My podcast w/ Paul Offit, one of the world's leading lights on vaccines, regarding #SARSCoV2 vaccine development
medscape.com/viewarticle/93… @Medscape
It's rich and I'll summarize key points here 🧵
1. "It's an unprecedented moment...as long as the Phase 3 trials don't get truncated"
2. Things we're learning about the virus
--not affected by seasons
--can cause a vasculitis
--unusual multi-system inflammatory syndrome in children
--strong predilection for nursing homes
3. What about #LongCovid?
4. Can any Phase 3 vaccine trial have a readout by the end of October?
" I don't see how it's possible"
Clinical endpoints are moderate or severed covid disease
5. The vaccine trials do not enroll people w/ known prior covid infections. What is the rate of people who are seropositive (determined after enrollment) not having a known infection?
1%
(that's remarkably different cf estimated seropositivity in the US ~15%)
6. How many events does the Data and Safety Monitoring Board need to make the call?
*None of the companies have published their data analysis plans*
*Or their stopping rules for unequivocal efficacy*
150 or 160 total events is what has been transmitted at various conferences
7. What is a Data and Safety Monitoring Board (DSMB)?
8. My experience is that the DSMB only talks to the clinical trialists and not to the company unless there are safety issues.
What is happening here?
"The DSMB reports to the company"
9. What is going to happen at the FDA Advisory Committee on October 22nd that you serve on?
Our committee gives advice. The FDA Commissioner can either take it or not.
Important: Unless the code is broken by the DSMB (to Pfizer or Moderna) we won't see any data at the committee
10. On safety of vaccines
Concerns about vaccine-induced immunopathology reviewed with prior vaccines including measles, Dengue, RSV
There could be rare events (such as Th1 or Th2 responses) which we'll only know more about when millions of people have been vaccinated
11. More on safety
Keep our eyes open regarding people with prior covid exposure
mRNA vaccines have a lipid delivery system
The replication-deficient virus programs give a lot of virus
Adenovirus vector
12. The trials are not representative for aged, children, underrepresented minorities. We won't know how long efficacy persists
"You have to also make sure people know what you don't know"
13. We'll be needing to wear masks for a long time, not just when vaccines are approved or start implementation.
Effective vaccines don't provide mucosal IgA immunity and will increase the rate of asymptomatic carriers
14. Vaccination at scale, hundreds of millions of doses, the need for two-dose vaccines and subsequent boosters, requiring acceptance of the public will be a major challenge

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More from @EricTopol

9 Sep
Today's a very big day fo #AI medical research
There are major publications of consensus statements and guidelines published @NatureMedicine @LancetDigitalH @bmj_latest on protocols, trial design, and reporting
Here's my commentary @NatureMedicine nature.com/articles/s4159…
Here are the Consensus Statements which reflect extraordinary, international, collaborative effort
Led by @DrXiaoLiu @Denniston_Ophth and colleagues
nature.com/articles/s4159…
nature.com/articles/s4159…
@NatureMedicine 👏👏👏🙏🙏
Read 5 tweets
4 Sep
These vaccine announcements tell us how it's virtually impossible to have Phase 3 complete by November 3rd
23,000 of 30,000 currently enrolled @Pfizer/@BioNTech_Group program

1/
That means another 24,000 participants need to get their 2nd dose still, which occurs a month after the 1st.
Then 2-3 weeks to get the full immune response.
Then exposure to infections
Then moderate or severe infections as events
2/
Pfizer CEO: "We expect by end of October, we should have enough...to say whether the product works or not."
The 1st interim analysis is at 32 events
statnews.com/2020/09/02/exp… @matthewherper @statnews
Even 32 events for placebo, 0 vaccine (likelihood ~0) wouldn't cut it to stop 3/
Read 6 tweets
3 Sep
Today we learned ~1/3 Big Ten athletes who were #COVID19 + had abnormal heart MRIs, consistent w/ myocarditis, even those without symptoms. If anyone still is questioning whether this virus attacks the heart, it's denialism.
There have been multiple reports of heart involvement with #COVID19, including young athletes, and replication of @GladstoneInst iPSC-> heart cell findings. Very little is known about heart inflammation among asymptomatics (unlike lung Δs)
Documented #SARSCoV2 particles in heart cells in a tragic case of an 11-year-old girl
Read 6 tweets
3 Sep
A little primer on independent Data and Safety Monitoring Boards (DSMB), who will be reviewing the #SARSCoV2 vaccine trials to adjudicate safety and efficacy, making recommendations to the clinical trialists 1/
Consists of a multidisciplinary group of several members: clinical trialists, biostatistician, bioethicist, and experts in topic (virologist, immunologist, epidemiologists, vaccinologists)
The timing/schedule of data review usually based on enrollment 2/
The data are teed up by the biostatisticians. The DSMB is blinded to vaccine or placebo groups. There is ordinarily a time lag/gap from the "cleaned" dataset reviewed by DSMB that is behind ongoing events 3/
Read 8 tweets
2 Sep
On the #SARSCoV2 immune response and vaccine I just did a podcast with Dennis Burton, a leading immunologist and vaccinologist and co-faculty @scrippsresearch. We covered so much a long🧵summary was needed
soundcloud.com/prescrippsions… 1/x
Optimism. "The pandemic is not going to be with us forever"
(This comes from a leader of the HIV vaccine program) 2/x
1st line of defense, interferons: will they likely be helpful given as an early intervention?
Yes, but we have to be very careful 3/x
Read 16 tweets
1 Sep
Very good news on durable IgG antibodies to #SARSCoV2 from the Iceland experience
Just published @NEJM
nejm.org/doi/full/10.10… >4 months out
Iceland was one of the best performing countries vs #COVID19, starting PCR screening in January, before there was even a patient diagnosed. As a result, along with tracing/isolation, they have a seroprevalence of only 0.9% (US is now >14%, estimated) and IFR 0.3%.
The editorial is rich with context
nejm.org/doi/full/10.10…
1. "Unprecedented snapshot of seroconversion rates" with various antibody isotopes, different antigens
2. 56% cases confirmed by virus (PCR) testing so 44% infections would've been missed w/o antibody
3. 2 Waves graphic
Read 4 tweets

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