FEATURE
“We need to make some
exceptions to the rules
to try to incorporate
more patients with
[disabilities] into adult
clinical trials.”
—CECILIA ARANA YI, MD
don’t want to finish it?”; and “What are the risks of be-
ing in this study?”). More than half (57%) were able to
answer all six questions correctly.
“Just because someone is not able to make good deci-
sions about his or her finances or health does not neces-
sarily mean he or she can’t give informed consent about
participating in a research trial,” said Dora Raymaker,
PhD, from Portland State University, who researches ways
to improve the lives of adults on the autism spectrum and
in other disability communities through community en-
gagement, accessible technology, measurement adaptation,
and other practices. “And just because an individual has
someone else who holds power of attorney does not mean
he or she can’t participate in shared decision-making, or
even be able to give the informed consent him- or herself.”
Explaining the potential risks of the study proved the
biggest challenge for the study participants in the 2013
study; this could be a larger stumbling block for more
invasive and higher-risk interventional studies – like
much of the research being conducted in the hematology/
oncology space. With more at stake, the importance of
clearly explaining risks increases and the bar for deter-
mining capacity rises.
However, Dr. Raymaker stressed that the rules of
ethical research do not apply differently depending on the
type of research being conducted. “The basic ethics are
basic for all research with human subjects,” she said.
Filling in the Gaps
Including people with intellectual and developmental dis-
abilities in all types of therapeutic clinical trials isn’t just
a nice thing to do – it’s good science. Conversely, limiting
participation may impose harm and impede scientific
progress.
“People with intellectual disabilities are as likely – and
more likely, in some cases – to develop any kind of health
need or health condition as anyone else, so we need to
make sure that our scientific record is inclusive of them,”
said Katherine E. McDonald, PhD, from the department
of psychology at Portland State University in Oregon.
“We need to know that the treatments work the same for
them as they do for other people.”
Dr. McDonald has studied and published extensively
on the issue of research participation for adults with
intellectual disabilities. She compares their systematic
exclusion from clinical trials to the exclusion of women
and ethnic minorities from research studies – something
the research world has long grappled with. However, al-
though United States federal funding agencies have man-
dated inclusion of women and racial minorities to ensure
that studies are representative of the larger population, no
such mandates exist regarding people with disabilities.
Individuals’ social and physical environments also can
affect their overall health, Dr. McDonald argued. ”People
ASHClinicalNews.org
with intellectual disabilities may be institutionalized,
have lower education levels, and live in poverty, and can
develop a host of preventable health conditions, giving us
a strong rationale for thinking about inclusion.”
Including patients with disabilities in clinical trials
can uncover specific risk factors and even chemotherapy
dose adjustments, as has been shown in patients with DS
and leukemia: The incidences of acute myeloid leuke-
mia (AML) and acute lymphocytic leukemia (ALL) are
approximately 10- to 20-fold higher in children with DS
than in those without.
“About 15 percent of all pediatric patients with AML
have DS,” explained Jeffrey W. Taub, MD, a childhood
leukemia researcher from Children’s Hospital of Michi-
gan at Wayne State University, “and about 3 percent of
children enrolled in clinical trials for ALL have DS, even
though they represent only about one in 700 children in
the general population.”
As Dr. Taub and colleagues reported in results from
the Children’s Oncology Group (COG) AAML0431
trial, though patients with DS and AML typically have
favorable survival outcomes with standard chemotherapy
regimens, their increased risk for treatment-related mor-
bidity and mortality complicates decisions about optimal
treatment intensity. 2
In the 204 patients enrolled in the AAML0431 study
(ranging in age from 0-4 years old), the researchers found
that, as with patients with AML and without DS, minimal
residual disease (MRD) status is a significant predictor of
outcomes. Patients who were MRD positive after the first
induction cycle had lower rates of five-year disease-free
survival than MRD-negative patients (76.2% vs. 92.7%;
p=0.01). “We actually were able to reduce the intensity of
daunorubicin treatment by 25 percent [in patients who
were MRD negative] to minimize side effects while main-
taining high cure rates,” Dr. Taub explained.
“Because we have research protocols specifically
designed for patients with DS, or treatment arms specifi-
cally for individuals with DS, we now have treatment pro-
tocols that take into account their potentially increased
risks of toxicity or, in the case of AML, their responses to
treatment and improved prognosis,” he added.
This is exactly the kind of research Dr. Arana Yi
would like to see in the adult DS/leukemia population,
she told ASH Clinical News, even though numbers of af-
fected individuals are considerably smaller.
“If we incorporated even just five or six patients
in a cohort of 1,000 patients, we would have some key
information about the basic genetic and molecular
mechanisms for this subset of patients, and we could
better understand why they develop secondary leukemia
or leukemia in adulthood,” she said. “We need to make
some exceptions to the rules