111 – REMS and Risk Mitigation Strategies (S8E6)

Okay, so today we're getting into something that
I think is super important when we talk about
medication and drugs and all that, and that is
risk evaluation and mitigation strategies, or
as most people probably know it, REMs. So we're
gonna really unpack what exactly REMs are, why
they even exist, what's their purpose in keeping
medications safe after they hit the market. and
kind of the ins and outs of how they work. Yeah,
absolutely. I think that's a really key part
of drug development, you know, looking at the
regulatory landscape, what happens to drugs once
they're on the market. And what's so interesting
is that even after like. You know so much scrutiny
of drugs before they're even approved There's
still this need for ongoing risk management and
that's where rems comes in. Yeah, that's right
So like we all know I mean, hopefully everyone
knows the drugs go through these super rigorous
clinical trials Yeah, right to make sure they're
safe make sure they actually work all that stuff
before they get approved But you know our sources
are pointing out that even these like the most
intense in -depth trials You know, they have
their limitations. Yeah, absolutely. I mean that's
One of the things that the swaps is kind of point
to is this inherent limitation in clinical trials
where you have a finite number of people. You're
testing in a very controlled setting over a relatively
defined period of time. So sometimes issues like
rare side effects that only emerge with much
wider use or much longer periods of time of use.
These might not actually show up until after
the drugs already approved and been used by lots
of people. And that's, I think, a really critical
part of why we have these programs for post -approval
monitoring of drug safety. It's so important.
So if a safety concern pops up after a drugs
out in the world, then what happens? How do the
mobile watch dogs step in? And it sounds like
that's exactly where these RMS. programs come
in, right? It's like the FDA and the drug companies,
they work together to create these plans for
managing risks. Yeah, and that collaboration
is a key part of this, right? It's not like,
you know, the regulators are like breathing down
the neck of the drug companies or anything like
that. It's really. more of a proactive approach
to addressing potential risks associated with
a particular drug, you know, and of course making
sure that patients are still benefiting from
the medication and that, you know, the benefits
still outweigh the risks. Right. So REMS programs
aren't, you know, just like one size fits all,
right? Like there are different elements to them.
There's this thing called ETAT -U. So that stands
for elements to assure safe use, which sounds
like the real like, you know, the meat and potatoes
of what a REMS program actually is, right? Yeah,
absolutely. These are the specific steps. actions,
the procedures that either patients or health
care providers have to follow to make sure a
drug is used as safely as possible. And what's
interesting here, like, it's not one size fits
all. There are a ton of different types of ETASU.
For example, a REMS could say that only doctors
with a certain kind of specific training or certification
can prescribe a particular drug. So kind of like
you need a special license to, you know, prescribe
that specific medication. Like if it has a you
know, potentially serious side effect or something.
Exactly. And there could be other itissus that
require the drug only be dispensed in certain
health care settings, maybe a hospital or a specialized
clinic where there's expertise to manage any
potential complications. There could also be,
you know, patient registries where data on patients
taking a drug is collected over time and used
to identify patterns or emerging safety concerns.
So that's like building in a system to monitor
for any sort of trends or problems. Absolutely.
And sometimes REMS also involve mandatory patient
monitoring or testing. So this could be, you
know, like regular blood tests or assessments,
all designed to catch potential aterus effects
as early as possible, really building in those
safety checks for the patients. That's so interesting.
OK, so that gives us a picture of Itasio. Now,
another part of REMS is communication plans.
And how do these play into safety? So communication
plans are all about getting information to the
healthcare providers that are prescribing a drug
and, of course, to the patients that are actually
taking it, making sure that they have everything
they need to use the drug as safely as possible.
And one common example is the development of
medication guides. Like the little pamphlets
that come with your prescription. Yeah, exactly.
Those leaflets outline, you know, the risks associated
with the medication, how to use it correctly,
what warning signs or symptoms to look out for.
It's about patient empowerment, really, and communication.
can also involve direct outreach to doctors,
you know, letters, educational programs, online
resources, all of that. It's kind of a multi
-pronged approach. Yeah, I see. So making sure
everyone is aware of the risks and knows what
to do. Makes sense. Now, our outline also mentions...
monitoring requirements, which I think is different
from the patient monitoring we talked about under
ETSU. Oh yeah, that's a really important distinction.
So while ETSU might include monitoring of individual
patients, the kind of broader monitoring requirements
of a REMS program are more focused on evaluating
how the whole program itself is working. So this
involves tracking things like the number of adverse
events reported for a drug, making sure that
prescribers and patients are actually following
the ETSU, and making sure the communication strategies
are actually getting through. to the right people
and being understood. So it's like monitoring
the whole program, not just the individual patients.
Got it. Now, our sources, I noticed, they don't
really give us specific cases of, you know, like
named RIMS programs. But the general principles
we've been discussing, I feel like really resonate
with the broader things our sources talk about
when it comes to drug safety, right? Oh, totally.
For example. There's a lot of discussion about
drug metabolism, like how the body processes
drugs. And sometimes there's a risk of interactions
between different drugs. And it's easy to see
how a drug with a high risk of serious interactions
might require a REMS program, you know, with
really specific prescriber training, very clear
warnings about which drugs to avoid, or think
about bioavailability, right? Like the importance
of taking medication correctly. at the right
time, with or without food, whatever it might
be, to ensure proper absorption. Right, right.
That all underscores why a REMS might include
very precise instructions on how to take a drug.
It's like everything we've learned about how
drugs are made, how they work in the body, how
they interact. All of that comes together to
determine, like, do we need a REMS program for
this drug? And if so, what should it look like?
Exactly, yeah. So who is actually responsible
for putting these programs into action? Well,
the primary responsibility for implementing and
adhering to a REMS program lies with the pharmaceutical
company that's marketing the drug. They're the
ones who have to set up the systems for the ETESU,
distribute those communication materials, and
carry out all the required monitoring. And what
about the regulator, the FDA? They don't just
set it and forget it, do they? Oh, definitely
not. No, they have a super active role in overseeing
REMS programs. They're constantly reviewing data
submitted by the drug companies, assessing whether
the program's actually hitting its goals. And
crucially, they have the authority to require
modifications if it's not working as well as
it should. That could mean adding near ETESU.
you know, changing the communication strategy,
ramping up the monitoring, lots of different
things. So it's a really dynamic process, always
evolving, always being adjusted. Sounds pretty
complicated. And speaking of complicated, our
outline also mentions some of the challenges
with REMS. I mean, just intuitively you can imagine,
right? Like getting everyone on board, doctors,
pharmacists, patients, following all these rules,
that's got to be tough. Oh, absolutely. It is.
That compliance piece is huge. You know, making
sure that everyone from the prescribers to the
dispensers to the patients themselves are all
adhering to those requirements. That's a major
challenge. Think about it, right? Like making
sure that every doctor prescribing a particular
drug has completed the required training, that
patients are actually sticking to their monitoring
schedules, that kind of thing. It takes really
robust systems and constant effort. And I bet
it's hard to really pin down how effective a
REMMS program is in preventing bad outcomes.
Oh, yeah. That's a huge one. I mean, we can track
things, like certain data points. But linking
a reduction in risk specifically to the REMES
program can be really tricky. I mean, there are
so many factors that could be influencing a patient's
health. But at the end of the day, the goal is
that these programs offer an extra layer of safety.
Yeah. It's interesting how all of this circles
back to the very beginning stages of drug development.
Like we touched on earlier, those preclinical
trials, clinical trials, that's where we start
to get an understanding of a drug safety profile.
Yeah, totally. All that knowledge that's built
from those very first experiments in the lab,
all the way through those large scale human trials,
it all informs our understanding of what the
risks might be. And that ultimately determines
whether a REMIS is needed and what it should
include. It's all connected. So it sounds like
REMIS programs, they're really a critical safeguard.
especially for certain medications that might
have unique risks. And it's this collaborative
effort between the regulatory agencies and the
pharmaceutical companies. And it's an ongoing
thing, not just, you know, set it and forget
it. Constant monitoring, constant adjustment.
I think that's a really good summary. And it
highlights that balancing act, right? Making
sure that medications are as safe as they can
be, while also ensuring that patients who need
them can actually get them. It's complex. For
sure. And it really makes you think... You know
with all the advancements that are happening
like in data collection and analysis You know
things we've talked about before on this show
could those things I wonder play a role in making
these are rems programs even more effective in
the future Something to think about definitely.
Well, that's all the time we have for today.
Thanks for joining us on the deep dive Thanks
for having me