e-Ethics AUGUST 2003
Whose "No" Means No?
Permission and Assent in Pediatric Research
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A t Karen Kinder's yearly physical,
Dr. Lewis invites her parents to
enroll Karen in a research study
evaluating a new insulin pump for
children. Karen was diagnosed with
juvenile diabetes at age five. Now
twelve, she is quite knowledgeable
about diabetes and administers her
own insulin injections. The Kinders
are enthusiastic about the study, but
when Karen learns that it requires
weekly clinic visits for two months,
then bimonthly visits for four
months, she refuses. "I won't have
time for music lessons or swimming
practice," she protests. "Anyway, I
don't mind the injections. I'm used
to them." Her parents think the
pump will be more convenient for
Karen, but acknowledge that participation
will curtail her routine.
Dr. Lewis knows the Kinders
well and believes that Karen will
eventually agree to enroll if her parents
insist. Should he accept
Karen's refusal, or should he encourage
her to participate?
Dr. Lewis's colleague, Dr.
Roberts, experiences a similar dilemma
with fourteen-year-old Frankie
Field, diagnosed six months ago
with cancer of the connective tissue
in his brain and spinal cord. He has
not responded to standard therapy,
and without further treatment will
probably die within six to twelve
months. Dr. Roberts knows of an
investigational treatment currently
offered at a nearby children's hospital,
and believes that Frankie meets
enrollment criteria.
Frankie's parents wish to begin
the research therapy immediately,
but Frankie wants nothing more to
do with hospitals, needles, doctors,
or nurses. Dr. Lewis understands
Frankie's frustration. There is no
guarantee that investigational treatment
will work. If Frankie has only
months to live, perhaps it would be
best not to spend them as a
research subject. On the other hand,
the treatment has prolonged the
lives of some children enrolled in
the study, although their long-term
survival is unknown. What should
Dr. Roberts do?
"Vulnerable populations" is a
regulatory term that includes children,
prisoners, pregnant women,
mentally disabled persons, and the
economically or educationally disadvantaged.
U.S. law specifically covers
these prospective research subjects
to prevent their exploitation or
coercion, and to protect them from
experiencing research burdens
unnecessarily. For example, children
should not be enrolled in
research when the problem to be
studied can be investigated using
adults. Minors should not be studied
merely because they are more
easily accessed and controlled.
Pediatric researchers are challenged
to guard children's welfare
while affording them opportunities
to benefit from investigational interventions.
Because children are
physiologically and psychologically
different from adults, it cannot be
assumed that they will respond as
adults do to medications, procedures,
and devices. Similarly, adult
subjects cannot be substituted in
studies of diseases that affect infants
or youths. Federal regulations and
ethical guidelines therefore take into
account the level of risk involved in
the research protocol and the degree
to which children enrolled are likely
to benefit directly.
Informed consent, the central
issue for both doctors here, has a
unique context in pediatric research.
Children are presumed incapable of
consent, yet one person cannot consent
for another. Only the person
who participates as a subject—the
one exposed to potential risks and
benefits—can consent. Therefore, in
pediatric studies "consent" is
achieved by permission and assent.
Parents give permission for children
to participate, and children assent by
indicating age-appropriate understanding
and accord. Federal regu-lations
require "affirmative agreement"
of children capable of assenting,
which has been interpreted to
mean that silent submission does
not qualify as assent.
Obviously assent is impossible
for infants or the very young, and
parents generally are given wide latitude
to know what serves the best
interests of their children. However,
obtaining assent requires attending
to children's experiences and preferences.
Federal regulations do not
include specific ages at which assent
must be sought. The American Academy
of Pediatrics (AAP) recommends that
children seven years of age and older be
given this opportunity. Because children
of the same age vary in abilities and
maturity, however, investigators are
expected to assess each child's capacity
to comprehend and assent.
Both Karen and Frankie, though relatively
young, can articulate how they
experience illness and treatment. Karen
has lived with chronic disease for seven
years, and appears to understand well
its nature and treatment. Frankie has
had less experience, and it is difficult to
know from the facts provided whether
his refusal expresses an aversion to
medical interventions, or is a reflective
response that includes understanding of
his terminal diagnosis. Both physicians
should converse with their child patients
to understand better their reasons for
not wanting to participate.
A child's refusal to enroll in research
should be carefully evaluated, but may
not preclude participation. In determining
whether to override a child's dissent,
the AAP urges investigators to consider
whether the child will directly benefit,
and whether such benefits are available
outside research protocols.
Frankie has not responded to standard
treatment. The research therapy is
not available elsewhere and has benefited some children. On this basis, Dr.
Roberts may decide to override Frankie's
dissent, particularly if he believes that
Frankie does not fully grasp the seriousness
of his cancer. If, however, he
determines that Frankie understands his
status and wants to die at home rather
than undergo additional therapy, he
should discuss that option with Frankie's
parents before overriding his young
patient's desires.
Dr. Lewis has less compelling reasons
for overriding Karen's refusal. Her
diabetes is well controlled by traditional
therapy and she has demonstrated
knowledgeable, responsible participation
in her own care. The fact that the
pump may prove more convenient is a
valid consideration, but not decisive if
Karen is opposed to participation.
Affording children the opportunity
to benefit from research while protecting
them as vulnerable subjects requires
appreciation of how they differ physiologically
from adults and how they
understand and experience illness and
treatment. Respecting children as children
involves careful attention to individual
differences and sensitivity to the
parent-child dynamic. Promoting children's
best interests in human subject
research may entail overriding their
desires, but their voices deserve to be
heard in the decision-making process.
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