Let the Data do the Talking – Discussing the Oxford AstraZeneca COVID-19 Vaccine and Blood Clot Concerns
Recent reports suggest that there may be a cause for concern with the Oxford AstraZeneca COVID-19 vaccine, with a suggested link between the vaccine and blood clots. Just how worried do we need to be? PHASTAR’s Vice President for Statistical Research and Consultancy, Jennifer Rogers, talks us through what we know.
Germany, France and Spain have become the latest in a collection of European countries who have suspended the use of the Oxford AstraZeneca COVID-19 vaccine for fear of a link between the vaccine and blood clots. But are these decisions justified by the data?
According to reports, a review from Norway’s medicines agency showed four new cases of “serious blood clotting in adults”. A BMJ report also states that the Danish Authority said that one person in Denmark had died after receiving the vaccine and Austria suspended the use of a batch of the vaccine after one person had multiple thrombosis diagnosed and died 10 days after vaccination, with another person being admitted to hospital with pulmonary embolism and now recovering. The European Medicines Agency (EMA) said that two other reports of thromboembolic event cases had been received from that batch.
As of 10th March 2021, 30 cases of thromboembolic events had been reported among the five million people given the AstraZeneca vaccine in the European Economic Area. But thromboembolic events happen anyway, so how do the numbers that we see here in this vaccinated population compare to what we would expect to see in the general population? According to this study in the Journal of Thrombosis and Haemostasis, the annual incidence rates of venous thromboembolism (VTE) range from 750 to 2,690 per 1,000,000 individuals in the population, increasing to between 2,000 and 7,000 per 1,000,000 among those aged 70 and older. Note that these are annual incidence rates, so let’s say that the incidence was 2,000 per 1,000,000 (given the fact that the majority of those vaccinated are older, this is arguably a sensible assumption). This would be 10,000 per 5,000,000. If this were to be spread evenly across the year, this would correspond to around 192 cases of VTE per week. So, these numbers suggest that the incidence of VTE among this vaccinated population is actually lower than what might be expected in the general population.
Anxiety around possible side effects for any new treatment is understandable. Anxiety about any of the COVID-19 vaccines is especially understandable given the apparent speed with which the vaccines were approved. But safety remains the number one priority for any new treatment and is monitored throughout all clinical trials. Looking at the results for the trials that led to approval of the Oxford AstraZeneca vaccine in the UK, we see that unsolicited adverse events were collected through 28 days post each dose and that 38% in the vaccine group reported side effects. But note that 28% in the placebo group also reported side-effects, so the vaccination process itself seems to account for almost three-quarters of all the reported harm in the vaccination group. Many of the additional side-effects in the vaccine group are adverse events such as fever, fatigue, chills, and headache.
During clinical trials, as well as collecting information on all adverse events, additional data is collected on “Adverse Events of Special Interest” (AESIs). One of the categories of AESI was “Thrombotic, thromboembolic, and neurovascular” and there were four cases in the vaccine group from 12,021 people and eight cases in the placebo group from 11,724 people. So, there were fewer events in the vaccine group than the placebo group.
Despite this, there is an acceptance that clinical trials are relatively short in the grand scheme of things and so once a new treatment is approved, it is not released into the real world, never to be looked at again. Many people who I talk to think that Phase III is the final phase of the clinical trial process, but this isn’t the case. Phase IV studies are surveillance studies that examine the continuing efficacy and the side-effects of a new treatment after it has been approved and is on the market. They look for side-effects that were not seen in earlier trials and can also identify side-effects that may only appear after a long period of time. Furthermore, the UK implements a “Yellow Card” system to report adverse reactions to all treatments. The most recent publication of the coronavirus vaccine Yellow Card reporting tells us that as of the week ending 28th February 2021, at least 20,275,451 people had received their first COVID-19 vaccination (across all vaccine types), with 815,816 second doses administered. Up to and including the 28th February 2021, the Medicines and Healthcare products and Regulatory Agency (MHRA) received and analysed 33,207 Yellow Cards reporting a total of 94,809 reactions. Whilst this is likely to be an underreporting of adverse events, it still only accounts for 0.16% of all people who have received at least one dose of the vaccine. The publication also reports: “For both vaccines, detailed review of all reports has found that the overwhelming majority relate to injection site reactions (sore arm for example) and generalised symptoms such as a ‘flu-like’ illness, headache, chills, fatigue (tiredness), nausea (feeling sick), fever, dizziness, weakness, aching muscles, and rapid heartbeat. Generally, these happen shortly after the vaccination and are not associated with more serious or lasting illness.”
So far, these vaccines appear to be safe. In the general population, events happen. People get sick. And whilst we are undertaking an enormous vaccination programme to vaccinate the entire global population, events will continue to happen, and people will continue to get sick. We need to be careful that we don’t unnecessarily attribute these to the vaccines. When serious events happen, it’s human nature to assume causal links between events, but for now, all reports suggest that there is no link between the Oxford AstraZeneca vaccine and blood clots. WHO experts are meeting today (16th March 2021) to discuss the jab and let’s hope that there’s a positive outcome. But when countries suspend their rollout of the Oxford AstraZeneca vaccine, perhaps prematurely and against the current scientific evidence, the associated media coverage can have a negative impact on vaccine confidence. There are individuals who may still be hesitant and undecided as to whether they will accept their vaccine invitation. Even if the WHO does confirm that the Oxford AstraZeneca vaccine is safe, it’s difficult to deny that the associated negative press over the last few days won’t be damaging to the rollout.