IRB

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IRB BASICS
Prepared for Regent University 11/21/07 St
an Hoegerman
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The Nuremberg Code The Nuremberg Code arose as
part of the trial of the United States v. Karl
Brandt. Karl Brandt and others were tried at
Nuremburg for crimes against humanity committed
in their roles as the Nazi high command. The code
has ten requirements
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1. The voluntary consent of the human subject is
absolutely essential. This means that the person
involved should have legal capacity to give
consent should be able to exercise free power
of choice without the intervention of any
force, fraud, deceit, duress, overreaching, or
other ulterior form of constraint or coercion and
should have sufficient knowledge and
comprehension of the elements of the subject
matter involved as to enable him to make an
understanding and enlightened decision. This
latter element requires that there should be
made known to him all risks, inconveniences
and hazards reasonably to be expected.
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2. The experiment should be such as to yield
fruitful results for the good of society,
unprocurable by other methods or means of study,
and not random and unnecessary in nature.
3. The experiment should be so designed and base
d on the results of animal experimentation and a
knowledge of the natural history of the disease
or other problem under study that the anticipated
results will justify the performance of the
experiment. 4. The experiment should be so con
ducted as to avoid all unnecessary physical and
mental suffering and injury.
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5. No experiment should be conducted where there
is a prior reason to believe that death or
disabling injury will occur, except perhaps, in
those experiments where the experimental
physicians also serve as subject.
6. The degree of risk to be taken should never e
xceed that determined by the humanitarian
importance of the problem to be solved by the
experiment. 7. Proper preparations should be m
ade and adequate facilities provided to protect
the experimental subject against even remote
possibilities of injury, disability or death.
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8. The experiment should be conducted only by
scientifically qualified persons. The highest
degree of skill and care should be required
through all stages of the experiment of those who
conduct or engage in the experiment.
9. During the course of the experiment the human
subject should be at liberty to bring the
experiment to an end if he has reached the
physical or mental state where continuation of
the experiment seems to him to be impossible.
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10. During the course of the experiment the
scientist in charge must be prepared to terminate
the experiment at any stage, if he has probable
cause to believe, in the exercise of the good
faith, superior skill, and careful judgment
required of him, that a continuation of the
experiment is likely to result in injury,
disability, or death to the experimental subject.
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From 1932 to 1972, in Macon county, Alabama, t
he United States Public Health Service treated a
group of 600 black men for syphilis. However,
the treatment never actually occurred, alth
ough the participants were told they were being
treated. While information from the study was pu
blished throughout the forty years it was in eff
ect, it was an Associated Press
story in 1972 that raised national awareness to
shut down the study and led to revised federal r
ules on human subjects research.
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(No Transcript)
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Do we have to concern ourselves with Virginia
law?
32.1-162.20. Applicability of federal policies.
Human research which is subject to policies an
d regulations for the protection of human
subjects promulgated by any agency of the federal
government shall be exempt from the provisions of
this chapter. http//leg1.state.va.us/000
/lst/LS423930.HTM and click on Applicability of
federal policies.
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Do we have to concern ourselves with Virginia law?
32.1-162.20. Applicability of federal policies.
Human research which is subject to policies an
d regulations for the protection of human
subjects promulgated by any agency of the federal
government shall be exempt from the provisions of
this chapter.
In other words, federally funded research has
been exempted from the VA regs. because it must
be reviewed by the Federal regs.
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In lieu of promulgating regulations pursuant to
the requirements of this chapter, an institution
may comply with this chapter by promulgating
regulations under the provisions of the
Administrative Process Act ( 2.2-4000 et seq.)
governing human research projects which
incorporate, explicitly or by reference, federal
policies and regulations for the protection of
human subjects.
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In lieu of promulgating regulations pursuant to
the requirements of this chapter, an institution
may comply with this chapter by promulgating
regulations under the provisions of the
Administrative Process Act ( 2.2-4000 et seq.)
governing human research projects which
incorporate, explicitly or by reference, federal
policies and regulations for the protection of
human subjects.
In other words, if we review all research using
the Federal regs., we dont have to follow the V
A regs.

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However, in the case of projects which are not
required, by reason of their nature, the source
of their funding, or the lack thereof, to comply
with federal policies and regulations, the
institution or agency may enforce compliance by
filing a petition for an injunction in the
appropriate circuit court. This section shall not
preclude any other enforcement action available
to the institution or agency.
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However, in the case of projects which are not
required, by reason of their nature, the source
of their funding, or the lack thereof, to comply
with federal policies and regulations, the
institution or agency may enforce compliance by
filing a petition for an injunction in the
appropriate circuit court. This section shall not
preclude any other enforcement action available
to the institution or agency.
In other words, the IRB has the clout to force
an investigator to accept review using the
Federal regs. even when the Federal regs. dont
require their use.
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BASIC IRB DEFINITIONS, RULES, PROCEDURES
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HUMAN SUBJECTS RESEARCH

• Whats RESEARCH?
• 2) Whats HUMAN?
• 3) Who are SUBJECTS?

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HUMAN SUBJECTS RESEARCH

• Whats RESEARCH?
• 2) Whats HUMAN?
• 3) Who are SUBJECTS?

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Whats Research?

• Research - defined by the regulations as "a
  systematic investigation, including research
  development, testing and evaluation, designed to
  develop or contribute to generalizable
  knowledge."
• Working definition Activities undertaken with
  the intent to disseminate the results. Such
  dissemination may take the form of
  
• Publication
• Presentation at a meeting/conference
• Inclusion in a grant application
• Inclusion in a textbook, etc.
• Note - Dissemination may be oral.

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• What isnt research (but looks like research)?
• Training exercises! A part of normal, typical
  coursework.
  
• This may include coursework in research methods
  in departments such as Education and Psychology.
  
  
• (But note Honors projects and research
• projects undertaken with extensive faculty
• guidance are to be considered research.)

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• There MUST be NO ex post facto approval of
  training exercises to legitimize turning these
  studies into approved Human Research.
  
• Similarly, it is not appropriate to approve
  projects that will include data from unapproved
  projects (e.g. class projects).
  

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• There MUST be NO ex post facto approval of
  training exercises to legitimize turning these
  studies into approved Human Research.
  
• Similarly, it is not appropriate to approve
  projects that will include data from unapproved
  projects (e.g. class projects).
  
• WHY?, you may ask.

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• There MUST be NO ex post facto approval of
  training exercises to legitimize turning these
  studies into approved Human Research.
  
• Similarly, it is not appropriate to approve
  projects that will include data from unapproved
  projects (e.g. class projects).
  
• WHY?, you may ask.
• Faculty will attempt end runs around the IRB.
• The philosophy of Its easier to get forgiveness
  than it is to get permission must not prevail.

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HUMAN SUBJECTS RESEARCH

• Whats RESEARCH?
• 2) Whats HUMAN?
• 3) Who are SUBJECTS?

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Whats Human?

• Human(s) are initially defined by the regulations
  as "living individual(s). Later, the definition
  is broadened to include fetuses and fetal parts.

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HUMAN SUBJECTS RESEARCH

• Whats RESEARCH?
• 2) Whats HUMAN?
• 3) Who are SUBJECTS?

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Who are Subjects?

• Subjects are defined by the regulations as
  "living individual(s) 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"

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Example

• An investigator reviews hospital records and
  compiles information on the relative frequencies
  of different diagnoses at the time of admission.

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Example

• An investigator reviews hospital records and
  compiles information on the relative frequencies
  of different diagnoses at the time of admission.

Is this Human Research?
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Example

• An investigator reviews hospital records and
  compiles information on the relative frequencies
  of different diagnoses at the time of admission.

Is this Human Research?
No. There is no intervention or interaction with
the individuals and identifiable information
(names, in this case) is not recorded
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And how about these guys? Are they doing Human
Research?
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And how about these guys? Are they doing Human
Subjects Research?
No way! Human Subjects Research
requires a living subject.
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What classes of Subjects are there?

• Primary Subjects are those who are the focal
  points of the research. For surveys, they are the
  ones who are questioned.
  
• 1) A Secondary Subject is anyone one learns
  information about through study of a primary
  subject.
  
• For example, if you ask men, whose names have
  been recorded by you, about their mothers
  health, the mothers become secondary subjects.

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What are the categories of
human research?
1) Exempt 2) Expedited Review 3) Full
Committee Review 4) Not Human Research
by the Federal definition
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What are the categories of
human research?
1) Exempt 2) Expedited Review 3) Full
Committee Review 4) Not Human Research
by the Federal definition
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Whats Exempt, whats eligible for
Expedited Review, and what requires Full Committ
ee Review?
See http//www.hhs.gov/ohrp/humansubjectsguidance
/decisioncharts.htm for the worst set of
decision-making flow charts I have ever seen.
But they are very useful for beginners.
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Is it research? Is it human subjects research
?
If Yes, go to Chart 2.
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Chart 2 helps you look for a way to exempt pro
posals for the need for additional review.
Chart 3.
(lets not go there)
Good grief! There are eight of these.
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Not Human Research
Exempt from Review
1a
Research
1b
2a
Expedited Review
3a
Human Research
Not exempt
2b
3b
Full Committee Review
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Not Human Research
Who makes the first decision?
1a
Research
1b
Human Research
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Not Human Research
Who makes the first decision? The Principle Inv
estigator
1a
Research
1b
Human Research
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Not Human Research
Who makes the first decision? The Principle Inv
estigator (PI)
Why?
1a
Research
1b
Human Research
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Not Human Research
Who makes the first decision? The Principle Inv
estigator Why? Because, otherwise, the IRB
will be a) universally hated and b) buried
under a mountain of paperwork
1a
Research
1b
Human Research
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Who makes the second decision?
Exempt from Review
2a
Human Research
Not exempt
2b
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Who makes the second decision? The IRB chair.
Exempt from Review
2a
Human Research
Not exempt
2b
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Who makes the second decision?
The IRB chair or committee members designated
to do it..
Why?
Exempt from Review
2a
Human Research
Not exempt
2b
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Who makes the second decision?
The IRB chair or committee members designated
to do it. Why? Because, if you let PIs do
it, 90 of them will exempt their own research
even if it doesnt qualify.
Exempt from Review
2a
Human Research
Not exempt
2b
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Who makes the third decision?
The IRB chair or committee members designated
to do it.

Expedited Review
3a
Not exempt
3b
Full Committee Review
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Who makes the third decision?
The IRB chair or committee members designated
to do it.
Why?
Expedited Review
3a
Not exempt
3b
Full Committee Review
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Who makes the third decision?
The IRB chair or committee members designated
to do it. Why? Because, if you let PIs do
it, 90 of them will elect Expedited Review even
if it doesnt qualify.
Expedited Review
3a
Not exempt
3b
Full Committee Review
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Who makes the decision to approve or not approve
a proposal eligible for Expedited Review? The
Federal regs. are mute on this point.
It could be the chair acting alone. It could
be a designated committee member (even the
member who ruled that the proposal qualifies for
Expedited Review). It could be an ad hoc sub
committee composed of the chair plus two other m
embers. It could be an ad hoc subcommittee com
posed of three members.
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Who makes the decision to approve or not approve
a proposal requiring Full Committee Review? D
uh! It must be the full committee. And a quorum
must be present. It must be a convened meeting.
Discussions and or voting by email are strictly
verboten! Conference calls are not expressly
prohibited. Probably a bad idea however.
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• What sorts of decisions may the committee
  render?
  
• Approval.
• Conditional approval. If the PI incorporates
• suggested alterations, the Chair may issue
  approval.
  
• 3) Suggest revision and resubmission. The
  proposal
  
• has serious flaws and must be revamped. A
  detailed
  
• list of shortcomings should be given to the PI.
• 4) Rejection unpolitical!

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A Practical Rule All proposals must have a fac
ulty mentor (or the equivalent). If proposals su
bmitted by students are incoherent, the chair ma
y return the proposal to the mentor with a reque
st that wording / procedures / techniques to be
used / whatever must be clarified.
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Informed Consent

• The voluntary consent of the human subject is
  absolutely essential.
  
• Potential subjects should have the legal
  capacity to give consent.
  
• A parent or guardian must give consent for
  the participation of
  
• children under the age of 18 or of mentally
  incompetent persons.
  
• The investigator must also have the assent
  of the potential subject.
  
• 2) They should be able to exercise free power of
  choice without any
  
• intervention involving force, fraud,
  deceit, duress, overreaching,
  
• or other form of constraint or coercion.
• Payment of large sums of money to encourage
  participation in
  
• projects with significant degrees of risk
  is not permitted.
  

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• They should have sufficient knowledge and
• comprehension of the subject matter to
  enable them
  
• to make an understanding and enlightened
  decision.
  
• Potential subjects should be well educated on
  the subject
  
• matter.
• 4) This latter element requires that all risks,
  inconveniences
  
• and hazards reasonably to be expected be
  made known
  
• to them.
• This has been expanded to require the
  inclusion of
  
• improbable side effects and the like.