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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To account for these need to do matching/case-control or logistic regression to find true odds ratio between infxn risk of vaxxed vs unvaxxed.
cf RCT where Chi-squared or T test test could do.
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NB I still do simple short cuts for twitter analysis with point estimates of field vax effectiveness...
But if we're being proper clinical scientists trying to get robust publishable/usable data we should have higher standards!
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For proper analysis the retrospective cohorts have to be much larger with many events (infections). ~10X or more vs RCT.
So far there have only been 3.4k B1.617.2 cases identified. Predominantly in unvaxxed young people - so the vaxxed v unvaxxed groups will be v unbalanced.
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To get to a point when confidence intervals no longer overlap it will take many more weeks if there is a small difference.
Applies to 1 dose only effectiveness too which is even more challenging due to differing time windows of population in that state/community infxn rate.
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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
We kept seeing 1 dose vax after prior infxn boosting Ab tires 3X higher than 2 doses at the standard 3 week interval. Some of us wondered if this was from optimised prime-boost interval at the time...
Fantasy commentary letter in Lancet (not a peer reviewed study)!
It's an unreasonable proposition for most countries like the UK to achieve elimination + constraints of reality negates claimed economic and liberty benefits if attempted...
From contact tracing of 4.1k households where index vaxxed >21days and contact positive 2-14 days of index
4 Jan 4 - 28 Feb from 365k households w/ single index case and 1m+ contacts
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No statistical difference between Ox/AZ and Pfizer efficacy for onward transmission
No statistical difference in effect by age
Well controlled:
adjusted for age of index case and contact, sex, region, calendar week, index of multiple deprivation quintile, household type
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limitations:
Pillar 2 symptomatic case only so may miss asymptomatic cases (=overestimate efficacy).
Assumed contact symptom >2days of index was transmission but cd be co-primary (=underestimate),
and all 2-14 days are household transmission not independent (=underestimate)
3/