Dr. Julie Lowery

1
IRB Chairs' Conference
Conducting Exempt and Expedited Reviews

• Dr. Julie Lowery
• Associate Director, VA Health Services
  ResearchAnn Arbor, MI
• and
• Dr. Joan P. Porter
• Deputy Chief OfficerOffice of Research
  OversightDepartment of Veterans Affairs
• November 15, 2006 Washington, DC

HumanSubjectProtection
LaboratoryAnimal Welfare
ORO
ResearchLaboratorySafety/Security
ResearchMisconduct
2
Agenda

• A brief review of regulator requirements in the
  Common Rule (38CFR16 for VA) for exempt and
  expedited review
• Case snippets for discussion
• Questions and your advice on where more help is
  needed

3
Exemptions 38 CFR 16.101(b)

• Unless otherwise required by department or agency
  heads, research activities in which the only
  involvement of human subjects will be in one or
  more of the following categories exempt from this
  policy.

4

• Research conducted in established or commonly
  accepted educational settings, involving normal
  educational practices such as

• Research on regular and special education
  strategies, or
• Research in the effectiveness of or comparison
  among instructional techniques, curricula, or
  classroom management methods

5

• Research involving the use of educational tests
  (cognitive, diagnostic, aptitude, achievement),
  survey procedures, interview procedures or
  observation of public behavior, unless

• Information obtained is recorded in such a manner
  that human subjects can be identified, directly
  or through identifiers linked to the subjects and
• Any disclosure of the human subjects responses
  outside the research could reasonable place the
  subjects at risk or criminal or civil liability
  or be damaging to the subjects financial
  standing, employability, or reputation

6

• (3) Research involving the use of educational
  tests (cognitive, diagnostic, aptitude,
  achievement), survey procedures, interview
  procedures, or observation of public behavior
  that is not exempt under paragraph (b)(2) or this
  section, if

• The human subjects are elected or appointed
  public officials or candidates for public office
  or
• Federal statute(s) require(s) without exception
  that the confidentiality of the personally
  identifiable information will be maintained
  throughout the research and thereafter.

7

• 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.

8

• Research and demonstration projects which are
  conducted by or subject to the approval of
  department or agency heads, and which are
  designed to study, evaluate, or otherwise
  examine

• Public benefit or service programs
• Procedures for obtaining benefits or services
  under those programs
• Possible changes in or alternatives to those
  programs or procedures or
• Possible changes in methods or levels of payment
  for benefits or services under those programs.

9

• Taste and food quality evaluation and consumer
  acceptance studies

• If wholesome foods without additives are
  consumers or
• If a food is consumed that contains a food
  ingredient at or below the level and for a use
  found to be safe, or agricultural chemical or
  environmental contaminant at or below the level
  found to be safe, by the Food and Drug
  Administration or approved by the Environmental
  Protection Agency or the Food Safety and
  Inspection Service of the U.S. Department of
  Agriculture.

10
Remember "Not human subject is not the same as
"exempt"

• In VA Investigators submit the proposed research
  and the request for exemption. The IRB Chair, or
  an IRB member designated by the Chair, must
  review all requests in a timely manner and make a
  determination based on Section 6.101, and record
  the decision. The decision must be communicated
  in writing to the investigator and the IRB
  Documentation must include the specific
  categories justifying exemption. The Research
  and Development Committee review regulations even
  though exempt.

• .102(f) Human subject means a living individual
  about when an investigator
• (whether professional or student
  conducting research obtains
• Data through intervention or interaction with
  the individual, or
• Identifiable private information . . .

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Expedited Review
38 CFR 16.110

• Expedited review procedures for certain kinds of
  research involving no more than minimal risk, and
  for minor changes in approved research

12

• (a) The Secretary, HHS, has established, and
  published as a Notice in the Federal Register, a
  list of categories of research that may be
  reviewed by the IRB through an expedited review
  procedures. The list will be amended, as
  appropriate, after consultation with other
  departments and agencies, through periodic
  republication by the Secretary, in the FEDERAL
  REGISTER. A copy of the list is available from
  the Office for Human Research Protections, HHS,
  or any successor office.

13

• An IRB may use the expedited review procedure to
  review either or both of the following
• Some or all of the research appearing on the list
  and found by the reviewer(s) to involve no more
  than minimal risk,
• Minor changes in previously approved research
  during the period (of one year or less) for which
  approval is authorized. (Note that if approved,
  the continuing review date does not change and if
  the change involves biosafety or ionizing
  radiation, the appropriate committee must be
  consulted prior to approving the change the
  consultation must be documented in the IRB file.

14
Also NoteAn IRB (or Privacy Board) may use the
expedited review process to review(3) waiver or
alteration of authorization for the use and/or
disclosure of Protected Health Information.
15
VA Procedures for Expedited Review

• The IRB Chair may carry out the review or
  delegate the review to one or more experienced
  reviewers from among IRB members.

(1) In reviewing the research, the reviewers may
exercise all of the authorities of the IRB except
that the reviewer may not disapprove the
research. A research activity may be disapproved
only after review in accordance with the
full-review procedures.
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(2) If a proposal has been initially approved
through the full review procedure, the continuing
review may not be done by the expedited review
procedure
Except
Continuing review of research previously approved
by the convened IRB as follows
(a) Research in which the enrollment of a new
subject is permanently closed all subjects have
completed all research-related interventions, and
the research remains active only for long-term
follow-up of subjects or (b) Research in which
no subject have been enrolled and no additional
risks have been identified, or (c) Research in
which the remaining research activities are
limited to data analysis.
17
In VA

• Each IRB that uses an expedited review process
  must adopt a method for keeping all members
  advised of research proposals that have been
  approved under this process.
• The minutes and/or the protocol files must
  reflect the expedited review eligibility category
  that the research meets.

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Categories of Expeditable Research
Remember (1) Research activities that present
no more than minimal risk and (2) involve only
procedures listed in one or more categories on
the expedited review lists. Remember Expedited
review procedures may not be used where
identification of the subjects and/or their
responses would reasonably place them at risk of
criminal or civil liability or be damaging to the
subjects (e.g. employability, insurability,
reputation), unless protectiions are in place to
minimize invasion of privacy and breach of
confidentiality so risks are no greater than
minimal.
19
Categories of Expeditable Research
(Paraphrased)

• Clinical studies of drugs and medical devices
  only when condition (a) or (b) is met.
• Research on drugs for which an investigational
  new drug application (21 CFR Part 312) is not
  required. (Note Research on marketed drugs
  that significantly increases the risks or
  decreases the acceptability of the risk
  associated with the use of the product is not
  eligible for expedited review.)
• Research on medical devices for which (i) an
  investigational device exemption application (21
  CFR Part 812) is not required or (ii) the
  medical device is cleared/approved for marketing
  and the medical device is being used in
  accordance with its cleared/approved labeling.

20

• Collection of blood samples by finger stick heel
  stick, ear stick, or venipuncture as follows
• From healthy, non-pregnant adults who weigh at
  least 110 pounds. For these subjects, the
  amounts drawn may not exceed 550 ml in an 8 week
  period and collection may not occur more
  frequently than two times per week or
• From other adults and children, considering the
  age, weight, and health of the subjects, the
  collection procedure, the amount of blood
  collected, and the frequency with which it will
  be collected. For these subjects the amount
  drawn may not exceed the lesser of 50 ml or 3 ml
  per kg in an 8 week period and collection may not
  occur more frequently than two times per week.

21
(3) Prospective collection of biological
specimens for each research purposes by
noninvasive means. Examples (a) hair and nail
clippings in a non-disfiguring manner (b)
deciduous teeth at time of exfoliation or if
routine patient care indicates a need for
extraction (c) permanent teeth if routine
patient care indicates a need for extraction
(d) excreta and external secretions (including
sweat) (e) uncannulated saliva collected either
in an unstimulated fashion or stimulated by
chewing gumbase or wax or by applying a dilute
citric solution to the tongue (f) placenta
removed at delivery (g) amniotic fluid obtained
at the time of rupture of the membrane prior to
or during labor (h) supra- and subgingival
dental plaque and calculus, provided the
collection procedure is not more invasive than
routine prophylactic scaling of the teeth and the
process is accomplished in accordance with
accepted prophylactic techniques (i) mucosal and
skin cells collected by buccal scraping or swab,
skin swab, or mouth washings (j) sputum
collected after saline mist nebulization.
22

• Collection of data through noninvasive procedures
  (not involving general anesthesia or sedation)
  routinely employed in clinical practice,
  excluding procedures involving x-rays or
  microwaves. Where medical devices are employed,
  they must be cleared/approved for marketing.
  (Studies intended to evaluate the safety and
  effectiveness of the medical device are not
  generally eligible for expedited review,
  including studies of cleared medical devices for
  new indications.)

23

• Research involving materials (data, documents,
  records, or specimens) that have been collected,
  or will be collected solely for non-research
  purposes (such as medical treatment or
  diagnosis).

24

• Collection of data from voice, video, digital, or
  image recordings made for research purposes.

25

• Research on individual or group characteristics
  or behavior (including, but not limited to,
  research on perception, cognition, motivation,
  identity, language, communication, cultural
  beliefs or practices, and social behavior) or
  research employing survey, interview, oral
  history, focus group, program evaluation, human
  factors evaluation, or quality assurance
  methodologies. (NOTE Some research in this
  category may be exempt from the HHS regulations
  for the protection of human subjects, 45 CFR
  46.101 (b)(2) and (b)(3). This listing refers
  only to research that is not exempt.)

26

• Continuing review of research previously approved
  by the convened IRB as follows
• Where (i) the research is permanently closed to
  the enrollment of new subjects (ii) all subjects
  have completed all research-related
  interventions and (iii) the research remains
  actively only for long-term follow-up of
  subjects or
• Where no subjects have been enrolled and no
  additional risks have been identified or
• Where the remaining research activities are
  limited to data analysis.

27

• Continuing review of research, not conducted
  under an investigational new drug application or
  investigational device exemption where categories
  (2) through (8) do not apply but the IRB has
  determined and documented at a convened meeting
  that the research involves no greater than
  minimal risk and no additional risks have been
  identified.

28
Useful Websites
OPRR Guidance on .101 (6)(5)Exemption for
Research and Demonstration on Public Benefit and
Service Program http//www.hhs.gov/ohrp/humansubje
cts/guidance/exmpt-pb.htm Office of Human
Research Protections (OHRP)Guidance on the Use
of Expedited Review Procedures http//www.hhs.gov/
ohrp/humansubjects/guidance/exprev.htm
Categories of Research that May be Reviewed by
the Institutional Review Board (IRB) through
Expedited Review Procedures http//www.hhs.gov/ohr
p/humansubjects/guidance/expedited98.htm
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Case Studies
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Case Study 1

• Investigator Chew is a dentist working as a WOC.
  He would like to collect photographs, dental
  plaque, and saliva from all his patients to see
  if there are characteristics of dental decay and
  ulcerations that can help predict HIV infection.
  He will
• Test the saliva and plaque for the presence of
  HIV.
• Obtain informed consent from his subjects.
• Keep the results of his findings in a locked
  cabinet in his office at the university.
• He must have his proposal reviewed by the IRB and
  the RD committee within 2 weeks to meet the
  deadline for funding. He requests that the IRB
  Chair expedite the project since he will be
  merely collecting dental plaque by routine
  methods that he would be doing anyway and he will
  collect sputum after saline mist nebulization.

31
Case Study 1 Continued

• Is Dr. Chews study Expeditable? Why or why not?
• If not, can the IRB and RD committee approve it
  tentatively by expedited means so that he can get
  the funding that would otherwise be swept?

32
Case Study 2

• Dr. Curio is going to look at medical records in
  the VA to determine if veterans with psoriasis
  have a high rate of diabetes and he wants to
  check records from May 2004 to May 2007. He
  will
• Be using the medical records at three sites in
  his VISN to see if there is any correlation
• Contact each of the medical centers, rather than
  using a VISN or central data base
• Not be recording nay names when he looks at the
  records from each site.

33
Case Study 2 Continued

• At his VA facility, the IRB chair says that the
  project is exempts, and because he is not
  recording any information by name or other
  identifiers, the IRB need not review the project
• The IRB in the second facility indicates that the
  project is not exempt, but that it could be
  expedited, but informed consent must be obtained
  to do an expedited project that has prospective
  data.
• The third IRB indicated that the project could be
  expedited and that informed consent can be waived
  by the RIB consultant who is doing the expedited
  review.
• Who is right?

34
Case Study 2 Continued

• Answer. All three responses have regulatory
  issues.
• For IRB 1 The project is not exempt. Some of
  the data will be collected prospectively.
• For IRB 2 Waiver of consent can be given if
  appropriately justified in accordance with
  Section .116 of the regulations.
• For IRB 3 The reviewer must be the Chair or a
  member or members of the IRB appointed by the
  Chair. A non-IRB member cannot do the expedited
  review.

35
Case Study 3- Analysis of Patient Data from
Secondary Sources

• This study includes analysis of patient data from
  existing VA databases (originally established for
  patient care and administrative purposes- not
  research) to compare statistical models of risk
  adjustment and mortality prediction. There is no
  direct patient contact, and scrambled patient
  identifiers are used to link data from various
  sources.
• Data are collected on 5,000 VA patients with ICU
  admissions. Subjects are to be identified from
  VA databases using diagnostic criteria.

36
Case Study 3 Continued

• Data collection
• Patient data to be collected include demographic
  information, date of birth, zip code, gender,
  ethnicity, ICU admissions, diagnoses, lab
  results, inpatient treatment information,
  mortality data, and other outcomes.
• These data are collected via database search
  (e.g., Austin data, Pharmacy Benefits Management
  data, DSS data) and will be used to test and
  compare risk adjustment methods.

37
Case Study 3 Continued

• Data Confidentiality
• The patient cohort will be obtained from existing
  VA databases using diagnostic criteria.
• Some of the databases contain real SSNs, others
  contain scrambled SSNs.
• After the study data, including SSNs and
  scrambled SSNs are pulled, all real SSNs will be
  converted to scrambled SSNs, using a file linking
  scrambled SSNs with the real SSNs obtained from a
  separate Austin database. Thus, as study files
  with patient data will include only scrambled
  SSNs.
• The file linking scrambled SSNs with real SSNs
  will be maintained by the research team as a
  separate file, in a password protected drive that
  is separate from the drive containing the study
  data.

38
Case Study 3 Continued

• What type of review should this application
  receive and why?

39
Case Study 3 Continued

• Chart 2 Is the research involving human
  subjects eligible for exemption under 45 CFR
  46.101(b)?
• Will the only involvement of human subjects be in
  one or more of the following research categories?
• Research conducted in established or commonly
  accepted educational settings, involving
  education practices?
• Research involving the use of educational tests,
  survey procedures, interview procedures, or
  observation of public behavior?
• Research involving the collection of existing
  data, documents, records, or pathological or
  diagnostic specimens?
• Research studying, evaluating, or examining
  public benefits or service programs?
• Research involving taste and food quality
  evaluation or consumer acceptance studies?

40
Case Study 3 Continued

• YES Research involving collection or study of
  existing data, documents, records, or
  pathological or diagnostic specimens.
• Exemption 45 CFR 46.101(b) may apply. Go to
  Chart 5.

41
Case Study 3 Continued

• Are these sources publicly available? (No.)
• Will information be recorded by the investigator
  in such a manner that the subjects cannot be
  identified, directly or through identifiers
  linked to the subjects?
• If no, research is not exempt. Go to Chart 8.

42
Case Study 3 Continued

• Has the research been previously reviewed and
  approved by the IRB? (No.)
• Does the research present no more than minimal
  risk to the human subjects? AND
• Does the research involve only procedure
  indicated in categories 1-7 on the list of
  categories that may be reviewed though an
  expedited review procedure? 45 CFR 46 110 (b)(1)

43
Case Study 3 Continued

• YES (category 5) Research involving materials
  (data, documents, records, or specimens) that
  have been collected, or will be collected, solely
  for non-research purposes (such as medical
  treatment or diagnosis).
• Is this research classified? (No.)
• Research is eligible for IRB review through
  expedited procedures. 45 CFR 46.110(d)

44
Case Study 3- Modification A

• Data Confidentiality
• Data obtained from these databases will include
  scrambles SSNs, which are needed to link patients
  across time and across multiple databases. The
  scrambled SSN for a given VA patient is the same
  across all Austin databases so, the scrambled
  identifier can be used to link data for a given
  patient across databases.
• All study files with patient data will include
  only scrambled SSNs. The file linking scrambled
  SSNs with real SSNs is in a database maintained
  in Austin.

45
Case Study 3- Modification B

• Data Confidentiality
• The SSNS of eligible patients are obtained are
  used to identify the patients electronic medical
  records, from which relevant clinical data for
  the study are obtained.
• These clinical data are entered into the study
  database, which doesn't contain any SSNs or
  linkages to patient identifiers.
• A file containing the list of SSNs of eligible
  patients- but no linkages and no other data- is
  temporarily maintained until all of the medical
  record data are obtained.

46
Case Study 4Observational Study Using Patient
Interviews and Questionnaires

• This study examines health related quality of
  life (QOL) for individuals in the VA health care
  system with a specific, non-sensitive chronic
  illness. Investigator propose to administer two
  QOL measures to patients at baseline and a
  follow-up structured interview every month for a
  1-year study period. They will use written
  informed consent, which will include a HIPAA
  authorization form.
• The subjects are 500 patients at 8 VAMCs. They
  are identified via VA databases and initially
  contracted and invited by letter to participate
  in the project. Interested patients are
  scheduled to meet with project staff at an
  upcoming clinic appointment to go over
  requirements for participation and sign the
  consent form.

47
Case Study 4 Continued

• Data Collection and Confidentiality
• Baseline interviews are conducted in person at a
  regularly scheduled clinic appointment, and
  follow-up interviews are conducted over the
  telephone.
• Data collected from patients include
  demographics/SES, general health information, and
  QOL data.
• Data are confidential but not anonymous- linkages
  are maintained in a crosswalk file to facilitate
  the monthly follow-up.
• The crosswalk file linking patient identifying
  data to study identification numbers will be
  maintained as a separate file, in a
  password-protected drive that is separate from
  the drive containing study data.
• No study data will be maintained with the patient
  identifying data.

48
Case Study 4 Continued

• What type of review should this application
  receive and why?

49
Case Study 4 Continued

• Chart 2 Is the research involving human
  subjects eligible for exemption under 45 CFR
  46.101(b)?
• Will the only involvement of human subjects be in
  one or more of the following research categories?
• Research conducted in established or commonly
  accepted educational settings, involving
  education practices?
• Research involving the use of educational tests,
  survey procedures, interview procedures, or
  observation of public behavior?
• Research involving the collection of existing
  data, documents, records, or pathological or
  diagnostic specimens?
• Research studying, evaluating, or examining
  public benefits or service programs?
• Research involving taste and food quality
  evaluation or consumer acceptance studies?

50
Case Study 4 Continued

• YES Research involving the use of educational
  tests, survey procedures, interview procedures,
  or observation of public behavior.
• Exemption 45 CFR 46.101(b)(2) or (b)(3) may
  apply. Go to chart 4.

51
Case Study 4 Continued

• Is the information recorded in such a manner that
  human subjects can be identified, directly or
  through identifiers linked to the subjects AND
• Could any disclosures of the human subjects
  responses outside the research reasonably place
  the subjects at risk of criminal or civil
  liability or be damaging to the subjects
  financial standing, employability or reputation?
• If yes, research is not exempt. Go to Chart 8.

52
Case Study 4 Continued

• Has the research been previously reviewed and
  approved by the IRB? (No.)
• Does the research present no more than minimal
  risk to human subjects? AND
• Does the research involve only procedure included
  in categories 1-7 on the list of categories that
  may be reviewed through an expedited review
  procedures? 45 CFR 46 110(b)(1)

53
Case Study 4 Continued

• YES (Category 7) Research on individual or
  group characteristics (including but not limited
  to, research on perception, cognition,
  motivation, identity, language, communication,
  cultural beliefs or practices, and social
  behavior) or research employing survey,
  interview, oral history, focus group, program
  evaluation, human factors evaluation, or quality
  assurance methodologies.
• Is this research classified? (No.)
• Research is eligible for IRB review through
  expedited procedures. 45 CFR 46 110(d)

54
Case Study 5Observational Study Using Provider
Interviews and Questionnaires

• This study will use provider interviews and
  written surveys to assess how a new clinical
  reminder system is working at 8 VAMCs. (This
  study is an investigator initiated research
  project, not a quality improvement project
  initiated by medical center management.)
• The subjects are 70 VA primary care physicians at
  8 VAMCs.

55
Case Study 5 Continued

• Data Collection and Confidentiality
• Data collected will include perceptions of
  barriers and facilitators to implementation of
  the system, provider self-efficacy, satisfaction
  with the system, and data about organizational
  structure.
• Data are confidential, but are not anonymous,
  since providers are interviewed in person and
  data from interviews and surveys must be linked.
• The crosswalk file linking provider identifying
  data to study identification numbers will be
  maintained as a separate file, in a
  password-protected drive that is separate from
  the drive containing the study data.
• No study data will be maintained with the
  provider identifying data.

56
Case Study 5 Continued

• What type of review should this application
  receive and why?

57
Case Study 5 Continued

• Chart 2 Is the research involving human
  subjects eligible for exemption under 45 CFR
  46.101(b)?
• Will the only involvement of human subjects be in
  one or more of the following research categories?
• Research conducted in established or commonly
  accepted educational settings, involving
  education practices?
• Research involving the use of educational tests,
  survey procedures, interview procedures, or
  observation of public behavior?
• Research involving the collection of existing
  data, documents, records, or pathological or
  diagnostic specimens?
• Research studying, evaluating, or examining
  public benefits or service programs?
• Research involving taste and food quality
  evaluation or consumer acceptance studies?

58
Case Study 5 Continued

• YES Research involving the use of educational
  tests, survey procedures, interview procedures,
  or observation of public behavior.
• Exemption 45 CFR 46.101(b)(2) or (b)(3) may
  apply. Go to chart 4.

59
Case Study 5 Continued

• Is the information recorded in such a manner that
  human subjects can be identified, directly or
  though identifiers linked to the subjects AND
• Could any disclosure of the human subjects
  responses outside the research reasonably place
  the subjects at risk of criminal or civil
  liability or be damaging to the subjects
  financial standing, employability, or reputation?
• If yes, research is not exempt. Go to Chart 8.

60
Case Study 5 Continued

• Has the research been previously reviewed and
  approved by the IRB? (No.)
• Does the research present no more than minimal
  risk to human subjects? AND
• Does the research involve only procedure included
  in categories 1-7 on the list of categories that
  may be reviewed though an expedited review
  procedure? 45 CFR 46 110(b)(1)

61
Case Study 5 Continued

• YES (Category 7) Research on individual or
  group characteristics (including but not limited
  to, research on perception, cognition,
  motivation, identity, language, communication,
  cultural beliefs or practices, and social
  behavior) or research employing survey,
  interview, oral history, focus group, program
  evaluation, human factors evaluation, or quality
  assurance methodologies.
• Is this research classified? (No.)
• Research is eligible for IRB review through
  expedite procedures. 45 CFR 46 110(d)

62
Case Study 5 Modification

• Data Collection
• Data collected will include information on how
  providers were education in the use of the
  system, and data about organizational structure.
• The providers will not be asked about their
  satisfaction with the system or their opinions on
  how the system could be improved.

63
Case Study 5 Continued

• What type of review should this application
  receive and why?

64
Case Study 5 Continued

• Chart 1 Is an activity research involving human
  subjects covered by 45 CFR Part 46?
• Is the study a systematic investigation designed
  to develop or contribute to generalizable
  knowledge? (Yes.)
• Activity is research. Does the research involve
  obtaining information about living individuals?
• If no, the research is not research involving
  human subjects.

65
Veterans Health Administration Ann Arbor HSRD
www.va.gov/annarbor-hsrd/irb/subjectsreview.htm
Guidelines for Human Subjects Review of Health
Service Research Studies
66
Contact Information
Dr. Julie LoweryAssociate Director VA Health
Services Research Phone [phone] (ext.
6222)Julie.Lowery_at_va.gov Dr. Joan P.
PorterDeputy Chief OfficerOffice of Research
Oversight (10R)Phone [phone]Joan.Porter
_at_va.gov
And, of course, COACH