January 28, 2025 • 19 mins
In this episode, we take you on an enlightening journey through the world of clinical trials, exploring how experimental drugs evolve from lab discoveries to life-saving medications in your medicine cabinet.
We break down:
- The phases of clinical trials: From Phase 1 safety studies with brave volunteers to Phase 3 large-scale trials and ongoing Phase 4 monitoring.
- Key study designs: How control groups, randomization, and blinding minimize bias and ensure reliable results.
- Innovative approaches: Exploring adaptive split-phase designs that accelerate discoveries, particularly in urgent fields like cancer research.
- The regulatory process: The rigorous reviews by agencies like the FDA to ensure only the safest and most effective drugs reach the market.
- Generic drugs: The streamlined pathways that make essential medicines more accessible and affordable.
This episode highlights the collaborative effort among researchers, clinicians, patients, and regulatory bodies, all working together to improve global health.
Takeaway Thought: Every new drug represents a triumph of science, safety, and human dedication, ensuring hope and progress for a healthier future.
Join us as we uncover the complexities and innovations behind clinical trials, and gain a deeper appreciation for the medicines we rely on every day.
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Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
(00:00):
All right, so we're diving into the world of clinical trials.
(00:04):
It's a pretty complex process.
Yeah.
Taking a drug from the lab to your medicine cabinet.
It really is.
So we're going to break it down into these different phases.
Yeah, and it's really interesting how all the phases
build upon each other, starting with a small group of people
and then expanding out.
OK, so let's start at the very beginning, phase one.
(00:24):
So phase one, it's all about safety
and how a drug behaves in the human body.
And this is where you have a small group of volunteers.
Real heroes.
Yeah, brave volunteers.
Exactly, often like 20 to 80 people who are healthy.
And they receive an experimental drug for the first time.
Wow, so they're really on the front lines then.
They really are.
Yeah, they're helping researchers
(00:45):
to determine if it's safe to move forward with testing.
OK, so what are researchers looking for in this phase?
So they're focused on understanding the drugs,
ADME, absorption, distribution, metabolism, and excretion.
OK.
So basically how the body processes the drug.
And then, of course, any potential side effects,
even mild ones.
(01:06):
Wow, that makes a lot of sense.
It's about gathering crucial safety data
before exposing a larger group.
Yeah, of course.
So if a drug passes these checks in phase one,
what happens next?
Then we move to phase two.
And this is when we start to include actual patients who
have the condition the drug is intended to treat.
OK.
And it usually involves a larger group, anywhere from 100
(01:29):
to several hundred patients.
Oh, wow.
Yeah.
And safety is still a top priority.
Of course.
But now researchers are also investigating
whether the drug is effective.
Oh, like a two-pronged approach then.
Yeah, exactly.
We're still monitoring the safety,
but also seeing if it works.
Exactly.
And this is where the concept of control groups comes into play.
Oh, the control group.
Yes.
So some patients will receive the experimental drug,
(01:50):
and others might receive a placebo
or the current standard of care.
And this allows researchers to compare outcomes
and determine if the new drug actually has a benefit.
Beyond like a placebo effect.
Yeah, beyond the placebo effects or existing treatments.
OK, wow.
So it's a balancing act then.
Right.
Separating out what the drug is actually doing.
(02:11):
It really is.
It helps ensure that the data is reliable.
That makes a lot of sense.
So let's say a drug has successfully gone through phase
one and phase two, good safety profile showing promise.
Then we move on to phase three.
Phase three is the pivotal stage.
OK.
This is where the drug is tested on a much larger and more
diverse group of patients, often thousands of participants
(02:34):
across multiple locations.
Wow.
Yeah, this helps researchers confirm effectiveness, monitor
side effects in a wider range of individuals,
and compare it to existing treatments
in a real world setting.
So gathering that robust data that the agencies
are going to look at.
Exactly.
And each of these phases can take years to complete.
Really?
Yeah, it's a very lengthy and meticulous process.
(02:55):
But it's worth it.
Oh, it's worth it to ensure that new medications are
safe and effective.
OK, that's good to know.
So if a drug makes it through all these phases
and gets approved, are we done then?
Not quite.
That's when phase four comes into play.
Phase four, tell me more.
So once a drug is approved and it's
available on the market, researchers
continue to monitor its long term effects.
And they gather additional data on its safety
(03:17):
and effectiveness in real world settings.
Wow, so it's like surveillance then.
It is ongoing surveillance, making sure
that the drug continues to perform as expected,
and identifying any rare side effects that may not
have been apparent in the earlier phases.
That's amazing.
So it's a continuous learning process, though.
It really is.
Even after it's already being used.
(03:37):
Yeah, exactly.
It's really striking how much emphasis is placed on safety
throughout this whole process from the very beginning.
Yeah.
Testing it on volunteers to ongoing monitoring.
Absolutely.
So safety is the guiding principle.
It is the cornerstone of drug development.
And to ensure that safety, there are these strict regulatory
requirements that every new drug must
(03:59):
meet before it can be approved and available to the public.
OK, so let's talk about those requirements.
What kind of hoops do these drug companies have to jump through?
Well, the process is rigorous.
It involves a lot of paperwork.
They need to submit a comprehensive application
to the relevant regulatory agency,
like here in the United States, the FDA.
And this application is often called a new drug
(04:21):
application, or NDA.
And it's basically a massive dossier
containing all the data from the clinical trials,
preclinical research findings, manufacturing, information
proposed labeling.
So it's like presenting their case to the court.
It really is, the scientific court.
And the regulatory agencies have a team
of experts who review all of that data.
(04:42):
Looking for problems.
Looking for red flags.
Inconsistencies.
Any signs that the drug might not
be as safe or effective as the company claims.
It's a lengthy process, sometimes taking several years.
But it's an essential safeguard to make sure
that only truly worthy drugs get approved.
That makes sense.
They have a huge responsibility to protect the public.
So what happens if they find issues during this review?
(05:04):
Well, it's actually quite common for the agency
to have questions or require additional information.
They might ask the drug company to conduct further studies
or clarify certain data points, address any specific concerns
they have.
It's a back and forth process.
Oh, so it's a good dialogue then.
It is.
It's a scientific dialogue, ensuring
(05:24):
that every aspect of the drug's development and testing
has been thoroughly vetted.
So it's very complex then, bringing a new drag to market.
It's not just about discovering a potential treatment.
It's about navigating a complex web of scientific research,
clinical testing, and regulatory oversight,
all with the goal of improving patient health and well-being.
Well, this has been incredibly enlightening so far.
(05:46):
We've covered these phases, the importance of safety
and these rigorous regulatory requirements
to ensure that the medications are safe and effective.
But we've only just scratched the surface.
We've only just begun.
There's so much more to explore.
We haven't even touched on study designs
and how researchers are always trying
to improve the way clinical trials are conducted.
That's a great point.
(06:07):
We'll dive into all of that and more in part two
of this deep dive.
Yes, we will.
We'll uncover the secrets of control groups,
randomization, and blinding, and explore
how these techniques help researchers
ensure the accuracy and reliability of clinical trial
results.
Welcome back to our deep dive.
You know, we've talked about the different phases
(06:28):
of clinical trials.
Yeah, but now I'm really curious to learn more
about those study designs.
Yeah.
And you know how researchers actually
make sure that the results are accurate and reliable.
That's a great question, because the design
of a clinical trial, it's really like the foundation.
Yeah.
It's crucial.
You know, if the foundation is weak,
the whole structure is at risk.
Yeah, so a poorly designed study could
(06:49):
lead to misleading conclusions.
Exactly.
Which could jeopardize the development of a treatment.
Yeah, or even put patients at risk.
Yeah, of course.
So researchers are really focused then
on making sure these studies are designed well.
Oh, absolutely.
They put a lot of emphasis on creating
studies that are robust and try to minimize the risk of bias.
OK, I'm intrigued.
(07:10):
So what are the key elements then of a well-designed trial?
Well, one of the most fundamental things
is the use of control groups, which we touched on a little
bit earlier.
So remember how in phase two and phase three
we're comparing the outcomes of patients
who get the experimental drug to those
who receive a placebo or the standard treatment?
Yes, but why is it so important to have those control groups?
(07:32):
I mean, couldn't researchers just see
if the patients taking the new drug improve and then
assume it's working?
Well, it's not that simple, unfortunately.
Imagine you're testing a new pain reliever.
You give it to a group of people and their pain decreases.
Sounds great, right?
But how do you know for sure that the improvement wasn't
(07:52):
just due to the placebo effect?
The placebo effect, where people feel better just because they
believe they're getting a treatment.
Exactly.
Even if it's just a sugar pill, the mind
is powerful.
And our expectations, they can have a real impact
on our experiences.
That's why having these control groups is so important.
By comparing the outcomes of those
receiving the actual drug to those receiving a placebo,
(08:15):
researchers can actually isolate the true effect of the drug,
separate it from those psychological factors.
So it's like a benchmark then.
It is.
To see if the new drug is actually doing something.
Exactly.
It's all about establishing that cause and effect.
We want to be confident that any improvement we see
is due to the drug and not something else.
(08:35):
That's a really good point.
So are there other ways then that researchers
try to eliminate bias in these clinical trials?
Absolutely.
Another important technique is randomization.
Randomization.
Which helps ensure that the groups being compared
are as similar as possible.
So does that mean assigning people to groups randomly?
(08:56):
You got it.
Like picking names out of a hat?
Yeah.
It's like shuffling a deck of cards to make sure everyone
gets a fair hand.
The goal is to make sure that the two groups, those
receiving the new drug, and those in the control group
are balanced.
In terms of factors like age, gender, overall health,
and other variables that could influence those results.
So like if you had a group of mostly young, healthy people,
(09:19):
and then another group of much older people
with other conditions that could skew the results.
It could make it hard to tell if the differences you're seeing
are because of the drug or just the characteristics
of the people.
Randomization helps to minimize that chance
that any of those pre-existing differences between the groups
will distort the findings.
(09:40):
And that allows researchers to really focus
on the true impact of the drug.
Makes sense.
So we've got control groups and randomization
both really important for minimizing bias.
Any other strategies?
Another powerful tool is blinding.
Blinding.
Which involves keeping certain people in the dark about who
is receiving the actual drug and who's receiving the placebo.
(10:02):
So not literally blindfolded.
You got it.
It's more metaphorical.
It's about controlling information to prevent bias.
There are different levels of blinding.
So in single blinding, the participants themselves
don't know what they're taking.
So they don't know if they're getting
the drug or the placebo.
Exactly.
And that helps to prevent their own expectations
from influencing their experience or reporting
(10:24):
symptoms.
So even the people taking the pills
don't know what they're getting.
Are there situations where the researchers don't know either?
Yes.
That's called double blinding.
Double blinding.
Where even the researchers administering the treatments
don't know who's getting what.
So that adds an extra layer of protection against bias.
Because it prevents the researchers
(10:44):
from subconsciously treating participants differently
or interpreting data in a way that favors
one group over the other.
So it's like next level objectivity.
It is.
It's all about letting the data speak for itself.
Eliminating as many sources of bias as we can.
So researchers can be more confident
that the results accurately reflect
the effects of the drug.
(11:06):
Wow.
So control groups, randomization blinding.
Yes.
Those are like the pillars then.
They have a well-designed trial.
Exactly.
Working together to create a fair and accurate testing
ground for new treatments.
And these principles apply to all phases.
All phases of clinical trials.
From the beginning to those large scale trials that
(11:26):
determine if a drug gets approved.
It's all about making sure that the data we collect
is as reliable and unbiased as possible.
So it's the recipe then for good scientific evidence.
It is the foundation for good science
and informed decision making.
Speaking of decision making.
I understand that the traditional clinical trial
designs are always being kind of refined and improved.
(11:47):
They are.
And there's this thing called split phase design.
Yes.
That is sort of a new innovation.
It is a more adaptive and flexible approach
to testing new treatments.
Especially in areas where time is really critical,
like cancer drug development.
OK.
So how do these split phase designs actually
differ from the traditional way?
So in a traditional trial, you've
(12:08):
got a fixed plan from the start.
You recruit a large number of participants,
assign them to groups, administer the treatments,
and then analyze the data at the end.
But in the LEPA phase design, the trial
is actually divided into stages.
And the data from each stage is used
to actually inform the design of the next stage.
So it's more dynamic.
Much more dynamic.
Allows the researchers to adjust course
(12:30):
based on the information they're gathering along the way.
Wow.
I like that.
So for example, let's say we're testing a new cancer drug.
Right.
And there are several potential dosage levels.
So in a split phase design, the first stage
might involve a smaller group of patients.
Right.
Just to figure out which dosage seems to be working the best.
(12:52):
Exactly.
And then in the next stage, we focus on that dosage.
Yeah.
With a larger group of patients.
That sounds incredibly efficient.
It is.
It can be really valuable when dealing
with serious conditions where time is really critical.
Of course.
So it could speed things up then.
It could lead to faster answers and more targeted treatments.
It's like a scientific detective story.
(13:12):
It is unfolding in stages, you know?
Yeah.
As researchers gather clues and adjust their investigation.
Based on the evidence.
Exactly.
It just highlights how much clinical research is evolving.
And that drive to find better, faster, and more efficient ways
to develop these treatments.
Well, this has been a really eye-opening journey so far.
(13:33):
From control groups, randomization blinding,
to split phase designs, it's clear
that researchers are doing so much to make sure
that their findings are accurate.
Absolutely.
It's essential to ensure that the medications we rely on
are truly safe and effective.
But there's another piece to this puzzle
that we haven't discussed yet.
OK.
The regulatory agencies.
Right.
(13:53):
They play a vital role in deciding
which of these new drugs actually make it to market.
That's right.
We talked about how important it is to get good data
from the clinical trials.
Right.
But how do they use that data to convince the agencies
that the drug is actually worthy of being approved?
That is a great question.
In the next part of our deep dive,
we'll delve into the world of those regulatory agencies.
(14:15):
OK.
We'll explore the hurdles a drug has
to clear before it can be sold.
Yeah.
And how those agencies make sure that patient safety is always
a top priority.
Welcome back to our deep dive.
We spend quite a bit of time talking
of those different phases of clinical trials.
We have, from those early safety studies
to the larger trials that confirm a drug's effectiveness.
(14:37):
Yeah.
And then, of course, those study designs.
All those things they use to try and minimize bias.
Control groups, randomization, and blinding.
Right.
All about getting that reliable data.
Exactly.
But now I'm really interested in learning more about the agencies
that have the final say.
Yeah.
Whether or not a new drug actually gets approved,
what are they looking for?
(14:57):
Well, the regulatory agencies, they have a huge role.
They're safeguarding public health.
Big responsibility.
It is.
They act as gatekeepers, making sure
that only medications that meet very strict standards
for safety, effectiveness, and quality
are actually available to patients.
Can you walk me through the process a little bit?
What happens once a drug company,
(15:18):
they think they have enough evidence
for their clinical trials.
They're saying, hey, this drug is safe and effective.
What happens next?
Well, the first step is to submit
a really comprehensive application
to the appropriate regulatory agency.
So here in the United States, that would be the FDA.
Right.
The Food and Drug Administration.
In Europe, it's the European Medicines Agency, or EM.
(15:40):
So each country has its own regulatory body.
So it's a whole network, then.
It is.
Looking out for everybody.
Global network of these scientific watchdogs,
you could say.
And that application itself sounds like a pretty massive
undertaking.
It is.
It's a lot of work.
It's called a new drug application, or NDA.
And it includes a ton of data from all the clinical trials,
(16:02):
preclinical research manufacturing information,
proposed labeling.
It's a really big report card.
So a lot of experts have to look at all this.
Oh, yeah.
The agencies themselves have teams of scientists,
clinicians, statisticians, and other experts.
And they look at every piece of that information.
So they don't just trust the drug companies?
No.
They conduct their own independent evaluation,
(16:25):
digging deep into the data, making sure everything
looks good.
That makes a lot of sense.
And I bet that takes a long time.
It does.
It can take several years.
So it's not a quick process.
No.
But patient safety is the most important thing.
Right.
So these agencies are committed to being thorough.
Yeah.
You know, they'll request more information.
Sometimes there are back and forth discussions
(16:47):
to address any concerns that come up.
So it's really a debate, then?
It is a very rigorous scientific debate
to make sure that every part of that drug's development
has been carefully vetted.
So at the end of all of this, the regulatory agency,
they make a decision.
They do.
They might approve the drug, as is.
(17:07):
They could request further studies,
or even reject the application if they believe the risks outweigh
the benefits.
Wow.
So there are all checks and balances, then?
There are, to make sure that only the safest and most
promising treatments are actually approved.
Well, we've been talking a lot about these new drugs
and the process they have to go through.
What about generic versions of drugs
(17:28):
that are already out there?
Do they have to go through the same thing?
That's a great question.
So generic drugs, they're basically
copies of brand-name drugs that have already been approved.
OK.
They have the same active ingredients,
but they're typically sold at much lower prices.
Yeah, which is why they're so important.
Absolutely.
It makes those medications much more accessible and affordable.
(17:50):
Right, so they don't have to go through all
those clinical trials again.
No, they don't.
They have a streamlined pathway called the 505b2 generic ANDA
pathway.
Can you break that down for me?
Yeah.
So NDA stands for Abbreviated New Drug Application.
Abbreviated, because it doesn't require all that original
research, like a brand new drug.
(18:10):
The 505b2 part just refers to a specific section of the US law
that outlines this pathway.
OK, so they're essentially leveraging that data that
already exists about the safety and effectiveness
of that original drug.
Exactly.
They still need to show that their version is bioequivalent,
meaning it acts the same way in the body,
but they don't have to repeat all those expensive and time
(18:31):
consuming trials.
So it's a win-win.
It saves time, money.
It does.
The generics get to market sooner, and it helps patients.
Absolutely.
It's a really good example of how these regulatory pathways
can evolve to meet the needs of patients in the health care
system, while still keeping those standards really high.
This has been a fascinating look into the whole world
(18:54):
of clinical trials and drug development.
It has.
We've talked about everything from those early safety
studies to those complicated study designs,
the regulatory agencies, and all those hurdles.
And those pathways for generic drugs.
Yeah.
What do you think is the most important takeaway
for our listeners?
For me, it's how collaborative this whole process is.
(19:14):
There are so many people involved, scientists,
researchers, clinicians, patients, the agencies.
Wow.
And they're all working together to bring these new treatments
to the people who need them.
That's really well said.
It's a great example of human ingenuity
and really the dedication to improving health.
Absolutely.
(19:34):
And we've only just scratched the surface here.
Clinical research is always evolving.
New discoveries and innovations are happening all the time.
Well, this has been really great.
Thanks for joining us on this deep dive
into clinical trials, a journey that's
all about hope and progress.
It has been a pleasure.
And ultimately, the pursuit of a healthier future for everybody.
All right, so we're diving into the world of clinical trials.
(00:04):
It's a pretty complex process.
Yeah.
Taking a drug from the lab to your medicine cabinet.
It really is.
So we're going to break it down into these different phases.
Yeah, and it's really interesting how all the phases
build upon each other, starting with a small group of people
and then expanding out.
OK, so let's start at the very beginning, phase one.
(00:24):
So phase one, it's all about safety
and how a drug behaves in the human body.
And this is where you have a small group of volunteers.
Real heroes.
Yeah, brave volunteers.
Exactly, often like 20 to 80 people who are healthy.
And they receive an experimental drug for the first time.
Wow, so they're really on the front lines then.
They really are.
Yeah, they're helping researchers
(00:45):
to determine if it's safe to move forward with testing.
OK, so what are researchers looking for in this phase?
So they're focused on understanding the drugs,
ADME, absorption, distribution, metabolism, and excretion.
OK.
So basically how the body processes the drug.
And then, of course, any potential side effects,
even mild ones.
(01:06):
Wow, that makes a lot of sense.
It's about gathering crucial safety data
before exposing a larger group.
Yeah, of course.
So if a drug passes these checks in phase one,
what happens next?
Then we move to phase two.
And this is when we start to include actual patients who
have the condition the drug is intended to treat.
OK.
And it usually involves a larger group, anywhere from 100
(01:29):
to several hundred patients.
Oh, wow.
Yeah.
And safety is still a top priority.
Of course.
But now researchers are also investigating
whether the drug is effective.
Oh, like a two-pronged approach then.
Yeah, exactly.
We're still monitoring the safety,
but also seeing if it works.
Exactly.
And this is where the concept of control groups comes into play.
Oh, the control group.
Yes.
So some patients will receive the experimental drug,
(01:50):
and others might receive a placebo
or the current standard of care.
And this allows researchers to compare outcomes
and determine if the new drug actually has a benefit.
Beyond like a placebo effect.
Yeah, beyond the placebo effects or existing treatments.
OK, wow.
So it's a balancing act then.
Right.
Separating out what the drug is actually doing.
(02:11):
It really is.
It helps ensure that the data is reliable.
That makes a lot of sense.
So let's say a drug has successfully gone through phase
one and phase two, good safety profile showing promise.
Then we move on to phase three.
Phase three is the pivotal stage.
OK.
This is where the drug is tested on a much larger and more
diverse group of patients, often thousands of participants
(02:34):
across multiple locations.
Wow.
Yeah, this helps researchers confirm effectiveness, monitor
side effects in a wider range of individuals,
and compare it to existing treatments
in a real world setting.
So gathering that robust data that the agencies
are going to look at.
Exactly.
And each of these phases can take years to complete.
Really?
Yeah, it's a very lengthy and meticulous process.
(02:55):
But it's worth it.
Oh, it's worth it to ensure that new medications are
safe and effective.
OK, that's good to know.
So if a drug makes it through all these phases
and gets approved, are we done then?
Not quite.
That's when phase four comes into play.
Phase four, tell me more.
So once a drug is approved and it's
available on the market, researchers
continue to monitor its long term effects.
And they gather additional data on its safety
(03:17):
and effectiveness in real world settings.
Wow, so it's like surveillance then.
It is ongoing surveillance, making sure
that the drug continues to perform as expected,
and identifying any rare side effects that may not
have been apparent in the earlier phases.
That's amazing.
So it's a continuous learning process, though.
It really is.
Even after it's already being used.
(03:37):
Yeah, exactly.
It's really striking how much emphasis is placed on safety
throughout this whole process from the very beginning.
Yeah.
Testing it on volunteers to ongoing monitoring.
Absolutely.
So safety is the guiding principle.
It is the cornerstone of drug development.
And to ensure that safety, there are these strict regulatory
requirements that every new drug must
(03:59):
meet before it can be approved and available to the public.
OK, so let's talk about those requirements.
What kind of hoops do these drug companies have to jump through?
Well, the process is rigorous.
It involves a lot of paperwork.
They need to submit a comprehensive application
to the relevant regulatory agency,
like here in the United States, the FDA.
And this application is often called a new drug
(04:21):
application, or NDA.
And it's basically a massive dossier
containing all the data from the clinical trials,
preclinical research findings, manufacturing, information
proposed labeling.
So it's like presenting their case to the court.
It really is, the scientific court.
And the regulatory agencies have a team
of experts who review all of that data.
(04:42):
Looking for problems.
Looking for red flags.
Inconsistencies.
Any signs that the drug might not
be as safe or effective as the company claims.
It's a lengthy process, sometimes taking several years.
But it's an essential safeguard to make sure
that only truly worthy drugs get approved.
That makes sense.
They have a huge responsibility to protect the public.
So what happens if they find issues during this review?
(05:04):
Well, it's actually quite common for the agency
to have questions or require additional information.
They might ask the drug company to conduct further studies
or clarify certain data points, address any specific concerns
they have.
It's a back and forth process.
Oh, so it's a good dialogue then.
It is.
It's a scientific dialogue, ensuring
(05:24):
that every aspect of the drug's development and testing
has been thoroughly vetted.
So it's very complex then, bringing a new drag to market.
It's not just about discovering a potential treatment.
It's about navigating a complex web of scientific research,
clinical testing, and regulatory oversight,
all with the goal of improving patient health and well-being.
Well, this has been incredibly enlightening so far.
(05:46):
We've covered these phases, the importance of safety
and these rigorous regulatory requirements
to ensure that the medications are safe and effective.
But we've only just scratched the surface.
We've only just begun.
There's so much more to explore.
We haven't even touched on study designs
and how researchers are always trying
to improve the way clinical trials are conducted.
That's a great point.
(06:07):
We'll dive into all of that and more in part two
of this deep dive.
Yes, we will.
We'll uncover the secrets of control groups,
randomization, and blinding, and explore
how these techniques help researchers
ensure the accuracy and reliability of clinical trial
results.
Welcome back to our deep dive.
You know, we've talked about the different phases
(06:28):
of clinical trials.
Yeah, but now I'm really curious to learn more
about those study designs.
Yeah.
And you know how researchers actually
make sure that the results are accurate and reliable.
That's a great question, because the design
of a clinical trial, it's really like the foundation.
Yeah.
It's crucial.
You know, if the foundation is weak,
the whole structure is at risk.
Yeah, so a poorly designed study could
(06:49):
lead to misleading conclusions.
Exactly.
Which could jeopardize the development of a treatment.
Yeah, or even put patients at risk.
Yeah, of course.
So researchers are really focused then
on making sure these studies are designed well.
Oh, absolutely.
They put a lot of emphasis on creating
studies that are robust and try to minimize the risk of bias.
OK, I'm intrigued.
(07:10):
So what are the key elements then of a well-designed trial?
Well, one of the most fundamental things
is the use of control groups, which we touched on a little
bit earlier.
So remember how in phase two and phase three
we're comparing the outcomes of patients
who get the experimental drug to those
who receive a placebo or the standard treatment?
Yes, but why is it so important to have those control groups?
(07:32):
I mean, couldn't researchers just see
if the patients taking the new drug improve and then
assume it's working?
Well, it's not that simple, unfortunately.
Imagine you're testing a new pain reliever.
You give it to a group of people and their pain decreases.
Sounds great, right?
But how do you know for sure that the improvement wasn't
(07:52):
just due to the placebo effect?
The placebo effect, where people feel better just because they
believe they're getting a treatment.
Exactly.
Even if it's just a sugar pill, the mind
is powerful.
And our expectations, they can have a real impact
on our experiences.
That's why having these control groups is so important.
By comparing the outcomes of those
receiving the actual drug to those receiving a placebo,
(08:15):
researchers can actually isolate the true effect of the drug,
separate it from those psychological factors.
So it's like a benchmark then.
It is.
To see if the new drug is actually doing something.
Exactly.
It's all about establishing that cause and effect.
We want to be confident that any improvement we see
is due to the drug and not something else.
(08:35):
That's a really good point.
So are there other ways then that researchers
try to eliminate bias in these clinical trials?
Absolutely.
Another important technique is randomization.
Randomization.
Which helps ensure that the groups being compared
are as similar as possible.
So does that mean assigning people to groups randomly?
(08:56):
You got it.
Like picking names out of a hat?
Yeah.
It's like shuffling a deck of cards to make sure everyone
gets a fair hand.
The goal is to make sure that the two groups, those
receiving the new drug, and those in the control group
are balanced.
In terms of factors like age, gender, overall health,
and other variables that could influence those results.
So like if you had a group of mostly young, healthy people,
(09:19):
and then another group of much older people
with other conditions that could skew the results.
It could make it hard to tell if the differences you're seeing
are because of the drug or just the characteristics
of the people.
Randomization helps to minimize that chance
that any of those pre-existing differences between the groups
will distort the findings.
(09:40):
And that allows researchers to really focus
on the true impact of the drug.
Makes sense.
So we've got control groups and randomization
both really important for minimizing bias.
Any other strategies?
Another powerful tool is blinding.
Blinding.
Which involves keeping certain people in the dark about who
is receiving the actual drug and who's receiving the placebo.
(10:02):
So not literally blindfolded.
You got it.
It's more metaphorical.
It's about controlling information to prevent bias.
There are different levels of blinding.
So in single blinding, the participants themselves
don't know what they're taking.
So they don't know if they're getting
the drug or the placebo.
Exactly.
And that helps to prevent their own expectations
from influencing their experience or reporting
(10:24):
symptoms.
So even the people taking the pills
don't know what they're getting.
Are there situations where the researchers don't know either?
Yes.
That's called double blinding.
Double blinding.
Where even the researchers administering the treatments
don't know who's getting what.
So that adds an extra layer of protection against bias.
Because it prevents the researchers
(10:44):
from subconsciously treating participants differently
or interpreting data in a way that favors
one group over the other.
So it's like next level objectivity.
It is.
It's all about letting the data speak for itself.
Eliminating as many sources of bias as we can.
So researchers can be more confident
that the results accurately reflect
the effects of the drug.
(11:06):
Wow.
So control groups, randomization blinding.
Yes.
Those are like the pillars then.
They have a well-designed trial.
Exactly.
Working together to create a fair and accurate testing
ground for new treatments.
And these principles apply to all phases.
All phases of clinical trials.
From the beginning to those large scale trials that
(11:26):
determine if a drug gets approved.
It's all about making sure that the data we collect
is as reliable and unbiased as possible.
So it's the recipe then for good scientific evidence.
It is the foundation for good science
and informed decision making.
Speaking of decision making.
I understand that the traditional clinical trial
designs are always being kind of refined and improved.
(11:47):
They are.
And there's this thing called split phase design.
Yes.
That is sort of a new innovation.
It is a more adaptive and flexible approach
to testing new treatments.
Especially in areas where time is really critical,
like cancer drug development.
OK.
So how do these split phase designs actually
differ from the traditional way?
So in a traditional trial, you've
(12:08):
got a fixed plan from the start.
You recruit a large number of participants,
assign them to groups, administer the treatments,
and then analyze the data at the end.
But in the LEPA phase design, the trial
is actually divided into stages.
And the data from each stage is used
to actually inform the design of the next stage.
So it's more dynamic.
Much more dynamic.
Allows the researchers to adjust course
(12:30):
based on the information they're gathering along the way.
Wow.
I like that.
So for example, let's say we're testing a new cancer drug.
Right.
And there are several potential dosage levels.
So in a split phase design, the first stage
might involve a smaller group of patients.
Right.
Just to figure out which dosage seems to be working the best.
(12:52):
Exactly.
And then in the next stage, we focus on that dosage.
Yeah.
With a larger group of patients.
That sounds incredibly efficient.
It is.
It can be really valuable when dealing
with serious conditions where time is really critical.
Of course.
So it could speed things up then.
It could lead to faster answers and more targeted treatments.
It's like a scientific detective story.
(13:12):
It is unfolding in stages, you know?
Yeah.
As researchers gather clues and adjust their investigation.
Based on the evidence.
Exactly.
It just highlights how much clinical research is evolving.
And that drive to find better, faster, and more efficient ways
to develop these treatments.
Well, this has been a really eye-opening journey so far.
(13:33):
From control groups, randomization blinding,
to split phase designs, it's clear
that researchers are doing so much to make sure
that their findings are accurate.
Absolutely.
It's essential to ensure that the medications we rely on
are truly safe and effective.
But there's another piece to this puzzle
that we haven't discussed yet.
OK.
The regulatory agencies.
Right.
(13:53):
They play a vital role in deciding
which of these new drugs actually make it to market.
That's right.
We talked about how important it is to get good data
from the clinical trials.
Right.
But how do they use that data to convince the agencies
that the drug is actually worthy of being approved?
That is a great question.
In the next part of our deep dive,
we'll delve into the world of those regulatory agencies.
(14:15):
OK.
We'll explore the hurdles a drug has
to clear before it can be sold.
Yeah.
And how those agencies make sure that patient safety is always
a top priority.
Welcome back to our deep dive.
We spend quite a bit of time talking
of those different phases of clinical trials.
We have, from those early safety studies
to the larger trials that confirm a drug's effectiveness.
(14:37):
Yeah.
And then, of course, those study designs.
All those things they use to try and minimize bias.
Control groups, randomization, and blinding.
Right.
All about getting that reliable data.
Exactly.
But now I'm really interested in learning more about the agencies
that have the final say.
Yeah.
Whether or not a new drug actually gets approved,
what are they looking for?
(14:57):
Well, the regulatory agencies, they have a huge role.
They're safeguarding public health.
Big responsibility.
It is.
They act as gatekeepers, making sure
that only medications that meet very strict standards
for safety, effectiveness, and quality
are actually available to patients.
Can you walk me through the process a little bit?
What happens once a drug company,
(15:18):
they think they have enough evidence
for their clinical trials.
They're saying, hey, this drug is safe and effective.
What happens next?
Well, the first step is to submit
a really comprehensive application
to the appropriate regulatory agency.
So here in the United States, that would be the FDA.
Right.
The Food and Drug Administration.
In Europe, it's the European Medicines Agency, or EM.
(15:40):
So each country has its own regulatory body.
So it's a whole network, then.
It is.
Looking out for everybody.
Global network of these scientific watchdogs,
you could say.
And that application itself sounds like a pretty massive
undertaking.
It is.
It's a lot of work.
It's called a new drug application, or NDA.
And it includes a ton of data from all the clinical trials,
(16:02):
preclinical research manufacturing information,
proposed labeling.
It's a really big report card.
So a lot of experts have to look at all this.
Oh, yeah.
The agencies themselves have teams of scientists,
clinicians, statisticians, and other experts.
And they look at every piece of that information.
So they don't just trust the drug companies?
No.
They conduct their own independent evaluation,
(16:25):
digging deep into the data, making sure everything
looks good.
That makes a lot of sense.
And I bet that takes a long time.
It does.
It can take several years.
So it's not a quick process.
No.
But patient safety is the most important thing.
Right.
So these agencies are committed to being thorough.
Yeah.
You know, they'll request more information.
Sometimes there are back and forth discussions
(16:47):
to address any concerns that come up.
So it's really a debate, then?
It is a very rigorous scientific debate
to make sure that every part of that drug's development
has been carefully vetted.
So at the end of all of this, the regulatory agency,
they make a decision.
They do.
They might approve the drug, as is.
(17:07):
They could request further studies,
or even reject the application if they believe the risks outweigh
the benefits.
Wow.
So there are all checks and balances, then?
There are, to make sure that only the safest and most
promising treatments are actually approved.
Well, we've been talking a lot about these new drugs
and the process they have to go through.
What about generic versions of drugs
(17:28):
that are already out there?
Do they have to go through the same thing?
That's a great question.
So generic drugs, they're basically
copies of brand-name drugs that have already been approved.
OK.
They have the same active ingredients,
but they're typically sold at much lower prices.
Yeah, which is why they're so important.
Absolutely.
It makes those medications much more accessible and affordable.
(17:50):
Right, so they don't have to go through all
those clinical trials again.
No, they don't.
They have a streamlined pathway called the 505b2 generic ANDA
pathway.
Can you break that down for me?
Yeah.
So NDA stands for Abbreviated New Drug Application.
Abbreviated, because it doesn't require all that original
research, like a brand new drug.
(18:10):
The 505b2 part just refers to a specific section of the US law
that outlines this pathway.
OK, so they're essentially leveraging that data that
already exists about the safety and effectiveness
of that original drug.
Exactly.
They still need to show that their version is bioequivalent,
meaning it acts the same way in the body,
but they don't have to repeat all those expensive and time
(18:31):
consuming trials.
So it's a win-win.
It saves time, money.
It does.
The generics get to market sooner, and it helps patients.
Absolutely.
It's a really good example of how these regulatory pathways
can evolve to meet the needs of patients in the health care
system, while still keeping those standards really high.
This has been a fascinating look into the whole world
(18:54):
of clinical trials and drug development.
It has.
We've talked about everything from those early safety
studies to those complicated study designs,
the regulatory agencies, and all those hurdles.
And those pathways for generic drugs.
Yeah.
What do you think is the most important takeaway
for our listeners?
For me, it's how collaborative this whole process is.
(19:14):
There are so many people involved, scientists,
researchers, clinicians, patients, the agencies.
Wow.
And they're all working together to bring these new treatments
to the people who need them.
That's really well said.
It's a great example of human ingenuity
and really the dedication to improving health.
Absolutely.
(19:34):
And we've only just scratched the surface here.
Clinical research is always evolving.
New discoveries and innovations are happening all the time.
Well, this has been really great.
Thanks for joining us on this deep dive
into clinical trials, a journey that's
all about hope and progress.
It has been a pleasure.
And ultimately, the pursuit of a healthier future for everybody.
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