Biobanking Research:
Opportunities and Challenges
Jody Harland, MS, CIP
Lead Regulatory Advisor, Indiana CTSI Regulatory
Knowledge and Support (RKS) Program
IUSM Department of Pediatrics
Biobanks
Objective:
 To consider a topic which presents challenges to researchers,
IRBs, and the public
– Biospecimen Banking
– What it is and how it works
– Special issues
– Issues of informed consent
– Attitudes of participants
– Resources
Biobanks defined
Biobanks
Collections include:
Large generic tissue banks, repositories
Materials collected in longitudinal studies (e.g., Framingham)
Unique collections (e.g., brain, Alzheimer)
Pathology specimens collected for clinical use
Newborn screening tests
Forensic DNA banks
Materials include:
Biopsy tissue
Blood (and its parts)
Tumor material
Umbilical cord blood
DNA
Guthrie cards
Urine
Biobanks are key resource
 Can be directed at specific medical
conditions OR as general collections
 Can be used to develop new therapy,
diagnostic tests, and personalized therapy
 One goal: contribute toward efficiencies in
research.
Benefits of studies using human
biological materials
 Cancer
 Studies of precancerous lesions of cervix lead to Pap smears
 Infectious disease
 Stored samples helped researchers sequence the SARS virus
 Medical Devices
 Artificial joints developed with research on stored blood, bone
 Pacemakers developed with research on cardiac tissue
Ways to use specimens
Examples of ways in which samples may be
used:
 DNA: identify genes and their functions to learn the progression of a
disease or to understand the response to certain treatment
 Plasma: used to measure drug concentrations
 Serum: used in metabolomics and proteomics studies
 Urine: used to measure certain bone markers, drug clearance, etc.
What do researchers do with the sample?
 Generally, aliquot and store in freezers until the time needed.
Biobanks: what makes them
even more powerful?
 Collection of samples is good.
 To be better, we need to know something about the person
who donated them.
 Options:
 Do nothing – just use the sample
 Case report form – selected amount of demographic information presumably
obtained at the time the sample is collected
 Connect to the electronic medical record and obtain data about the
individual.
 Can require other safety measures, e.g., barcoding system; firewalls;
prospective informed consent from subject
Vocabulary
Biobank = biorepository
De-identified vs. anonymized?
 De-identified = no identifiers attached to samples; code is
kept separate
 Anonymized = after de-identification, code is destroyed.
Vocabulary
Collection/storage protocol is the protocol
where samples/data are collected and
stored.
 Consent obtained from subjects for:
 Future, unspecified uses
 If doing this, linkage to EMR data in perpetuity (sometimes – at
least )
 Potential additional opportunity for subject to consent to be recontacted in the future (not required though)
 IRB approval required.
Vocabulary
 Usage protocol is the protocol by which the
samples/data will be used (e.g., the specific
project).
 Subject’s consent usually not needed again (e.g., ‘waived’
because already gave consent for sample/data to go into
the biobank and to be used for future, unspecified
research)
 IRB approval required.
Vocabulary
 Governance: how are the samples/data
managed? Distributed for projects?
 Structure should exist.
 Committees which make determinations about usage of
samples/data
 Steering Committee
 Scientific Review Committee
 Consider issues of feasibility
 Scientific merit of project
 Is data there?
 Is the amount of sample requested reasonable? Is there enough of the
sample to distribute?
 IRB will look for it to be described in the protocol.
Vocabulary
 Certificate of Confidentiality (CoC)
 Document that can be obtained from NIH which protects investigators
and institutions from being compelled to release information that could
be used to identify subjects with a research project.
 CoC’s allow the investigator and others who have access to the
research records to refuse to disclose identifying information in any civil,
criminal, administrative, legislative, or other proceeding, whether at the
federal, state, or local level.
 Examples of sensitive research activities include:
 Collecting genetic information
 Collecting info on psychological well-being of subjects
 Collecting info on subjects’ sexual attitudes, preferences, or practices
 Collecting data on substance abuse or other illegal risk behaviors
Vocabulary
Genetic Information NonDiscrimination Act (GINA)
 Federal law which generally makes it
illegal for health insurance companies,
group health plans, and most employers
to request the genetic information from
this research and discriminate against
individuals based on their genetic
information.
Vocabulary
Genome-Wide Associations Studies (GWAS)
 Purpose of GWAS is to discover genetic factors that contribute to the
development, progression, or treatment options for a particular
disease or trait.
 Whole genome information, when combined with clinical and other
phenotype data, offers the potential for increased understanding of
basic biological processes affecting human health, improvement in
the prediction of disease and patient care, and ultimately the
realization of the promise of personalized medicine.
 As a result, the NIH has established a centralized GWAS data
repository to advance science for the benefit of the public.
 Potential for public benefit to be achieved through sharing GWAS
data is significant.
 Results of such studies can be sensitive – INFORMED CONSENT IS KEY!
Vocabulary
Metabolomics
 Scientific study of chemical processes involving metabolites,
e.g., the "systematic study of the unique chemical fingerprints
that specific cellular processes leave behind."
Proteomics
 Large-scale study of proteins, particularly their structures and
functions. Proteins will vary with time and distinct
requirements, or stresses, that a cell or organism undergoes.
Cellomics
 Study of cell structure, function and generation and
application of cellular products.
What do the regulations say?
 Permits some forms
of research involving
specimens to be
expedited and/or
exempt
 Still differs
somewhat in
requirements from
those in HIPAA
VA-Specific Regulations
 When involving VA patients in studies where specimens are collected
and/or stored for future research purposes beyond the scope of the
work in the original protocol/ICS or for those which are collected
under a specific biobank protocol, certain regulations pertain. (VA
Handbook 1200.12)
 VA regulatory requirements will be based upon a variety of
considerations, including:
 Where/how/by whom samples are to be stored
 HIPAA
 Timelines for destruction of samples (e.g., outside of VA firewall? Can’t
keep as long.)
 For-profit (heavier restrictions) vs. Non-profit
 Simple (1 or 2 PIs; VA owns it and manages) vs. Complex (multiple PIs on
multiple sites; different databases/data-broker services) determinations
VA-Specific Regulations
 Contact Marta Sears (marta.sears@va.gov) with any
questions.
 Reference VA Handbook (1200.12):
 Use of Data and Data Repositories in VHA Research
http://www.va.gov/vhapublications/ViewPublication.asp?pu
b_ID=1851
5 major biobanks at IU
Healthy
Affected
Area
Future
unspecified
use?
NCRAD (Foroud)
Yes
Yes
Alzheimer's
No
No
CRC
(Shekhar)
Yes
Yes
Variety
Yes
Yes
Pediatrics
(Ragg/Schadow)
Yes
Yes
Neo; GI;
Endo;
Cardiology;
Cancer
Yes
Yes
Komen
(Storniolo/Clare)
Yes
Yes
Breast
No
No
Indiana Biobank
(Shekhar)
Yes
Yes
Variety
Yes
Yes
Biobank
Linked to
medical
records?
Questions at this point?
Special Issues Related to
Biobanking Research
Issues of informed consent
Attitudes toward biobanking research
Special Issues Related to
Biobanking Research
Issues of informed consent
Attitudes toward biobanking research
Belmont Principles
Respect for persons
• Individuals should be treated as autonomous agents
• Persons with diminished autonomy are entitled to protection.
Beneficence
• Human subjects should not be harmed
• Research should maximize possible benefits and minimize
possible harms.
Justice
• The benefits and risks of research must be distributed fairly.
*The Belmont Report (1979) - National Commission for
the Protection of Human Subjects of Biomedical and
Behavioral Research
IRB SOP on Biospecimen
Banking
• From the IUPUI/Clarian IRB SOP on “Biological
Specimens in Research”, IRB review is required under
Collection
2 scenarios:
– retrospective use of previously stored specimens, and
– prospective studies requesting the collection, storage or use of
specimens for current and/or future research.
• Two categories of specimens:
Protocol
Use Protocol
– those obtained initially for clinical or diagnostic purposes only, and
– those obtained solely for research purposes.
• IRB approval criteria (45 CFR 46.111) must be met for
these projects (the same as any other human
subjects research project) – unless the projects are
reviewed as ‘exempt’.
Criteria for IRB Approval
(45 CFR 46.111)
Risks to subjects are minimized.
Risks to subjects are reasonable in relation to anticipated benefits .
Selection of subjects is equitable.
Informed consent will be prospectively obtained and documented (unless
waived).
Adequate provisions exist to monitor the data and ensure subject safety.
Adequate provisions exist to protect privacy of subjects and maintain
confidentiality of data.
The influence of payments … is not coercive or do not present undue
influence to potential subjects.
If … subjects are likely to be vulnerable to coercion or undue influence,
additional safeguards exist.
Biospecimen Banking Issues of Consent
• Potential Challenges
– Informed Consent – assure comprehension and
voluntary participation
• Proposed use(s)
• Security and maintenance of sample
• Privacy and confidentiality of data attached to sample
and results generated from sample analysis
• Obtaining results from analyses
• Possible future contact for additional studies?
• Impact of genetic studies and returning results
• Impact upon families, employability, insurability, etc.
• Potential third party access to samples – oversight
Issues of Consent: Henrietta Lacks
• 1951: 30 year-old poor,
uneducated African-American
woman visits Johns Hopkins and is
diagnosed with cervical cancer.
• Required radiation treatments for
next several months.
• During her first two-night stay at
hospital, doctors removed several
pieces of tissue from her tumor and
placed them in a dish.
• Neither Lacks nor her family gave
permission for her cells to be taken.
Issues of Consent:
Henrietta Lacks
• Dr. George Gey (head of tissue-culture research at Hopkins) was
interested in growing first ‘immortal’ human cells (a continuously
dividing line of cells that all descend from one original sample).
To date, he had been unsuccessful.
• Her cancer cells grew well and doubled in number every 24
hours.
• Dr. Gey named the cells “HeLa” cells after Lacks and began
sending cells to scientists all over the world for research.
• Six months after her diagnosis, Lacks died.
Issues of Consent:
Henrietta Lacks
• HeLa cells have been used to:
•
•
•
help develop the polio vaccine (Tuskegee Institute)
study cancer and viruses
lead to advances like in vitro fertilization (IVF), cloning,
and gene mapping
• HeLa cells piled onto a scale = more than 50
million metric tons (100 Empire State
Buildings)
• HeLa cells have generated a multimillion dollar
industry.
Issues of Consent:
Henrietta Lacks
• Twenty years after cells were taken, family learned that
they were being used.
• Family was living in poverty in Baltimore – could not
afford health insurance and had limited
education.
• Family struggled to understand what existence of her
cells really meant.
………To date, family has not been compensated for this
contribution; however, various foundations have been
established to ensure access to healthcare and
education, for example, for her grandchildren.
Issues of Consent:
Henrietta Lacks
•
Issues – gender, race, education:
•
•
What if she had been presented with the
opportunity to give permission?
What topics should that conversation have
covered?
Issues of Consent Havasupai Case
• Havasupai Indian Tribe Case
(Mello & Wolf, 2010; Harmon 2010)
• Havasupai Indians live at bottom of Grand Canyon.
• Beginning in the 1960’s, high incidence of diabetes leads
to amputations – tribe members can’t hike out of the
canyon – forced to leave to obtain dialysis.
• Late 1989, tribal member approaches ASU anthropologist
who had gained the tribe’s trust to ask for help in
preventing the spread of diabetes.
• Anthropologist approaches ASU geneticist for help (Pima
Indians have genetic variant related to high rate of
diabetes).
• 1990 diabetes study in which ASU researchers collected
more than 200 blood samples from tribe members.
Issues of Consent –
Havasupai Case
• Consent form (in simple English) described the project as
studying “the causes of behavioral/medical disorders,” but
pre-study communications with tribal leaders apparently
focused on diabetes.
• Havasupai hoped that if found a cure to diabetes, their
people wouldn’t have to leave the canyon.
• Students obtained consent (written and verbal).
 Researchers used samples in multiple studies unrelated to
diabetes, sharing them with other investigators.
• Examined several genes (schizophrenia, metabolic disorders,
alcoholism and found little to pursue - also did not share the gene
variant linked to diabetes similar to Pima)
Issues of Consent –
Havasupai Case
• 2003 – grad student comes up with new technology to
discern variations in the Havasupai DNA and wrote
dissertation
• Carletta Tilousi stops by anthropologist’s office and he invites her to
the doctoral presentation.
• His presentation doesn’t match what she and others thought they
donated blood for.
• Two dozen publications based upon those blood samples.
• 2004 – tribe members filed a $50 million lawsuit alleging:
•
Fraud
•
Breach of fiduciary duty
•
Negligence
•
Trespass
Issues of Consent –
Havasupai Case
• Tribe members objected to 3 uses:
• Study evaluating the genetic basis of schizophrenia
• Study examining inbreeding (stigmatization issues and
concern related to cultural belief that inbreeding brings
harm to one’s family)
• Evolutionary-genetics studies suggesting that, contrary to
Tribe’s origin story, its ancestors migrated across the Bering
Sea.
• Case law pretty clear – biospecimen donors do not
retain property interests in samples collected and used in
accordance with properly obtained informed consent.
• What is adequate informed consent?
Biospecimen Banking Issues of Consent
• April 2010, ASU agrees to:
• Pay $700K to 41 members of the Havasupai Indian tribe to
settle legal claims.
• Return all blood samples in its possession.
• Return documents like lab books, genealogy materials
containing research derived from the samples.
• IRBs at universities in the suit cannot approve ongoing or
new research involving the samples.
• Provide a list to the tribe of entities to which it previously
transferred the samples.
Issues of Consent –
Havasupai Case
 What did individuals understand about what their blood
samples were to be used for?
 Community consultation?
 What did the consent form say?
 What was the IRB’s role?
 Risks to participants – what about risks to entire communities?
 Any parallels to studies at IU?
Special Issues Related to
Biobanking Research
Issues of informed consent
Attitudes toward biobanking research
Informed Consent:
What Do We Know?
IU Cancer Patients
 ~85% agreed that stored tissue could be used in
unspecified future research
 60-70% would not require re-contact each time
tissues were used

Helft , Champion, Eckles, Johnson, Meslin, (2007)
Parental Attitudes-—Pediatric Biobanking
•
•
•
•
68% agree/strongly agree pts should have
chance to be in research
81% somewhat/very likely to permit child’s blood
to in biobank
91% have fair/great deal of trust in hospitals to
protect confidentiality
62% oppose/strongly oppose commercialization

Harland, Miller, Meslin, Wolf, Denne (2010)
Women and Pregnant Mothers
 77% felt predictive health research was
worthwhile
 Most supported consent for future use

Haas, Renbarger, Meslin, Drabiak, Flockhart (2008)
Physicians and Nurses—Pediatric Biobanking
 MD and RN attitudes toward pediatric biobanks
are similar
 Broad support for a pediatric biobank from HCP,
including support for unspecified use of samples

Denne, Wolf , Harland, Miller, Meslin et al (2008)
[Unpublished]
Biospecimen Banking Assessing Attitudes
Parental Attitudes Toward Pediatric Biobanks
(Harland, Miller, Meslin, Wolf, and Denne)
 Will parents/guardians have particular areas of
concern about participation in a biobank?
• Areas of concern would relate to confidentiality and
commercialization.
 Because the point of contact for biobank entry will be
the Hospital environment, we asked whether there
would be any differences between the perspectives of
parents/guardians of inpatients vs. outpatients?
• Parents/guardians of inpatients would be more in favor of
biobanking research than parents of outpatients.
Biospecimen Banking -
Parental Attitudes toward Participation
 Methods
 Survey questions developed by multi-disciplinary group.
 MDs, RNs, survey research expert, hospital parent support representative,
bioethicist, IRB regulatory expertise, parent.
 Questions field-tested by a small group of parents/guardians.
 Parents/guardians of pediatric inpatients and pediatric
outpatients at Riley Hospital were offered paper-and-pencil
surveys in person.
 English and Spanish language versions of the survey were available.
Biospecimen Banking Parental Attitudes toward
Participation
 General questions about child’s health
 Attitudes toward medical research
 Biobank questions
• Support for biobanking
• Use of samples
• Child’s health, age
• Future contact
• Confidentiality
• Commercialization
General Support for Medical
Research
“All Riley Hospital patients should have a
chance to be in medical research.”
40
35
33
35
68% “strongly
agree” or “agree”
with this
statement.
28
30
25
20
15
10
3
5
1
0
Strongly
Agree
Agree
Neutral
Disagree
Strongly
Disagree
Support for Biobanking
“In general, how likely would you be to allow your
child’s blood to be included in the Riley Hospital
biobank?”
50
45
47
81% are “very
likely” or
“somewhat
likely” to do
so.
40
35
34
30
25
20
15
12
10
5
4
4
0
Very likelySomewhat likely
Somewhat unlikely
Very unlikely Don't know
Confidentiality
“If your child were to participate in a biobank study,
how much do you trust Riley Hospital to maintain the
confidentiality of your child's personal health
information?”
70
62
60
91% have “a
great deal” or
“fair amount”
of trust.
50
40
29
30
20
7
10
2
1
Not much
None
0
Great deal
Fair amount
Don't know
Commercialization
“Some biobanks are set up to allow the sale of
samples for a profit. How much would you
support or oppose such an arrangement at
Riley Hospital?”
45
39
40
35
30
22
25
62% “strongly
oppose” or
“oppose” the
sale of samples
for a profit.
23
20
15
10
6
10
5
0
Strongly
support
Support No opinion Oppose
Strongly
oppose
Comments Received
 “I want to learn more about it. Never heard about it ‘til now.”
 “Extremely concerned--privacy, discrimination, misuse/abuse issues.”
 “Would this child’s sample of blood be used to research cloning of any
kind?”
 “I believe that sometime in the future if a child was born with a genetic
defect, like my child, it would help someone else to know what has
happened.”
 “My daughter has a rare disorder and more knowledge needs to be given to
physicians.”
 “Help get answers, cures, and some hope for other parents.”
Biospecimen Banking -
Attitudes Toward Participation
 Parents/guardians generally are supportive (80%) of
biobanking initiatives and research activities.
 Parents/guardians may not be as concerned about
confidentiality issues in biobanking research. 91%
expressed a ‘great deal’ or ‘fair amount’ of trust.
 Parents/guardians are generally opposed (61%) or
perhaps need more information (22% expressed ‘no
opinion’) about commercialization issues.
Summary
 Biobanking research promises to be extremely
valuable research in an era of personalized
medicine.
 Very real ethical and regulatory concerns.
 Ultimately, a question of how do we ensure
adequate informed consent?
 Do we talk with individuals, communities?
 How do we describe the potential possibilities in
a meaningful way?
 How will case law and ethics evolve?
Summary
 As researchers, we must be transparent in what
we know to be true, what we expect to be true,
and what we just don’t know.
 Individuals need to trust in the “institution” (thus,
we need to be trustworthy!)
 Ultimately, biobanking research with adequate
informed consent promises to be an immense
opportunity to advance our understanding of
human health.
Resources
 Indiana Biobank (IB)
 Indiana CTSI Recruitment Office
 Regulatory Knowledge and Support (RKS) Program
 Clinical Research Center (CRC)
 Project Development Teams (PDTs)
http://www.indianactsi.org/
Questions?
Contact info:
Jody Harland, MS, CIP
UH 5525
harlandj@iupui.edu