The LÆGEMIDDELSTYRELSEN, the Danish Medicines Agency, published guidance describing the extraordinary measures for clinical trials in the context of the outbreak of the Coronavirus Disease 2019 (COVID-19).
COVID-related Regulatory Background
The Danish Medicines Agency acknowledges the significant impact caused by COVID-related factors and additional difficulties medical device manufacturers face during the pandemic due to extraordinary and temporary measures, such as quarantine or travel restrictions. In the context of clinical trials, this results in issues related to access to healthcare institutions that are reduced nowadays to prevent further spreading of infection. In these circumstances, it becomes quite difficult for medical device manufacturers that are conducting clinical trials to maintain compliance with the applicable requirements, especially ones related to protocols of clinical trials. As it is stated by the Agency, due to the impact caused by the aforementioned factors, the number of deviations in clinical trial protocols submitted by the medical device manufacturers has increased significantly. Thus, the authority finds it necessary to implement special measures in order to assist industry representatives and ensure the availability of vitally important medical devices during the pandemic.
The Agency confirms that the shortage of personnel of healthcare facilities could be one of the factors impacting the effectiveness of clinical trials. The Danish Medicines Agency acknowledges that during the COVID-19 outbreak a significant part of the staff could be engaged in COVID-related activity. Thus, the sponsor of the trials (usually it is the medical device manufacturer) should take this into account when developing a plan of the clinical trials.
Additionally, the Agency also acknowledges that COVID-related factors could also impact the ongoing clinical trials. At the same time, the authority encourages the sponsor to continue the trials to the greatest extent possible providing that all necessary protective measures are properly taken in order to ensure the safety of the patients and healthcare personnel.
EU Guidelines on Clinical Trials
The Danish Medicines Agency explicitly confirms that special provisions introduced by the appropriate European guideline are also applicable in Denmark. In particular, the document describes special measures related to clinical trials carried out during the pandemic. At the same time, the authority provides some additional rules and clarifications regarding the way the procedures described in the aforementioned European regulation should be applied.
- Notification rules should be applied exactly as prescribed by the European guidelines,
- Remote data source verification is allowed in Denmark,
- The IMP could be provided directly to the trial participants.
Clinical Trials for COVID-related Medicinal Products
The document published by the Danish Medicines Agency also described special rules to be applied in case if the medicinal product subject to assessment is intended to be used in the context of combating COVID-19, its complications, and respiratory illness associated thereto. The Agency states that all requests related to such products should be prioritized due to their significant importance in the context of public health protection.
According to the general rule that still remains applicable, the clinical trials should be carried out in compliance with Good Clinical Practice (GCP), as well as with other requirements set forth by the applicable legislation. The Agency also states that if the sponsor of the trials has any doubts regarding the way the clinical trials should be performed, it should contact the GCP units to obtain additional clarification.
The authority also recommends the sponsors to provide the information related to the planned clinical trials in advance since this would allow the authority to react in a timely manner on all associated requests. It is also important to mention that the indication «COVID-19» should be included in all related requests.
However, in case if COVID-related factors actually prevent the sponsor from conducting clinical trials in accordance with the pre-defined plan, such factors could be the basis to postpone the commencement of the trials or recruitment of participants. At the same time, such trials should be initiated when the impact of COVID-related factors would be no longer valid.
Additional Rules For Clinical Trials` Sponsors
The document published by the Danish Medicines Agency also describes additional rules covering the most important aspects related to clinical trials, namely:
- All changes implemented to address the impact of COVID-related factors should be treated as «Urgent Safety Measures». Due to their nature, they are allowed to be implemented immediately without making a prior notice. At the same time, if such changes could impact significantly the benefit/risk balance, the regulating authority should be informed accordingly. In the course of such notification, the sponsor should provide a high-level trial-specific risk assessment describing the impact caused by the changes in question to the patients` safety. Since COVID-related restrictions could prevent the regulating authority form carrying out the on-site inspections, they could be postponed, and the telephone consultations should be performed instead. In case it is reasonably necessary to make significant changes to ongoing trials, such changes should be implemented in accordance with the general rules. The sponsors are also allowed to submit the applications covering several clinical trials at once.
- As soon as the COVID-related restrictions would be suspended and normal business operations and regulatory procedures would be restored, the sponsors of clinical trials would have to submit all notifications in a way prescribed under the general rules. In particular, the sponsor shall provide the Agency with a detailed description of all deviations made to the initial plan of the trials. The Agency also encourages sponsors to check the possibility to restore normal regulatory procedures and perform this as soon as it will be reasonably possible due to the COVID-related circumstances. According to the guidance, the aforementioned notification on deviations should be submitted immediately upon restoring the normal operations.
- The risk assessment procedures should be also amended accordingly considering the impact caused by COVID-related factors. The on-site monitoring should be performed to the maximum extent possible unless it will expose patients and healthcare professionals to unnecessary risks. At the same time, the Agency emphasizes that rules related to safety monitoring could be subject to changes in case if the situation with the infection, in general, will change.
Another important point highlighted in the guidance published by the Danish Medicines Agency is related to the remote source data verification. Nowadays remote technologies are widely used in the context of the pandemic to ensure efficient communications and data transfer in spite of any restrictions and quarantine. At the same time, any remote data transfer technologies used by the sponsor of clinical trials should comply with the requirements set forth by the Danish Data Protection Agency to ensure the highest level of patients` data protection.
Summarizing the information described here above, the present guidance issued by the Danish Medicines Agency is dedicated to the clinical trials, and the way they should be carried out during the pandemic.
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