The Medicines and Healthcare products Regulatory Agency (MHRA) have updated their guidance document on managing clinical trials during COVID-19 with a new section pertaining to the management of non-COVID-19 trials in the context of the current COVID-19 vaccination programme.
This addition to the guidance has been made to help Sponsors understand what new activities they need to carry when trial participants are offered and/or receive a COVID-19 vaccine.
Initially, a risk assessment should be conducted for the concomitant use of a COVID-19 vaccine for each specific (Investigation Medicinal Product) IMP being studied, with consideration for the trial population. If the outcome of a risk assessment:
- Is that a vaccine will be considered a simple concomitant medication with no interaction, then the Sponsor should notify the MHRA in the next substantial amendment as a non-substantial update.
- Highlights potential issues that need to be mitigated (e.g. trials with immunosuppressive elements), then a substantial amendment needs to be submitted to the MHRA and the Research Ethics Committee (REC).
Further activities concern managing blinded trials which include:
- Determining whether subjects would require unblinding to receive a vaccine.
- Giving participants information (approved by the REC) asking them to contact the Sponsor when they receive an invitation to get vaccinated.
- Ensuring that all participants who are unblinded and wish to receive a vaccine must have an “end of study/treatment” visit. This should be similar to protocol visit assessments done when a subject is discontinued early to ensure that they have a complete status before they become unevaluable for the trial arm they were in.
Other activities that a Sponsor must conduct include:
- Recording the details of the administered vaccine in the medical notes, and maintaining the pre-existing schedule of study visits (where possible).
- In cases where a potential interaction between a COVID-19 vaccine and an IMP has been identified, the protocol must take into account the vaccine’s safety profile and whether there needs to be a period of time between dosing with the vaccine and a dose of the trial IMP.
- Safety reporting, particularly if the IMP and COVID-19 vaccine have an overlapping safety profile. Since the COVID-19 vaccine is not considered to be an IMP, any adverse events or suspected adverse drug reactions can be reported using the MHRA Yellow Card system. In scenarios where an AE is considered to be caused by an interaction between a trial’s IMP and the vaccine, then the clinical trial pharmacovigilance rules should be followed. If the event is serious and related to both the IMP and the vaccine then it is classified as a serious adverse reaction and SUSAR reporting will be initiated.
- Updating the statistical plan, whether by censoring subjects in the analysis at the time of their vaccination or by conducting further analyses.
For new trials to avoid the need for substantial amendments later on, Sponsors are encouraged to accommodate any potential vaccinations in their protocol and design appropriate flexibilities.
To read the updated guidance in full, click here.