FDA warns against freestyling vaccination schedules, dose sizes

Yesterday, Ed discussed some proposals to stretch out the available supply of vaccines by either reducing the amount of vaccine given to each patient or to delay the second dose (the so-called “First Doses First” approach). Several states have recently been making suggestions along those lines, but it appears to be a controversial topic in the medical community. The conversation definitely caught the attention of the Food and Drug Administration, however. They put out a statement last night saying that they can’t support such plans. And Dr. Fauci agrees with them, for whatever that’s worth these days.

We have been following the discussions and news reports about reducing the number of doses, extending the length of time between doses, changing the dose (half-dose), or mixing and matching vaccines in order to immunize more people against COVID-19. These are all reasonable questions to consider and evaluate in clinical trials. However, at this time, suggesting changes to the FDA-authorized dosing or schedules of these vaccines is premature and not rooted solidly in the available evidence. Without appropriate data supporting such changes in vaccine administration, we run a significant risk of placing public health at risk, undermining the historic vaccination efforts to protect the population from COVID-19…

We know that some of these discussions about changing the dosing schedule or dose are based on a belief that changing the dose or dosing schedule can help get more vaccine to the public faster. However, making such changes that are not supported by adequate scientific evidence may ultimately be counterproductive to public health.

We have committed time and time again to make decisions based on data and science. Until vaccine manufacturers have data and science supporting a change, we continue to strongly recommend that health care providers follow the FDA-authorized dosing schedule for each COVID-19 vaccine.

I’ve read through the full FDA statement several times now in an attempt to figure out exactly how they arrived at this decision. As a layman (laywomyn?), it’s easy enough to figure out what they’re telling us to do, but parsing how they arrived at those conclusions is a bit murkier. They still want the Pfizer vaccine administered in two doses of the specified size, 21 days apart. The two doses of the Moderna vaccine are to be given 28 days apart.

The FDA addresses the questions raised by some of the recent proposals I alluded to above in a rather simple fashion. Would a half dose work just as well, if at all? Would the same amount of immunity be observed if you waited significantly longer before administering the second dose? The answer is… they don’t know. And the reason they don’t know is that neither pharmaceutical company tried those variations during their rapid testing protocols prior to seeking emergency authorization to begin distributing them. It’s possible that making those changes would work out well enough, but it’s also possible that it wouldn’t, and the risk of rolling the dice on this question is higher than the FDA is willing to tolerate.

For example, the FDA notes that there were indeed some people in both the Pfizer and Moderna trials who either didn’t receive the second dose or received it at a different interval than the one being prescribed. But they go on to say that those test subjects “were generally only followed for a short period of time, such that we cannot conclude anything definitive about the depth or duration of protection after a single dose of vaccine from the single-dose percentages reported by the companies.” In other words, they don’t know what level of immunity was conferred to those people.

Looking around online, I’ve seen some people (including some medical professionals) who are arguing in favor of a “first doses first” approach. We’re seeing a similar, if less definitive push in both the New York Times and the Washington Post to “consider” either delaying the second dose or going to half-doses.

I’ve had to take something of a crash course over the past few months in how vaccines are tested and deployed along with everyone else studying these questions. But that doesn’t make someone like me a doctor or any sort of expert, so I’m loath to second guess the FDA here. Reading a few of the more digestible articles on how these particular vaccines work reveals that the doses essentially act as a classroom for your immune system that’s delivered in two pieces.

The first dose “teaches” your system to recognize a new, but relatively harmless intruder that mimics the actual virus and produce antibodies in response. The second dose is delivered at a time their testing shows that your system needs to have the “lesson” reinforced or it might start “forgetting” what it’s supposed to do. This double-dose allegedly produces a more durable level of immunity. If the second dose never arrives or arrives significantly later than the suggested interval, your body may have “forgotten” so much of the original “lesson” that you’ll never reach the full level of immunity the vaccine is capable of delivering. But we won’t know that for sure until the pharmaceutical companies have time to expand their testing trials to cover these alternate scenarios. Operation Warp Speed simply didn’t allow enough time to sort this all out.

As I suggested above, this is dangerous territory for the laymen in the commentariat to be lecturing the medical community. I know the FDA has given some of us many reasons to grouse over the course of this pandemic, but this is the sort of job they were designed to do. Perhaps we should stick to the schedule ordered by Pfizer and Moderna, at least until they can fully test these alternate delivery scenarios and focus more on maximizing production and getting the states to clean up their frequently inept distribution schemes.