115 – Labeling Changes & Post-Market Commitments (S8E10)

You ever get that prescription right and you
see that big old folded up paper? And it's easy
to think like, okay, that's it, right? Like science
is done, they figured it out. It's a common thought
for sure, but it's a lot more complicated than
that. Yeah, so that's what we're gonna dive into
today, right? We're gonna look at how those drug
labels, those drug labels can change, even after
the FDA gives it the green light. Yep. And we've
got some really cool stuff to look at today.
We've got, you know, guides on how a drug is
developed from its very beginnings and then all
the way through, like, how it works in your body.
Ah, the pharmacokinetic stuff. Yeah, all the
pharmacokinetics, the clinical trials, and all
the regulations. And so basically, the whole
shebang. The whole nine yards. Our mission today
is to figure out why those drug labels, which
seem so simple, aren't set in stone. Right. They
can change. They're not just like carved, you
know? Right. And how do we keep making sure that
all the meds out there are safe and effective?
Right. OK, so let's get into it. So what's the
first thing that could make them change a label?
After a drug is already out there, like people
are taking it. Well, the initial approval is.
It's a huge deal, it's based on a lot of data,
mostly from those clinical trials. But the thing
is, those trials are really controlled. They
use a specific number of patients, and they go
for a certain amount of time. Right, so kind
of limited. Very limited, right. So then, when
the drug's actually out there, it's used by so
many more people, people with all sorts of different
health problems. Yeah, all sorts of different
lifestyles. Lifestyles, everything. And that's
when sometimes new info pops up. Makes sense,
right? It's kind of like testing a new phone
in a lab versus, you know, like using it out
in the world. Oh, yeah, for sure. Like when it's
raining, you're juggling groceries, that kind
of thing. Exactly. So it sounds like, you know,
that initial approval. It's not the end of this
story at all. It's really just the beginning.
OK, cool. So this new information, like what
exactly can it reveal? What are we talking about
here? All sorts of things. You know, sometimes
side effects. like brand new side effects that
nobody saw in the trials, or maybe side effects
that were already known, but now they're happening
way more often than they did in the trials. Or
maybe they're way worse. Or they're more severe,
exactly. And any of that can lead to an update
to that jug label. So when we say update, what
kind of update are we talking about? Is it just
changing a word or two, or is it more than that?
Oh, it's way more than that. one major one is
safety updates. Like, if there's new data about
some serious risk or, you know, like we said,
if side effects are happening more often or they're
getting worse, that's gonna go right on the label.
Yeah, you definitely want doctors and patients
to know about that stuff. Absolutely. Then there's
what we call new indications. Okay. So that's
when, you know, more trials are done. And it
turns out, hey, this drug is also good for something
else. Something that it wasn't originally...
approved for. Oh, that's cool. So, you know,
maybe a drug that was approved for, I don't know,
like high blood pressure. Right. Ended up helping
with migraines, too. Exactly. And then there's
black box warnings. Black box warnings. That
sounds serious. Those are the big ones. Yeah.
Those are the most serious warning the FDA can
give. Wow. They mean there's a chance, you know,
of a life threatening risk or a really, really
bad side effect. And you'll see it right on the
label. It's in a black box. You can't miss it.
Yeah, I guess that gets your attention. It definitely
does, both for doctors and for patients. That's
a little scary to think about that, you know,
even after a drug is approved, there could still
be something that serious. Yeah, it's definitely,
you know, it's something to consider. It makes
you wonder, like, what does it take for them
to issue one of those warnings? I mean, the evidence
must be pretty strong, right? It has to be very
strong because it means, you know, that for some
patients, the risk might be bigger than the benefit.
Okay, that makes sense. So all of this, this
is part of what they call post -market surveillance,
right? Exactly. So it's not like the FDA says
approved and that's the end of it. Nope. They're
still watching even after it's on the market.
It's like an ongoing investigation. That's pretty
reassuring, actually. And they get info from
all kinds of places. So like what kind of places?
Well, like healthcare professionals, they can
report adverse events. Right, if they see something
going wrong. Exactly, and patients can report
them too. And then there are special studies
specifically designed to look at the drug's safety
over the long term. So they're looking at like
how it works for different groups of people,
maybe different doses. Yeah. How long the treatment
should last. Exactly. Things that they maybe
couldn't see in their shorter trials before approval.
So filling in those gaps, basically. Exactly.
Wow. So it's a lot of moving parts. It is. So
like if my doctor, let's say, she starts noticing
that a bunch of her patients who are taking the
same drug, they're all having the same weird
side effect that could actually trigger a review.
It absolutely could. Wow. Because that real world
observation is so valuable. Makes you feel like
you're part of the process a little bit. You
are, absolutely. Okay, so one thing that's important
to understand, and you kind of touched on this
before, is that when a label changes, it doesn't
necessarily mean that something went wrong with
the initial approval. It's more like, we're learning
more as we go. It's more about, yeah, our understanding
is evolving. It's good that it's not set in stone.
It's a good thing. It means the system is working.
It's working to keep us safe. Okay, so we know
the labels can change. We know why they change.
Let's talk about what the companies, the drug
companies, what are they required to do after
the drug is approved? to keep all this info up
to date. Good question. It's not just, like,
an honor system, right? Well, there's gotta be
some rules. There are definitely rules. It usually
comes with specific obligations. Like, what kind
of obligations are we talking about? Well, we
call them post -market commitments. Okay. You
can think of them like conditions that come with
the approval. Ah. So they have to do these things.
They gotta do them. It makes sure that the company
keeps gathering info, you know, after the drug
is out there. Keeps an eye on things. And they
gotta deal with any problems that pop up. Got
it. So what are the main types of commitments?
Like, what do they actually have to do? So two
of the big ones are post -market studies, which
are often these things called phase four clinical
trials. Oh. And then there's REMS, which stands
for risk evaluation and mitigation strategies.
REMS -S. OK, so post -market studies, I mean,
we all know about phase one, two, and three trials,
right? Those are the ones before a drug is approved.
Right. But what's the point of doing a study
after it's already out there? Well, phase four
studies, those happen after the drug is approved.
OK. And they have a few really important jobs.
One is they can get even more data about the
drug's safety. More data. So even after all that
data they collected before? Even more. Because
now they can look at a much bigger group of patients,
and they can look for a longer time. OK. Yeah.
And they can look at more diverse patients? Exactly.
Like different ages, different backgrounds, all
of that. So it's about getting the full picture.
Really? Exactly. And they can also see how well
the drug works for different types of patients.
Oh, right. Because everyone's different. Exactly.
Like, maybe different doses work better for some
people, or maybe the treatment should last longer
for certain groups, that kind of thing. And I
guess they can also look at really long -term
effects. Oh, right. Effects that might not show
up in those shorter trials before approval. That
makes sense. So it's all about getting more details,
filling in the gaps. So basically making sure
it really works the way we think it works. That's
it. And these studies, sometimes the FDA requires
them as part of the approval. Ah, so they're
not optional. Sometimes not. But sometimes companies
do them voluntarily, too. OK, why would they
do that if they don't have to? Well, you know,
they want to learn more about their drug. Maybe
find new ways to use it. New uses, that's interesting.
Yeah, could be good for business, too. So it's
a win -win. They get more info. And maybe they
can sell more of the drug. It can be. And the
important thing for us is the findings from these
phase four studies, those can definitely lead
to more changes in the drug label. Yeah. So if
they find out something new, either good or bad,
they've got to update that label. They've got
to update it. OK, that makes sense. Now let's
talk about REMs. That sounds pretty intense.
REMs are definitely designed to handle those
serious risks. So this is specifically for drugs
where there's like a higher chance of something
bad happening. Exactly. The FDA requires them
when the risks are big enough that we need to
take extra steps to make sure the benefits are
worth it. It's all about balancing the good with
the bad, right? Exactly. So these REMS programs,
remember that's R -E -M -S, they're tailored.
Tailored to the specific drug. Tailored to the
specific drug and its risks. And they can include
all sorts of stuff like, one common thing is
medication guides for patients. Oh, yeah, I've
seen those. Yeah, they explain things in plain
language. Right, not all that medical jargon.
Exactly. They tell you about the warnings, the
precautions, and how to use the medications safely.
And those usually come right with the prescription,
right? Right in the bag. So you get all the info
right away. It's right there. That's good. RMS
can also involve, like, communication plans for
health care providers. So making sure the doctors
and pharmacists know what's up. Exactly. know
all about the risks and how to minimize them.
And sometimes, it sounds like, it can even affect
how the drug is distributed. That's right. For
the really serious cases, there might be restricted
distribution systems. What does that mean, restricted
distribution? So maybe the drug can only be given
out by certain pharmacies. Oh, wow. Only ones
that are specially certified. OK. Or maybe it
can only be prescribed under very specific conditions.
So there's a lot of extra hoops to jump through.
And sometimes there are even monitoring requirements.
What does that mean, monitoring? So, like, the
patient might need to get specific tests done.
Oh, wow. While they're taking the drug. OK. You
know, to make sure they're not having those bad
side effects. So they're keeping a really close
eye on things. Really close. It's all to make
sure the drug is being used as safely as possible.
Yeah, it's a balancing act for sure. It is. You
want people... to be able to get them as they
need, but you also don't want them to get hurt.
Exactly, so all these REMs, they're really important.
They sound important. Okay, so let's say a label
does change, like we've been talking about. Okay.
How do they get that new info out? to everyone.
Right, to the doctors, the pharmacists, and most
importantly, the patients. Yeah, you got to tell
everyone. Communication is key. So there are
a few ways they do it. One big one is these Dear
Healthcare Professional letters. OK. So those
are letters that go straight from the drug company
to the doctors, the pharmacists, everyone who
prescribes meds. So it's going right to the source,
right to the people who need to know. Exactly.
It tells them about any big safety updates or
other important changes to the label. Makes sense,
what else? Then there are those updated medication
guides we talked about. The ones that come with
the prescription. Right, those are key because
they explain everything to the patient in simple
language. So it's not just for the doctors, it's
for everyone. It's for everyone. And then the
FDA, they put out public announcements. Public
service announcements, kinda? Kinda, yeah. They
let everyone know about any important... Drug
safety info so they might put it on their website
or like send out a press release Exactly, and
that reaches a much wider audience. It does and
then you've got professional societies You know
like groups of doctors and medical organizations,
right? They also tell their members about label
changes So they might put it in their newsletter
or talk about it at a conference. That's right.
So they're really trying to get the word out
in as many ways as possible. They don't want
anyone to miss it. Exactly. In all this communication,
it has to be really clear. Yeah, clear and simple.
Right. Absolutely. It's got to be easy for everyone
to understand, not just the doctors, but the
patients, too. Yeah, because not everyone went
to medical school. Right. Everyone needs to know
what's going on. OK. So we've talked about why
labels change. how they change and how they get
that info out to everyone. Let's look at some
real world examples. Yeah. Let's see how this
works in practice. Can you think of any specific
cases where there were big label changes that
really show what we've been talking about? Oh,
yeah. Like opioids, for example. Opioids. That's
a big one. It is, and, you know, over time, we've
learned a lot more about the risks of opioids.
Yeah, the addiction, the overdoses, all that.
All of that, and that's led to a lot of changes
in the labels. Like, what kind of changes? Well,
they've put much stronger warnings on the labels.
Mm -hmm, to make people really aware of the risks.
Exactly, and they've created RM's programs specifically
for opioids. Right, to try to make sure they're
being prescribed safely. And they've given doctors
much more detailed guidance on how to manage
patients who are taking opioids. So it's really
a multi -pronged approach. It is. It has to be,
because it's such a serious problem. Yeah. And
we've all seen how much attention the opioid
crisis has gotten. Right. It's a huge public
health issue. So it makes sense that they would
use drug labels as one way to try to address
it. They're a key tool. What about other examples?
Oh, there are plenty. Like biologics, for instance.
Biologics, yeah. Those are different from regular
drugs, right? They are. They're more complex.
They're made from living organisms. And because
they're so complex, they can sometimes trigger
an immune response in the body. Oh, so your body
might think it's being attacked. Kind of, yeah.
We call that immunogenicity. Immunogenicity,
OK. And because of that, their labels often have
a lot of specific info. More than regular drug
labels. More details, yeah, like how to give
the drug. Like how to inject it or whatever.
Exactly, and how to watch for any immune reactions.
Yes, those could be serious, right? They could
be. And the thing is with biologics, new safety
issues can pop up even after they're approved.
Oh, wow. So they have to keep updating the label.
They do. And they also often find new uses for
biologics. So a drug that was approved for one
thing might end up being good for something else.
Right. Because they're often very targeted therapies.
So they're really specific to certain conditions.
Exactly. That makes sense. What about other types
of drugs? Well, let's talk about high risk drugs
in general. High risk drugs. So these are the
ones where there's a good chance of serious side
effects. Exactly. Even when they're used correctly
at the right dose. So they have to be really
careful with those. Very careful. And their labels
are usually super detailed. More so than other
drugs. They have a lot of info. Yeah, they have
clear warnings. They tell you when you shouldn't
use the drug. When it's dangerous to use it.
Right. And often they come with REMS programs
too. Right. Those extra safety. All to make sure
the benefits are worth the risks. So, for these
high -risk drugs, the label is really important.
It's crucial. It's like a roadmap for using them
safely. This has been really eye -opening. I
never realized how much goes on behind the scenes
with these drug labels. It's more complicated
than people think, for sure. Yeah, it's not just
a piece of paper. It's like a living document.
It keeps changing. That's a good way to put it.
It evolves as we learn more. And all this work
that the companies have to do, these post -market
commitments, and all those ways they communicate
the new information, that's all super important.
It's all about keeping patients safe. Absolutely.
You know, just learning about all this, it makes
me feel more informed as a patient. That's the
goal. It's about empowering people. Yeah, to
understand what they're taking and what the risks
are. Exactly. And to be able to talk to their
doctors and ask good questions. So we're not
just blindly following orders. Right. It's about
being an active participant in your own health
care. I like that. So one last thought. OK. We've
seen how much we keep learning about a drug,
even after it's approved. and people are taking
it. What does that tell us about the whole process
of scientific discovery? It tells us that science
is never really finished. It's always evolving.
Always evolving. We're always learning new things,
especially when it comes to the human body. Right.
It's so complex. It's incredibly complex. So
we have to stay vigilant. We have to keep learning
and adapting. Yeah. There's always more to discover.
That's the beauty of it. And that's what makes
medicine so exciting, right? It's never boring.
That's for sure.