The Guidance provides recommendations for sponsors and investigators on how to manage clinical trials and the people who participate in these trials. The Guidance notes that the situation is evolving and that pragmatic actions may be required. It stresses that priority should be given to the impact on health and safety of trial participants. Due to the rapidly evolving situation, it is likely that the guidance will be further updated.
The Guidance aims to serve as an EU-level harmonized set of recommendations. However, in the EU, clinical trials are authorized and supervised at EU Member State level. Therefore, sponsors and investigators are advised to check whether there is specific national legislation and guidance in place to complement or take priority over this new guidance. Local guidance has, for example, been issued in EU Member States Belgium, Italy, and Spain, as well as in the UK.
Concrete information is provided on changes and protocol deviations which may be needed in the conduct of clinical trials to deal with extraordinary situations. Such a situation could occur when participants need to be in self-isolation or quarantine. Furthermore, the Guidance includes a harmonized set of recommendations to ensure the safety of trial participants across the EU while preserving the quality of the data generated by the trials. The Guidance also provides specific advice on the initiation of new clinical trials for treatments of COVID-19.
In general, the Guidance stresses that the impact of COVID-19 on several stages of clinical trials needs to be considered. In addition, actions should be proportionate and based on benefit-risk considerations and on contingency provisions taken nationally and locally by the authorities.
The Guidance provides a number of specific recommendations with regard to:
- Changes in ongoing trials: suggestions relate to conversion of physical visits into phone or video visits, temporary halt of the trial, suspension of patient recruitment etc.;
- Risk assessment: all decisions to adjust clinical trials should be based on risk assessment by the sponsor. Measures should be implemented that prioritize subject safety and data validity, and it is stressed that in the case that those two conflict, subject safety should always prevail;
- Communication with authorities;
- Agreement with and communication to sites;
- Changes to informed consent;
- Changes in the distribution of the investigational medicinal products: the Guidance addresses potential redistribution of investigational medicinal products (IMPs) between sites and potential delivery of investigational medicinal products directly to trial subjects' homes;
- Changes to monitoring;
- Protocol deviations;
- Reimbursement of exceptional expenses; and
- Initiation of new trials aiming to test new treatments for COVID-19: it is noted that the EU Member States support the submission of large multinational clinical trial protocols for the investigation of new treatments for COVID-19. It is also noted that the EMA provides a full fee waiver and fast-track procedure for scientific advice for developers of medicines or vaccines against COVID-19.
Authored by Hein van den Bos, Petra den Boer, and Wouter van Beek