Lia Barros, DNP and Tijana Milinic, MD - phaware® interview 529
Jul 16, 2025
Dr. Tijana
Milinic and Lia Barros, DNP, from the University of Washington take
a deep dive into the world of pulmonary arterial hypertension (PAH)
clinical trials and discuss why diversity and inclusion matter.
They explore the hidden biases in medical research and the
real-world consequences of exclusion.
Lia Barros, DNP:
My name is Lia Barros and I'm a pulmonary vascular disease nurse
practitioner specialist. I work at the University of Washington,
where I've been practicing as a pulmonary vascular disease
specialist for about the last four years. I was born and raised in
this area. I'm really passionate about diversity and equity
inclusion in clinical trials as I'm the daughter of an immigrant.
This is something that I believe has affected me personally. It’s
something that I see a lot professionally, that's sort of led me
into this intersection of trying to understand equitable inclusion
in the space of pulmonary arterial hypertension.
Tijana Milinic,
MD:
Hi, my name is Tijana Milinic. I am a pulmonary and critical care
physician here at the University of Washington in Seattle. Much of
my work is as a pulmonary specialist. I also am a physician
scientist. I specifically study equity and inclusion in clinical
trials in pulmonary disease. I came into this work because I'm very
passionate about having equal access
to care for all groups of people. I, myself, am a refugee from
Eastern Europe. Similarly, my background really is the reason why I
have such a passion for people having access to medical therapies,
and specifically new and potentially life-saving medical therapies
in clinical trials.
The work that Lia and I did together
was the paper focusing on equity and inclusion in PAH, pulmonary
arterial hypertension studies. The crux of the paper highlights
that certain groups, specifically those who are ethnically and
racially minoritized in the United States are not represented
fairly in clinical trials.
First, what do we mean by ethnically
and racially minoritized people? Specifically, we're talking about
individuals who have racial, ethnic, or cultural identities that
have historically or presently experienced discrimination,
marginalization, or unequal treatment in society. When we talk
about clinical trials, we're specifically thinking about those
studies that look at medications or new drugs, and evaluate whether
they work or cause unintended side effects, whether they're safe
and effective. Overall, what we found and what we know based on a
lot of the research we've done is that clinical trials don't
represent the overall population of people that will eventually end
up taking a medication or therapies. In the United States, and this
is generally among all disease conditions, we know for example,
that over 20,000 studies done in the US, out of those only 43%
included or reported race or ethnicity.
Today, we'll be talking a little bit
more specifically about PAH and we'll discuss a little bit about
the inclusion in PAH trials, but we'll give kind of a broad view of
who's included in the registry and also who's included in clinical
studies.
In order to understand who is
included into clinical studies, we really have to have a good
understanding of who has the disease overall. Specifically, for
pulmonary arterial hypertension, we do that in something called
disease registries. What we do know is that black African-American,
Hispanic, Latinx, and indigenous communities, but more specifically
for black and Hispanic communities, in pulmonary disease in
general, we know that those populations experience worse health
outcomes and potentially have limited access or more limited access
to medical care in general. In PAH, there's some signal with small
studies, for example, objective measures like how people are
feeling or things like six-minute walk tests or functional status,
may be worse in specifically groups that are historically
ethnically or racially minoritized. When there is limited access to
things like clinical studies that further worsens those already
comparatively worse health outcomes.
Lia Barros, DNP:
If we take a step back and we think
about pulmonary arterial hypertension, this is a rare and severe
clinical condition that is characterized by progressive remodeling
of the pulmonary vasculature. So when you are operating with a rare
disease state, sometimes it becomes challenging to understand the
data and demographics being an example of that across the
population. Over the last several decades, there's really been a
proliferation of therapies that have been approved for patients
with PAH that have made really meaningful improvements in outcomes.
However, little is known about the inequity in the care of patients
with PAH. Even less is known about racial and equitable inclusion
in participants with PAH in clinical trials. When we were preparing
for this paper, what we really discovered is that we don't know. Is
this something that we need to continue to explore or study? As
Tijana mentioned, the way we try to understand do these clinical
trials offer an equitable representation of patients living with
pulmonary arterial hypertension?
We went to look at these voluntary
registries. We found that many of these registries did not report
race or ethnicity. Several of the registries did not have patients
selecting or informing how they identify with their race or
ethnicity. So, there are many different challenges when trying to
understand the population at large. If you go all the way back to
when the first registry was published in the 1980s, this showed
that patients living with PAH were predominantly young white women.
This racial and ethnic impression was further reflected with
subsequent registries that included the Reveal Registry, as well as
the PFAR and SPHERE Registry.
In general, they reported somewhere
between 70% and 80% of participants reported their racial or ethnic
background as white. About 10% to 15% would report identifying with
black, and 9% would be Hispanic. Is this consistent with the
broader range of racial and ethnic demographics within our country
at large? What we found when we looked at that is that patients who
were historically ethnically marginalized, were under-reported in
these patient registries. What we wonder and what we reflect on is
the barriers for patients to participate in voluntary registries…
maybe those same barriers impact people and patient's abilities to
participate in clinical trials. What happens is we get this false
belief that because this representation is seen in the registries,
that therefore our clinical trials do have equity in their
representation. When in reality just both struggle from the same
systemic barriers.
Tijana Milinic, MD:
When we think about the mechanisms
that produce a lot of these systemic inequities, I think it's
really helpful to approach it across multiple levels. What I mean
by that is going from the level of the individual or person and the
barriers they may experience, all the way to large systemic policy
barriers, in the United States for example. All of these could
equally apply to participating in a clinical trial or a drug trial
and to participating in something like a registry.
The first level is kind of the
individual level or the level of the person, whether a person can
take time off work, the cost of transportation to getting to study
centers, the burden of potentially participating in a study for
example. Clinical trials involve things like lab draws or more
invasive procedures. Depending on what kind of study it is, could
involve more barriers and more burden to participating. That also
lends itself to thinking about the risks of participating. So, on
an individual level, for a person living with PAH, the risks of
trying a new drug could potentially outweigh the benefits of
symptom relief or feeling better for example.
The next level we looked at in our
study was the interpersonal levels, things like how a person when
they go to a study center with the study staff. When we think about
participating in a trial or even in a registry, there may be a
certain level of bias. Even though the person is there and has
access to go to their appointments, there may be bias in whether
staff thinks that they are a candidate for the study or would be
willing to participate or would consistently be available to
participate. That bias can be conscious or unconscious. But we know
based on studies that we've done outside of PAH that that's a known
barrier to people having access to studies.
Along the same lines, the diversity
of a study team really impacts someone's care in general, but also
whether they can participate in studies. If people don't see other
individuals that potentially identify with their culture or race,
they're less likely to participate. Also, we actually know based on
studies that when there's cultural congruency, that someone's race
or ethnicity aligns with their providers, that they actually
receive better medical care. That, we think, also is related to
some of the biases that exist.
Another similar barrier is
translation services. In something like clinical drug trials,
consenting is a really important part of the process. So talking
about the risks of participating or the benefits and talking about
really explicitly about what the drug involves or the trial
involves is a really complex and difficult conversation to have.
So, not having adequate translation services is yet another known
barrier. One specific thing to point out is when that translation
service happens. So how early on in a study also influences whether
people have access to the study. Specifically, who I mean, is those
who do not speak English as a primary language.
Organizational and more center and
study level barriers are the next level. When we think about
organizational barriers, we think about things like the inclusion
criteria of a study. So, whether somebody is eligible to
participate depends on whether they fit the inclusion or exclusion
criteria. In PAH, that's often things like six-minute walk tests or
other objective clinical measures, BMP, people's functional status.
When we design studies, if those criteria are too limited, then
that restricts how many people can participate potentially, and
could potentially restrict in a biased way who can participate.
Along those same lines, the level of bias within those objective
measures is also really important to think about.
In pulmonary disease, in general, we
think about things like the lung function. Some of the equations we
use actually are biased toward the estimating lung function
incorrectly among black or African-Americans. I use that as an
example not specifically related to PAH, but just to think about
that some of our objective measures can also be biased and
influence whether somebody participates.
When we design our studies, we have
to think about the level of time commitment involved, whether that
excludes certain groups of people because for example, they have
multiple jobs or they are responsible for child care. Then, the
geography of a study could potentially be restrictive. If an
academic center or a PAH center is in a large city for example,
that could increase the distance to travel or the commitment for
people who live in more rural areas. That could potentially limit
the population of people, especially if they are in a specific
minoritized racial and ethnic group.
On a community level, we often
discuss the idea of mistrust in communities. For clinical trials
specifically, there is a history of exploitation of black
African-Americans and Hispanic and Latinx people in the United
States. Oftentimes, people cite studies like the Tuskegee trial,
but there are multiple studies where the process of consent was
taken away or undue harm was caused on a population of people. That
legacy has left mistrust in the medical community, but we also
highlight that it's made medical research less trustworthy. That
affects whether people feel comfortable to participate in medical
research and even in registries where part of the risk in
participating in a registry could potentially be loss of privacy of
information and so on.
On a broad scale, we also have to
think about how national policies in the United States that don't
necessarily even affect medical research, how those can
disproportionately disadvantage groups of people, and therefore
indirectly affect whether people can participate or are asked. It's
a really complex system that operates on multiple levels, and
that's what makes it really hard to study and to think about,
because there's so many different levels that can affect whether
somebody is asked to participate in a registry or even a trial and
whether they can. That also makes the solutions difficult to
address as well, because of that level of complexity.
Lia Barros, DNP:
Taken all together, when looking at
the population of patients living with PAH, what we believe to
understand is that about 20% to 30% of those patients identify as a
minority, while about 70% to 80% identify as white. There could be
a very cautious support that this is a good representation of the
actual population living with PAH. If we look at the US census,
that suggests about 71% of people in 2020 identified as white and
about 65% or so percent identified as white only. So, while
understanding the demographics of the PAH population at large is
likely imperfect, the breakdown of what we understand could be a
reasonable benchmark when we look at the clinical trials within
therapies for patients with PAH, to say, are they representing the
population that they're trying to serve? So, looking at PAH
clinical trials, we found that the landmark study looking at
epoprostenol actually did not include race or ethnicity at all
within their trial. But, following the next decade or so, there
were a proliferation of studies that did include this
information.
Time and again, what we found is
that white participants seem to be overrepresented ranging anywhere
from about 80% to 86% of the participants in the studies. Even
looking at more contemporary trials, in the last few years, this
representation continues to persist. Most specifically, I think
it's important for us that we highlight that black participants are
consistently underrepresented. When we talk about barriers to
participation, understanding the history in America becomes
important when we think about why this may be true. When we look at
different clinical trials, consistently, participants who
identified as black only made up anywhere from about 2% to 4% of
participants in those clinical trials, which is far less than we
would expect based on the US census and based on what we understand
about PAH demographics at large.
Tijana Milinic, MD:
When we're thinking about study
design, it's also important that patients are involved through the
whole process. First, we actually start by evaluating what the
community's needs are, whether the study that we're doing even
addresses a community's needs. Specifically, this is important for
minoritized communities, because historically these communities and
their voices have been marginalized. Their voices, their needs,
have not historically been addressed. So, community engaged
research is actually a really important and powerful tool to bring
patients to the table and include patients throughout the whole
process.
First, we start by understanding the
needs of the community. Then, we incorporate and include the
community into the research design process. Then, we actually bring
our results back to the community and give them an idea of what
we're finding and how we're doing the research so far. This allows
our research to center the voices of marginalized people and people
who've historically been excluded from studies, and also to ensure
that our trial conduct is safe for those communities, and is
welcoming.
Lia Barros, DNP:
I think just sort of in summary,
that these inequities in PAH clinical trials are important. They're
important for us to name, and they're important for us to
understand. Clinical trial recruitment that doesn't represent a PAH
population more broadly may impair our understanding in drug
effects, may impair our understanding and understanding outcomes of
treatment. I think overall, is a disservice to those we serve as
clinicians. I think that from this paper, one of the things that's
really hit home for both of us is that more effort needs to go into
understanding who is living with PAH, and are we including those
patients when studying therapies targeted for their
disease.
Thank you for listening. My name is
Lia Barros…
Tijana Milinic, MD:
And I'm Tijana Milinic, and we're
aware that our patients are rare.
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