Transcript Banking Biological Samples for Pediatric Research Botkin

Banking Biological
Samples for Pediatric
Research
Jeffrey R. Botkin, M.D., M.P.H.
Professor of Pediatrics and Medical Ethics
Associate Vice President for Research
University of Utah
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Stored Human Tissues
• “The most serious and intractable
issues in health law and ethics
today are raised by the collection,
storage, and future use of tissue
samples. Imagine the vast amount
of personal information contained
in stored tissue samples …”
Professor Lawrence O. Gostin,
Georgetown University
Treuman Katz Center for Pediatric Bioethics - 2008
Conference
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Tissue Banking
• Increasingly common element of
clinical research protocols
– Genotype – phenotype correlations
– Environmental – phenotype
correlations
– Pharmacogenomic research
– Toxicogenomic research
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Tissue Banking
• Storage of tissue permits easy
access to “human subjects”
– Tissues acquired for clinical or
research purposes
– Research can be conducted that
is remote in time and place
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Tissue Banking
• Linkage of results of biological
assays with informational
databases
– Medical records
– Family history records
– Cancer registries
– Public health records
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Research with Human Subjects
• 45CFR46: Human subject means a
living individual about whom an
investigator (whether professional
or student) conducting research
obtains
(1) Data through intervention or
interaction with the individual,
or (2) Identifiable private
information.
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Research with Human Tissues
• Use in research is human subjects
research if tissue source can be
identified
– What constitutes “de-identification?”
• 45CFR46 the identity of the subject may
readily be ascertained by investigator
• HIPAA: removal of 18 identifiers or expert
opinion
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
What are the ethical issues
raised by research with human
tissues?
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Ethical and Regulatory Issues
• Who “owns” tissue samples?
• Defining the risks to individuals
from research with tissue samples
• Defining the risks to racial or ethnic
groups from research with tissues
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Ethical and Regulatory Issues
• What sort of consent should be
obtained for research with tissue
samples?
– Is consent for unrestricted future
use acceptable?
– What is the role of child assent?
– Should consent be obtained when
subjects become adults?
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Case Discussion
Retention and research use of
residual newborn screening blood
spots
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Residual Newborn Screening Specimens
• Virtually all newborns are screened for
multiple conditions using dried blood spots
• State-based public health programs
• Residual dried blood spots are available for
almost all infants
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Reasons for Specimen Storage
• Confirmation of test results
• Quality assessment of current test
modalities
• Forensic uses
– Post-mortem disease identification
– Identification of remains
• Research
– Related to newborn screening
– Unrelated to newborn screening
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Reasons for Discarding Specimens
• Uncertainty over stability of sample
– DNA appears stable
• Storage costs and space
• No clearly defined justification for
storage
• Lack of informed consent for retention
• Potential legal liabilities
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
NBS Retention
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•
•
•
•
< 6 months
1 year
2 - 7 years
21 - 23 years
indefinitely
24 programs
6 programs
7 programs
6 programs
8 programs
• 37 states have policies governing use of
residual samples
• 23 programs have written usage policy
Source: Therrell et al. Pediatrics 2006;117:S212
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Research Options
“Anonymized” specimens
•
Pros
– Valuable for epidemiologic research
– Research does not involve “human subjects”
under US regulations
– Minimal IRB review
• IRB defines exempt research
• IRB may review de-identification process
– No consent usually necessary for anonymous
use (consent may be appropriate for collection
and storage)
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Research Options
“Anonymized” specimens
• Cons
– Unable to link with health outcome of child
• Cannot detect false positives and false
negatives
– Unable to contact family with beneficial health
information
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Research Options
Linked samples (identifiable)
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Pros
– Health tracking possible
– Return of health information possible
Cons
– IRB review and oversight necessary
– Informed permission may be necessary
• Undermines value of having a specimen
already
– Return of information may pose risk to child
and/or family
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Informed Permission in NBS
•
Permission usually not sought for NBS
– Only 2 states and DC have permission
process for NBS
– No infrastructure for obtaining permission
• Acquire permission for retention of sample for
research purposes?
• Acquire permission for research use?
– Research specific to newborn screening
conditions?
– Broad authorization for other research
uses?
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Waiver of Consent
Permitted under 45 CFR 46.116d if all criteria are
met:
1) research involves no more than minimal
risk
2) waiver would not adversely affect rights
and welfare of the subject
3) research could not be practicably carried
out without waiver
4) when appropriate, subjects can be provided
with pertinent information after participation
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Policy Questions
• Should state health departments be
able to retain NBS specimens without
parental permission?
• Is biomedical research permissible with
retained specimens without parental
permission?
– Anonymous specimens only?
– Identifiable specimens?
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Treuman Katz Center for Pediatric Bioethics - 2008 Conference