Credit ACIP/CDC
As we've noted before, no pandemic plan survives contact with the virus. For the past two decades, most of the world's (admittedly, limited) pandemic planning focused on an emerging novel influenza virus, and we've ended up with a much more complicated coronavirus instead.
In 2019, in Manufacturing Pandemic Flu Vaccines: Easier Said Than Done, we looked at some of the problems that vaccine manufacturers have faced previously in meeting production goals.
More recently we discussed the daunting logistics of getting a 2-dose vaccine into the arms of a significant number of people in the opening months of 2021 (see also Sanofi & GSK Announce Substantial Delay In Delivery Of Their COVID-19 Vaccine).
While it is remarkable that any (EUA) COVID vaccine was produced and released in late 2020, the quantity of vaccine available, and the initial roll out, have been less than hoped for even as little as a month ago.
Add in the rapid spread of a variant COVID (B.1.1.7) across the UK (and around the globe) - which has been blamed on a sharp rise in hospitalizations - and there is a strong sentiment to abandon the 2-dose regimen for now, and give as many people one shot as possible.
On December 30th, the UK's CMOs announced their support of the idea, in Statement from the UK Chief Medical Officers on the prioritisation of first doses of COVID-19 vaccines:
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. Operationally this will mean that second doses of both vaccines will be administered towards the end of the recommended vaccine dosing schedule of 12 weeks. This will maximise the number of people getting vaccine and therefore receiving protection in the next 12 weeks.
But for the UK government, which is facing a potential collapse of their NHS, it's hard to worry about the creek rising when their house is on fire.
Similarly concerned over the prospect of a more transmissible variant virus, India has apparently approved a COVID vaccine which has yet to complete Phase III human trials (see BBC report Covaxin: Concern over 'rushed' approval for India Covid jab).
Whether abandoning the 2-dose vaccination regimen is a praiseworthy pivot in the face of a rapidly changing viruscape - or if it will come back to bite us in the behind - is something no one can truly know right now.
Like many others, I have some misgivings about going `off book' with the vaccine scheduling without the benefit of some clinical trials to back it up, but I can see why UK feels the need to move more aggressively with vaccinating the public.
The debate over doing the same thing here in the United States is beginning to rise, and if the pandemic should worsen substantially in the weeks ahead, I expect calls to do so will grow louder.
But for now, the FDA's position is to stay the course, and go with the 2-dose regimen which was used in the clinical trials.
FDA Statement on Following the Authorized Dosing Schedules for COVID-19 Vaccines
For Immediate Release:January 04, 2021Statement From: Commissioner of Food and Drugs - Food and Drug Administration
Stephen M. Hahn M.D. Director - Center for Biologics Evaluation and Research (CBER) Peter Marks M.D., PhD.
Two different mRNA vaccines have now shown remarkable effectiveness of about 95% in preventing COVID-19 infection in adults. As the first round of vaccine recipients become eligible to receive their second dose, we want to remind the public about the importance of receiving COVID-19 vaccines according to how they’ve been authorized by the FDA in order to safely receive the level of protection observed in the large randomized trials supporting their effectiveness.
We have been following the discussions and news reports about reducing the number of doses, extending the length of time between doses, changing the dose (half-dose), or mixing and matching vaccines in order to immunize more people against COVID-19. These are all reasonable questions to consider and evaluate in clinical trials. However, at this time, suggesting changes to the FDA-authorized dosing or schedules of these vaccines is premature and not rooted solidly in the available evidence. Without appropriate data supporting such changes in vaccine administration, we run a significant risk of placing public health at risk, undermining the historic vaccination efforts to protect the population from COVID-19.
The available data continue to support the use of two specified doses of each authorized vaccine at specified intervals. For the Pfizer-BioNTech COVID-19 vaccine, the interval is 21 days between the first and second dose. And for the Moderna COVID-19 vaccine, the interval is 28 days between the first and second dose.
What we have seen is that the data in the firms’ submissions regarding the first dose is commonly being misinterpreted. In the phase 3 trials, 98% of participants in the Pfizer-BioNTech trial and 92% of participants in the Moderna trial received two doses of the vaccine at either a three- or four-week interval, respectively. Those participants who did not receive two vaccine doses at either a three-or four-week interval were generally only followed for a short period of time, such that we cannot conclude anything definitive about the depth or duration of protection after a single dose of vaccine from the single dose percentages reported by the companies.
Using a single dose regimen and/or administering less than the dose studied in the clinical trials without understanding the nature of the depth and duration of protection that it provides is concerning, as there is some indication that the depth of the immune response is associated with the duration of protection provided. If people do not truly know how protective a vaccine is, there is the potential for harm because they may assume that they are fully protected when they are not, and accordingly, alter their behavior to take unnecessary risks.
We know that some of these discussions about changing the dosing schedule or dose are based on a belief that changing the dose or dosing schedule can help get more vaccine to the public faster. However, making such changes that are not supported by adequate scientific evidence may ultimately be counterproductive to public health.
We have committed time and time again to make decisions based on data and science. Until vaccine manufacturers have data and science supporting a change, we continue to strongly recommend that health care providers follow the FDA-authorized dosing schedule for each COVID-19 vaccine.
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.
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Like everything else in a fast moving crisis, this plan is subject to change.
Stay tuned.
