Clinical Trials, the FDA and “Label”

One doesn’t realize the absolute ignorance of our media until they report on an area where one has expertise. You also realize the degree to which the media relies on the public’s ignorance. The conflation of FDA approval of an expanded use of an approved drug or drugs and efficacy for that expanded or new use in the above article is astounding.

Everyday, a physician somewhere prescribes a drug for a use for which it was not originally approved. Everyday. But just because the drug is not approved for the use the physician makes of it does not mean it is ineffective. On the contrary, the drug is quite effective and has found an “off label use.”

A drug developer obtains a very narrow approval for the use of their drug. It’s efficacy and safety must be demonstrated for the treatment of a certain disease state for which approval is sought. When the FDA issues it’s approval, it is with a “label” of approved uses and also a laundry list of statistically significant side effects. Stray from that label even a micron in marketing that drug (or device) and it is trouble of galactic proportions

But as I said, often a new ( and more lucrative) use is found for the drug. It is hell keeping your sales force in line with sticking to the label when they know their customers (the doctors and hospitals) are using it for something else that will generate more sales. Sure, a manufacturer can expand the label, but with some exception, it requires clinical trials as if approving the drug de novo. That is a long and expensive process.

Depakote- it was originally approved as an anti-epileptic. But someone (my friend) discovered its use (at higher dosages) for treating bi-polar disorder. It was also discovered (at lower dosages) to treat migraines. It’s label may have been expanded for these uses (or not) but before it was, it was prescribed heavily for the additional uses.

Now doctors are trying a similar expanded use employing hydrocloroquine and azithromycin (with zinc) to treat COVID-19. By all reports, those on the front lines are calling for its use or are eager to try this as a mitigating factor, that mitigation being the shortening of hospital stays which is significant in not overwhelming our hospitals. Overwhelming our hospitals was the core reason for “flattening the curve.” It was the core reason for the lockdown nation we now live in.

I get it when the bureaucrats like Dr. Fauci, and he is a bureaucrat first, decries the lack of approval. Approval is a government process aimed at assuring that the drug works as claimed and doesn’t harm anyone. Fauci is married to process and his bureaucrat mind perceived the President as if he were promoting a drug for a non-approved has, as if he were the original developer. Fauci’s as a government functionary can’t fathom anything being promoted outside of process. I get that. I don’t agree with it, but understand his mindset.

But these aren’t new drugs and their side effects are well known. In general, they are very well tolerated. This isn’t some kind of cowboy experiment.

One can only conclude that our media is actively rooting for this virus. A bunch of 20 and 30 somethings writing these stories in either ignorance or knowing full well that we are are ignorant. When this is over, someone needs to take The NY Times standard of actual malice and toss it in the ash bin. The media needs to be taken to account for its falsities.

And on the subject of the sacrosanct “FDA Approval” now being touted by our media. Here is a drug that was FDA approved. How did that work out:

https://www.fiercebiotech.com/biotech/novartis-shuts-down-protez-shelves-400m-antibiotic-program

Therein lies the not so funny comedy of this situation. When approved drugs kill or harm people, the same media that lauds the FDA today as being necessary m, decried the FDA yesterday as a means to attack “Big Pharma.” Either way, our 1984 media wins.

But the bottoms line is this, the FDA, with some exceptions, was never meant to come between a doctor and the practice of medicine like is being suggested by our media now. Their attacks on the President are not just biased, they are dangerous

Thanks Flip for this - so much confusion about off-label.

You correctly mention that a company's sales force must painfully avoid promoting their drug for such an off-label use. A non-company associated clinician could publish a study on off-label use and the FDA would prohibit the company from distributing copies of the publication. The Supreme Court had to intervene and slap FDA down for such anti-1st amendment efforts.

What is happening before us is a situation where otherwise knowledgeable doctors got into Manchurian Candidate zombie mode when asked about prescribing HCQ/Zpack to their v sick corona patients: "Gee IDK, the data on its effects on corona are not definitive".

There is a reason for this gobsmakingly dopey behavior: 50 years of poor TORT law that breeds ambulance chasing lawyers. FDA approval gives doctors cover as their lawyers can argue "best practices". Hence we are witnessing dangerous conditioned behavior.

FDA does not regulate doctors but they over-regulate their tools. The C19 Task Force has bitchslapped the FDA down to dog-catcher status and hopefully we will see real FDA reforms after all this.

May I add to it?

For the FDA to approve a drug for indicated use, it, of course, insists on proof. Proof of safety, and of efficacy. Efficacy is showing it does, indeed, do what you think it does, in patients. Safety means it doesn’t significantly harm or kill.

I’ll talk Efficacy only. “Proof” of efficacy means showing data from studies. Typically, scientific studies are done, carefully controlled and monitored. It’s a very formal experiment.

Protocols are written, approval sought, patients recruited, med centers chosen...finally, the experiment is run according to the protocol. Data is gathered and analyzed, statistical proof sought and demonstrated. Patients monitored long after initial trial is over. Initial, because very few people are in the study at first. If it all goes well, the study is expanded to a larger population...long, drawn out process.

And expensive!!! Sometimes patients are paid. Dr.s paid. Hospitals reimbursed, for the entire patient stay. Test paid for. Patient monitors hired and paid...huge $$$. Can run to hundreds of millions, just for the clinical trials! Cost to create a drug and get it to market is usually over $1 Billion.

Drug Manufacturers always seek first to compare a new drug to an old one, or other treatment, that has a known efficacy. Then see if the new one has better, worse, or the same outcomes. If no other treatment is available, they use a placebo instead (sometimes they do both). Placebos have no effect.

But if there is a decent chance of serious injury or death from your disease, and the new drug may save you, you sure as heck don’t want the placebo. In fact, it is considered unethical, by most industry people, to even allow it. What doctor would prescribe “nothing” to his mother instead of the drug that could work? What patient would say, “OK” to it?

The “Gold Standard” is a “Double Blind” experiment (trial). Where the patient doesn’t know if they are on either drug or placebo, and the medical workers don’t know, either. Prevents bias. Double Blind is the biggest, most expensive, longest type of clinical trials there are.

Sometimes they allow deviations, ahead of time, after long argument and delays, for certain, exceptional cases. Ahead of time, because drug makers (manufacturers) include the FDA people in the loop before asking for approval to go for the trial. Yes, the manufacturers need FDA approval to run their clinical trials, and that is a battle, always.

Let’s call the new drug “A,” the existing treatment “B,” and the Placebo “Placebo.” Pretty much any controlled A against B trial is better than A against Placebo, as B will at least give some relief to the sick patients. It can also reduce the sample size (number of patients enrolled), and possibly (though discouraged, and somewhat rare) historical data can be used for B, with or without requiring new B proof.

As of today, there is no approved drug treatment (“B”) to treat or mitigate Covid-19. Hence the moon shot effort to find one, the first A, and use it.

Yet A against Placebo is the worst type of study, ethically, you can do. Patients must agree to the trial. Who wants to sign and give approval for a possible placebo when you have Covid-19? For Hydroxychloroquine, that is what Dr. Fauci wants. That is what the FDA insists upon, by default, by internal and external policies and regulations.

The FDA has insisted on these type of trials for many years, for a new drug to be approved, or to approve a new, marketed, use. Long, drawn out, Hydroxychloroquine against Placebo trials. Fauci is dug in, like the FDA always is. They know only one way, and any deviations are head exploding. “Off Label” use makes their heads explode, spin around on their necks, and puke green vomit.

Bad stuff, eh?

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