ETHICAL AND REGULATORY ASPECTS OF USE OF TISSUE SAMPLES FOR RESEARCH

1
ETHICAL AND REGULATORY ASPECTS OF USE OF TISSUE
SAMPLES FOR RESEARCH

• VA RESEARCH DAY
• SAN DIEGO, CALIFORNIA
• OCTOBER 28, 2004
• Rina Hakimian
• DHHS Office for Human Research Protections
• Phone[phone]
• Fax [phone]
• Email rhakimian_at_osophs.dhhs.gov

1
2
REGULATORY/LEGAL FRAMEWORK FOR RESEARCH

• Federal regulations
• Human subject protections (Common Rule and FDA)
• Health Information privacy (HIPAA)
• State laws
• International guidelines
• Guidance OHRP, NBAC

2
3
FEDERAL REGULATIONS/COMMON RULE

• Basic DHHS Policy for Protection of Human
  Research Subjects (First adopted 1974, revised
  1991)
• Federal Policy for the Protection of Human
  Subjects
• Subpart A The Common Rule (1991)
• Additional protections for vulnerable populations
  in Subparts B-D
• Applies to human subjects research funded by any
  of 17 federal agencies

3
4
APPLICABILITY OF REGULATIONS

• Research involving human subjects conducted or
  supported by HHS that is not otherwise exempt
• Non-exempt human subjects research conducted at
  an institution holding an applicable Assurance of
  Compliance

4
5
APPLICABILITY OF THE HHS REGULATIONS
Research 45 CFR 46.102(d)? Human subjects 45
CFR 46.102(f)? Exempt 45 CFR 46.101(b)?
17
6
FEDERAL REGULATIONS COMMON RULEWHATS COVERED
BY 45 CFR 46?

• DEFINITION OF RESEARCH
• A systematic investigation, including research
  development, testing and evaluation, designed to
  develop or contribute to generalizable knowledge.
  45 CFR 46.102(d)

5
7
FEDERAL REGULATIONS COMMON RULEWHATS COVERED
BY 45 CFR 46?

• DEFINITION OF HUMAN SUBJECT
• A living individual about whom an investigator
  obtains either data through intervention or
  interaction with the individual or
• Identifiable private information
• 45 CFR 46.102(f)

6
8
FEDERAL REGULATIONS COMMON RULEWHATS EXEMPT 45
CFR 46?

• WHATS EXEMPT?
• Exemption 45 CFR 46.101 (b) 4
• Research involving the collection or study of
  existing data, documents, records, pathological
  specimens, or diagnostic specimens, if these
  sources are publicly available or if the
  information is recorded by the investigator in
  such a manner that subjects cannot be identified,
  directly or through identifiers linked to the
  subjects.

9
WHATS MEANT BY EXISTING?

• Specimens and data are existing at the time the
  research is proposed to an institutional official
  for a determination of whether the research is
  exempt
• Since research repositories and databases often
  continually accrue new specimens/data, Exemption
  4 may not apply

19
10
WHATS MEANT BY PUBLICLY AVAILABLE?

• Available without restrictions or conditions
• Since research repositories and databases often
  impose restrictions or conditions on access,
  Exemption 4 may not apply

20
11
WHATS MEANT BY RECORDED BY THE INVESTIGATOR IN
SUCH A MANNER THAT SUBJECTS CANNOT BE IDENTIFIED
DIRECTLY OR THROUGH IDENTIFIERS

• Information recorded is not directly or
  indirectly identifiable
• Information cannot be coded
• Even if all specimens and data to be obtained are
  existing at the time the research is proposed,
  researchers often need individually identifiable
  or coded information thus Exemption 4 may not
  apply

21
12
HOWEVERMOST RESEARCH THAT INVOLVES OBTAINING
SPECIMENS OR INFORMATION FROM REPOSITORIES CAN
PROBABLY BE CONDUCTED WITHOUT OBTAINING
IDENTIFIABLE INFORMATION, AND THUS WOULD NOT
BE HUMAN SUBJECTS RESEARCH UNDER 45 CFR PART 46
22
13
RESEARCH REPOSITORIES DATABASES 3 PATHS TO
HUMAN SUBJECTS RESEARCH

• Creating a research repository/database through
  intervention or interaction with individual
• Creating a research repository/database by
  obtaining identifiable private information
• Obtaining identifiable private information from a
  research repository/database.

24
14
OHRP GUIDANCE COMPONENTS OF REPOSITORIES

• Repository activities involve three components
• the collectors of tissue samples
• the repository storage and data management
  center and
• the recipient investigators.
• Each component must satisfy certain requirements

25
15
OHRP REPOSITORY GUIDANCE (1997)
Tissue collector
Recipient Investigator
Repository Storage And Data Management Center
Tissue collector
Recipient Investigator
Tissue collector
Recipient Investigator
IRB Review Informed Consent Submittal
Agreement Assurance of Compliance
IRB Review Sample Informed Consent Certificate
of Confidentiality Assurance of Compliance
Recipient Agreement Local Policies
26
16
FEDERAL REGULATIONS COMMON RULE WHEN IS
RESEARCH USING CODED DATA IS NOT HUMAN SUBJECTS
RESEARCH?

• OHRP GUIDANCE ON RESEARCH INVOLVING CODED PRIVATE
  INFORMATION OR BIOLOGICAL SPECIMENS (2004)

7
17
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.
• 45 CFR 46.102(f)

8
18
IDENTIFIABLE PRIVATE INFORMATION

• Private information must be individually
  identifiable in order for obtaining the
  information to constitute research involving
  human subjects. 45 CFR 46.102(f)

9
19
IDENTIFIABLE PRIVATE INFORMATION

• Individually identifiable The identity of the
  subject is or may readily be ascertained by the
  investigator or associated with the information.
• 45 CFR 46.102(f)

10
20
RESEARCH USING CODED DATA/BIOLOGIC SAMPLES

• Private information or samples that retain a link
  to individually identifying information is
  ordinarily considered by OHRP to be individually
  identifiable to the investigator.
• But, there are exceptions

11
21
EXAMPLES OF WHEN CODED DATA/BIOLOGIC SAMPLES ARE
NOT INDIVIDUALLY IDENTIFIABLE TO INVESTIGATORS

• The key to the code is destroyed
• The investigator and the holder of the
  individually identifying information sign an
  agreement prohibiting the release of individually
  identifying information to the investigator under
  any circumstances, until the individuals are
  deceased

12
22
EXAMPLES OF WHEN CODED DATA/BIOLOGIC SAMPLES ARE
NOT INDIVIDUALLY IDENTIFIABLE TO INVESTIGATORS

• There are IRB-approved written policies and
  operating procedures for a repository or data
  management center that prohibit the release of
  individual identifiers to the investigator under
  any circumstances, until the individuals are
  deceased or
• There are other legal requirements prohibiting
  the release of the link to the investigator,
  until the individuals are deceased.

13
23
IN THESE EXAMPLES, THE RESEARCH DOES NOT INVOLVE
HUMAN SUBJECTS BECAUSE INVESTIGATORS CANNOT
READILY ASCERTAIN THE IDENTITY OF THE INDIVIDUALS.
14
24
OHRP GUIDANCEUSAGE AGREEMENTS

• Recipient-investigators should not be provided
  access to the identities of donors or to
  information through which the identities of
  donors may readily be ascertained thus not
  conducting human subjects research (HSR).
• If recipient-investigators receive identifiable,
  private information they are engaged in HSR and
  need to obtain an Assurance of Compliance and IRB
  review of the proposed research.

15
25
TWO CAVEATS ABOUT THE EXAMPLES

• Person(s) doing coding of data/samples and
  person(s) holding codes are not part of research
  team.
• Samples/data not being obtained for the specific
  research in question by an interaction or
  intervention with living individuals.

16
26
INFORMED CONSENT

• IF
• Samples collected for research purposes OR
• Samples are associated with information that
  allows investigators to readily identify the
  donor,

• THEN informed consent must be obtained
• unless appropriately waived by the IRB.

27
27
INFORMED CONSENT

• A clear description of
• Operation of the specimen repository.
• Specific types of research to be conducted.
• Procedures for protecting the privacy of subjects
  and maintaining the confidentiality of data.

28
28
INFORMED CONSENT

• Possible consequences of genetic testing (e.g.,
  insurance risks, misattributed paternity), when
  appropriate.
• Future withdrawal of the samples from the study
  (i.e., state whether subjects may, in the future,
  request that their samples be destroyed or that
  all personal identifiers be removed from
  samples).

29
29
INFORMED CONSENT

• Length of time that samples will be stored. If
  storage time is indefinite, so state.
• Subjects' access to information learned from the
  research, if they so choose.

30
30
INFORMED CONSENT

• Conditions under which data/specimens will be
  released to recipient-investigators e.g.
• No secondary use.
• Subjects have option to allow secondary use.
• Only release samples stripped of all identifiers.
• Only release of coded samples.
• Subjects to be contacted for additional consent
  for secondary use.

31
31
FEDERAL REGULATIONSHUMAN SUBJECTS RESEARCH

• WAIVER OR ALTERATION OF INFORMED CONSENT
• Minimal risk to subjects
• No adverse effect on subjects rights and welfare
• Research could not practicably be carried out
  otherwise
• Whenever appropriate, subjects provided
  additional pertinent information following
  participation

32
32
OHRP PLANS TO ISSUE FURTHER GUIDANCE ON

• Research repositories and databases
• Exemptions under 45 CFR 46.101(b)

33