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:n18Read our latest coverage of the coronavirus outbreak
Opinion
Covid-19 vaccines: to delay or not to delay second doses
Opinion
How do you take your vaccine—one lump or two?
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Dear Editor
The short answer to the question posed on the headline[1] is, the evidence is mainly based on data in relation to AstraZeneca. It is now well known, Pfizer does not have data to support the governments' decision to extend dosing interval upto 12 weeks. The possible and likely health & safety implications of extending the dosing interval for Pfizer vaccine do not seem to be a major concern for the government, but pressing ahead with their contentious policy primarily in the interest of wider benefit to the public.
The blanket application of such controversial policy could create substantial health & safety risks to vulnerable groups including frontline NHS staff in particular. Clearly, NHS frontline staff are prone to substantially higher risks and such risks are greater among BAME background staff. The deafening silence of the government as to possible risks and implications particularly on front line staff by going against the vaccine manufacturer's advice is simply astonishing. Is it really necessary to expose such critical group of employees to such preventablle health & safety risks?
Notably, the Minister for vaccine deployment, Nadhim Zahawi, is reported as saying[2], "GPs should use their own discretion to decide whether to honour existing appointments to administer second doses of the Pfizer and BioNTech covid vaccine". If GPs' are permitted to exercise discretion per the Minister, then there is no proper justification to prevent GPs and other vaccine prescribers adhering to Pfizer's advice, and/or the WHO's advice to administer the second dose upto six weeks after the first one.
Hence, if NHS Trusts are genuinely keen to protect their vulnerable staff groups, then there are sufficient grounds to provide the second dose to them in accordance with Pfizer's advice, and Nadhim Zahawi's remarks[2] seem to be consistent with such an approach. The health and safety of NHS employees is surely more important than an untested, controversial government policy riddled with risks.
Blanket applications of policies can lead to injustices and adverse impacts on certain vulnerable groups and the aforesaid controversial policy seems to be one that's falling into this category.
References
[1]BMJ 2021;372:n18
[2]https://www.bmj.com/content/372/bmj.n46
Competing interests: NHS doctor
Dear Editor
The ‘Global Fight’ against the ‘COVID-19 Pandemic’ is ‘Programmatically Signposted’ with the ‘Approved COVID-19 Vaccine Interventional Milestones’! The clear ‘Programmatic Difference’ between ‘Vaccines’ and ‘Vaccinations’ is increasingly a ‘Yawning Interventional Difficulty’!! The ‘Vaccines-Vaccinations Programmatic Metamorphosis’ is replete with ‘Poked Holes’ ascribable to the evolving ‘2nd Dose Uncertainties’[1-11]!! With further unfolding ‘Programmatic Difficulties’ quaking the ‘Vaccines-Vaccinations Metamorphosis’, this ‘Communication’ disposes more emerging ‘2nd Dose Uncertainties’!!!
Additional emerging ‘2nd Dose Uncertainties’ are disposed vide infra:
1. ‘2nd Dose and Booster’: Emerging ‘Conversation’ now entertains the possibility of ‘Booster Doses’ after the ‘2nd Dose’: Not ‘Clinical Trials Data’-based but occasioned by ‘Programmatic Difficulties’ and ‘COVID-19 Interventional Distortions’; Troubled ‘Global Fight’ against the ‘COVID-19 Pandemic’! Evolving ‘Contemporary Conversation’ suggests ‘Booster Doses’ are heading towards the ‘Vaccination Programme Front-Burner’!! The ‘Booster Doses’, possibly not initially part of the ‘Vaccination Programme’, will soon attain another ‘Locus’ for ‘Contemporary Vaccination Conversation’!!!
2. ‘2nd Dose and Signed Informed Consent Form’: People are made to sign the ‘Informed Consent Form’ ostensibly predicated on ascertained ‘Understanding and Acceptance’ of the ‘Undergirding Terms’ for ‘Receiving the Vaccine’ including: Number of Doses, Interval between Doses among others[12,13]!! There are implications for the altered ‘Terms’ re: ‘Informed Consent Form’-‘Informed Consent’ including the ‘2nd Dose Specifics’!!!
3. ‘2nd Dose and Indemnity’: There is ‘Indemnity’ for Manufacturers, Distributors and Administrators/ Vaccinators in case of ‘Adverse Reactions’ arising from the ‘Vaccine’ provided the ‘Anticipated Authorization Parameters’ are ‘Intact/ Unaltered’[12-14]!!
4. ‘2nd Dose and Other Legal Issues’: A ‘Contract’ is an ‘Actionable Agreement’! The ‘Vaccines Availability’ is one issue and ‘Vaccination’ is yet another denominated in ‘Vaccines in the Arms’ according to ‘Actionable Agreement’ with the ‘Vaccine Recipients’. Therefore, any breach is a basis for ‘Legal Tango’!
5. ‘2nd Dose and Emergency Use Authorization Basis’: The rush to the ‘Vaccines Marathon Finish Line’ took cognizance of ‘Clearly Distilled Conditions’ predicated on verifiably available ‘Transparent Clinical Trials Data’ situate with ‘Best Practices’-‘Robust Research Governance Principles’. These ‘Conditions’ are reflected in the ‘Anticipated Authorization Parameters’ which enable the ‘Vaccines’ to be ‘Administered into Arms’ (Vaccinations)! Adherence to the strict ‘Anticipated Authorization Parameters’ is sacrosanct and must be so incontrovertibly disposed!!
6. ‘2nd Dose and Epidemic Curve Realities’: It is rather bothersome that ‘Authorities/ Experts’ certainly knowledgeable about the ‘Terms’ of the ‘Vaccine Administration’ will be kowtowing to the ‘Pressures’ due to the ‘COVID-19 Epidemic Curve Realities’ to justify/ rationalize ‘1st Vaccine Dose’ ahead of ‘2nd Dose’ with the inherent dangers and potentiality of ‘Vaccine Inefficacy/ Ineffectiveness’ and ‘Vaccine Resistance’!!
7. ‘2nd Dose and Health Services Strain’: Here is another tenuous stance for prioritizing ‘1st Dose’ ahead of the ‘Scheduled 2nd Dose’ believing that with more persons receiving the ‘1st Dose’, there will be less ‘Infections’ and less ‘Hospitalizations’ with ‘Reduced Strain’ on the ‘Stretched Resources’ of the Health Services; ‘Complete Vaccination’ is determinant!!
8. ‘2nd Dose and Contraindications’: Are there clearly stated ‘Contraindications’ for the ‘2nd Dose’ and what should be done to assure ‘Complete Vaccination’ and ‘Protection’ while minimizing possible ‘Health Hazards’ and ‘Vaccine Resistance’?
9. ‘2nd Dose Delays, Vulnerable Groups and Consequences’: Previous Report indicates that a particular ‘Approved Vaccine’ is more effective in the 18-55 years bracket and less so in those over 55 years[14]! Another Report indicates ‘Immune Response’ from ‘1st Dose’ is not sustained beyond 42 days[15]!! What then is the fate of the more vulnerable ‘Persons over 55 years’ and are beyond 42 days waiting for rescheduled ‘2nd Dose’ to end of 12 weeks[2]?
10. ‘2nd Dose Delays, Interval Infection and Burden-Cost’: In the event of an ‘Interval Infection’ while waiting for the rescheduled ‘2nd Dose’, who is responsible for the ‘Burden’ and ‘Cost’ of care and any liabilities for the breach of the ‘Anticipated Authorization Parameters’ and the ‘Signed Informed Consent Form’?
11. ‘2nd Dose and Dose Reduction’: With the ‘Vaccine Production-Supply Chain Logistics Difficulties’, there are ‘Projected Vaccine Availability Distortions’! Reductions in ‘Vaccine Doses’ are being considered and may affect both the ‘1st Doses’ and the ‘2nd Doses’[16]!!
12. ‘2nd Dose and Shipment Supplies in Reserve’: Indeed, there are strategies to support ‘Front-Loading’ for the ‘1st Dose’ against the ‘Halving of Shipments in Reserves’ for the ‘2nd Dose’ with implications[17]!
13. ‘2nd Dose, ‘Vaccination Coverage’ and ‘Complete Vaccination’: The ‘Science of Vaccinology’ and the ‘VIP Triad/ Concept’ are important for this discourse. ‘Vaccination’ begets ‘Immunization’ and ‘Immunization’ results in ‘Protection’[18]!! Of course, there are ‘Confounding Variables’ which assure the ‘VIP Triad Transformation’ but the ‘Vaccination’ that is of ‘Determinant Impact/ Importance’ is ‘Complete Vaccination’ which requires the ‘2nd Dose’ as a Sine Qua Non! The mass spreading of the ‘1st Dose’ impacts on ‘Vaccination Coverage’ but it is the ‘2nd Dose’ that assures ‘Complete Vaccination’!!!
14. ‘2nd Dose, Vaccine Production-Supply Chain Logistics and International Politics-Transparency’: The WHO recommends that ‘National Unity’ and ‘Global Solidarity’ are necessary for the successful ‘Global Fight’ against the ‘COVID-19 Pandemic’! With ‘Vaccine Availability Difficulties’, the envisioned recommended ‘Global Solidarity’ is being fractured! The European Union is raising concerns and alert regarding the ‘Agreements’ with ‘Vaccine Manufacturers’ seemingly being disrupted by some interested Countries as Parties!! Germany recently indicated its intention not to delay the ‘2nd Dose’ suggesting no ‘Global Solidarity’ on the ‘Issue’[19]!!
15. ‘2nd Dose and Inverse Equity Hypothesis-‘Vaccine Nationalism’’: The High-Income Countries are ‘Bulk Buying and Blocking-Trapping Vaccines’ away from the ‘Reach’ of the Low-Income Countries! The Low-Income Countries in need are not likely to benefit timeously from the ‘Approved Vaccines’ amplifying the ‘Inverse Equity Hypothesis’. Within Countries, ‘Inequitable Distribution’ is a ‘Huge Issue’!! The ‘Vaccine Nationalism’ of this ‘Vaccine Distribution Inequity’ to protect ‘Country Nationals’ is different from the previously reported ‘Vaccine Nationalism’ of some Countries ‘Crossing’ the ‘Vaccines Marathon Finish Line’ before getting to the ‘Finish Line’: ‘Approving’ and ‘Using’ the ‘Candidate Vaccines’ while still in the ‘Phase III Clinical Trials’[20]!!
The ‘2nd Dose Issue’ is increasingly quaking the ‘COVID-19 Vaccination Programmes’! It was recently suggested: ‘Vaccine Dose Delayed is Vaccine Dose Never Received’!! This ‘Communication’ is a further ventilation of this extant ‘COVID-19 Vaccination Programmatic Difficulty’ re: ‘2nd Dose Uncertainties’!!
REFERENCES
1. NHS. Letter to chief executive of all NHS trusts and foundation trusts. 30 Dec 2020. https://www.england.nhs.uk/coronavirus/wp-content/uploads/sites/52/2020/... -December-2020.pdf.
2. Department for Health and Social Care. Letter to the profession from the UK chief medical officers regarding the UK covid-19 vaccination programmes. 31 Dec 2020. https://www.gov.uk/government/publications/letter-to-the-profession-from....
3. Voysey M, Clemens SAC, Mahdi SA et al. Oxford COVID Vaccine Trial Group. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomized controlled trials in Brazil, South Africa and the UK. Lancet 2020; S0140-6736(20)32661-1.doi:10.1016/S0140-6736(20)32661-1.pmid:33306989
4. EU says interval between Pfizer vaccine doses should be respected. Reuters. 4 Jan 2021. https://www.reuters.com/article/us-health-coronavirus-ema-pfizer-idUSKBN...
5. Mahase E. Covid-19: Order to reschedule and delay second vaccine dose is ‘totally unfair’ says BMA. BMJ2020; 371:m4978
6. Branswell H. Britain takes a gamble with Covid-19 vaccines, upping the stakes for the rest of us. 4 Jan 2021. https://www.gov.uk/government/publications/regulatory-approval-of-covid-....
7. Robertson J et al. Covid-19 vaccines: to delay or not to delay second doses. BMJ Opinion. 5 Jan 2021. https://blogs.bmj.com/bmj/2021/01/05/covid-19-vaccines-to-delay-or-not-t....
8. Mahase E. Covid-19: Vaccine brands can be mixed in ‘extremely rare occasions’ says Public Health England. BMJ 2021; 372:n12
9. Branswell H. Britain takes a gamble with Covid-19 vaccines, upping the stakes for the rest of us. Stat 2021. https://www.statnews.com/2021/01/04/britain-takes-a-gamble-with-covid-19....
10. British Society for Immunology. Statement on covid-19 vaccine dosing schedules. https://www.immunology.org/policy-and--public-affairs/briefing-and-posit....
11. Eregie CO. COVID-19 Pandemic, beyond the ‘Vaccines Marathon Finish Line’ and ‘Post-Vaccine Approval Programmatic Haze’: The evolving ‘2nd Dose Uncertainties’. https://www.bmj.com/content/372/bmj.n18/rr-12 of 24th January 2021
12. Public Health England. Green Book. Chapter 14a: Covid-19-SARS-CoV-2. Dec 2020.https://assets.publishing.service.gov.uk/government/uploads/system/uploa...
13. lacobucci G, Mahase E. Covid-19 Vaccination: What is the evidence for extending the dosing interval? BMJ; 3021:n18
14. Public Assessment Report-Gov.uk. https://www.assets.publishing.service-gov.uk/
15. EU says interval between Pfizer vaccine doses should be respected. Reuters. 4 Jan 2021. https://www.reuters.com/article/us-health-coronavirus-ema-pfizer-idUSKBN...
16. Ehley B. Feds may cut moderna doses in half so more people get shots. Warp Speed Adviser says. https://www.politico.com/news/2021/01/03/moderna-vaccine-doses-warp-speed
17. Tufekci Z. The Mutated Virus is a Ticking Time Bomb. https://www.theatlantic.com/science/archive/2020/12/virus-mutation-catas...
18. Swell HF, Agius RM, Kemdrick D, Stewart M. Vaccines, convalescent plasma and monoclonal antibodies for Covid-19. BMJ 2020; 370:m2722
19. Reuters Staff. Germany says does not intend to delay second COVID-19 vaccine shot. Thhps://www.reuters.com/article/us-health-coronavirus-germany-spahn/germany
20. Altmann D. Finding the best covid-19 vaccine should not be a race: 14th August 2020. https://blogs.bmj.com/bmj/2020/08/14/finding -the-best-covid-19-vaccine-should-not-be-a-race.
Professor Charles Osayande Eregie,
MBBS, FWACP, FMCPaed, FRCPCH (UK), Cert. ORT (Oxford), MSc (Religious Education),
Professor of Child Health and Neonatology, University of Benin, Benin City, Nigeria.
Consultant Paediatrician and Neonatologist, University of Benin Teaching Hospital, Benin City, Nigeria.
UNICEF-Trained BFHI Master Trainer,
ICDC-Trained in Code Implementation,
*Technical Expert/ Consultant on the FMOH-UNICEF-NAFDAC Code Implementation Project in Nigeria.
*No Competing Interests.
Competing interests: No competing interests
Dear Editor
For the ‘COVID-19 Pandemic’, the rush towards the ‘Vaccines Marathon Finish Line’ (‘Vaccine Approval’) appeared to be the envisioned ‘Magical COVID-19 Pharmaceutical Panacea’! The World was, however, forewarned of the difficult ‘Post-Vaccine Approval Issues’ as potential ‘Cogs’ in the ‘Wheel of Progress’ [1-12]!! The ‘Issues’ are protean and ventilated previously[12]!! The ‘Contemporary Conversation’: Clear ‘Programmatic Difference’ between ‘Vaccines’ and ‘Vaccinations’!!! The ‘VIP Triad and Concept’ is yet another matter not ventilated further in this ‘Piece’. For this ‘Communication’, the focus is on the evolving raging ‘Vaccine Schedules-2nd Dose Uncertainties’!!!
The ‘2nd Dose Uncertainties’ are assuming ‘Difficult Programmatic Interventional Proportions’! For ‘Tantalizing Teasers’, a few are distilled vide infra:
1. ‘2nd Dose Required’: Varied ‘Approved Vaccine Administration Schedules’: Recommended ‘2-Dose Schedules’: Pfizer-BioNTech, Moderna and Oxford-AstraZeneca Vaccines!! The Johnson and Johnson Vaccine is currently the only ‘1-Dose Schedule Vaccine’ but yet to be approved!! These expectedly are guided by verifiably available ‘Clinical Trials Data’-‘Research Governance Principles’!!! This appears not to be the case and, hence, the call to protect against the ‘Vulnerabilities’ of ‘Science’[13]!!!
2. ‘Interval Before 2nd Dose’: Different ‘Recommended Interval Before 2nd Dose’: 3 weeks for the Pfizer-BioNTech Vaccine and 4 weeks for the Moderna Vaccines! Difficulties with ‘Vaccine Availability’ have elevated this ‘Vaccine-specific Dose-Interval Recommendation’ to an extant ‘Programmatic Interventional Conversation’[11,12]!!
3. ‘Extended Interval Before 2nd Dose’: This is an exciting extant ‘Extended Interval Before 2nd Dose Conversation’[14]! It is reported by NHS England that the 4 United Kingdom Chief Medical Officers agreed on the extension of the ‘2nd Dose’ to the end of 12 weeks (Recommended 3-4 weeks); Priority is given to the ‘1st Dose’ to protect most at-risk persons over the shortest possible time re: reduced mortality, disease severity and hospitalizations[15]!! The major justification for the ‘Recommended Shift’: ‘Vaccine Shortages’ from ‘Vaccine Availability Difficulties’[16]!!! The ‘UK Position’ is hinged on the fact that ‘Immune Response’ occurs after 10 days[17] and greater ‘Immune Response’ occurs with greater than 6 weeks ‘Interval between the 1st and 2nd Doses’[7]!!!
A ‘Joint Statement’ reportedly credited to Pfizer and BioNTech: ‘No data that ‘Protection’ after the 1st Dose is sustained beyond 21 days’[14]! The European Medicine Agency also reportedly suggests that ‘Interval’ for Pfizer-BioNTech Vaccine should not exceed 42 days; Any alteration requires ‘Marketing Authorization’ to avoid ’Off-label Use’[18]!! The British Medical Association reportedly considers the ‘UK Positon’ unfair and unreasonable[19]!! The UK is reportedly becoming a ‘Living Laboratory’ with the mining of data from ‘Subsets of Subsets’ of participants in ‘Clinical Trials’[20]!! If the longer the ‘Interval’ the better the ‘Immune Response’, the basis of the ‘Recommended Intervals’ becomes questionable and, perhaps, unjustifiable[21]!!! Indeed, Pfizer reportedly indicated that different ‘Vaccine Administration Schedules (Dosage Regimens)’ were not evaluated in the ‘Clinical Trials’[14]!!!
4. ‘Dosage for 2nd Dose’: With ‘Vaccines Rollout Difficulties’, ‘Reduced ‘2nd Dose’ Dosages’ are being touted with possible implications for ‘Vaccine Efficacy’!!
5. ‘Vaccine Type for 2nd Dose’: Permitted ‘Mixing of Vaccine Brands’ in ‘Extremely rare Circumstances’[7,22]! This exposes further the ‘Vulnerability’ of the ‘Science of Vaccinology’ and may, indeed, undermine the ‘Robust Research Governance Principles’-‘Transparent Clinical Trials Data’[13]!!
6. ‘2nd Dose After Adverse Reaction to the 1st Dose’: What should be done with the ‘2nd Dose’ after an ‘Adverse Reaction’ to the ‘1st Dose’ may be gleaned from ‘Public Health England Green Book (PHE Green Book) Guidance’[7]!!
7. ‘1st Dose in Clinical Trials’: Recipients of ‘1st Dose’ during the ‘Vaccine Clinical Trials’ should be referred to the ‘Investigators’ for ‘Proper Record and Documentation’ and subsequently appropriately administered the ‘2nd Dose’ with the same ‘1st Vaccine’[7]!
8. ‘2nd Dose After Unknown 1st Dose’: In this extremely rare situation, ‘Mixing Vaccine Brands’ may be permitted7,22 but this should be critically reviewed for ‘Vaccine Efficacy’ and ‘Vaccine Safety’[13]! The ‘Science of Vaccinology’ should be upheld situate with ‘Transparent Clinical Trials Data’!!
9. ‘Prioritizing 2nd Dose Before 1st Dose for Others?’: A ‘Difficult Programmatic Interventional Knot’ to be disentangled! Who gets the ‘Priority Administration; The ‘Individual’ for the ‘1st Dose’ to have more ‘Vaccination Coverage’ or the ‘2nd Dose’ for ‘Vaccination Completion’? Other ‘Confounders’ should be considered in addition to ‘Differential COVID-19 Risk-Status’!
10. ‘2nd Dose After Inadvertent 1st Dose in Pregnancy’: A ‘1st Dose’ may be inadvertently administered to a ‘Pregnant Women’ with undiagnosed gestation! Several ‘Confounders’ may be reviewed but ‘Complete Vaccination’ may be considered[7]!!
11. ‘2nd Dose and Co-Administration with Other Vaccines’: Appointments for the ‘2nd Dose’ must be properly scheduled to avoid ‘Co-Administration with Other Vaccines’ for reasons of appropriately discerning responsibility for ‘Adverse Reactions’ and ‘Monitored Immune Response’ among others[7]!
12. ‘2nd Dose Availability and Vaccine Production-Supply Chain Logistics Difficulties’: The ‘Hallmark’ of ‘Poor National Vaccine Production-Vaccination Plans’! Promised ‘Local’ and ‘Imported Manufactured Vaccines’ with ‘Supply Chain Difficulties’ and resultant ‘Vaccine Availability Issues’ are forcing uncomplimentary ‘2nd Dose Delays’ with untoward consequences!!
13. ‘Delayed 2nd Dose and Vaccine-resistant SARS-CoV-2 Strains’: Reported ‘SARS-CoV-2 Variants’ in the United Kingdom, South Africa and Brazil with some identified in many States in the USA! Avoidable undue ‘2nd Dose Delays’ may encourage ‘SARS-CoV-2 Mutations’ that may confer ‘Vaccine-Resistance’[23] further confounding the ‘Virus Variants Difficulties’!!
14. ‘2nd Dose and Previous Incomplete Vaccination’: For ‘Incomplete Vaccination’, the ‘1st Dose’ should be ascertained and not repeated; The ‘2nd Dose Administration’ seeks ‘Vaccination Completion’[7]!
15. ‘2nd Dose, Vaccination Completion and Herd Immunity’: The surest ‘Programmatic Intervention’ to achieve ‘75% Population Immunity’ (‘Herd Immunity’) is through successful ‘National Vaccination Plans’! ‘Herd Immunity’ is achieved through successful ‘Complete Vaccinations’ for which appropriate ‘2nd Dose Administration’ is a ‘Sine Qua Non’!!
‘Vaccines Development’ through ‘Rushed Clinical Trials’ requires ‘Best Practices’ and strict compliance with ‘Robust Research Governance Principles’! These MUST be strictly upheld to protect against the ‘Vulnerabilities’ of Science!! This has implications for ‘Confidence’ and ‘Trust’ and ‘Vaccine Uptake’[24]!!!
This ‘Communication’ is a modest ‘Contribution’ to the extant ‘2nd Dose Uncertainties’ likely to compound ‘Vaccine Efficacy’, ‘Vaccine Safety’ and ‘Complete Vaccinations’ which are determinants of desired ‘Herd Immunity’ in the ‘Global Fight’ against the ‘COVID-19 Pandemic’!
REFERENCES
1. Mahase E. Covid-19: Where are we on immunity and vaccines? BMJ 2020;370:m3096
2. Antibodies Brouwer PJM, Caniels TG, Straten K et al. Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability. https://science.sciencemag.org/content/2020/06/15/science.abc5902
3. Deeks JJ, Dinnes J, Takwoingi Y, et al. Antibody tests for identification of current and past infection with SARS-CoV-2. Cochrane Database Syst Rev 2020; 6:CD013652
4. Eregie CO. Covid-19 Pandemic, SARS-CoV-2 antibodies and testing: Still searching for more facts. https://www.bmj.com/content/369/bmj.m2584/rr of 16th July 2020
5. Altmann D. Finding the best covid-19 vaccine should not be a race: 14th August 2020. https://blogs.bmj.com/bmj/2020/08/14/finding -the-best-covid-19-vaccine-should-not-be-a-race.
6. Torreele E. The rush to create a Covid-19 vaccine may do more harm than good. BMJ 2020; 370:m3209
7. Public Health England. Green Book. Chapter 14a: Covid-19-SARS-CoV-2. Dec 2020.https://assets.publishing.service.gov.uk/government/uploads/system/uploa...
8. Coronavirus: BMJ urges NYT to correct vaccine ‘mixing’ article. BBC News 2021 Jan 3. https://www.bbc.co.uk/news/uk-55519042
9. Wu KJ. Britain opens door to mix-and-match vaccinations, worrying experts. New York Times 2021 Jan 1. https://www.nytimes.com/2021/01/01/health/coronavirus-vaccines-britain.html.
10. Mahase E. Covid-19: UK approves Oxford vaccine as cases of new variant surge. BMJ 2020; 371:m3968
11. Godlee F. Speaking truth to power. BMJ 2021; 372:n24
12. Eregie CO. COVID-19 Pandemic and COVID-19 Vaccinations: Beyond the ‘Vaccines Marathon Finish Line’; The Unfolding ‘Works in the Work’ https://www.bmj.com/content/372/bmj.n24/rr-1 of 20th January 2021
13. Eregie CO. COVID-19 Pandemic and vulnerability of science to assault: Imperatives to uphold research governance principles. https://www.bmj.com/content/372/bmj.n12/rr-4 of 22nd January 2021
14. Mahase E. Covid-19 Vaccination: What is the evidence for extending the dosing interval? BMJ; 3021:n18
15. NHS. Letter to chief executive of all NHS trusts and foundation trusts. 30 Dec 2020. https://www.england.nhs.uk/coronavirus/wp-content/uploads/sites/52/2020/... -December-2020.pdf.
16. Department for Health and Social Care. Letter to the profession from the UK chief medical officers regarding the UK covid-19 vaccination programmes. 31 Dec 2020. https://www.gov.uk/government/publications/letter-to-the-profession-from....
17. Voysey M, Clemens SAC, Mahdi SA et al. Oxford COVID Vaccine Trial Group. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomized controlled trials in Brazil, South Africa and the UK. Lancet 2020; S0140-6736(20)32661-1.doi:10.1016/S0140-6736(20)32661-1.pmid:33306989
18. EU says interval between Pfizer vaccine doses should be respected. Reuters. 4 Jan 2021. https://www.reuters.com/article/us-health-coronavirus-ema-pfizer-idUSKBN...
19. Mahase E. Covid-19: Order to reschedule and delay second vaccine dose is ‘totally unfair’ says BMA. BMJ2020; 371:m4978
20. Branswell H. Britain takes a gamble with Covid-19 vaccines, upping the stakes for the rest of us. 4 Jan 2021. https://www.gov.uk/government/publications/regulatory-approval-of-covid-....
21. Robertson J et al. Covid-19 vaccines: to delay or not to delay second doses. BMJ Opinion. 5 Jan 2021. https://blogs.bmj.com/bmj/2021/01/05/covid-19-vaccines-to-delay-or-not-t....
22. Mahase E. Covid-19: Vaccine brands can be mixed in ‘extremely rare occasions’ says Public Health England. BMJ 2021; 372:n12
23. Branswell H. Britain takes a gamble with Covid-19 vaccines, upping the stakes for the rest of us. Stat 2021. https://www.statnews.com/2021/01/04/britain-takes-a-gamble-with-covid-19....
24. British Society for Immunology. Statement on covid-19 vaccine dosing schedules. https://www.immunology.org/policy-and--public-affairs/briefing-and-posit....
Professor Charles Osayande Eregie,
MBBS, FWACP, FMCPaed, FRCPCH (UK), Cert. ORT (Oxford), MSc (Religious Education),
Professor of Child Health and Neonatology, University of Benin, Benin City, Nigeria.
Consultant Paediatrician and Neonatologist, University of Benin Teaching Hospital, Benin City, Nigeria.
UNICEF-Trained BFHI Master Trainer,
ICDC-Trained in Code Implementation,
*Technical Expert/ Consultant on the FMOH-UNICEF-NAFDAC Code Implementation Project in Nigeria.
*No Competing Interests.
Competing interests: No competing interests
Dear Editor,
On 5th November 2020, I wrote a letter to my MP, Alex Burghart, a precis of which was:-
This country is in an unprecedented crisis. Lives, Livelihoods, Businesses, Basic freedoms are all being lost. Education, Mental Health, Medical research, vital medical treatments are all depleted. All age groups are suffering. The Quickest way out must be found. The crisis is deepening. We need to “think outside the box”.
I understand that normally, Vaccine proving follows a prescribed formal three stage process which is followed by a process of Regulatory Review and Approval.
The Oxford vaccine has successfully passed the first two processes. The safety has been shown to be very high: I believe there hasn’t been a single death in tens of thousands of tests. The vaccine has been shown to produce strong antibody production. Now in the third stage, which has been going on for some months, the efficacy and safety has been tested on over 18,000 people. Normally the third stage would continue for some time longer, and be subject to analysis of the results.
However, it is my contention, that in the dire situation we find ourselves, the Medicines & Healthcare products Regulatory Agency must immediately allow a Special Stage 4 trial.
This would entail producing and distributing the vaccine to VOLUNTEERS in NHS, Social care, high risk and over 60 groups, initially in areas with high infection rates. The volunteers would all report infection or side effects. The Stage 3 double blind tests could continue and the licence issued as normal. It should be made clear that this is an exceptional move in exceptional circumstances.
The existing infection control and reduction measures would be continued. If the vaccine is effective, the R number should reduce in areas where the Vaccine is deployed (if in significant numbers) If the vaccine is ineffective, no harm will be done, as long as it is not assumed to be effective, before it shown to be effective or not.
There is a far greater upside to this policy than any downside. If successful the death rate will decline rapidly and restrictions can be safely gradually removed, Business and the economy can revive.
I would suggest that people entering the country should have to have a vaccination certificate or be in isolation for 10 or 14 days until all the above named groups have been vaccinated. Another factor is how long it takes for the vaccine to work, but this should come to light fairly soon.
Alex Burghart's Secretary replied that the government had carried out a consultation and would be putting legislation forward very soon. That doesn't seem to have happened.
Since then, there was a delay of 2 months while the Pfizer and then the Oxford vaccine were put through the MHRA in series, the Government has ignored advice and allowed a 3rd wave over Christmas. The 2 vaccines are no safer or more effective, no more knowledge of their properties has been gathered and the decision to go against the manufacturers and most experts has been taken to quadruple the period between doses.
This morning on the BBC Today programme, Sir Richard Sykes said that he didn't think there was any shortage in the supply of vaccines, but there were problems in the logistics of distribution. This means that the delay in the 2nd Pfizer shot could be solved by getting EXPERTS to solve the distribution logistics. The use of the the proper experts has characterised the whole of the Governments handling of this crisis.
Competing interests: No competing interests
Dear Editor
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.
(1) https://app.box.com/s/iddfb4ppwkmtjusir2tc/file/762970779302
(2) Porter F. UK government grants Pfizer civil legal indemnity for COVID-19 vaccine. Jurist 2020 Dec 6
(3) https://www.bmj.com/content/372/bmj.n13/rr-1
Competing interests: No competing interests
Dear Editor
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
Dear Editor
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.
References:
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. p.badrinath@suffolk.gov.uk
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.
Dear Editor
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.
Dear Editor
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
Re: Covid-19 vaccination: What’s the evidence for extending the dosing interval?
Dear Editor
May I ask why neither the green book on vaccinations (1) nor the official eLFH module on covid vaccination has been updated to allow for a delayed second dose of the Pfizer vaccine? (The Astra Zeneca does say 4-14 weeks.)
If the science is so strong why aren't these 2 frameworks we have to sign to say we are following not being changed?
Also somewhat confusing is that people can now book their second jab on line but they may not realise which vaccine the site they are booking into is using.
John Sharvill
Deal, Kent
(1) https://assets.publishing.service.gov.uk/government/uploads/system/uploa...
Competing interests: I consent and vaccinate people