One dose for the time being?

The Quarantine Zone
1

An article in today’s Times suggests that for the time being people be given only the first dose until such time as everyone who wants it has gotten one dose. I don’t know if the article is paywalled, but you get a few freebies a month: https://www.nytimes.com/2020/12/18/opinion/coronavirus-vaccine-doses.html
Here is the most relevant paragraph:

Here is the byline on the article:

They go on to admit that they don’t know how long this protection lasts. There were some volunteers who didn’t come back for a second dose, but they haven’t been studied and there weren’t enough of them to draw firm conclusions.

2

OK, so I’m not an epidemiologist (etc) but what struck me about all the well known vaccines was that the Phase III clinical study programs all seem to investigate a regimen of two doses. Given the compressed timeframe of the clinical programs, I don’t see any way that phase II studies could have established that two shots actually work better than one (though I’m sure some phase II studies looking at aspects of a two shot regime must have been performed).

From where I sit it looks like two shots was a “best guess” given the need for fairly good efficacy very fast - a best guess based, you would assume, on prior experience with “similar” vaccines.

If that’s your kicking off point, then it may be that the need for a second dose has never really been investigated. We just wanted a vaccine that worked. Now we have vaccines, our priorities have been tweaked, and the next question up is, could we roll it out twice as fast? From a regulatory perspective, my thinking is that you cannot approve a single shot regime because there are no data to evaluate (save for the few who didn’t go back for a second dose - to few to evaluate). A clinical program to answer that question would take another six months.

It’s one thing to expedite an emergency approval on the basis of hastily gathered data. It’s quite another to approve a dosage regime that has never been tested.

j

3

Yes, certainly.

It’s generally considered unethical to conduct human “challenge” trials where you deliberately expose human subjects to a pathogen. So the nature of the Phase 3 trials is that the treated & untreated groups go off and continue their lives as normal, and you just have to wait until enough people get sick in the untreated group that you have enough statistical power to estimate the effectiveness of the treatment.

It already takes tens of thousands of volunteers and months of time for enough events to occur to test one protocol against placebo. Testing multiple protocols involves either adding tens of thousands more subjects, or extending the time.

The only reason that we had data for two protocols with the AstraZenecas vaccine was an error in dosing. It allowed the comparison, but with smaller sample size thus less statistical power.

4

Well, the reason this could be contemplated is that the safety aspect has obviously been tested. It’s not plausible that any harmful effect would be greater for a single dose. So, to draw a legal analogy, using a “preponderance of evidence” approach rather than “beyond a reasonable doubt” could be acceptable.

5

I’m probably coming at this from a rather European slant (I worked in drug regulation for a couple of decades, primarily European) but what I would say is this. A regulator’s thinking process is: we give a vaccination to produce benefits which outweigh the risks. Every medicine has risks and benefits. Until you demonstrate a benefit, we cannot agree that the benefits outweigh the risks. Therefore the single shot regimen is not approvable. (Demonstrate a benefit, in this context, means a clinical benefit and therefore a (phase III) clinical study).

I would imagine (and hope) that the US position would be the same. FWIW, it isn’t always that simple.

j

6

It seems to me a no-brainer that, if there are shortages of supplies, especially in the most at-risk segment, one should use all available doses for the first shot and only thereafter have the booster vaccine.

The efficacy of one dose only was tested with the Moderna vaccine and was around 80%. This was done on a smallish arm of phase 3, but only up to one month post-shot. The Moderna and the Pfizer vaccines are almost equivalent.

The efficacy of the Pfizer one-shot regimen was not tested per se. However, there is a very marked decline of Covid-19 cases after 2 weeks have passed, (until the booster on the 21th day). Look at the graph and text here.

In general, a 21-day delay between the initial and booster shots, as in the Pfizer vaccine is very small. There is barely the time to form a specific immune response before the second shot. Most probably, a longer wait would be better for long-time immunity. However, I presume that the 21 days were chosen because of 2 reasons. One - nothing was known about the efficacy of one shot, so there might be a long window of vulnerability. Second - everyone was under extreme time pressure to be able to get a vaccine out of the door. I presume that 21 days was the minimum reasonable time between the shots. Being a cynic, I suppose that double the money also played a role in Pfizer’s strategy of not having even a smallish single-shot arm.

A relatively good summary of these issues can be found in Scientific American here.

It seems to me quite trivial that, if the one-shot regimen can protect twice the people, even at 70% instead of 95% it should be adopted, and we should delay the booster for 2-3 months. Of course, this should be monitored, and if there is a significant amount of sick people 3 or more weeks following the initial shot, this strategy should be reversed.

I am getting the second shot in 2 days, but I live in Israel :blush:. I should have been vaccinated 2 weeks earlier, but I took a flu immunization just before the large scale Covid-19 vaccination started - and they insisted on a 2 week delay.

Up to now about 37% of the eligible population (over 16 y/o) was vaccinated with the first shot, and 12.5% with both shots. I guess that there will be enough persons not getting the second shot after 21 days, so that we will have a good answer to this question.