The Telegraph
Revealed: Why the British regulator missed the link between the AstraZeneca jab and rare blood clots
In early March, about four weeks after the first AstraZeneca vaccine was administered in Europe, few signals – such as flares – began to go off across the continent. Only in Austria, on March 7, and days later in Denmark, Norway and Iceland, did European health care regulators start reporting small amounts of blood clots and deaths among people who had been vaccinated. On March 15, Germany then announced seven cases and three deaths and, like others, suspended the use of the vaccine. The AstraZeneca jab was associated with a ‘conspicuous accumulation of a special form of very rare cerebral arterial thrombosis associated with a platelet deficiency and bleeding’, said the Paul-Ehrlich Institute, the well-known medicine regulator in Germany. But in Britain, where the rollout of AstraZeneca began a full month earlier and 11 million doses have already been administered, there was nothing. On 11 March, the UK’s newly sovereign Regulatory Agency (MHRA) issued a statement saying it could not see any evidence of a problem. “We are constantly monitoring the safety of vaccines to ensure that the benefits outweigh any potential risks,” said Dr Phil Bryan, the MHRA’s leader on vaccine safety. ‘Reports of blood clots received so far do not exceed the number that would naturally occur in the vaccinated population. “Public safety will always come first.” But the MHRA was, it seems, wrong. An investigation by The Telegraph has determined that signals have been shooting unnoticed in the UK’s Yellow Card database for at least a month, perhaps longer. In January, a patient developed a brain clot after the first dose of AstraZeneca jab, The Telegraph confirmed. In early February, two similar cases followed, including a death and a life-altering CVST blood clot in a young adult. All had low blood platelets and all were reported in the yellow card system. The MHRA told The Telegraph on Friday: ‘We are aware of thrombo-embolic events that took place in January, but our first report was received in the week beginning on February 8 …. we cannot disclose information about individual cases to protect the patient and reporter. confidentiality. The benefit of taking the AstraZeneca jab is undoubtedly outweighed by the risk now associated with the vaccine. This is not only the judgment of the MHRA, but also of the European Medicines Agency (EMA) and the World Health Organization (WHO). The risk of developing cerebral venous sinus thrombosis (CVST) in combination with a low platelet count or thrombocytopenia after receiving the vaccine is negligible and is estimated in only 1 in 100,000 cases, perhaps less. That, says Sir David Spiegelhalter, the biggest risk expert in Britain, is about the same chance of dying from a general anesthesia, or guessing the last five digits of a stranger’s cellphone number correctly. According to Covid himself, the risk of CVST alone is estimated to be eight to ten times higher, according to an analysis of US data published last week. The MHRA nevertheless faces serious questions as to why it did not detect the signals sooner. The issue is not that it was left flat-footed, or that earlier detection would necessarily change his advice, but that the delay is international policy and confidence in the fight against Covid 19 for the world. Prof Stephan Lewandowsky, a psychologist at the University of Bristol who is studying the deployment of Covid-19 vaccines, told the Financial Times on Friday: ‘The MHRA is responding slowly to the emergence of a specific constellation of symptoms related to the AstraZeneca vaccine and slow to communicate what they found – and I’m not the only one who thinks so. Why then was the MHRA slower than others to spot the early signals? The Telegraph investigation indicates that the issue is related to the algorithms he had to interrogate the UK data and the limited access to early emerging data from Europe. Observers say this should be seen in the context of the ‘operational and logistical challenges’ facing the regulator in the run-up to the UK formally leaving the EMA on 31 December, and that the MHRA for the first time in January became a sovereign regulator. 1. The key to fast-moving pharmaceutical supervision is to sift wheat efficiently from the chaff. When a new drug introduces thousands of side effects, it begins to engage patients as well as clinicians in the reporting systems. According to the analysis of published MHRA data by Dr Hamid Merchant, a pharmaceutical scientist, a total of 532 “blood system events”, including 20 deaths, occurred from 4 January to 14 March through the UK’s Yellow Card system related with the AstraZeneca jab. at the University of Huddersfield. There were also thousands of unrelated reports. Of the thrombotic events recorded, four were related to CVST (but no deaths were recorded), 55 were non-site specific and there were 64 and 66 cases in the lungs and deep veins respectively. There were then 267 general hemorrhages and six deaths, three of which were due to cerebral hemorrhage. Finally, there were 60 cases of thrombocytopenia, including 2 deaths. To sift such data, regulators build algorithms that must balance a “sensitivity” to bone work. The more sensitive the algorithm, the more warning signals it will produce to investigate – and many of these labor-intensive investigations will be fruitless. It is not known exactly what parameters the MHRA set, but it is clear that it was not as sensitive as those used by some regulators in Europe. The MHRA said it followed a principle of applying ‘statistical techniques that can make us wise if we see excessively more cases than we would expect to see based on what is known about background figures in the absence of vaccination’ . This is reflected in the regulator’s initial statement when he said that coagulation reports are not above normal. But other countries have raised the sensitivity meter to 11. “Our policy is that it is immediately related to a death, or a serious adverse drug reaction,” said David Benee Olsen, senior adviser at the Norwegian Medicines Agency. , The Telegraph said. ‘I think you have to be careful to look at the background figure, because in this case doctors told us, for example, that this rare combination, this thrombocytopenia and CVST have never been seen in these kind of patients, young patients, so it was very difficult to do a background figure versus appearance. ‘There are also cultural differences in paternalism and transparency between regulators. An extreme example of the latter was shown in the US last week when the distribution of the Johnson and Johnson Covid vaccine was ‘interrupted’ and a public hearing was called to discuss the six cases of CVST and thrombocytopenia that caused it. A similar approach was followed in Europe. In Norway, the first suspect was reported dead on the day it took place, March 12 – the day after similar reports appeared from neighboring Denmark. On March 13, Norway identified three more cases, and all patients were flown to the same hospital for treatment and real-time analysis by a single team of specialists. Once again, the incident was immediately made public in an attempt to build trust. When the Pfizer jab was first introduced in the UK, it seems that the MHRA decided to follow the same, very modern approach. On December 9, just a day after the vaccination began in the UK, the regulator announced that three people had severe allergic reactions after receiving the Pfizer jab, warning that ‘any person with a history of anaphylaxis against a vaccine, medicine or food ‘does not have it. The approach-as-it-worked approach worked perfectly and hardly a word was written on the issue until the advice was withdrawn a month later when more information showed it was not a risk. Unfortunately, the MHRA may not have followed the same approach with the issues surrounding the AstraZeneca jab – or at least it may not. The MHRA says it received its first report on thrombocytopenia in the week of February 8, but the regulator only told the public on March 18 when it announced five cases. This was done just moments before the EMA opened a sensational personal information session on the issue, which at the time dominated the world headlines. Since then, the MHRA has made three further announcements on new cases identified in the UK. Late on Good Friday, after most people voted for the bank holiday weekend, he said it recorded a total of 30 cases, including seven deaths. On April 7, again during a high-profile EMA press conference, the score appears to have risen to 79 and 19 deaths. The latest figures, which were quietly released on Thursday night, show that the number of coagulation cases in the UK with thrombocytopenia stands at 100 with 22 deaths. It is not known how many of the 22 deaths are covered in the Yellow Card data that Dr Merchant analyzed between March 4 and 14, but it seems likely that a large number of them – perhaps the largest part – will date from that period. Despite requests from several newspapers, including The Telegraph, the MHRA did not disclose the dates on which the deaths occurred or were reported in the Yellow Card system, citing the need to maintain patient confidentiality. There is also no suggestion that the MHRA treated the report on CVST with thrombocytopenia; it has only noticed the problem that has not yet been proven, in other cases. Another reason for the MHRA’s slower response, observers say, may be that it lost access to Eudravigilance, the extensive European database that reported all adverse drug reactions, when the UK left EMA regulation on 31 December last year . An EMA spokesman told The Telegraph: ‘The MHRA only has access to the EudraVigilance gateway. This allows them to submit cases (or receive Northern Irish cases), but they cannot check the data in EudraVigilance. “If the MHRA needs data, they will have to ask for it … In addition, of course, they can look at the data published on the adverse drug response (ADR) website.”