March 18, 2020
Comparison: how do the CEE regulators react to SARS-CoV-2 when it comes to clinical trials
What advice do we get from the drug regulatory agencies in respect of clinical trials these days?
There is no unified/aligned approach by the regulators, very different situations in each country.
Here is an overview of how regulators in selected CEE countries react to COVID 19 pandemic.
Short summary first, followed by a link to the regulator´s webpage with the respective guidance.
1. Czech Republic
A) Regulatory authority (SUKL) issued guidance, English version not available, links below.
Changes in visits or trial participants’ affiliation to an investigator site:
It should be considered whether physical visits can be converted into phone visits, postponed or canceled completely to ensure that only strictly necessary visits are performed at sites in order to guarantee the safety of trial subjects. It is not necessary to inform SÚKL or the ethics committee, this change should be properly documented including justification about the current situation into the source documentation. The sponsor should include this change in the annual reports of the clinical trial. It is essential to ensure in advance of any visit that the trial subject is not in quarantine lives with a person in quarantine or is infected with coronavirus and agrees with an alternative procedure (telephone visit, transport of IMP to patients’ home via authorized courier, etc.). It the visit is necessary to be performed at the site, it is essential to arrange the visit in advance by telephone and ensure that all protective equipment for medical staff and the subject is provided.
Changes to shipment/handling of IMP:
It is mandatory to apply for SÚKL approval in case that IMP will be delivered to the patient without a visit at the site. The sponsor’s request should include any information about IMP, details, and safety of transportation, verification and confirmation of receipt from a patient via e.g. telephone. If possible, provide IMP to subjects for a longer period than originally planned within the upcoming visit. There will be the need for delivery of IMP directly to trial subjects to avoid subjects coming to the site with a consequent risk of infection. An authorized courier of the sponsor may be used to transport IMP, following by confirmation of receipt from the trial subject via telephone and recording in the source documentation. In the case of intravenous application, if the protocol allows, it is recommended to postpone the IMP administration. If not, it is possible to arrange the administration of IMP at the site in compliance with safety requirements or in an emergency to provide administration of IMP at the patient’s home ensuring such administration is provided by appropriately qualified and trained medical personnel. It is required that the patient retain the unused/used IMP until safety precautions will be withdrawn.
Changes in monitoring:
Changes in the monitoring plan, in order to postpone on-site monitoring or replace it with remote monitoring visits via telephone, need not be reported to SÚKL or ethics committee. It is mandatory to properly document and justifies reasons in the clinical trial report.
To ensure the safety of subjects, SÚKL does not recommend:
A) No guidance issued by RA so far.
Patients are advised to avoid hospitals and outpatient. People exposed or suspected of exposure to the coronavirus are put under 14-days home- or hospital quarantine in order to decrease the risk of coronavirus’ transmission. All hospitals have strict rules for visitors and many of them are being restructured to serve as infectious-diseases hospitals from now on. On-site monitoring and travel restrictions have been imposed in many of the companies. It is expected that due to the ongoing crisis number of protocol deviations will rise. For now, it is important to document them in the best way possible.
Currently, Polish competent authority - the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products operates as usual and has not yet issued any specific recommendations regarding conduct and registration of clinical trials in Poland. Officers at the Office only inform that in case of an event that could affect the safety of study participants, sponsors and clinical investigators are obliged to take measures to ensure the safety of trial participants.
A) Regulatory authority (OGYÉI) issued guidance, English version not available, links below.
A monitoring visit is forbidden. As always patient safety first, second priority is the validity of the data. All deviation must be properly documented. Electronic IC/PI still not allowed. Urgent Safety Measures are applied immediately. In case the site is re-located, notification to the authority is sufficient to continue the clinical trial. Granting access to the patient electronic database of the institution is not allowed for monitoring purposes. Remote monitoring or Central EDC monitoring must be focused on data necessary for the conduct of the clinical trial to minimize the load of the site.
A) Regulatory authority (ŠÚKL) issued guidance, English versions available, link below.
ŠÚKL recommended that changes due to COVID-19 should be handled as ‘Urgent Safety Measures’ and can be implemented without approval from ŠÚKL, however, ŠÚKL has to be notified without delay. The sponsor’s detailed risk assessment should be provided with the notification.
ŠÚKL acknowledges the need to adjust the monitoring of clinical trials in order to overall risk assessment due to COVID-19. The risk assessment should take into consideration whether recruitment should be stopped temporarily. The sponsor should assess whether clinical trials should be put on a temporary halt. On-site monitoring can be performed after agreement from the site, if it is not possible to follow an on-site monitoring plan, monitoring should be supplemented with centralized monitoring.
There is a possibility in case of a shortage of IMP to potentially redistribute IMP between sites in accordance with GMP. There will be the need for delivery of IMP directly to trial subjects during the COVID-19 pandemic to avoid subjects coming to the site with a consequent risk of infection. IMP can be also dispensed to a relative at the site after telephone verification with the trial subject. Subject acceptance should be verified via telephone and recorded in the source documentation. Also, an authorized courier of the sponsor may be used to transport IMP, following by confirmation of receipt from the trial subject via telephone and recording in the source documentation.
ŠÚKL recommends the sponsor to consider the transfer of trial subjects to another site (e.g. to less affected areas) if all sides agree. It should be considered whether physical visits can be converted to phone visits, postponed or canceled completely to ensure that only strictly necessary visits are performed at sites. In case it is not feasible for the site to continue participation at all, the sponsor should consider it the trial site should be terminated.