Covid Vaccine Dosing Trials ?
I asked if, given the data collected in Phase III trials, it might be wise to delay second doses of the Pfizer and Moderna Covid 19 vaccines until supplies are ample.
Since then the UK government has decided to give second doses three months after the first dose. The reason is explicitly to get first doses in more people quickly. This is highly controversial. I’m just going to name drop (actually link drop) to show I am not the only person outside of the UK who supports this.
Another approach to vaccinating more people with limited supplies of vaccine is to reduce the dose. This was proposed by the now former head of the US program formerly known as Warp Speed. Here the logic is based on a clinical trial — with a sample size of 42 — the Moderna Phase 1 trial . The trial includes an estimate of the amount of infection blocking antibodies in participants serum. The measure is the blocking antibody titer — how much the serum has to be diluted before it blocks only half of the virus from infecting cells. After the first dose and before the second, a dilution of 8:1 (the lowest) allowed more than half of the control infection (of cells in vitro). However, even with a dose of vaccine of 25 micrograms per kilogram (half of the dose of 100 micrograms per kg which people are getting) there was a high average titer by day 43 soon after the second dose.
The phase 1 results explain why 2 doses were used in the phasee III trial (and in Pfizer phase 1-2-3 all merged to speed things up trial). It also makes the rareness of infection in the phase III trials more than 10 days after the first dose a bit surprising. My guess is that the rapid induction of blocking antibodies after the second exposure is enough to block infection even if the second exposure is infection with Sars Cov2 and not a second vaccination. However note that I am not an immunologist (my dad is an immunologist and he said better half the dose twice than the full dose once back when I started talking about this — as usual he knew what he was talking about).
The 14 who got 25 compared to the 14 who got 100 strongly suggest giving 50 micrograms per kg twice is a better way to spread out the vaccine.
However, there is no way either will be done in the USA without a large clinical trial. Also there is no way that there will be a large clinical trial (who would pay for it for one thing). But the point of this post is to ask how such a trial could be ethical if it were financed (the cost is negligible compared to Federal Covid relief spending and roughly equal to the cost of a delay of effective herd immunity of about one hour). I’d say if people are given the chance to get a first dose sooner than they otherwise could (and the second dose as soon as they would be allowed to get the first if they weren’t in the trial) then it is ethical. The trial can’t be double blind (or at least people who get a second shot have to be told if their first was placebo so they should get a third shot which will be the second of actual vaccine).
Similarly people can be invited to get half a dose if the alternative is no dose (with option to get full dose when it would be granted even if they weren’t in the trial). I think this can be done. I think it should be done. I am sure this won’t be done.
update: There is evidence from Israel that one dose of the Pfizer vaccine is less effective than was suggested by the few person-days of evidence in the phase III trials. In Israel “over 12,400 have people tested positive for coronavirus after receiving vaccine shots” Israeli health officials estimate that one shot is about 50% effective after 14 days . The control group is not matched, it’s not a randomized trial, but it is enough evidence that it’s hard to argue for clinical trials (as I did above).
Are you a doctor of do you have some form of medical degree? I want to understand this so that I can properly weigh your opinion.
I have to ask the question; “Did you read his post completely?” Pose your question and/or commentary as he has a source for additional info. if needed. You might have missed this comment;
“I am not an immunologist (my dad is an immunologist and he said better half the dose twice than the full dose once back when I started talking about this — as usual he knew what he was talking about).”
“The 14 who got 25 compared to the 14 who got 100 strongly suggest giving 50 micrograms per kg twice is a better way to spread out the vaccine.”
14 people vs 14 who got a different dose? Economists need to learn when to step back a bit.
State your case. I always love talking to doctors caring for me as some hand down edicts without supporting information. When you question what they are suggesting, they get huffy (not that you are being so now) with you. When they can not find the reason for your disorder, problem, or illness and the patient has done everything correctly as suggested by science, it gets interesting.
I would like to know your reasoning.
Among people who have received two doses and have 95% immunity — the 5% who become infected have a 0% death rate — nobody dies. Now if we only knew what the death or serious illness rate among single dose recipients we could factor that into policy formulation.
For instance, if we knew that the death and serious illness rate among single dosers was 20X less than among no dosers, then, we could go ahead and vaccinate on a single dose basis freely — assuming that our vaccinations would ever get ahead of our distribution.
@George I am not a medical doctor. I do not claim intellectual authority. I link to peer reviewed articles which I can read and understand.
@ Denis Drew There have been no deaths among the people who received one dose and have not yet received the second. During the period 10 days after the first dose and before the second, the rate of infection among the vaccinated was about one tenth the rate for the unvaccinated (this is from both the Pfizer and the Moderna trials).
The sample of person days at risk and total infections control group and one dose is small, but the point estimate is that one dose is 85% to 90% effective *during* that period. There is no way to know how long the immunity from one dose lasts.
There will be non controlled trial evidence from the UK — millions of people will be walking around after their first and before their second dose. Their rate of infection can be compared to an ad hoc ex post pseudo control group.
@ Jerry Brown I am not responsible for the fact that the phase 1 trial had a sample size of 14. The idea that it was extremely important is not due to economists. The paper to which I linked was published in the top number 1 medical journal.
Have you clicked the link and read the paper ? I think you would not dismiss it if you had.
well, i have to admit i don’t know enough to have an opinion worth sharing, even with myself.
but i am glad to learn that the people who are responsible are looking at all, or so many, of the possible combinations and presumably getting the math right.
not terribly interested in people who think if you don’t have the right degree you are not worth talking to, or think you are the final authority if you do have the right degree.
a sample size of 14 may be pretty small, but it is enough to go on if you are in a hurry and have the sense to modify as bigger sample sizes come in.
i suspect there are limits, but i would expect that a treatment that has dramatically lower incidence of infection, and no unconscionable rate of serious side effects, has earned the right to continue until further evidence comes in.
as long as i am allowed to make my own personal evaluation of the risks to me and my children before a hysterical mob forces me to submit to their idea of cure or prevention.
“Israel’s coronavirus tsar has warned that a single dose of the Pfizer/BioNTech vaccine may be providing less protection than originally hoped, as the country reported a record 10,000 new Covid infections on Monday.
In remarks reported by Army Radio, Nachman Ash said a single dose appeared “less effective than we had thought”, and also lower than Pfizer had suggested.
By contrast, those who had received their second dose of the Pfizer vaccine had a six- to 12-fold increase in antibodies, according to data released by Sheba Medical Center in Tel Hashomer on Monday.”
I just received my first dose of the Pfizer inoculation on Monday. We were surprised to be called in so early in the process.
@Run,Congratulations on getting the first shot. Keep some ibuprofen handy for the booster.
@Joel Thanks for the important link. It has been known since the phase 1 trial that the neutralizing antibody titer is low after one dose of the Moderna virus. I am not sure if Ash is referring to infection of people who have had one dose (news and surprising given the data from a small number of patient-days in the phase III trials) or about the titer (not news given the phase I results with a tiny sample).
OK It’s data on infection which is news
Too much noise in this article. One group says one thing and another says something else. Who is in charge in Israel and was Pfizer’s data BS? If they have issues with the efficacy, then perhaps they should slow their mass inoculation down and wait for further proof or a better medicine? 50% is about right for efficacy. It also sounds or is made to appear like people were a little less cautious after an inoculation.
I am not sure what a re-inoculation with a different drug might evolve into for them. Israel is one of the few nations which has performed more tests than their population, ranks 14th in the world for cases per million and 57th for deaths per million.
Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine
WorldOMeter – Covid