If Our Patients Are Diverse, Why Are Clinical Trials So White?
March 31, 2022
How many times have you been told to put on sunscreen to
prevent skin cancer? About 71% of US adults use some form of sun protection
when outdoors on a warm, sunny day – an increase of 3% from 2008.
Now, what if I told you that despite these public health initiatives
to increase the use of sunscreen, the benefits of this may only be seen by a
select few members of the population?
According to the largest study (to date) in different racial
and ethnic populations across the US, there was no evidence to support the
association of UV exposure and melanoma incidence in black or Hispanic
populations – studies assessing the association of UV radiation and melanoma
exclude patients of darker skin types.
Worryingly, this lack of diversity in clinical trials is
common not only in dermatology, but across healthcare as a whole, ranging from
oncology to cardiology, especially when pertaining to marginalized populations.
Despite facing worse health outcomes, marginalized
populations are often left out of clinical trials and miss the opportunity to
participate in research on potentially life-saving treatments.
“Although 20% of the people living with multiple myeloma in
the US are African Americans, they only account for 6% of all patients in
clinical trials.”
Clinical research is needed to determine the efficacy,
effectiveness, and safety of new therapies. Subgroups of patients (i.e.
different ethnicities and genders) may respond differently to each therapy, and
that’s why it is essential that all patients are represented.
Including diverse populations in clinical trials, especially
marginalized communities, will not only ensure the medicine is efficacious
across the general population, it also contributes to progress in health
equity.
There are many benefits to including diverse patients in
clinical trials. From a business standpoint, including individuals who share
certain biomarkers may lead to faster and less expensive trials. This is
because it is possible to include surrogate endpoints as an alternative way of
measuring outcomes.
Going back to basic statistics, if a sample size is too
small or poorly selected, the results cannot necessarily be applied to the
broader population.
The data from a smaller, but representative, pool of
patients can be extrapolated and generalized to predict the results in the
larger patient population. Including diverse patients reinforces this
assumption and provides more confidence in the generalizability of results.
The current and historic lack of diversity in clinical
trials
Unfortunately, the healthcare industry has historically
underrepresented demographic groups, particularly women, people of color, and
the elderly. People of color in particular have not been represented in
clinical trials, implying that access to medicine is reserved for the
privileged few. In 2009, almost all participants (96%) involved in genome-wide
association studies (GWAS) were of European descent.
In 2016, the number dropped to 81%. However, the 15%
increase in non-Europeans was comprised of mostly populations from Asian
ancestry – leaving all other populations severely underrepresented, especially
those from African and Hispanic descent.
As it happens, clinical research is more likely to happen at
research or academic institutions. By the time people have failed multiple
lines of therapy and are referred to these institutions, they are already
ineligible for first- or second-line studies. As a result, it’s very likely
that only wealthier people from urban areas will begin their treatment journey
at these larger research institutions with the proper resources for and access
to clinical trials. Due to a variety of factors, the people that live in these
areas are usually Caucasian.
Healthcare professionals outside of centers of excellence
may be unwilling to refer patients for trials, there may be a lack of clinical
trial availability, or they may fear that trials create a financial burden to
the practice.
Simultaneously, financial and logistical barriers may also
prevent those from less privileged backgrounds participating in clinical
trials. For example, a lack of transportation, child-care, the inability to
take time off work, or other time commitments may make it more difficult to
travel to the clinical trial site.
Often hospitals serving minorities, especially those in
underprivileged areas, are understaffed and underfunded and this can lead to
worrying failings in patient care. A recent paper published in ‘Nature’ reports
that Black or Hispanic infants with very low birth weight are more likely to be
born in non-magnet hospitals with higher neonatal morbidity and mortality
rates, in comparison to their white peers.
The authors report a myriad of concerning factors in
minority-serving hospitals, including higher rates of infection, discharge
without breast milk, nurse understaffing, and higher workloads for staff.
Meanwhile, evidence has come to light that suggests doctors are less likely to
treat black patients’ pain effectively, and black women are 2.5 times more
likely to die in childbirth than white women.
Mistrust and ‘bad blood’
Patients in marginalized or vulnerable communities may also
mistrust medical or research systems. This is understandable when you consider
the West’s history of mistreating minorities. In the African American community
alone, this ranges from the barbaric slave trade of the 17th century, through
to the segregation and hyper- segregation of the 20th century, which persisted
after the Civil Rights Act of 1968 and still exists in some forms today.
In medicine, this includes transgressions such as the
dehumanizing 1 Tuskegee Syphilis Experiment, in which African American men were
promised treatment for “bad blood” – a term which included syphilis, anemia,
and fatigue – by the US government. Instead, the researchers observed the men
to better understand what happens if syphilis is left untreated. The outcome
was fatal.
It’s no surprise that this decreased trust in healthcare and
clinical trials. According to one survey in 1999, 80% of African American men
believed the doctors had injected the trial participants with syphilis.
“Clinical trials need more diverse patient populations
because right now they don’t properly represent vulnerable populations that are
more at risk for diseases”
Case study of multiple myeloma
Although 20% of the people living with multiple myeloma in
the US are African Americans, they only account for 6% of all patients in
clinical trials.
Ninlaro is an oral treatment for multiple myeloma indicated
for patients who have received at least one prior therapy. One of the endpoints
of the trial was a progression free survival (PFS) of 6 months, leading to
Ninlaro’s Food and Drug Administration approval in 2015.
However, despite the fact that African Americans are more
than twice as likely as white Americans to be diagnosed with multiple myeloma,
only 13 out of 722 (1.8%) of participants in Ninarlo’s clinical trial
(TOURMALINE-MM1) were African American.
In fact, in an analysis of 31 cancer drugs approved since
2015, African American participation reached 10% in trials relating to just two
drugs. One of these is Darzalex, another drug for multiple myeloma that is
indicated across all lines of therapy.
Darzalex is made by Janssen Oncology, a company under
Johnson & Johnson. In the past year, J&J announced a “strategic shift
in its approach to clinical trials, focusing efforts on educating diverse
communities about the importance of participating.”
“Clinical trials need more diverse patient populations
because right now they don’t properly represent vulnerable populations that are
more at risk for diseases.”
Other efforts to be more inclusive are underway, such as the
All of Us research program by the National Institute of Health, which aims to
deliver precision medicine by “taking into account individual differences in
lifestyle, environment, and biology.”
All of Us is developing a diverse database that can inform
studies of a variety of health conditions, uncovering risk factors for certain
diseases, and determining which treatments work best for people of different
backgrounds. Janssen is not alone in trying to make clinical trials more
representative.
These initiatives are evidence that inclusion of diversity
in clinical trials and research in general isn’t impossible and we can get
there, but change needs to happen at both a systemic level and a grassroots
level – all stakeholders play a role. Every stakeholder has to make this a
priority, whether they work in research, manufacturing, distribution, or
marketing these life-changing therapies.
Clinical trials need more diverse patient populations
because right now they don’t properly represent vulnerable populations that are
more at risk for diseases. These same populations are the ones that have worse
health outcomes because of their social determinants of health. In pharma, we
talk a lot about making our brands patient- centric and giving patients the
opportunity to have better lives with treatment, but we can’t expect people to
be healthy if we can’t facilitate patient access. Nor can we expect treatment
to apply to the broad population if we don’t represent every patient affected.
References:
https://www.cdc.gov/cancer/skin/statistics/behavior/
sunprotection.htm
https://www.ncbi.nlm.nih.gov/pubmed/15837865
https://www.sciencedirect.com/science/article/pii/
S0146280618301889
https://www.statnews.com/2019/01/17/diversity-clinicaltrials-
good-science-better-medicine/
https://www.eupati.eu/clinical-development-and-trials/
biomarkers/
http://www.appliedclinicaltrialsonline.com/importance-
agediversity- clinical-trials
https://www.nature.com/news/genomics-is-failingon
diversity-1.20759
The color of health: how racism, segregation, and inequality
affect the health and well-being of preterm infants and their families,
Beck et al, Pediatric Research, 87, 227-234 (2020)
https://www.myeloma.org/diversity/how-myeloma-
differentafrican- americans
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4843483/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2702151/#__
ffn_sectitle
https://www.propublica.org/article/black-patients-missout-
on-promising-cancer-drugs
https://clinicaltrials.gov/ct2/show/results/NCT01564537
https://www.jnj.com/johnson-johnson-releases-inauguralyou- belong-diversity-inclusion-impact-review