FDA senior scientists

“The White House considered issuing an executive order greatly expanding the use of investigational drugs against the new coronavirus, but met with objections from Food and Drug Administration scientists who warned it could pose unneeded risks to patients, according to a senior government official.

The idea to expand testing of drugs and other medical therapies was strongly opposed by the FDA’s senior scientists this week, the official said, and represented the most notable conflict between the FDA and the White House in recent memory.”

Ahem.  Here is the full WSJ piece.

Comments

Re: Ahem

The Ahem word in the comment is concerning.

Do you have a cold? If you have a fever, and a cold, and severe respiratory distress, it will go away by April.

If the FDA review of a CDC botched test for covid was anywhere as good as a hurried up test for new drugs, Houston, we have a problem.

Why should we listen to scientists if we don't understand what they are saying. After all, I knew this was a pandemic months ago. It'll just run through us so what's the hurry.

Senior FDA scientists are still blocking recognition of the miracle cure Silver Solution, as seen on TV. Take it now, and the problem will certainly be over by August.

And, cal me, I have abridge to sell you.

Should only be used as a last resort for patients likely to die. I worked for twenty years in drug discovery- the first hard hurdle for any drug candidate was the toxicity tests that had to be run, first in animals, then in Phase 1 with healthy volunteers.

Now, you can try things for off-label use- those have already passed clinical trials.

Most of these are drugs already in development for others uses. Tox would certainly already have been done. New vaccines is another story. Notably, the most advanced candidates are brand new therapeutic classes with very little data in humans.

I can’t read the article because I don’t subscribe to the WSJ. Did this senior FDA scientist identify himself?

The safety trials of phase 1 are conducted recruiting healthy people, not sufferers of the ailment the drug is supposed to have effect on. These people are paid well, the equilibrium price that attracts enough subjects, desperate individuals that risk serious adverse effects, potentially including death (I think to remember that one young guy died in a test conducted by Astra Zeneca a decade ago).

So, the FDA wants to first administer the treatment to perfectly healthy people to be sure it is safe enough to administer to dying people for whom it could be a possible cure.

You can’t make this stuff up.

You may recognize killing people as a thing medicines are not supposer to do.

Too true!!! Better to avoid a few thousand accidental deaths in trial than a few million oncoming obvious deaths plus a global depression.

I much prefer preserving the sanctity of the FDA and preventing accidental deaths. Who needs to stop a million death pandemic plus a global depression.......

"Better to avoid a few thousand accidental deaths"

It is a shame Doctor Mengele is not available to oversee the "accidental" deaths. For the greater good, I mean.

They’re voluntary human trials.....

There’s no pretty answer here. But understand the FDA foot drag kills way more people directly and maybe even more with the economic response...

"It is a shame Doctor Mengele is not available to oversee the "accidental" deaths. For the greater good, I mean."

Probably a troll post but, anyway, ethical guidelines on medical trials are pretty well-codified at this point. They are covered in U.S. federal regulations and each trial must be overseen by an independent Institutional Review Board that is responsible for implementing those guidelines.

The foundation of modern medical ethics is informed consent. Volunteers must typically be adults of sound mind, free from any sort of coercion, and the amount of compensation they receive must not be so high that it opens up the possibility of volunteers putting themselves at unreasonable risk just for money. Prisoners are typically excluded and there is a higher threshold to cross for testing on patients who are minors or have diminished mental capacity.

People volunteer to serve as combat soldiers and firefighters. We can certainly expect to find some volunteers willing to test out a life-saving drug.

That clearly, we need to throw them out.

And as an answer to our prayers, Solver Solution is still available, like a miracle, even against the opposition of those unwilling to recognize that it offers the best chance to allow one's faith to work against any weakness of the flesh.

It makes more sense when you realize they’re minimizing potential blame, not potential suffering. This is partly from asymmetric public outrage, as with Vioxx in 2004. Because of the unseen effect, few will be outraged that the standards of scientists were set too high.

Indeed, Alastair. It is the first rule of any bureaucrats, codified by some Sumerian tax-collector 5.000 years ago: “First, cover your ass”.

Note that almost everybody here try to show how either the FDA or the White House are right, no comments about asking the guy dying. Once you get in the big State machine you do not have the right to express an opinion about your life anymore, you are just too ignorant to disturb the highly complex, National-security questions that are reserved to Those who studied or Those who were elected.

"You can’t make this stuff up."

Yeah, I know I didn't make up "First, do no harm."

"First, do no harm" is from Hippocrates, from his book "Of the Epidemics":

https://www.health.harvard.edu/blog/first-do-no-harm-201510138421

Your link argues *against* both of your points:

1. “Yes, the pledger [in the Hippocratic Oath] commits to avoiding harm, but there’s nothing about making it a top priority... there is no clear priority given to the avoidance of harm over the goal of providing help.”

2. “if physicians took ‘first, do no harm’ literally, no one would have surgery, even if it was lifesaving. We might stop ordering mammograms, because they could lead to a biopsy for a non-cancerous lump. In fact, we might not even request blood tests — the pain, bruising, or bleeding required to draw blood are clearly avoidable harms.

But doctors do recommend these things within the bounds of ethical practice because the modern interpretation of ‘first, do no harm’ is closer to this: doctors should help their patients as much as they can by recommending tests or treatments for which the potential benefits outweigh the risks of harm. Even so, in reality, the principle of ‘first, do no harm’ may be less helpful — and less practical — than you might think...

The fact is that when difficult, real-time decisions must be made, it’s hard to apply the ‘first, do no harm’ dictum because estimates of risk and benefit are so uncertain and prone to error.”

You can’t make this stuff up!

You quote from the article:

The fact is that when difficult, real-time decisions must be made, it’s hard to apply the ‘first, do no harm’ dictum because estimates of risk and benefit are so uncertain and prone to error.”

That is absolutely correct. I made my point badly by referring to something Hippocrates said. But my point still stands, which is that "Massimo" appears to be claiming there's some sort of insane situation when doctors first try medicines on healthy volunteers, then try medicines in placebo-controlled double-blinded studies, and only then give medicines to sick people. But it's not an insane situation. It's science.

I will yield to no one in my defense of trying medications based on informed consent. But it's hardly "informed" when some doctor wants to try a drug that hasn't even being through clinical trials on an extremely ill patient who may have multiple other medical conditions (e.g. chronic obstructive pulmonary disease, heart failure, diabetes, etc.).

I'm guessing that neither you nor Massimo has a medical background. That's fine, I don't either. But I do know that there are solid scientific reasons why drugs go through the trial process that Massimo seems to find so ridiculous.

I suggest you read “Bad Pharma” of Ben Goldacre. You will find that the way trials are structured today is to protect the large Big Pharma companies. It is a typical example of industry capture of the regulator.

But my main point is that nobody seems to listen to the patients, here. If I am judged too old, and I am left in a room without respirator and filled up with benzodiazepine (to die quietly) and morphine (to die happy and fast), I would be very willing to give my consent to try something new on me. I will actually try to understand how the drugs are supposed to work and I will try to negotiate what drug I want, assumed that more than one are available. Moribund people have agency.

"But my main point is that nobody seems to listen to the patients, here."

I strongly agree with listening to patients. For example, in cancer care, I think it's profoundly immoral to deny patients the right to be used as "guinea pigs." Part of that's because, if I'm ever in the unlucky situation of having terminal cancer, I'd want to try a "guinea pig" treatment.

My concern was, in this particular instance, that these patients are probably profoundly ill, and the illness has come on suddenly. So they and their families simply don't have the time to become very "informed" about treatments. Again, this is in contrast to, for example, cancer patients who generally have months or even years to become informed about their condition.

So in this particular instance, I'm concerned about patients who simply don't have the time or the ability to become informed. You give a person who is coughing his lungs out a sheet of paper with writing on it that says, "Blah blah blah blah blah..." and tell them that the drug may help them, they'll sign it. But I don't really consider that "informed consent."

Bad logic. To put it in economics terms there are opportunity costs to giving a dying person an untested drug. There is always another treatment. You may hate that the other treatment has long odds, but literally no one has proven that this new drug has better odds. Indeed the reason to test it on a healthy person is to make sure it doesn't kill you, the more sick and vulnerable person more quickly!

You got me!! Thanks, now I go to the hospital here in Modena and tell those pesky guys triaged out of the ventilators that they are left to die because the Opportunity cost.

Did you think your risky new experimental drug came with a free ventilator?

An irrational deference to the Precautionary Principle
Vs
The leader of the free world.

Who would win?

“expanding the use of investigational drugs against the new coronavirus...could pose unneeded risks to patients.”

As opposed to the *needed* risk of drug lag? The perfect drug means little to those who‘ll die in waiting. At the margin, cost of no drugs > cost of riskier-than-normal drugs.

Individually, how risky is too risky? Let patients be the judge of that. Institutionally, we can automatically accept drugs approved in other rich countries and fast-track the rest.

The stock market dropped all the way down to the level of Trump's inauguration. Trump must be so happy to relive those days all over again!

Trump made my retirement account 2016 again.

Haven’t you got something better to gloat about, Mr Krugman?

You are posting something completely unrelated to the thread, gloating about the poor stock market reaction to a world pandemic. Clearly, you're a smart, well adjusted guy. /s

I'm glad you can be happy about the local political effects of thousands of people dying across the globe. I'm sure all those dead victims were glad to help you out in your chance to score a cheap political point.

I don't like the looks of this:

"New C.D.C. data showed that nearly 40 percent of patients sick enough to be hospitalized were aged 20 to 54. "

These people will likely survive but will see financial hardship (if you are on the left) or become a drain on society (if you are on the right).

https://www.nytimes.com/2020/03/18/health/coronavirus-young-people.html

Maybe:

Almost 100% of patients sick enough to be hospitalized were hospitalized. The rest were not. :-)

I would trust the domain experts on this. They have a lifetime of experience of how drugs fail testing. That is with what negative consequences.

We should trust the experts who outlawed a known test for Corona (PCR) and repeatedly threatened doctor Helen Chu for daring to use an influenza study to investigate a pandemic. Repeatedly. Threatened. Told to stop investigating “or else.” Because of IRB.

Compare Taiwan, South Korea, Japan and Singapore to your government. The US experts are completely incompetent at best, more likely actively harmful in spreading the disease.

Trump deserves to be thrown out of office for not overruling the experts. But he’s one of many who deserve termination.

He has been perfect - read the transcript.

If you keep saying "outlawed" that just shows that you still have not processed what happened. Researchers and drug companies kept working on their tests at full speed. It was a question of which tests were qualified for diagnostic use under the FDA system.

Chu bent the rules on research rules, and good for her, but you should be aware that one of her primary roadblocks was US privacy law. Her research subjects signed a release for a flu study. Full stop. That means they had not released their samples for a coronavirus study. She went ahead and did it anyway.

Lol you get what you get. With an FDA like this you get what you get.

So a virus projected to kill well over a million people globally and cause a significant global recession if not depression, can’t be cured quickly because we are worried about killing people in the trial phase?

Sorry guys reality isn’t optional. YOU GET WHAT YOU GET. Run the trials and let them die!!!!

Either this is straight up cowardly and honorable, or it is parody of some shady comments above.

"dishonorable"

This and all the other 'try the drugs' arguments above presume that these drugs, or at least one, would be effective and that trial deaths would then be justified.
But there is another possibility: that you would kill people for no gain.

Well yes of course. But that is inherently the nature of risk. Every time a fire fighter goes into a burning building to save someone and it collapses on him before he gets out, he died for no gain.

Would you argue that fire fighters should never be allowed to go into burning buildings attempting to save another human?

The FDA is best at protecting itself, not the public. Alistair and Richards, above put it right.

But hell, the CDC couldn't even put a bunch 'a dumb chemicals in a box and send it away. Then the FDA made sure that couldn't be fixed quickly. The institutions are crappy.

"bunch 'a dumb chemicals in a box"

More parody?

Looks like the rest of the world was able to put the right dumb chemicals into boxes, only in the US were the wrong dumb chemicals put into boxes.

Looks like Italy is prepared to ship a half million of these boxes to the US.

See below on false positives and negatives, and dumb chemicals.

They aren't full kits. Just the swab kits. Italy is a major producer of medical swabs.

"I want a treatment" brought to you by the same people who said "I want a test!"

In both cases you need a certain quality level to keep your efforts from being self-defeating.

Especially given wide reports of effective off-label treatments online.

https://amp.theguardian.com/world/2020/mar/18/japanese-flu-drug-clearly-effective-in-treating-coronavirus-says-china

“You need a certain quality...”
You’re joking, right? We’re you paying attention to the test rolled out in the US? Beginning to think you’re the parody account here.

Or are you less informed?

A report out of China was that fully half of their positive results were false positives. That means if you're doing contact tracking you're doing twice as much, and then twice the isolation of contacts, than you would need to do.

Which of course assumes you have the resources to do twice as much as you need to do.

You think it's better to do no contact tracing at all than to do twice as much as you need to eliminate the virus as China has????

And of course if you have some significant number of false negatives, then all that work is not containment at all.

A report out of China this morning is that they have no new cases. It would be interesting to know if this is purely a test based result, or knowing about the false positives they now require that you be both symptomatic and positive to be "a case."

At some point the reliability of tests will improve, surely.

There are plenty of healthy people who would voluntarily risk death while trying out experimental drugs during a pandemic. We find these people in occupations like military special ops, helicopter linemen, and specialized firemen.

We (society) give them appropriate respect, compensation, and life insurance. And we take care of their loved ones.

Of course this mindset is alien to "FDA senior scientists" or j-skool grads in their respective bubbles.

And the biggest opponents to helicopter-drops are monetary-policy quacks.

What is it about specialization...that leads to extremism?

There are as we speak a number of trials going on. Some with existing drugs designed for something else.

I understand the arguments for both sides.

Maybe it should go this way.

How would you suggest taking these ten potential treatments to distribution in two months?

Two months! the bureaucrats exclaim.

Actually a month and a half, but we thought we would be generous.

Impossible!

Fine. I give you two hours to come up with a list of people who could come up with the answer if you can't.

But there are only three of them that could possibly work!

Much better. So you are saying you could do it in a month?

If the models are anywhere close to correct, the choice is going to be between letting people die via triage, or have something that could potentially help them.

I'm starting to see the foundations of my prediction that by the end of the week the media and hangers on will be complaining that this is overblown and an overreaction.

If you think it is really bad, it is a no brainer that figuring out a way to hurry testing and trials of potential treatments is the way to go. But if you are a denier, then it is profoundly important that the treatment be developed according to set practices and be ready in three to five years.

China, Europe, Japan--all these countries could run clinical trials of these drugs.

They don't have an FDA.

Although we believe they are not as smart as we are, why aren't they running trials?

Why is it only us that considers we should run the risk on our citizens by cutting short parts of the clinical evaluation?

Haven't we been told that some other country's value life less than we do?

Here's an example:

https://www.independent.co.uk/news/world/asia/coronavirus-treatment-anti-viral-drug-favipiravir-avigan-wuhan-china-a9408066.html

Why would anyone with the least bit of awareness of how the CCP operates--especially regarding the CCP-Coronavirus--take anything they have to say at face value? For all we know, the CCP is conducting trials.

China has the NMPA
Japan has the PMDA
Europe has the EMA

All three can be more onerous than the FDA depending on the situation

I didn't mean quite literally that they didn't have a regulatory regime, it's just that they characterize FDA as some unique blocker that blocks everything that moves. Of course I am also aware of clinical trials abroad and how folks search out, say, Germany or other countries to test through academic associations.

In other words, everyone tests drugs first, not just us, and if there were a faster path, Pfizer would find it.

For those who think we have capacity to somehow magically quickly produce quantities of any drug, even if one should get through testing and prove effective (itself an unlikely event): we can't even produce the tests.
As of today (March 18) my state - Minnesota - is no longer testing, period, except for three instances: medical personnel, residents in 'congregate living' (ie: nursing homes) and at-risk patients already in hospital with other problems. 1700 tests remain frozen and cannot be analyzed due to lack of supplies. This is after repeated appeals to, and promises from, Federal officials. Everything you have heard from them about availability is a flat lie.
That's the state of our production ability. That's the state of our knowledge about the spread of Covid-19: we have no effing clue.

That's not lack of production capability, Wally, nor even lack of knowledge. It's simply that bureaucrats have made themselves immune to doing anything at all risky to them.

There is even a Chinese and a German test PUBLISHED ON THE WEB. Apparently tests are coming on stream everywhere except here.

As noted above, the ultimate head of the FDA has already given an opinion about the need for tests. “The virus that we’re talking about having to do, a lot of people think that goes away in April, with the heat, as the heat comes in, typically that will go away in April,”

This is after repeated appeals to, and promises from, Federal officials. Everything you have heard from them about availability is a flat lie. That's the state of our production ability. That's the state of our knowledge about the spread of Covid-19: we have no effing clue.

Yes, it's too bad Donald Trump isn't the kind of guy--and I doubt Joe Biden is any more this kind of guy--who has someone give a daily press briefing about how many tests were performed nationwide, and with a state-by-state breakdown. And then makes a prediction for how many tests will be performed a week from now.

And then takes questions about what is being done to expand the testing, and what the problems are, and what the potential solutions are.

Rather than talking about paying laid off people, the federal government should be talking about how much money is being funneled to states and to companies to continuously increase the testing rate. And I'm talking about doubling every week for at least the next five weeks.

I'm thinking that the people that have the scientific knowledge to evaluate this debate are being awfully quiet. Perhaps they're busy right now. Sure is a good thing that we who don't are volunteering to step up to the plate.
Good god.

Alas, it's not so much about scientific knowledge as about risk aversion on the part of the bureaucracy.

There ought to be a parameter that would be reset in the agency's cost benefit analysis that would make the result come out positive in more cases as the benefit from a cure now would be multiplied by the additional persons not infected. This would not meant that just anything goes.

I have 20+ years of experience in drug discovery and development. Tyler and friends should not be talking about drug discovery, they have no clue. Go to the In the Pipeline blog for a more realistic view of the world.

I have 20+ years of experience in drug discovery and development. Tyler and friends should not be talking about drug discovery, they have no clue. Go to the In the Pipeline blog for a more realistic view of the world.

In this particular post, Tyler said, "Ahem." You don't think he should say, "Ahem"? (Note: I'm not even sure what "Ahem" means!)

I don’t know what “ahem” is supposed to mean either, I only know that Tyler or Alex do not understand drug discovery and healthcare - they prove this at least once a month, right here on Marginal Revolution. I find this quite amusing, and I’m not the only one. All I’m saying: if you want to understand drug discovery have a look at Lowe’s blog and don’t waste your time here.

I don’t know what “ahem” is supposed to mean either, I only know that Tyler or Alex do not understand drug discovery and healthcare - they prove this at least once a month, right here on Marginal Revolution.

OK, it's good to have expertise. Point out their mistakes. To my knowledge, they don't censor comments. So have at it if you think they're wrong.

Perhaps I should, but I simply do not have the time to do so.

This website always confuses me on FDA issues; I have worked a bit in drug discovery and the FDA scientists are bang-on right here. Look, compassionate use excpetions are nearly always granted. But the potential here for snake oil that will harm patients, especially in this atmosphere, is not small, and it is irresponsible and foolish to pretend otherwise.

I don't know anything about drug discovery, but that was my thought, too.

I'm particularly concerned when decisions are being made by people whose minds are focused on politics, and who know nothing about medicine.

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