What’s ‘safe enough’ for a Covid-19 vaccine?

Understanding the risks and benefits in the first lines of defense against the pandemic.

NIAID SARS CoV2

Covid-19 vaccines are being developed by the dozen.  In the best of all possible worlds, these would all be highly effective, with minimal side effects, since we need to treat people by the billions.

In the real world, in the Moderna Therapeutics phase 1 clinical trial, we know that a healthy 29-year-old fainted after receiving a second dose. He was given the highest dosage of the mRNA vaccine candidate, which has been dropped from the phase 2 trial now launching.

Infectious disease experts remain cautiously optimistic about the vaccine in lower dosages. They wish, however, that Moderna would be more transparent about its early clinical results—avoiding the mere brief upbeat press release.

“What we would have preferred to do, quite frankly, is to wait until we had the data from the entire Phase 1 — which I hear is quite similar to the data that they showed — and publish it in a reputable journal and show all the data,” National Institute of Allergy and Infectious Diseases head Anthony Fauci told STAT’s Helen Branswell.

Given that Moderna has been awarded almost half a billion dollars of federal funding for the effort, such public reporting doesn’t seem too much to ask.

As the biotech and dozens of its peers ramp up to test their various vaccines among tens of thousands of volunteers, we also want to boost the public discussion about what to expect from whichever treatments eventually are approved.

A vaccine’s effectiveness will only be reliably known once a sufficiently large number of people in the trials eventually become exposed to the virus. But my non-expert guess is that the tricky part of vaccine approvals will not be about effectiveness, given the bluntness of our other medical defenses.

Instead, the biggest issue may be safety: What’s good enough to give the billions of the rest of us?

There’s limited safety evidence from other coronaviruses; there are no approved vaccines for SARS  (severe acute respiratory syndrome) or MERS (Middle East Respiratory Syndrome). Moderna has worked on a MERS vaccine but not pushed it along into the clinic.

The company, and some of its rivals, have taken mRNA vaccine candidates for other types of viruses into phase 1 trials. Among them, a Moderna study of a Zika vaccine is underway. Additionally, the company has reported positive results for earlier studies of vaccines against pandemic avian H10N8 and H7N9 flu viruses. None of the trials, Moderna says, saw any vaccine-related serious adverse events.

But what does that tell us about covid-19 vaccines?

Maybe annual flu vaccines will give the best guidance on how we balance risks and benefits. Glancing over papers that review each flu season’s results, I was struck by how the authors focus almost exclusively on vaccine effectiveness (yes, a huge problem!) rather than safety.

Of course, that’s not because safety issues are irrelevant in flu vaccines. Instead, these issues have become well understood over the decades—and addressed by intense focus at every step of design, manufacture and delivery. The results are very low rates of risk among vaccine recipients—for example, about 1.6 cases in a million suffer anaphylactic shock.

Given months rather than decades of experience with covid-19, vaccine risks are under a particularly intense global spotlight. Moderna’s planned phase 3 trial will “very carefully look at safety, even more so than is done in a regular trial,” Fauci told STAT.

In this imperfect world, particularly with anti-vaxxers so loud, we will need an informed consensus about what will be “safe enough”.*

 

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