FOI release

Freedom of Information request on COVID-19 vaccines and the risk of thromboembolic events, and the use of COVID-19 vaccines in children (FOI 21-525)

Published 13 August 2021

16th June 2021 FOI 21/525

Dear

Thank you for your emails of 18 May, 1 June and 3 June regarding COVID-19 vaccines and the risk of thromboembolic events, and the use of COVID-19 vaccines in children.

COVID-19 vaccines and thromboembolic events

The potential risk of thrombosis with the COVID-19 Vaccine AstraZeneca is that of extremely rare reports of thrombosis occurring concurrently with thrombocytopenia following the first dose of the vaccine. The evidence to date does not suggest that the COVID-19 Vaccine AstraZeneca causes venous thromboembolism in the absence of thrombocytopenia. Also, there have been no safety concerns identified for thrombosis with thrombocytopenia, or thrombosis without thrombocytopenia following vaccination with the Pfizer-BioNTech or Moderna COVID-19 vaccines, or with the 2nd dose of the AstraZeneca COVID-19 vaccine.

The MHRA undertook a thorough review of UK reports of all thromboses with thrombocytopenia following COVID-19 Vaccine AstraZeneca vaccination. The reports were analysed by the Government’s independent advisory body, the Commission on Human Medicines (CHM) and its COVID-19 Vaccines Benefit-Risk Expert Working Group, which includes lay representatives and advice from leading haematologists. The background rate of thromboses (including the more unusual thromboses such as cerebral venous thrombosis and portal vein thrombosis) with thrombocytopenia in the unvaccinated population, as well as the risk of thromboses in COVID-19 disease was taken into consideration as part of the review. The review concluded a possible link between COVID-19 Vaccine AstraZeneca and thrombosis with thrombocytopenia and, whilst we continued to investigate cases, we issued new precautionary advice that the benefits of vaccination with COVID-19 Vaccine AstraZeneca continued to outweigh any risks but that careful consideration be given to people of any age who are at higher risk of blood clots because of an underlying medical condition. The MHRA did not recommend age restrictions in COVID-19 Vaccine AstraZeneca use. The data available at the time suggested a slightly higher incidence reported in the younger adult age groups and the MHRA advised that the evolving evidence be taken into account when considering use of the vaccine.

At this point it’s worth noting that MHRA does not advise on vaccination policy - the Joint Committee on Vaccination and Immunisation (JCVI) is responsible for advising the Government on vaccination policy. As you’re aware on 7 April 2021, the JCVI advised that adults aged less than 30 years without underlying health conditions which put them at severe risk of COVID-19 disease should be offered an alternative to the AstraZeneca COVID-19 vaccine. This advice was updated on 7 May 2021 when, JCVI taking a precautionary approach, advised a preference for adults aged 30-39 without underlying health conditions to receive an alternative to COVID-19 Vaccine AstraZeneca – where available and only if this does not cause substantial delays in being vaccinated. These decisions were based on the latest available evidence on the age-stratified benefit-risk profile of the vaccine. This took into consideration the latest data and advice from the MHRA on reported cases of thrombosis and thrombocytopenia, the COVID-19 infection rate at the time, the scale and pace of the vaccine programme, the portfolio of vaccines available in the UK in the upcoming months as well as modelling of the timing and size of any third pandemic wave. Between the 7 April and 7 May announcements, the MHRA had continued to review the cases of thrombosis with thrombocytopenia, including those reported retrospectively - data on the frequency of these events by age became more precise. At the same time the COVID-19 infection rate, hospitalisation and deaths were low in the UK and vaccine availability forecasts had been updated.

The slides from the 7 April 2021 announcement communicating the age stratified benefit-risk profile of the AstraZeneca COVID-19 vaccine are available here: PowerPoint Presentation (publishing.service.gov.uk). The updated age stratified benefit-risk profile of the AstraZeneca COVID-19 vaccine considered by JCVI in formulating its latest advice announced on 7 May 2021 can be accessed on the University of Cambridge Website: Winton Centre Cambridge. Please note that although not specified in these links, the MHRA risk data used in the benefit-risk analyses includes reports of all types of thromboses with concurrent thrombocytopenia; it does not include cases of thrombosis reported in the absence of concurrent thrombocytopenia.

The updated advice issued by JCVI on 7 May 2021 together with the rationale for the advice, can be found in full at: Use of the AstraZeneca COVID-19 (AZD1222) vaccine: updated JCVI statement, 7 May 2021 - GOV.UK (www.gov.uk).

The MHRA continues to thoroughly analyse each and every report of thrombosis with thrombocytopenia for each of the COVID-19 vaccines as we receive them. In addition, the MHRA’s assessment of new cases, together with significant information shared with the MHRA from other vaccine regulatory authorities around the world (including the US Food and Drugs Administration and Centre for Disease Control, the Australian Therapeutic Goods Administration, and the European Medicines Agency) and newly published literature on this issue is considered weekly by the CHM’s COVID-19 Vaccines Benefit-Risk Expert Working Group.

The MHRA publishes a weekly report of suspected adverse reactions reported via the Yellow Card Scheme for the COVID-19 vaccines. Information on the number of cases of thrombosis with thrombocytopenia reported for each of the COVID-19 vaccines is included in this report, as well as age and sex stratified data for the COVID-19 Vaccine AstraZeneca. The most recent of these reports was published on 10 June and can be accessed via the following link: Coronavirus vaccine - weekly summary of Yellow Card reporting - GOV.UK (www.gov.uk).

With regards to your request for data on the number of cases of CVT and PVT and other thromboses individually for each of the COVID-19 vaccines, further breakdown of the data currently published is due to be released. As such, we have determined that this information is exempt under Section 22 of the of the Freedom of Information Act. Section 22 is a qualified exemption, which means that we have considered whether the public interest in releasing the information is outweighed by the public interest in not giving the information. In favour of disclosure, we consider that there is a general public benefit from publishing this information, however, we consider that the public interest will be better served by releasing the information when it is in its complete form, rather than the Agency releasing an incomplete version of the data prematurely. Please be assured that when assessing the cases of thrombosis with thrombocytopenia reported for COVID-19 vaccines, reports are stratified by the type of thrombosis (ie usual vs more unusual thrombosis such as CVT) and are analysed accordingly by the MHRA, the CHM and its COVID-19 Vaccine Benefit-Risk Expert Working Group.

COVID-19 vaccines for children

You will be aware that since you sent your most recent email, on 4 June 2021 the MHRA authorised the Pfizer-BioNTech COVID-19 vaccine for use in 12- to 15-year olds in the UK.

We have carefully reviewed clinical trial data for the Pfizer/BioNTech vaccine in over 2000 children aged 12 to 15 years of age and have concluded that that the benefits of this vaccine outweigh any risk and that it is effective and acceptably safe in this age group. This data has also been reviewed by the independent CHM, its COVID-19 Vaccine Benefit Risk Expert Working Group, as well as the Paediatric Medicines Expert Advisory Group.

No new side effects were identified and the safety data in children was comparable with that seen in young adults. As in the young adult age group, the majority of adverse events were mild to moderate, relating to reactogenicity (e.g. sore arm and tiredness.)

The CHM met on 27 May 2021 to consider the application to extend the existing Pfizer-BioNTech COVID-19 vaccine authorisation to include children aged 12 – 15 years old. The CHM considered the results of randomised, placebo-controlled clinical trials in over 2000 children aged 12 – 15 years.

The immunogenicity results (showing how well the vaccine works), studied in approximately 200 children, demonstrated similar neutralising antibody levels in adolescents aged 12-15 years compared with the levels in young adults aged 16-25 years. These results are supported by a very high level of short-term efficacy data in adolescents against symptomatic disease after 2 doses of vaccine 21 days apart. In participants with no prior evidence of infection there were no cases of COVID-19 in the vaccinated group from 7 days after the second dose compared with 16 cases in the placebo group. Consistent with what was seen in adults there was evidence that the vaccine provides protection even before the administration of dose 2. There were no cases seen in the vaccine group from 11 days after dose 1 compared to 31 in the placebo group. Prior to day 11 there were 3 cases in the vaccine group and 4 on placebo.

Safety data in children aged 12-15 years is available from one clinical trial. This safety data is supported by the safety data from the clinical trials in individuals aged 16 years and over, together with a large amount of real-world data on the safety of the Pfizer/BioNTech COVID-19 vaccine in individuals aged 16 years and over. This has been closely monitored as the vaccine has been rolled out both in the UK and internationally. This experience has reinforced the conclusion that the benefits of the Pfizer/BioNtech COVID-19 vaccine continue to outweigh any possible side effects. The Public Assessment Report (Regulatory approval of Pfizer/BioNTech vaccine for COVID-19 - GOV.UK (www.gov.uk)) will be updated to include the data which the CHM looked at to approve this vaccine, this will be available in due course.

Other regulatory authorities around the world, including the European Medicines Agency (EMA), US FDA and Health Canada, have also approved the use of the vaccine in 12 – 15 year olds.

As mentioned above, the MHRA has authorised the vaccine for use in those aged 12 to 15 years but it will be the JCVI who will decide the COVID-19 vaccination policy for children. The MHRA has in place a comprehensive safety surveillance strategy for monitoring the safety of all UK-approved COVID-19 vaccines and this surveillance will include children aged 12 to 15 years should the vaccines be deployed in this age group.

Thank you for taking the time to write to us. Please be assured that the MHRA continues to closely monitor the safety of the COVID-19 vaccines and will carefully consider any new information which becomes available, taking action to protect public health where necessary.

I hope the information provided is helpful, but 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