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When the World Health Organization last week called for a moratorium on giving Covid-19 booster shots, except in rare circumstances, it said it was concerned wealthy countries would start giving their populations a third dose before the people at highest risk from the disease — health workers and older adults — in many countries get their first.

But Kate O’Brien, the WHO’s director of immunization, vaccination, and biologics, recently insisted on an additional reason: Providing booster shots without strong evidence that the shots are needed is ill-advised. “If we’re not really grounded in that clarity, we’re going to be in a place where we have forever uncertainty about what actually should be done,” she cautioned.

STAT spoke to O’Brien to about what she meant by that warning — sparking a discussion about why she thinks the current use of Covid vaccines is “out of kilter.”

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Excerpts from the conversation are below, lightly edited for length and clarity.

What did you mean when you said we could be left in a permanent state of uncertainty if decisions to authorize booster shots aren’t based on solid evidence?

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I’ll give you an example. In the U.S., the use of pneumococcal conjugate vaccine is a four-dose schedule for infants. The vast majority of other countries around the world are giving either three doses or two doses of that vaccine. You have to ask the question — I do — why is the U.S. still giving four doses of pneumococcal vaccine when demonstrably other countries have [gone to] two doses or three doses?

And the answer is it’s a really hard step for policymakers to step back from doses, because there is a trade-off. There’s almost always an incremental benefit to somebody of getting a dose more than what we’re already giving. So the policy question is always — when we’re expanding doses — do we have a strong evidence base on which a population-level recommendation will be made to invest those resources and ask people to go ahead and get whatever that expanded dose is?

When we are in a position where the evidence is weak and yet people proceed with the intervention, it’s really difficult to walk back from that. One can envision that there would be a world five years from now, 10 years from now where we’ve sort of backed our way into giving doses where we actually can’t fully defend the evidence on which that decision was reached.

Pfizer-BioNTech and Moderna have been saying they think booster shots are going to be needed. Are they saying, “Our vaccine should be three doses the first time you get it,” or are they talking about something like a tetanus booster — an additional shot given at a later date? Do you know?

You’re asking a really spot-on question. We’re talking about in general — let’s put [the one-dose] Johnson & Johnson aside because that sort of complicates things — but we’re talking about third doses here. And there’s a lot of different language that’s being used. It’s being referenced as “a booster dose.”

But the timing of that dose, and the rationale that some stakeholders are making, is not about boosting. It’s actually about whether or not you need a third priming dose, for a primary series — for certain populations.

For some vaccines, for some of the studies and for some subpopulations, there seems to be evidence coming forward, more about people who are having a failure of the primary series and evidence on whether or not a third priming dose would help.

Like people who are immunocompromised?

Right.

And yet the bigger conversation is around whether or not additional doses will be needed for everyone, and then you have to say: needed for what? Is it needed for maintaining the effectiveness that the vaccines have already had? Is it about needing additional doses to enhance the effectiveness around variants of concern?

I think it’s fair to say that the majority of the experts that we’re engaging with, we’re seeing evidence from, the people who are involved in policymaking — the general view is that the evidence does not speak in favor at this time of a need for advancing to third doses in a general sense.

Israel has announced it is giving a third dose to everybody over 60. Britain is starting a booster-shot campaign in early September for older adults and care home residents. Is there a consensus on using an age cutoff as a proxy for “these people need more boosting”?

I think the much more important message is we really have huge inequity right now in just getting primary doses to people. And I think what we’re really trying to say is: Does a third dose need to be given? I think you can draw your own inferences about, well, wait a minute, how many [national advisory] committees have actually made this decision? It’s precious few.

At this point, we’ll just continue to emphasize that we’re looking at the evidence around this broad topic. And it is there’s no compelling, clear answer of “There is a need for X, Y and Z.”

You talked about how hard it is to unring the bell once the decision is made to add doses. Could these decisions lock countries into giving annual shots? If you start giving a third shot in the autumn of 2021, aren’t you going to be pushed to give a fourth shot in the autumn of 2022?

I think you’re asking excellent questions, the kind of questions that should be asked to the committees that have been making those decisions to move forward. Those are exactly some of the questions that the SAGE Covid vaccine working group is deliberating on. [SAGE is the WHO’s Strategic Advisory Group of Experts on Immunization.]

And I think the important part is: Can we point to the evidence that we’re all looking at that says you should move forward with giving a third dose?

Now, it’s legitimate that different groups will come to different conclusions. Clearly, countries have their own country context. But what we’re really trying to say is a country may be looking at this from their own country context, but they live in a world of a global context. And so I think we’re really just trying to emphasize the importance of realizing we need a strong evidence base in order to make decisions that have implications for the whole world.

The focus [of Covid vaccination] really is on reducing serious disease, hospitalizations, and death. And when you look at the deployment of the vaccines globally, a whole lot of those vaccines have gone to people who have extremely low risk of that happening, while at the same time there are huge numbers of people who do fall into that risk group who haven’t been vaccinated.

We’re just really out of kilter here.

I think people are uncomfortable with waiting until vaccine protection is clearly waning and the amount of serious disease among vaccinated people starts to rise before deciding to deploy boosters. The notion that we should wait till vaccine protection starts to fail. Is that part of the problem?

Why would we wait to vaccinate people who haven’t even had a first dose?

I have no answer to that.

That is the point here. There are hard choices that need to be made. We are in a supply-constrained environment. If there was full supply, the conversation would be a different conversation.

I think the question is actually being framed in a way that is not [reflective] of the reality of what’s actually going on right now. The question is: Where is the biggest impact that will be felt? And the biggest impact that will be felt is assuring that everybody who’s in that high-risk category — health workers, elderly people in every country — that they are protected. And people in one country are not more important than the humans in another country.

What about vaccinating kids? You would get no traction in the United States in a debate about whether it makes sense to hold off vaccinating teens and children so that elderly people and health care workers in other parts of the world could get vaccinated.

When the initial rollout was happening in the U.S., do you think there was anybody who was advocating that kids should be vaccinated in advance of health workers or elderly people? People supported the stratification, that we immunize certain groups first, we work our way down. People were ready to wait for their turn.

So it’s curious that actually there’s acceptance of stratified vaccination when the remit is your own state or your own country. But the idea of stratified vaccination when it’s beyond your borders and what we’re talking about is not a national policy, but a global policy, now it becomes unacceptable.

It’s just curious. It is the same thing. It’s just what tribe, what border do you respect?

Does it dismay you that the answer appears to be, “The lines that were drawn around my own particular country”?

Yeah.

I’ve worked in vaccines my whole career. I’ve worked on equity my whole career. Of course, it’s very dismaying.

Human life and human health is a right that everybody has. It should not be connected to your ability to pay, nor should it be connected to what country you happen to be born in.

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