We have the protocols. Now we know how there will very likely be an Emergency Use Approval (EUA) for a vaccine prior to November 3. The company and political motivations are fully aligned. 1. The criteria for an EUA is that it "may be effective" fda.gov/regulatory-inf…
2. Nearly every day we hear from @pfizer's CEO @AlbertBourla that they will know if their vaccine is working by the end of October.
Only the Data and Safety Monitoring Board is reviewing the data at specific intervals, the interim analyses
So how will they (Pfizer) know that?
3. The 1st interim analysis for that trial is at 32 events, infections, which can and likely will be mild. The stopping rules as reviewed by @biosbenk@EmoryRollins are "aggressive" and "unusual" for the number of interim analyses (4) and Bayesian approach github.com/benkeser/pfize…
4. As presented in a poll, ≥ 26 infections in the placebo group at the 1st interim of 32 events would fulfill the stopping rule and support a claim of efficacy.
But the EUA only requires *"May be effective"* so even <26 placebo events could qualify
5. The DSMB reports to the sponsor. The trial data should not be unblinded unless it has been stopped (for futility, safety, or efficacy stopping rule) or completed. But it is easy to discern which group (vaccine or placebo) by the early adverse effects without unblinding.
6. Note the similarity in some symptoms for #COVID19 (which are the endpoint) and the early adverse effects of the vaccine (dose of 100 ug was used in Phase 3) nejm.org/doi/full/10.10…
7. So with or without fulfilling pre-specified efficacy criteria at the 1st interim look, which will occur within weeks, Pfizer can apply for an EUA with the low threshold of "may be effective"
(If Pfizer hits the stopping rule and doesn't stop the trial, that's another story)
8. The EUA criteria are so minimal that even the Phase 1/2 serology data (NEJM paper above) could fulfill "may be effective" and that would equate to the Russian vaccine approval and roll out.
10. What if the FDA says NO, the data from 32 infections isn't enough? Clearly at that juncture there would be very limited data for the vaccine's safety.
The HHS can override that an issue the vaccine approval.
And we've already seen @HHSGov do that with FDA LDTs weeks ago.
11. The same issues apply for the @moderna_tx first interim analysis at 53 events, but a conventional O'Brien-Fleming stopping rule is being used and the 1° endpoint definition of infections is tighter
12. This is obviously a rush job—a race between companies with big political stakes. Once an EUA is issued for a vaccine, the whole landscape shifts. Safety issues could crop up later and engender mistrust. Ability to conduct placebo-controlled trials could be impaired.
13. These are the most important clinical trials of our lifetime. There's no need for this rush. We need to do them right; get the Phase 3 trials completed as planned at 150-160 events. That will only require waiting weeks, it'll give us more confidence about efficacy and safety
14. Just as pressure was applied to @pfizer@BioNTech_Group and @moderna_tx to release their protocols, we need to apply intense pressure to the companies, the FDA, and HHS to preempt any EUA until Phase 3 trials are *fully* completed.
15. Translation, TLDR:
We need a shot in the light, not in the dark.
A matter of weeks to nail the efficacy issue down is well worth the wait.
Zero tolerance for company or governmental shortcuts and related back door BS.
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.
My oped on the JN.1 variant and the 2nd biggest US wave of infections (after Omicron) since the pandemic began
@latimes @latimesopinion #LongCovid latimes.com/opinion/story/…
Recent @CDCgov #SARSCoV2 wastewater data for current wave (vs Omicron Jan 2022 and subsequent waves), graph by @luckytran
Sorry, @washingtonpost, but this is not "another Covid-19 uptick" as you put it in your Health Alert. You ignore the best metric for infections that we have at present—wastewater—focusing only on hospitalizations washingtonpost.com/health/2024/01…
3 New #LongCovid reports 1. Vaccination protection—1 dose 21%, 2 doses 59%, 3 doses 73% among ~590,000 people in Sweden (strong association) bmj.com/content/383/bm…
2. 3-year prospective follow up of a cohort of ~1350 participants, hospitalized in China
—Lung function restored back to baseline in most
—Higher risk of reinfection that people w/o Long Covid
—Half w/ persistent symptoms thelancet.com/journals/lanre…
3. At @RSNA annual meeting, brain MRI with microstructure imaging (DMI), participants with #LongCovid vs controls had microstructure changes associated with impaired cognition, sense of smell and fatigue eurekalert.org/news-releases/…
Big news #ESC2023 and @NEJM
In a placebo-controlled randomized trial of people with obesity + heart failure (with preserved ejection fraction). semaglutide (Wegovy) markedly improved symptoms, exercise time, reduced inflammatory markers (and weight loss) nejm.org/doi/full/10.10…
This also tells us something about the underlying mechanism of heart failure with preserved EF—metabolic dysfunction and attendant systemic inflammation—not previously acknowledged or confirmed
The accompanying editorial lays this finding out well. Prior studies of weight loss didn't help HFpEF
Two new papers @NatureMedicine and @JAMAInternalMed shed light on #LongCovid at 2-years. But there's no shortage of known unknowns.
Reviewed in a new Ground Truths (link in my profile, because that would be it X-suppressed)
The EG.5 variant continues to show a growth advantage in the latest US genomics surveillance, from 11->17% in past 2 weeks
FL.1.5.1 also on the rise. The XBBs are on the wane. https://t.co/50Eq338zXLcovid.cdc.gov/covid-data-tra…
EG.5.1 rise seen in many other places, nicely summarized in @kallmemeg 's thread about the new @UKHSA report
https://t.co/Ba3GZmwVWF
Highlighting the evolution of these variants from XBB in @dfocosi's convergence map. The added F456L mutation may reflect impact of monoclonal antibody treatment escape mutation (see ) https://t.co/bZtWCt1oMH