Covid-19 vaccines may not arrive quite as soon as people
hoped. An October surprise didn’t happen, there will be no vaccine by Election
Day, and even Thanksgiving might be pushing it.
Front-runner Pfizer Inc.'s oft-repeated suggestion that it
might have vaccine data by Halloween was wrong, and Anthony Fauci now suggests
an immunization might not be available on even a limited basis until January.
Efforts to speed results and availability have been historic, but they have
limits. Specifically, quick vaccine hopes have a math problem. To clear a high
statistical bar and prove effective enough to get emergency use authorization
from the Food and Drug Administration, early candidates would have to be both
very protective and quite lucky. That won’t be easy.
Here's how it works. In these Covid-19 clinical trials, some
participants get a vaccine, some get a placebo, and researchers measure how
many get sick in each group. They examine the data at several points in the
trial to see if the vaccinated participants have a lower rate of illness. In order
to gain FDA authorization for use against the coronavirus, a vaccine needs to
show firm evidence that it protects at least half of those inoculated. Barely
clearing 50% isn't good enough to
declare success after just a few months, however. This is because at the first checks, when the number of
confirmed cases is low, there's a higher statistical likelihood that what looks
like a protective effect results from chance rather than the vaccine's good
work. The most advanced vaccine trials accounted for this mathematical
truth by setting a higher bar for the first look -- efficacy of around 75%.
Just one extra case amid thousands of vaccinated
participants could swing early analyses because the numbers are small. That's
where luck comes in. Moderna
Therapeutics Inc., another leader in the vaccine race, underscored the issue
during its third-quarter earnings call last week. The company's presentation
noted that success will be essentially a coin flip after 53 cases — when
it will take its first peek at the data — even if the vaccine is ultimately
capable of preventing Covid-19 in three-quarters of those who get it. If that
initial look is inconclusive, the board overseeing the 30,000-person trial
won't reassess the shot until cases double. Pfizer faces even more uncertainty because it plans a peek
after just 32 confirmed symptomatic infections.
This particular issue doesn’t even come into play until
there are enough infections. As of Pfizer’s own third-quarter earnings release
last Tuesday, the drug giant hadn't hit its first-look threshold, and its failure
to reach just 32 cases in a trial that is larger than Moderna’s suggests
participants may be catching Covid-19
less frequently than expected. One
possible explanation is "functional
unblinding," whereby the presence or lack of side effects might let volunteers
guess if they got the vaccine and lead them to take different virus risks,
potentially slowing and skewing trial data. Two other leading candidates
only just restarted trials after pauses to investigate potential safety issues.
The recent spike in Covid-19 cases may increase the rate of
infection in these trials, removing one roadblock in getting to the threshold
for looking at initial trial data. But that look will come when the odds of
success are at their lowest. What this all means is that the wait for results
and FDA authorization may still prove long, and the wait for broad availability
and distribution even longer. Vaccines will get here, but anyone thinking it’ll
happen anytime soon should re-set expectations.
This column does not necessarily reflect the opinion of the
editorial board or Bloomberg LP and its owners.
To contact the author of this story:
Max Nisen at mnisen@bloomberg.net
To contact the editor responsible for this story:
Beth Williams at bewilliams@bloomberg.net
No comments:
Post a Comment