Covid-19: Order to reschedule and delay second vaccine dose is “totally unfair,” says BMABMJ 2020; 371 doi: https://doi.org/10.1136/bmj.m4978 (Published 31 December 2020) Cite this as: BMJ 2020;371:m4978
All rapid responses
I write this piece to raise awareness about the pitfalls of the current government guidance of delaying a second dose of the Pfizer vaccine for healthcare workers (beyond the manufacturer's recommendations). This delay has been a hot topic over the last week particularly as it's not supported by Pfizer.
It is critically important to separate discussion around introducing delay for frontline health workers from introducing it as a public health strategy. The latter may be justifiable.
There are many articles that explain why giving more people the first dose quicker leads to significantly less deaths overall as a public health measure. The evidence is not what you would call level 1 or even 2a but the scientific advisors for the government believe it's strong enough to support. However when it comes to health care workers I don't think the same principles apply at all.
Healthcare workers have more persistent and constant exposure by nature of their job (as opposed to a low risk member of the public in lockdown). A strong argument can be made for frontline workers to receive the Pfizer/Moderna vaccine only, and at the correct time intervals to protect them quicker and more comprehensively. It is dangerous not to separate this from the public health approach. There is also the associated reduction of hospital acquired infection, which is a huge thing but which I only touch on. The government surely would not send its NHS soldiers to war without the best protection.
This is not about public health measures and reducing overall mortality but more specifically of giving workers the best tools possible to do their jobs. The cold hard reality is that if sickness levels amongst frontline staff continue to rise the NHS services are at risk of collapse over the next few months. Most areas are already over stretched and working beyond capacity. This delay strategy is also likely putting more patients at risk of hospital acquired infection over the next 6 months as more staff will get infected and pass this on. I believe we would be doing better by patients and staff by providing healthcare workers with more comprehensive protection as soon as possible.
Competing interests: No competing interests
The comment that delaying the second dose of the Pfizer vaccine is "unfair" is incorrect.
It’s actually "unethical".
The decision must be reversed.
It’s vaccinating quickly vs achieving immunity.
Competing interests: No competing interests
The emotive idea of administering just one dose of vaccine, postponing the second, to as many at-risk individuals as possible to protect the greatest number in the shortest possible time is laudable on a humanitarian level.1 Whilst it has been suggested that this strategy “will have the greatest impact on reducing mortality, severe disease and hospitalisations, and in protecting the NHS and equivalent health services”,2 is there evidence in favour of this admirable goal?
The Pfizer/BioNTech mRNA vaccine, the first of two vaccines to be approved in the UK, is recommended to be administered in two doses (at least) 21 days apart. Published trial data has shown the vaccine was highly effective at 95% in preventing Covid-19 beyond 7 days after the second dose.3 Vaccine efficacy was a much lower 52% in the interval between the two doses, starting 12 days after the first dose. The timeline of further decay in immunity without the booster dose is unknown.
The adenovirus vector-based Oxford/Astra-Zeneca vaccine has also been approved to be administered in two doses, the second dose between 4 and 12 weeks after the first dose. Different international studies of this vaccine had (unplanned) variations in the administered first dose of vaccine (in a sub-group of the UK cohort) but the intended timing of the second dose across the studies was 28 days (but up to 12 weeks in the Brazilian study).4 Intriguingly, it has been claimed on the basis of data not available in the public domain that vaccine efficacy between dosing intervals was around 70% beyond day 22 after the first dose.5 This is seemingly incongruous to the published trial data with reported vaccine efficacy after two doses of 62% in participants who received two standard doses and 90% in participants who received a low dose followed by a standard dose with overall vaccine efficacy across both groups of 70%.4 Furthermore, this vaccine was originally designed to be administered as a single dose but the trial protocol was changed to a two-dose regime when it was found that immunogenicity was superior after a second dose with the booster dose given at the earliest possible time.6 B-cell responses induced by the first dose of the vaccine produce a low level of antibody titres with low affinity. The booster dose produces a more robust long-lasting immunity, with high affinity antibodies.
A third vaccine, Moderna, approved for use in North America, has been reported to have an efficacy of 94.1% after two doses given 28 days apart.7 Although vaccine efficacy was 95.2% starting 14 days after the first dose, it should be noted that the effect of the second dose was included in this analysis.
Whilst large-scale vaccination is the need of the hour, limited vaccine supplies (which have been refuted by the manufacturers) have been cited as one reason for deviation from the recommended dosing interval. In our opinion, a more honest appraisal of the situation is the logistical challenge of distributing and administering the vaccines at pace, an obstacle likely to become more apparent if the numbers of vaccine recipients are doubled in the same time-frame. A vaccination strategy contrary to the available evidence risks undermining public faith in the face of high prevalence of pre-existing vaccine scepticism (for example, up to 41% in France).8,11 Imperfect vaccination further requires greater proportion of the population to be vaccinated due to reduced vaccine efficacy. Furthermore, while not widespread, vaccine resistance in viruses can occur, and any transmission of virus from vaccinated people is associated with more virulent ‘hot’ strains and requires intense genomic surveillance.9,10 The basis of such a risky strategy must be closely examined as unintended consequences could include suboptimal protection on the one hand and a false sense of security and abandonment of key public health measures on the other. Decisions to control the pandemic must remain grounded in science and robust public health principles, which translate into long-term gains even if short-term gains may appear sub-optimal. Whilst ongoing trials seek to establish the efficacy of alternative dosing schedules, the public roll out of vaccination should use proven vaccine regimens. Where this is not possible, in mitigation vaccine recipients should be robustly counselled and provided with sufficient information based on data from scientific trials and an informed consent taken after discussing pros and cons of the delayed dosing; continued vigilance and practice of public health measures should be emphasized as people can remain at risk whilst awaiting the delayed second dose. With several other vaccines already in limited use or approaching clinical use in many countries, such as Sputnik V from Russia, Covishield (a franchise version of the Oxford/Astra-Zeneca vaccine) and Covaxin from India, and CoronaVac and Sinopharm vaccines from China, the world is looking to the UK as the first to execute mass vaccination for any lessons to be learned.
There may yet be one silver lining to a delayed second dose. The current designer vaccines have precise – perhaps too precise – viral immunogenic targets. The emergence of new SARS-CoV-2 strains in Denmark, the UK and South Africa have highlighted the risk of emergence of further variants with the potential for “immune escape” from the current vaccines.11,12 In such event, the delayed second dose may allow a longer window for developing and administering updated versions of vaccine designed for new viral immunogenic targets.
Akheel A. Syed, Consultant endocrinologist, Salford Royal NHS Foundation Trust, Salford, UK
Farheena N. Mecci, General practitioner, Manchester, UK
Shyam Kalavalapalli, Consultant endocrinologist, Institute of Diabetes Endocrinology & Adiposity IDEACLINICS, Hyderabad, India
Joseph Tony, Medical Director, Potters Bar Clinic, Hertfordshire, UK
Susanne Luedtke, Honorary Senior Clinical Research Fellow, Department of Risk and Disaster Reduction, University College London, London, UK; Head of Infection Control, COVID-19 management group, and Vaccine Implementation team, Public Health Authority (Gesundheitsamt), Nuremberg, Germany
Halinder S. Mangat, Adjunct Assistant Professor, Weill Cornell Medical College, New York, New York, USA
1. Mahase E. Covid-19: Order to reschedule and delay second vaccine dose is “totally unfair,” says BMA. BMJ 2020 doi: 10.1136/bmj.m4978
2. Letter to chief executives of all NHS trusts and foundation trusts, all PCNs and all GP practices. COVID-19 vaccination – for immediate action. London: NHS England, 2020.
3. Polack FP, Thomas SJ, Kitchin N, et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med 2020;383(27):2603-15. doi: 10.1056/NEJMoa2034577
4. Voysey M, Clemens SAC, Madhi SA, et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet 2020 doi: 10.1016/s0140-6736(20)32661-1
5. Mahase E. Covid-19: UK approves Oxford vaccine as cases of new variant surge. BMJ 2020 doi: 10.1136/bmj.m4968
6. Folegatti PM, Ewer KJ, Aley PK, et al. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. Lancet 2020;396(10249):467-78. doi: 10.1016/s0140-6736(20)31604-4
7. Baden LR, El Sahly HM, Essink B, et al. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med 2020 doi: 10.1056/NEJMoa2035389
8. Lazarus JV, Ratzan SC, Palayew A, et al. A global survey of potential acceptance of a COVID-19 vaccine. Nat Med 2020 doi: 10.1038/s41591-020-1124-9
9. Fraser C, Read AF, Baigent SJ, et al. Imperfect Vaccination Can Enhance the Transmission of Highly Virulent Pathogens. PLoS Biol 2015;13(7) doi: 10.1371/journal.pbio.1002198
10. Kennedy DA, Read AF. Monitor for COVID-19 vaccine resistance evolution during clinical trials. PLoS Biol 2020;18(11) doi: 10.1371/journal.pbio.3001000
11. Wise J. Covid-19: New coronavirus variant is identified in UK. BMJ 2020 doi: 10.1136/bmj.m4857
12. Dyer O. Covid-19: Denmark to kill 17 million minks over mutation that could undermine vaccine effort. BMJ 2020 doi: 10.1136/bmj.m4338
Competing interests: No competing interests
Suppressing the pandemic quickly is more important and urgent
It is perfectly reasonable to move forward and focus on the first dose of the vaccine in order to vaccinate as many vulnerable people as possible. We are aware of the speed at which the new variant is spreading in UK (60,000 new infections daily, with nearly 600 daily deaths on average). In this situation would one want to vaccinate a few thousand with two shots or millions with the first shot? Everyone is seeking evidence. The published report in NEJM  clearly shows immunity starts building after the first week and peaks at 82% at 3 weeks after the first dose. The immunity stays at 52% between the first and second dose. We don’t have data on antibody levels in the event that the second dose is delayed, however, many millions could receive the first dose and be protected during this period where the speed of transmission is at its highest.
Together with national lockdown, this would save thousands of lives immediately. Recent reports on the new UK variant suggests that it is spreading fast and may be mutating fast, further mutations could change the course of this pandemic . Suppressing the pandemic quickly is more important and urgent. We also have to realise that the demand and supply of the vaccine may not be balanced and production might hit a bottleneck. Furthermore, vaccinating the masses is a mammoth task and will take months even if primary care physicians give up their routine work. Hence vaccinating as many with the first dose will prove wise.
And we are not alone in this. The US is considering giving half doses of the Moderna vaccine in order to reach double the number of people as soon as possible in the first instance .
As of today, 1 in 50 people in the UK are infected, we have more than 1 million people infected with COVID-19, 3000 are admitted to hospitals everyday (40% higher than during the first wave) and only 1.3 million people have been vaccinated so far . Considering the scale of this vaccine campaign we need thousands of sites and channels to vaccinate 13 million vulnerable people in the first instance. This justifies the current strategy.
1. Covid-19: UK daily coronavirus cases top 60,000 for first time. https://www.bbc.co.uk/news/uk-55550906
2. Safety and Efficacy of the BNT162b2 mRNA Covid-19 VaccineFernando P. Polack, M.D., Stephen J. Thomas, M.D., Nicholas Kitchin, M.D., Judith Absalon, M.D et al,N Engl J Med 2020;383:2603-15.,DOI: 10.1056/NEJMoa2034577
3. New variant of SARS-CoV-2 in UK causes surge of COVID-19,Tony Kirby, https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00005-9/fulltext January 05, 2021DOI:https://doi.org/10.1016/S2213-2600(21)00005-9
4. REUTERS, MON JAN 4, 2021 / 8:11 PM IST, U.S. may cut some Moderna vaccine doses in half to speed rollout, official says. Brendan Pierson
Competing interests: I have had my 1st Jab of Pfizer vaccine in the first week
Irrespective of the scientific rationale for delaying a second vaccine dose, doing so may create legal uncertainties both for vaccine manufacturers and for those healthcare professionals charged with administering them.
It is a well-established principle that drug manufacturers receive civil immunity when their products are prescribed outside of the terms of the license (prescribing ‘off-label’). Companies cannot prevent off-label use, hence making them accountable would be like chasing carmakers for parking-tickets.
Covid19 vaccines are being granted temporary authorisation under Section 174 of the UK’s Human Medicines Regulation (HMR), which pertains to the spread of pathogenic agents. Use of this provision also activates HMR Section 345, which confers immunity upon not only manufacturers and suppliers, but also upon the healthcare professionals administering the injections.
Providing immunity to doctors and nurses seems entirely necessary given that they are being asked to use a medicine that does not yet have a complete evidence package. It seems even more necessary when you consider that the same is being asked of myriad other professions – from physiotherapists to dieticians – whose unions and professional indemnity insurance are unlikely to offer much protection in the event of problems.
Without this immunity, suppliers might refuse to supply, and vaccinators might refuse to vaccinate.
Last autumn it was realised that HMR s174 did not allow the MHRA to specify the terms of temporary licences, also known as the Product Information (PI or SmPC). Therefore, Section 174A was added which states that the licensing authority “may attach conditions” to temporary authorisations.
However, 147A was drafted in such a way that the validity of a temporary licence, and of the immunity, is contingent on all parties demonstrating continued adherence to the newly created ‘conditions’.
The conditions for the Pfizer vaccine are codified in Conditions of Authorisation  and also, by virtue of cross-reference, in Information for UK Healthcare Professionals . The latter resembles a standard PI, specifying who may be vaccinated (age, gender, diagnosis etc.) and how they should be vaccinated (dose, frequency, route etc.). Therefore, using the vaccine off-label would seem to breach the licence conditions and, in turn, invalidate both license and civil immunity.
Could any of this impact manufacturers or vaccinators? Absolutely.
When first licensed, the Pfizer/BioNTech PI specified a treatment regimen of “two doses (0.3mL each) 21 days apart”. Accordingly, administering the second dose up to 12 weeks later would surely breach the temporary licence conditions. To negate this problem, the PI has simply been changed to “two doses (0.3mL each) at least 21 days apart”. Unfortunately, the manufacturer does not seem to agree.
Product Information is normally arrived at via a process of negotiation. Indeed, the temporary licence states that “Pfizer/BioNTech must liaise with the Agency to provide suitable instructions for usage” and that “the instructions that will be agreed with Pfizer/BioNTech are to be considered as conditions of this authorisation.”
We therefore have the unusual situation of the PI making recommendations for which the manufacturer has no supportive data, and seem to dispute, yet they must ‘recognise’ if they are to continue supplying the vaccine and enjoying civil immunity.
It is not entirely clear how these positions can be reconciled. The dichotomy will only be deepened if patients do indeed receive different vaccines for their first and second doses; a possibility that has been raised by the Joint Committee on Vaccines and Immunisation (JCVI).
What of the healthcare profession?
The circumstances under which vaccinators might lose immunity are more complex, requiring not only a breach of the conditions but also a “risk of death or personal injury that is wholly or partly attributable to that breach”. Nevertheless, the issue of off-label vaccine use has been causing consternation for some time.
Minutes  from the JCVI’s July meeting, held prior to any licence having been issued, show NHS England asked whether the committee would consider recommending Covid19 vaccines for “off-label use for under 18s or pregnant women”. JCVI responded that it would “consider off-label use, as had been done with other vaccines.”
At the time, it was reasonable to doubt that MHRA would recommend the use of the Covid19 vaccines in children, because they had no data for under 12s and little for under 18s. Precisely why under 18s might be a priority was not documented but when, on November 27th, draft guidance on Covid19 vaccine prioritisation was published (Greenbook Chapter 14a), it acknowledged the potential to prescribe to persons under 18 who are working in residential care-homes.
A few days later, the Pfizer/BioNTech vaccine was licensed and the PI was published. Somewhat surprisingly, given that paediatric data were scant, it permitted treatment of patients as young as 16 years of age, rather than 18. This effectively removed the potential problem of off-label prescribing to some care-workers, who can be as young as 16. When Greenbook Chapter 14a was subsequently finalised, it simply aligned itself with the license conditions.
Now, the issue has returned. While amending the PI to state “at least 21 days” partly addresses one issue, others have, and will, continue to appear. In fact, Greenbook 14a has just been amended again, now proposing that children with neuro-disabilities might still receive vaccination, even if under 16.
Instead of changing the PI again, the Greenbook attempts to resolve this conflict another way: by advising that vaccinating children would constitute use of a ‘special’ under HMR Section 167. Unfortunately, this too appears to be a conflict, because MHRA guidance  on Specials specifically excludes any medicine authorised in response to a pathogenic agent from scope.
Clearly, there are operational challenges associated with the availability and roll-out of Covid19 vaccines, dealing with which can throw up some conflicts. However, due to the delicate interplay between science, law and public confidence, attempting to resolve these conflicts by varying the terms of licence may not be the best solution. Doing so could erode confidence and introduce still greater uncertainty for healthcare professionals, industry, and patients alike.
Sincerely, Tom Macfarlane.
Competing interests: I work as a consultant to industry and have previously undertaken strategic work for both the pharma industry, including Pfizer, and the MHRA. All views expressed in this letter are entirely my own.
Where is the evidence that extending the dosing interval for the Pfizer mRNA vaccine from 3 weeks to 12 weeks is effective and safe?
The four Chief Medical Officers (CMOs) of the United Kingdom and the Deputy CMO for England wrote to the profession on 31 December 2020 to explain their rationale for the dosing schedule for the Oxford vaccine and the change to the dosing schedule for the Pfizer vaccine, to maximise the public health benefits of the vaccine roll-out this winter (1). They supported their arguments with a report from the Joint Committee on Vaccination and Immunisation (JCVI) Optimising the COVID-19 vaccination programme for maximum short-term impact, 31/12/20 (2).
Table 1, Annex A of the report tabulates vaccine efficacy (VE) for the Pfizer vaccine at 15-21 days, 22-28 days and 15-28 days after the first dose (2). The VE at 15-28 days (one week either side of the booster dose on day 22) is 91% (95%CI 74-97). The post-hoc analysis behind this estimate preserves randomisation, is based on apparent reasonable assumptions about time lags before a clinical response to vaccination and is supported by data-derived evidence for the separation of symptomatic Covid-19 incidence curves in the two trial arms (3). Such a high VE so early is reassuring, particularly as the lower bound of the 95% confidence interval for the Pfizer vaccine at 15-28 days is 74%. Although the booster on day 22 may have some effect before day 28, in line with a reported increase in 50% neutralizing antibody titre between days 21 and 28 (4), a VE of 89% (52-97) at 15-21 days is also reassuring (2).
The JCVI present a convincing argument that most of the benefit of the Pfizer vaccine occurs early and that we can anticipate a greater public health benefit in the short term if we accelerate recruitment by postponing the booster and vaccinating twice as many people with a single dose initially (2).
But what then? Patients will be reassured that initial protection with the first Pfizer vaccine dose alone is almost as good as that following a prime-boost regime with a 3-week dosing interval (89% at 15-21 days (2) compared to 95% from day 29 onwards with a prime/boost regime (3)) but they will want to know how long this level of protection after only one dose will last, and how any extended dosing interval will affect the response to a booster in terms both of efficacy and duration.
As a GP, I will struggle to answer their questions because of weaknesses in the quality of evidence presented by the JCVI, who state that “the second dose is still important to provide longer lasting protection and is expected to be as or more effective when delivered at an interval of 12 weeks from the first dose” (2).
Expected is the key word here. We must bear in mind that: (a) SARS-CoV-2 is a newly emerged pathogen – clinicians and researchers experienced in infectious diseases advise us to be humble and cautious in our assumptions about the behaviour of new pathogens; (b) the correlates of protection against infection, infectiousness, symptomatic or severe Covid-19 disease are not known, nor whether these might vary (say) by age (5); (c) neither the Pfizer BNT162b2 nor Moderna mRNA1273 vaccine trials that have been reported so far were designed to evaluate different dosing intervals (3,6); (d) mRNA-based vaccines are a new technology – even though there is a strong foundation of pre-clinical research using various mRNA platforms (7,8), BNT162b2 and mRNA1273 are the first such vaccines to have been approved for use against infectious disease in a broad section of the population.
The JCVI document reads, in part, like an Olympian pronouncement (2). This contrasts with the reasoning in reports that clinicians are accustomed to reading from NICE, whose technology appraisals and guidelines contain explicit acknowledgements of uncertainty and limits to evidence. Clinicians and the public understand the imperative to act despite imperfect evidence because of the rapidly evolving pandemic. However, a lack of transparency about some of the evidence behind current decision making does not sit well with earlier reassurances that no corners have been cut in the expedited development and deployment of Covid-19 vaccines.
So, what is the evidence for and against an extended prime-boost vaccine dosing interval against respiratory viruses in humans, and how might this be relevant to mRNA vaccines against SARS-CoV-2? How well might any such evidence about vaccine use in children translate to adults?
Key questions include the effects of an extended prime-boost vaccine dosing interval on:
1. Safety, immunogenicity, efficacy and duration of the immune response in humans?
2. The patterning of antibody binding and T cell specificity to different target epitopes, bearing in mind the potential for new variants of SARS-CoV-2 to emerge?
3. The direction of skewing of T-cell responses?
4. Coordination between different arms of the adaptive immune response, including mucosal immunity?
Does such evidence depend on the type of vaccine technology? Is there any evidence specifically for mRNA vaccines, besides the limited data in a report by Feldman et al that prolonging the dosing interval (in only 5 participants) for an mRNA vaccine against H7N9 influenza from 21 days to 6 months increased, or at least preserved, immunogenicity 3 weeks after the second dose, as judged by haemagglutination inhibition assay titres or microneutralization assay titres, respectively (9)?
1. https://www.gov.uk/government/news/statement-from-the-uk-chief-medical-o... (accessed 3 January 2021)
2. https://m.box.com/shared_item/https%3A%2F%2Fapp.box.com%2Fs%2Fiddfb4ppwk... (accessed 3 January 2021)
3. Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA covid-19 vaccine. N Engl J Med. 2020 Dec 31;383(27):2603-2615. doi: 10.1056/NEJMoa2034577. Epub 2020 Dec 10. PMID: 33301246; PMCID: PMC7745181.
4. Walsh EE, Frenck RW Jr, Falsey AR, et al. Safety and immunogenicity of two RNA-based covid-19 vaccine candidates. N Engl J Med. 2020 Dec 17;383(25):2439-2450. doi: 10.1056/NEJMoa2027906. Epub 2020 Oct 14. PMID: 33053279; PMCID: PMC7583697.
5. Plotkin SA. Updates on immunologic correlates of vaccine-induced protection. Vaccine. 2020 Feb 24;38(9):2250-2257. doi: 10.1016/j.vaccine.2019.10.046. Epub 2019 Nov 22. PMID: 31767462.
6. Baden LR, El Sahly HM, Essink B, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2020 Dec 30. doi: 10.1056/NEJMoa2035389. Epub ahead of print. PMID: 33378609.
7. Sahin U, Karikó K, Türeci Ö. mRNA-based therapeutics - developing a new class of drugs. Nat Rev Drug Discov. 2014 Oct;13(10):759-80. doi: 10.1038/nrd4278. Epub 2014 Sep 19. PMID: 25233993.
8. Pardi N, Hogan MJ, Porter FW, Weissman D. mRNA vaccines - a new era in vaccinology. Nat Rev Drug Discov. 2018 Apr;17(4):261-279. doi: 10.1038/nrd.2017.243. Epub 2018 Jan 12. PMID: 29326426; PMCID: PMC5906799.
9. Feldman RA, Fuhr R, Smolenov I, et al. mRNA vaccines against H10N8 and H7N9 influenza viruses of pandemic potential are immunogenic and well tolerated in healthy adults in phase 1 randomized clinical trials. Vaccine. 2019 May 31;37(25):3326-3334. doi: 10.1016/j.vaccine.2019.04.074. Epub 2019 May 10. PMID: 31079849.
Competing interests: I work as a GP in Yorkshire. I am a former member of the NICE technology appraisal committee A, which did not have responsibility for vaccines. I was briefly an employee of Pfizer in 1998 (2 months) and did not work on vaccines. Neither I nor any member of my family hold stock or shares in Pfizer or any other pharmaceutical company. I received the first dose of the Pfizer vaccine in December 2020.
Who is the decision to maximise the number of people protected in the short term by immunisation “unreasonable and totally unfair” to?
The “most vulnerable, at risk patients” would have their emotional well-being better protected if we were able to explain that evidence-based medicine (ie professional judgement based on scientific fact) is not blind obedience to ‘trials shackled prescribing’ peddled by big pharma. Immunisation in general has an extensive history in protecting both individuals and populations. Evidence in Covid19 is that a single infection gives 6 months protection (1) so why not a single dose of vaccine with a booster at 3 months? Despite this we are assailed by population based figures alleging percentage protection as if that were the impact on the individual patient. A direct comparator is in contraception, where each individual can only be 100% pregnant: if highly effective contraceptives such as the pill are in short supply we would surely recommend condom use to avoid an undesired pregnancy based on lower population efficacy data.
A "scientifically validated justification" for the new approach has been laid out by Tony Blair but he encouraged professionals to base judgement on science rather than restricting practise to that on which big pharma has provided data on its preferred regimens to regulators.
The BMA has a duty to its members to flag up the inconvenience of a public heath response designed to protect more people but is there an ethical inconsistency in trading off the lives of the unvaccinated against our professional inconvenience?
Pfizer stands to make huge profits by insisting on its trials-based regimen rather than permitting well respected senior colleagues to make evidence-based judgements on the basis of evidence. The not for profit Oxford Vaccine has only just arrived so no-one will need to be rescheduled anyway. The BMA should be careful to avoid competing interests such as alleged professional inconvenience (it will be a large practice that has 2000 patients in the first wave of immunisations): members of the GP Committee may wish to discuss this response with their appraisers.
1. Lumley SF, O’Donnell D, Stoesser NE, et al., Oxford University Hospitals Staff Testing Group. Antibody status and incidence of SARS-CoV-2 infection in health care workers. N Engl J Med2020. doi:10.1056/NEJMoa2034545. pmid:33369366
Competing interests: I am a former member of BMA Council I have been a recipient of the Pfizer vaccine in Scotland where the second dose is due 4 weeks after the first ( which does not comply with Pfizer's data in any event).
It appears that this decision to delay the second dose of Covid-19 vaccines by the UK Chief Medical Officers is political and administrative, designed to “protect the NHS hospitals”, rather than “based on the science”.
It has been stated that the Oxford vaccine gives 60-70% protection and the Pfizer vaccine 95%, after two doses. To delay the second dose of either for those who have already had one dose, who have given informed consent to a two dose regimen, is both unethical and potentially dangerous, having no scientifically proven basis, according to manufacturers. If doctors decline to give the second dose and patients contract the illness and die, while waiting three months or longer for the second dose, will they be liable?
In order to immunise the most vulnerable quickly, would it not be most sensible to use the Pfizer vaccine for the ‘Over 70’ age group, who are both more vulnerable immunologically and more likely to be admitted to hospital if infected, giving them 95% protection? The Oxford vaccine could be given to younger age groups, who are statistically better able to survive their (most likely) less severe bouts of illness, giving them 60-70% protection. This policy would have the double benefit of keeping more of the most vulnerable out of hospitals and immunising the largest number in the shortest time, using the vaccines in accordance with the manufacturers’ proven efficacy. The pressure on NHS bed occupancy would thereby be reduced.
The Charity sector of our economy is mainly staffed by volunteers in the ‘Vulnerable Over 70’ age group. If these elderly people are given the Oxford vaccine (60-70% protection only), few , if any of them will take the risk of returning to ‘face to face’ contact in museums, village halls and community fundraising and support activities, for three months or more. They may even give up the work altogether, until the pandemic subsides completely, judging that if they are given the Oxford vaccine, they will have a 30-40% chance of catching Covid-19, mutations and all.
Competing interests: No competing interests
The article focussed on GP concerns about disruption of the vaccination programme as a consequence of the government decision to give priority to the first vaccine dose and delay the second dose by up to 12 weeks.
The more important issue is what level of protection is offered by the first dose and what evidence there may be from trials to substantiate this. Pfizer’s Chief Executive has publicly stated that there is no information from its trials as to efficacy of the first dose. AstroZenica has proffered no evidence or comment. Various persons and newspapers have stated that first dose efficacy is 50% and 70% but none provide concrete evidence of this claim from trials.
How is it right or possible to proceed with the first dose programme in the absence of reliable evidence on efficacy?
John D Pell
Competing interests: No competing interests