Transcript Human Subjects Research, Ethics & the Role of the

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“The first step in the
evolution of ethics is a
sense of solidarity with
other human beings.”
Albert Schweitzer
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Office of Research Integrity and
Compliance (ORIC) Core Areas
1. Human research protections
 AAHRPP reaccreditation received
2. Animal care and use in research
3. Conflict of interest in research
4. Institutional biological safety
5. Export control
6. Responsible conduct of research education and
training (CITI online, courses & seminars)
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Human Research Protections: IRB
 Any human subjects research conducted by or
under the auspices of any WVU faculty, student
or staff, using WVU facilities or data, or
accessing WVU staff, patients or students as
participants must be reviewed by the WVU IRB.
 These human subject research projects must be
submitted to the IRB office for review.
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Authority of IRB
 Requirement of review
 Approve, disapprove or modify
 Conduct continuing review
 At any time and in person if desired
 Must be done at least once per year
 Observe/verify changes
 Suspend or terminate approval
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Human Research Protections (IRB)
 Flexibility is a primary characteristic of WVU
IRBs.
 Minimal risk studies will receive a thorough
but quick review.
 More than minimal risk research will receive
full board review at a convened meeting.
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Levels of Review
 4 Primary Levels of Review:
 NHSR
 Exempt
 Expedited
 Full Board
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Reasonable Expectations
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At this point in time the major
responsibility for insuring ethical
decision making in human research
rests with the IRBs in terms of
empowerment, flexibility and
discretion.
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Points to Keep in Mind
1.
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Keep protocol/consent up-to-date with who is involved in the
study and be sure it is up-to-date. Common mistake is to copy
one from the file.
If a person is consenting, they need to be on the protocol and
consent.
If a person leaves or is added to the study, notify the IRB
(amendment) and update the protocol/consent
Other than signatures, do not write on the consent (no patient
data, medical history, contact numbers, etc) and do not crossout or whiteout which results in invalidation.
In accordance with confidentiality/privacy procedures, separate
the consent from the data collection form. This also means do
not put the subjects name on the data collection form.
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Human dignity and social justice in
an economically and politically
unbalanced world
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History of Human Research Gone
Awry
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Nazi Experiments (Nuremberg)
Milgram Obedience Experiments
Radiation Experiments
Willowbrook
Wichita Jury Taping Study
Jewish Chronic Disease Cancer Study
Thalidomide Tragedy
Syphilis Experiments (Tuskegee, Guatemala)
Jesse Gelsinger
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Ice Bath Experiments at Dachau
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Nuremberg Trial
Dec 9, 1946 - Aug 20, 1947
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Nuremberg Code
 The Nuremberg Code is primarily remembered for
the first sentence of the first of the 10 principles:
“The voluntary consent of the human
subject is absolutely essential.”
 It is to this statement that we trace the modern
requirement for seeking the voluntary consent of
research subjects.
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Nuremberg Impact
 American researchers thought something
like that could never happen here
 There was no rule that one had to follow
the Code
 Public got more serious and demanding
when things went wrong in America
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Guatemala
A man holds a ruler next to
the arm of a woman who
had been infected with a
venereal disease in the late
1940s in Guatemala
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Willowbrook State School
Staten Island, 1956-1963
 Institutionalized
children
 Infected with hepatitis
A on purpose
 Only allowed in the
school if they
participated in the
study
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DECLARATION of HELSINKI “MORE SPECIFIC
RESEARCH RULES”
 Consent should be in writing
 Research should build on previous work
 Research must follow written plan
 Review by an independent committee
 Caution if participant is in dependent
relationship with researcher
 Participants must receive best proven
care
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“Ethical lapses are almost
never cases of bad people,
doing bad things, for no good
reason. Rather, they are good
people, doing bad things, for
good reasons.”
Marcia Angell, MD
former Editor, NEJM
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Tuskegee Syphilis Study
Macon County, Alabama
1932-1972
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Nurse Rivers, Dr. John Cutler & other
PHS Doctors in the early ’50’s
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Syphilis Study (Tuskegee) Impact
 National Research Act (1974) required federal
regulations for the protection of human subjects
 required informed consent
 required review and monitoring of research by an institutional
review board (IRB)
 created the National Commission for the Protection of Human
Subjects of Biomedical and Behavioral Research
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Respect for Persons
 How is this principle exhibited in clinical research?
 Informed consent
 Privacy, confidentiality, i.e.,
autonomy
 Increased protection for those
with diminished autonomy
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Beneficence
 How is this principle manifested in clinical research?
 By ensuring that the benefits of the research outweigh
the risks.
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Justice
 How is this principle manifested in clinical research?
 By ensuring that one societal group does not unduly
shoulder the risks (burden) of research or be excluded
from the benefits of research.
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The New Electronic System is on its Way
 The WVU Research Office and OIT are working together to replace the
current electronic system known as BRAAN with a new KC IRB module.
 This new system’s first stage will be put into place in April 2012.
 Investigators will continue to be able to create and manage IRB
protocols.
 The KC IRB system will operate in parallel with BRAAN for one year as
protocols are manually transferred by the investigators to the new
system through the new protocol and renewal application process, with
BRAAN eventually becoming an archive system for historical data only.
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 Collaboration
between
Kuali
Coeus
(KC)higher education institutions
 Over 40 schools participating in Kuali Coeus
 Sample Participating Partner Schools include:
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Colorado State
Clemson University
Cornell University
Indiana University
Michigan State
MIT
The University of Arizona
University of California System
West Virginia University
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 When in doubt, please always err on the side of
caution regarding any Human Subjects Research.
 Call the IRB office for advice on submitting a
protocol for IRB review or conducting human
subjects research as it relates to IRB matters. This
can prevent misunderstandings and will ensure
that your research is in compliance with federal
regulations.
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The research protection system
fundamentally revolves around
mutual trust and responsibility.
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CRITERIA FOR APPROVAL OF RESEARCH
45 CFR PART 46.111
To approve research, an IRB should determine
that all of the following conditions exist:
1. Risks to subjects are minimized.
2. Risks are reasonable in relation to
anticipated benefits, if any, to subjects and
to advancement of knowledge.
3. Selection of subjects is equitable.
4. Informed consent will be sought.
5. Informed consent will be documented.
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CRITERIA FOR APPROVAL OF RESEARCH
45 CFR PART 46.111
6.
7.
8.
Where appropriate, research plan makes
adequate provision for monitoring the data
collected to insure safety of subjects.
There are adequate provisions to protect
the privacy of subjects and to maintain the
confidentiality of data.
Where any of the subjects are likely to be
vulnerable to coercion or undue influence,
additional safeguards have been included in
the study to protect subjects.
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Basic Elements of Informed Consent Process
(45 CFR 46.116a)
1.
2.
3.
4.
Statement that study involves research;
explanation of purposes of research and
expected duration of subject’s participation;
description of procedures to be followed and
identification of any procedures which are
experimental.
Description of risks or discomforts to subject.
Description of benefits to subject or to others.
Disclosure of alternative procedures, if
appropriate.
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Basic Elements of Infromed Consent Process
(45 CFR 46.116a)
5.
Description of the extent to which confidentiality
will be maintained.
FDA: statement that FDA may inspect records.
6. For research involving more than minimal risk,
explanation as to whether compensation and
medical treatments are available if injury occurs.
7. Explanation of whom to contact if questions
arise about the research, the subject’s rights or
whom to contact if research-related injury occurs.
8. Statement that participation is voluntary, that
refusal to participate involves no penalty or loss
of benefits, and that subject may discontinue at
any time.
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Ensure that language and
readability are appropriate to
the subject.
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Additional Elements of Informed Consent
45 CFR 46.116b
When required by the IRB, one or more of the
following elements shall be provided to each
subject:
1.Statement that procedure may involve
unforeseeable risks;
2.Description of circumstances under which
subject’s participation may be terminated by
the investigator without subject’s consent;
3.Additional costs to subject resulting from
participation in research;
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Additional Elements of Informed Consent
45 CFR 46.116b
4.
Consequences of subject’s decision to
withdraw from research;
5. Statement that significant new findings
developed during research which may
relate to subject’s willingness to continue
will be provided to subject;
6. Approximate number of subjects involved
in study.
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46.116 Consent - the Process
Process of information exchange which should
include:
 written materials (CF, letters, debriefs)
 verbal instructions
 questions & answers after reading ICF with
subject
 setting/timing (family/friends consultation)
 agreement/documentation
 reaffirmation/re-consent
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Take away points:
* Make sure protocol/consent up-todate
* Don’t write on consents other than
name & signature
* Reasonable Expectations
* Better Safe Than Sorry: If in
Doubt, Contact ORIC!
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Above all else, strive to “do
the right thing”.
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