EU Allows More Flexibility In Managing Trials During COVID-19
Guidance Explains How Medicines Can Be Distributed To Participants
Executive Summary
The EU has issued revised guidance to ensure that clinical trials can continue taking place during the COVID-19 pandemic.
The EU guidance on managing ongoing clinical trials during the COVID-19 pandemic has been updated with more recommendations on simple and flexible measures that sponsors can take to mitigate disruptions without compromising data quality and patient safety.
The joint European Commission, European Medicines Agency and Heads of Medicines Agencies guideline now offers more flexibility and clarification relating to the distribution of medicines directly to trial participants, the remote verification of source data, and notifying regulatory authorities of urgent actions taken to protect trial participants or to support data robustness.
The Alliance for Regenerative Medicine, an international advocacy group for companies, research bodies and patient organizations working in the area of advanced therapy medicines, welcomed the updated guideline as it addresses many of the questions posed by its EU regulatory committee earlier.
The commission noted that the measures listed in the guideline are meant for exclusive use during the coronavirus pandemic, and that these will be revoked once the current health crisis in the EU and European Economic Area is over. (Also see "EU Urges Sponsors To Assess COVID-19 Impact Before Starting New Trials" - Pink Sheet, 23 Mar, 2020.)
The revised guideline includes measures to ensure that patients participating in clinical trials across the EU can continue receiving their medicines, while taking into account social-distancing measures and possible limitations in trial site and hospital resources. It outlines various factors that should be considered in cases where a decision is made to ship the investigational medicinal product (IMP) directly to the trial participant’s home.
It states, for example, that the IMP should be delivered from trial sites (eg hospital pharmacies) and that the sponsor should bear the cost of the shipment and also provide logistical assistance to the trial site if needed, such as for the selection of an appropriate courier or transporter.
If, however, the trial site is not able to handle the additional burden of IMP shipments, then in exceptional circumstances a distributor can be appointed for this task. The distributor should be independent from, and acting on behalf, of the sponsor, in line with national law or temporary national emergency measures. The guideline explains the processes and necessary agreements that sponsors should put in place before appointing such a distributor.
Source Data Verification
On the topic of remote source data verification (SDV), the commission believes this approach will only be considered necessary for very few trials. It may be suited for trials involving medicines intended to prevent or treat COVID-19 or in the final data cleaning steps before database lock in pivotal trials investigating serious or life-threatening conditions with no satisfactory treatment option.
For COVID-19 trials starting now where remote SDV is foreseen, the guideline states this approach should be described in the initial protocol application and informed consent form.
For ongoing trials, plans for introducing remote SDV should be submitted to the concerned national competent authority, in line with national law or temporary national emergency measures, via a substantial amendment. The guideline adds that trial investigators should not be unduly pressurized into accepting remote SDV and should always give priority to patient care.
It says that data subject to remote SDV “are likely to require re-monitoring” especially “if it was based on pseudonymised documents, which cannot be considered as source documents, and considering that remote monitoring is expected to only have focused on the most critical information.”
Notifying Urgent Actions
Noting that it may be necessary for sponsors to initiate urgent actions to protect trial participants against any immediate hazard or other changes affecting patient safety or data robustness, the revised guideline explains the classification and notification of these actions.