I hope people are aware of the enormous added value of HIV clinical trial networks. Groups who have been working on vaccine & treatment trials for decades leapt into action to work on COVID. OWS vaccine trials directly benefitted from the expertise of these groups. A big success!
There's a lot we can learn from this experience about:
- Leveraging existing networks
- Coordination between companies and researchers to standardize protocols across trials
- Using a centralized DSMB for oversight
- Pooling data, as planned for immune correlates analysis
A recent pub with more info:
"A single 11-member DSMB monitors all government-funded trials to ensure coordinated oversight, promote harmonized designs, and allow shared insights related to safety across trials." @SteveJoffe et al. academic.oup.com/jid/advance-ar…
The ability to pool safety data strikes me as particularly beneficial. If a rare side effect were detected in one trial, they can query the other trials to look for similar evidence. This enables more prompt detection of any safety signal, to maximize participant safety.
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How will we know if we need COVID vaccine boosters?
If we observe that: (1) Vaccine protection wanes over time. (2) New immune escape variants emerge, resulting in a vaccine-strain mismatch.
These are distinct reasons. We can imagine how we would distinguish these in the data.
(1) Immunity wanes over time.
We would see that:
- Breakthrough cases occur most frequently in people who were vaccinated longest ago.
- These breakthrough cases include all types of strains.
(2) New immune escape variants emerge.
We would see that:
- Breakthrough cases are similarly common in people vaccinated recently and vaccinated longest ago.
- Breakthrough cases are disproportionately of the new variant type.
In the US, we're rapidly building immunity thanks to highly effective vaccines. Cases have been quickly dropping. What might we expect in the coming months?
A few tweets on how I think about our patchwork of outbreaks... 1/6
Immunity will not be spread evenly throughout the population. While we track vaccination coverage at the national or state level, infectious disease dynamics are inherently local. Pockets of unvaccinated people who have not previously been infected will exist. 2/6
These pockets with lower immunity will remain at risk for outbreaks. While populations with high immunity may no longer be at risk for large outbreaks, movement between areas (and from across the globe) will lead to regular re-introductions and onward cases. 3/6
Yes. A vaccinated person is less likely to transmit because they are less likely to ever be infected. At a population-level, this translates to reduced transmission. cdc.gov/mmwr/volumes/7…
2) But if a vaccinated person gets infected, are they less infectious?
This is hazier. Maybe they have lower viral load, shorter duration of infection. Maybe virus is contained to the nose only. But less infectious does not equal non-infectious.
A few replies mentioning the UK household study estimating 50% reduction in infectiousness. Studies of close contacts can provide valuable real-world evidence, and estimates from these studies will accrue over time. khub.net/documents/1359…
“Everyone believes in coordination, but no one wants to be coordinated.”
In today’s @WHO forum, Sir Michael Jacobs (@RoyalFreeNHS) with a call to action to improve collaboration for therapeutics research. 1/4
He provides a successful example of three large-scale platform trials collaborating to harmonize protocols for antithrombotics. Data are more valuable when they can be combined and compared. 2/4
He provides another example of countries having committees to prioritize new drugs for trials. Within the last few months, the committees have realized the advantage of sharing briefing documents and resources. Reduces duplication of effort and minimizes risk of omission. 3/4
The imminent FDA authorization of a vaccine for 12-15 year olds is great news, and adolescents should be able to access vaccine. But in the short term, we must also grapple with the ethics of vaccinating adolescents ahead of high-risk adults in other countries.
I had the opportunity to write a comment about findings from a large vaccination cohort study in Scotland. I use the comment to discuss some of the challenges of observational vaccine studies and the potential for lingering bias.
THREAD 1/11
Confounding is a key challenge in observational studies. One way to gain confidence in findings is to check for bias in results where we know the answer (usually, where we know there is no relationship). 2/11
.@_MiguelHernan describes using this approach in an Israeli cohort. They verified that they didn't see a protective effect of vaccines earlier than observed in randomized trials. At first they did see this, so they adjusted for more covariates. 3/11