Developing A Repository Protocol

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Developing A Repository Protocol

• Kathleen T. Uscinski. MBA, CIP
• April 25, 2006

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Agenda

• The Basics Objective, Definitions, Key Terms
• Creation of Repositories and Databanks
• Regulations and Guidance
• IRB Considerations
• Attributes of a Repository Protocol
• Ownership of Tissue and Data

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Definitions

• Research A systematic investigation, including
  testing and evaluation, designed to develop or
  contribute to generalizable knowledge. that may
  assist in improving the care of currently unknown
  beneficiaries in the future.
• Human Subject a living individual about whom an
  investigator conducting research obtains
• 1) data through intervention or interaction
  with the individual, or
• 2) identifiable private information.

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Collections and Databanks

• Databases are often created not for a specific
  research project but as resources for future
  research.
• Tissue banks and collections of identifiable
  biologic materials containing patient material
  with identifiable patient data are similarly
  created and maintained.

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• Specific concern is the collection of
  data/biologic
• samples and the secondary uses of the
• information/materials by
• Colleagues at the same or other
  institutions/hospitals that collect the
  data/tissues through clinical interventions.
• Researchers who collect the data/tissues as part
  of a primary study and who wish to conduct, or
  wish to share the info with colleagues who wish
  to conduct, secondary research eventually.
• Commercial or other research sponsors to which
  data/tissues have been given during the course of
  primary research.

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What May Apply

• Ethical Obligations
• Clinical Trial Agreements
• HIPAA
• Common Rule (OHRP Guidance Nov 1997 and August
  2004)
• FDA Regulations and Guidance
• State Laws and Litigation
• Publication Requirements (ICMJE standards)
• Industry Codes (PhRMA)
• Voluntary Accreditation Standards for IRBs

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Informed Consent and IRB Review OHRP Guidance
Recipient Investigator Recipient
Investigator Recipient Investigator
Data/Tissue Collector Data/Tissue
Collector Data/Tissue Collector
Repository Storage Data Management
IRB Review Sample Informed Consent Certificate of
Confidentiality Assurance of Compliance
IRB Review Informed Consent Submittal
Agreement Assurance of Compliance
IRB Review Informed Consent/Waiver Recipient
Agreement Local Policies
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IRB Considerations of Repository Protocols

• Key Questions
• Is it appropriate for the HIC to approve a
  consent form
• for a study repository that is vague or broad
  with
• respect to possible future uses by researchers?
• The HIC may not have enough information to
  adequately assess risks to subjects, or that
  information may not be adequately conveyed in the
  ICF.
• The HIC could approve a collection protocol that
  contemplates unspecified future uses by
  institutions investigators (if subject is so
  informed), but new HIC review (and consent or
  waiver) would be required before initiating any
  such future research.

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IRB Considerations of Repository Protocols (cont.)

• Who will have access to the information for
  future research purposes? Is it possible to even
  predict this?
• What identifiers will remain associated with the
  data/materials? What coding will be done?

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Considerations for Future Uses

• Is the proposed use of the data or identified
  biologic material consistent with the subjects
  likely understanding of how it would be used
  under the terms of the consent form?
• Is collection consent sufficient?
• Can consent be waived, or must it be obtained?

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Research Regulations Informed Consent and HIC
Review

• OPRR (OHRP) guidance for IRB review of consent
  for a collection study
• Informed consent should include a clear
  description of
• the operation of the repository
• the specific types of research to be conducted
• the conditions under which data and specimens
  will be released to recipient-investigators and
• procedures for protecting the privacy of subjects
  and maintaining the confidentiality of data
• Informed consent information describing the
  nature and purposes of the research should be as
  specific as possible.
• Where human genetic research is anticipated,
  informed consent information should include
  information about the consequences of DNA typing
  (e.g., regarding possible paternity
  determinations)

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Repository Protocol Attributes

• University-wide vs. Departmental Repositories
• Duration
• The IRB should review and approve a protocol that
  describes the nature and purposes of the research
  as specifically as possible
• The purpose of this study is to create a Yale
  School of Medicine Neuro-Oncology data bank that
  will be used for future research projects
  involving the study of brain cancer biology and
  brain biology and related medical issues.

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Protocol Attributes Banking Data

• Conditions under which data will be accepted
• The data bank will be created from adult patients
  (age gt18) who are receiving on-going care for
  brain tumors in the Departments of Neurosurgery,
  Radiation Oncology and Section of Medical
  Oncology.
• Subject info that will be entered into the
  database and may be used for future research
  purposes Name, age, medical record numbers,
  surgery date, clinical test results (such as MRI,
  lab tests and neuropsychological results), the
  duration of symptoms, risk factors for tumors and
  other diseases, past medical history and other
  pertinent medical information.

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Protocol Attributes Banking Data

• The Protocol should state the conditions under
  which data will be shared
• Data collected by the PI or other researchers
  listed on
• this protocol will be distributed for secondary
  research
• purposes only after the recipient investigator
  has
• obtained IRB approval for the proposed research
• objective or after having received an IRB
  exemption or
• a determination that research is not considered
  human
• subject research.
• Data will be distributed for research projects of
  the
• same nature and purpose specified in this
  protocol and
• by the donor-subject in his/her ICF and HIPAA
• authorization documents.
•  
•  

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Protocol Attributes Banking Data

• The Principal Investigator is responsible for
  receiving appropriate attestation by recipient
  investigators prior to permitting access to the
  database for activities considered preparatory to
  research. Attestation will be obtained by using
  the Request for Access to Protected Health
  Information for a Research Purpose Form.
  http//info.med.yale.edu/hic/hipaa/index.html
• Data released to collaborators for IRB approved
  research will be assigned a unique code, unless
  permission is granted by the HIC to include
  specific identifiers.
• 1996 OPRR Guidance strongly recommends that
  collector-investigators not provide
  recipient-investigators with access to the
  identities of donor-subjects.

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Research Oversight

• Federal regulations require HIC review and
  approval of all
• research studies involving human subjects, unless
• Research is determined to be exempt involves the
  collection or study of existing data, records,
  pathological specimens, or diagnostic specimens,
  if sources are publicly available or if the
  information is recorded by the investigator so
  that subjects cannot be identified, either
  directly or through identifiers linked to the
  subjects, or
• Research is determined to be Not Human Subjects
  Research or not subject to IRB review
• Use of coded private information or specimens, or
• De-identified data/biologic samples.

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Research Oversight

• Federal regulations and Yale University policy
  require that someone OTHER THAN THE PI determine
  whether a research project is exempt, considered
  not to be human subject research OR does not
  require IRB oversight.
• Journals require a letter of IRB approval or
  oversight.

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Protocol Attributes Banking Data

• Risks to subjects are minimized, use procedures
  consistent with sound research design and which
  do not unnecessarily expose subjects to risk.
• 45 CFR 46.111(a)(1)
• De-identification
• Risks to subjects are reasonable in relation to
  anticipated benefits, if any, to subjects, and
  the importance of the knowledge that may
  reasonably be expected to result. 45 CFR
  46.111(a)(2).
• What if the data is used for genetic testing?

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Protocol Attributes Banking Data

• Adequate provisions to protect the privacy of
  participants.
• Provisions to maintain the confidentiality of
  data.
• 45 CFR 46.111(a)(7)
• Information about the subject-donors will be
  maintained in a password-protected computer and
  password-protected data files. Only researchers
  responsible for operating the data bank, will be
  provided with access. Information resides on a
  server considered by ITS-Med to adhere to the
  HIPAA Security Rule.
• Should IRB should inquire about security?

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Protocol Attributes Banking Data
Conditions whereby the subject can withdraw their
participation Donor-subjects may withdraw their
consent for the use of any data at any time. In
this event, the Principal Investigator will
indicate in the data base that consent from the
donor-subject is no longer active and that data
can no longer be used. Anonymize vs.
Destroy the data?  
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Protocol Attributes Banking Data

• DSMP and provisions for reporting serious and
  unanticipated and related adverse events.
  Examples loss of lap top, break-ins to data and
  servers.
• In the unlikely event of a serious adverse event
  or breach in confidentiality, the event will be
  reported to the HIC within 48 hours of it
  becoming known to the PI.
• The PI will periodically review the collection,
  storage and distribution practices associated
  with this data bank and determine whether changes
  to enhance confidentiality and privacy are
  required.

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• Specific concern is the collection of
  data/biologic
• samples and the secondary uses of the
• information/materials by
• Colleagues at the same or other
  institutions/hospitals, that collect the
  data/tissues through clinical interventions.
• Researchers who collect the data/tissues as part
  of a primary study and who wish to conduct, or
  wish to share the info with colleagues who wish
  to conduct, secondary research eventually.
• Commercial or other research sponsors to which
  data/tissues have been given during the course of
  primary research.

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IRB Considerations

• What constitutes a new or different study as
  opposed to future uses that are really part of
  the primary research study?
• Therapeutic trial with a banking component.
• Is it appropriate for an IRB to approve a consent
  form for a study that is vague or broad with
  respect to possible future uses?
• __I hereby grant permission forto be used for
  future trials related to lung cancer
• __I hereby grant permission forto be used for
  future trials related to cancer and other
  diseases.
• __I hereby grant permission forto be used for
  any future research purpose.

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IRB Considerations

• Will multiple primary studies support the
  repository?
• One consent or two?
• Opt out or not?
• Protocols (Consents documents) from primary
  studies must be reapproved annually to permit the
  data to be stored and used for future research
  projects.
• HIPAA RAF limited to single purpose.

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• Specific concern is the collection of
  data/biologic
• samples and the secondary uses of the
• information/materials by
• Colleagues at the same or other
  institutions/hospitals that collect the
  data/tissues through clinical interventions.
• Researchers who collect the data/tissues as part
  of a primary study and who wish to conduct, or
  wish to share the info with colleagues who wish
  to conduct, secondary research eventually.
• Commercial or other research sponsors to which
  data/tissues have been given during the course of
  primary research.

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IRB Considerations

• Is it appropriate for the HIC to approve a
  consent form for a study that is vague or broad
  with respect to possible future uses by a
  sponsor?
• GC and HIC policies de-identified use of
  tissue/data for study on same drug or disease.
• Can researchers seek on behalf of sponsors a
  consent broader than the consent that researchers
  could legally seek for themselves?

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Commercialization of Data/Materials Who Has
Ownership and Control?

• 1996 OPRR (OHRP) Guidance
• Unacceptable (Exculpatory) Language
• By agreeing to this use, you should understand
  that you will give up all claim to personal
  benefit from commercial or other use of these
  substances.
• I voluntarily and freely donate any and all
  blood, urine, and tissue samples to the U.S.
  Government and hereby relinquish all right,
  title, and interest to said items.
• By consent to participate in this research, I
  give up any property rights I may have in bodily
  fluids or tissue samples obtained in the course
  of the research.
• Acceptable Language
• Tissue obtained from you in this research may be
  used to establish a cell line that could be
  patented and licensed. There are no plans to
  provide financial compensation to you should this
  occur.
• By consenting to participate, you authorize the
  use of your bodily fluids and tissue samples for
  the research described above.

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Ownership

• Washington University v. William Catalona
• Tissue is property of Washington University.
• Subject forfeits ownership upon donation signing
  informed consent.
• Voluntary withdrawal from the research
  repository does not equate to directing use or
  transferring ownership.

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On The Horizon

• April 16, 2006 NYT Magazine Article Taking the
  Least of You (by Rebecca Skloot)
• Proprietary rights belong to subject if cells are
  still within the subject.
• Anonymization and use of tissue and data
  violates the intent of the Belmont Report.
• Bio-ethicists may be more conservative on the
  issue than the general public.
• Sharing results back with subjects.

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Conclusion

• Collect information under a protocol approved by
  the HIC and via subject consent.
• Think broadly.
• Keep abreast of changing guidelines and policies.