Results for “fda” 324 found
Friday assorted links
1. “Consistent with growing evidence of skin color’s importance for Whites, we demonstrate that darker-skinned Whites—measured via a light-reflectance spectrophotometer—identify more strongly with their White racial identity and are more likely to hold conservative political views on racialized issues than lighter-skinned Whites.” Link here.
2. People unable to think outside the box (on vaccines). And a further update: the FDA may delay EUAs for vaccines, in part because they don’t have the stones to endorse other ways of running the trials, such as HCTs or for that matter a massive increase in clinical trial infrastructure funding.
3. “Update: Manu called again. He is lost and needs directions.” Link here, You need to click through once or twice to read the whole thread, recommended. At some point you will think you have read it all, but you have not. Click through then for more.
6. New bookstore in Dujiangyan, China. Good links today.
Should government improve the quality of its software?
From a GitHub repository:
This GitHub repository is a back up of my FAERSFix scripts.
The FDA Adverse Effect Reporting System is a horrifically dysfunctional quagmire of shockingly bad data. The data is not just bad for severe epistemological reasons, it is also poorly organized and riddled with flagrant absurd errors.
These scripts smooth over the very messy process of acquiring and basic debugging of the data. At the end of the process a user can arrive at a local repository of the FAERS data that is sane enough to begin to think about some kind of sensible analysis. To understand the disastrous state of the original source data, see the source code of the scripts which is designed to be a readable self-documenting manual demonstrating how to correct this mess.
Since the FDA’s gremlins never rest, these scripts will become obsolete. If you would like to contribute updates or fixes, feel free to send me a patch or a pull request. Good luck!
I thank Chris E. for the pointer.
From the AstraZeneca comments
Saturday assorted links
Monday assorted links
1. On the history and use of EUAs (NYT).
3. Sara Lowes on ethnographic and field data in economics.
4. Saez and Zucman respond to their critics in great detail.
5. The value of rapid self-testing for Covid-19. Yes it works and the medical professionals and the FDA are wrong on this one.
6. Logistical problems with supplying monoclonal antibodies, important. It is time to stop dumping on this treatment people, and get our act together. Now. Let’s not have another fiasco. And a good NYT story on the whole topic, you can feel the media mood shifting toward the positive and away from the skeptical.
7. Can you even win at the Japanese crane game? What else is like this?
8. The captain of Operation Warp Speed (WSJ).
9. How it enters your brain. Or might.
10. A Fine Theorem on Milgrom and Wilson, recommended, note that Milgrom also does not have a Ph.D. in economics.
The Great Forgetting: How to Stop Tooth Decay
What if I told you that a cheap, effective and painless method of stopping tooth decay had just been invented! You’d be pretty happy. What if I told you that a cheap, effective and painless method of stopping tooth decay was invented over 100 years ago and has been available in other countries for decades but only now is it starting to be used in the United States as a non-FDA approved, off-label treatment? I hope you would be angry. Well, I did tell you this in 2016 in The FDA Versus the Tooth and now the Washington Post has an update.
Studies show silver diamine fluoride stops decay in 60 to 70 percent of cases with one application. A second application six months later boosts the treatment’s long-term effectiveness to more than 90 percent.
In addition to killing cavity-causing bacteria, the treatment hardens tooth structure, desensitizes the tooth and even stops new cavities from forming. Applying the liquid on the exposed root surfaces of older adults once a year is “a simple, inexpensive, and effective way” to prevent cavities, a 2018 study concluded.
One of the most important benefits of the application on older patients is that the liquid can reach decay that forms under existing dental work such as crowns and bridges, said dental hygienist Michelle Vacha, founder of Community Dental Health, which runs clinics in Colorado Springs and Pueblo, Colo.
Previously, a dentist would have had to remove the crown, drill out the cavity and make a new crown — a traumatic, time-consuming procedure with a typical cost of $1,000 or more, Vacha said. Unable to afford the cost, many patients would instead have the tooth pulled.
The paint-on liquid is significantly cheaper than traditional treatment. Estimates vary, but a private dentist may charge $10 to $75 for one application, compared with $150 to $200 for a filling. Hygienists often have lower fees. At Vacha’s community clinics, the cost is $10 a tooth.
…Silver diamine fluoride has been used in other countries for decades, and studies have proved it safe. Its biggest downside is that it permanently turns the decayed area black — a turnoff, in particular, for people with decay on a front tooth. Dental providers say the black spots can be covered by tooth-colored material for an extra cost. For older adults, Geiselhofer said, a dark spot is a small price to pay for a treatment that stops cavities quickly, with no drilling, needle prick or trip to the dentist required.
The FDA deserves some of the blame but incredibly lost science is more common than you might think. You probably know that in 1797 the British Navy required lemon juice on all foreign service to prevent scurvy but did you know that by the early 20th century scurvy had returned because the cure had been forgotten or discounted?
Mental Floss: Yes, this really happened: scurvy was “cured” as early as 1497, when Vasco de Gama’s crew discovered the power of citrus…but this cure was repeatedly lost, forgotten, rediscovered, misconstrued, confused, and just generally messed around with for hundreds of years, despite being a leading killer of seafarers and other explorers. By the 1870s the “citrus cure” was discredited, and for nearly sixty years, scurvy — despite being cured, with scientific research to back it up — continued killing people, including men on Scott’s 1911 expedition to the South Pole. This went on until vitamin C was finally isolated in 1932 during research on guinea pigs.
It’s tempting to think that these forgettings are a product of the past but the more than 100 year loss of silver as a treatment for tooth decay is a painful modern example.
Hat tip: Ari Armstrong and M. Pettengill.
Our Antibodies, Our Selves
In 2013 I wrote, Our DNA, Our Selves, arguing against the FDA’s crackdown on genetic readouts from firms like 23andMe. The FDA, however, proved succesful in its crackdown and that is why rapid at-home antigen tests are not available today and why tens of thousands of people are dying from COVID unnecessarily. Regulations have unintended consequences.
Let’s recap:
Consider, I swab the inside of my cheek and send the sample to a firm. The idea that the FDA can rule on what the firm can and cannot tell me about my own genes is absurd–it’s no different than the FDA trying to regulate what my doctor can tell me after a physical examination or what my optometrist can tell me after an eye examination (Please read the first line. “G T A C C A…”).
The idea that the FDA can regulate and control what individuals may learn about their own bodies is deeply offensive and, in my view, plainly unconstitutional.
Let me be clear, I am not offended by all regulation of genetic tests. Indeed, genetic tests are already regulated. To be precise, the labs that perform genetic tests are regulated by the Clinical Laboratory Improvement Amendments (CLIA) as overseen by the CMS (here is an excellent primer). The CLIA requires all labs, including the labs used by 23andMe, to be inspected for quality control, record keeping and the qualifications of their personnel. The goal is to ensure that the tests are accurate, reliable, timely, confidential and not risky to patients. I am not offended when the goal of regulation is to help consumers buy the product that they have contracted to buy.
What the FDA wants to do is categorically different. The FDA wants to regulate genetic tests as a high-risk medical device that cannot be sold until and unless the FDA permits it be sold.
Moreover, the FDA wants to judge not the analytic validity of the tests, whether the tests accurately read the genetic code as the firms promise (already regulated under the CLIA) but the clinical validity, whether particular identified alleles are causal for conditions or disease. The latter requirement is the death-knell for the products because of the expense and time it takes to prove specific genes are causal for diseases. Moreover, it means that firms like 23andMe will not be able to tell consumers about their own DNA but instead will only be allowed to offer a peek at the sections of code that the FDA has deemed it ok for consumers to see.
Ten years later we now need rapid antigen tests but the issue, as Michael Mina points out in an excellent interview with Malcolm Gladwell, is that we have medicalized all tests and readouts. Instead of thinking about the individual as having a right to know about their own body, we treated every test or readout as if the only user were a physician. Thus, instead of thinking about the value of these tests for individuals and for public health, the FDA failed to approve rapid antigen tests because it regarded them as inferior to PCR tests, for a physician diagnosing disease.
Here’s Mina (roughly transcribed and lightly edited)
The only pathway that we have to evaluate tests like this are medical diagnostic pathways, pathways designed specifically to ensure that a physician like a detective is getting all the information they need to diagnose a sick person… We have so devalued and defunded public health…that we don’t have a regulatory pathway to approve a test whose primary objective is stopping an epidemic versus diagnosing a sick person. And that has held everything up. All the companies that could be producing these rapid tests in the millions and millions, they have been sitting on these tests trying to hone them so they can pass FDA standards as a medical diagnostic.
It’s not just slowing down their approval it’s actually bottle necking the companies into creating tests that are not going to be as scalable as they are having to use more expensive reagents and packing the tests with instruments so they can pass FDA review when in reality they are just these little pieces of papers. If we can do the cheap version they can be made very fast but the just won’t get through the FDA.
Gladwell: I find your explanation unconvincing. How dumb is the FDA?…If you make the exact argument you made to me…the FDA is not going to see your logic?
It’s not that they are not smart it’s that this is a regulatory body, they just don’t have a pathway. You can’t apply for approval for a public health test tool…In our country the medical establishment is extremely strong, you can’t go to get a cholesterol test without getting a prescription from your doctor. Why can’t we know that? It’s all through this very heavy medical lens and changing that, getting that big ship to turn is turning out to be a very, very difficult task but leading to potentially tens or hundreds or thousands of deaths that don’t need to be happening.
Monday assorted links
1. Gottlieb and McClellan, both former FDA heads, call for accelerated vaccine approval for designated groups, without relaxation of broader standards (WSJ).
3. A time-lapse map of every nuclear explosion through 1998.
4. “We find no evidence of manipulation of Chinese COVID-19 data using Benford’s Law.”
6. Open-air winter schools in New England, in pre-complacency times.
7. Life on Venus? No one cares about that either…(NYT) As a kid I was convinced there was life on Venus, and was never persuaded by the impossibility arguments. So today (while this remains uncertain) I am feeling ever so slightly vindicated in one of my earlier specific beliefs.
This is Not Fine
Why is California burning? The experts all know the answer–CA was made to burn and if you don’t do controlled burns, CA will burn uncontrolled. Here’s ProPublica in an article titled They Know How to Prevent Megafires. Why Won’t Anybody Listen?
Academics believe that between 4.4 million and 11.8 million acres burned each year in prehistoric California. Between 1982 and 1998, California’s agency land managers burned, on average, about 30,000 acres a year. Between 1999 and 2017, that number dropped to an annual 13,000 acres. The state passed a few new laws in 2018 designed to facilitate more intentional burning. But few are optimistic this, alone, will lead to significant change. We live with a deathly backlog. In February 2020, Nature Sustainability published this terrifying conclusion: California would need to burn 20 million acres — an area about the size of Maine — to restabilize in terms of fire.
…When I reached Malcolm North, a research ecologist with the U.S. Forest Service who is based in Mammoth, California, and asked if there was any meaningful scientific dissent to the idea that we need to do more controlled burning, he said, “None that I know of.”
So why doesn’t it happen? Liability law, risk-aversion, rent seeking and vetocracy. Here’s Pro-Publica on excess risk aversion in the fire service (driven by a risk averse public.) (Compare with my analysis of why the FDA is too risk averse.)
Burn bosses in California can more easily be held liable than their peers in some other states if the wind comes up and their burn goes awry. At the same time, California burn bosses typically suffer no consequences for deciding not to light. No promotion will be missed, no red flags rise. “There’s always extra political risk to a fire going bad,” Beasley said. “So whenever anything comes up, people say, OK, that’s it. We’re gonna put all the fires out.”
The ProPublica piece is actually remarkably radical as it offers as one solution, privatized burning!
Fire is not just for professionals, not just for government employees and their contractors. Intentional fire, as she sees it, is “a tool and anyone who’s managing land is going to have prescribed fire in their toolbox.” That is not the world we’ve been inhabiting in the West. “That’s been the hard part in California,” Quinn-Davidson said. “In trying to increase the pace and scale of prescribed fire, we’re actually fighting some really, some really deep cultural attitudes around who gets to use it and where it belongs in society.”
Here’s a bit on vetocracy:
Planned burns are human-made events and as such need to follow all environmental compliance rules. That includes the Clean Air Act, which limits the emission of PM 2.5, or fine particulate matter, from human-caused events. In California, those rules are enforced by CARB, the state’s mighty air resources board, and its local affiliates. “I’ve talked to many prescribed fire managers, particularly in the Sierra Nevada over the years, who’ve told me, ‘Yeah, we’ve spent thousands and thousands of dollars to get all geared up to do a prescribed burn,’ and then they get shut down.”
…“One thing to keep in mind is that air-quality impacts from prescribed burning are minuscule compared to what you’re experiencing right now,”
Francis Fukuyama also pointed to liability law, risk-aversion, rent seeking and vetocracy as factors driving dysfunction at the forest service in a 2014 article in Foreign Affairs but the forest service was only the jumping off point for his pieced titled, America in Decay The Sources of Political Dysfunction (jstor). I don’t agree with everything in that piece but it’s well worth reading to drive home the point that pandemics, forest fires, electrical shortages and more are deeply connected.
Hat tip: Garett Jones.
Monday assorted links
1. Might changes in proton density, spurred by solar wind, predict earthquakes? If true, this would really be something.
2. Violates Godwin’s Law right upfront anyway speak for yourself! I genuinely find such hostile intentions difficult to understand.
3. Will a growth drug undermine “dwarf pride”? (NYT).
4. Robin Hanson on how and why remote work will matter.
5. Economics of the energy transition. Some subtle and underpromoted points in this one.
6. Why we can’t have good things: I am not sure how much public health experts are to blame for the problems in this article about why we don’t have home testing. The FDA won’t approve it? Do something about that! (Where is the outcry, other than from Paul Romer?) The American people aren’t ready for it? Well, are they ready for the alternatives you are proposing? Overall I found this NYT piece a depressing sign of American and perhaps also public health malaise.
7. Using banned cell phones for prison extortion by calling loved ones back home, excellent NYT piece, amazing investigative journalism.
Friday assorted links
1. PBA cards, and implicit trades with police.
2. Australia: “Lawyers and civil liberty groups have expressed concerns about the way a pregnant woman was arrested at her home in Ballarat for allegedly encouraging people to take part in an anti-lockdown rally.” I guess she didn’t have a good enough PBA card.
3. The football culture that is Fargo. 10,000 at an indoors game? And is a two-puffin photo twice as good as a one-puffin photo?
5. New data on the Russian vaccine.
The Beginning of the End?
It’s taken far too long and it’s still not FDA approved for at-home use or for asymptomatic individuals but the new $5,15-minute, easy to use, Abbott test and the Trump administration’s promise to purchase 150 million of them is a big deal. Abbott has been building capacity for months according to their lead scientist interviewed in the Atlantic by Alex Madrigal and in a few weeks will be producing 50 million tests a month:
Madrigal: Fifty million tests a month is a huge number. That’s more than twice the number of tests the U.S. completes in a month. How did you ramp up production so massively?
Hackett: This was the challenge of this program. We needed some sort of reliable testing that could be affordable and that doesn’t require instrumentation. You need scale. The more frequently you could test people, frankly, even tests with lower sensitivity would be very effective at identifying people quickly and slowing the spread. As we were developing the test, there were people working in parallel looking at supply chain and logistics. Abbott took a lot of risk—hundreds of millions of dollars were spent building two new manufacturing facilities focused solely on those tests. We hoped we could come to a solution that would be where we needed it from an overall accuracy perspective, but if you weren’t building capability simultaneously, there was no way it could be the answer.
The US has performed about 80 million tests since the pandemic began, so an additional 50 million tests a month is a big increase in capacity. As noted, the test is not approved for at-home use but it’s a CLIA-waived test which means that a doctor’s office, a CVS or Walmart clinic, even a school nurse could qualify for a waiver and perform the tests. The test is not approved for asymptomatic individuals but I suspect that won’t mean much in practice, it can be prescribed off-label although the fact that a prescription is required is limiting. I hope the necessity for a prescription will be lifted as we get more experience with these tests. False positives (~1.5%) are low and by taking the strain off the PCR system we can improve triage and afford to do more double checks. False positives will be more of an issue as we wipe out the virus but that will take time.
I hope these tests will open up air travel within a month or two. I also hope to see more of these types of tests approved. Derek Lowe has more technical details.
It won’t be all smooth sailing, Abbott may not be able to produce as much or as quickly as they say they can and quality in the field may fall. The government may distribute the tests poorly. The virus could pickup in the fall, as in 1918. I expect more problems and challenges but we now have a chance to get ahead of the virus which is very welcome news.
Addendum: This type of public-private partnership with private firms building capacity in advance of approval for tests and vaccines on the foundation of government push and pull funding is exactly the structure that the Accelerating Health Technologies team has been recommending both to the US government and to governments around the world.
Tuesday assorted links
1. 538 on why NBA scoring has been so high.
3. Derek Lowe on convalescent plasma.
4. “Most of the time, most people do not know (precisely) what they are talking about.”
6. Valuable perspective on Covid-19 reinfection, not yet the worry it might seem to be. This associated, linked Science piece is excellent not only for its content, but also for showing how reasoning ought to be done.
7. Update on the FDA and test regulations, recommended for those who care.
The new quicker, cheaper, supply chain robust saliva test
The FDA has just approved a new and important Covid-19 test:
“Wide-spread testing is critical for our control efforts. We simplified the test so that it only costs a couple of dollars for reagents, and we expect that labs will only charge about $10 per sample. If cheap alternatives like SalivaDirect can be implemented across the country, we may finally get a handle on this pandemic, even before a vaccine,” said Grubaugh.
One of the team’s goals was to eliminate the expensive saliva collection tubes that other companies use to preserve the virus for detection. In a separate study led by Wyllie and the team at the Yale School of Public Health, and recently published on medRxiv, they found that SARS-CoV-2 is stable in saliva for prolonged periods at warm temperatures, and that preservatives or specialized tubes are not necessary for collection of saliva.
Of course this part warmed my heart (doubly):
The related research was funded by the NBA, National Basketball Players Association, and a Fast Grant from the Emergent Ventures at the Mercatus Center, George Mason University.
The NBA had the wisdom to use its unique “bubble” to run multiple tests on players at once, to see how reliable the less-known tests would be. This WSJ article — “Experts say it could be key to increasing the nation’s testing capacity” — has the entire NBA back story. At an estimated $10 a pop, this could especially be a game-changer for poorer nations. Furthermore, it has the potential to make pooled testing much easier as well.
Here is an excerpt from the research pre-print:
The critical component of our approach is to use saliva instead of respiratory swabs, which enables non-invasive frequent sampling and reduces the need for trained healthcare professionals during collection. Furthermore, we simplified our diagnostic test by (1) not requiring nucleic acid preservatives at sample collection, (2) replacing nucleic acid extraction with a simple proteinase K and heat treatment step, and (3) testing specimens with a dualplex quantitative reverse transcription PCR (RT-qPCR) assay. We validated SalivaDirect with reagents and instruments from multiple vendors to minimize the risk for supply chain issues. Regardless of our tested combination of reagents and instruments from different vendors, we found that SalivaDirect is highly sensitive with a limit of detection of 6-12 SARS-CoV-2 copies/μL.
No need to worry and fuss about RNA extraction now. Here is the best simple explanation of the whole thing.
The researchers are not seeking to commercialize their advance, rather they are making it available for the general benefit of mankind. Here is Nathan Grubaugh on Twitter. Here is Anne Wyllie, also a Kiwi and a Kevin Garnett fan. A further implication of course is that the NBA bubble is not “just sports,” but also has boosted innovation by enabling data collection.
All good news of course, and Fast at that. And this:
“This could be one the first major game changers in fighting the pandemic,” tweeted Andy Slavitt, a former acting administrator of the Centers for Medicare and Medicaid Services in the Obama administration, who expects testing capacity to be expanded significantly. “Rarely am I this enthusiastic… They are turning testing from a bespoke suit to a low-cost commodity.”
And here is coverage from Zach Lowe. I am very pleased with the course of Fast Grants more generally, and you will be hearing more about it in the future.
Bill Gates is Angry
But people aren’t getting their tests back quickly enough.
Well, that’s just stupidity. The majority of all US tests are completely garbage, wasted. If you don’t care how late the date is and you reimburse at the same level, of course they’re going to take every customer. Because they are making ridiculous money, and it’s mostly rich people that are getting access to that. You have to have the reimbursement system pay a little bit extra for 24 hours, pay the normal fee for 48 hours, and pay nothing [if it isn’t done by then]. And they will fix it overnight.
Gates is correct. If companies were paid for speed they would increase capacity and move immediately to a stack processing (LIFO) model, as I described yesterday.
The whole interview is worth reading. Gates is restrained but you can tell he is angry. Bill has had it with the FDA, Trump, Mark Zukerberg, stupid anti-vaxxers like Robert Kennedy (who he was forced to listen to to get access to Trump), Congress and much more. I don’t blame him one bit. I am angry too.
That is from MR commentator Sure. And also from him:
Perhaps things will improve in a few weeks’ time.