The most robust data for vax effectiveness waning is from randomised control trials. Pfizer👇
2doses holds up well- but still complete the course and boost!
This is real world data. Prospective randomisation only reduces confounding we face in retrospective observations.
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Sources of bias/confounding in observational data (eg UKHSA case control study below):
▪️ accrued natural immunity in control (>45% 🏴 infected) & only a fraction tested
▪️ difficulty of retrospective matching/case controlling (high clinical risk vaxxed first, not just age)
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▪️ break throughs disproportionately sample higher risk (immunocompromised, preexisting conditions, etc)
▪️ lower test seeking behaviour in unvaxxed
▪️ pop highest risk of infection (urban, young, ethic minority, high deprivation) also lower vax uptake
So why, if waning with better data a smaller issue, do I still think completing a 3 dose course (AKA boosting) is so important?
On personal level symptomatic VE remains ~80% at 6 months vs ~95% a month after 2nd dose from RCT data
(scope for medical/regulatory conservatism)
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1. However, that is 3-4 FOLD increase in post vax infection risk ie 'break throughs'
2. When integrating into whole population epidemiology w/ variant as transmissible as Delta R0 ~7 +/-20% seasonality we face higher pop infections & prevalence
LSHTM modelling over next yr demonstrates clearly: vaxxing <50s 3rd dose reduces deaths an estimated 18k and hospitalisation 88k. From less spillover into boosted vulnerable >50s if general prevalence high.
Pre-March 2020 wld be largest single year PH intervention in Hx.
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Not only this but 3 doses produces an overall vaccine regime effectiveness far higher than ever after the initial 2 doses. Likely >98% vs immunonaive for symptomatic protection.
Grateful for the hard work of dedicated public health scientists at @PHE_uk like @kallmemeg and unsung others who work overtime to produce excellent reports on the variant of concern B1.617.2 🇮🇳
🧵analysis of vax effectiveness, and why interpretation of reduced VE limited.
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PHE did a 'test negative case control study' w/ logistic regression as I outlined yday.
From test and vax databases they retrospectively created a control cohort of 99k who tested negative and compared to 6.4k test positive for B117 & 1k for B1.617.2
The longer it takes to statistically tell difference between vax effectiveness against variants the smaller the actual dip (if any) in protection will be.
In randomised control trials we can be confident in vax effect after only 100+ infections because selection bias and confounding variables between the vaxxed and unvaxxed comparison populations are (e)limited by the randomisation process.
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This is not the case when we do retrospective observational studies - like vax effectiveness against variants in the field.
The statistical analysis is more challenging. There are biases in who is vaxxed or infected, living, working, mixing patterns, medical health/immunity.
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