"These are some of the most important clinical trials in history, affecting a vast majority of the planet’s population. It’s hard to imagine how much higher the stakes can be to get this right. Cutting corners should not be an option." 1/ nytimes.com/2020/09/22/opi… @nytopinion
The primary endpoint in these trials— infections—will likely be mostly mild. For example, in the @pfizer trial, a sore throat and a + PCR test counts as an event. Are these the infections that we want to suppress with a vaccine? Is that a good proxy of effectiveness? 2/
There are interim analyses, some w/ stopping rules during the trials
—4 looks for Pfizer, 1st is at 32 events
—2 looks for Moderna, 1 look in Astra Zeneca (US) trial
—A trial could be stopped on the basis of very limited number and severity of such events, declaring efficacy 3/
"Giving a vaccine to hundreds of millions of healthy people based on such limited data requires a real leap of faith."
Each trial has 30K-44,000 participants.
There's a difference of fulfilling a statistical endpoint vs extrapolation to the masses. Compelling evidence req'd 4/
Compelling evidence would be to power the trials on moderate to severe covid illness, which is a secondary endpoint of the trials. That adjustment to the 1° endpoint could easily be made by an amendment to the protocols. 5/
It is worth taking the extra weeks to get this right—to ice it—so that we have unequivocal proof of efficacy and a longer temporal window into safety.
Further, it is essential these trial go to completion of the 150-164 events. 6/
Any shortcuts to "declare a winner" (which has major ramifications👇) would be based on a soft endpoint and incomplete ascertainment of safety and efficacy. There should be no emergency approval (EUA) by @US_FDA until a/the trial(s) are completed 7/
We are well aware of the company & political interests to obtain an EUA ASAP. And that @HHSgov can override FDA.
It will take all of us to stand up for proper completion of the trials, avoiding shortcuts, getting this right. This will promote public trust, which is critical. 8/
New US Covid genomic surveillance
The KP.3.1.1 variant is on the move to become dominant, more of a challenge to our immune response than KP.3 and prior variants (especially without new KP.2 booster when we need it for high-risk individuals)
It's the deletion 31/31 that makes the KP.3.1.1 spike different, but otherwise 2 mutations away from KP.2 (R346T and Q493E)
Buckle up; this wave isn't over yet d/t KP.3.1.1's emergence
We've known about KP.3's marked growth advantage since April and could have made the call then to make the new booster. That would have been aligned well with the current wave (available in July) 2/5 erictopol.substack.com/p/are-we-flirt…
But the FDA has tried to force fit Covid into an annual shot like flu, even though all data tells us it doesn't follow an annual pattern. Even the CDC acknowledges this now
3/5cdc.gov/ncird/whats-ne…
New CDC genomic data shows continued rise of the KP.3 variant that accounts for 1 of 3 Covid cases.
LB.1 is gaining, too, as JN.1 fades away
This variant growth advantage plot by @BenjMurrell (H/T @siamosolocani) shows why this is the case. Note KP.3 is the one at far left w/ almost 3-fold advantage to JN.1.
Reinforces why the decision to develop the KP.2 vaccine booster (instead of JN.1) was a good one
Spike mutation map to show the differences betweem KP.3 and JN.1 (and LB.1, KP.2)
The connection between #SARSCoV2 and neurodegeneration
@TheLancetNeuro
Quotes below: 1. SARS-CoV-2 infection should be considered as a risk factor for Alzheimer’s disease, even though the distinction between causation versus disease acceleration is not clear.thelancet.com/journals/laneu…
2. Inflammation in patients with COVID-19, and controlled experiments show prolonged neuro-inflammation after mild SARS-CoV-2 infection
in macaques.
3. A direct correlation has been reported
between prior SARS-CoV-2 infection and increased risk
of Alzheimer’s disease (figure).
4. So far, the estimated lifetime cumulative risk of dementia due to hospitalisation for any viral infection is 1·48 (95% CI 1·15–1·91).
Breaking down the risks and benefit for lecanemab, the amyloid beta-directed antibody vs Alzheimer's drug approved @US_FDA last year. It doesn't look good.