LONG THREAD. Received questions in my DM about Pfizer vaccine and will attempt to explain based on available info. Early readout of the Phase III clinical trial of Pfizer’s mRNA vaccine trial results after 94 symptomatic COVID-19 cases is very positive (90% effectiveness). 1/n

7 days after the second dose - corresponding to 28 days after the first dose. No serious adverse events have been reported so far among trial participants. It is unclear whether the vaccine was effective against mild and/or severe COVID19 disease. 2/n

Full trial will require 164 cases of COVID19. It is reasonable to expect Pfizer will get their full symptomatic COVID19 caseload within the next 2-3 weeks. The estimated efficacy of the vaccine could change but is likely to be in the range of 85-95% effective. 3/n

Pfizer’s early readout is separate from the NIH Data and Safety Monitoring Board (DSMB) for the Warp Speed vaccines that took federal money for the research and development phase. As of November 8, Pfizer has enrolled 43,538 participants (42% of whom had diverse backgrounds). 4/n

38,955 participants have received both doses of the vaccine, which requires two doses about 21 days apart. The FDA requires observation on trial participants for two months after immunization to detect possible early serious side effects. 5/n

It is hard to know how the FDA will decide on the 2-month requirement. It is unlikely they will require 2 months follow-up for every trial participant as that decision would delay the vaccine Emergency Use Authorization (EUA) until mid-January. Pfizer will file for an EUA to 6/n

distribute the vaccine when half of the patients in their study have been observed for any safety issues for at least two months following their second dose. Pfizer expects to cross that threshold in third week of November. Given the surge in COVID cases in the US, my guess 7/n

is the FDA will recognize the urgency of the situation and will give an EUA if the vaccine appears safe & effective. An EUA offers liability protections to vaccine makers, and it remains in effect as long as there is a public health, military, or national security emergency. 8/n

An EUA allows the FDA to stage the authorization and the access to the vaccine to different high-risk groups while they continue to collect post market data on the vaccine. This process effectively establishes a registry to continue collecting safety and efficacy data on 9/n

millions of people as they get vaccinated. The FDA likely will limit initial use to healthcare providers. Pfizer will receive $1.9B from the US govt for manufacturing 100M doses of the vaccine. Sufficient Pfizer vaccine for 20M people will be available by the end of Dec. 10/n

CDC estimates there are 17-20M health-care workers in the U.S. alone, almost the entire # of vaccine doses the U.S. expects to have by the end of 2020. The FDA plans to convene an open to the public session of its Vaccines and Related Biological Products Advisory Committee 11/n

prior to issuance of any EUA for a COVID-19 vaccine to discuss the EUA request and whether the available safety and effectiveness data support the authorization. A problem stems from thorny ethical questions about whether once a vaccine has been cleared for use by the FDA, 12/n

the people who were randomly assigned to receive a placebo in its clinical trial must be informed and offered vaccine. Vaccinating the people who received placebo injections would end the ability to continue to compare the two groups after what would have been a short trial. 13/n

Pfizer has indicated they plan to unblind their trial and offer vaccine to people in the placebo arm. Early unblinding of these trials runs counter to the FDA’s advice. FDA is urging vaccine manufacturers to keep their trials blinded as long as possible, to collect as much 14/n

data as they can. There is concern use of a vaccine under an EUA would interfere with long-term assessment of safety and efficacy in ongoing trials and potentially even jeopardize product approval and not only the first vaccine, but maybe even follow-on vaccines. Pfizer is 15/n

advancing its vaccine manufacturing programs and expected to be able to provide 100M doses by March 2021, enough for 50M people, and probably have about 40M doses, enough for 20M people, by the end of 2020. The vaccine will cost about $20 per dose, with two doses required, 16/n

the U.S. gvt acquired the initial doses and expects to provide them to the US public for free. I don't know about the plan for Kenya. Moderna with a similar mRNA vaccine is closely on the tail of Pfizer and will release their trial results soon. If their vaccine efficacy has 17/n

similar efficacy of the Pfizer mRNA vaccine, it will be strong validation of the utility of that novel vaccine platform. Moderna is contracted with the US gvt for $1.5B to produce 100M doses of the vaccine that also requires two doses. While it may take 2-3 weeks for the FDA 18/n

to give an EUA to Pfizer, the process afterwards will take 3-5 days. The Advisory Committee on Immunization Practice, is a committee within the CDC that provides advice and guidance on effective control of vaccine-preventable diseases in the U.S. civilian population (Kenya?) 19/n

There will be an emergency meeting of ACIP within 24-48 hours after the FDA has made its recommendations on the approval. At that meeting, ACIP members will vote on recommendations on dosage and a list of priority groups, which will become part of public health guidance 20/n

issued by the CDC to states and territories, on how to vaccinate populations effectively against COVID19. Those guidelines will also signal the federal government to start shipping vaccine vials out to hospitals and vaccination sites across the country. The goal is to begin 21/n

immunizations within 24 hours of ACIP recommendations. CDC has asked states to expedite the approval process for medical supply company McKesson so it can set up coronavirus vaccination sites across the U.S. by early November. The vaccine will be distributed in four phases, 22/n

with health-care workers, the elderly and people with underlying health conditions getting vaccinated first. Essential workers, teachers and people in homeless shelters as well as people in prisons would be next on the list, followed by children and young adults. 23/n

Currently it is unclear how long protection from any Covid vaccine would last. The duration of protection will only become clear after the vaccines are in use for a while. I am cautiously optimistic that mRNA vaccines from Pfizer and/or Moderna will begin immunization by 24/n

Christmas 2020 and will generally be available for vulnerable populations including elderly by Easter 2021. That timing from the first cases of COVID19 in January 2020 to effective and safe immunization in December 2020 will be a major biomedical success. That is for the US. 25/n

The above thread tells how organized and methodical things are in other countries. I am not sure our situation here is the same. With devolved health service delivery in Kenya, I am a strong proponent of a CDC-like institution to manage Public Health matters including pandemics.