Is ‘first dose first’ the right vaccination strategy?

21st January, 2021

What a difference a couple of weeks makes. In mid-December, I asked a collection of wise guests on my BBC radio programme How to Vaccinate the World about the importance of second doses. At that stage, Scott Gottlieb, former head of the US Food and Drug Administration, had warned against stockpiling doses just to be sure that second doses were certain to be available, Economists such as Alex Tabarrok of George Mason University had gone further: what if we gave people single doses of a vaccine instead of the recommended pair of doses, and thus reached twice as many people in the short term? This radical concept was roundly rejected by my panel.

“This is an easy one, Tim, because we’ve got to go with the scientific evidence,” said Nick Jackson of the Coalition for Epidemic Preparedness Innovations. “And the scientific evidence is that two doses is going to provide the best protection.”

My other guests agreed, and no wonder: Jackson’s view was firmly in the scientific mainstream three weeks ago. But in the face of a shortage of doses and a rapidly spreading strain of “Super-Covid”, the scientific mainstream appears to have drifted. The UK’s new policy is to prioritise the first dose and to deliver the second one within three months rather than three weeks. Cynics argue that this change is a wearingly familiar display of dishonesty and short-termism, designed to produce flattering figures about the number of people vaccinated. Yet the recommendation comes not from ministers but from the Joint Committee on Vaccination and Immunisation (JCVI).

Strikingly, many scientists have given the move their approval. Others remain sceptical and are alarmed both by the shift in policy and by the way it was announced. There are several different issues to untangle here.

The first is the short-term benefit of the shift to what we might call “first dose first”. That depends on how good a single dose is in the short term (pretty good in the case of the first vaccine from BioNTech/Pfizer), whether it will still be good enough for the elderly people at the front of the queue (we don’t know) and whether a delay will ruin the booster effect of the second dose (we don’t know that, either; it might even help).

Cars are better with two headlights, and bicycles are better with two wheels. But while a bicycle with one wheel is useless, a car with only one headlight might be good enough in a pinch. The judgment here is that a single dose is more like a car with a single headlight than a bike with a single wheel. Given that these vaccines probably prevent the spread of the virus as well as preventing disease, it is possible that even people at the head of the queue might benefit if their second dose was temporarily redirected: if forced to drive in the dark, I would rather that every car on the road had one headlight than some two and some none. With a dangerous virus in wide circulation, we are all driving in the dark.

But the shift to “first dose first” creates other dangers. One is vaccine resistance. Half-vaccinated people encourage vaccine-resistant strains of the virus. Some scientists think this is a modest risk compared to the selection pressure from millions of people who have already developed some immunity after infection. Others think it is a catastrophe waiting to happen.

A further problem is public trust. The UK’s move smacks of desperation, and the detail behind the JCVI’s recommendation has not been published. People have been vaccinated with the promise of a second dose, only to be told the second dose will be delayed; some will feel betrayed.

My own instinct has long been that the “first dose first” strategy was worth a try. But I have never believed that “Tim Harford’s instinct” is a sound basis for life-or-death public-health decisions. So, having made this leap, the government now needs to step up its communication and its gathering of evidence.

Nicole Basta, an epidemiologist at McGill University, points out that while clinical trials study the protective benefit to an individual of a vaccine, they don’t study vaccination strategies. There is nothing wrong with making our best guess. But the government needs to be honest about the uncertainties Those studies are now urgently needed.

The University of Dundee is planning to launch a study called VAC4COVID, focusing on safety and side effects. The ZOE COVID Symptom Study app provides another window into the experiences of people who have been vaccinated. But we need much more.

We need rigorously randomised trials comparing different doses, delays between doses, and mixed-dose vaccinations too. We can also learn a lot simply by studying what happens to different people who have received different vaccination regimes. What we learn would allow the fine-tuning of mass vaccination months and years into the future.

Some of these studies will happen but I worry that many will not. Danny Altmann of Imperial College laments the lack of a large-scale monitoring effort — there seems to be no plan even for something as simple as calling people back to test their blood for antibody levels after vaccination.

In any case, solid evidence will take time to assemble. Meanwhile, there is nothing wrong with making our best guess. But the government needs to be honest with the doctors and the public about where the uncertainties lie. It needs to support rapid collection of new evidence to reduce those uncertainties. And it would be wonderful if it could shake the appearance of making things up as it goes along.

Let’s not fool ourselves into thinking that the choice is easy or the evidence is clear. “First dose first” is a gamble. So are all the alternatives.

Written for and first published in the Financial Times on 8 January 2021.

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