Results for “fda”
461 found

*The Messenger*

The author is Peter Loftus, and the subtitle is Moderna, the Vaccine, and the Business Gamble That Changed the World.  An excellent book, here is one very short excerpt:

The FDA usually follows a rigid process of interacting with the drug companies it regulates.  Normally, it can take months for a company to schedule an in-person meeting with the FDA.

Culture dies hard, here is Alex on the Invisible Graveyard.  And this:

…Moderna executives expressed confidence they could hit the enrollment targets without significantly slowing down overall enrollment.  But Fauci and Slaoui said they actually wanted Moderna to slow down overall enrollment in order to ensure they enrolled more minorities.

The book estimates the delay here at three weeks — how many lives was that in winter of 2020/2021?

Labor Unions Reduce Product Quality

A very nice paper in Management Science by Kini, Shen, Shenoy and Subramanian finds that labor unions reduce product quality. Two strengths of the paper. First, the authors have relatively objective measures of product quality from thousands of product recalls mandated by the FDA, the Consumer Product Safety Commission and the National Highway Traffic Safety Administration covering many different industries. Second the authors use 3 different methods. First, they find that unionized firms are more likely to have recalls than non-unionized firms (a simple difference in means subject to many potential cofounds but I still like to see the raw data), second they find that in a panel model with industry and year fixed effects and other controls that firms which are more unionized have a greater frequency of product recalls. Finally they find that firms where the union just barely won the vote are more likely to have subsequent product recalls than firms for which the union just barely lost the vote–a regression discontinuity study.

In this paper, we study the impact of labor unions on product quality failures. We use a product recall as our measure of quality failure because it is an objective metric that is applicable to a broad cross-section of industries. Our analysis employs a union panel setting and close union elections in a regression discontinuity design framework to overcome identification issues. In the panel regressions, we find that firms that are unionized and those that have higher unionization rates experience a greater frequency of quality failures. The results obtain even at a more granular establishment level in a subsample in which we can identify the manufacturing establishment associated with the recalled product. When comparing firms in close elections, we find that firms with close union wins are followed by significantly worse product quality outcomes than those with close union losses. These results are amplified in non–right-to-work states, where unions have a relatively greater influence on the workforce.

The authors put more weight on financial strains caused by unionization as a mechanism whereas my story would be that unionization prevents firms from disciplining shoddy workers and that leads to lower product quality. Note that my theory would also cover teachers unions which the author’s mechanism would not.

Hat tip: Luke Froeb.

Photo Credit: Joe Piette.

Operation Warp Speed Should Not have Been Disbanded

Operation Warp Speed produced a new vaccine for a novel virus in record time but when Operation Warp Speed was disbanded by the Biden administration, vaccine research and development slowed from warp speed to impulse power. It’s ridiculous that it is taking longer to develop and deploy tweaks to the mRNA vaccines to deal with new variants than it took to develop the original vaccines from scratch. By the time we get an Omicron-specific vaccine that variant will have disappeared. This is no way to run a civilization.

We should be investing in a universal vaccine for all sarbecoviruses (of which SARS-COV-II is a member) and, as I have long argued (and here) a nasal vaccine. We need not exaggerate, for the vaccinated the dangers are no longer acute, but we should be better prepared for future variants and the savings from less sickness alone easily trump the costs. Indeed, the issue isn’t even so much the cost as the need to coordinate regulatory agencies, as OWS did, to speed approvals and reduce bureaucracy.

Patrick Collison, writing at Slow Boring, has the details (as Tyler also noted):

Despite excellent technology and promising early results in animal models, we estimate that the very earliest we will have access to these vaccines in humans is 2024. These groups need to run primate trials, then run human clinical trials, and then ramp manufacturing and distribution. Beyond having to jump through a lot of hoops, we’ve observed that they’re frequently tripped up by stupid things outside of their control, any one of which may hold their work back by months. (One group’s monkeys have been delayed by US Customs, which will push the start of their primate trial back ‘till September. Another is struggling to obtain necessary adjuvants. Multiple groups are unable to get access to current mRNA vaccines for research purposes because of legal barriers.) All groups we’ve interacted with are underfunded compared to what would be ideal.

Broadly speaking, the holdups involve some combination of logistical challenges and regulatory requirements, and the intersection between both. (You don’t in principle have to run a primate trial, but the FDA makes it harder to run a human trial if you don’t. You don’t in principle need to use “acute infection” as a trial endpoint; you could also use neutralizing antibody titers, which would be much faster and simpler.)

To speed things up:

  • We should lower the barrier for human clinical trials and use simpler endpoints. For many vaccine candidates, we could run human trials concurrent with primate trials (once basic safety data has been obtained). In humans, we don’t need to repeat Phase I trials for platforms that have already been validated and derisked. (In this vein, the FDA’s recent announcement about not requiring trials for updated platforms was encouraging.)
  • We should help these groups to scale manufacturing faster. Operation Warp Speed itself cost $10 billion; a second incarnation, with a tenth of that budget, could almost certainly accomplish a great deal.

…In our view it is probably true that, with competent execution, we could roll out pan-variant COVID vaccines before the end of 2022. Actually making that happen would require significant and coordinated logistical, regulatory, and administrative action. However, it would by no means be impossible. Not having pan-variant vaccines in 2022 is best thought of as a choice.

A Bloody Waste

Image by Satheesh Sankaran from Pixabay

Hemochromatosis is a disorder in which extra iron builds up in the body. A potential treatment is phlebotomy so patients with hemochromatosis want to donate blood and donate regularly. The American Red Cross, however, does not permit people with hemochromatosis to donate blood. Why not? The blood is safe and effective. The blood of these patients doesn’t have much, if any, extra iron (the iron builds up in the body not so much in the blood per se). The “problem” is that people with hemochromatosis benefit themselves by giving blood and for this reason their blood is considered tainted by the American Red Cross.

The American Red Cross, which controls about 45% of the nation’s blood supply, does not currently accept donations from people with known hemochromatosis. Everyone agrees that the blood is safe and of high quality. There is no risk of passing on a genetic disease through blood transfusions. But the Red Cross has a long-standing policy that potential donors are not allowed to receive direct compensation for their donation (beyond the usual orange juice and cookie). Because people with hemochromatosis would otherwise have to pay for their therapeutic phlebotomies, they would in effect be getting something of value for being able to donate for free. Thus the Red Cross has ruled that such donations violate their policy.

The FDA does allow patients with hemochromatosis to donate blood so long as there is no charge for phlebotomy (i.e. so long as patients don’t have an incentive to lie to obtain free phlebotomy via donation.) Some countries and some blood banks within the US do accept donations from people with hemochromatosis as do some Kaiser locations. But the American Red Cross is the biggest collector of blood and so it is very often the case that when people with hemochromatosis get a phlebotomy their blood is simply thrown away.

Once a week, Dan Gray pays to have a pint of blood taken at Franklin Memorial Hospital. And once a week, that blood is thrown out rather than donated to someone in need.

It frustrates him.

“You could take a pint out of me, a pint out of you and a pint out of somebody else and play three-pint monte with it and they wouldn’t know whose is whose,” Gray said. “As far as the analysis of it, no one would know.”

and here:

The Cape Fear Valley Blood Donor Center put out a desperate call this past week for blood donations.

…Every time Carol Barbera hears of such pleas, she gets upset. She was once an avid blood donor and would be one still.

She also has plenty of blood to give.

A medical condition requires her to have a pint of blood drawn at least every two months. The blood is perfectly usable as donor blood. Instead, it goes straight into medical waste.

The Red Cross’s antipathy towards donations from people with hemochromatosis appears to stem from a confused ethical view that incentivized donations are either “coerced” or “non-altruistic” and an old bias against paid donations coming from Titmuss. Actual studies of paid donation, however, show that incentives increased donations without reducing quality.

Thus, as far as the evidence is concerned, there are no good reasons to prohibit people with hemochromatosis from donating blood and given the repeated shortages of blood in the United States there are many good reasons for allowing them to donate.

Hat tip: The tireless Peter Jaworski.

Testing Freedom

I did a podcast with Brink Lindsey of the Niskanen Center. Here’s one bit on the FDA’s long-history of banning home tests:

Brink Lindsey: …it’s on the rapid testing that we had inexplicable delays. Rapid tests, home tests were ubiquitous in Europe and Asia months before they were in the United States. What was going on?

Alex Tabarrok: So I think it’s not actually inexplicable because the FDA has a long, long history of just hating people testing themselves. So the FDA was against pregnancy tests, they didn’t like that, they said women they need to consult with a doctor, only the physician can do the test because literally women could become hysterical if they were pregnant or if they weren’t pregnant, this was a safety issue. There was no question that the test itself was safe or worked. Instead what the FDA said, “We can regulate this because the user using it, this could create safety issues because they could commit suicide or they could do something crazy.” So they totally expanded the meaning of safety from is the test safe to can somebody be trusted to use a pregnancy test?

Then we had exactly the same thing with AIDS testing. So we delayed personal at-home tests for AIDS for literally 25 years. 25 years these tests were unavailable because the FDA again said, “Well, they’re dangerous.” And why are they dangerous? “Well, we don’t know what people will do with this knowledge about their own bodies.” Now, of course, you can get an HIV test from Amazon and the world hasn’t collapsed. They did the same thing with genetic tests from companies like 23andMe. So I said, “Our bodies ourselves, our DNA ourselves.” That people have a right to know about the functioning of their own bodies. This to me is a very clear violation of the Constitutions on multiple respects. It just stuns me, it just stuns me that anybody could think that you don’t have a right to know, we’re going to prevent you from learning something about the operation of your own body.

Again, the issue here was never does the test work. In fact, the labs which produce these tests, those labs are regulated outside of the FDA. So whether the test actually works, whether yes, it identifies this gene, all issues of that nature, what is the sensitivity and the specificity, are the tests produced in a proper laboratory, I don’t have a lot of problem with that because that’s all something which the consumers themselves would want. What I do have a problem with is then the FDA saying, “No, you can’t have access to this test because we don’t know what you’re going to do about it, what you’re going to think about it.” And that to me is outrageous.

Here’s the full transcript and video.

Infant Formula, Price Controls, and the Misallocation of Resources

For the week of April 3, at least 12 states faced out of stock rates higher than 40 percent, including Connecticut, Delaware, Montana, New Jersey, Rhode IslandI’ve been reluctant to write about the shortage of infant formula simply because it’s so tiring to say the same thing over and over again. Obviously, this is a classic case where the FDA should allow imports of any food or baby formula approved by a stringent authority. (Here’s the US Customs and Border Patrol bragging about how they nabbed 588 cases of infant formula from Germany and the Netherlands as if it were cocaine.) Scott Lincicome has an excellent run down which covers not just the FDA but the problems caused by trade regulation and the WIC program as well.

What I want to do is focus on something less discussed: Why does the shortage vary across the country and even city by city?

I believe one reason is implicit price controls, either due to fear of regulatory backlash, regulatory constraints through other programs, or a misplaced desire not to upset consumers.

Price controls create shortages–that much is well known–but they also create a misallocation of goods. No doubt you have seen pictures from the 1970s of long lines of cars waiting to get gasoline. But there weren’t lineups everywhere at all times–rather we had the strange situation where there were shortage of gasoline in some places while, just a hundred miles away, there was plenty. Or shortages one day and surpluses the next.

Prices rationally allocate goods across space and time in response to shifts in demand and supply. If demand increases in one place, for example, prices rise, creating an incentive to bring in supplies from elsewhere. A rising price signals where supplies are needed and creates an incentive to deliver. Or, as Tyler and I put it, A price is a signal wrapped up in an incentive. A price controlled below the market price creates a shortage and it also kills the signaling and incentive function of prices. The result is allocational chaos: Shortages in some places and times and excess supply in other places and times.

In fact, price controls in a capitalist economy give you a window onto a planned economy. If you think of communism as a system of universal price controls this allocation chaos is the essence of why a communist state cannot rationally allocate resources.

Tyler and I discuss allocational chaos in our chapter on price controls in Modern Principles of Economics. See also this excellent video.

Saturday assorted links

1. Thomas Schelling 1963-64 syllabus and final exam.

2. On Srinivasan and sex.

3. Transitioning to post-quantum cryptography?

4. Do insects have culture?

5. There are fewer Karens.

6. “The FDA won’t allow European formulas to be sold here because of inane labeling concerns…

7. “New funding effort will deploy a corps of scientist ‘scouts’ to spot innovative ideas.

8. Biden administration seeking to stymie charter schools (NYT).  #TheGreatForgetting

China’s Bizarre Authoritarian-Libertarian COVID Strategy

It’s difficult to understand China’s COVID strategy. On the one hand, China has confined millions of people to their homes, even to the extent of outlawing walking outside or having food delivered. Many thousands of other people have been taken from their homes and put into quarantine centers. On the other hand, vaccination is not mandatory! I can understand authoritarianism. I can understand libertarianism. I have difficulty understanding how jailing people, potentially without food, is ok but requiring vaccinations is not. (Here’s a legal analysis of China’s vaccine policy.) Moreover, put aside making vaccines mandatory because as far as I can tell, China has only recently started to get serious about non-coercive measures to vaccinate the elderly. The Washington Post notes:

The vaccination drive has been mild compared to some of the other pandemic-control measures and did not prioritize the elderly. Some younger people have been required to get vaccinated for their jobs, but vaccination of retirees remains optional. Incentives like eggs, grains and other foodstuffs — a staple of China’s vaccination drive since last year — are now being bolstered by home checkups, mobile clinics and the widespread mobilization of public servantsto ensure the elderly get shots.

China is shutting down factories costing its economy trillions of dollars and the best they come up with to get elderly people vaccinated is egg incentives???!

It’s difficult to understand what the Chinese leadership is thinking. It’s conceivable that the Chinese vaccines are much less effective than we have been led to believe but that seems unlikely. As far as we can tell the Chinese vaccines are not quite as good as the mRNA vaccines but good enough to prevent severe disease and pass FDA approval in the United States. My best guess is that President Xi Jinping is so powerful and insulated from reality and alternative viewpoints that he is just soldiering on either oblivious to the pain and foolishness of his policies or indifferent, much like Mao before him during the great famine.

Thursday assorted links

1. Kafka and sexual shame.

2. Do beautifying filters improve your job chances?

3. Brian Eno documentary on the way.

4. FDA still crazy with the vaccines for kids.  Keep in mind the only thing the “experts” have ever resigned over is when boosters were pushed through.

5. Can the Solomons PM use Chinese police to stay in power?  Don’t they know about Lando K.?

6. How to read intellectuals like a portfolio.  Including Ann Coulter and Matt Yglesias and yours truly, among others.

What Operation Warp Speed Did, Didn’t and Can’t Do

Operation Warp Speed was a tremendous success and one that I was pleased to support from the beginning. Many people, however, are concluding from the success of OWS that big Federal funding can solve many other problems at the same speed and scale and that is incorrect.

First, it’s important to understand that OWS did not create any scientific innovations or discoveries. The innovative mRNA vaccines are rightly lauded but all of the key scientific ideas behind mRNA as a delivery mechanism long predate Operation Warp Speed. The scientific advances were the result of many decades of work, some of it supported by university and government funding and also a significant fraction by large private investments in firms such as Moderna and BioNTech. It was BioNTech recall that hired Katalin Karikó (and many other mRNA researchers) when she couldn’t get university or government funding. Since OWS created no new scientific breakthroughs there isn’t much to learn from OWS about the efficacy of large scale programs for that purpose.

Second, it’s important to understand that we got lucky. OWS made smart bets and the portfolio paid off but it could have failed. Indeed, some OWS bets did fail including the Sanofi and Glaxo-Smith-Klein vaccine and the at-best modest success of Novavax. Many other vaccines which we didn’t invest in but could have invested in also failed. To be clear, my work with Kremer et al. showed that these bets and more were worth taking but one should not underestimate the probability of failure even when lots of money is spent.

So what did Operation Warp Speed do? There were four key parts to the plan 1) an advance market commitment to buy lots of doses of approved vaccines–this was important because in past pandemics vaccines had entered development and then the disease had disappeared leaving the firms holding the bag with little to show for their investment 2) the lifting of FDA regulations to allow for accelerated clinical trials, for example, phase 3 trials could start before phase 2 trials were fully complete 3) government investment in large clinical trials–clinical trials are the most expensive part of the development process and by funding the trials generously, the trials could be made large which meant that they could be quick 4) government investment in capacity, building factories not just for the vaccines but also for the needles, vials and so forth, even before any of the vaccines were approved–thus capacity was ready to go. All of these steps shaved months, even years, off the deployment timeline.

The key factor about each of these parts of the plan was that we were mostly dealing with known quantities that the government scaled. It’s known how to run clinical trials, it’s known how to produce vials and needles. The mRNA factories were more difficult but scaling problems are more easily solved with investment than are invention problems. It’s also known how to lift government regulations and speed the bureaucracy. That is, no one doubts that lifting regulations and speeding bureaucracy is within our production possibilities frontier.

It also cannot be underestimated that OWS funded people who were already extremely motivated. The Pfizer and Moderna staff put in near super-human effort–many of them felt this was the key moment of their life and they stepped up to their moment. OWS threw gasoline on fire–don’t expect the same in a more normal situation.

Another factor that people forget is that with vaccines we had a very unusual situation where the entire economy was dependent on a single sector–a macroeconomic O-ring. As a result, the social returns to producing vaccines were easily a hundred times (or more) greater than any potential vaccine profits. Thus, by accelerating vaccine production, OWS could generate tremendous returns. Most of the time, markets internalize externalities imperfectly but reasonably well which means that even if you accelerate something good the total returns aren’t so astronomical that you can’t overspend or spend poorly. Governments can spend too much as well as too little so most of the time you have to factor in the waste of overspending even when the spending is valuable–that problem didn’t really apply to OWS.

So summarizing what do we need for another OWS? 1) Known science–scaling not discovering, 2) Lifting of regulations 3) Big externalities, 4) Pre-existing motivation. Putting aside an Armageddon like scenario in which we have to stop an asteroid, one possibility is insulating the electrical grid to protect North America from a Carrington event, a geomagnetic storm caused by solar eruptions. (Here is a good Kurzgesagt video.) Does protecting the grid meet our conditions? 1) Protecting the electrical grid is a known problem whose solution does not require new science 2) protecting the grid requires lifting and harmonizing regulations as the grid is national/inter-national but the regulations are often local, 3) The social returns to power far exceed the revenues from power so there are big externalities. Indeed, companies could have protected the grid already (and have done so to some extent) but they are under-incentivized. (The grid is aging so insulating the gird could also have many side benefits.) 4) Pre-existing motivation. Not much. Can’t have everything.

I think it’s also notable that big pandemics and solar storms seem to occur about once in every one hundred years–just often enough to be dangerous and yet not so often that we are well prepared.

Thus, while I think that enthusiasm for an “OWS for X” is overblown, there are cases–protecting the grid is only one possibility–where smart investments could pay big returns but they must be chosen carefully in light of all the required conditions for success.

Your Presidential Picks

Conor Friedersdorf asks:

“You can appoint any American citizen to one term as president,” I wrote earlier this week, “so long as your choice has never run for president before. Who do you appoint to the White House and why?”

and gets some interesting answers including these two:

“Austin makes a case for the public-radio host Kai Ryssdal, highlighting parts of his résumé I’d never known about:

Born in the U.S., but grew up partially overseas. MA in national security studies from Georgetown. [Flew] airplanes off of aircraft carriers in the US Navy. Pentagon staff officer. U.S. Foreign Service. Great communication skills, as heard on his hit radio show Marketplace, where he breaks down economics and markets both foreign and domestic. After he left the Navy he would ride his bike to work at a Borders for $7 an hour. He’s got an unbelievably impressive résumé with real world experience in National Security, International Relations, China Policy, US Military policy, economics, and the markets. Plus he knows what it’s like to work a real job like the rest of us. And he speaks Chinese! That’s huge. I would get behind him any day of the week.

Russell picked one of my favorite public intellectuals:

I’d like to appoint Tyler Cowen as president—besides being an uber-rationalist, we should give him a chance to put his state capacity libertarianism idea into practice. He is also one of the best identifiers of talent possibly on Earth, so we know we would get a dream team administration, likely composed of heterodox thinkers of diverse and opposing views who could shake everyone out of complacency. Finally, he has studiously managed to avoid being labeled as particularly associated with either party, so it’s possible that popular opinion wouldn’t know what to make of it all, giving the Cowen administration a chance to chart some new path, independent of pre-established partisan biases. Magical thinking? Maybe, but no less than we’ve got permeating our politics now.”

Good picks. I’d imagine that Cowen would appoint a pretty good FDA commissioner, or at least try.

How many lives were lost because of the vaccines holdup?

…economist Garett Jones recently opined that Trump’s scuttled hopes to release a COVID-19 vaccine a few weeks earlier “likely would have saved at least 100,000 American lives.”

…Pfizer did not reveal its trial’s favorable results until November 9—six days after the election. The company had originally planned to consider submitting an EUA request to the FDA with just 32 data points; instead it gathered 94, and it waited another 11 days to accrue the requested safety data, plus even more data showing how well the vaccine worked, before making its filing.

…If a compassionate use program for COVID-19 vaccines had gone forward, doctors would have been able to prescribe them to nursing-home residents, even as the vaccine makers completed their clinical trials with integrity and gathered all the safety data requested under the “EUA Plus” requirements.

According to Marks, Birx asked Anthony Fauci and FDA Commissioner Stephen Hahn to encourage Pfizer and Moderna to apply for that program…

The actual timing of the COVID-19 vaccines’ release resulted from a complicated mix of bureaucratic caution, political calculations, and the choices made by vaccine manufacturers. While the benefits of the vaccines have become very clear since then, the precise human cost of that short delay remains a mystery.

Here is the full Brendan Borrell piece in The Atlantic, excellent throughout.  And don’t forget Brendan’s new and exciting book The First Shots: The Epic Rivalries and Heroic Science Behind the Race to the Coronavirus Vaccine.

Via Rich Dewey.

Raise your hand if you think this is a good idea

…if the Food and Drug Administration decides to update Covid-19 vaccines to take better aim at Omicron or other variants, it is unlikely to go it alone.

Instead, a senior FDA official told STAT, the agency expects to take part in an internationally coordinated program aimed at deciding if, when, and how to update Covid-19 vaccines. The approach would ensure decisions are not left solely to individual vaccine manufacturers.

“We can’t have our manufacturers going willy-nilly [saying], ‘Oh well, the EMA decided they wanted this composition, but FDA wanted that composition,’” the official said, referring to the European Medicines Agency. “So we are very much of the mind that we would like to be part of a more global process in helping to come to what vaccine composition there should be now.”

Designed for flexbility and speedy response?  I guess we’ll see.  Here is the full StatNews article.  And obviously, the entire public health community is up in arms about this…