Covid-19 vaccination: What’s the evidence for extending the dosing interval?BMJ 2021; 372 doi: https://doi.org/10.1136/bmj.n18 (Published 06 January 2021) Cite this as: BMJ 2021;372:n18
All rapid responses
This article frames questions that a lot of people will be asking having been initially told that the vaccine schedule was a two dose event spaced 21 days apart.
Many will have signed a vaccine consent form on that very understanding. Some will have been given follow up appointments 3 weeks after the first vaccination. Those accessing the “REG 174 Information for UK RECIPIENTS” (equivalent of the PIL) will have read for themselves that the authority permitting the vaccine on to the UK market was dependant on a two dose schedule, 3 weeks apart. Many will be aware of numerous bodies such as the JCVI, the BMA and the MHRA advocating and / or endorsing the original schedule. Others will have learned of the original programme from documents created by the manufacturers themselves.
Against that backdrop, legitimate questions are being asked re the evidence that was relied upon to extend the spacing. It is entirely understandable that a confused, apprehensive population might seek reassurance as to the safety and efficacy of the new schedule.
Perhaps this cautious approach should not be viewed as a reticence to invoke the Dunkirk spirit and advance against the unseen enemy but more as an indication of the confusion and uncertainty that has been created in changing the schedule in the absence of any published pre marketing surveillance data evidencing the fact that it is safe to do so. A cautionary approach in the circumstances is perhaps justified. Some might argue that anything less would be foolhardy whatever the circumstances.
Many very important questions remain unanswered including how the changed schedule might impact on the legal issues involved. Both the indemnity (provided to the vaccine manufacturers, suppliers and administrators) and the issue of informed consent would have to be revisited.
The JCVI, as recently as 30th November 2020, having agreed the 2 dose schedule 21 days apart, considered the legal implications of altering the schedule, thereby placing it outside the “anticipated authorisation parameters”, with the committee ultimately deciding in favour of the original programme.
“Given the current epidemiology and the potential legal implication of advising a schedule outside of the anticipated authorisation parameters, the Committee agreed a two-dose schedule with the previously agreed interval.”(1)
A month later the JCVI advised extending the spacing between doses to 12 weeks but what of their earlier concerns re the legal considerations? Has a new Authorisation for use been submitted and approved by the MHRA to include the change?
The indemnity was issued under the Human Medicines Regulation 2012 in respect of damage arising through “use of the vaccine” in accordance “ with recommended use”
As the original recommendations for use have been altered, does it not follow that the indemnity will have to be revisited and updated?
The December 2020 edition of “The Jurist” reminds us that the indemnity created under Regulation 345 of the Human Medicines Act 2012 only covers any damage incurred through the use of the vaccine “in accordance” with its recommended use. (2)
Given the changed schedule and the fact that some patients will have already signed a consent form for the course specified in the PIL, will these now have to be destroyed and new ones obtained?
To some this may seem a minor issue in the present crisis but as Noel Thomas points out, court judgements from recent cases evidence the fact that a failure to lawfully obtain informed consent has been a very costly mistake for some.(3) The personal cost to the patients involved has been devastating. Every care should be taken to ensure that informed consent is lawfully obtained whatever the circumstances.
While it may be tempting to adopt a battle plan which due to the severity of the situation favours a rallying cry to advance at all costs, it is only right that legitimate questions be asked and informative answers be provided as to the risk/benefit balance of doing so.
(2) Porter F. UK government grants Pfizer civil legal indemnity for COVID-19 vaccine. Jurist 2020 Dec 6
Competing interests: No competing interests
What I take from this article is the following:
Giving the two Pfizer jabs 12 weeks apart is a huge gamble.
Giving the two Oxford/AZ jabs 12 weeks apart is a slightly lesser gamble.
I would need to see much more evidence to change my mind about this.
Competing interests: No competing interests
I read with great interest your news item titled “Covid-19 vaccination: What’s the evidence for extending the dosing interval?” (1). In the early stages of the pandemic this section of the BMJ carried my war cry (2) and more recently drew the analogy of reaching the Dunkirk moment (3). As a nation we are at war with an unseen enemy who is threatening to overwhelm our National Health Service putting the health and welfare of our fellow citizens in grave danger which will lead to avoidable deaths (4). Fortunately, now we have three vaccines that are approved for emergency use in our country, a key tool in our COVID battle. A decision has been made unanimously by the Chief Medical Officers of all the four nations, Joint Committee on Vaccination and Immunisation and the regulator MHRA to increase the time interval between the first and second dose of the COVID vaccine (5). The rationale is to maximise the impact of the vaccine programme in its primary aims of reducing mortality and hospitalisations and protecting the NHS and equivalent health services. This appears to be the only way to ensure that the NHS can continue to cater for the sick and needy to alleviate their suffering. The move to prioritise the first dose has drawn criticism from General practitioners (6).
Two issues are worthy of consideration; the logistics and difficulties associated with delaying the second dose and the evidence base behind the decision. Those on the frontline who need to implement the delay in second dose will receive support to implement this policy (7). Still there appears to be no national consensus (8) on the policy that is already being pursued by the NHS. Each country must devise its own strategy depending on its demography, epidemiology and stage of the pandemic there are in. The priority groups countries have chosen to vaccinate vary across the world (9) including in Europe, with France deciding to prioritise homeless, psychiatric patients and prisoners (10). Countries are exploring options including cutting the dose by half (11) to increase supply and achieve quick population coverage of the vaccine. Some Canadian provinces have decided to vaccinate now as much as possible without holding half in reserve and will administer the booster with future supplies. It has been estimated that this type of front-loading can help “avert between 34 and 42 per cent more symptomatic coronavirus infections, compared with a strategy of keeping half the shipments in reserve (12).
With the new variant spreading fast the need of the hour is to vaccinate as many people as quickly as possible (13) and the strategy of prioritising the first dose will help us to achieve this. The UK Government has an ambitious plan to vaccinate all UK adults by the autumn of 2021 (14). Let us join this noble task of protecting our communities by vaccination. Let us invoke the Dunkirk spirit and bring on those little boats to do our bit to ensure that this vaccination programme succeeds which will ultimately save lives and livelihoods.
Dr Padmanabhan Badrinath, Consultant in Public Health Medicine,
Public Health Suffolk, Suffolk County Council.
1 Iacobucci Gareth, Mahase Elisabeth. Covid-19 vaccination: What’s the evidence for extending the dosing interval? BMJ 2021; 372: n18 [accessed 10th January 2021]; Available from https://www.bmj.com/content/372/bmj.n18
2 Let us fight COVID-19 with Compassion, Optimism, Versatility, Inspiration, Determination and invoke the Blitz spirit [BMJ] 13th March 2020. [accessed 10th January 2021]; Available from: https://www.bmj.com/content/368/bmj.m1053/rr-0
3 Badrinath P. COVID19: Battle for lives and livelihoods – Is this our Dunkirk moment? BMJ 23rd December 2020. [accessed 10th January 2021]; Available from: https://www.bmj.com/content/371/bmj.m4857/rr
4 Chief Medical Officer, Professor Chris Whitty writes about the UK's battle with Covid-19 [Internet] 10th January [accessed 10th January 2021]; Available from: https://www.gov.uk/government/news/statement-from-chief-medical-officer-...
5 Statement from the UK Chief Medical Officers on the prioritisation of first doses of COVID-19 vaccines [Internet] 30th December [accessed 10th January 2021]; Available from: https://www.gov.uk/government/news/statement-from-the-uk-chief-medical-o...
6 GPs hit out at 'grossly unfair' plan to delay follow-up COVID-19 jabs [Internet] 31st December [accessed 10th January 2021]; Available from: https://www.gponline.com/gps-hit-grossly-unfair-plan-delay-follow-up-cov...
7 COVID-19 vaccination programme [Internet] Updated 8th January 2021[accessed 10th January 2021]; Available from: https://www.bma.org.uk/advice-and-support/covid-19/gp-practices/covid-19...
8 Covid-19 vaccines: to delay or not to delay second doses [Internet] 5th January [accessed 10th January 2021]; Available from: https://blogs.bmj.com/bmj/2021/01/05/covid-19-vaccines-to-delay-or-not-t...
9 EXPLAINER - Why Indonesia is vaccinating its working population first, not elderly [Internet] 4th January 2021 [accessed 10th January 2021]; Available from: https://news.trust.org/item/20210104063432-yquaj/
10 Priority cases for Covid-19 vaccination in France [Internet] 27th January 2021 [accessed 10th January 2021]; Available from: https://www.connexionfrance.com/Practical/Health/Priority-cases-for-Covi...
11 Feds may cut Moderna vaccine doses in half so more people get shots, Warp Speed adviser says. [Internet] 3rd January 2021 [accessed 10th January 2021]; Available from: https://www.politico.com/news/2021/01/03/moderna-vaccine-doses-warp-spee...
12 The Mutated Virus Is a Ticking Time Bomb [Internet] 31st December 2020 [accessed 10th January 2021]; Available from: https://www.theatlantic.com/science/archive/2020/12/virus-mutation-catas...
13 How Dangerous Are New COVID-19 Strains? [Internet] 7th January 2021 [accessed 10th January 2021]; Available from: https://www.cfr.org/in-brief/how-dangerous-are-new-covid-19-strains
14 Every adult to be offered vaccine by autumn' [Internet] 1oth January 2021 [accessed 10th January 2021]; Available from: https://www.bbc.co.uk/news/live/world-55605009
Dr Padmanabhan Badrinath, Consultant in Public Health Medicine, Suffolk County Council & Associate Clinical Lecturer, University of Cambridge. Directorate of Public Health, Endeavour House, Suffolk County Council, Ipswich, IP1 2BX. firstname.lastname@example.org
Disclaimer: The views expressed here are the personal view of the author and in no way represent the views of his employer, Suffolk County Council.
Competing interests: Conflict of interest: The author works in a local authority Public Health Department and leads the local specialist COVID response team.
I would love to be immunised properly. And that means-
1.Careful attention to any contraindications ( eg, past history of Stevens Johnson Syndrome diagnosed after the event)
2. Full attention to the vaccination regime laid down by the manufacturer.
This means that the vaccinator does not alter the interval between the first and second doses.
And it means that the second jab is from the same manufacturing technique as the first one.
A vaccinator going off-label will render the consent to vaccination invalid.
I would challenge the NHS to contradict me.
Competing interests: I have just been invited for the Jab. I am 88. My presumed absence of immunity has complicated the life of my relatives.
The MHRA Public Assessment Report Authorisation for Temporary Supply COVID-19 mRNA Vaccine BNT162b2 (BNT162b2 RNA) (last updated on 11th December 2020) is based upon a two dose schedule of the vaccine given 21 days apart.
It states that “immunogenicity data” for the vaccine is currently available “up to 1 month after the second vaccine dose” ie covering a seven week period in total from administration of the first dose when 21 day spacing between doses is employed.
In addition it states that “BNT162b2 elicited robust SARS-CoV-2 neutralisation and S1-binding antibody responses at 1 month after dose 2. SARS-Cov-2 neutralising titres and S1-binding antibody concentrations were higher in younger subjects (18-55years) compared with the older subjects (56-85years)” (1)
Might it be the case that, in extending the 21 days to 12 weeks to allow a greater number of individuals to have a first vaccine, an unacceptable level of vulnerability will be created in the over 55’s?
Does the data, evidencing the fact that more lives will be saved in more people getting a first dose of the vaccine, take into consideration the possible impact on the levels of antibody concentrations in the over 55’s throughout the additional 9 week delay between doses?
The fact that the original Authorisation was granted on a 2 dose schedule 21 days apart suggests that there was good reason for it being implemented in that way so as to provide optimum protection to recipients.
The JCVI announcement prioritising a first dose delivery and altering the time scale from 3 weeks to 12 falls short of what is required to reassure the public when stating that immunity following the first dose of vaccine is “likely” to last for that period of time based upon “unpublished data”
“Protective immunity from the first dose likely lasts for a duration of 12 weeks (unpublished data)” (2)
We the public are constantly being advised to trust the data, trust the science, but that would be more readily achieved if we able to access it for ourselves and bodies like the JCVI were able to state unequivocally based upon previously generated data, that immunity created after the first dose, in switching the spacing between doses to 12 weeks, is going to last that long.
We need reassurance that we are not solving one problem ie. low supply numbers of vaccine at the risk of creating another.
(1) Public Assessment Report - Gov.uk
https://assets.publishing.service.gov.uk › uploads › file
(2) Optimising the COVID-19 vaccination programme for maximum short-term impact. Short statement from the Joint Committee on Vaccination and Immunisation. 31 December 2020.
Competing interests: No competing interests
Your article seems to suggest that Germany might support the UK idea of delaying the second dose of the Covid19 vaccine. It seems now that this is not true: https://www.reuters.com/article/us-health-coronavirus-germany-spahn/germ...
Competing interests: No competing interests