Recommendations for the conduct of clinical research at the time of restrictive measures due to the coronavirus
UPDATE 2 April 2020: Information on deferred consent in clinical trials in an emergency situation, see last bullet.
CCMO receives many queries on problems caused by the coronavirus and its effects on the conduct of clinical research.
Examples concern the delivery of study medication, subjects unable to come to the investigational site as a result of which certain study procedures cannot be carried out, and the postponement of monitoring activities. CCMO wishes to emphasise that in all cases the safety of research subjects and the health of healthcare professionals is paramount. As a sponsor or investigator, you should consider whether the clinical research, or parts of the clinical research, can be temporarily halted or not. CCMO realises that in many cases this is not possible with ongoing research. For example, because the subjects have to be given the study medication or because tests have to be carried out to ensure the safety of the subject. This may lead to protocol deviations, substantial modifications, urgent safety measures, temporary halt of the research or otherwise.
CCMO provides a number of recommendations in this respect, in which in some cases the review committee (CCMO or accredited MREC) must be informed:
- Set up a risk analysis on the consequences of the coronavirus on the conduct of the clinical research , whereby the safety of the participants is paramount;
- Record all deviations from the protocol and the standard procedure in writing; unless the subject’s safety is at stake, these protocol deviations need not be submitted to the review committee;
- A deviation from the protocol or a protocol modification due to urgent safety measures to eliminate immediate hazards to the subject can take place without prior approval by the review committee. However, this must be reported immediately to the review committee;
- Study medication can be sent directly to the research subject by courier from the (hospital)pharmacy for reasons of subject safety; you need not inform the review committee about this, but do record this temporary procedure in writing;
- If the trial is (partially) suspended, for reasons of subject safety, this must be reported immediately to the review committee ; a temporary halt for other reasons should be reported within 15 days;
- If the study is terminated prematurely, this must be reported to the review committee as soon as possible, but at the latest within 15 days;
- The procedure for submitting a substantial amendment to the review committee has not been changed. If it concerns an amendment which has an impact on the safety of research subjects and requires a fast-track assessment procedure given the emergency of the situation, you are advised to contact the review committee about the procedure to be followed.
- The obligation to submit a cover letter with a wet signature for initial applications and substantial amendments to the review committee and/or the competent authority has been suspended. Instead, a digital or scanned signature of the applicant is sufficient.
In case a subject is unable to provide (re)consent to (continue to) participate in a clinical trial in an emergency situation, obtaining consent can be deferred under specific conditions. The applicable conditions for such a deferred consent are described in the CCMO memorandum with flow chart Deferred Consent (in Dutch). To be able to use the possibility of deferred consent it is mandatory to obtain approval by the review committee (MREC/CCMO).
The procedure for notifications to the Dutch competent authority both during and after the study has not been changed.
The European Commission, the European Medicines Agency (EMA) and national Head of Medicines Agencies (HMA) have published a guidance for sponsors and investigators on how to manage the conduct of clinical trials during the coronavirus disease (COVID-19) pandemic.