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Blog: Decision regarding dosing of COVID-19 vaccines

Saad Shakir on Pharmacovigilance:

Decision regarding dosing of COVID-19 vaccines

Since last week’s approval of the AstraZeneca/ Oxford University COVID-19 vaccine, there has been some debate about the reasons behind the regulator’s decision to schedule the second dose of both the AZ and Pfizer vaccines 12 weeks after the first. Here I set out the rationale for this decision.

Decisions by the Commission on Human Medicines (CHM), Medicines and Healthcare products Regulatory Agency (MHRA), Joint Committee on Vaccination and Immunisation (JCVI) and UK Chief Medical Officers (CMOs) have been based on: 

  1. Analysis of data not only from individual and pooled studies per protocols, but also pooled post-hoc exploratory analyses for subgroups and different time intervals.
  2. Efficacy of the Oxford/AstraZeneca and Pfizer/BioNTech vaccines the week before the second dose were 73% and 88% respectively.
  3. Consideration of the current steep rise in COVID-19 cases, hospitalisations and deaths in the UK.
  4. Assertion that the benefit of the first dose of a vaccine offers short term protection, while the second dose is for the protection in the medium term.
  5. The efficacy of other vaccines is higher with longer duration between the first and second doses (to a limit).

Dosing statements in the MHRA Product Information for both vaccines:

The Oxford/AstraZeneca vaccine is administered in two equal doses with second dose administered between 4 and 12 weeks after the first dose.

This decision by the MHRA for the 4-12 weeks interval rather than the 4 weeks in the clinical trials, is based on an exploratory analysis which is: “The level of protection gained from a single dose of the AstraZeneca vaccine was assessed in an exploratory analysis that included participants who had received one dose. Participants were censored from the analysis at the earliest time point of when they received a second dose or at 12 weeks post dose 1. In this population, vaccine efficacy from 22 days post dose 1 was 73.00% (95% CI: 48.79; 85.76 [COVID-19 Vaccine AstraZeneca 12/7,998 vs control 44/7,982]).”

Dosing recommendation for the Pfizer/BioNTech vaccine remains unchanged; the second dose should be given 3 weeks after the first administration.

Decision by JCVI:

“Delivery plans should prioritise delivering first vaccine doses to as many people on the JCVI Phase 1 priority list in the shortest possible timeframe. This will allow the administration of second doses to be completed over the longer timeframes in line with conditions set out by the MHRA and advice from the JCVI. This will maximise the impact of the vaccine programme in its primary aims of reducing mortality and hospitalisations and protecting the NHS and equivalent health services.”

Statement by the UK chief medical officers:

“Based on JCVI expert advice, it is our joint clinical advice that delivery plans should prioritise delivering first vaccine doses to as many people on the JCVI Phase 1 priority list in the shortest possible timeframe. This will allow the administration of second doses to be completed over the longer timeframes in line with conditions set out by the independent regulator, the MHRA and advice from the JCVI. This will maximise the impact of the vaccine programme in its primary aims of reducing mortality and hospitalisations and protecting the NHS and equivalent health services.”