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.
EudraCT has posted below notification:
As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period.
The transition period began on 1 February 2020 and is due to end on 31 December 2020.
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.
On November 28, 2019, a new version of the Clinical Trial Application form was launched, as referred in EudraLex. Updates regard the footnotes section. This does not have an impact on the clinical trial application form that is created through this website, since footnotes are not included in it.
Need help? Contact us! has been updated with more useful information. Also, the FAQs have been updated and can be found here.
On Nov 7, the EC published an updated Draft Questions and Answers Document (Version 2.2) (Eudralex Volume 10 – Clinical trials guidelines – Set of documents applicable to clinical trials under Regulation EU No 536/2014)
Q&As that were added or revised include, 1.6, 2.2, 2.7 (NEW), 2.8 (NEW), 3.3 (NEW), 6.2:
- THE SCOPE OF CLINICAL TRIALS REGULATION IN THE EU — 1.6 Is the definition of ‘medicinal product’ relevant for the scope of the Clinical Trials Regulation?
- APPLICATIONS LIMITED TO PART I — 2.8 Will the assessment report on part I and II be made public at the time of decision?
- SUBSTANTIAL MODIFICATIONS — 3.3 What are the sponsor’s responsibilities regarding changes to a clinical trial which are not substantial modifications (SM), but are relevant for the supervision of the trial (Art. 81.9)?
- SUBMISSION OF RESULTS OF CLINICAL TRIALS — 6.2: Which endpoints need to be summarized in the lay summary of results of a clinical trial?
In October 2019, EMA’s Management Board endorsed the six-monthly monitoring report on the development of the CTIS, which assesses the performance of the IT supplier against agreed key performance indicators. The Board agreed that actions proposed in the report should be further developed, for example improving the quality of the work delivered by the supplier and selecting the critical items needed for audit, as well as extending the monitoring period for at least three releases.
The product owners validated the first release developed in the agile, iterative delivery in September 2019, confirming that all 79 items had been delivered.
The release enhanced CTIS functionalities for the submission of clinical trials and the assessment process, user management and included other general improvements.
The product owners will begin to carry out an operational assessment of the system to identify critical business blockers, in order to enable EMA’s Management Board to consider the timing of the audit of the system.
New updates on the EudraCT website: