The MHRA Papers - Part 14
The parable of the Oxford AstraZeneca vaccine
SUMMARY
Hailed as a triumph for British science, the vaccine vanished in a year despite the downplaying of its harms - the long read of a “business as usual” story.
We continue reviewing the minutes of the MHRA’s Commission on Human Medicines (CHM) COVID-19 Vaccines Benefit Risk Expert Working Group meeting.
The Oxford Astra Zeneca vaccine was approved in the UK on 30 December 2020, making the UK the first country to do so. The UK ordered 100 million doses—enough to vaccinate 50 million people. Prime Minister Boris Johnson described the development as "a triumph" for British science: "We will now vaccinate as many people as quickly as possible."
Hancock couldn't contain himself when he told the Commons the approval was "a huge British success story" and "the single biggest stride that we've been able to take since this pandemic began."
However, cracks in the data were appearing by the end of January.
On 22 January, the EWG heard a summary of fatal cases in the UK following vaccination with the AstraZeneca vaccine in those aged 65 – 96. The events reported in fatal cases were explained away as expected due to the patient's age and comorbidities. The EWG also requested more information on the cases of toxic epidermal necrolysis and the fatal instances in which the onset of symptoms occurred within 25 minutes of vaccination.
On February 4th, the EWG meeting heard that reports of cases of Bell’s Palsy and transverse myelitis, which are adverse events of special interest, had been received. These were being monitored closely, and Observed vs Expected and Rapid Cycle analyses were also being performed. The EWG found the safety data reassuring.
On 25 February, a signal for immune thrombocytopenia (ITP) was noted but ignored. ITP is a rare autoimmune disorder causing low platelet counts and increased bleeding risk. The EWG deemed initiating risk minimisation for ITP premature, arguing that warnings in product information could unjustifiably fuel vaccine hesitancy. Their solution was to enhance monitoring instead.
On March 9th, The EWG stated there was potentially an ‘increased signal of Guillain Barre’ Syndrome (GBS), particularly with the AstraZeneca vaccine’ and that reports of GBS - yes, you have guessed it - should be closely monitored. The EWG minutes reported that ‘A formal epidemiological study was not indicated’ with no rationale for why this was the case.
The meeting of the 17th March reviewed venous thromboembolism and thrombosis with thrombocytopaenia reported following the AstraZeneca COVID-19 vaccine.
The EWG reported that the ITP notifications received through the Yellow Card scheme remained substantially below the expected amount. The meeting noted a cluster of 7 thrombotic events occurring in conjunction with thrombocytopenia, predominantly in younger patients. The meeting heard evidence of a signal of thromboembolic events occurring with thrombocytopenia that the European Medicines Agency had raised following the suspension of the AstraZeneca vaccine in several EU member states.
While other countries suspended the vaccine, the EWG determined that a detailed examination of the clinical cases was necessary. They agreed to rapidly gather data, with input from clinical specialists, to address the evolving situation. The meeting concluded that this issue should be promptly further evaluated as a potential signal.
The Group concluded that there was no evidence of an increased risk of peripheral venous thromboembolism or thrombocytopenia alone. However, due to the seriousness of thrombosis with thrombocytopenia, they advised gathering further information quickly.
Communications were mobilised to downplay the issue: ‘Public messaging around the signal would need to be very carefully handled to maintain public confidence.’
On March 11, Health authorities in Denmark, Norway and Iceland suspended AstraZeneca's vaccine following reports of blood clots in the vaccinated. Austria earlier stopped using a batch of AstraZeneca shots while investigating death from coagulation disorders and one from pulmonary embolism.
The MHRA responded that ‘this is a precautionary measure by the Danish, Norwegian, and Icelandic authorities. It has not been confirmed that the AstraZeneca COVID-19 Vaccine caused the blood clot reported. People should still get their COVID-19 vaccine when asked to do so.’
Nothing to see here, then.
On 15 March, The Netherlands and Ireland temporarily halted the vaccine use following reports of blood clotting and low platelet counts.
AstraZeneca said, "A careful review of all available safety data of more than 17 million people vaccinated in the European Union and UK with the COVID-19 vaccine of AstraZeneca has shown no evidence of an increased risk of pulmonary embolism, deep vein thrombosis or thrombocytopenia, in any defined age group, gender, batch or in any particular country."
By 17 March. Norway kept the vaccine on hold for another three weeks after a small number of younger inoculated people were hospitalised for a combination of blood clots, bleeding and a low count of platelets, some of whom later died.
On 23 March, the EWG was presented with a summary of the cases of thromboembolic events with concurrent thrombocytopenia in the UK and worldwide. A potential case definition was also presented to the EWG.
Experts found that some cases of anti-PF4 antibodies were recorded, though caution was advised in linking this to the vaccine without a clear mechanism, which has led to past misunderstandings. A risk analysis indicated that fewer doses of the AstraZeneca (AZ) vaccine would lead to events of CVST with thrombocytopenia in younger individuals compared to older ones. Most reported cases were females and involved only first doses, with significant missing information. AstraZeneca provided an overview of potential mechanisms, questioning if they were unique to its vaccine or common across all COVID-19 vaccines related to the spike protein.
The EWG advised caution in assuming a link to the vaccine without establishing a mechanism, as they said this had led to erroneous associations in some past cases.
At the meetings, more obfuscation occurred. The members commented that the cases lacked significant information at present, that there was insufficient evidence to establish causality, and that the events that have been reported are rare. Instead of taking action, the EWG wanted more information on possible risk factors in cases.
Allowing AstraZeneca to comment on the challenges of an epidemiological study of the combined event of thromboses with thrombocytopenia introduced more delays. The company was allowed to ignore the issue further by reassuring that it was engaged with NHSE to develop a protocol to study the potential association further.
By 24 March, the EWG noted a worsening situation, having received reports of over 30 cases of thromboembolic events with thrombocytopenia linked to AstraZeneca since the 23 March meeting. This included cases with and without confounding factors.
The EWG reported that the background rate of thromboembolic events with thrombocytopenia is unknown. They discussed ways to gather this information, such as using laboratory, radiological, or UK Biobank databases. One possible approach was to identify clinical cases of CVST and examine platelet counts to assess concurrent thrombocytopenia. The EWG also noted that the reported CVST cases with thrombocytopenia linked to the AstraZeneca vaccine included instances without predisposing factors, which is atypical compared to earlier reports, where patients usually had risk factors.
No background work seems to have been done; surely, a review was needed. The occurrence of CVST without predisposing factors should have raised significant concern. The EWG noted that updates to the AstraZeneca vaccine information will be considered at a future meeting when more data, including cases related to the Pfizer vaccine, become available. No action is needed, then.
By the end of March, the MHRA found 79 people had suffered rare blood clots after vaccination - 19 of whom had died. Nearly two-thirds of the cases of rare clots were seen in women, with three of them aged under 30.
Those under 30 were to be offered an alternative Covid vaccine to AstraZeneca’s due to the evidence linking it to rare blood clots.
Watch the reassurance here:
At the 12 April meeting, a summary of the AstraZeneca COVID-19 Vaccine case reports highlighted 19 confirmed cases of thrombocytopenia linked to CVST or non-CVST events. Of these, 5 cases were obese, 4 had no reported comorbidities, and one was treated for hypothyroidism, with the majority being Caucasian. The overall fatality rate has dropped to 22%. Notably, a possible pregnancy case and a case after the second dose were reported, with around 1 million second doses administered primarily to older individuals in the UK. The EWG also reviewed adverse events of special interest for the Pfizer/BioNTech vaccine, including fatal cases, anaphylaxis, Bell’s palsy, Guillain-Barré syndrome, and cardiac issues like myocarditis and pericarditis.
The EWG stated that evaluating individual risk-benefit profiles for sub-populations based on age-stratified data for the AstraZeneca COVID-19 Vaccine is not feasible. However, the overall benefit-risk balance was still acceptable.
They cautioned against interpreting UK Yellow Card dose data since dose reporting wasn't mandatory until February 2021. The EWG discussed Guillain-Barré and Bell’s palsy, noting a reduced background population rate of Guillain-Barré during the pandemic, which has also been linked to COVID-19. They recommended ongoing monitoring of Bell’s palsy safety data related to the Pfizer/BioNTech and Moderna vaccines and requested future updates on breastfeeding exposure cases.
At the 19th April meeting, the EWG was asked whether, based on the evidence presented, it considered the benefit-risk balance favourable for all patients and all age groups.
The EWG advised that the AstraZeneca COVID-19 vaccine still had a favourable benefit-risk profile. However, the benefits for individuals under 30 were less clear and may be outweighed by risks as incidence rates rise, depending on the severity of the pandemic. The benefit-risk ratio remained positive for those aged 30-39 but required careful monitoring. No further regulatory action is needed at this time. Seven days later, at the April 16 meeting, the answer changed to” the benefits of immunisation in individuals under 30 years may be outweighed by the potential risks.” However, despite this change, the EWG still had not identified any potential trigger for urgent regulatory action.
By the 10 May meeting, benefits in individuals under 40 years were considered to be “probably outweighed by the potential risks,” It’s unclear what information the EWG used to change the risk-benefit in over 40s.
On May 5th, the BMJ reported that 59 venous thromboembolic events occurred in individuals vaccinated with the Oxford-AstraZeneca vaccine in Denmark and Norway, compared to 30 expected from general population incidence rates. This resulted in a standardised morbidity ratio of 1.97 and an excess of 11 events per 100,000 vaccinations.
On May 7th, the Joint Committee on Vaccination and Immunisation (JCVI) advised that the Oxford/AstraZeneca vaccine should not be offered to people under 40. As of 28 April 2021, the MHRA had received 242 reports of blood clotting cases in people who also had low platelet levels following the use of the Oxford/AstraZeneca vaccine.
On May 12, Norway discontinued the AstraZeneca vaccine due to the risk of rare but harmful side effects. Over the next week, more than a dozen countries followed suit.
By August 2022, the UK had no plans to order more supplies of the AstraZeneca Covid vaccine. In May 2024, the European regulator said that the approval for AstraZeneca’s Vaxzevria had been withdrawn “at the request of the marketing authorization holder.”
Oxford/AstraZeneca arrived in a blaze of glory, yet it had all but disappeared within a year. This was due to the poor interpretation of the signals of harm and the regulatory delays that caused the field to act.
This post was written by two old geezers who would like readers to think of the poor souls who were ill or died, when all this could be prevented with what was once known as independent regulation.
This post was written by two old geezers who
The EWG discussed the lack of data on severe cases of Covid-19 and the lack of data in the elderly. The bulk of efficacy data is in the 18-55 years of age group. A subgroup analysis in the group 18-55 years vs the group > 55 years should be requested from the Company. The EWG agreed to return to the issue of age once these data are received.
I am not surprised by all this, having followed every accessible (outside MSM) event with regards to the products, from well before they were rolled out. But it sickens me to the stomach. In February 2021 a fit woman aged about 60, a runner, was paralysed by the AZ vaccine after one dose and was in hospital for nearly a year. Her brother reported that the hospital didn't have a clue what was wrong and apparently (although unbelievably) AZ medical associates went to the hospital to advise. Of course it was GBS. (My partner knows both the woman and her brother, and spoke to the latter about her, so this is not gossip). A bit later that year, in the same week two women, very fit and healthy, were hospitalised after the AZ for brain bleeds. Another man I know had a heart attack after his AZ jab, and he told me the hospital were querying where his medical history could be found - when he told them he had "no medical history", being a fit and healthy man, always out with his dog, never taking medication if he could help it, they were apparently amazed, as whatever presentation he had - requiring several stents, ultimately - it appeared to them as a chronic condition (compare Dr Aseem Malhotra's account of his father's heart attack).
Worst of all, when I told a group of people I was with about the woman with GBS, shortly after she was hospitalised, no-one reacted beyond - literally - a shrug of the shoulders. I can't understand why people aren't more enraged - I didn't have the stuff and I am angry!
(I could list dozens more effects in people I know but don't want to drag on my first post on here , as a new subscriber, ad nauseam.
Two main issues as I see it.
In the past, vaccines were withdrawn quite quickly if side-effects were suspected. Why not in this case?
Secondly, by hiding and downplaying these possible issues, informed consent went out of the window.