On 28 April 2020, the European Commission published further Guidance on the Management of Clinical Trials during the COVID-19 (Coronavirus) Pandemic (the “Guidance”), supported by the European Medicines Agency (EMA) and the national Heads of Medicines Agency (HMA). The Guidance is an update to the previous version published in late March (see InsideEULifeSciences blog post here).
As outlined in the Commission’s press release, the Guidance’s objective is to mitigate clinical trial disruption in Europe during the COVID-19 pandemic. The Guidance introduces pragmatic and harmonizing measures that facilitate changes to trials
“…to ensure the necessary flexibility and procedural simplifications needed to maintain the integrity of the trials, to ensure the rights, safety and wellbeing of trial participants and the safety of clinical trial staff…”
As clinical trials in the EU are authorized at the national level, the Guidance encourages Member States to implement its recommendations “to the maximum possible extent” and to add to the Guidance where clarity on national legislation and derogations is needed. The Guidance does not supersede any current national legislation and derogations and the measures introduced will be revoked once the COVID-19 pandemic has passed.
The Guidance’s recommended measures include, amongst others, the following:
- Initiating new trials: Sponsors must assess the “feasibility and immediate necessity” of starting a new clinical trial. Sponsors should submit any large, multinational trial protocols for the investigation of new treatments for COVID-19 via the accelerated ‘Voluntary Harmonisation Procedure’. Further, developers of medicines or vaccines against COVID-19 are invited to e-mail the EMA via email@example.com.
- Changes to ongoing trials: The Guidance recommends possible changes to restrict site visits to those “strictly necessary”, e.g., temporarily halting trials or closing trial sites, slowing down the recruitment of new trial participants, converting physical site visits into phone or video visits, or even, in exceptional cases, running routine diagnostic tests at a relevant local, authorized clinical facility rather than the trial site itself.
- Changes to safety reporting: Investigators may collect adverse events from the trial participant through alternative means, e.g., by phone calls or telemedicine visits, as appropriate.
- Changes to informed consent: Where written consent by the trial participant is not possible, consent mat be given orally by the trial participant in the presence of an impartial witness. The witness must sign and date the informed consent form. Further, where re-consent for changes to trial conduct is necessary, a site visit should be replaced with oral consent, where possible.
- Changes in the distribution of the investigational medicinal products (“IMP”): The Guidance recommends measures to limit site visits and pre-empt possible supply chain failures, e.g., by storing larger amounts of IMP at the site, making larger amounts of IMP available to trial participants, delivering IMP to trial participants’ homes directly, and even, in exceptional cases, permitting distributors to deliver to trial participants directly in order to alleviate the sponsors’ increased burden of IMP shipments.
- Changes in the distribution of in vitro diagnostic and medical devices: The Guidance recommends measures to pre-empt possible supply chain failures, e.g., by maintaining appropriate stock of devices. Any such stockpiling must not pose a risk to the treatment of patients outside the trial.
- Changes to monitoring: There should be a risk-based approach to any changes to monitoring. The Guidance recommends measures to replace or reduce on-site monitoring where it cannot be cancelled or postponed by conducting monitoring by, e.g., phone calls, video visits, and centralized monitoring of data acquired by electronic data capture systems, or, in exceptional cases and bearing in mind trial participants’ data protection rights, remote Source Data Verification (“SDV”) of medical records. Annex I of the Guidance outlines certain controls to protect trial participants’ rights during remote SDV.
In relation to communication with authorities, the Guidance emphasizes that the relevant competent authorities and ethics committees must be informed of:
- substantial amendments;
- urgent safety actions; and
- other COVID-19 related changes not related to participants safety and that do not seriously affect the benefit-risk balance for the participants and the scientific value of the trial.
Sponsors should mark all such communications with COVID-19 in the subject field. The Guidance also provides a non-exhaustive list for the classification of mitigation measures such as: (i) substantial amendments; (ii) urgent safety actions; or (iii) other measures.
Going forward, Health and Food Safety Commissioner, Stella Kyriakides, emphasized that “…it is absolutely crucial that we show flexibility in our rules to maintain research on critical treatments…” Due to the rapidly evolving situation, the Commission has advised sponsors and investigators that further updates to the Guidance are possible and likely.