One question I had with the Pfizer results - is it possible that all cases were in younger (risk-taking) adults? Unlikely, but I couldn't tell. So it's great to see a breakdown of those 95 cases across different subpopulations. Representation is important! 6/10
Nice safety profile, and participants will continue to be followed. Remember - evaluation of vaccine safety never stops, even after vaccines are approved and deployed. We have an adverse event reporting system to continually monitor all vaccines. 7/10
Another key point - the Moderna vaccine has been formulated to not require the same intensive cold chain as Pfizer's vaccine (mRNA is unstable!). This has the potential to greatly simplify the logistics of rolling out the vaccine. 8/10
What I am still very interested in seeing as the trial continues:
- Data on infection as measured by seroconversion to a non-spike protein (this is a secondary endpoint in Moderna's trial)
- Data collected over time on the durability of the effect
9/10
I am so proud of the scientific community for their determination and innovation. Given our current national situation, I think we are all grateful for the good news!

What questions do you have about the results? (I'll check in throughout the day.) 10/END
For some reason Twitter didn’t include Tweet 5/10 from my Moderna vaccine thread today. Sharing again it hopes it can be seen!
(Take two) For some reason, I can see my 5th tweet in this thread, but no one else can. (Is this Twitter jail?) Here is a screenshot!

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More from @nataliexdean

16 Nov
Another exciting Monday morning for COVID-19 vaccines! Moderna is reporting 94.5% efficacy for their mRNA vaccine.

Read on for a biostatistician's breakdown of the interim results. 10 tweets on severe disease, subgroup analysis, and more.

Press release: investors.modernatx.com/news-releases/…
Of course, I'll start with the topline result of 94.5% efficacy (90 placebo cases, 5 vaccinated cases). For a high efficacy vaccine, 95 cases is a lot of data. In event-driven trials, the number of cases matters more than the number of participants. 2/10
Both Pfizer and Moderna's vaccines are mRNA-based. Thus, it's reasonable that results are similar. Still great to see! This is exciting because mRNA vaccines are designed for pandemics but were previously unproven. Adding a new tool to our toolbox! 3/10
Read 4 tweets
9 Nov
Big news from Pfizer, with apparent high efficacy (>90%) based on 94 confirmed COVID-19 cases at their interim analysis.

A thread on how I interpret this news. Briefly:
"Celebrate, but let the process play out over time as intended."
1/8
pfizer.com/news/press-rel…
Vaccine trials are "event-driven." They continue until enough endpoints have accrued (here, lab-confirmed *symptomatic* infections). Statisticians can take planned "early looks" at the data, and so allow us to tell if a product is working exceptionally well (or not at all). 2/8
When the vaccine is highly effective, we need less data to see it. While trials are planned for 150+ total events, this is what we need for a 60% efficacy vaccine. I say this because 94 events is a lot of data for a vaccine trial, and even more so when efficacy exceeds 90%. 3/8
Read 8 tweets
22 Oct
With @mlipsitch, our new piece in @ScienceMagazine on the open questions that may remain even after vaccine efficacy trials are completed. How well does the vaccine work in high-risk subgroups? And how well does the vaccine reduce onward transmission? 1/5
science.sciencemag.org/content/early/…
Vaccine efficacy trials are designed to measure individual-level protection, which serves as the basis for regulatory decision-making. But when we think about vaccination strategy at a population-level, other features like indirect protection come into play. 2/5
As a motivating example, to best protect high-risk groups like the elderly, we either need a vaccine that directly protects the elderly or we need a vaccine that can prevent younger people from transmitting to the elderly (ideally both!). 3/5
Read 5 tweets
28 Sep
VACCINE EFFICACY 101: A biostatistician's primer

Ten tweets to cover:

- How is vaccine efficacy calculated?
- Distinguishing between infection, disease, & severe disease.
- Measuring reduced infectiousness.
- Vaccine efficacy vs. effectiveness!
2) Vaccine efficacy (VE) measures the relative reduction in infection/disease for the vaccinated arm versus the unvaccinated arm. A perfect vaccine would eliminate risk entirely, so VE = 1 or 100%. This can be calculated from the risk ratio, incidence rate ratio, or hazard ratio. Image
3) Vaccine efficacy of 50% roughly means you have a 50% reduced risk of becoming sick compared to an otherwise similar unvaccinated person. Or you have a 50% chance of becoming sick given that you were exposed to enough infectious virus to make an unvaccinated person sick.
Read 10 tweets
22 Sep
What is the best endpoint for Phase 3 vaccine trials? Disease of any severity? Severe disease? Infection? Most trials have selected the first, but this @PostOpinions piece is critical of counting mild cases. A thread in defense of what is being done. 1/6
washingtonpost.com/opinions/2020/…
First, this has been the plan for a while now. The WHO target product profile for covid vaccines was published in April, and lists that efficacy can be evaluated with respect to disease, severe disease, shedding, or transmission. 2/6
who.int/blueprint/prio… Image
Similarly, the FDA's guidance to industry was released in June. It states that either disease or infection are acceptable endpoints. 3/6
fda.gov/media/139638/d… ImageImage
Read 6 tweets
18 Sep
A thread for fellow statistical analysis plan nerds (warning: math ahead).

From Pfizer's protocol, vaccine efficacy will be estimated by the incidence rate ratio. A tutorial on how this corresponds to their planned beta-binomial analysis. 1/6
pfe-pfizercom-d8-prod.s3.amazonaws.com/2020-09/C45910…
Even though vaccine efficacy is estimated by the incidence rate ratio VE=1-IRR=1-(m1/T1)/(m0/T0), the underlying test is an exact test for a single binomial proportion. The proportion in question is what fraction of total endpoints are in the vaccine arm p=(m1/(m1+m0)). 2/6
Under 1:1 randomization, we have roughly equal follow-up time across both arms (T1=T0). If our null hypothesis was VE=0, we would expect p=50%, with the same number of events across arms. This null can be expressed as a function of the follow-up time p=T1/(T1+T0). 3/6
Read 6 tweets

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