The scientific case for delaying the second dose of the COVID-19 vaccine

Original author: Fahad Razak, Gerald Evans & Arthur Slutsky

Published: March 17, 2021


The development of highly effective vaccines against COVID-19 within one year of the start of the pandemic is a towering scientific achievement. Three of the four vaccines currently approved in Canada use two-dose regimens. Randomized control trials studying the Pfizer-BioNTech and Moderna vaccines administered the second dose three to four weeks after the first dose, and for the AstraZeneca vaccine this interval was four two 12 weeks after first dose.

Under ideal conditions these vaccines would be administered using exactly the same protocol as the trials that tested them. In fact, regulatory agencies like Health Canada approve vaccines within the constraints of clinical trial evidence, with little to no consideration about vaccine availability. But Canada’s current reality is far from ideal, with substantially less vaccine available at present than hoped for, and new variants of concern rapidly spreading through our population.

To address this reality, the National Advisory Committee on Vaccination (NACI) has recommended that delays in the second dose of up to four months be considered. This recommendation has led to marked discord in the scientific community.

The major argument against delaying a second dose to four months is that this recommendation is not “evidence-based.” We know from clinical trials that a second dose of the Pfizer or Moderna vaccine, when given between three and four weeks after the first dose is about 95 per cent effective versus placebo; but we don’t know from the trials how effective it would be when given at four months.

Therefore, the argument goes, that the second dose should be given exactly as in the trials, i.e., follow the evidence.

We believe that this criticism of a delayed second vaccine dose strategy is overly narrow. A broader consideration of the totality of scientific evidence and real-world constraints supports a Canadian strategy of delaying the second dose. Rather than just a question of applying evidence, the problem we face is one of optimizing benefit.

First let’s be clear about what the trials tell us: The effectiveness of the first dose in the Pfizer and Moderna trials was about 85 per cent, even before the second dose was given. So, the thought experiment we need to consider is as follows: Does it makes sense to provide a second dose of vaccine to increase protection from 85 per cent to 95 per cent, while leaving an equal number of people with zero protection?