COVID-19 Vaccination in Non-covid Clinical Trials

With regard to frequent questions associated also with the extended guideline of MHRA (The Medicines and Healthcare Products Regulatory Agency), the British drug agency, on clinical trials at the time of the pandemics, on the vaccination of trial subjects enrolled in non-covid clinical trials, SÚKL hereby issues its opinion.  

The “COVID-19 Vaccination Strategy for the Czech Republic”, published on 22 December 2020 by the Ministry of Health the Czech Republic, does not include trial subjects enrolled in clinical trials. This category is completely missing from the vaccination plan.

With a view to the aforementioned, how should COVID-19 vaccination be approached in subjects of non-covid clinical trials?

1)     Each clinical trial protocol should include permitted and forbidden concomitant treatments. If the protocol permits vaccination, it means that COVID-19 vaccination with authorised vaccines is allowed, providing the vaccination conditions set forth by the respective marketing authorisation (consistent with the respective Summary of the Product Characteristics; SmPC) are observed. Where an interval between the administration of the investigational medicinal product and the possible vaccination is established, it shall apply also to COVID-19 vaccination.

2)     If the section of the clinical trial protocol on permitted and forbidden concomitant treatments does not mention vaccination at all, the sponsor should issue an amendment to the protocol or, if appropriate, in the form of a “Dear Doctor Letter” (DDL) or “Dear Investigator Letter” (DIL), advising whether the concerned trial subjects should be recommended the vaccination or not with a view to the investigational medicinal product and the diagnosis. This is very important, as patients in clinical trials should always consult their investigator about the use of any other medicinal product along with the IMP, and for this reason, the investigators should be able to answer also questions regarding the possibility of COVID-19 vaccination. Some general practitioners may require the investigator´s opinion on the vaccination of their patient enrolled in a clinical trial.

Should the sponsor conclude that the administration of a COVID-19 vaccine is risky with a view to the investigational medicinal product, the enrolled trial subjects should be informed to this effect.

3)     Should the sponsor require that the enrolled trial subjects be vaccinated with a COVID-19 vaccine, such requirement must be voluntary for the enrolled subjects, with the option for some to decline the vaccination, as is the case also in routine practice. Furthermore, the organisation of vaccination would be the responsibility of the sponsor, as the Vaccination Strategy of the Czech Ministry of Health does not give this group of patients any preference. In those cases where the vaccine would be supplied by the sponsor, the non-covid trial subjects could be vaccinated only with vaccines authorised in the Czech Republic.

4)     In cases where COVID-19 vaccination is allowed in the course of a non-covid clinical trial, it is important for the sponsor to set up a reporting system for adverse drug reactions that could be associated with the application of the COVID-19 vaccine, and to distinguish such reports from the reporting of adverse drug reactions associated with the administration of the investigational medicinal product.

5)     Where the sponsor does not want the enrolled trial subjects to be vaccinated against COVID-19 in the course of the clinical trial – for whatever reason, such as possible interactions, etc., and this restriction is not covered by the clinical trial protocol, such information has to be supplemented by means of an amendment to the Patient Information Sheet, including a rationale thereof, and an amendment to the protocol or a DDL.

 

Done on 24 March 2021

Department of Clinical Trials on Medicinal Products