It’s hard to tell whether the most recent statement on COVID-19 vaccines, out of the FDA, represents a change of policy or not. On the face of it, it seems to.
Three weeks ago, the FDA said that every vaccine must pass through all phases of testing before being approved (Post #773). That certainly seemed clear and unambiguous, with no possibility of exception.
Yesterday, it looks like FDA did an about-face, and said they’d approve a vaccine before testing was completed. Details are given below.
I wonder which one is correct, if either?
Herd immunity seems unlikely at the FDA vaccine approval threshold
The Washington Post article cited below also details the low bar that any vaccine must meet: Prevent infection or reduce severity of infection in at least 50% of the people who get it. So at least we’re getting some picture of what we can plausibly expect from these vaccines. In which case, if 50% is the bar, and that includes people who got infected (just not as severely), we can pretty much forget about herd immunity (generally thought to require 70% or more of the population to be immune).
That is, by the way, substantially worse than the performance of the best years of the seasonal flu vaccine. In a good year, the flu vaccine outright prevents infection in 60% of vaccinated persons.
So we’re shooting for a fairly low bar here, consistent with (I think) a dire need for any effective vaccine. I have to wonder if the FDA chose that with some foreknowledge of how these vaccines are likely to turn out. Or is this just a classic round number?
At the FDA threshold, we can forget herd immunity acquired via mass vaccination. The arithmetic is that if A% get the disease and recover, X% are willing to be vaccinated, and the vaccine is Y% effective in preventing infection, then you get:
- Fraction of the herd that is immune = A + X*Y
The value for A is debatable, in part because studies of antibody prevalence so far have only used “samples of convenience”, mostly people who had blood drawn for some other reason or were seen at an outpatient clinic. The CDC’s initial (and current) analysis suggested an average of bout 10 undiagnosed cases for every case diagnosed, but that varied widely by geography.
Here’s a graph of estimated prevalence of antibodies to COVID-19, but bear in mind that this is several months old:
The CDC’s results seem to cluster around 3% of the population had antibodies to COVID-19, but that measurement reflects roughly mid-April, when the US only had about 1M coronavirus cases. We now have about six times that many diagnosed cases. If the total grew in proportion, we’d have about 18% of the population with antibodies to COVID-19. That doesn’t seem quite plausible, to me. I’d take that as an upper bound for the US.
In Virginia, a roughly mid-June estimate was obtained by a seroprevalence survey managed by UVA. Again, this was a sample of convenience taken from people visiting one of five hospital outpatient clinics and blood-draw laboratories. They found just 2.4% of the adults in the sample had antibodies to COVID-19. Inflating that for growth in total cases since mid-June, we’d expect that just over 5% of the Virginia population would have antibodies to coronavirus now.
But take that with a grain of salt, given the underlying sample-of-convenience. For one thing, dating that to mid-June and comparing to the count of diagnosed cases, that would imply that total cases were just 3 times the count of diagnosed cases. That ratio seems far below what other sites were reporting almost contemporaneously. Contrast that with results results from May, from Minneapolis-St. Paul, showing 10 times the number of diagnosed cases, or from Philadelphia, showing 7 times.
That said, the patterns of seroprevalence reported in that study look about right. Hispanics have a vastly higher reported prevalence of antibodies. Prevalence is higher in Northern Virginia (which had higher overall infection rates).
At some point, you have to go with the data point you have. I’d guess a good number for Virginia, for A, is 5%. As cases grow, that number will grow.
For X, the willingness to be vaccinated, a number of surveys all show that about one-third or more of adults say they will not get vaccinated. So we can take (say) 0.7 as a plausible Virginia value for that.
And then, if the vaccine manages to prevent infection in half of cases (which is a stronger criterion that the FDA requires. They’ll require that it prevent infection or lessen the severity of infection in half of cases, then the value of Y for Virginia is about 0.5.
And so, for Virginia, at something like the FDA approval threshold, we get something line this:
- Fraction of the herd that is immune = A + X*Y
- …………………………………………………………. = .05 + (.7*.5)
- …………………………………………………………. = .40 (i.e., 40%)
I don’t think anybody has suggested that 40% population immunity will achieve herd immunity for COVID-19. We’d best hope that the actual vaccines are much better, or that people are more willing to get vaccinated. Otherwise, the only point at which this will stop is when A — the fraction of the population that has survived the virus — gets large enough. And that may take years, and result in considerable morbidity and mortality.
Is vaccine double-dipping possible, and will it be allowed?
I have yet to see an article address what I think is a critical question, which is, can you get several vaccines? In the current context, if the one the FDA fast tracks (which will of course be Moderna, as anyone who has been paying attention would know, and which will of course be done so that a vaccine is released before election day, ditto) — anyway, if that’s a dud, will that interact with any subsequently available and better vaccines? Do you get only one shot at this, or can you get a redo if the fast-tracked Moderna vaccine is a dud?
From what little I know of the medicine and the mode of operation, I’m guessing that you can mix-‘n’-match. The two earliest vaccines will trick the body itself into producing a key coronavirus surface protein, which your body then produces antibodies for. Other vaccines are more traditional killed-virus vaccines that introduce that protein into your body by literally injecting the dead virus. Presumably, there’d be no more problem in getting two or more vaccines than there would be in getting seasonal flu shots in successive years, or getting a tetanus “booster” a few years after a tetanus vaccine.
My acid test for whether or not the vaccine actually works
Given how frankly untrustworthy our current government is, how will we know if the fast-tracked (Moderna) vaccine actually works? Or, by contrast, whether they just made up the numbers that justify releasing it?
Here’s my best guess. If the vaccine is distributed to all states fairly and equitably, based on some objective measure of need, then that’s a pretty good guarantee that it’s worthless. This administration isn’t going to give up the opportunity to punish enemies over something as trivial as a deadly pandemic. If they hoard it and favor battleground states or those with loyal Republican governors, then my guess is that it’s worth taking.
Finally, assuming I’m reading this right, this is yet another favor that the Federal government is bestowing it’s anointed vaccine candidate, Moderna. So we can add this to the list (Post #789, Post #776). I mean, we’ll see if that actually is the vaccine that’s going to get approved before the clinical trials are done. Based on what I’ve seen so far, that would be my guess. I can believe that the government apparatus that chose that firm would allow any other firm to beat it to the US market.
Timeline of FDA policy on vaccine release.
Detail follows, in the form of a few key quotes. Even as much as I’d like to see the FDA hustle up on the vaccine front, this is not the way to do it.
August 5, 2020
Source: Washington Post.
A few key quotes, emphasis mine.
Large-scale clinical trials already have begun for several promising vaccine candidates. The data from these trials will enable the scientists at the FDA to determine which of these candidates has the greatest potential to provide protection from the virus, what the possible side effects are and how long immunity is likely to last. FDA scientists will need the information to decide whether approval of the vaccine for general use is justified. This fall, we expect to start identifying which vaccine candidates are truly viable. Success will hinge, of course, on the data that emerges from clinical trials. This testing by its very nature takes time: It takes time for the human body to develop immunity, and it often takes time for side effects to emerge. While speed is essential in this global emergency, we at the FDA are committed to maintaining strict scientific principles and protection of those who volunteer as vaccine test subjects.
August 23, 2020:
August 30, 2020