Ethical and Regulatory Issues in Biobanking

1
Ethical and Regulatory Issues in Biobanking

• Jeffrey R. Botkin, MD, MPH
• Professor of Pediatrics
• Associate Vice President for Research

2
Case

• 1989 study of type I diabetes was conducted at
  Arizona State University
• Havasupai Indians recruited and 400 clinical
  histories, family histories, and blood samples
  obtained
• Late 1990s, discovered that research was
  conducted on schizophrenia and population
  migration studies using study materials
• Allegedly without additional consent

3
Case

• Allegation Research had been conducted at ASU
  and multiple other institutions around the
  country
• Havasupai tribe sued ASU, litigation on-going

4
What Is A Biobank?

• Any collection of biospecimens or genetic
  material
• with or without associated information
• Retained for sharing and/or future uses
• May be with or without identifiers
• May be de jure
• biorepository designed for storage and sharing
• IRB-approved scope, consent forms, oversight
• May be de facto
• materials kept in lab freezer accidental bank
• casual sharing creates accidental bank

5
The Biobanking Boom

• Big banks needed/wanted
• HapMap project
• gene-environment interactions
• Genome-Wide Association Studies
• Guthrie cards (newborn blood spots)
• Families with a disease or condition worldwide
• Statewide national disease registries
• Adding biospecimen collection to large
  longitudinal studies
• Linking to medical records and other info,
  continually updated

6
Banking Specimens for Future Research

• Two stage process for an IRB
• OHRP considers the establishment of a research
  resource, like a biobank, to be under IRB
  oversight
• Protocols to use biobanked specimens require
  separate IRB approval

7
Ethical Issues

• How much control should individuals have over
  tissues removed for clinical or research
  purposes?
• What are the risks to sources from research using
  tissues?
• What are the risks to ethnic/racial groups from
  genetic research with tissues?
• When should research results be returned?

8
Regulatory Issues

• When is research with tissues human subjects
  research?
• 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
• The individual must readily identifiable to
  investigators under 45CFR46

9
Regulatory Issues

• HIPAA requires removal of 18 potential
  identifiers for the sample to be de-identified
• Samples may be de-identified with respect to the
  Common Rule but identifiable with respect to
  HIPAA

10
Regulatory Issues

• The regulations exempt research on existing
  databases, records or specimens if these
  resources are publicly available or if the
  resource has been stripped of all individual
  identifiers.

11
University of Utah Policy

• If tissues are to be de-identified, the process
  should be under IRB oversight
• Research conducted with tissue specimens
  obtained from identifiable individuals, whether
  living or dead shall be subject to IRB oversight

12
OHRP 2004 Guidance

• Investigator A obtains tissues from research
  participants and retains a link to individual
  identifiers
• Investigator A shares tissues with Investigator
  B.
• Investigator B cannot determine the identity of
  the tissue sources but they remain linked
• If Investigator B agrees not to attempt to
  identify the identities of the tissue sources,
  research by Investigator B is NOT human subjects
  research.
• No stipulation that agreements are under IRB
  oversight

13
Consent Issues

• Consent must be obtained for tissue banking for
  future research
• May the University of Utah or its research
  partners retain your ltlttissue/blood/urine/body
  fluidgtgt sample(s) after the end of this research
  project for use in future research?
• YES, my sample(s) may be saved for future
  ltltspecify a specific condition/diseasegtgt research
• NO, my sample(s) must be destroyed at the end of
  this research project

14
Consent Issues

• If yes, may the University of Utah or its
  research partners keep your name and other
  identifying information with your sample(s)?
• YES, my personal identifiers and medical
  information can be kept with my sample(s). All
  information will be kept secure and confidential
• NO, my name and identifiers must be removed from
  my sample(s). My sample(s) cannot be linked back
  to me.

15
Consent Issues

• Scope of permissible consent is controversial
• 45CFR46 permits consent for unspecified future
  research
• HIPAA requires that the nature of the research be
  disclosed in the consent process
• Increasingly sponsors are requesting language in
  the consent document for unspecified future
  research

16
Consent Issues

• Permission for re-contact necessary?
• Permission to share tissues with collaborators
  within and outside the University of Utah is
  encouraged

17
Returning Results

• Re-contact if medically significant information
  is found?
• No ethical or regulatory requirement to disclose
  results that are not clinically significant
• What is significant?
• nature, magnitude, likelihood, timeliness
• Privacy tradeoffs
• how long is contact information kept?
• Whose duty is this?
• who has the knowledge to determine medical
  significance?
• contact information and knowledge may be widely
  separated
• Information and oversight infrastructure could be
  extensive (and expensive)

18
Returning Results

• Research participants (and potential
  participants) should be informed about whether
  results of the research will be returned
• Review consent forms for return of results
  information!

19
Interpretation Dissemination

• Group interests and group harms
• IRBs usually do not consider, but their
  significance is acknowledged (and growing)

20
Ownership of Tissues

• Law offers few cases on point
• OHRP has not taken a position
• Legal cases
• Moore v Regents of University of California 793P.
  2d 479 (Cal.1990)
• No property interest, depends on other state law
• Consent provisions concerning commercial uses
• Greenberg v Miami Childrens Hospital
• Specimens contributed for Canavan disease
  research
• Dispute over intellectual property
• Court found that participants donated tissue

21
Ownership of Tissues

• Washington University v Catalona 2006
• William Catalona, M.D., leading investigator of
  prostate disease at WU
• 3500 prostate tissue samples, 100,000 serum
  samples, contributed by Dr. Catalona (25) and
  colleagues (75)
• Dr. Catalona planned to take tissues to
  Northwestern University, WU refused
• Dr. Catalona asked his patients to request that
  their samples be sent to Northwestern

22
Catalona Case

• Opinion
• Numerous documents verifying that repository was
  established and supported under the auspices of
  WU
• Subjects donated their samples to Washington
  University
• Right to withdraw from research does not imply
  right to control disposition of samples
• Washington University owns all biologic materials
  in the repository

23
Ownership Issues

• Catalona Case Clarifies that research
  institutions own tissues obtained through
  research
• Moore Case No obligation to share financial
  gains with subjects that might be obtained
  through IP development
• Informed consent document should state that the
  participant will not share in financial returns
  from products developed from their tissues

24
Withdrawal from Research

• Regulations require that participants can
  withdraw from research at any time
• Withdrawal from a tissue bank means removal of
  sample from the bank and destruction (not return
  to individual)
• Data obtained from research prior to withdrawal
  need not be destroyed
• These provisions should be in consent process

25
When Children Provide Biospecimens

• Should the IRB require re-consent for tissue
  research when the minors become adults?
• May depend on the nature of the research

26
Review Considerations

• Does the consent document adequately describe the
  tissue banking aspect?
• Does consent ask for unspecified future uses?
• If so, is this justified?
• Are participants informed of lack of financial
  gain?
• Are participants informed of withdrawal
  implications?
• Are participants informed about return of
  results?
• Does the consent permit sharing with
  collaborators?