Regarding vaccine safety, regulators are in a tough position. Transparency is a good principle. But one thing to do better is to limit the dead time between an announcement and the details of its rationale (the media briefing). Here be dragons. 1/3
The media briefing provided important context, that this is intended to be a short pause. That the aim is to increase awareness to (1) strengthen reporting and (2) make sure doctors use the correct drugs to treat this rare condition. They scheduled a rapid ACIP meeting. 2/3
In the dead time, the media scrambles for insights but everyone is short on details. Even states trying to set policy and provide vaccines don’t have all the information. So it’s a hard job, but there’s more to be done to get that important first version of the message right. 3/3
I saw @zeynep make this point earlier, but it is buried in a thread. Attaching here.
The % vaccine breakthroughs in a population depends on:
- Vaccine efficacy
- Amt of virus circulating
- Length of time since vaccination
When you see 0.008% breakthroughs in fully vaccinated people, remember that many of these people haven't been exposed. wsj.com/articles/cdc-i…
I love to see small numbers as much as anyone, but know that numbers like this cannot be directly interpreted as a measure of vaccine efficacy (although I have a feeling they will be). We can only interpret them against a background rate in unvaccinated people.
Similarly, "most breakthroughs have been in elderly adults" should not be read as the vaccine is less effective in elderly adults. The majority of vaccinations (and the longest amount of follow-up time) have been in elderly adults. Again, we need more info to interpret.
The news about Pfizer's adolescent trial is excellent. As some debate whether we have enough data to reliably estimate vaccine efficacy in this subgroup, some important context is that efficacy was not even the primary outcome of the trial. 1/4 statnews.com/2021/03/31/pfi…
The 12-15 subgroup was comparatively small (an extension of the existing trial), and the focus was to measure safety and immunogenicity, although efficacy data was also collected. Though we don't have full details, the trial was unlikely powered for efficacy. 2/4
When we think about bridging a known efficacious vaccine to a new (here, younger) population, the bar for evidence is lower. Clearly we need high quality safety data. For immune response data, we see even higher antibody responses in adolescents than adults. 3/4
Early on in the pandemic, I tweeted about the need to triangulate results across diverse sources. Vaccine efficacy trials were an exception, being high quality and randomized. With vaccine effectiveness studies based on real-world data, we move back into the first category. 1/3
An advantage is that we can compare real-world insights against the trials themselves, although we may not have had enough trial data to answer certain questions. We also have a sense of biological plausibility, like that vaccines take time to start working. 2/3
But result from observational studies should not be taken at face value the way trial results are. Our understanding will build over time as results are replicated. We also assess the quality of the study design used (and not only the speed at which it is published). 3/3
There are different ways to measure test positivity that result in modest differences. (Ignore the blue line of only people who have never been tested before, which is less useful at this stage of the pandemic.) Tracking trends is more useful than focusing on a raw number.
Out today -- my piece in @nature on a topic I feel very strongly about = the need to coordinate and harmonize observational vaccine studies! If you think it is hard to compare vaccine trials, you haven't seen anything yet.
A thread. 1/6 nature.com/articles/d4158…
With randomized vaccine trials becoming increasingly challenging to conduct, we will rely on observational studies to guide important policy decisions. For example, these studies can help us understand the durability of vaccines or how well they work against new variants. 2/6
We can easily expect hundreds of separate observational vaccine studies, some conducted at only a single site. Each using different endpoints, covariates, eligibility, and so on. It will be extraordinarily hard to sort through these differences in meta-analyses. 3/6
THINK LIKE AN EPIDEMIOLOGIST: Lately I have been asked why we are seeing a dramatic turnaround in cases in the US. Is it vaccines? Herd immunity? An artifact due to a drop in testing? Behavior change? Weather?? A few tweets about how I step through this question. 1/6
To start, I look to see whether the drop is an artifact. While testing has dropped somewhat, it's not enough to explain the rapid drop in cases. A drop in testing would also not explain the drop in hospitalizations that is consistent across regions. 2/6 covidtracking.com/data/charts
I then consider the similarity of the drop across locations, looking by subregion and by state. The similar patterns seen are relevant because different places have different vaccination coverage, levels of acquired immunity, and weather. Why the turnaround at a similar time? 3/6