Our presidential election is only days away. Forty eight
million people in America are uninsured and healthcare costs are rising two to
three times faster than our nation’s GDP. Where will America’s healthcare
system be in 5 years?
Welcome to ReachMD’s monthly series focussed on public
health policy. This month, we explored many questions facing healthcare today.
Some estimate that more than one out of every five drugs
prescribed in the United States is for an off-label use. As doctors, it seems
like we should be concerned about this issue, yet I am not sure no one are
prescribing drugs off label.
You are listening to ReachMD XM 157, the Channel for
Medical Professionals. Welcome to the Business of Medicine. I am your host, Dr.
Larry Kaskel and joining me today Mr. Mark Herman, partner
at the law firm of Jones Day and he defends drug and device companies in
product liability cases, he also co-hosts a blog known as the Drug and Device
Mr. Herman, thank you for joining me.
Thank you very much for inviting me. It’s good to be here.
Off label is any use that is not indicated in the package
insert. So if you prescribe a drug for a different disease then the insert
says it is indicated for or a different patient population, it is indicated in
adults but you prescribe it in a pediatric patient or a different route of administration
or dose or frequency, it is an off-label use. It is important to know off-label
use is entirely legal. Doctors are allowed to prescribe drugs for any
appropriate use. The FDA does not control the prescription of drugs, but
manufacturers are not allowed to promote drugs for off-label use. So the
doctor can use it for that use, but the manufacturer cannot encourage the use.
They typically say they cannot answer it and they are permitted
to put you in touch with typically physicians on staff with the drug company,
who are allowed to answer it, but the drug reps cannot promote off-label uses.
Yes, as a legal matter that is absolutely true.
Unless something goes wrong.
It is certainly very, very common. That is you said in the
lead that it was about 20%, I have seen estimate saying that from 25% to 65% of
all prescriptions are off-label; and in certain specialties <_____> oncology,
the numbers are up at 65% or more prescriptions being off label, at least early
in AIDS treatment and maybe still today, just about all patients were getting at
least one off-label prescription, so it is hugely commonly place. Whether or
not the doctors know that a particular prescription is off label, I will defer
to you that is I do not know what doctors know about labelled indications and
that might vary by specialty, by whether it is a drug or device, but certainly
it is happening all the time. It is an absolutely routine to have off-label
I do not know how many lawsuits were filed against the
doctors in that case. So I can’t tell you what the answer is, but the question
of course is different for the doctor than it is for the drug company. For the
doctor, the question is did you meet the standard of care, and for the drug
company, at least in the criminal case, or the case brought by the FDA, the
question is, did you promote the drug for an off label use? So, different
alleged seen, and you could have a different result in the lawsuit.
The first question is what you should do and the answer is of
course meet the standard of care, if the label indication is the standard care,
use the labelled indication, and if an off-label use is the standard of care,
then use the off label indication, because you are thinking about the patient
and you have to do what is best for the patient. The problem is if you
prescribe it off label and something goes wrong and there is a lawsuit, what
happens then, and the difficulty is that if the plaintiff can come up with an
expert witness who says that your off-label prescription fell beneath the
standard care, then you have your expert witness saying that you met the
standard of care, but they have their expert witness saying that you fell
beneath the standard of care and they have the package insert that they would
put in front of the jury showing that look it is not even an approved use, how
could the doctor who have done it? So they have that little added bonus if
they come after you in a malpractice case of being able to point to the package
insert in addition to the expert’s testimony.
Let us move on to a medical device. I do not particularly
prescribe a lot of them, but I am curious how you would use a medical device
Sure, in the case that went to the Supreme Court involved a
cardiac catheter, it was not indicated for use in patients with calcifications
in the artery, but this patient had calcification. It was indicated a balloon catheter,
was supposed to be inflated only to a certain pressure, and when that pressure
did not work, the physician inflated it to a higher pressure. So, it is off
label and that it is not an indicated patient population and it is not an
indicated route of administration, and then of course, the patient has an ill
effect, which has what prompted the lawsuit.
And in that case, what was decided?
In the context of
devices for that type of medical device, the manufacturer was entitled to
preemption defense, so the manufacturer could not be sued. The physician could
be sued and the question in the case against the physician would be whether or
not he met the standard of care. I am fairly confident there was a lawsuit
against the physician, but do not know what the result of that was.
Yeap, the only way to
sell either a prescription drug or a prescription medical device in the United
States is to have the FDA approval.
And what if they want to get an off label use? Do they have
to go back in front of the FDA?
Yeap, that is you start with no labelled uses, your drug,
which say it is the that is drug is not even on the market, so you go through
the whole testing process of laboratory tests and animal tests and preliminary
safety tests and efficacy tests and then you get one labelled indication, then
you are on the market for that labelled use, but either you see other possible
usage or physicians using the drug, see other possible uses, and there are
off-labeled uses out there in the world, either speculated about or actually
being used, then the drug company has to go back and do an entire new set of
clinical trials to show that the drug is safe and effective for that new
indicated use, and if it gets it, the FDA will add that use to the approved
But that is a very expensive, lengthy process you have just
You got it. You are talking about tens of millions of
dollars in many years.
So do they do it or do they do not have to because they see
that they are getting the business irrespective of having to do the trial?
I mean does it become standard of care just by everybody
It may. There are certainly some-off label uses that are
standard of care, and for the drug company there are whole collections of
things to think about on it. Sometimes, the drug company is already doing the
clinical trials for the off-label use and it’s standard of care when it is just
the matter of the FDA reviewing the data and looking at it and finally giving
you the indication and then what has already become standard of care becomes
labelled. But there are other situations where drug company simply is not
going to bother, getting the off-label use indicated. If it is a tiny little
patient population, you are not going to spent 10 million dollars to one
clinical trial to sell two doses of the drug and make 2000 dollars in profits.
So it may simply not make sense to get a labelled indication for a drug.
I would like to go back to day-to-day operations and back to
that question of informed consent. Do you see in any of your trials that a
physician has actually sat down with the patient and had them sign an informed
consent and that actually helped them in their defense?
The question of
whether or not physicians had to disclose that they were prescribing off-label
uses with a huge, huge spat back in the middle 1990s. Basically, every State
that has spoken about it says that off-label use is not a required piece of the
informed consent process. So it is the law currently is there is no legal
obligations to tell patients that we are going to make an off-label
prescription. There has recently been some scholarly literature that has
suggested that that is incorrect and that physicians ought to tell patients if
they are making off-label uses of drugs, but to-date anyway, no court has
adopted that theory. If you wanted to, you could put it in your informed
consent form or you could tell patients I am going to prescribe this drug, it
is going to be off label and you would have to be very sensitive about how you
explain that so that the patient was not scared away from taking the beneficial
Well, a federal bureaucracy is always going to be slower than
physicians treating patients. You have somebody in your office you have to
treat him. You cannot say stop. We are going to run clinical trials for 3
years and see whether or not this works. So there is no way that you are ever
going to have labelled indications that precisely match what is going on in the
practice of Medicine. The question that is what is the best regulatory scheme
to have? What we have now is sort of a slower FDA and a faster practice of
Medicine and you hope that those two schemes work in together provide topnotch
Are there better agencies in other countries around the world
than the FDA.
There are different agencies. Most developed countries have
some type of agency that is passing judgment on drugs. Some of them approve
drugs more quickly than the FDA, some of them more slowly. Whether or not that
is good, of course depends on <_____> on whether or not the drug had any
unexpected side effects. If the drug comes on the market quickly and is good
and it is saving lives, then it was a good thing the agency act quickly, but if
the agency acted quickly, put a drug on the market and then there were
unexpected in severe side effects, the agency will be criticized for having
acted too quickly. So there are.
DICTATION ENDS ABRUPTLY.