EU Guidance on Conduct of Clinical Trials During COVID-19 Pandemic and Specific Advice on Initiation of Clinical Trials for Treatments of COVID-19
The European Commission, the European Medicines Agency (EMA) and the national Heads of Medicines Agencies (HMA) released on 20 March 2020 guidance for clinical trial sponsors on how to manage their clinical trials during the COVID-19 pandemic (the Guidance; available here). The Guidance aims to serve as an EU-level harmonised set of recommendations on changes and protocol deviations which may needed due to, e.g., trial participants being in self-isolation/quarantine, limited access to public places (including hospitals) due to the risk of spreading infections and health care professionals being reallocated.
Furthermore, the Guidance provides specific advice on the initiation of new clinical trials for potential COVID-19 treatments or vaccines.
Guidance on Conduct of Clinical Trials During COVID-19 Pandemic
The key objective of the Guidance is to ensure the safety of trial subjects across the EU while preserving the quality of the data generated by the trials. According to the Guidance, sponsors should consider specific measures such as:
- postponing or cancelling site visits or converting physical patient visits into phone or video visits;
- temporarily halting the trial at some or or all trial sites;
- suspending or slowing down recruitment of new trial participants;
- extending the duration of the trial;
- postponing trials or activating sites that have not yet been initiated;
- closing sites; and/or
- if unavoidable, transferring trial subjects to, for instance, investigational sites away from risk zones or closer to their home, or to sites already participating in the trial.
The Guidance emphasises that, when changes in ongoing trials are considered, the overall well-being and best interests of the trial subjects should be duly considered (e.g., in trials for patients with life-threatening or severely debilitating conditions, when participants require to stay on trial treatment) as well as the legitimate interest of trial sites in avoiding further burdens in terms of time and staffing during the COVID-19 pandemic.
Additionally, the Guidance discusses matters such as:
- the risk assessment to be carried out by sponsors, which should consider the added challenges due to COVID-19 and pay particular attention to the interests of patients enrolled in ongoing trials who may be at risk for COVID-19 or who are in trials involving therapies which may increase such risk;
- communication with authorities (authorities will give priority to new clinical trial applications for the treatment or prevention of COVID-19 infection and/or substantial amendment applications to existing clinical trials necessary as a result of COVID-19);
- alternative ways to seek informed consent;
- changes in the distribution of the investigational medicinal product (e.g., to remove avoidable visits to sites and to provide the patients with needed treatments);
- alternative ways for sponsors to monitor clinical trial conduct at sites; and
- protocol deviations.
Importantly, the Guidance emphasises that “there might be specific national legislation and guidance in place, which they should consult and which can be used to complement this guidance, or, with respect to particular matters may take priority over these recommendations”. For example, the Belgian Federal Agency for Medicines and Health Products (FAGG/AFMPS) has already announced that, on 25 March 2020, it will publish national guidelines covering specific issues, including that of direct-to-patient supplies of investigational medicinal product (see, here (Dutch version) and here (French version)).
Due to the rapidly evolving situation, further updates to the Guidance “are possible and likely”.
Similar guidance was issued by the US Food and Drug Administration (FDA) on 18 March 2020.
Specific Advice on Initiation of Clinical Trials for Treatments of COVID-19
In line with a call issued by EMA’s Committee for Medicinal Products for Human Use (CHMP) for robust trial methodology in clinical trials for potential COVID-19 treatments or vaccines, the Guidance notes that “[t]he Member States support the submission of large, multinational trial protocols for the investigation of new treatments for COVID19”.
In its call, CHMP had noted being “concerned about the amount of planned small studies or compassionate use programmes across Europe that are unlikely to be able to generate the required level of evidence to allow clear-cut recommendations”. According to CHMP, “[s]uch studies would not be in the best interests of patients”. Therefore, it favours instead “[m]ulti-arm clinical trials investigating different agents simultaneously” as such trials “have the potential to deliver results as rapidly as possible across a range of therapeutic options according to the same evaluation criteria”. CHMP added that “[i]t would be important that all EU countries are considered for inclusion in such trials”.
The Guidance encourages sponsors to consider the submission of any applications for COVID-19 related clinical trials for an accelerated Voluntary Harmonisation Procedure (VHP) assessment when possible.
Additionally, EMA provides a full fee waiver and a fast-track procedure for scientific advice (see also, here).
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