By Dorit Rubinstein Reiss
In the past weeks, three companies in advanced stages of COVID-19 vaccine trials reported good news. Moderna and Pfizer reported, respectively, 94.5% and 95% effectiveness of their mRNA vaccines in preventing symptomatic disease and similarly high effectiveness in preventing severe disease.
This was shortly followed by news that the AstraZeneca vaccine had over 70% effectiveness, and 90% with a different dosage regime.
The companies have also reported a favorable safety profile, with no serious harms attributed to the vaccine, though the vaccines do cause a high rate of temporary and unpleasant side effects, including local reactions and temporary flu-like symptoms.
Pfizer has already applied for an Emergency Use Authorization (EUA) from the FDA, and I would expect Moderna and AstraZeneca to follow suit.
What does this mean? First, a note of caution. These are reports from the companies; the FDA has not yet finished examining the data. Examination may raise questions. The data submitted has to pass dual review.
Experts in the FDA’s Center for Biologics Evaluation and Research will review the data. These experts are, for the most part, civil servants with tenure and considerable experience in evaluating vaccine research, and a history of being very demanding. These are not political appointees. In addition, the FDA has scheduled a meeting of its expert advisory committee – the Vaccines and Related Biological Products Advisory Committee (VRBPAC) – to examine the data on December 10, 2020. VRBPAC is a committee of experts, most of them (though not all) outside of government.
Earlier concerns about the FDA’s independence were well justified; but Commissioner Hahn has since taken steps to suggest he is willing to protect the integrity of the process.
We have an intensive review process in place for a reason, and that if the FDA’s very independent expert committee sees a problem, the FDA will likely send the companies back to work. It’s also important to remember that the data will undergo a second round of review before the CDC’s Advisory Committee of Immunization Practices (ACIP), another expert committee, which created a large workgroup that has followed the vaccines since April.
That said, if the data pans out, these are really, really good numbers, beyond expectations.
But the next steps will not be easy. First, the FDA will have to decide whether to grant an EUA. This is not as simple as it may seem: in its last meeting, VRBPAC expressed concerns about an EUA, not just because it means acting on limited data, but also because it could interfere with further assessment of the vaccines.
Once an EUA is approved, it becomes hard to refuse the authorized immunization to the placebo arm in ongoing and future COVID-19 vaccine trials. People can pull out of trials at any time; those who think they got the placebo might pull out and seek a vaccine. And, ethically, it may be problematic to deny vaccines to people in the trial who are at high risk of getting COVID-19 or having severe COVID-19. But unblinding and offering the vaccine to the placebo arm may make it impossible to generate long-term data.
Further, historically, an EUA has never been granted for a vaccine for the general population. EUA or equivalent authorizations have only been granted for specific populations, in limited circumstances. This is why a group of experts recently recommended using expanded access, instead.
On the other side are the serious harms of COVID-19. Over a quarter million people have died from it in the United States, and over a million world-wide. Hospitals are struggling with ICU bed shortages, many are sick, and the economic impacts have been tremendous.
People are anxiously awaiting a vaccine. And these are, again, very strong numbers. Delaying an EUA on this data may also be unconscionable, given that people will be harmed and killed while a preventive is at hand.
FDA traditionally leans towards caution in approval, even when it means people may die for lack of a treatment that has not met the strong requirements in place to show that it is safe and effective. But it still is a balance, and during this pandemic, the pressure to allow access to a vaccine with strong data behind it is strong – and reasonably so.
An EUA would be just the first step, if approved. The vaccines still need to be distributed, which also raises a number of questions. Distributing hundreds of millions of vaccine doses is a large undertaking. The CDC has been preparing for it in collaboration with states, with states submitting distribution plans and the CDC reviewing and finalizing them, but recent investigative journalism has raised questions about how those plans will be funded.
Also, because mRNA vaccines – which both Moderna’s and Pfizer’s are – require storage at very cold temperatures and prompt use once removed from those temperatures, there are practical problems to solve.
Also important is the question of allocation. Early on, there will not be enough vaccine for all those who want it. Several groups are addressing this issue. In a detailed report, an NASEM commission set out an allocation framework. The ACIP workgroup on COVID-19 vaccines is setting out allocation guidelines, too.
Communities of color are disproportionally impacted by the virus, seeing higher rates of COVID-19, deaths from COVID-19, and harms from COVID-19 – mostly, again, because of historical injustices. But at least some members of these communities express understandable concerns about being guinea pigs. In other words, there are indications that vaccine hesitancy may be a barrier to uptake, especially in communities with historical reasons to mistrust government and scientists. The challenge is how to avoid a situation where this historically valid mistrust causes more harm to the community by deterring it from using the available protection. Is there a way to prevent past wrong from contributing to continuing harm?
Also unhelpful is the fact that promoters of misinformation are already working to create doubts about COVID-19 vaccines by misrepresenting the data to claim their risks are higher than the data shows, and their benefits lower.
And even in the best of circumstances, it will take time to achieve herd immunity through vaccination. Other measures – social distancing, masks, closing some businesses – will have to remain in place, in a population already suffering from fatigue due to previous restrictions, and facing harms and injustices. So far, our policy makers have not provided comprehensive support to counter the harms of the pandemic itself and pandemic control measures, and such support is still badly needed. Experts have proposed measures that can help, and the government needs to act on these recommendations, and fast.
The new data on COVID-19 vaccines is extremely promising, but we have a lot of work to do to help people through the pandemic. We cannot relax now.