Results for “fda” 360 found
Here is the audio, video, and transcript, I found it a very substantive and also illuminating episode. Carpenter is very, very smart and also very well-informed historically. Here is part of the summary:
Daniel Carpenter is one of the world’s leading experts on regulation and the foremost expert on the US Food and Drug Administration. A professor of Government at Harvard University, he’s conducted extensive research on regulation and government organizations, as well as on the development of political institutions in the United States. His latest book Democracy by Petition: Popular Politics in Transformation, details the crucial role petitions played in expanding the franchise and shaping modern America.
Here is an excerpt from the non-FDA section, much of which focuses on (non-FDA) regulation:
COWEN: What kinds of records should the Postal Service keep about itself?
CARPENTER: [laughs] Great question. There’s a whole set of things that they don’t since the Griswold decision and since the First Amendment decisions. They don’t keep as much records of what goes through the mail. They can’t prohibit things like pornography, contraception.
I guess it depends on what you mean by “itself.” I would start with the idea that basic privacy restrictions, which governed the postal system as much through norm as by law in the 19th century and early 20th century, should govern the system.
It’s a crime if I were to walk past your mailbox and open your letter. I’m committing a federal crime, but there were also norms that seals were not to be broken, things like that. I do think whichever way the Postal Service goes — and it’s quite possible that you could imagine an electronic platform for the US postal system — I think basic privacy restrictions have to be guaranteed.
Actually, in some respects, I think we need to know a fair amount about what postal workers do without, say, calling for Amazon tracking. But if we think that postal workers are misplacing ballots or not providing birth control pills or something like that, then we should probably have some way of picking up on that kind of nefarious behavior.
In the FDA section I got mad at him, the first (but not last?) time that has happened in a CWT, do read or listen to the whole section, the two of us really had at it! Here is a tiny sliver from it:
COWEN: But shouldn’t there be a button within the FDA that can be pushed, where the FDA goes into a kind of wartime mode?
I don’t want to misrepresent Carpenter by an ill-chosen excerpt, so please do digest his full set of replies. Recommended.
NYTimes: The Covid-19 pandemic has forced the Food and Drug Administration to postpone hundreds of drug company inspections, creating an enormous backlog that is delaying new drug approvals and leading the industry to warn of impending shortages of existing medicines.
…In an interview, F.D.A. officials said they sharply curtailed the inspections to protect their investigators, following guidelines from the Centers for Disease Control and Prevention, which discouraged federal employees from travel during the pandemic.
But some people in both industry and public health communities say that federal drug inspections are essential, and that the agency should bypass travel restrictions by taking precautions, including wearing proper personal protective equipment.
…In interviews, F.D.A. officials denied that the dramatic drop in inspections has slowed drug approvals. But a number of drug companies, including Spectrum Pharmaceuticals, Biocon Biologics and Bristol Myers Squibb, has issued statements noting deferred F.D.A. action because of the agency’s inability to conduct inspections.
In October, Spectrum announced that the F.D.A. had deferred action on its application for Rolontis, a treatment for cancer patients who have a very low number of certain white blood cells, because it could not inspect the manufacturing plant the company uses in South Korea.
In late December, Biocon Biologics notified shareholders that the F.D.A. deferred action on its joint application with Mylan for a proposed biosimilar to Avastin, a cancer drug.
Bristol Myers Squibb announced in November that the F.D.A. would miss its November deadline for taking action on a lymphoma treatment, lisocabtagene maraleucel because it could not inspect a third-party Texas manufacturing plant. The agency eventually did complete its inspection and approved the drug last month.
Grocery store workers are working, meat packers are working, hell bars and restaurants are open in many parts of the country but FDA inspectors aren’t inspecting. It boggles the mind.
Let’s review. The FDA prevented private firms from offering SARS-Cov2 tests in the crucial early weeks of the pandemic, delayed the approval of vaccines, took weeks to arrange meetings to approve vaccines even as thousands died daily, failed to approve the AstraZeneca vaccine, failed to quickly approve rapid antigen tests, and failed to perform inspections necessary to keep pharmaceutical supply lines open.
I am a long-time critic of the FDA and frankly I am stunned at the devastation.
After the FDA advisory committee voted in favor of Pfizer’s EUA last Thursday–as almost everyone thought they would–the FDA had difficulty finishing the paperwork. The NYTimes reported:
People familiar with the F.D.A.’s situation say that regulators are now racing to complete a fact sheet, information for physicians and other required documents that go with the authorization.
The paperwork delay meant that the FDA was going to wait to issue the EUA until Monday. That’s when Trump called the FDA “a big, old, slow turtle” and yelled at Hahn to “Stop playing games and start saving lives!!!.” The FDA then sped up and issued the EUA on Friday. As a result, the first tranche of vaccines are being delivered today.
The advisory committee for the Moderna vaccine meets this coming Thursday. Here’s a polite request of the FDA–please have the fact sheet, information for physicians and other required documents ready to go. Thanks.
P.S. We would also be really grateful and, you know, it might save some lives if you allowed Moderna to start shipping now so the vaccine is on-site and ready to go on Friday. Please give it some thought and thanks again for your kind consideration. It’s been very stressful seeing thousands of people dying every day.
Two to three thousand people a day are dying from COVID. Thus anything that delays rolling out a vaccine has a very high cost in human lives. People want to deny this, perhaps because it is so horrifying. I get a lot of pushback when I say that FDA delay is deadly. Let’s dispense with a few objections. It is true, of course, that the people who are dying today can’t literally be saved by a vaccine today but they could have been saved had they been vaccinated four or five weeks ago and similarly projecting forward.
Another response that many smart people tell me is that a vaccine can’t be rolled out immediately so even under the best scenarios you couldn’t save that many people immediately. That’s true but irrelevant. Since a lot of people are getting this wrong, I want to show this in a simple model using pictures. Red is for deaths. Green is for life. Suppose two thousand people are dying from COVID a day as in panel 1. Let’s for the sake of the simple model assume that you could deliver a vaccine to everyone on Day 1. You would then save 2000 lives a day going forward for however long the pandemic would have lasted as shown in panel 2. If you delay by one day then two thousand people die who would have lived without the delay, as shown in panel 3. Pretty obvious so far.
Now assume that the vaccine can’t roll out to everyone immediately. For the sake of this simple model let’s assume that on day one you can only vaccinate half the population. By doing so you save 1000 lives on day 1 and 2000 lives every day thereafter for the length of the pandemic. That’s the fourth panel. Now suppose we delay the vaccine rollout by one day. 2000 people die on Day 1 but you save 1000 on Day 2 and 2000 on Day 3 and every day thereafter for the length of the pandemic. How many people were killed by the delay? Compare the 4th and 5th panels. 2000 exactly as before! The slow ramp up doesn’t change the number of deaths caused by delay it just spreads them out over different days. You can adjust the ramp so that it occurs over 10 days or 30 days. Doesn’t change much on the delay margin unless you delay for so long that the pandemic is close to being over.
What could matter is if delay increases the speed at which you can ramp up. I doubt that this is true. We were ready to go with millions of doses in late October (guess why?). (In fact we had a vaccine in January and millions of doses around March-April.) We won’t really be better prepared tomorrow than we are today. It’s learning by doing that matters. See the point Tyler made earlier about economic time versus calendar time.
As Tyler noted, this is hardly the final analysis but many people are not even conceptualizing the problem correctly and this is a good place to begin.
Many people are asking me this question. I don’t mean to relitigate the question of whether the FDA should be moving faster, rather consider this an exercise in how to think about the trade-offs. I thus am going to hold the safety and quality of the vaccine constant.
To proceed, consider the distinction between processes defined by economic time and processes defined by calendar time. In Virginia it may snow in February but not in October, and that is defined by calendar time, not caused by local gdp. But for many inventory processes, they do not restock until the shelf is emptied by buying customers, and that is economic time. They don’t check to see if it is June or July.
Let us say that only economic time matters, though I will drop that assumption shortly.
Now, given how late we are in “the season,” it is easier to think about pushing the approval date back rather than moving it forward. Let’s say that the FDA postponed the December 10 meeting to January 10. Some number of people would die of Covid during that month — the current clip being around 2600 a day but changing — and then around Jan.10 some kind of vaccine-related health and economic recovery would move into fuller gear.
If only economic time matters, it seems the Dec.10 recovery and the Jan.10 recovery run about the same. The net difference between the two scenarios is the lives lost in the meantime, to oversimplify say 2000 x 30 days, or 60,000 lives plus accompanying lost jobs and gdp.
I do not think that losing those lives would somehow speed the later, Jan.10-starting recovery process, and it may in some ways render it more fractious.
On top of that, the postponed recovery period likely will imply some kind of grinding uncertainty in the meantime, and possibly intertemporal substitution from some agents (like me!) who are waiting for the change to come before going to the barber. The true net costs are thus higher than what I listed two paragraphs above.
Now, how might the introduction of calendar time alter those estimates?
First, the production of complementary goods for vaccines (say freezers, but the point is more general) may be on a clock of its own, more or less on automatic pilot and requiring time. When approval comes later, more of those complementary goods are in place, and thus the later recovery is a more powerful one. That factor tends to lower the cost of delaying approval.
(Of course to the extent those same complementary inputs depend upon economic time, that is reason not to delay approval! The sooner you approve, the sooner they will get working on getting those freezers in place, which of course boosts recovery power. Supply is elastic with respect to approval, as suggested for instance by stock market reactions to approval decisions.)
Second, the seasonal effects will differ. Ideally you want the spread of vaccines to be covering some of the more infectious and thus more difficult winter months. February is worse than March, and so on. Given the current clock, this is a big reason to be hurrying.
You might think of other ways calendar time could matter. You also might think of various non-linear effects and interactions, though I am not sure whether they would make delay more or less costly.
Overall it seems to me that the costs of approval delay are likely very high. They are not obviously overturned or minimized by citing the relevance of complementary inputs. The import of complementary inputs might be more ruled by “economic time,” or the seasonal effects may be a stronger quantitative magnitude, again favoring faster speed of approval.
I do understand this is far from a final analysis, rather it is a starting point for conceptualizing the problem.
As a Johns Hopkins scientist who has conducted more than 100 clinical studies and reviewed thousands more from the scientific community at large, I can assure you that the agency’s review can be done within 24 to 48 hours without cutting any corners. They just need to work harder.
Contrary to popular belief, the FDA process is not hands-on—it does not interview vaccine trial patients or look under a microscope at the immune cells. It’s doing a statistical analysis and looking at data. For the vaccine trial, the data set is small and straightforward. If my research team, normally tasked with analyzing data on millions of patients, was asked to review the smaller Pfizer vaccine study of 43,000 patients, it would take about one hour.
The FDA also reviews manufacturing data from Pfizer on how they made the drug. But not only can that data be reviewed in a few hours, it should have been done months ago when it was available. While the FDA was waiting for Pfizer’s long-term vaccine results to come in, the agency should have anticipated this step and done it early.
The final step of the FDA review is to look at the outcomes of the study volunteers, including rates and severity of infection and side effects in the vaccine and placebo groups. Again, there is no plausible reason why this basic analysis cannot be done in 24 hours. The FDA and external scientists have a simple task: confirm or reject the review already conducted by the trial’s independent data safety monitoring board before FDA submission.
That is from Marty Makary, who also details an ongoing history of FDA delays during the pandemic, starting with the very first Covid testing attempts from the University of Washington, which the FDA tried to nix, but continuing throughout. And:
FDA insiders say the agency and its approximately 17,000 employees were dark for the four-day Thanksgiving holiday, including those working on the vaccine approval.
For those of us who lived through the 2008 financial crisis (agencies other than the Fed were not on the ball in response), or who have studied (and indeed practiced) the economics of bureaucracy for forty years, or who know the extensive literature on how the FDA operates, will not be surprised by a lack of urgency. Or from the NYT:
Dr. Fauci said the politicization of the pandemic in his own country had led regulators to move a little more cautiously than the British, to avoid losing public support.
Sorry people, but I read that as “for political reasons we did not go more quickly.”
Here from Statnews journalists Matthew Herper and Nicholas Florko defend the FDA, going into considerable detail, do read it. Here is one excerpt, in direct contradiction to some of the above:
The agency’s staff “were eating turkey sandwiches on Thanksgiving while reviewing documents,” Peter Marks, who heads the FDA center conducting the vaccine reviews, said on a Thursday webcast run by the Journal of the American Medical Association.
Additionally, members of an FDA advisory committee that will convene Thursday to review the data and issue its recommendations, have expressed no desire to meet sooner. STAT spoke to four members of the panel and all said the agency should not try to move any faster.
My view is this: if your agency is saying “usually we move five to ten times more slowly,” it is highly unlikely their current procedures are optimized for speed. It is fast organizations that are good at moving fast, right Usain Bolt?
We’re now at the point where Covid-19 is the single leading cause of death in this nation.
Why not sooner?
Inquiring minds wish to know. Was the meeting hard to schedule?
If you think the FDA has been slow at approving new coronavirus tests just look at their process for approving sunscreen products.
According to EWG, the Environmental Working Group, the FDA has been too slow to test old ingredients for safety and too slow to allow new ingredients on the market thus leaving us with sunscreen products which are neither as safe nor as effective as they should be. In particular, Europe has better sunscreen protection than the United States. Here’s EWG:
Americans have fewer choices and notably poorer protection than Europeans do from ultraviolet A rays in their sunscreen options. Although most U.S. sunscreens prevent sunburn effectively when used correctly, they aren’t as good as European sunscreens at preventing the more subtle skin damage produced by lower-energy UVA radiation. UVA rays have less energy and don’t burn the skin, but they can cause the skin to age, suppress the immune system and contribute to the development of melanoma.
…Between 2003 and 2010, sunscreen makers applied for FDA permission to use eight sun-filtering chemicals developed by European companies. Four of these – Tinosorb S, Tinosorb M, Mexoryl SX and Mexoryl XL – appear to be more effective than avobenzone, the most common UVA filter permitted by the FDA. The FDA’s failure to respond to these applications prompted Congress to pass the Sunscreen Innovation Act of 2014 (FDA 2014). This act requires the FDA to review new applications for sunscreen active ingredients within 300 days, but it doesn’t relax the standards companies must meet to prove new ingredients are both safe and effective.
In 2015, the FDA responded that the companies involved had not submitted enough information to prove their chemicals were, in fact, safe and effective for use (FDA 2015). The agency asked for more data, including complete study results, measurements of ingredient levels in people’s blood, and long-term studies on systemic toxicity and potential endocrine system disruption. The FDA has also proposed that all sunscreen ingredients, including those already in use, need to have adequate safety testing data.
Some information the FDA wants, such as complete copies of studies, might be easy for sunscreen makers to produce. But in other cases, the companies could take years to satisfy FDA requests. In the meantime, Americans are being shortchanged.
I first wrote about this issue in 2013 and seven years later, despite Congress passing a law in 2014, the FDA still has not acted.
My rule is very simple. I don’t think the FDA is better than the EMA so if any drug or device is approved in Europe it ought to be available for purchase in the United States with a label saying “Approved by the EMA. Not approved by the FDA.” (By the way, we do have reciprocity type agreements with Canada and New Zealand for food so this would not be unprecedented.)
Hat tip: John Thacker.
Addendum: You should actually get more sun to avoid vitamin D deficiency which is bad for a variety of reasons including, in my estimation, greater susceptibility to COVID.
The FDA has announced they will no longer forbid pooled testing:
In order to preserve testing resources, many developers are interested in performing their testing using a technique of “pooling” samples. This technique allows a lab to mix several samples together in a “batch” or pooled sample and then test the pooled sample with a diagnostic test. For example, four samples may be tested together, using only the resources needed for a single test. If the pooled sample is negative, it can be deduced that all patients were negative. If the pooled sample comes back positive, then each sample needs to be tested individually to find out which was positive.
…Today, the FDA is taking another step forward by updating templates for test developers that outline the validation expectations for these testing options to help facilitate the preparation, submission, and authorization under an Emergency Use Authorization (EUA).
This is good and will increase the effective number of tests by at least a factor of 2-3 and perhaps more.
In other news, Representative Beyer (D-VA), Representative Gonzalez (R-OH) and Paul Romer have an op-ed calling for more prizes for testing:
Offering a federal prize solves a critical part of that problem: laboratories lack the incentive and the funds for research and development of a rapid diagnostic test that will, in the best-case scenario, be rendered virtually unnecessary in a year.
…We believe in the ability of the American scientific community and economy to respond to the challenge presented by the coronavirus. Congress just has to give them the incentive.
The National Institutes of Health (NIH) have already begun a similar strategy with their $1.4 billion “shark tank,” awarding speedy regulatory approval to five companies that can produce these tests. Expanding the concept to academic labs through a National Institute of Science and Technology (NIST)-sponsored competition has the added benefit ultimately funding more groundbreaking research once the prize money has been awarded.
This is all good but frustrating. I made the case for prizes in Grand Innovation Prizes for Pandemics in March and Tyler and I have been pushing for pooled testing since late March. We were by no means the first to promote these ideas. I am grateful things are happening and relative to normal procedure I know this is fast but in pandemic time it is molasses slow.
Now we know:
An F.D.A. spokesperson said home collection kits raised additional concerns about safety and accuracy that required the agency’s review. The issue in the Seattle case appears to be that the test results are being used not only by researchers for surveillance of the virus in the community but that the results are also being returned to patients to inform them.
The two kinds of testing — surveillance and diagnostic — fall under different F.D.A. standards. In a pure surveillance study, the researchers may keep the results just for themselves. But coronavirus testing has largely revolved around getting results returned to doctors who can share the results with patients.
My long-running skepticism about the safety and efficacy of the FDA is fast becoming conventional wisdom. Even normal people can’t believe what they are doing. This piece on the FDA in the New York Times reads like something I might have written for CATO.
An innovative coronavirus testing program in the Seattle area — promoted by the billionaire Bill Gates and local public health officials as a way of conducting wider surveillance on the invisible spread of the virus — has been ordered by the federal government to stop its work pending additional reviews.
…the program, a partnership between research groups and the Seattle and King County public health department that had been operating under authorization from the state, was notified this week that it now needs approval directly from the federal government. Officials with the Food and Drug Administration told the partnership to cease its testing and reporting until the agency grants further approval.
…the Seattle program …has wide backing, including from public health leaders, the Fred Hutchinson Cancer Research Center and Mr. Gates, whose foundation has been deeply involved in fighting the pandemic. The Centers for Disease Control and Prevention also provided an in-person technical adviser to the project.
Dr. Eric Topol, the director of the Scripps Research Translational Institute, who is not involved in the Seattle group, said it had “emerged as leading lights in this whole Covid-19 crisis.” He said it was “bizarre” that the F.D.A. would halt such a project.
By the way, Dr. Helen Chu, one of the leaders of the Seattle project, was one of the first Emergent Ventures prize winners for her work fighting the coronavirus (excellent pick, Tyler!). As you may recall, Chu started testing for coronavirus in an already running flu study without permission. Until she was shut down.
To repurpose the tests for monitoring the coronavirus, they would need the support of state and federal officials. But nearly everywhere Dr. Chu turned, officials repeatedly rejected the idea, interviews and emails show, even as weeks crawled by and outbreaks emerged in countries outside of China, where the infection began.
By Feb. 25, Dr. Chu and her colleagues could not bear to wait any longer. They began performing coronavirus tests, without government approval.
Federal and state officials said the flu study could not be repurposed because it did not have explicit permission from research subjects; the labs were also not certified for clinical work. While acknowledging the ethical questions, Dr. Chu and others argued there should be more flexibility in an emergency during which so many lives could be lost. On Monday night, state regulators told them to stop testing altogether.
The failure to tap into the flu study, detailed here for the first time, was just one in a series of missed chances by the federal government to ensure more widespread testing during the early days of the outbreak, when containment would have been easier. Instead, local officials across the country were left to work in the dark as the crisis grew undetected and exponentially.
History repeats itself, first as tragedy then as farce.
Addendum: I see now that Tyler covered this a bit earlier in the post below. I’ll leave this post up, however, as I have more details including Tyler’s connection.
The KN95 mask is China’s version of the N95 mask. 3M, America’s largest manufacturer of N95 masks, said in January that the masks are equivalent. But the FDA is not allowing KN95s into the country.
Buzzfeed: The KN95 mask is a Chinese alternative to the scarce N95 mask, but the FDA refuses to allow it into the country.
…By law, masks, along with most medical devices, can’t be imported or sold in the United States without the Food and Drug Administration’s say-so. Last week, to ease the national shortfall of protective gear, the FDA issued an emergency authorization for non-N95 respirators that had been certified by five foreign countries as well as the European Union. It conspicuously left the KN95 masks out of the emergency authorization.
The omission was all the more startling because in late February the Centers for Disease Control and Prevention said that KN95 masks were one of numerous “suitable alternatives” to N95 masks “when supplies are short.”
…Allowing the importation and use of KN95 could help to greatly alleviate the scarcity.
“The KN95 masks are far more readily available,” said Bob Tilton, who owns a New Jersey–based cosmetics packaging importer and earlier this month decided to use his familiarity with Chinese supply chains to bring in masks and other personal protective equipment to sell to hospitals. “The N95s are much harder to grab.”
Yet without the FDA’s seal of approval, importers are hesitant to order KN95 masks because they worry they’ll get held up at customs.
It’s not just the FDA that is to blame, however. America’s legal system is also to blame:
Many hospitals are refusing to accept them, even as free donations, because they fear legal liability should a health care worker get ill while using a nonpermitted device…Although some hospitals flat-out reject KN95 masks at any price on advice of their lawyers, people rounding up masks to give to hospitals have found that individual doctors or nurses will often accept the donations, given the dire need.
Consider that last bit of insanity. The ethical and common-law type rule is very simple: Do everything reasonable to protect your hospital workers. But what some feckless hospital administrators are actually doing is following “the law” even if it conflicts with the ethical rule.
TechCrunch…the U.S. Food and Drug Administration (FDA) has updated its Emergency Use Authorization guidelines to private labs that specifically bar the use of at-home sample collection. This means startups, including Everlywell, Carbon Health and Nurx, will have to immediately discontinue their testing programs in light of the clarified rules.
The FDA issued the updated guidance on March 21, and though some of the companies had already begun to ship their sample collection kits to people, and even begun to receive samples back to their diagnostic laboratory partners, even any samples in-hand will not be tested, and will instead be destroyed in order to comply with the FDA’s request
The tests are collected at home but the tests themselves are done in certified labs under quality-control standards (CLIA). It is of course possible, even likely, that tests collected at home are not as accurate as those collected by a trained nurse. But we don’t want trained nurses to be testing everyone–they have other things to do right now. Furthermore, some of these errors will be detected at the lab and can be fixed with a retest. False negatives are possible but going to a hospital or standing in line to get a test also comes with risk. False negatives will also become apparent to the extent that symptoms worsen at which time patients can seek medical assistance. Yes, of course, delay and false reassurance are also not without risk. Welcome to the world of tradeoffs. But at this point in time we need to unleash American ingenuity and enterprise and evolve our way to the frontier as conditions improve.
We need to learn now, regulate later.