The most important thing to know about AstraZeneca’s Covid-19 vaccine is that it’s safe and it works — in spite of the missteps that have marred nearly every stage of its rollout.
New data shared Monday showed the vaccine was 79 percent effective in preventing symptomatic infections in a trial of over 32,000 people, and the company said it would prepare to apply for emergency authorization from the Food and Drug Administration in the coming weeks.
But health officials said Tuesday that the results from the trial may have relied on “outdated information” that “may have provided an incomplete view of the efficacy data”.
AstraZeneca said Tuesday that it plans to announce results from the primary analysis within 48 hours.
The study findings shared Monday briefly boosted confidence in the vaccine after the last week’s disaster for AstraZeneca: As coronavirus cases rose in a third surge across Europe, reports began to emerge that a handful of people who received AstraZeneca’s vaccine experienced rare but serious and unusual blood clotting. More than a dozen nations suspended use of the vaccine. The European Medicines Agency quickly reaffirmed the benefit of getting the vaccine and said the clotting cases would be investigated further.
As AstraZeneca’s drama plays out in public, many public health advocates have watched with horror, afraid they are witnessing the legitimacy of global vaccine development being destroyed. But this process, warts and all, is how vaccine safety is supposed to work. And if the AstraZeneca vaccine deserves people’s confidence after months of stumbles, this process is how it will earn it.
From the very beginning, AstraZeneca made errors that led to a loss of trust. When it first reported early clinical trial results of the vaccine it developed in partnership with the University of Oxford, the company was swiftly met with criticism over the trials’ design and how the data was shared. A subset of the people in the trial had been given the wrong — but ultimately more effective — dose of the two-shot vaccine by mistake; the company had inappropriately pooled data from differently designed, multinational studies; and company personnel had consistently shared safety and efficacy data with industry analysts and investors before disseminating information to the public.
By the end of November, as Pfizer-BioNTech and Moderna awaited emergency use authorization for their vaccines in the United States, AstraZeneca was enduring widespread criticism for its lack of transparency and rigor. Its vaccine is still not approved in the United States, where the F.D.A.’s review process is typically more intense and time-consuming than that of other countries’ regulators. The clinical trial data released on Monday is an important step toward the vaccine’s application for emergency authorization.
AstraZeneca’s vaccine got approval in the European Union in January and formed the backbone of many countries’ vaccine campaigns. But the company has continued to find itself on its heels, as production challenges in its Belgian factory left the European Union with significantly fewer doses than it was expecting this quarter.
The latest fiasco, over the clotting cases, appeared to be a particularly damaging setback for both the drugmaker and public health more broadly. Last week, public health authorities gave stern warnings against halting vaccinations while investigating the clotting cases, with some experts arguing that the suspensions were politically motivated and would open the door to an even steeper rise in cases across Europe. Epidemiologists furiously differentiated association from causation; many have argued that a handful of blood clots in recently vaccinated millions signifies nothing.
But the public nature of this process is a crucial part of restoring trust in it.
Vaccine pharmacovigilance — the process of determining vaccine safety — is a science. Before rolling out a vaccine, epidemiologists list things that might go wrong after vaccination, whether the health issues are caused by the vaccine or not. They then select the most likely ones, which might include problems associated with other vaccines or conditions caused by the disease the vaccine is intended to prevent (such as blood clotting, which is a known symptom of Covid-19 infection).
Before the vaccine is distributed, scientists determine how common these health issues are in the general public to create a baseline to measure against if they see the health events among people getting the vaccine. As people receive immunizations, scientists repeatedly analyze real-time adverse event data, hunting for rates that exceed what they would typically expect. Elevated event rates — called “safety signals” — often lead to extensive reviews of patient information, results of which are shared publicly in a timely way.
It can be tricky to explain to people why a few cases of blood clots among the millions of people who were vaccinated constituted a red flag. Several experts have said the rate of clots in AstraZeneca vaccine recipients is not higher than what’s expected in the general population.
But in this case, it’s not the general population that the findings should be compared against, says Daniel Salmon, who directs the Institute for Vaccine Safety at the Johns Hopkins Bloomberg School of Public Health. In a report published last Tuesday, German health ministry scientists wrote that six of seven clotting events had taken place in relatively young, recently vaccinated women. The group whose baseline rate they should be compared against isn’t the general population — it’s other, unvaccinated, relatively young women, says Dr. Salmon.
Making that calculation publicly — and explaining why its results are concerning — signals to members of the public how seriously scientists take their safety. And that is how the vaccine safety process builds trust rather than undermines it: by showing plainly how methodical and uncompromising it is.
During a pandemic, vaccine safety questions make headlines. And a world where pandemic vaccine safety is not sensationalized by the news media and misunderstood by the public, either willfully or accidentally, is a fantasy. Experts’ concerns about vaccine safety protocols playing out in public are rooted in these communication failures. If we don’t have these conversations the right way, they fear, people will get the wrong message — they’ll think all vaccines are unsafe.
But being transparent can only improve the perceptions of safety. After all, the bulk of AstraZeneca’s current problems are a consequence of being inadequately public and timely about its earlier mishaps. While its product has enormous potential, it cannot reach people without trust — and it’s not clear that the company has the currency necessary to build trust on its own.
The vaccine safety process exists to do what AstraZeneca, for whatever reason, has been unable to do for itself: Prove that the vaccine is worth the trust its makers haven’t earned.
Keren Landman is a physician who specializes in infectious diseases and a journalist who writes about public health.