The drastic actions taken to fight the current COVID-19 pandemic pose enormous challenges for the conduct of clinical trials on medicinal products and medical devices in accordance with the pertinent rules and regulations. Patients may not be able to come to the investigational sites for their study visits according to the protocol. Thus, their supply with investigational products might be interrupted. The usual sponsor monitoring of the conduct of clinical trials at the investigational sites is hardly possible under the current conditions. Sponsors and investigators therefore face the need to find solutions that would under normal circumstances not comply with applicable regulatory requirements.
In this exceptional situation regulatory authorities, ethics committees and other institutions publish guidances and recommendations for actions to be taken in clinical trials.
This article attempts to summarize the various available recommendations for the current and very dynamic situation.
German Higher Authorities
Federal Institute for Drugs and Medical Devices (BfArM):
BfArM has issued Supplementary Recommendations to the EMA Guidance Documents (see below) on the management of clinical drug trials during the COVID-19 pandemic. The most recent version of these Supplementary Recommendations of 25 February 2021 addresses the conditions for source data verification (SDV) during remote monitoring. BfArM has summarized further recommendations regarding clinical trials during the COVID-19 pandemic on its website (now available in English).
Together with the Working Group of Medical Ethics Committees BfArM has also adapted its recommendations to the situation in clinical trials with medical devices. These adapted recommendations can be found on the BfArM website.
Paul Ehrlich Institute (PEI):
On its website PEI has published Additional Recommendations identical to those issued by BfArM and otherwise refers to the Eudralex Volume 10 website where the EMA Guidance Document (see below) can be found.
Ethics Committees
Working Group of Medical Ethics Committees in Germany:
On its website (relevant parts not available in English) the Working Group emphasizes that with all actions to be taken the safety and well-being of subjects must remain paramount and supply of investigational products to the trial subjects must be guaranteed. The Working Group furthermore clarifies under which circumstances the ethics committee in charge has to be notified of a stop of recruitment or a premature termination of a clinical trial. For further guidance the Working Group refers to the first EMA document (see below). As mandatory GCP trainings for investigators can no longer be conducted as classroom courses, the Working Group announces that such trainings may now be conducted online or as web-based seminars. The Working Group has summarized its recommendations and information in an FAQ list (not available in English) to be updated on an ongoing basis.
Foreign Authorities
European Medicines Agency (EMA):
Meanwhile the European EMA has published Version 4 (04/02/2021) of a comprehensive Guidance Document on management of clinical trials during the COVID-19 pandemic.
A second Guidance Document focussing on methodological aspects had been published as a draft version for public consultation until 25 April 2020 and is now available in final form (Revision 1, 29-Jun-2020).
Heads of Medicines Agencies (HMA):
The European network of the Heads of the National Competent Authorities has published a list of weblinks to national recommendations that supplement EMA's Guidance Documents.
Medicines and Healthcare products Regulatory Agency (MHRA):
In a blog the British MHRA Inspectorate informs that a pandemic-related increase in protocol deviations does not have to be reported as Serious Breach unless patient safety is at risk. MHRA also recommends a brief risk assessment for all alternative measures now taken in order to ensure medical care of trial subjects.
Meanwhile MHRA has summarized its recommendations on its website. This includes Guidances to sponsors and investigators on handling clinical trials on medicines and clinical investigations of medical devices during the COVID-19 pandemic.
Food and Drug Administration (FDA):
The US-American FDA has also summarized its recommendations in a comprehensive Guidance Document which was last updated on 27 January 2021.
(last update: 14 April 2021)
Recent Updates:
14-Apr-2021: reference to latest update of BfArM/PEI Supplementary Recommendations added / reference to latest update of FDA Guidance added
15-Feb-2021: reference to latest update of EMA Guidance added
21-Jul-2020: reference to finalised EMA Guidance added / reference to latest update of FDA Guidance added
05-Jun-2020: reference to latest update of FDA Guidance added
22-May-2020: reference to latest update of BfArM/PEI Supplementary Recommendations added / reference to latest update of FDA Guidance added
13-May-2020: reference to latest update of FDA Guidance added
28-Apr-2020: reference to latest update of EMA Guidance added
20-Apr-2020: reference to BfArM recommmendations for medical devices trials added
17-Apr-2020: reference to latest update of FDA Guidance added
16-Apr-2020: reference to FAQ list of the Ethics Committee Working Group added
03-Apr-2020: recommendations of the Ethics Committee Working Group updated / additional link on PEI website / updated version of FDA Guidance
30-Mar-2020: reference to English version of BfArM's COVID-19 website added / reference to MHRA Guidances added
28-Mar-2020: references to Supplementary Recommendations by PEI and BfArM added / reference to Version 2 of EMA Guidance added / reference to HMA added
27-Mar-2020: recommendations of the Ethics Committee Working Group updated
26-Mar-2020: reference to draft version of second EMA Guidance Document added
20-Mar-2020: references to EMA's Guidance Document added / reference to new MHRA recommendations added
19-Mar-2020: initial release of the article