IRB: Overview of Function and Process

1
IRB Overview of Function and Process
Benjamin Kennedy, MAIRB Administrator Septem
ber 6, 2006
2
Institutional Review BoardHuman Research
Protection Program Department of University
Safety Assurances
3
OBJECTIVES

• Background Overview
• History of Research Ethics
• What is the Institutional Review Board (IRB)?
• Federalwide Assurance (FWA)
• Research and Other Definitions
• Types of IRB Review
• Informed Consent
• IRB Process

4
OBJECTIVES

• Background Overview
• History of Research Ethics
• What is the Institutional Review Board (IRB)?
• Federalwide Assurance (FWA)
• Research and Other Definitions
• Types of IRB Review
• Informed Consent
• IRB Process

5
Background Overview History of Research Ethics

• Research in Nazi Germany
• Dr. Josef Mengele, the Angel of Death
• Experimenting on eye color children were
  injected with blue dye directly into the eyeball
• Nuremberg Code (1949)
• Cornerstone of modern regulations
• Tuskegee Syphilis Study (1932-1973)
• 400 African-American men in Alabama with syphilis
  were enticed into the study with offers of free
  medical treatment to study Bad Blood. No
  treatments were ever given and penicillin was
  withheld from the subjects after it was found to
  be a safe and effective treatment.
• Willowbrook Studies (1956-1972)
• Physicians in New York infected 800 mentally
  incompetent children with the hepatitis virus.
  Entry into Willowbrook State School was based on
  parents consenting to the hepatitis research.

6
Background Overview History of Research Ethics

• Milgrams Obedience Experiment (early 1960s)
• The subjects (teachers) were persuaded to
  administer high voltage electrical shocks to
  learners. The subjects suffered extreme
  psychological distress.
• Tearoom Trade Study (mid 1960s)
• PhD student wanted to study the sexual habits of
  men in public washrooms. After tracing down the
  subjects by their license plates, he attempted
  to interview them at their home.

7
Background Overview History of Research Ethics

• Belmont Report (1979)
• National Commission for the Protection of Human
  Subjects of Biomedical and Behavioral Research
  was formed and was charged to identify the basic
  ethical principles governing the conduct of
  biomedical and behavioral research involving
  human subjects.
• Three Basic Principles
• Respect for Persons Treating subjects with
  dignity and autonomy while affording those with
  diminished autonomy with additional protections.
  It underlies the importance of informed consent.
• Beneficence An obligation to not harm subjects
  to maximize benefits and minimize possible harms.
• Justice Fairness in the selection of research
  subjects fairness in the distribution of
  benefits and risks.

8
OBJECTIVES

• Background Overview
• History of Research Ethics
• What is the Institutional Review Board (IRB)?
• Federalwide Assurance (FWA)
• Research and Other Definitions
• Types of IRB Review
• Informed Consent
• IRB Process

9
Background Overview What is the IRB?

• Code of Federal Regulations
• Basis of the IRBs function
• Department of Health and Human Services
• Office of Human Research Protections
• Title 45 Public Welfare, Part 46, Protection of
  Human Subjects
• Food and Drug Administration (FDA)
• 21 CFR 50, Protection of Human Subjects
• 21 CFR 56, Institutional Review Boards
• Etc.

10
Background Overview What is the IRB?

• Federal regulations and UW-Milwaukee policy
  requires research involving human subjects to be
  reviewed and approved by the Institutional Review
  Board (IRB).
• An IRB is the group or committee that is given
  the responsibility by an institution to review
  that institution's research projects involving
  human subjects. The primary purpose of the IRB
  review is to assure the protection of the safety,
  rights and welfare of the human subjects.
• UWMs IRB
• IRB Committee consists of UWM faculty, staff,
  consultants, and non-affiliated community
  members.
• Chairperson
• Voting members
• IRB Administrators
• Benjamin Kennedy
• Institutional Official (John Krezoski, PhD)

11
OBJECTIVES

• Background Overview
• History of Research Ethics
• What is the Institutional Review Board (IRB)?
• Federalwide Assurance (FWA)
• Research and Other Definitions
• Types of IRB Review
• Informed Consent
• IRB Process

12
Federalwide Assurance (FWA)

• Federalwide Assurance (FWA)
• An FWA is a document that designates the IRB that
  will review and oversee the research. It also
  specifies the ethical principles under which the
  research will be conducted and names the
  individuals who will be responsible for the
  proper conduct of the research. UWM has its own
  FWA (FWA00006171) for research conducted at UWM.
  Under the FWA, the IRB is also charged with the
  responsibility for assuring that all human
  subject research conducted under the auspices of
  UWM (e.g., investigators and facilities) is
  conducted in compliance with federal law.

13
OBJECTIVES

• Background Overview
• History of Research Ethics
• What is the Institutional Review Board (IRB)?
• Federalwide Assurance (FWA)
• Research and Other Definitions
• Types of IRB Review
• Informed Consent
• IRB Process

14
Research and Other Definitions

• How does the IRB define research?
• DHHS, 45 CFR 46.102
• Research a systematic investigation, including
  research development, testing and evaluation,
  designed to develop or contribute to
  generalizable knowledge
• 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

15
Research and Other Definitions

• Principal Investigator (PI) The scientist or
  scholar who holds primary responsibility for the
  design and conduct of a research study.
• Minimal Risk The probability and magnitude of
  harm or discomfort anticipated in the research
  are not greater in and of themselves than those
  ordinarily encountered in daily life or during
  the performance of routine physical or
  psychological examinations or tests. (45 CFR
  56.102(i)).
• Private Information Information that is
  individually identifiable. Private information
  must be individually identifiable (i.e., the
  identity of the subject is or may readily be
  ascertained by the investigator or associated
  with the information) in order for obtaining the
  information to constitute research involving
  human subjects.

16
OBJECTIVES

• Background Overview
• History of Research Ethics
• What is the Institutional Review Board (IRB)?
• Federalwide Assurance (FWA)
• Research and Other Definitions
• Types of IRB Review
• Informed Consent
• IRB Process

17
Types of IRB Review

• The IRB is involved in the following stages of a
  research study
• Initial Review Before a research study can
  begin, it must be submitted to the IRB for review
  and approval.
• Continuing Review Once a study receives IRB
  approval, federal regulations require an annual
  review of research studies no less than once per
  year.
• Modifications/Amendments - Once a study receives
  IRB approval, any changes to the research study
  must be approved by the IRB before
  implementation.
• Adverse Events - Any occurrences that may present
  itself during the conduct of a research study
  that ultimately harms the subject.

18
Types of IRB Review

• The IRB uses three (3) types of review when
  evaluating a study.
• Exempt
• Expedited
• Full Board
• Even though the Principal Investigator identifies
  the type of review when s/he completes the
  submission, the IRB makes the final
  determination.

19
Types of IRB Review

• Exempt Under federal regulations, certain types
  of research may be exempt from Full Board IRB
  review if the study involves no more than
  minimal risk and falls into one or more of six
  categories.
• Six Categories
• EXEMPTION 1Research conducted in established
  or commonly accepted educational settings,
  involving normal educational practices, such as
  (i) research on regular and special education
  instructional strategies, or (ii) research on the
  effectiveness of or the comparison among
  instructional techniques, curricula, or classroom
  management methods.
• EXEMPTION 2Research involving the use of
  educational tests (cognitive, diagnostic,
  aptitude, achievement), survey procedures,
  interview procedures or observation of public
  behavior, unless (i) information obtained is
  recorded in such a manner that human subjects can
  be identified, directly or through identifiers
  linked to the subjects and (ii) any disclosure
  of the human subjects' responses outside the
  research that could reasonably place the subjects
  at risk of criminal or civil liability or be
  damaging to the subjects' financial standing,
  employability, or reputation.

20
Types of IRB Review

• Exempt categories continued
• EXEMPTION 3Research 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) of this section, if (i) the human
  subjects are elected or appointed public
  officials or candidates for public office or (ii)
  Federal statute(s) require(s) without exception
  that the confidentiality of the personally
  identifiable information will be maintained
  throughout the research and thereafter.
• EXEMPTION 4Research 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.
• EXEMPTION 5Research 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 (i) Public benefit or service programs
  (ii) procedures for obtaining benefits or
  services under those programs (iii) possible
  changes in or alternatives to those programs or
  procedures or (iv) possible changes in methods
  or levels of payment for benefits or services
  under those programs.
• EXEMPTION 6Taste and food quality evaluation
  and consumer acceptance studies, (i) if wholesome
  foods without additives are consumed or (ii) 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.

21
Types of IRB Review

• At UWM, a project that is exempt
• Is not subject to the submission deadlines for
  Board meetings
• Does not require full review by a Full Board
• Does not need to be reviewed annually
• General characteristics of all exempt research
  include the following
• With very few exceptions, private identifiable
  information cannot be recorded by the
  investigator or members of the research team.
• Exemptions do not apply to research involving
• Prisoners
• Fetuses
• Pregnant Women
• Human In Vitro Fertilization

22
Types of IRB Review

• Expedited Under federal regulations, certain
  types of research may be reviewed in an expedited
  manner if the study involves no more than
  minimal risk and falls into one or more of nine
  categories.
• Nine Categories
• CATEGORY 1Clinical studies of drugs and
  medical devices only when condition (a) or (b) is
  met. (a) 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 risks
  associated with the use of the product is not
  eligible for expedited review.) (b) 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.
• CATEGORY 2Collection of blood samples by
  finger stick, heel stick, ear stick, or
  venipuncture as follows (a) from healthy,
  nonpregnant 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 2 times per
  week or (b) from other adults and children2,
  considering the age, weight, and health of the
  subjects, the collection procedure, the amount of
  blood to be 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 2
  times per week.

23
Types of IRB Review

• Expedited categories continued
• CATEGORY 3Prospective collection of biological
  specimens for research purposes by noninvasive
  means. Examples (a) hair and nail clippings in a
  nondisfiguring 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.
• CATEGORY 4Collection 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.)

24
Types of IRB Review

• Expedited categories continued
• CATEGORY 5Research involving materials (data,
  documents, records, or specimens) that have been
  collected, or will be collected solely for
  nonresearch purposes (such as medical treatment
  or diagnosis). (NOTE Some research in this
  category may be exempt from the HHS regulations
  for the protection of human subjects. 45 CFR
  46.101(b)(4). This listing refers only to
  research that is not exempt.)
• CATEGORY 6Collection of data from voice,
  video, digital, or image recordings made for
  research purposes.
• CATEGORY 7Research 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.)

25
Types of IRB Review

• Nine Categories continued
• CATEGORY 8 (Continuing Review Only)Continuing
  review of research previously approved by the
  convened IRB as follows (a) 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 active only for long-term
  follow-up of subjects or (b) where no subjects
  have been enrolled and no additional risks have
  been identified or (c) where the remaining
  research activities are limited to data analysis.
• CATEGORY 9 (Continuing Review Only)Continuing
  review of research, not conducted under an
  investigational new drug application or
  investigational device exemption where categories
  two (2) through eight (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.

26
Types of IRB Review

• At UWM, a project that is expedited
• Is not subject to the submission deadlines for
  Board meetings.
• Does not require full review by a Full Board.
• Needs to be reviewed annually under 45 CFR 46.109
  (e).
• Categories one (1) through seven (7) pertain to
  both initial and continuing IRB review.
  Categories eight (8) and nine (9) pertain to
  continuing IRB review only.
• Standard requirements for informed consent (or
  its waiver, alteration, or exception) apply.
• Expedited Review does not apply to research
  involving
• 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 financial standing, employability,
  insurability, reputation, or be stigmatizing,
  unless reasonable and appropriate protections
  will be implemented so that risks related to
  invasion of privacy and breach of confidentiality
  are no greater than minimal.
• Classified research involving human subjects.

27
Types of IRB Review

• Full Board According to 45 CFR 46.110(b), full
  board review is required of all research studies
  that are neither exempt, nor subject to expedited
  review.
• IRB Committee must review and vote at a fully
  convened meeting.
• Meeting held once a month
• Is subject to the submission deadlines for Board
  meetings.
• Studies with greater than minimal risk
• Special/ Vulnerable Populations
• Deception/ Non disclosure of information to
  subjects
• Needs to be reviewed annually under 45 CFR 46.109
  (e).
• Standard requirements for informed consent (or
  its waiver, alteration, or exception) apply.

28
OBJECTIVES

• Background Overview
• History of Research Ethics
• What is the Institutional Review Board (IRB)?
• Federalwide Assurance (FWA)
• Research and Other Definitions
• Types of IRB Review
• Informed Consent
• IRB Process

29
Informed Consent

• The ethical principle of Respect for Persons
  and federal regulations require that all subjects
  must consent to participate in a study and be
  willing to take part in the study after being
  informed of all aspects of the study that might
  influence their decision to participate.
• Informed Consent is a process. It can take place
  before, during and after the study.
• Types of informed consent
• Written and documented (signed)
• Written (information letters)
• Verbally
• Assent
• Passive

30
Informed Consent

• Under certain circumstances, informed consent may
  be waived by the IRB.
• Justification is needed
• Required elements of informed consent
• study involves research
• purpose of the research
• duration of participation
• description of procedures, identifying those that
  are experimental
• description of risks
• description of benefits
• disclosure of alternatives
• extent confidentiality will be maintained
• contact for research, subjects rights
• participation is voluntary, refusal to
  participate will involve no penalty or loss of
  benefits to which the subject is otherwise
  entitled, and the subject may discontinue
  participation at any time without penalty or loss
  of benefits to which the subject is otherwise
  entitled.

31
OBJECTIVES

• Background Overview
• History of Research Ethics
• What is the Institutional Review Board (IRB)?
• Federalwide Assurance (FWA)
• Research and Other Definitions
• Types of IRB Review
• Informed Consent
• IRB Process

32
IRB Process

• Complete the Human Subjects Training
• The IRB office tracks completions
• Complete the IRB forms
• Cover sheet
• Abstract
• Consent forms
• Obtain the appropriate signatures
• Faculty Advisor
• Exempt

33
IRB Process

• Have the right number of copies
• Exempt (1) original (2) copies 3 total
• Expedited (1) original (2) copies 3 total
• Full Board (1) original (14) copies 15 total
• Be aware of deadlines
• Submit all materials to the IRB office
• By mail or drop-off
• All materials means consents information
  letters scripts data collection sheets survey
  and interview instruments letters from other
  institutions etc.

34
IRB Process

• The IRB will conduct an initial review
• Completeness
• Appropriate IRB review (exempt, expedited, full
  board)
• If the study requires Full Board review, it will
  be placed on the agenda for the next scheduled
  meeting based on the submission deadline.
• If the study requires Exempt or Expedited review,
  it will be forwarded to the designated IRB member
  for review.
• Revising your study based on the conditions set
  forth by the IRB
• The study may receive Conditional Approval, or
  Approved Pending Modifications
• The IRB Administrator will email the Investigator
  
• The study does not have approval
• Study cannot begin
• Submit the email requesting the changes and the
  revisions back to the IRB office with the changes
  highlighted, bolded, or underlined.

35
IRB Process

• Receiving a letter notifying approval status of
  study
• Approved, or
• Disapproved
• Begin your research!

36
Thanks!Questions?
September 6, 2006