'Not going to end the pandemic': Why those hopeful vaccine trial results are not all that they seem

It’s possible the vaccine actually prevented infection, and not just the resulting illness, but the results so far don’t show that, experts say

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The trial results reported over the past week for two COVID-19 vaccines generated understandable buzz worldwide.

Pfizer and Moderna said their products, both using an innovative new technology, had proven to be well over 90 per cent effective, a tantalizing hint about how the pandemic could eventually end.

But upbeat company newsreleases and media coverage have overlooked some of the nuances of the data and their consequences, experts say.

If approved by regulators, for instance, the vaccines could become the new standard of care for preventing COVID-19, making it ethically difficult to conduct placebo trials of the dozens of other products in the pipeline — products that may have other advantages, such as needing only one dose per person.

And it may surprise some that the impressive efficacy rates claimed by both manufacturers are not for the vaccines’ ability to prevent infection. Detailed trial protocols, though not the news releases, indicate the phase-3 clinical trials primarily tracked cases where participants actually developed symptomatic disease.

Studies have estimated that 20 to 80 per cent of people who contract the virus causing COVID never experience symptoms, yet can still potentially transmit the disease to others.

“The problem is that the messaging is very different than what the public is being told,” said Ed Mills, a Vancouver-based clinical trials expert and part-time McMaster University professor. “We’re told this is going to end the pandemic. It’s not going to end the pandemic. It’s going to hopefully prevent people from getting sick, but it’s not going to stop transmission. That’s not what they measured.”

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Millls does not fault either company’s trial design and agrees there is still lots to be encouraged about, but said the story is more “complicated” than has been portrayed. Other experts say even a vaccine that just stopped people becoming ill from COVID-19 would be a major advance.

Both products are based on messenger RNA technology, which essentially injects genetic material into the body, prompting cells to produce COVID virus parts called antigens, which in turn trigger production of antibodies against the germ.

Pfizer said its phase-three trial of 43,000 people showed its shot to be 95 per cent effective. It reported 170 “cases,” which according to the trial protocol means people who developed certain symptoms, then tested positive for the SARS-Cov-2 virus. Of those, 162 were in the group that got a placebo, eight in the arm that received the vaccine.

Moderna reported that its trial involving 30,000 people found the firm’s vaccine was 94.5 per cent effective, the protocol defining cases in a similar way. Of the 95 people who got sick, 90 had been given the placebo.

But the companies have yet to release full results or publish peer-reviewed papers.

“There’s lots still to be said in the background of the exciting news releases,” said Dr. Gerald Evans, head of the infectious-diseases division at Queen’s University’s medical school.

To prevent infection completely is a very high bar to achieve

It’s possible the vaccine actually prevented infection, and not just the resulting illness, but the results so far don’t show that, experts say.

“If (infections) were not lab confirmed with routine testing in all participants, then we would not know the impact on asymptomatic disease,” said Julie Bettinger, a University of British Columbia professor and vaccine-safety scientist.

Still, that may not be as worrisome as it sounds, even though asymptomatic people can spread the virus.

Actually preventing infection — as opposed to just averting symptoms or severe disease or death — is something relatively few vaccines accomplish, said Dalhousie University immunologist Dr. Scott Halperin.

A vaccine that managed merely to “downgrade” COVID-19 from a sometimes-deadly virus to a common cold would be very welcome, he said.

“To prevent infection completely is a very high bar to achieve,” said Halperin.

Evans agreed, saying a vaccine that provided “sterilizing immunity” — staving off infection itself — would be an amazing development. But even one that just afforded “protective immunity” — preventing people, especially the most vulnerable, from getting sick when they contract the virus, would be a “huge step forward,” he said.

Meanwhile, experts are debating how approval of the Pfizer and Moderna vaccines — the first to get to the finish line in a massive global effort — will affect those still to come.

The ethics of clinical studies suggest it would be challenging to carry out a trial comparing other vaccines to a placebo once products already proven effective are widely accessible.

“Let’s say these vaccines were out and they were available to you and somebody said to you ‘How would you like to participate in a trial where you have … 50 per cent chance of not getting a vaccine,’ ” said McMaster University’s Dr. Gordon Guyatt, a world-renowned expert in medical-research methods. “How enthusiastic would you be?”

Those shots in the late phases of testing are unlikely to be impacted, but many products are further back in the process.

“The vaccines in early stages of clinical trials are now as good as dead because nobody will agree to take a placebo,” argued Amir Attaran, a health policy expert at the University of Ottawa.

Yet it is still important to open the door to alternative vaccines that, unlike the Pfizer and Moderna drugs, don’t require two doses or sub-zero cold storage, said Mills.

One option is to conduct a trial that compares the new vaccine to one already approved, instead of a placebo. But that requires a far bigger and longer study to be statistically significant, since fewer people would get sick, and the difference between the two arms would be more subtle, said Halperin.

Another option, he said, is to use results from the completed vaccine trials to identify alternate indicators that a vaccine works, like the antibody response it generates, said Halperin. That would mean future manufacturers could potentially skip phase-3 trials entirely.

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