Covid-19: Reports from Israel suggest one dose of Pfizer vaccine could be less effective than expected
BMJ 2021; 372 doi: https://doi.org/10.1136/bmj.n217 (Published 22 January 2021) Cite this as: BMJ 2021;372:n217Read our latest coverage of the coronavirus outbreak
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Dear Editor,
Extending the time to the second dose of the Pfizer vaccine without the informed consent of the patients is unethical. As this dosage regime was not tested in the Pfizer clinical trials it cannot be licensed by the MHRA. It therefore can only be lawfully adminitered in a clinical trial (ref 1). To conduct a clincal trial, in addition to obtaining approval by MHRA it must be approved by an independent ethics committee which approves the informed consent form. The person receiving the medicine must then be informed about the risks before signing the consent form.
When I had my vaccination on 7th January I was given form "Reg 174 Information for UK Recipients". In Section 3. How COVID-19mRNA Vaccine BNT162b2 is given, it stated: "If you receive one dose of COVID-19 mRNA Vaccine BNT162b2, you should receive a second dose of the same vaccine 21 days later to complete the vaccination series. Protection against COVID-19 may not be effective until at least 7 days after the second dose." That section was crossed out with red ballpoint. There was no explantion given on the sheet or by the vaccinator and I didn't have to sign a consent form.
The need for ethics committees to be independent of Government was debated in the House of Lords on 19 May (ref 2), when Earl Howe moved that the Medicines for Human Use Clinical Trials Regulations 2004 be annulled because the proposed organisation of Ethics Committee would establish a UK Ethics Committee Authority whereby the Government could establish or abolish an ethics committee, appoint the Chairpersons, Vice Chairs and members among other powers. As a result of his intervention the system of oversight of Ethics Committees was altered to separate it from Government. The advice of the Joint Committee on Vaccination and Immunisation: advice on priority groups for COVID-19 vaccination, 30 December 2020, updated on 6 January 2021 states in the section headed Pfizer-BioTech vaccine; "while there is some evidence to indicate high levels of short-term protection from a single dose of vaccine, a 2-dose vaccine schedule is currently advised as this is likely to offer longer lasting protection (see below)".
"See below" refers to the Vaccine Schedule where they advise, based on epidemiological data that the second dose of the Pfizer and AstraZeneca vaccines "may be given between 3 to 12 weeks following the first dose.
It is unclear from the Government's announcements who has decided to alter the dosing regime for the Pfizer vaccine but it does not appear to be part of a clinical trial or have had the approval of an independent ethics committee or the informed consent of those receiving it which seems to be unlawful and unethical.
1. The Medicines for Human Use (Clinical Trials) Regulations 2004;
2. Hansard: HL Deb 19 May 2004 vol 661 cc845-68.
Competing interests: No competing interests
Dear Editor,
This study is a reminder of reality in that clinical trials and real-time evidence are not always equivalent - 52.4% vs. 33%. The opinion on whether to delay the second dose of the Pfizer vaccine by 12 weeks, even by erstwhile authorities, is divided. The push must be to complete Pfizer's second dose as recommended, 21 days after the first, sufficient vaccine supplies and immunization staff notwithstanding. Mahase's paper (1) clearly supports a review of the speculated delay. Israel has achieved a remarkable rate of vaccination, yet even that nation would still appear vulnerable.
We must bear in mind the prima facie thought that every health authority wants to protect and vaccinate as many people as possible, for priority groups and all possible others, including health professionals at the forefront. However, if the immunity after the first dose of Pfizer vaccine does drop off before receipt of a second dose, strong mention must be made to remain rigorous in maintaining protective action against possible sources of exposure and infection.
Where has that been reiterated? Wearing the best mask possible, not just a scarf, maintaining social distancing, and washing hands with soap and water or sanitizer as a substitute cannot be overemphasized at this early stage of any vaccination program. The three procedures remain the mainstay of safety. No one should be blamed for any sub-optimal roll out of vaccines. However, the public too has the responsibility of cooperating and to fully understand the outcome of non-compliance with multiple ministries' Covid-19 guidance on self-care. We all need to work together in this pandemic, and while we discuss merits, we should not introduce division but unity in the objective goal ahead, to save as many lives as possible.
(1) Mahase E. Covid-19: Assess the effects of extending Pfizer vaccine dosing interval, expert urges. BMJ2021;372:n162. doi:10.1136/bmj.n162 pmid:33468515
Competing interests: No competing interests
Dear Editor
In view of this uncertainty, myself and many colleagues working at PHE locations are tested monthly for the presence of coronavirus antibodies. If some of us were to be vaccinated with the first dose of the Pfizer vaccine the true drop off of antibody level could be established. In the meantime, I would recommend keeping to the 3 week interval recommended by Pfizer for vulnerable patients as otherwise there is a chance the vaccination would be wasted, which would be worse.
The gov policy should be data driven where possible, and in this case there is an opportunity which should not be wasted.
Best wishes
Competing interests: No competing interests
Dear Editor
With respect, the 33 percent effectiveness as measured by PCR regardless of symptoms and the 50 percent efficacy as measured by PCR in symptomatic vaccinees may be totally compatible.
The difference could be asymptomatic cases. The two groups are not comparing apples with apples.
Ron Law
Risk & Policy Adviser
Competing interests: No competing interests
Dear Editor
First dose: Half way up or half way across?
From a public health point of view, the prioritisation of 1st dose vaccination and delaying the 2nd dose makes sense.
But there are so many unknowns. It remains to be seen whether partial immunisation would favour viral mutations that can lead to emergence of vaccine resistant variants.
There is no data to indicate whether a 2nd dose would result in significantly more protection against the Brazil and South African variants compared to 1st dose only.
Is a single dose the equivalent of half way up to higher ground away from a flooded river, or is it half way across a wide river? Only time will.
Competing interests: No competing interests
Dear Editor,
The decision to delay the second dose of vaccine against covid-19 is a sensible approach to maximize benefit to the greatest number but does come with a clear risk. Having large numbers of partially vaccinated people in the middle of an epidemic does increase the risk of developing vaccine resistant variants.
Concern has already been expressed that patients vaccinated may act differently, and increase the risk of spread; but the concern must be that the government may also act differently as the numbers vaccinated increase.
The failure of the UK to suppress the virus has likely encouraged the development of a more virulent strain; let's hope we do not foster a vaccine resistant one as well.
Competing interests: No competing interests
Dear Editor
It is now reported, JCVI "is examining data from Israel indicating that immunity after a first dose of Covid-19 vaccine could be as low as 33%" [1]. This clearly adds to the worries about the government's contentious decision to widen the dosing interval to12 weeks particularly in relation to Pfizer vaccine. A policy based on alleged public interest alone would not justify ignoring grave potential dangers due to non-compliance with Pfizer's scientifically-based instructions; proponents of this controversial JCVI's policy are simply attempting alleviate safety concerns by speculatively citing data in relation to a different (AstraZeneca) vaccine.
As the government appears to be playing hardball in this regard [2], I have urged the BMA to consider initiating urgent judicial review proceedings in the High Court [3]; as this a highly time critical issue, the BMA must get their act together without delay. This is also a good time that all frontline NHS staff unite and vaccinate colleagues in line with Pfizer's advice despite the potentially unsafe, unreasonable, and arguably irrational policy decision of the government. I also urge that the BMA writes to all NHS Trusts asking that they consider giving the second Pfizer-dose to all frontline staff without breaching manufacturer's advice and that of the WHO.
Sadly, it appears, frontline staff would once again be compelled to seek leftover second doses (of the Pfizer vaccine) in the interest of their own health & safety.
References
[1] https://www.theguardian.com/world/live/2021/jan/24/coronavirus-live-news...
[2] https://www.theguardian.com/world/2021/jan/24/uk-vaccine-adviser-says-de...
[3] https://www.bmj.com/content/372/bmj.n162/rapid-responses
Competing interests: NHS doctor
Dear Editor
We read this report with disquiet.
NHS frontline staff have been surprised in the last few weeks: initially to see international colleagues first in their countries for COVID-19 immunisation while NHS workers have been second in line. They have now been refused their second, recommended, dose of the Pfizer vaccine which will be delayed by months to allow greater numbers of the population to have one initial dose. This despite the manufacturer saying there is “no evidence” for this approach, and evidence that immunity from one dose may well be absent.
It seems certain that this delay will result in some UK health workers being more vulnerable to infection, compared to standard of care. Healthcare workers are likely to die because of this policy.
Reasons to optimally immunise healthcare staff are to avoid them becoming infected themselves, to avoid them infecting their patients, and to demonstrate professional confidence in the “Antivax” era. Some professional bodies have raised concern over the scientific basis for modifying dosage schedules. Neither author has the expertise to define the risk of transmission in part-immunised doctors and nurses, or to comment on the social psychology of vaccination uptake.
But we suggest there is another reason, and one which carries with it a moral imperative for the Government.
Earlier this year (2) we compared the morale of NHS workers without PPE to soldiers who feel they lack the kit to fight properly. The two groups are similar inasmuch as they both risk their lives to protect loved ones and country. Health staff treating COVID-19 patients are putting themselves, in harm’s way to help others. Unlike in war, their families are also at immediate increased risk. They deserve the highest protection society can afford them.
We have seen anger in the last few decades in soldiers of all seniority, due to problems such as a failure to provide adequate communications kit, or to plan for the same level of casualty evacuation as our partners in theatres of operation such as Iraq and Afghanistan. There, UK medics performed with distinction but often had to borrow transport. The use of unarmoured Snatch Land Rovers when dealing with improvised explosive devices (IEDs) was another area which sapped morale when better options were available to our allies. Soldiers fight better if they know they and their mates will be protected, and looked after if wounded.
NHS frontline staff were four or five times more likely than others to contract COVID-19 during the first wave last year (3). As a soldier must obey a lawful command on the battlefield, NHS staff must go to work with COVID positive patients. Thus a very cogent case can be made for them being fully immunised, even putting aside the moral argument to protect them
Soldiers accept the risk of injury or death, but expect to be given the best protection and weaponry available. It seems bizarre that NHS staff should expect to be treated differently during a pandemic. Nobody would suggest it appropriate that our armed forces should be sent to war with the same protective equipment as the average citizen, but this does appear to be what is being offered to NHS workers with modified vaccination.
The words of Jesus in our title, “Physician, heal thyself” are generally held to speak against hypocrisy. But in this matter we would suggest that leaving the healers at risk is both practically and morally unacceptable. They should not be considered equal to members of the general public in this regard, even if modifying vaccination intervals makes sense for overall population protection numbers. Most doctors and nurses know a colleague in hospital or ITU with COVID-19 at the moment: their loyalty is being tested.
Nobody is banging saucepans for NHS staff this time around: better to fully immunise them instead.
refs:
1 Luke 4:23, Vulgate Bible
2 BMJ 2020; 369 doi: https://doi.org/10.1136/bmj m1540
3 BMJ 2020; 370 doi: https://doi.org/10.1136/bmj.m2717
Conflict of interest: GHM has had a single dose of the Pfizer vaccine, and has a family he does not want to infect.
Competing interests: No competing interests
Covid-19 Vaccination in Israel, observation on effectiveness and fluctuation of disease incidence at different times of the year.
Dear Editor,
The report on the observation of the post mass vaccination situation in Israel is interesting [1].
Since Israel is one of the areas that the mass vaccination is already performed, the data from this area is very interesting. The effectiveness of a single dose of the new vaccine might be lower than that which was previously reported by the manufacturer. Many factors might affect the effectiveness of the new vaccine. As a new respiratory infection, we still have limited knowledge on the fluctuation of disease incidence at different times of the year. In many diseases, such as dengue and influenza, incidence fluctuates. If there is a fluctuation of incidence during the monitoring of vaccine effectiveness, the measured outcome might be affected.
References
1. Covid-19: Reports from Israel suggest one dose of Pfizer vaccine could be less effective than expected
BMJ 2021; 372 doi: https://doi.org/10.1136/bmj.n217 (Published 22 January 2021)
Cite this as: BMJ 2021;372:n217
Competing interests: No competing interests