Transcript Research with Children

Research with Children
Anne K. Swisher PT, PhD, CCS
WVU Division of Physical Therapy
Why Study Children?
• Children are a society’s most precious
resource
• Some diseases only affect children
• Some diseases/conditions are expressed
differently in children than in adults
• Children learn in different ways than adults
• We have an obligation to learn about, and
optimally care for, our children
Historical Approach to Children
children are just “little adults”
1.
–
Assumption that what works for adults
will work the same in children
children don’t have any rights
(property)
2.
–
3.
18th and 19th century experiments on
vaccinations
we can trust parents/guardians to act
in a child’s best interest
–
–
18th century use of orphans and wards of
the state as research subjects
Edward Jenner and Benjamin
Waterhouse both vaccinated their own
children then exposed them to smallpox
More Examples
(CITI program)
• Alfred Hess, medical director of the
Hebrew Infant Asylum in NY, used his
wards to test pertussis, mumps, varicella
and nutritional deficiencies
• Louis Pasteur tested diphtheria vaccine on
orphans
• Karl von Ruck tested TB vaccine on
orphans before performing animal testing
Recent Example
(CITI program)
• Willowbrook, a facility for mentally
retarded children, was the site of studies
on hepititis in the 1950s and 1960s
Federal Response
• National Research Act (1974)
– Established National Commission for the
Protection of Human Subjects (1st review
organization)
– Included charge to “identify the requirements
for informed consent to participation in
biomedical or behavioral research by children”
– Report from the Commission (1977)
incorporated into 45 CFR 46 (subpart D)
detailing additional protections for children
So, you want to do research with
children as subjects….
• 1. is it an important question?
• 2. what risk is involved?
– A. no greater than minimal risk
– B. Greater than minimal risk but with potential direct
benefit (to the subject)
– C. Greater than minimal risk, but with no prospect of
direct benefit (to the subject)
• 3. use of specially protected children
– Wards of the state (orphans, abandoned children)
Is the Question Important?
• The IRB is charged with
determining the scientific
validity of all proposals
– Adequate sample
– Appropriate analysis
– Adequate justification based
on prior studies or pilot data, if
available, or sound principles
No Greater than Minimal Risk
• “the probability and magnitude of physical or
psychological harm that is normally encountered
in the daily lives, or routine medical or
psychological examination, of healthy children”
(CITI)
• Examples: blood sample (limited number), urine
collection (non-invasive), x-ray (minimal
exposure to radiation), psychological tests
(reasonable length and types of questions),
classroom observation (not intervention)
Greater than Minimal Risk but with
Prospect of Direct Benefit
• Must potentially benefit THIS subject (not
others with the condition)
• Example: new antibiotic regimen for ear
infections that might involve shorter
treatment time
Greater than Minimal Risk without
Potential for Direct Benefit
• Example: new laboratory test for bone
marrow cells in children with leukemia that
will require additional collection of a
sample but not change treatment for that
child
• Example: new training program to teach
children how to accurately report
inappropriate touching
Levels of Approval Needed
• No more than minimal risk
– Assent and consent of one parent
– May qualify for expedited review
• More than minimal risk, but potential for direct
benefit
– Assent and consent of 1 parent
– If benefit to child would not be available except by
participating in the research, assent is not required
(e.g. cancer drug study)
• Greater than minimal risk, without potential for
direct benefit
– Assent and consent of both parents
Research Not Otherwise
Approvable
• Projects not covered on the previous
categories, but hold potential to
understand, prevent or alleviate a serious
problem affecting the health or welfare of
children (CITI)
• Reviewed by a panel of experts appointed
by the Secretary of the DHHS.
Research on Wards of the State
• Extra protections involved due to the history
discussed earlier
• Important to improve health and welfare of these
children
• Important not to embarrass these children by
excluding them from activities in which their peers
in a group setting would participate
• IRB review is very strict
• Must have an advocate for EACH child who is
independent of the research or guardian
organization appointed by the IRB
Reasons to Include Children
(reprise)
• 1998 NIH Guidelines of the Inclusion of
Children as Participants in Research
Involving Human Subjects
– Children cannot be excluded in NIHsupported research unless there are scientific
or ethical reasons to do so
– Example—very little information exists on
risks and benefits of drugs in children,
especially those younger than 6 years
– What we don’t know COULD hurt us!
Pediatric Research Equity Act
(2004)
• Enables FDA to REQUIRE testing of drugs
intended for pediatric use to be tested on
children
So, there are good reasons to
involve children in research…
Protocol Issues
• What level of review?
– Exempt—commonly accepted educational
practices, observations in public, studies
using existing data
• NOT for interviews/surveys or observations in
which the researcher participates
– Expedited—no more than minimal risk
– Quorum—all other studies of children
Informed Consent
• Applies to parents/guardians
• Must specify exact procedures,
information being collected, expected
outcomes
• Language is “your child will….”
Informed Assent
• Written document
– Most appropriate for older children
• (typically > age 7)
– Must be written at an appropriate level for the
child’s education
– Describes all risks, benefits, procedure, etc.
• Language is “you will….”
Informed Assent
• Waiver
– Limited use, but may be appropriate for
youngest children or when research cannot
be done otherwise
• Child is at risk by answering (e.g. child abuse)
• Mentally unable (use short/oral forms)
• Child’s health is at risk (e.g. cancer study)
– Still need to indicate how you will determine
assent
• Body language, verbal agreement, etc
Documentation of Consent/Assent
• Likely more than just a signed form
• Researchers are responsible for showing this
• Considerations
– Safeguards against coercion
• E.g. my Mom will be mad if I don’t do this…
– Use of appropriate incentives
• E.g. $100 gift card for a 5-year-old
– Continuing assent
• E.g. child begins to cry during questioning
• There are no SET answers for all situations.
Consent as a Process,
Not a Document
• AAMC is working on this issue
• Involves elements of:
– Research design
– Document detailing risks, benefits,
confidentiality
– Appendix materials for study information,
such as schedule of study visits
– Training of staff and process
The Fundamental Problem
• The document is held above the process
• There is no way a long (in some cases, 30
pages or more) document truly informs
• Asking a potential subject to initial every page in
a 30 page document denigrates the meaning of
the informed consent process, since clearly a
step of that sort is more “for the record” (read
“lawyers”) than a part of informing or truly
receiving consent
AAMC Goal
• Use the consent document as a means to
meet the goals of the process
– To inform
– To assure comprehension
– To assure voluntariness
Target
• A four to five page consent document that
meets federal regulations and enhances
the process of informing potential research
participants
Readability Issues
(PRISM Readability Toolkit)
Sample of Rewording
• “We are interested in the negotiation and
articulation of gender roles in childhood
recreational activities”
– (grade level = 16.2)
• Versus
• “We want to find out why boys or girls
might choose different sports”
– (grade level = 2.1)