Pfizer vs AstraZeneca vaccine: first comparative data

For update May 7th on the effectiveness of the Pfizer vaccine in controlling the pandemic visit the post https://makingsenseofcovid19withs.com/2021/05/07/high-vaccine-uptake-can-control-pandemic-even-with-lifting-social-distancing/

The number one question that people in the UK when chatting to each other in the past few weeks is “Which vaccine did you have?”!

Yesterday (22^nd February) the Scottish Government published preliminary data from their first 1.1 million people who had been enrolled in the national vaccine roll out programme.  This programme, like the rest of the UK, involved using both the Pfizer and AstraZeneca vaccines.  These data are the first real world information on whether there are any differences between the success rates from these 2 vaccines. 

What did we know before this Scottish Study

• Both vaccines target the spike protein of the virus
• They do this in slightly different ways*:
  • Pfizer by providing the genetic instructions – mRNA – to make the spike protein 
  • AstraZeneca by providing an earlier stage of the same genetic instructions which are bolted onto to a harmless virus to then make the spike protein
• By targeting the same spike protein, indeed the same genetic version of the spike protein, in theory both vaccines should be equally successful
• The key clinical trials before the vaccines were licensed however showed that
  • Pfizer gave 95% protection against being ill with 2 doses 3 weeks apart
  • AstraZeneca gave a lower protection but this could reach 85% with 2 doses 3 months apart

*See post: https://makingsenseofcovid19withs.com/2020/11/22/how-do-dna-and-rna-vaccines-work/

Other challenging news for AstraZeneca 

• These headline differences in the results between these trials seemed to suggest that Pfizer might be superior 
• It is not possible to compare the results of two trials done in different populations at different times – why not?
  • Because the overall background infection risk may have been different in the volunteers in the trials
  • The way that the 2 studies were designed meant that they had different ways of identifying the cases of Covid-19 that emerged during the follow up
• Nonetheless further support for Pfizer’s success came from the results from Moderna vaccine – an almost identical vaccine to the Pfizer – which produced the same very impressive reduction  
• AstraZeneca also had not included many elderly people (aged over 65) in their trial, and this lack of data – in the population most at risk of serious consequences from the infection – raised concerns that the AstraZeneca vaccine might not be effective in older people
• On the back of that concern, many European countries in high profile declarations, suggested they would not be using the AstraZeneca vaccine

• Further, recent data from a study in young South Africans showed the AstraZeneca vaccine did not reduce mild to moderate infection: the trial was abandoned and the South African government threatened to return their supply of the AstraZeneca vaccine
• This concern was fuelled by the emergence of the new South African variant, which was responsible for the cases in that study

• The UK is currently the only country routinely using both the Pfizer and AstraZeneca vaccines in any number
• In all 4 nations of the UK, who receives which vaccine is determined by logistics issues and vaccine availability and patients have no choice 
• (For interest my wife and I had our first doses just 3 days apart at the same centre, she had Pfizer, I had AstraZeneca!)
• Thus, the first data on the relative success of these two vaccines is of substantial interest as many people in the UK ask – although they have no choice – ‘which should I have?’

The Scottish Study published yesterday

• As with all these studies, although this is a publication from the government agency – Public Health Scotland (PHS) – it has not been peer reviewed and we should treat the results as preliminary
• To be honest, the report I have seen is not well written and I have a number of questions about the data. I accept that their headline results are probably accurate.
• The question they asked was a simple one:“How much do the vaccines reduce the risk of being admitted to hospital with Covid-19”
• Unlike the recently published preliminary studies from Israel, this study was based on a stronger epidemiological approach
  • They studied data from the entire Scottish population
  • They linked these 3 national databases

• It is having access to the whole population that makes this study so powerful
• This is how they analysed their data

• Their access to general practice data allowed them to identify individuals who had, and who had not, been vaccinated – the dark green boxes
• They identified all people who had been in hospital with Covid-19, but only included those cases who had a positive PCR test – the light green boxes
• They then compared the rates of being admitted between people who had and had not been vaccinated – the red and purple bordered light green boxes
• The most impressive part of their study was that having access to these data, especially the computerised primary care records, they were able to account for the fact that people who were vaccinated may be different from those who were not vaccinated in these ways:
  • Age
  • Gender
  • The area where they lived in terms of deprivation 
  • Their background health disorders
• Plus they were able to allow in part for the fact that those who were vaccinated were more likely to be health or care workers and hence more exposed to becoming infected 

• They then determined the success of the vaccine programme by working out how far fewer were the number of cases who had been vaccinated compared to the non-vaccinated
  • They compared the numbers in the red bordered boxes with those in the purple bordered boxes
  • Thus, if there were only half the risk of PCR positive hospitalised cases in the vaccinated group to that in the unvaccinated group, this was a vaccine efficacy of 50%
• In doing these calculations they took into account the other differences between the 2 vaccine groups listed above (eg age etc)
• As the research assumed vaccine efficacy would increase with the more days after the first dose, they compared the efficacy of the vaccines at the different time periods
• All the data refer to the success of the vaccine in terms of days after the first dose
• This is what they found

• Compared to those who had not been vaccinated,  there was a reduction of around 40% in those who had Pfizer and 70% in those who had had AstraZeneca in the second week (7-13 days) after the first dose
• By 5 weeks (28-34 days) both vaccines were increasingly effective at reducing the number of cases – by over 85% in those who had the Pfizer and 94% in those who had the AstraZeneca 

Cautions

• As mentioned above, these are preliminary data and have not been peer reviewed
• Both vaccines, as everyone knows, are designed to be given as 2 doses, but that will only increase their success
• The data refer to hospitalised cases only and may not reflect how the vaccines work at preventing mild or asymptomatic infection

But on the positive side:

• Two thirds of those vaccinated were over 65 and almost 20% over 80, so answering the question about success in the elderly
• Most cases were of the new ‘English’ variant* whereas the trial data were collected before this variant was widespread
• Who got which vaccine was likely to be random, as this was determined by the logistics of the vaccination programme
• They could take into account the background differences in risk of severe Covid-19 between those in Scotland who had or had not been vaccinated by the time of this analysis

*There are too few cases so far of the other variants for any of the vaccines to provide robust data

Conclusion:

At this stage there is strong reassurance that the two vaccines are both very effective at preventing serious infection after one dose and no suggestion that the AstraZeneca vaccine is any less effective

New post April 28th: Pfizer might be the only vaccine available for children: for the discussion on this see: https://makingsenseofcovid19withs.com/2021/04/28/vaccinating-children-arguments-for-and-against/

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