FOI release

Freedom of Information request on the weekly summary of yellow card reports and the COVID-19 vaccines (FOI 22/419)

Published 31 May 2022

FOI 22/419

1st March 2022

Dear

Thank you for your enquiry dated the 31st January, where you requested the below further information regarding the ‘weekly summary of Yellow Card reporting and the COVID-19 vaccines.

1. References to the ‘additional sources of evidence’.

2. The names and titles of those in the team of safety experts.

3. Details and evidence of the statistical techniques used to confirm if there are more events than you would expect to see.

4. The number of events you would expect to see for a typical vaccination campaign.

5. Details of the data and techniques used for establishing ‘background rates of illness in the absence of vaccination’.

6. Details and evidence of the clinical characteristics used ‘to see if new patterns of illness are emerging’.

The MHRA continuously monitors the safety of vaccines through a variety of pharmacovigilance processes including the Yellow Card scheme. The scheme relies on voluntary reporting of suspected adverse drug reactions (ADRs) by health professionals and patients and there is also a legal obligation for pharmaceutical companies to report ADRs for their products.

As part of our signal detection processes all ADR reports received by the Yellow Card scheme are individually assessed and cumulative information reviewed at regular intervals. Our assessments are supplemented with epidemiology studies including analysis of data on national vaccine usage, anonymised GP-based electronic healthcare records and other healthcare data to proactively monitor safety. Furthermore, we consider the international experience based on data from other countries using the same vaccines. We also receive independent advice from the Commission on Human Medicines (CHM) which is responsible for advising on the impact of safety issues on the balance of risks and benefits of COVID-19 vaccines. For further information on the CHM please follow this link: https://www.gov.uk/government/organisations/commission-on-human-medicines/about.

Data are subjected to statistical analysis of all drug reaction combinations on the database. An established statistical approach known as empirical Bayes geometric mean (EBGM) is used to facilitate signal detection. This identifies ‘signals’—drug-reaction combinations that occur more frequently than

would be expected when compared to the background frequency of other drug-reaction combinations in the database. Signals that meet defined criteria are evaluated further to assess the likelihood of causal relationship between the drugs and reported reactions.

Public Health England (PHE), the MHRA and the Health Protection Research Unit (LSHTM) use the Clinical Practice Research Datalink (CPRD) to identify any potential safety signals using sequential testing methods for a pre-specified set of events of interest. Another component of the signal detection for the COVID-19 vaccines is identifying whether the number of reports has exceeded the expected number for that specific condition in the same population in the absence of vaccination, to evaluate any potential signals compared to a historic baseline. This work will generate backgrounds rates using hospital admission data (Hospital Episode Statistics (HES) for a list of prespecified conditions of interest.

The total number and the nature of the majority of Yellow Cards received so far is not unusual for a new vaccine. The reporting rate for spontaneous ADRs is variable and can depend on a multitude of factors, as it is influenced by public awareness and seriousness of events as well as publicity around the use of vaccines. These estimates should not be used as indicators of the reporting rate for COVID-19 vaccines, for which there is a higher than normal public awareness of the Yellow Card scheme and the reporting of suspected reactions. We consider the variable levels of reporting which can be stimulated due to events of interest, media attention and our collaborative work with healthcare professionals where we ask for reports of any suspicions to be submitted. Please be assured we evaluate all aspects of the data including the variability in levels of reporting as part of our ongoing monitoring procedures.

Several vaccinations campaigns such as the Human papillomavirus (HPV) and swine flu pandemic had been considered to deliver estimated adverse drug reaction volumes at the start of the COVID-19 vaccination campaign. Although these campaigns were used as models to estimate volumes of reports, there are key differences such as the patient population who received the vaccine and the influence of reporting from social media. Actual volumes are dependent on the reactogenicity of the vaccine used, number of dosages, use of concurrent treatments (for instance to suppress fevers) and publicity around campaigns. These estimates were used as a baseline with the anticipation that volumes would increase depending on the nature of the campaign, such as authorisation of use in different patient populations including children. The introduction of multiple dosages including booster dose would not have been considered at the time of these estimates and would therefore influence volumes also. As with previous correspondence, it is important to consider the increased work the MHRA has carried out to raise awareness around reporting to the Yellow Card scheme which has exceeded that of other campaigns.

Further information on all of the above can be found in the MHRA’s COVID-19 vaccine surveillance strategy: https://www.gov.uk/government/publications/report-of-the-commission-on-human-medicines-expert-working-group-on-covid-19-vaccine-safety-surveillance/report-of-the-commission-on-human-medicines-expert-working-group-on-covid-19-vaccine-safety-surveillance#proactive-vigilance-for-covid-19-vaccines

Unfortunately, we are unable to provide the names and titles of those in the team of safety experts as it relates to the processing of personal data in accordance with the UK General Data Protection Regulation (UK GDPR) and the Data Protection Act 2018 (DPA) and it is therefore exempt under the Section 40 of FOIA.

If you are dissatisfied with the handling of your request, you have the right to ask for an internal review. Internal review requests should be submitted within two months of the date of this response; and can be addressed to this email address.

Yours sincerely,

FOI Team,

Vigilance and Risk Management of Medicines Division