One-dose vaccine strategy elevates PR over science

I fear that the U.K. policy of one-dose vaccines will backfire, and cause the pandemic to continue longer than necessary. Here are several reasons why.

Partial protection provides a convenient excuse for vaccinated people to do away with inconvenient mitigation measures

Assuming that the trial results hold, people receiving two vaccine shots have a very low chance of getting infected, and thus, it is acceptable that they return to normal living after vaccination. (I myself would not, since I think two doses are closer to 70 percent effective in reality, and we don't know that the vaccine stops asymptomatic spread, and so continuing to reduce contacts is advisable. Yet, under this scenario, one should not begrudge people who decide to return to normalcy.)

If people are given partial protection through just the first shot, it is irresponsible to return to normal living. Even the vaccinated must continue to wear masks, maintain social distancing, and stay at home as much as possible for the foreseeable future. Even now, it has proven impossible to enforce mitigation measures - at least not in the U.S. where I live. Vaccination presents a convenient justification for non-compliance.

This behavioral problem alone should have doomed the one-dose lobby.

One-dose treatment solves a problem that does not exist

The first weeks of vaccination has shown that the problem is demand not catching up to supply, not the other way round. We have more doses shipped than doses that are going into arms. If people don't like your cakes, you can't solve this problem by selling half-cakes!

The high efficacy of single doses is wishful thinking

Anyone who believes that the efficacy of the first dose is 90% lives in a fantasy world. Such a conclusion requires cherry-picking the best-case scenario, ignoring results that don't fit the theory, ignoring the margin of error, assuming that the second shot is essentially worthless, and assuming that the first shot is effective for the pertinent period of time without any boost from the second shot. The last two assumptions expose the one-dose strategy as a tautology - a conclusion that stems directly from one's assumption.

In a prior post, I explained how any guess of single-dose efficacy requires an assumption of (a) the efficacy of the second dose and (b) the duration of protection of the first dose, for neither of which do we have direct evidence coming from the vaccine trials.

It's a jigsaw puzzle, not a Barbie doll

People who propose the one-dose strategy are treating the clinical trial results like a Barbie doll. They are switching the green dress with the red skirt, or the high heels with flats. In fact, the toy is a jigsaw puzzle, in which each piece has its exact place, and cannot be haphazardly substituted.

For example, the headline vaccine efficacy numbers of 95% - recall the decimal obsession by Moderna - is based on a case definition in which they only count cases that occur at least 7 to 14 days after the second shot. You simply can't talk about that number in the same breath as efficacy for the first shot which requires counting cases after the first shot and before the second shot. They are not comparable numbers.

Use the scientific method properly

What supporters of the one-dose strategy should do is to lobby the FDA and/or pharmas to immediately start new clinical trials to test the one-dose strategy against the two-dose treatment.

From a scientific perspective, the biggest problem is post-hoc theorizing. Let's use stock market performance as an example. Do you feel like the business press are having it both ways? If stock prices went down yesterday, it's because the unemployment numbers were terrible. But if stock prices went up yesterday, it's because the terrible unemployment numbers were not as bad as imagined, or because businesses expected the job market to start improving, or because executives shrugged off the terrible unemployment numbers. They end up fitting a story to the observed data, as opposed to using the observed data to confirm a hypothesis.

Given the setup of the vaccine trials, before seeing these results, no one would have argued for one dose. The argument emerges after one sees the particular outcome from the trial. Trouble is, if the trial were run many times, would we have seen the same efficacy curve? (The variance across different trials already tells us the answer is NO.)

If the front part of the curve looks less favorable (say 30%), these same people would say we can't draw inferences about one dose (as opposed to one dose isn't going to work). In other words, this analysis contains an optimism bias, as does any theorizing after peering at the data.

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Despite what I said above, I rate it as likely that certain countries will eventually follow the U.K. example and allow one-dose treatment. (As of now, the FDA has sensibly decided not to go down this path.)

Politicians score easy PR points by claiming they are helping "more people" when in reality, such a policy will lengthen the public-health crisis. Previously, I already noted that the PR agency of the UK government should be given an award.

 

P.S. Sadly, it appears that the incoming Biden administration is intent on elevating PR over science, as news has emerged that they will "release all available vaccines" and "not withhold second doses". This is euphemism for giving out one dose to everyone (as opposed to reserving the second doses for those who have gotten the first dose). For those "scientists" who are jumping behind this policy, I'd request that they answer the questions listed on my previous post. I can be persuaded that the one-dose strategy will lead to a better outcome but I'm having trouble understanding what set of assumptions lead to such a policy.

Added to the problems listed above, I think this latest news may persuade some of us to become vaccine skeptics. Those of us who believe the data show the vaccine needs two doses to work, and who do not get assurance that the second dose will be available in the right time frame, may decide to opt out of the vaccine.

 

P.P.S. In justifying this misguided policy, people are going to say "don't let the perfect be the enemy of the good". This is the cue that they are about to ignore the science. No one ever said the vaccine trial results are "perfect"; in fact, many of us believe they are less than perfect. I have written frequently about the shortcuts that were taken. We are not letting the perfect be the enemy of the good; we are opposing letting the unknown replace the good enough.

Other than some handwaving, I have not heard any description of what "the good" entails. If you can't quantify it, it's not science. If we are not going to argue about the science, then we must debate the assumptions, and evidence supporting such assumptions. Let's go!

Comments

[Michael Droy]

Glad to say that the elderly UK patients I went in with are getting their 2nd dose (one 2 days ago, one later this week).
the hospital decided that patients had consented frmally to a 2-dose treatment and not to a 1-dose treatment so it would be unfair to stop half-way. But not all UK services have done the same.

Of course it is not patients that need to be immunised. Most have little to fear. It is governments and media that need immunisation from crazy policies and the closing down of the economy and health services. For them any placebo will do & the sooner the better

[Dan Vargo]

A couple of rebuttals:
"Partial protection provides a convenient excuse for vaccinated people to do away with inconvenient mitigation measures"

I live in Arizona, this is not a concern for me since we seem to be doing just fine ignoring mitigation measures. This is the case for a lot of other locations, as well. More people less well protected is very likely a net positive in areas like mine.

I am also of the belief that once vaccinated individuals are not rare you will see the general public VERY quickly dropping all inconvenient protection measures. If this is the case, first doses first will absolutely save more lives than the alternative.

"The first weeks of vaccination has shown that the problem is demand not catching up to supply"

A lot of this is because of a) the phased rollout -- 1B+ group members can't jump in to fill vacancies b) poor communication; state and local governments were not given adequate instruction or resources. This will likely be reduced as they gain experience and possibly resources via the next Presidential and Congressional administrations.

"Anyone who believes that the efficacy of the first dose is 90% lives in a fantasy world"

I think you're using a straw man, here -- I don't think many people believe 1 dose is AS effective, just somewhat effective. In terms of R0 reduction 2x50% (or even 40%) could be better than 1x95%.

[Kaiser]

DV: Point #1, if the subpopulation you're talking about is already "ignoring mitigation measures", then my argument cannot apply because the behavior is not changing regardless.

Point #2, the reporting has not caught up with what are the real bottlenecks.

Point #3, it's not a straw man because I lifted it from here or here. These are written by "experts" who call themselves "scientists".

Lastly, both of those groups explained what pieces of data they cherry-picked from the pile but those pieces do not say 2x40% ie better than 1x95% (plus 1x0%). They failed to tell us how they bridged the gap. For example, what's the model of transmission chains? It's not defensible as science; it can be justified for other reasons.