The Annual COVID19 Booster

"Has there ever been a more common medical question without any data on which to answer it?”

Recently on my substack I had a two part post about who should get the fall 2023 COVID19 booster, and a follow post analyzing the differences between the COVID19 shot and the flu shot. Both posts lamented the lack of evidence for these annual products.

A wise doctor recently told me about the fall 2023 COVID booster, “in our careers, has there ever been a more common medical question without any data on which to answer it?”

That is spot on. I make both my posts available here to articulate how the current administration’s vaccine regulation has failed.

Vinay Prasad

PART 1:

The Biden administration seems set on pushing out a fall booster for all age groups. The CDC director has alluded to it in recent videos, and hospitals are emailing staff to be prepared to receive it. Even David Leonhardt, writing for the Times, who is more balanced on COVID19 policy than his colleagues, say about the fall booster, “all adults should consider getting a booster shot. Many Americans have now gone more than a year without one, and immunity has waned.”

In contrast, the UK government disagrees. Here, is there fall guidance:

Ultimately the UK is more sensible, but everyone is wrong. The fall 2023 booster is essentially a widespread medical intervention made with zero data. It should not be offered with no ongoing or conducted RCTs.

Consider the spectrum of risk. Of course, older people might have more to gain than younger people. People who never had covid (not many left) might have more to gain than those who have had it (especially multiple), and young men have the most to lose. Every time you alter the spike sequence, you may have less myocarditis or more!

Walid Gellad notes that the FDA has failed to enforce the post marketing commitment and as such pushing more doses in young men seems reckless. Why is FDA waiving this requirement?

Ultimately, however, only randomized controlled trials can tell us who has a net benefit. Yet, this administration does not want any. Pfizer made 100 billion in their peak year, and can afford to generate data, and yet the white house, which has now pushed Gruber and Krause out of FDA, has decided to generate no data.

Observational data will not help. B/c the people who seek boosters will be different than those who don’t. We explained that more in NEJM.

In the absence of data, and with no ongoing or planned RCTs, I have the following conclusions:

1. The Biden Administration is not science based. They are as ignorant as the anti-science fringe they decry. I would watch for conflicts of interest as Califf, Jha, Murthy and others move into the private sector.

2. I will never get another COVID19 shot until someone shows it lowers the risk of severe disease for someone of (a) my age and (b) who already had 3 doses (2 against my will) and (c) COVID. Practically, given the anti-science admin, this will be never.

3. I would not advise anyone healthy <65 to get the vaccine.

4. I would not advise anyone healthy who had COVID already to get the vaccine.

5. For those >65 with medical problems, and no prior covid, there are no data. I suspect nearly none of these people will want the booster, and I won’t push back. I have no data to fight with.

6. I would discourage all COVID19 vaccination of anyone healthy <30 (this is most insane); Especially <18. At this point, all have had covid and no data show further doses help them.

7. Colleges & hospitals should NEVER mandate this booster

8. I will continue to oppose the universal booster program without data, and this anti-science administration.

My position of how to handle the fall booster is in line with longstanding principles of medicine, including ‘you can’t push things on healthy people without good data,’ ‘beware conflicts of interest and optimism bias’ and ‘all medicines have diminishing returns’— these principles have been forgotten.

The Biden administration’s handing of COVID19 vaccine policy was a disaster, which I detail here. The fall booster enriches Pfizer and does not generate data for 300 million people who may be curious. It looks like they will double down on their errors. The people driving the bus are ignorant of medicine, and worse: they want to keep the rest of us ignorant on boosters.

PART 2:

Yesterday I described the situation with the COVID-19 vaccines. Specifically, the administration has marched forward with an annual vaccination in the absence of any clinical data. They are pushing the dose in young people, who are at risk of myocarditis, and have staggeringly little to gain from continued boosting. Two senior FDA officials resigned over this idea (boosters for all).

The current US guidance is counter to guidance from the United Kingdom to restrict the use largely to the elderly. Neither group has good data to justify their choice, but the US decision is particularly illogical and heavy-handed.

How does the flu vaccine compare? Each year a new dose is debuted without randomized data at the time of approval and, often, even thereafter. Is the flu vaccine like the COVID shot?

First, let’s consider ways they are different

1. Annual covid shots are far more immunogenic than flu shots. People feel worse after the dose. More people take a day off work. Rates of pain and rigors and fevers are greater. This matters for public policy considerations. The days of life lost (spent in bed) count against this campaign.

2. Annual covid shots are different because the age risk gradient is far steeper for covid-19 than flu and the upper bound benefit to younger people is more debatable. We also know less about the future risk of COVID to a 55 yo than the future risk of flu to a 55 yo.

3. Annual covid shots have one serious safety concern— myocarditis, and likely excess in cardiovascular mortality among young men. This and other safety concerns— tinnitus etc.— have been inadequately studied as the current climate is hostile to vaccine safety research.

4. In contrast with flu shots, COVID shots have a pending, and postponed post marketing commitment to generate data on subclinical (troponin leak) myocarditis in young men. The FDA and the company seem disinterested in generating these data.

5. Gruber and Krause never resigned over flu shots, and no president leaned on FDA to grant EUA.

Now let's consider how they are similar

1. From the 2018 Cochrane review for healthy adults “Inactivated vaccines can reduce the proportion of healthy adults (including pregnant women) who have influenza and ILI, but their impact is modest. We are uncertain about the effects of inactivated vaccines on working days lost or serious complications of influenza during influenza season”

2. From the 2018 update on kids, “In children aged between 3 and 16 years, live influenza vaccines probably reduce influenza (moderate‐certainty evidence) and may reduce ILI (low‐certainty evidence) over a single influenza season. In this population, inactivated vaccines also reduce influenza (high‐certainty evidence) and may reduce ILI (low‐certainty evidence). For both vaccine types, the absolute reduction in influenza and ILI varied considerably across the study populations, making it difficult to predict how these findings translate to different settings. We found very few randomised controlled trials in children under two years of age.

3. For the elderly, “Older adults receiving the influenza vaccine may have a lower risk of influenza (from 6% to 2.4%), and probably have a lower risk of ILI compared with those who do not receive a vaccination over the course of a single influenza season (from 6% to 3.5%). We are uncertain how big a difference these vaccines will make across different seasons. Very few deaths occurred, and no data on hospitalisation were reported.”

4. In other words— flu shots WOULD benefit from more randomization. We know nearly nothing about more important endpoints such as hospitalization or transmission dynamics. These can include trials early in the season— and can occur alongside implementation. Pragmatic design where tens of thousands of people are continually randomized till endpoint is met, or even…

5. Randomized trials of deployment similar to this proposal.

6. Challenge trials— aka Randomized studies— could also be performed.

7. In the absence of randomized trials, we rely on test negative case control studies to assess flu vaccine efficacy, which is the CDC’s preferred method. In my opinion, this method exaggerates effectiveness over RCTs, but to prove this claim (or the counterclaim— that it is accurate) one has to compare this method to concurrent RCTs, which has not been done. Here is the CDC’s VE from flu shots. Ranging from 10% to 60%.

These numbers are low, and this suggests immediately that each season a multi-arm RCT can be conducted of different vaccine formations and control arm, and the winner could be advanced. The entire idea of one shot prior to the season may be suboptimal— even if flu shots work, why not have several candidates and pick the best one?

8. Putting this all together, I agree with the attached essay by Doshi. I think there is little justification for mandatory HCW vaccination. I do not push influenza vaccines in young, healthy people. Vaccinating children 6mo-2yo has particularly low credibility data.

   Dozens of RCTs are needed, and in the absence, Doshi’s concerns— articulated in the BMJ 10 years ago— are salient. Many doctors I know decline the annual flu shot if that is an option. I suspect this is under discussed due to the nature of the subject. I attach the full PDF for those interested.

Doshi Clean Copy

366KB ∙ PDF file

Download

Download