patient data by default cannot be used in the clinical trial, since transfer of source data is presumably not feasible in the current situation, and cannot be controlled later either.”
The agency also stressed that the primary objective of ensuring further participation of clinical trial subjects was that they could have continuous access to the investigational treatment they were likely to benefit from.
Czech Republic
The Czech agency, SÚKL, said sponsors would need to check the capacity of the Czech site to accommodate new subjects, and that they should help with arranging transport and covering travel costs.
It pointed out that in view of the conflict in Ukraine, source data were unlikely to be available. “The sponsor has to take into account the possibility that these data obtained from Ukrainian TS [trial subjects] will not be included in the final statistical processing of the clinical trial results, nor can they be used for the product registration or a change to the registration.”
Investigational medicinal products (IMPs) would have to be secured and delivered to centers in the Czech Republic so that trialists can continue on the same treatment, SÚKL said, adding that it was currently not possible to have the IMP sent from Ukrainian sites.
As case report forms (CRFs) are now in electronic form, “there should be no problem for Czech centers to continue filling them in,” the agency said. “The information from CRF should also make it clear at what phase of the clinical trial the trial subject is.” Similarly, electronic versions of the patient information and informed consent forms will be available in Ukrainian or Russian, and subjects should sign the current version of the document after transfer to the Czech center.
Poland
The Polish Office for Registration of Medicinal Products, Medical Devices and Biocidal Products said it was not necessary to seek its permission to relocate trial participants from Ukraine to Polish trial centers.
“When conducting relocation, it is necessary to take into account the recruitment possibilities of research centers and the availability of the study drug,” it noted.
Under normal circumstances, sponsors carrying out clinical research in Poland and Ukraine cooperate on the exchange of information, but “the violence of hostilities in Ukraine often leads to a situation in which there is no such possibility,” the office said. “In this case, the key element that should be considered when deciding whether to allow the continuation of the study to a patient from Ukraine is the availability of his source documentation.”
In Poland, it noted, clinical trials are subject to civil liability insurance of the investigator and the sponsor. “Before carrying out relocation, it should be analyzed whether the insurance for a given study should not be changed due to the changing number of participants in Poland (the amount of the guarantee sum depends on the number of participants receiving the drug or being in the control group).”
Austria
The Austrian Federal Office for Safety In Health Care (BASG) said sponsors should submit an informal notification to the BASG within one week of the transfer of a trial participant to an Austrian site. This should include confirmation of the notification to the ethics committee, information on the site to which the patient has been transferred, and whether they are receiving treatment or are “only in follow-up.”
“If the same trial is not authorized in Austria, the patient could be recruited into another trial (such as a catch-up protocol) or an authorized compassionate-use program,” the agency suggested. They could also receive treatment under the named-patient rules, although it points out that this would require a treating physician in Austria.
Where the IMP is administered by the investigator or other study personnel, labeling in Ukrainian is not required, the BASG said. However, where the product is managed by the participant, the investigator should ensure the trialist understands the minimum information required by the Austrian regulations.