Results for “first doses first” 100 found
The rollout of the Monkeypox vaccine hasn’t been without problems but we are making fewer mistakes. I feel pretty good that my work on first doses first for COVID (as well as that of Tyler, Michael Mina, Robert Wachter and others) pushed the Overton window. This is good to see.
Canada’s National Advisory Committee on Immunization (NACI), a scientific advisory group to the government, has made a forceful and dramatic statement strongly favoring First Doses First (delay the second dose.) This is a very big deal for the entire world. Basically NACI have endorsed everything that Tyler and I have said on First Doses First since my first post tentatively raised the issue on December 8. I am going to quote this statement extensively since it’s an excellent summary. No indentation.
Based on emerging evidence of the protection provided by the first dose of a two dose series for COVID-19 vaccines currently authorized in Canada, NACI recommends that in the context of limited COVID-19 vaccine supply jurisdictions should maximize the number of individuals benefiting from the first dose of vaccine by extending the second dose of COVID-19 vaccine up to four months after the first. NACI will continue to monitor the evidence on effectiveness of an extended dose interval and will adjust recommendations as needed. (Strong NACI Recommendation)
- In addition to emerging population-based data, this recommendation is based on expert opinion and the public health principles of equity, ethics, accessibility, feasibility, immunological vaccine principles, and the perspective that, within a global pandemic setting, reducing the risk of severe disease outcomes at the population-level will have the greatest impact. Current evidence suggests high vaccine effectiveness against symptomatic disease and hospitalization for several weeks after the first dose, including among older populations.
- By implementing an extended four month interval strategy, Canada will be able to provide access to first doses of highly efficacious vaccines to more individuals earlier which is expected to increase health equity faster. Canada has secured enough vaccines to ensure that a second dose will be available to every adult.
- As a general vaccination principle, interruption of a vaccine series resulting in an extended interval between doses does not require restarting the vaccine series. Principles of immunology, vaccine science, and historical examples demonstrate that delays between doses do not result in a reduction in final antibody concentrations nor a reduction in durability of memory response for most multi-dose products.
- Assessment of available data on efficacy and effectiveness of a single dose of mRNA vaccine was a critical factor in assessing the impact of a delayed second dose at this time. The two available clinical trials for mRNA vaccines (Pfizer-BioNTech and Moderna) provide evidence that indicates that efficacy against symptomatic disease begins as early as 12 to 14 days after the first dose of the mRNA vaccine. Excluding the first 14 days before vaccines are expected to offer protection, both vaccines showed an efficacy of 92% up until the second dose (most second doses were administered at 19-42 days in the trials). Recently, real world vaccine effectiveness data presented to or reviewed by NACI assessing PCR-positive COVID-19 disease and/or infection from Quebec, British Columbia, Israel, the United Kingdom and the United States support good effectiveness (generally 70-80%, depending on the methodology used and outcomes assessed) from a single dose of mRNA vaccines (for up to two months in some studies). While studies have not yet collected four months of data on effectiveness of the first dose, the first two months of population-based effectiveness data are showing sustained and high levels of protection. These data include studies in health care workers, long term care residents, elderly populations and the general public. While this is somewhat lower than the efficacy demonstrated after one dose in clinical trials, it is important to note that vaccine effectiveness in a general population setting is typically lower than efficacy from the controlled setting of a clinical trial, and this is expected to be the case after series completion as well.
- Published data from the AstraZeneca clinical trial indicated that delaying the second dose to ≥ 12 weeks resulted in a better efficacy against symptomatic disease compared to shorter intervals between doses.
- The duration of protection from one or two doses of COVID-19 vaccines is currently unknown. Experience with other multi-dose vaccines after a single dose suggests persistent protection could last for six months or longer in adolescents and adults. Longer-term follow-up of clinical trial participants and those receiving vaccination in public programs will assist in determining the duration of protection following both one and two doses of vaccination. NACI will continue to monitor the evidence on effectiveness of an extended interval, which is currently being collected weekly in some Canadian jurisdictions, and will adjust recommendations as needed if concerns emerge about waning protection.
- Although effectiveness after two-doses will be somewhat higher than with one dose, many more people will benefit from immunization when extending the interval between doses in times of vaccine shortage; offering more individuals direct benefit and also the possibility of indirect benefit from increasing population immunity to COVID-19 disease. Everyone is expected to obtain the full benefit of two doses when the second dose is offered after 4 months.
- Internal PHAC modelling reviewed by NACI based on Canadian supply projections suggested that accelerating vaccine coverage by extending dose intervals of mRNA vaccines could have short-term public health benefits in preventing symptomatic disease, hospitalizations, and deaths while vaccine supply is constrained. Even a theoretical scenario analysis in which intervals were extended up to six months and protection was lost at a rate of 4% per week after the first dose also showed that extending the mRNA vaccine dose intervals would still have public health benefits. External modelling results have also suggested that extending dose intervals can avert infections, hospitalizations and deaths.
- The impact on variants of concern by extending the interval between doses is unknown, but there is currently no evidence that an extended interval between doses will either increase or decrease the emergence of variants of concern. COVID-19 mRNA vaccines and AstraZeneca vaccine have shown promising early results against variant B.1.1.7. As effectiveness of the first dose against other variants of concern is emerging, ongoing monitoring will be required.
- Vaccine distribution will be optimized through this strategy, and current vaccine supply projections will work well with an extended dose strategy that aims to immunize as many Canadians as efficiently as possible. Extending the dose intervals for mRNA vaccines up to four months has the potential to result in rapid immunization and protection of a large proportion of the Canadian population….
The Canadian province of British Columbia has moved to First Doses First (as I suggested they would) with a four month (not three as in Great Britain) delay on the second dose. Quebec is already using FDF. I believe that the rest of Canada will follow shortly:
Also on Monday, the province announced it is extending the time between first and second doses of COVID-19 vaccine to four months. The change, as well as Health Canada’s approval of a third vaccine, means every eligible person in B.C. will receive the first dose of their vaccine by mid- to late July.
Provincial Health Officer Dr. Bonnie Henry said data from the B.C. Centre for Disease Control — and countries around the world such as the United Kingdom and New Zealand — shows “miraculous” protection of at least 90 per cent from the first dose of a Moderna or Pfizer-BioNTech vaccine.
She said the National Advisory Committee on Immunization is expected to issue a statement to align with B.C.’s decision, which frees up 70,000 doses for younger age groups.
“This is amazing news,” said Henry. “These vaccines work, they give a very high level of protection and that protection lasts for many months.”
As I wrote earlier:
… first doses first will save lives in the US but delaying the second dose and other dose-stretching policies are even more vital in countries [such as Canada] where vaccines supplies are more limited than in the United States.
Meanwhile in the United States we are vaccinating relatively quickly but in the last week we have given out more second doses than first doses. Overall, we have given out 25 million second doses–under first doses first we would have vaccinated 25 million more people benefiting them and the unvaccinated by lowering transmission rates.
The US FDA is not following the science.
A new study from Public Health England shows that both the Pfizer and AstraZeneca vaccine work well from the first dose. If that sounds familiar it’s because the results are similar to those found in Scotland. The results cover all adults in England aged 70 years and older (over 7.5 million people).
Vaccination with either a single dose of BNT162b2 or ChAdOx1 COVID-19 vaccination was associated with a significant reduction in symptomatic SARS-CoV2 positive cases in older adults with even greater protection against severe disease [approximately 80% effective at preventing hospitalisation, AT] . Both vaccines show similar effects. Protection was maintained for the duration of follow-up (>6 weeks). A second dose of BNT162b2 provides further protection against symptomatic disease but second doses of ChAdOx1 have not yet been rolled out in England. There is a clear effect of the vaccines against the UK variant of concern.
Score three for the land of Reverend Bayes: first doses first, approve AstraZeneca, approve AstraZeneca for the elderly.
The US FDA is not following the science.
The FDA panel voted unanimously to authorize the J&J vaccine. Good. Note, however, that the single-shot J&J vaccine is quite comparable to the first dose of the Pfizer and Moderna vaccines. Yet, few people are demanding that J&J be required to offer a second shot at all, let alone in 3-4 weeks (What about vaccine escape! How long does immunity with a single-shot last! What about the children!). It really is scandalous how these objections to a single-shot have disappeared. This is evidence of what I call magical thinking–an undue focus on the clinical trial design as having incantatory power.
Why did J&J focus on a single-shot? Was this because of “the science”, i.e. something unique about their vaccine? No. J&J focused on a single-shot vaccine for the same pragmatic reasons that I favor First Doses First.
J&J representatives said they chose to begin with the single shot because the World Health Organization and other experts agreed it would be a faster, more effective tool in an emergency. (emphasis added).
My view is that it would be good if the J&J vaccine was followed by a booster–perhaps of some other vaccine–but that it’s individually fine and in fact socially beneficial to get more people protected quickly by delaying the booster for at least 12 weeks to when vaccines are less scarce. I don’t currently see a reason for thinking differently about the Pfizer and Moderna vaccines.
…With such a highly protective first dose, the benefits derived from a scarce supply of vaccine could be maximized by deferring second doses until all priority group members are offered at least one dose. There may be uncertainty about the duration of protection with a single dose, but the administration of a second dose within 1 month after the first, as recommended, provides little added benefit in the short term, while high-risk persons who could have received a first dose with that vaccine supply are left completely unprotected. Given the current vaccine shortage, postponement of the second dose is a matter of national security that, if ignored, will certainly result in thousands of Covid-19–related hospitalizations and deaths this winter in the United States — hospitalizations and deaths that would have been prevented with a first dose of vaccine.
Danuta M. Skowronski, M.D.
British Columbia Centre for Disease Control, Vancouver, BC, Canada
Gaston De Serres, M.D., Ph.D.
Institut National de Santé Publique du Québec, Quebec City, QC, Canada
That’s from a letter to the NEJM which also includes a debate on delaying the second dose and a poll (vote for delaying the second dose!). What I want to point out today is that the authors are experts from Canada. I believe that first doses first will save lives in the US but delaying the second dose and other dose-stretching policies are even more vital in countries where vaccines supplies are more limited than in the United States.
Here from a podcast is Michael Osterholm, Regents Professor, McKnight Presidential Endowed Chair in Public Health, the director of the Center for Infectious Disease Research and Policy (CIDRAP) and state epidemiologist for the Minnesota Department of Health.
…Imagine you are setting across the table from two people both of whom are 65 or older, both with underlying health conditions. You have two doses of vaccine, one in each hand. And you say to them I can give two doses to you or to you but then the other person gets nothing. Or I can give one dose to both of you. And this is what I know. At the very least, one dose is likely to prevent serious illness, hospitalization and death. Two doses will probably even prevent clinical disease with B.1.1.7. But the other one of you; if you get infected with this virus, which I think substantial numbers of Americans will, things are not looking good for you. What do you want me to do?
If that is your Mom or Dad. Your Grandpa or Grandma. What would you do?
This is where the rubber meets the road. I think if the data bears it out we can save so many lives in the upcoming weeks and we are missing that opportunity.
I have already made my choice. I am postponing my second dose. I want my second dose. But I am confident that I can wait. And I can only hope that my second dose, which I have just deferred, will go to someone who it will save their life. It will make a totally different world for that family.
You know some could argue that this could be the end of my career. But I could not sleep with myself at night if I didn’t do this. I just know in my heart of hearts that this is something we must do if we are going to save lives.
The entire podcast is worthwhile, this is from around minute 44:30 (my imperfect transcription).
Hat tip: Anon.
Addendum: Many other countries should be looking very closely at dose-stretching policies.
In other news, South Korea approves the AstraZeneca vaccine. It’s not like we have anything to learn from South Korea about managing a pandemic, right? Right?
A lot of new information has dropped recently about the efficacy of First Doses First.
First, as I mentioned yesterday, we now have epidemiologists and vaccine researchers saying that for people previously infected with COVID a second dose is not necessary and may be “overkill.” Given how many people have had COVID, this increases the net benefit to First Doses First for everyone significantly.
Second, an important new study verifies that for the AZ vaccine a longer delay for the second dose is better because it generates a more powerful immune response (picture from the FT). This is a common finding for vaccines. The authors write:
ChAdOx1 nCoV-19 vaccination programmes aimed at vaccinating a large proportion of the population with a single dose, with a second dose given after a 3 month period is an effective strategy for reducing disease, and may be the optimal for rollout of a pandemic vaccine when supplies are limited in the short term.
In addition “Analyses of PCR positive swabs in UK population suggests vaccine may have substantial effect on transmission of the virus with 67% reduction in positive swabs among those vaccinated.” In other words, the vaccine cuts transmission risk.
As I have said before “the US failure to authorize the AstraZeneca vaccine in the midst of a pandemic when thousands are dying daily and a factory in Baltimore is warmed up and ready to run is a tragedy and dereliction of duty of epic proportions.”
Third, the New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG), a scientific advisory group to the British government, recently considered the risks of immune escape from the delayed second dose strategy and concluded that although the risk is real it is likely small, especially in comparison to other sources of immune escape such as therapeutics and natural infection. Moreover, the risk is outweighed by the measurable benefits of getting more does out quickly.
It is not currently possible to quantify the probability of emergence of vaccine resistance as a result of the delayed second dose, but it is likely to be small.The UK currently has more than 1,000 COVID-19 related deaths each day and has limited supplies of vaccine. In the current UK circumstances the unquantifiable but likely small probability of the delayed second dose generating a vaccine escape mutant must be weighed against the measurable benefits of doubling the speed with which the most vulnerable can be given vaccine-induced protection.
..a single dose of vaccine does not generate a new/novel risk. Given what we have observed recently with the variants B.1.1.7 and B1.351, it is a realistic possibility that over time immune escape variants will emerge, most likely driven by increasing population immunity following natural infection.
The 4 UK Chief Medical Officers agree with the JCVI that at this stage of the pandemic prioritising the first doses of vaccine for as many people as possible on the priority list will protect the greatest number of at risk people overall in the shortest possible time and will have the greatest impact on reducing mortality, severe disease and hospitalisations and in protecting the NHS and equivalent health services.
Fifth, the US public health experts are beginning to come around to the economic point of view. Consider Experts tout delaying 2nd COVID vaccine dose as US deaths mount which notes:
“The maximum public health benefit would come from giving a single dose to as many people as possible, and following up with a second dose when supply improves,” said Neal Halsey, MD, of Johns Hopkins University, in an interview. Halsey and Stanley Plotkin, MD, co-authored a letter in Clinical Infectious Diseases last week explaining how delaying a second dose of vaccine would accelerate the US vaccine rollout.
Halsey said data from both companies show the first dose of the vaccine offers significant protection against COVID-19 in the short term, for at least 1 to 3 months after injection. He also said he and Plotkin believe this was the most beneficial public health strategy even before the arrival of new variants of the virus was discovered.
“There are a number of examples of changing [vaccination] course because ACIP takes into account public health impact,” Halsey said. “We asked the ACIP to review in depth this strategy to give one dose as rapidly as possible. Such a meeting should be scheduled as soon as possible.”
The University of Minnesota’s Michael Osterholm, PhD, MPH, said yesterday on “Meet the Press” that he believes the United States has to change direction on vaccine strategy in light of the possibility of a surge of new infections coming from variant strains.
I believe that the US will go to First Doses First. The only question is will we go to First Doses First soon, when it can still help, or will we be forced to do it later in an act of desperation and agony.
Pascal Soriot, CEO of AstraZeneca, in an interview:
I think the UK one-dose strategy is absolutely the right way to go, at least for our vaccine. I cannot comment about the Pfizer vaccine, whose studies are for a three-week interval….First of all, we believe that the efficacy of one dose is sufficient: 100 percent protection against severe disease and hospitalisation, and 71-73 percent of efficacy overall.
The second dose is needed for long term protection. But you get a better efficiency if you get the 2nd dose later than earlier. We are going to do a study in the US and globally to use two-month dose interval to confirm that this is indeed the case, there are many reasons to believe it is the case with our vaccine. We have a different technology. First of all, when you look at level of antibody production, this is higher if you give the second dose three months or two months later than one month later. Also, if you look at Ebola, its vaccine, which is also using the Adenoviral vector like the Covid one, the second dose needs to be given eight weeks later. Finally, the J&J vaccine with Adenoviral vector also are performing studies on a two-month interval. And J&J has the same technology as ours. Therefore, for our vaccine, there is no doubt in my mind that the way the UK is going is the best way, because right now you have a limited amount of vaccine, but also you have a limited number of doctors and nurses able to inject people. So you maximize the number of people who get one dose. You give them enough protection for two or three months, then you give them the second dose after 3 months.
By the way, the US failure to authorize the AstraZeneca vaccine in the midst of a pandemic when thousands are dying daily and a factory in Baltimore is warmed up and ready to run is a tragedy and dereliction of duty of epic proportions. The AZ vaccine should be given an EUA immediately and made available in pharmacies for anyone who wants it while continuing to prioritize Moderna and Pfizer for the elderly and essential workers.
Yesterday I pointed out How Rapidly ‘First Doses First’ Came to Britain. The United States is also moving in that direction but more slowly. First we ended holding second doses in reserves. Now the CDC has new policies:
CNBC: The Centers for Disease Control and Prevention quietly changed its guidance on Covid-19 vaccine shots, saying it’s now OK to mix Pfizer’s and Moderna’s shots in “exceptional situations” and that it’s also fine to wait up to six weeks to get the second shot of either company’s two-dose immunization.
We will see what happens if new variants start to takeoff in the US, as seems likely, and as the number of people immunized starts to slow as we move from first does to having to vaccinate people for the second dose. More second doses means fewer resources for first timers. Biden’s 100 million in 100 days, for example, was already under-ambitious but it’s not even 100 million people it’s 100 million doses or only about 67 million people given that some will be in line twice.
Tim Harford writes about the whiplash he experienced from the debate over delaying second doses in Britain.
What a difference a couple of weeks makes. In mid-December, I asked a collection of wise guests on my BBC radio programme How to Vaccinate the World about the importance of second doses. At that stage, Scott Gottlieb, former head of the US Food and Drug Administration, had warned against stockpiling doses just to be sure that second doses were certain to be available, Economists such as Alex Tabarrok of George Mason University had gone further: what if we gave people single doses of a vaccine instead of the recommended pair of doses, and thus reached twice as many people in the short term? This radical concept was roundly rejected by my panel
…. “This is an easy one, Tim, because we’ve got to go with the scientific evidence,” said Nick Jackson of the Coalition for Epidemic Preparedness Innovations. “And the scientific evidence is that two doses is going to provide the best protection.”
My other guests agreed, and no wonder: Jackson’s view was firmly in the scientific mainstream three weeks ago. But in the face of a shortage of doses and a rapidly spreading strain of “Super-Covid”, the scientific mainstream appears to have drifted. The UK’s new policy is to prioritise the first dose and to deliver the second one within three months rather than three weeks…..the recommendation comes not from ministers but from the Joint Committee on Vaccination and Immunisation (JCVI).
Strikingly, many scientists have given the move their approval.
See also Tyler’s previous post on this theme.
By the way, if the J&J single-dose vaccine comes in at say 80% effective it is going to be interesting to see how people go from ‘a single-dose at 80% effective is too dangerous to allow for 8-12 weeks’ to ‘isn’t it great we have a single-dose 80% effective vaccine!’.
Here is an excellent Reason segment on vaccine policy and First Doses First including extensive interview with me.
Time and time again, its proposals meet fierce resistance at first but later become policy. https://t.co/hvCxGXRLkX
— Alan Cole (@AlanMCole) January 8, 2021
Of course on this particular issue, Alex was the one who started the intellectual campaign…
It isn’t clear to me who in the United States is legally entitled to make this decision. An FDA EUA is required before a vaccine can be used in the U.S. But once an EUA has been issued, is “off-label use” permitted? The CDC’s Advisory Committee on Immunization Practices recommends how scarce vaccine doses should be prioritized, but “states” (governors?) are free to make contrary prioritization decisions. Can states also decide to give half-doses or lengthen the interval between first and second doses? Can a hospital, a nursing home, or an individual doctor make such a decision? (If so, can it also deviate from its state prioritizations?) Can HHS or the President specify how these decisions must be made, or alternatively can they explicitly free lower-level decision-makers to use their own judgment?
You’re not a specialist in pharmaceutical law, I realize. But I doubt you’ll let that stop you! When you recommend a less risk-averse approach to COVID-19 vaccination, to whom are you addressing the recommendation? Who has a right to implement it?
That is from MR reader Peter Sandman. Can any MR reader inform us on this?
The simplest argument for First Doses First (FDF) is that 2*0.8>.95, i.e. two vaccinated people confers more immunity than one double vaccinated person. But there is more to it than that. Perhaps more important is that with FDF we will lower R more quickly and reach herd immunity sooner. Here’s an extreme but telling example.
Suppose you have a pop of 300 million, need 2/3 to get to herd immunity and you have 100m doses and can vaccinate 100m a month. Then with FDF you vaccinate 100m in first month and a new 100m in the second month and then you are “done.” i.e. you can then do 2nd doses more or less at leisure since you are at herd immunity (yes, I know about overshooting, this is a simple example). If instead you do second doses you vaccinate 100m in first month and the same 100m in the second month which leaves 100 million at risk for another month. Under second doses you don’t reach herd immunity until the third month. Thus, under FDF you save a 100m infection-month which is a big deal.
Now when you put this into a more sophisticated SEIR model you won’t get as strong a result but the result will be in the same direction. Note also that getting to herd immunity sooner is probably the best thing we can do to prevent further mutations.
See also Youyang Go’s thread where he discusses his modeling of similar ideas. He notes:
Reaching herd immunity two or three months sooner will have profound benefits throughout society, ranging from fewer cases & deaths to faster economic recovery.
Addendum: Please read Tyler’s post, FDF?-Show Your Work! before you comment.