Off-Roading with the FDA
It appears the FDA is now willing to deviate from its “bedrock mission” of guiding the public with accurate science-based information to a different road emphasizing variable political interests.
“The deep state, or whoever, over at the FDA is making it very difficult . . . @SteveFDA“, addressing you directly with your Twitter handle (trump).
FDA is endorsing twitter as a mechanism to broadcast actions with and by Commissioner Dr. Hahn. Tweeting:
“I have been criticized for remarks I made Sunday night about the benefits of convalescent plasma. The criticism is entirely justified. What I should have said better is that the data show a relative risk reduction not an absolute risk reduction.” SteveFDA.
It would appear the FDA is now under direction of trump who is taking it down roads not traveled by the FDA in the past with the medical profession in the back seat. Some are not so willing to go along for the ride.
“We cannot entrust the health of 330 million Americans to a person who is subservient to President Trump’s whims, unprecedented promotion of unproven therapies, outrageous lies, and political motivations.” Dr. Eric J. Topol, MD, the editor-in-chief of Medscape
Medscape has three interesting articles critiquing the FDA. The first article reviews the expansion of remdesivir usage, the second covers FDA Commissioner Dr. Stephen Hahn actions, and the last is questioning the FDA’s Covid decisions. The first two articles were published on August 31st and the last on September 2nd. Typically, I read the articles and then go on to the comments section to see what medical practitioners have to say. I would suggest you too read the articles and then read the comments which can reveal a different perspective. The comments can be useful and insightful.
First article; “FDA Expands Remdesivir Use for All COVID-19 Hospitalized Patients” regardless of when it was contracted. It is my understanding remdesivir is a drug which has its greatest impact early on before the Covid virus replicates.
The second article I am linking too is(?) a letter written by Dr. Eric J. Topol, MD, the editor-in-chief of Medscape to the current FDA Commissioner: “Dear Commissioner Hahn: Tell the Truth or Resign.” Dr. Eric Topol has written an open letter to Dr. Stephen Hahn who replaced Dr. Scott Gottlieb as Commissioner of the FDA. In it he accuses Dr. Hahn of misusing “emergency use authorizations” (EUAs) to promote 3 drugs having little scientific evidence in support of their efficacy. Here again, I would ask you to read the article and then go to the comments (>450). There is good information there which you may not get ordinarily by surfing the web. The comments are informative about the drugs being promoted without completing the clinical trial requiem and subsequent decisions being made which may be in error due to a lack of testing.
The last Medscape article asks; “What Do You Think of the FDA’s COVID-19 Decisions?” The article has a questionnaire to be answered by medical personnel, which I skipped and went to the posted results. It has some interesting data information reviews the “three emergency use authorizations (EUAs)” DR, Topol states are not evidence-based:
– One EUA for hydroxychloroquine on March 30 (revoked in June for lack of evidence),
– one for convalescent plasma on August 23, and
– an expanded EUA for remdesivir to treat “any” hospitalized COVID-19 patient, not just those with severe disease.
My opinion, which others may dispute what I have to say:
Every article I have read on HCQ, the failures in countries in question or US entities (such as the VA) have used different dosages (higher) than what was used in Korea, France, Costa Rica and a few other places. As I read, the failed treatment were started later, after Covid was discovered, and beyond the initial ten days in which success was achieved. The testing facilities did not duplicate what was done in prior successful patterns of treatment. Why would any entity not try to duplicate the “supposed” treatment plan which was touted to be successful? If the process is duplicated, the hypothesis is tested. You can form your own conclusion to that question. Henry Ford Health System in a multi-hospital assessment, tested HCQ utilizing ~2500 patients participating. “Treatment with hydroxychloroquine, azithromycin, and in combination in patients hospitalized with COVID-19.” The data is there have at it.
The second article is discussing a process and procedure utilizing convalescent plasma which is barely off the ground in the treatment of Covid. HHS Secretary Alex Azar; a “35% improvement in survival is a pretty substantial clinical benefit. If the data continues to pan out, of 100 people who are sick with COVID-19, 35 would have been saved because of the admission of plasma.”
Dr. Eric Topol; “The statement was based on a preprint, which by definition has not been peer-reviewed and published by Mayo Clinic’s Michael Joyner and coauthors. It is a retrospective, observational study of over 35,000 patients who received convalescent plasma, without any controls or untreated patients for comparison. The claim of reduction of mortality is totally unsubstantiated. If the preprint data held up in a proper randomized controlled trial, it would be avoiding deaths of 3 or 4 people per 100 who would have died. ”
We are reminded by Dr. Topol of the FDA’a goal:
“FDA is responsible for advancing the public health by helping to speed innovations that make medical products more effective, safer, and more affordable and by helping the public get the accurate, science-based information they need to use medical products and foods to maintain and improve their health.”
Finally, we come to Gilead’s remdesivir. “Gilead Sciences announced that it would begin charging a US price of $3,120 for a 5-day course of remdesivir as a treatment for COVID-19.” The pricing has been modeled by the ICER, which everyone says is expensive for a 5-day treatment course of action. Not to justify the price of it, maybe I am missing some additional information for their reasoning?
“Remdesivir is an expensive drug, costing approximately $3000 per treatment,” Dr. Topol
There is something in error as the cost is far less than what is being said here. Perhaps I am misreading? Cost recovery for remdesivir has been mostly achieved. I am assuming Dr. Topol means the pricing for remdesivir has been established by the ICER which Gilead stated as a “5-day treatment course.” The “initial ICER-COVID model suggested a price of approximately $4,500 per treatment course, whether that course is 10 or 5 days.”
Remdesivir is effective when used early on after contracting Covid (I am not going to discuss why). It has shown limited ability in later stages of treatment the same as HCQ in combination with other drugs. There is a history to Gilead’s remdesivir being approved as an orphan drug initially and then being switched back. It is all in the demand and the returns. Covid is no longer a rare disease as expected and more profit can be made from remdesivir under normal pricing due to demand. Declared orphan drugs have a lower demand and are given special consideration due to the rarity of the disease and low demand (<200,000). A drug can still be an Orphan drug if declared such before it exceeds 200,000 also. Timely declaration is important.
Simplistically stated, how does remdesivir (GS-5734) work? Nucleoside/tide analogues (remdesivir) mimics the structure of a natural nucleoside or nucleotide such that they are recognized by viruses and attach to them. Due to those structural modifications they stop or interrupt viral replication which prevents the virus from multiplying and infecting more cells in the body. They are known as direct-acting antivirals. This is the case for remdesivir, which works by blocking the coronavirus’s RNA polymerase – one of the key enzymes this virus needs in order to replicate its genetic material (RNA) and proliferate in an infected person. It is a pro-drug. Remdesivir is metabolized and undergoes a sequence of five bioactivation steps before it becomes triphosphate, the active compound that impedes replication of the virus. You are probably wondering why I am going to such a lengthy explanation. Be patient, I am getting there.
Gilead has another antiviral nucleoside analogue (I picked up a whole new vocabulary since the onslaught of Covid). GS-441524, a pro-drug the body converts into a GS-441524 triphosphate in just three steps.”GS-441524 is either similar too or more potent than remdesivir against SARS-CoV-2 in cell culture causing some researchers arguing that GS-441524 would be better than remdesivir for the treatment of COVID.”
It was originally thought remdesivir would activate quicker than GS-441524 in human cells infected with the SARS and MERS coronaviruses. Data from primary human airway epithelial cells showed no statistically significant difference in potency between the two compounds. The data aligns with previous reports on the similar effectiveness of remdesivir and GS-441524 in coronavirus-infected cat cells. GS-441524 was used to treat cats with feline infectious peritonitis, a progressive and usually fatal disease caused by a coronavirus. It displayed remarkable safety and therapeutic efficacy, with 96% of cats recovering after treatment. Gilead should perhaps focus on remdesivir’s ancestor rather than remdesivir. It has been claimed it will convert to a triphosphate faster.
Back to MedScape articles. Read them and then go to the comments section to see what the medical practitioners are saying. You will find most of the doctors will not administer a drug unless it has been FDA approved. Secondly, hospitals are against administering convalescent plasma. Thirdly, the letter from Dr. Topol to trump-appointed FDA Commissioner Dr. Hahn is condemning as Hahn is approving drugs without clinical trials which in one case the drug labeled HCQ was reversed. To be redundant, I usually read the article and then go on to read the comments by the medical people. The comments can be useful, insightful, and interesting.
Thank you. It takes me more time to write this stuff than others at AB which causes me to be jealous of their spontaneity. The links are good and support my observations
I think the word you’re looking for is “insightful.”
That’s it? I was expecting a bit more than a word-meaning error. Thank you though. I will have a word with my proof – reader.
Thank you though. It is like you proof read and proof read looking for misspellings, run-on sentences, punctuation, meaning, does this make sentence(?) sentences and paragraphs, and still you miss things. I used to consult for Ingersoll Engineers on supply chain issues, ways to improve, and do it. Spent much time editing their reports before they went to the customer as asked by my mentor at the time. I can write and I am not perfect. The topic is foreign to me and I will have to read some more to make it more of my own.
Thank you for hanging around Angry Bear.
Flipper babies coming soon.
I think it is a well-written piece. I didn’t intend the spell-check to be insulting. I skimmed the piece, and that was the only flaw I could spot.
I’m pretty cynical about the impact of convalescent serum. Yes, if it saved my life, I’d consider it impactful, but there will never be enough for a pandemic.
Think of convalescent serum like snake antivenom, which is also passive immunity. It’s a lifesaver if you get it in time, but very few people get bitten by deadly snakes. This therapeutic approach doesn’t scale.
Thank you for your kind comment. I went back and changed some of the dialogue to make it a better read and changed such words as requiem and a second inciteful (sigh). Not perfect by any means and I do make mistakes. Appreciate the guidance on convalescent serum. I spent almost 4 weeks in the hospital trying to get my platelets back. Steroids failed this time around and a dose of a mixed platelets did not work either. I spent my time wandering around the hospital. I wandered into one hall where they had a lists of people who had graduated out of medical school by year.
In the morning walkabouts by doctors, One hematologist said to me; “if you fall and bump your head while walking, we will never get to you in time.” One day I am on my laptop reading away and writing, the same Hemo-guy comes in and says “Are you always on that thing?.” I said: “Yes, this is my newspaper. I guess I could go out for a walk instead?” Rituxan worked for me this time after Medicare approved it.
We are almost at a stand still on developments with Covid. People are not staying home and resisting masking. My house and property are a pretty safe place to be right now. Take care of yourself and be safe.
“We are almost at a stand still on developments with Covid.”
That’s an illusion. There are several phase 3 trials underway or about to start for a variety of vaccine trials. While these things take time to get right, would you say that a pregnancy at three months is at a standstill? I wouldn’t.
You are doing what I hoped you would do. Supply more information and talk to us. I read a lot so I can write. I do not know everything though. Which are going to trial 3?
If you asked my wife what pregnancy was like from EOM 3 to the end, she would say it took too long and was at a standstill. Thank goodness we are not like elephants.
“Which are going to trial 3?”
The Astrozenica trial with recombinant adenovirus is in phase 3 trial. It has been paused because of a single adverse event. I expect that was chance and it will resume soon.
The Moderna mRNA trial. I have a FB friend who got her second injection yesterday and I’ll get mine tomorrow. They still haven’t enrolled their 30K goal.
There are four other trials, at least two of which are recombinant spike antigen, slated to start in St. Louis, but I don’t know if they’ve started enrolling yet.
As for your wife’s comment, it makes my point beautifully. She perceived a standstill at a time when the fetus was daily undergoing transformative change. You have to know where to look.
Here’s a COVID-19 vaccine trial tracking site:
Just heard that there were two adverse events associated with the AstraZenica trial. Both apparently involved individuals with MS. Guess a recombinant chimp adenovirus vaccine might not be a good idea for people with an autoimmune disorder.
I guess I will not be taking that one – recombinant chimp adenovirus.
Plenty of other vaccines in the pipeline.
I have been reading them in the article you gave me. I am assuming you do not know whether you are receiving a placebo or the real thing. Although the impact of the effects from the real drug should alert you to what you have been given. Unless you make yourself believe.
Nice. Thanks, Bill.
Correct. The Moderna trial is double-blinded. From reading the results of the Phase 1/2 trial, though, the vaccine side effects would seem to unblind it. I know where I can get the antibody test if I want to find out my status. So far, my surmise is still that I’m in the placebo arm. Which is still an essential role in a controlled study like this.
No “fatigue, chills, headache, myalgia, or pain at the injection site?” That could be just you as we could react differently or not at all. After all is said and done, I think I would go for the test before getting in line for an official inoculation. Just add it to my yellow card list of inoculations.
I waded through most of the way through the ones in phase three (or starting) and links. I will probably comment on them, with a short writeup, this weekend and just identify the others.
Have you read Dr. Eric Topol’s critique (letter) of FDA Commissioner Dr. Stephen Hahn’s misuse of EAUs? Interesting stuff. There is also a survey (Medscape) from early this month supporting Topol’s position on the misuse of EAUs by the FDA. It is obviously trump influence is involved. I did reference it.
No need to openly side with either, just curious.
I may have posted too soon. By 1 AM I developed a headache and joint/muscle pain sufficient to drive me into the bathroom for ibuprofen. I’ve held off on the NSAIDs since and by mid-morning, I spiked a mild fever.
Since I’m not allowed to volunteer for another coronavirus trial for two years, I haven’t been assiduously perusing the literature on the other trials.
Needless to say, I side with Topol and the valorization of data over politics.
This sounds like one of those commercials where the two older kids say to each other, “Let ‘Mikie’ eat it” as they hand off a piece of food they do not want to try to a young kid. Sounds about right. At least, you know what you got may be real.
Hope you feel better.
Front row seat. Neat.
I feel better this morning, so much so that I’m headed out for a 30 mile bike ride in about an hour. I’ll get the antibody test at my own expense to see if I’m actually in the vaccine arm.
Hopefully, you have a companion going with you or have a means of contact along.
Thanks for your concern. At my wife’s demand, I bring a cell phone whenever I ride. I do ride alone these days. In the event, I covered the distance in about two hours uneventfully. The vaccine side effects appear to be behind me, and there are no additional boosters scheduled.