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Covid-19

Pfizer vaccine study: some more answers to key questions

Following my post yesterday, both in comments received and from the media reports, there are other questions that require an answer even at this stage: 

  1. Did the vaccine protect against asymptomatic infection?
  2. Were the numbers of cases really big enough to be confident of the vaccine’s success?
  3. Any reason why the Oxford/Astra Zeneca vaccine has not produced its results?
  4. In general, how will it be decided, if more than one vaccine works, which will be chosen?

1. Did the vaccine protect against asymptomatic infection?

  • The short answer is this was not reported
  • It is difficult logistically to know when a participant might have developed an asymptomatic infection as it would require testing with a swab test all the participants say every two weeks
  • It is also reasonable to argue that the vaccine might not protect against contracting the infection, what it does is to stop it causing a clinical problem.  Hence it may not matter that (possibly) it does not stop the infection
  • Although that could still mean a vaccinated person could pass on the infection to others

2.  Were the numbers of cases really big enough to be confident of the vaccine’s success?

  • This is an interesting question 
  • At one level the difference in the numbers of people infected between the groups was substantial and that difference is too large to have arisen by chance
  • Being a nerd, I’ve done some calculations which for those who like figures are shown below this paragraph
  • The recruitment took place in 6 countries, we don’t know the breakdown of which countries recruited how many patients
  • It is likely that the rate of infection in the placebo group would have varied between the countries
  • My calculation is that the rate of infection in their entire placebo group from all 6 countries was 40/10,000 participants per month
  • As a comparison, in the UK
    • In September –  when infection rates were low – the incidence of new infections was around 30/10,000/month
    • In October – when infection rates were higher – the incidence of new infections was around 200/10,000/month
    • These UK rates include people who at the time of testing were asymptomatic so not a totally fair comparison
  • Thus, the ‘background’ infection rates in the Pfizer groups studied may have been lower than the rates in Western European countries
  • Does this matter?
    • It might indicate that the subjects who were recruited to the study were low risk or by being research interested were also compliant with Covid-19 safe behaviours
    • This however would not be enough to explain why the active vaccine group had a lower number of cases than the placebo group
  • My conclusions
    • The results of the success of the vaccine can only be considered in terms of the protection offered for 1-2 months after the end of the vaccination course
    • We don’t know if the success of the vaccine is the same when the infection is more widespread in the population (but also we  don’t know it isn’t!)

My calculation of the background rate of infection in the people in the Pfizer trial 

3. Any reason why the Oxford/Astra Zeneca vaccine, has not produced its results?

  • The Oxford vaccine was first ‘out of the blocks” so (for an Oxford academic like me!) I wondered why they did not get their results out first!
  • Firstly, the trial was to begin with smaller that the Pfizer trial
  • Originally it started recruitment in the UK alone and then enlarged to include recruitment in South Africa and Brazil
  • A figure of around 15,000 in total from those countries was reported
  • It was planned to recruit up to a further 30,000 from the USA
  • A pause was announced in the USA because of a concern about side effects and this was only lifted at the end of October
  • So, for sure the numbers recruited, even though they started earlier in the summer, were lower than the Pfizer study
  • Lower numbers would mean (everything  else being equal) that the study would need to go on for longer for enough patients in the placebo group to develop an infection
  • Secondly if the underlying rates of infection in the countries where the Oxford vaccine was being tested were lower than in the countries with the Pfizer vaccine, then for the same reason as above it would take longer to show statistically the Oxford vaccine was successful
  • Although, the above may not be relevant as my calculations above showed that the rate of infection in the Pfizer study were  lower than prevailing in the UK at the same time
  • Thirdly and of course worryingly to the developers, the Oxford vaccine may not prove to be as successful as the Pfizer vaccine
  • The Oxford vaccine as explained in a post on this blog*, whilst ‘attaching to the same spikey bit of the virus, works in a very different way
  • The Oxford vaccine was successful in inducing immunity in the laboratory but it is possible it might not be as successful at reducing clinical infection
  • Conclusion is that we will have to wait, but possibly the vaccine may not achieve the same success rate as that reported by Pfizer, subject to all the other qualifications discussed in this post and yesterday  

* https://wordpress.com/post/makingsenseofcovid19withs.com/230

4. If more than one vaccine works, how will the ‘best’ one be selected?

  • This is an interesting question and we could assume that vaccines (including the Oxford vaccine), other than the Pfizer one, will also reduce the rate of infections without causing undue side effects
  • There will not be a direct trial comparing (say) pairs of vaccines so the authorities will only be able to compare the results of the clinical trial. 
  • These, though, will have been done in:
    • different countries
    • at different time points
    • in populations with different underlying risks apart from obvious differences such as age which can be allowed for (for example their ethnic background or pre-existing disorders)
  • Thus, drawing conclusions between vaccines by directly comparing the results of the different research studies may be misleading.
  • Regulators who licence vaccines: (FDA/MHRA/EMA) will not make the decision on which vaccine is best, they will judge each vaccine on its own merits against their standards for safety and efficacy (a posh word for how well it works)
  • Regulators will also monitor very closely uniformity in quality of production – vaccine production at scale is going to provide immense new challenges and regulators will be very keen to keep tabs on quality 
  • After granting a licence, regulators will also insist on continuing surveillance by the manufacturer to provide more data on safety  and efficacy in the real world (ie outside the research studies) 
  • It will be up to health providers, such as the NHS in the UK, to make the choice of which vaccine to go for.  This will depend on the kind of things you might expect:
    • Safety would be the prime concern – there would be a willingness to sacrifice a small gain in efficacy for a similar sized gain in safety
    • Cost
    • Ease of use including storage/shelf life etc
    • Availability
  • My guess, and this is such a unique situation, is that health providers would ideally like to stick to one vaccine and one producer, but this may not be possible    

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