Results for “fda” 461 found
The First Dose is Good
WSJ: The Covid-19 vaccine developed by Pfizer Inc. and BioNTech SE generates robust immunity after one dose and can be stored in ordinary freezers instead of at ultracold temperatures, according to new research and data released by the companies.
The findings provide strong arguments in favor of delaying the second dose of the two-shot vaccine, as the U.K. has done . They could also have substantial implications on vaccine policy and distribution around the world, simplifying the logistics of distributing the vaccine.
A single shot of the vaccine is 85% effective in preventing symptomatic disease 15 to 28 days after being administered, according to a peer-reviewed study conducted by the Israeli government-owned Sheba Medical Center and published in the Lancet medical journal. Pfizer and BioNTech recommend that a second dose is administered 21 days after the first.
The finding is a vindication of the approach taken by the U.K. government to delay a second dose by up to 12 weeks so it could use limited supplies to deliver a single dose to more people, and could encourage others to follow suit. Almost one-third of the U.K.’s adult population has now received at least one vaccine shot. Other authorities in parts of Canada and Europe have prioritized an initial shot, hoping they will have enough doses for a booster when needed.
Preliminary data also suggest that the other widely used vaccine in the U.K. developed by AstraZeneca PLC and the University of Oxford could have a substantial effect after a first dose .
The Israeli findings came from the first real-world data about the effect of the vaccine gathered outside of clinical trials in one of the leading nations in immunization against the coronavirus. Israel has given the first shot to 4.2 million people—more than two-thirds of eligible citizens over 16 years old—and a second shot to 2.8 million, according to its health ministry. The country has around 9.3 million citizens.
…”This groundbreaking research supports the British government’s decision to begin inoculating its citizens with a single dose of the vaccine,” said Arnon Afek, Sheba’s deputy director general.
The Israeli study is here. Data from Quebec also show that a single dose is highly effective, 80% or higher (Figure 3) in real world settings.
It’s becoming clearer that delaying the second dose is the right strategy but it was the right strategy back in December when I first started advocating for First Doses First. Waiting for more data isn’t “science,” it’s sometimes an excuse for an unscientific status-quo bias.
Approximately 16 million second doses have been administered in the US. If those doses had been first doses an additional 16 million people would have been protected from dying. Corey White estimates that every 4000 flu vaccinations saves a life which implies 4000 lives would have been saved by going to FDF. COVID, of course, is much deadlier than the flu–ten times as deadly or more going by national death figures (so including transmission and case fatality rate)– so 40,000 deaths is back of the envelope. Let’s do some more back-of-the-envelope calculations. Since Dec. 14, there have been approximately 10 million confirmed cases in the United States and 200,000 deaths. There are 200 million adults in the US so 1/1000 adults has died from COVID, just since Dec. 14. If we use 1/1000 as the risks of a random adult dying from COVID, then an additional 16 million vaccinations would have saved 16,000 lives. But that too is likely to be an underestimate since the people being vaccinated are not a random sample of adults but rather adults with a much higher risk of dying from COVID. Two to four times that number would not be unreasonable so an additional 16 million vaccinations might have avoided 32,000-64,000 deaths. Moreover, an additional 16 million first doses would have reduced transmission. None of these calculations is very good but they give a ballpark.
It is excellent news that the vaccine is stable for some time using ordinary refrigeration. Scott Duke Kominers and I argue that there is lot of unused vaccination capacity at the pharmacies and reducing the cold storage requirement will help to bring that unused capacity online. The announcement is also important for a less well understood reason. If Pfizer is only now learning that ultra-cold storage isn’t necessary then we should be looking much more closely at fractional dosing.
When I said that we should delay the second dose, people would respond with “but the companies say 21 days and 28 days! Listen to the science!”. That’s not scientific thinking but magical thinking. Listening to the science was understanding that the clinical trial regimen was designed at speed with the sole purpose of getting the vaccines approved. The clinical trial was not designed to discover the optimal regimen for public health. Don’t get me wrong. Pfizer and Moderna did the right thing! But it was wrong to think that the public health authorities could simply rely on “the science” as if it were written on stone. Even cold-storage wasn’t written on stone! Now that the public health authorities know that the clinical trial regimen isn’t written in stone they should be more willing to consider policies such as delaying the second dose and fractional dosing.
We are nearing the end in the US but delaying the second dose and other dose-stretching policies are going to be important in other countries.
Canada and First Doses First
…With such a highly protective first dose, the benefits derived from a scarce supply of vaccine could be maximized by deferring second doses until all priority group members are offered at least one dose. There may be uncertainty about the duration of protection with a single dose, but the administration of a second dose within 1 month after the first, as recommended, provides little added benefit in the short term, while high-risk persons who could have received a first dose with that vaccine supply are left completely unprotected. Given the current vaccine shortage, postponement of the second dose is a matter of national security that, if ignored, will certainly result in thousands of Covid-19–related hospitalizations and deaths this winter in the United States — hospitalizations and deaths that would have been prevented with a first dose of vaccine.
Danuta M. Skowronski, M.D.
British Columbia Centre for Disease Control, Vancouver, BC, Canada
[email protected]Gaston De Serres, M.D., Ph.D.
Institut National de Santé Publique du Québec, Quebec City, QC, Canada
That’s from a letter to the NEJM which also includes a debate on delaying the second dose and a poll (vote for delaying the second dose!). What I want to point out today is that the authors are experts from Canada. I believe that first doses first will save lives in the US but delaying the second dose and other dose-stretching policies are even more vital in countries where vaccines supplies are more limited than in the United States.
Canada and Novavax
Canada has made some smart moves with the Novavax vaccine. First, they initiated a rolling review of the Novavax vaccine in late January which suggests that they might authorize the vaccine based on the British trial before the US trial is concluded. The FDA will probably wait until the US trial is concluded. Second, Canada also signed a production agreement to bring some capacity online in Canada, although that will take time. That agreement, however, is on top of an advance purchase of 52 million doses with an option on another 24 million doses.
In short, if they act quickly, Canada could approve the Novavax vaccine before the United States and get a jump on its own vaccination efforts.
Against Regulatory Nationalism
I’ve long argued that if a drug or medical device is approved in another country with a Stringent Regulatory Authority it ought to be approved in the United States. But, of course, the argument is even stronger in the other direction. Drugs and devices approved in the United States ought to be approved elsewhere. Indeed, this is how much of the world actually works because most countries do not have capability to evaluate drugs and devices the way the FDA or say the EMA does. Although it’s the way the world works, few will admit it because that would violate pretensions of regulatory nationalism. Moreover, keeping up with pretenses means transaction costs and unnecessary delays.
The price of such regulatory nationalism can be very high as indicated in this interview with Adar Poonawalla, chief executive of the Serum Institute of India (SII), the world’s largest producer of vaccines.
Some people think the reason that rollout has been slow in many countries is because the developers who hold the patents on the vaccines have licensed too few manufacturers to make them. Do you agree?
No. There are enough manufacturers, it just takes time to scale up. And by the way, I have been blown away by the cooperation between the public and private sectors in the last year, in developing these vaccines. What I find really disappointing, what has added a few months to vaccine delivery – not just ours – is the lack of global regulatory harmonisation. Over the last seven months, while I’ve been busy making vaccines, what have the US, UK and European regulators been doing? How hard would it have been to get together with the World Health Organization and agree that if a vaccine is approved in the half-dozen or so major manufacturing countries, it is approved to send anywhere on the planet?
Instead we have a patchwork of approvals and I have 70m doses that I can’t ship because they have been purchased but not approved. They have a shelf life of six months; these expire in April.
Did you get that? Regulatory nationalism has added months to vaccine delivery and now threatens to put to waste millions of stockpiled doses.
Addendum: See also Scott Sumner on the costs of regulatory nationalism.
Half Doses of Moderna Produce Neutralizing Antibodies
A new phase II study from Moderna shows that half-doses (50 μg) appear to be as good as full doses (100 ug) at generating correlates of protection such as neutralizing antibodies.
In this randomized, controlled phase 2 trial, the SARS-CoV-2 vaccine candidate mRNA-1273, administered as a two-dose vaccination regimen at 50 and 100 μg, exhibited robust immune responses and an acceptable safety profile in healthy adults aged 18 years and older. Local and systemic adverse reactions were mostly mild-to-moderate in severity, were ≤4 days of median duration and were less commonly reported in older compared with younger adults. Anti-SARS-CoV-2 spike binding and neutralizing antibodies were induced by both doses of mRNA-1273 within 28 days after the first vaccination, and rose substantially to peak titers by 14 days after the second vaccination, exceeding levels of convalescent sera from COVID-19 patients. The antibodies remained elevated through the last time point assessed at 57 days. Neutralizing responses met criteria for seroconversion within 28 days after the first vaccination in the majority of participants, with rates of 100% observed at 14 and 28 days after the second vaccination. While no formal statistical testing was done, binding and neutralizing antibody responses were generally comparable in participants who received the 100 μg mRNA-1273 and the 50 μg dose at all time points and across both age groups. Overall, the results of this randomized, placebo-controlled trial extend previous immunogenicity and safety results for mRNA-1273 in the phase 1 study in an expanded cohort including participants older than 55 years of age [16, 19].
[These data] confirm that a robust immune response is generated at both 50 and 100 ug dose levels.
As I wrote earlier, halving the dose is equivalent to instantly doubling the output of every Moderna factory.
See my piece in the Washington Post on getting to V-day sooner for an overview of dose stretching strategies.
Addendum: France says one dose is sufficient for previously COVID infected.
The Big Push: A Plan to Accelerate V-Day
In the Washington Post I have an extensive piece on accelerating progress to V-day, Vaccine or Victory day, the day everyone who wants a vaccine has gotten one. I cover themes that will be familiar to MR readers, including First Doses First, Fractional Dosing, Approving More Vaccines and DePrioritization to Expand Delivery. I won’t belabor these points here but the piece is useful at collecting all the arguments in one place and there are lots of authoritative links.
One point I do want to make is that all the pieces of the “Tabarrok plan,” if you will, fit together. Namely, use First Doses First to make a big push to get as many people vaccinated with first doses as possible in the next 90 days. Approve more vaccines including Johnson & Johnson, AstraZeneca and others and make them available to anyone, anywhere–that is possible because these vaccines don’t require significant cold storage, J&J is a single shot and AZ is better with a second shot at 12 weeks or later all of which eases distribution.
…some people argue that adding a third (or fourth) vaccine might not help because of persistent delivery logjams at the state and local levels. But we know there is unused distributional capacity, even for the supply we do have. The United States is currently administering about 1.5 million coronavirus vaccine shots per day. While that sounds like a lot, for comparison consider that in September — during the pandemic, when social distancing measures were in full effect — we vaccinated for the seasonal flu in some weeks at the rate of 3 million people a day.
There are two main reasons the rollout has been so slow. First, the Moderna and especially the Pfizer vaccines require ultracold storage. (The Johnson & Johnson and AstraZeneca doses can be stored at ordinary refrigerator temperatures.) Second, we have tried to prioritize vaccinations using a confusing mishmash of age, health conditions and essential-worker status that differs by state and sometimes even by county. “Confirming such criteria is complicated at best, and it’s probably not even feasible to try under conditions of duress,” as Baylor’s Hotez puts it.
Arguments continue about prioritization lists, and the idea of tossing them entirely would cause a political fight. But there is a compromise at hand: Quickly approve the Johnson & Johnson and AstraZeneca vaccines and make them — and only them — available to anyone, anywhere. Keeping things simple is a sure way to increase total vaccinations. With no cold-storage requirement, the new vaccines could be administered by any of the 300,000 pharmacists and more than 1 million physicians in the United States authorized to deliver vaccines, most of whom are not now giving Pfizer or Moderna shots.
Friday assorted links
1. Ezra Klein on California (NYT), right on the mark.
2. Interview with Michael Mina, too much common sense for it ever to be heeded.
3. Developing versatile vaccine platforms.
4. The Biden Administration hesitates to name an FDA head.
5. Pigs can play video games with their snouts.
6. Father of Britney Spears must share conservatorship.
8. Military officials were unaware of danger to Pence’s nuclear football during the riots.
The Rot is Deep
It’s not just the FDA, or the CDC, or Trump. The rot is deep.
Defense News: Imagine that, for years, the U.S. intelligence community warns about a specific national security threat that could come to pass. One day, it finally does. International observers sound the alarm. The press picks up the scent. Within two weeks, the threat breaches U.S. defenses, and two weeks after that, Americans begin to die. But it takes six months for the U.S. Army to agree to fill the capability gap with a counter-weapon of its own design, and more than a year after the first American casualties, the Army rolls it out.
This, in fact, just happened. It’s the timeline of the Army’s response to the COVID-19 pandemic, an unambiguous threat to life and livelihoods.
It took a full year for the service to design, approve and distribute a face mask — called a Combat Cloth Face Covering, or CCFC — for its soldiers, an effort that required an additional $43.5 million in contracts to provide temporary solutions. That comes out to about $45 per mask, if you assume every active-duty, National Guard and Reserve soldier received one. A pack of 20 N95 masks at Home Depot costs about $20.
And yet, the Army congratulated itself on the “expedited” timeline, compared to the 18- to 24-month procurement cycle such an effort would normally take.
“The system worked as designed,” tweeted a former Marine.
And that is precisely the problem.
Sunday assorted links
1. The regulatory, status quo bias in public health commentary: “Do any of the experts arguing that it’s wrong for Americans to demand access to the AstraZeneca vaccine also advise residents of the UK, EU, and 15 other countries to delay taking it until our FDA grants authorization?”
3. People are fed up with broken vaccine appointment tools — so they’re building their own (Technology Review).
4. NASA prize to make food on the Moon, Mars.
5. The UK put a venture capitalist in charge of its vaccine procurement.
6. Cuba will allow more small business.
7. Ross Douthat on the Romney family plan (NYT).
8. It seems fear of kidnapping is severely limiting mobility in Haiti, even for the non-wealthy (NYT).
How to Double the Number of Moderna and Pfizer Factories
Theory and data both suggest that a much smaller dose–perhaps as low as 1/4 the current dose—of both the Moderna and Pfizer vaccines are as effective as a larger dose. Half doses of Moderna and Pfizer would be equivalent to instantly doubling the number of Moderna and Pfizer factories and would save hundreds of thousands of lives and be worth hundreds of billions of dollars in world GDP. Clinical data from adults 18-55 from the Moderna Phase II trial already suggest that quarter-doses are effective, which is why Operation Warp Speed chief, Moncef Slaoui has advocated for half-doses (leaving plenty of margin).
“We know that, for the Moderna vaccine, giving half of the dose to people between the ages of 18 and 55, two doses [at] half the dose … we know it induces identical immune response” to the currently authorized dose, Slaoui added.
Another way of putting this is that new clinical trials on dosing would be tremendously valuable. Ideally, we could use correlates of protection and do a bridging trial to infer the effectiveness of half-doses. The FDA has already said they will accept a bridging trial for new mRNA vaccines for variants, which is the right decision. The FDA should also accept a bridging trial for new dosing.
If new clinical trials are deemed necessary, dosing trials could be run as challenge trials but instead of comparing half-doses to placebo we would compare full-doses to half-doses. Thus, everyone in the challenge trial would be vaccinated, massively lowering risks. If we can’t do challenge trials even with vaccinated volunteers (!) then let’s get started on clinical trials. The NIH created the ACTIV program to speed clinical trials. Use it.
New clinical trials are valuable not just for dosing but also for approving new vaccines. Equivalence trials on the Sputnik and Sinopharm vaccines, for example, could be very valuable. In other words, we would trial Sputnik and Sinopharm against Pfizer and Moderna. A lot of people would be quite willing to join a trial in which the worst outcome is most likely getting a somewhat less effective vaccine–that’s much better than no vaccine!
The value of experiments, or let’s call them pilot studies, right now is immense. We can do pilot studies on half dosing for Moderna and Pfizer vaccines much faster and cheaper than we can build twice as many factories. So let’s do it!
Just A Few Weeks Delay
NYTimes: Federal regulators could decide within a few weeks whether to allow Moderna, the Massachusetts biotech company that developed one of the two federally authorized Covid-19 vaccines, to increase the number of doses in its vials — which could accelerate the nation’s vaccination rate.
Moderna is hoping to raise the number of doses in its vials to as many as 15 from the current 10 doses, a potential 50 percent increase. The proposal reflects the fact that the company has been ramping up production of its vaccine to the point where the final manufacturing stage, when it is bottled, capped and labeled, has emerged as a roadblock to expanding its distribution.
The FDA will decide in a few weeks???! That is not quick, bold, and decisive action.
Thousands of people have already died over a few weeks delay–multiple times. It’s true that there are tradeoffs but the FDA has no special knowledge or ability to navigate those tradeoffs. Let Moderna make the decision in consultation with vaccinators on the front lines.
The Experts are Very Worried
Here is an interview with Dr. Peter Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine and the lead developer of a COVID vaccine being produced in India. He thinks the AstraZeneca vaccine should be approved immediately, as I have long argued.
President Biden himself announced Tuesday that we’re going to have maybe enough additional doses of the mRNA vaccines to fully vaccinate 300 million Americans by the end of summer or fall.
I’m saying, “Well, no, that’s that’s not gonna work.” Telling us “by the fall” is like telling us “when the glaciers are gonna come back down from Quebec.” I mean, that’s not adequate.
We’re going to have to figure out a way to vaccinate the American people by late spring. That’s a tall order. To beat back the virus we need to give two doses to three-quarters of the population, to 246 million Americans. That’s half a billion immunizations. To get there, we’d need a rate of immunizations two or three times higher than what’s proposed.
….We need vaccinations now.
..things have been slowed down with the AstraZeneca-Oxford adenovirus vaccine. My understanding is that the FDA insisted that they conduct a full-scale Phase Three trial in the U.S., and we won’t have results for that until April. Meanwhile, the European Medicines Agency, the EMA, is going to make a ruling on the AstraZeneca Oxford vaccine on Friday based on studies done in Europe and also probably on data from Brazil and South Africa. [The EMA authorized, AT].
Those are large, reliable studies?
Yeah….Because of these new variants, there’s great urgency here in the U.S. So I’m saying that sometimes we have to do things that take us out of our comfort zone in order to save lives. That means, rather than focusing only on the new study that we’re doing in the U.S., we also look at the dossier presented to the EMA.
As a regulatory agency the EMA is up there with our U.S. FDA. They’re the two best regulatory agencies in the world. So if they sign off, I think we should say, “Look, let’s do it. Let’s use that vaccine.”
We’ve already bought 300 million doses of the AstraZeneca-Oxford vaccine. We’ve paid for it — over a billion dollars — so let’s use it.
…And there’s also the recombinant protein vaccine our lab has developed at Baylor College of Medicine and Texas Children’s Hospital. In India they’re scaling that up to a billion doses. Nobody from the White House has approached us to say, “Hey, Peter, what can we do to bring that vaccine in.”
There seem to be blinders: All they can see is getting the mRNA vaccines. I don’t quite know what’s driving that. We have to figure out a way to bring the other ones on board.
And soon! We’re in the eye of the hurricane.
Hat tip: Jim Ward.
Saturday assorted links
1. Henry Farrell reviews Mike Konczal.
2. Wombats, Cowen’s Second Law, and to the benefit of all. It is an article that keeps on surprising you.
3. Why was autocratic rule more stable in China than in Europe?
4. One guy who helped to drive GameStop (WSJ).
5. A review of the definition of market manipulation, for those of us who need it.
6. Our FDA regulatory state is failing us against Curative as well.
7. Game theory and the search for life, clever.
Scott Sumner on Vaccine Nationalism
EconLib: Experts in the UK have looked at the AstraZenaca vaccine and found it to be safe and effective. And yet Americans are still not allowed to use the product. So if paternalism is not the actual motive, why do progressives insist that Americans must not be allowed to buy products not approved by the FDA? What is the actual motive?
The answer is nationalism. The experts who studied the AstraZenaca vaccine were not American experts, they were British experts. Can this form of prejudice be justified on scientific grounds? Obviously not. There has been no double blind, controlled study of comparative expert skill at evaluating vaccines. We have no way of knowing whether the UK decision is wiser than the FDA decision. Instead, the legal prohibition is being done on nationalistic grounds. We are told to blindly accept the incompetence of British experts, without any proof. (And even if you believed there was solid evidence that one country’s experts were better than another, it would not explain why each developed countries relies on their own experts. They can’t all be best!)
These debates always end up being like a game of whack-a-mole. Shoot down one argument and regulation proponents will simply put forth another. Their minds are made up. You say people shouldn’t be allowed to take a vaccine unless experts find it to be safe and effective? OK, the UK experts did just that. You say that only the opinion of US experts counts because our experts are clearly the best? Really, where is the scientific study that shows that our experts are the best? I thought you said we needed to “trust the scientists”? Now you are saying we must trust the nationalists?
…what’s wrong with the following three-part system of regulation as a compromise solution:
1. FDA approved drugs can be consumed by anyone in America.
2. Drugs approved by any of the top 20 advanced countries (but not the FDA) can be consumed by anyone willing to sign a consent form indicating that they understand the FDA has not approved this product. I’ll sign for AstraZeneca. (The US government puts together a list of 20 reputable countries.)
3. Drugs approved by none of the top 20 developed economies will still be banned.
This is what regulation would look like if paternalism actually were the motivating factor. But it’s not. It’s Trump-style nationalism that motivates progressives to insist that only FDA approved drugs can be sold in America. They may look down their noses at Trump, but they implicitly share his nationalism.
I agree, of course, and have long supported Pharmaceutical Reciprocity.
The Invisible Graveyard is Invisible No More
We called it the invisible graveyard, the place they buried people killed by FDA delay. Back then only a few of us–mostly libertarians long practiced in seeing the invisible hand–could see the invisible graveyard. Normal people looked at us oddly and quickly ran away when we frantically pointed to the dead. “There! there! Can’t you see the bodies?” Now, however, the veil has been lifted and even normal people see.
Here is Ezra Klein writing in the NYTimes:
The problem here is the Food and Drug Administration. They have been disastrously slow in approving these tests and have held them to a standard more appropriate to doctor’s offices than home testing. “The F.D.A. needs to catch up to the science,” Mina said, frustration evident in his voice. “They are inadvertently killing people by not following the science.” On my podcast, I asked Vivek Murthy, President Biden’s nominee for surgeon general, whether the F.D.A. had been too cautious. “I do think we’ve been too conservative,” he told me. Murthy went on to argue that there’s a difference between the diagnostic testing doctors do and the surveillance testing the public could do and that the F.D.A. had failed to appreciate the difference. Speeding the F.D.A. on this issue will be an early, and crucial, test for the Biden administration. In this case, Democrats need to deregulate.
Even back in December when I was tweeting from the rooftops things like:
Your daily reminder that 14,696 people have died from COVID in the United States since Pfizer applied for an EUA from the FDA.
people argued that I was exaggerating the simple math of FDA delay. Today, however, the reality of deadly delay is almost conventional wisdom. Here’s Klein again:
The new strains spread quickly. The speed of our countermeasures will decide our fate. What feel like reasonable delays in our normal experience of time — a few weeks here for Congress to debate a bill, a few weeks there for the F.D.A. to hold meetings — could lead to the kind of explosive infections that overwhelm our hospitals and fill our morgues.