How to rebuild trust in the Oxford-AstraZeneca vaccine

My cousin Iman, who lives in Cairo, Egypt, called me earlier this week to tell me that she had just been offered the Oxford-AstraZeneca Covid-19 vaccine. I congratulated her upon hearing the news; vaccines are, of course, one of the best available tools to defeat this pandemic and Egypt, like many countries in the Global South, has only recently begun its vaccine rollout.

While Iman knew that she was in a fortunate position, she was hesitant, having heard about the safety concerns purportedly associated with the AstraZeneca vaccine. This is not unusual; many people around the world are still on the fence about the Covid-19 vaccines. In many European countries like France, Spain and Italy, where vaccine hesitancy remains high, regulators temporarily suspended the use of the Oxford-AstraZeneca vaccine last week as a precautionary measure over concerns about potential side effects.

But regulators and vaccine safety experts still consider the vaccine to be overwhelmingly safe and effective, and many of the countries that halted the use of the vaccine have since reversed course. Nevertheless, there is a great deal more work that needs to be done to rebuild trust in the vaccine.

This is not what we expected — throughout 2020, the Oxford-AstraZeneca vaccine was rightly lauded for its easy storage requirements, relatively low production costs and cheap price point, which led many governments to place more orders of this Covid-19 vaccine than any other. However, development has been a bumpy ride for the Oxford and AstraZeneca partnership, and the mixed messages that have emerged as a result have likely caused a loss in confidence among the general public, especially in Europe.

In September 2020, clinical trials for the Oxford-AstraZeneca vaccine were temporarily paused due to an unexplained illness in one of the volunteers. As expected, this incident was thoroughly investigated and ultimately not a cause for concern for regulators, but it did delay the product’s approval.

The vaccine was found to be more effective among trial participants who received a weaker first dose compared to those who received a standard one. When a half-strength dose was followed by a standard one, the vaccine was 90% effective, compared to two full dose shots leading to 62% efficacy. This raised some concerns about the robustness of the trial design.

However, the higher efficacy was thought to be the result of a longer interval between the two doses and the vaccine has since been approved in countries for the standard two-dose regimen, which is backed by sufficient clinical data and positive efficacy results.

There were further obstacles when the efficacy of the vaccine in those over the age of 65 was questioned in Europe due to a perceived lack of trial data. While experts often disagree about how much evidence is needed, early clinical data from blood tests showed that the vaccine had triggered an immune response among older patients, similar to what was seen in younger participants. Further, gold-standard, real-world evidence from the UK’s extensive vaccination program has since convinced regulators from other parts of the world that the vaccine is safe and effective for people in this age group.

Most recently, suspected blood clots led to a halt in the Oxford-AstraZeneca vaccine in more than a dozen countries. According to the European Medicines Agency (EMA), a review of around 20 million people who had received the vaccine in the UK and Europe as of March 16 found 18 cases of cerebral venous sinus thrombosis, which can prevent blood from draining out from the brain and seven cases of blood clots in multiple blood vessels.

The World Health Organization pointed out that thromboembolic events are known to occur frequently under normal circumstances, while the EMA’s Pharmacovigilance Risk Assessment Committee, noted “that the number of thromboembolic events reported after vaccination, both in studies before licensing and in reports after rollout of vaccination campaigns was lower than that expected in the general population.”

While the EMA said it could not rule out a link to a small number of rare clots, especially in females, who are more at risk of thrombosis in general, regulators around the world, including the UK’s Medicines and Healthcare products Regulatory Agency, have emphasized that the vaccine clearly protects populations from the risk of hospitalization and death due to Covid-19 — a much greater threat.

In the meantime, the EMA has recommended that health care professionals and patients are made aware of these rare cases of clotting by updating the summary of product characteristics and the package label.

None of this is unusual. Clinical trials can only run for a set period of time, and are typically managed under controlled conditions with relatively healthy participants, and so new safety signals are always observed once a new medicine or vaccine is approved and in use. We, of course, expect our regulatory bodies to operate with an abundance of caution to ensure that medicines and vaccines are as safe as possible. This example shows that the regulatory system and safety monitoring procedures are working as they should.

However, the mixed messaging on vaccine safety from different regulators, government officials, academics, and the media has the potential to erode public trust in not just the Oxford-AstraZeneca vaccine, but all of the available Covid-19 vaccines. While transparency is vital, these officials have a responsibility to clearly convey the full context of any risks and balance the potential harms with the overall benefits.

As many countries in Europe face a third wave of Covid-19 cases, partly driven by new variants, some of which are more transmissible and may cause more severe disease, increasing the uptake of vaccines could not be more essential. One way to do that is through improved global cooperation on Covid-19, which could include prioritizing high-risk groups such as health care workers around the world for vaccination, sharing real-time safety data, increasing the transparency of approval processes, and working together to harmonize vaccine messaging so that it is clear, concise and balanced.

After explaining the rare occurrence of these clotting events and talking through the benefits of taking the vaccine compared to the risk of falling ill with Covid-19, Iman has now agreed to get the Oxford-AstraZeneca shot. Our primary goal should be to ensure that all populations around the world can quickly access the available vaccines, including the Oxford-AstraZeneca one.