September 16, 2020 – Barry Bloom, Joan L. and Julius H. Jacobson Research Professor of Public Health, discusses the coronavirus vaccine development process and how to persuade people to get vaccinated
Q: Given the intense landscape surrounding the development of a coronavirus vaccine—pressure from the Trump administration to roll out a vaccine quickly, questions about recent Food and Drug Administration (FDA) decisions regarding COVID-19 treatments, and the potential financial windfall that big pharma could get if they develop an effective vaccine—do you trust the current process?
A: The key ingredient of any vaccine is trust. And I do trust the process. There are several reasons why.
The FDA has issued regulatory guidance to the pharmaceutical companies on what they would expect for anyone who wants to put in a Biological License Application for a coronavirus vaccine. I’ve read the guidance document. It’s extremely well-crafted. It’s standard for any vaccine to establish safety and efficacy, with a timeline not being at all relevant.
These guidelines, by the way, have been worked through for all the other vaccines that we use for kids. The safety requirements for childhood vaccines have to be really high because they, unlike drugs, are given to healthy children. Nobody wants to hurt kids, so we have to be really cautious.
In a randomized controlled trial, you need to get statistical power to ascertain whether the intervention is protective or not and how protective it is. For the current coronavirus vaccine trials, it’s been determined by a blue-ribbon National Institutes of Health committee that you need around 30,000 people to get a statistically significant result—15,000 people who receive the vaccine and 15,000 in the control group who receive a placebo—and you need to wait until you see about 150 cases of COVID-19 from among the participants. These cases are termed the endpoints that should allow a meaningful decision regarding the safety and efficacy of the vaccine. How long that takes depends on the time to get enough cases .
In addition, all trials, which are double-blinded—meaning that neither the researchers nor the participants know who’s getting a vaccine and who’s getting a placebo—are monitored by a data and safety and monitoring board (DSMB). This board is independent of the government and the companies. The board includes independent scientists who are the only people who know what’s going on in the trials—who’s in the control group, who’s in the vaccinated group—and they’re the ones who would look at any major concern or hospitalization to see if it’s likely to be related to the vaccine, such as the recent instance in which a participant in the AstraZeneca trial developed a neurological problem. In that case, the trial was temporarily stopped, then restarted after a review board gave the okay. It is the DSMB members who initially recommend a trial to be stopped for specified reasons, including adverse effects, failure to produce results, or overwhelmingly positive results such that the trial need not go further.
Notably, the nine companies running trials have signed a joint pledge saying they will wait until they have the necessary efficacy and safety data before filing an application for either emergency use or for a biological license to bring a vaccine to market.
In addition, the top civil servants at the FDA vowed in a USA Today op-ed that they would continue their work independent of political influence. Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, has said that if anybody mucks with the vaccine data or stops a trial early, before there’s overwhelming evidence to show that the vaccine is safe and effective, he’ll quit. And Moncef Slaoui, who heads Operation Warp Speed—the federal program aimed at developed a vaccine in record time—unequivocally indicated in press reports that he would resign if he believed there was political influence on the recommendations on trials.
It’s true that the FDA’s recent track record invites skepticism. They gave emergency use authorizations for hydroxychloroquine, for which there was no scientific justification, and for convalescent plasma, for which there are no randomized controlled trials to show that it does anybody any good. That’s clear reason for people to be skeptical of anything that comes out of the FDA. Reducing that skepticism will require making the data on the vaccine trials available to the public. How many people were vaccinated? How many people got sick? How many people were protected in the vaccine group as opposed to the placebo group, and what is the probability that could have occurred by chance? Those are numbers that should be made public in any trial.
Q: Recent polls suggest that roughly a third of Americans don’t plan to get a COVID-19 vaccine, even if one becomes available. And more than two-thirds who do plan to get one say they will wait several months before getting their shots, to see if it’s safe. What are some concrete ways that health officials and practitioners can respond to vaccine hesitancy?
A: We need another layer of public education targeted to various communities, particularly those most at risk, including Black and Latinx communities, with the information endorsed by everyone from trusted community leaders to religious leaders to entertainers. This sort of major advocacy campaign should ideally be led by the private sector—not the government, because there is such distrust of government. Who will take the leadership is less than clear. There are lots of very rich people in Silicon Valley, for example, who could take the leadership either collectively or individually to pay for effective ad campaigns.
Q: You were quoted in a recent article as saying that vaccines won’t end the pandemic. Why not?
A: The first reason is that no vaccine is 100% effective. You typically get a huge curve of how long immunity lasts in individuals in the population. For example, with SARS-CoV-1, among people who recovered from infection, some of them were still making antibodies 18 years later. And some people probably lost their antibodies within six months. It’s very idiosyncratic—we don’t know why the same vaccine in different people lasts for different periods of time. That’s one of the research questions you follow up on in post-vaccine surveillance.
Second, not everybody will take the vaccine, or can.
Third, as we’ve seen in a number of countries, when social distancing and public health interventions are removed, the disease can flare up. And that’s in a world where global travel is almost at a complete shutdown. Eventually, people will be traveling more. So even if we vaccinate people in America, if we don’t vaccinate people in Nigeria and South Africa and Kenya and Thailand and India, there will be cases introduced into this country over a long period.
Vaccines have the unique power to do what is critically important in any infectious disease outbreak—to prevent or interrupt transmission. That’s where we start from. The other way to limit transmission is to use public health measures, like masks, social distancing, small gatherings, and careful travel constraints. There are limitations for each, so for maximum effectiveness we need the whole shooting match.