Covington & Burling posted an alert on March 30th regarding the Italian Medicines Agency (AIFA) guidance on the management of clinical trials in Italy during the COVID-19 emergency which was issued on March 12th. The Guidance covers all the phases of clinical trials (i.e., submission of authorization requests of clinical trials); Ethics Committees’ evaluation; management of clinical trials outside investigational sites. The Guidance also provides some exemptions from the current EU and Italian legislation (i.e., management of the Investigational Medicinal Product); closure of a clinical trial site; clinical tests; clinical trial monitoring; reimbursement of exceptional expenses; possibility for Sponsors to enter into agreements directly with specialized agencies to carry out activities related to the Continue reading “March 2020: Management of Clinical Trials During COVID-19 Pandemic – Italian Guidance”
The German Regulatory Authority (BfArM) issued a supplementary guidance March 26th on Clinical trials during the COVID-19 pandemic. This is supplemental guidance to the European Guidance on the Management of Clinical Trials during the COVID-19 pandemic which was issued March 20th. The German supplemental guidance notes:
“As the details of clinical trials are mainly regulated by individual provisions of the Member States, this European guidance document cannot recommend a harmonised procedure for all issues. Therefore, after consultation with the Land authorities and in cooperation with the German Association of Medical Ethics Committees, the federal higher authorities have issued a paper on monitoring and the potential shipment of investigational medicinal products.
Although the guideline consists of harmonised recommendations at EU level, which is co-developed and fully supported by Germany, there are specific national laws and guidelines in many EU member states, including Germany, regarding certain topics in clinical trials that must be taken into account and may take precedence over the European recommendations. Therefore, such areas require closer consideration and interpretation. These topics include, in particular, temporarily applicable measures for source data verification, if on-site monitoring at trial sites is not indicated owing to the COVID-19 (coronavirus) pandemic, and the shipment of investigational medicinal product (IMP) to the trial subject, in case IMP distribution to the trial subject at the trial site is not possible.”
Arnold & Porter posted an advisory March 27th on Latest Guidance of the EMA and European and UK National Authorities on Crisis Management of Clinical Trials and Medicine Supplies During the COVID-19 Pandemic noting the recent EMA and MHRA guidances but also discusses the March 25th national Belgian Addendum to the EMA guidance:
On 25 March 2020, the Belgian Federal Agency for Medicines and Health Products (FAMHP) issued a national Belgian Addendum to the EMA guidance. Consistent with other national policies, the FAMHP gives priority to clinical trial applications for treatments of COVID-19 and applications for substantial amendments to the protocols of ongoing existing clinical trials during the COVID-19 pandemic.
FAMHP further clarifies the following points:
- Sponsors are not permitted to ship the investigational medicinal product directly to patients. The product may be shipped from clinical trial sites to patients under the direct responsibility of principal investigators without any involvement from sponsors.
- The safety and rights of the patients must be protected (e.g., confidentiality) and the investigational medicinal product must be suitable for transport, storage and administration at home.
- The process of home drug-administration must be documented, including the training provided to patients for the self-administration or the involvement of a healthcare professional for the administration at the patient’s home.
The FAMHP guidance also discusses the administrative steps for the notification of substantial amendments to the protocol and changes to the informed consent form related to the direct supply of the investigational product, but also temporary halts of the clinical trial, urgent safety measures and protocol deviations.
The FAMHP guidance also highlights that remote verification of data source is not permitted in Belgium as it violates the rights of the patients.
The Government of Estonia has declared an Emergency Situation until 1 May, 2020 due to the pandemic of COVID-19.
The State Agency of Medicines (SAM) has issued a guidance document on the management of clinical trials in Estonia during the COVID-19 situation. The guidance is in effect until the end of the emergency situation and will be updated as the situation progresses.
Any reported changes to the trial conduct must be specific and applicable to Estonian study sites and Estonian trial subjects. General descriptions of possible measures that may or may not be used in Estonia are not accepted. Continue reading “March 2020: Estonia Guidance on Clinical Trial Management in the Context of COVID-19 Pandemic”
As per the update on March 27, 2020, EMA and the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) encouraged all researchers to register their pharmacoepidemiological studies related to the COVID-19 pandemic in the EU PAS Register. They should also upload and make their study protocols public, with a description of the data collected or planned to be collected. This is to facilitate collaborations and speed up the design of observational studies by others. Researchers should include ‘COVID-19’ in the study title to allow easy retrieval of all COVID-19-related studies via the ‘Title of Study’ search filter.
This recommendation does not further comment on the publication of the trials on EudraCT.
Covington & Burling posted March 25th that European Commission plans to postpone the application date of the Medical Device Regulations in response to COVID-19 will be postponed one year due to Covid-19. Below is a link to the Commission’s March 25th press release:
With EMA invoking the Business Continuity Plan on March 11th, one might anticipate that the implementation of the CTIS audit could also be delayed from the current start date of December 2020.
The European Medicines Agency (EMA) on March 25th released for consultation a new draft guideline on Points to consider on implications of Coronavirus disease (COVID-19) on methodological aspects of ongoing clinical trials. While noting that “it is not possible to give general applicable advice on how the different aspects related to the pandemic should be handled, as implications on clinical trials are expected to be manifold,” the EMA’s Biostatistics Working Party calls on sponsors “to pre-plan how systematic deviations resulting from the measures and individual decisions related to the COVID-19 pandemic are captured,” as well as to record such deviations and the related reasons for them.
Last week the EMA released initial guidance on conducting trials during the pandemic, in tandem with the US FDA guidance along with other regulatory agencies on conducting clinical trials during the COVID-19 Pandemic.
In light of pauses by sponsors regarding on-going clinical trials, the EMA guideline notes that sponsors should collect a “sufficient amount of information on pandemic-related measures and whether trial patients or trial conduct were affected, as well as on the subpopulations of exposed/non-exposed, and infected/non-infected patients will be necessary to study the impact on the treatment effect. Sponsors should collect this information to the extent feasible, and in a pragmatic manner.”
In some cases, the guideline says an independent Data Monitoring Committee may be necessary, particularly to help sponsors re-start usual trial operations, adjust the trial sample size and/or to deal with any potential sources of bias.
Comments on the draft guideline are due April 25th.
Clinical Trials Information System (CTIS) Development
In March 2020, EMA’s Management Board endorsed the audit methodology for CTIS enabling the process for the selection of the supplier for the audit of the system to commence.
EMA, together with product owners, is carrying out a second readiness assessment in the first months of 2020 to identify critical items that must be addressed prior to the audit. This will be followed by a further operational assessment (including of the public portal) to determine the full scope of the auditable version. Specialised users, in collaboration with the product owners, have already assessed the ‘union control’ and ‘inspection’ modules of CTIS.
EMA is closely monitoring performance of the IT supplier to ensure timely delivery of a reliable audit version of CTIS.
The audit of the system will commence in December 2020.
As per the news released on March 20, 2020, the European Commission, the European Medicines Agency (EMA) and national Head of Medicines Agencies (HMA) have published new recommendations for sponsors on how to manage the conduct of clinical trials in the context of the coronavirus disease (COVID-19) pandemic. The impact of the pandemic on European health systems and more broadly on society, will make it necessary for sponsors to adjust how they manage clinical trials and the people who participate in these trials.
The guidance provides concrete information on changes and protocol deviations which may be needed in the conduct of clinical trials to deal with extraordinary situations, e.g. if trial participants need to be in self-isolation or quarantine, access to public places (including hospitals) is limited due to the risk of spreading infections, and healthcare professionals are being reallocated.
This guidance includes a harmonised set of recommendations, to ensure the utmost safety of trial participants across the European Union while preserving the quality of the data generated by the trials. It also advises how these changes should be communicated to authorities.
In the EU, clinical trials are authorised and supervised at national level. Sponsors are advised to also check whether there might be specific national legislation and guidance in place to complement or in some cases to take priority over this new guidance.
Clinical Trials Information System (CTIS) development
In December 2019, EMA’s Management Board endorsed to commence the audit of the system in December 2020, following an audit readiness assessment carried out by the nominated product owners, EMA and the IT supplier.
The aim of this assessment was to identify critical business blockers and resulted in an updated plan outlining items that still need to be developed or fixed for audit. The product owners will work with EMA and the IT supplier to analyse and design these items in the first few months of 2020, in a way that ensures efficient delivery.
The latest release of the system, which was validated by the nominated product owners in December 2019, enhances CTIS functionalities for processing the evaluation of clinical trial applications, data submission and view of data, management of user access, users’ oversight of activities and data transparency. These enhancements relate mainly to the authority and sponsor workspaces in the system.