dr. melissa frumin does not have any financial
TRANSCRIPT
Dr. Melissa Frumin
DOES NOT HAVE ANY FINANCIAL
RELATIONSHIPS WITH A COMMERCIAL
ENTITY PRODUCING HEALTH-CARE
RELATED PRODUCTS AND/OR SERVICES
Overview of the Ethical Foundation
of Human Subject Protection
Melissa Frumin MD, MS
Chair, Partners IRBs - MGH and BWH
Neuropsychiatrist,
Assistant Professor of Psychiatry
Harvard Medical School
My Career - Currently!
30 % IRB administration
Chairing IRB Panel meetings, non-compliance investigations, policy development, education
70 % Clinical Care
– BWH Behavioral Neurology Clinic
– General Psychiatry Practice
I’m not a medical ethicist
Topics
Overview of Partners IRB
IRB Guiding regulations/requirements to
approve
Research ethics
Case discussions: you are the IRB
Thanks to Dr. Hohmann for the use of
some of her slides
IRB
Institutional - Partners
Review
Board
Partners Human Research Committee PHRC : MGH/BWH
>230 volunteer members; ~45 administrative staff; 10 scientific chairs
Human Subjects Research
Definition Federal Law:
Collection and dissemination of information
about identifiable living human subjects.
IRB Mission
Protect the rights and welfare of human subjects
in clinical research.
Scientific and ethical review board.
Minimize the risks to human subjects.
Oversee/supervise ongoing research.
Set research policies and procedures.
Set limits, institutional tone and standards.
Report to and interact with investigators and
federal regulators (usually OHRP, FDA).
What are IRBs?
Required by federal law to review federally funded research on human subjects (FWA).
5 people minimum.
1 scientist, 1 nonscientist, 1 nonaffiliated.
Physicians, Scientists, RNs, Lay members, Patients, Clergy, Statistician, Ethicists, Pharmacists, Genetic Counselors, Lawyers, and at least one psychiatrist on each panel
We have 7 panels at MGH/BWH- 5 panels meet twice/month
IRB Chairs Elizabeth Hohmann MD, Overall Chair (ID)
Lawrence Tsen MD (Anesthesia)
Melissa Abraham PhD (Psychology)
Melissa Frumin MD (Psychiatry)
Steven McAfee MD (Oncology)
Megan Morash RN (Tissue Banking)
Judy Scheer RN (Clinical Research)
Julian Seifter MD (Nephrology)
Robert Schleipman, RT (Radiology)
Benjamin Silverman MD (Psychiatry)
David Smith MD (Hem/Onc)
Steven Vacirca MD (Radiology)
Quantity of Work- Approximatley
New Submissions - 2,000
Continuing Review – 5,000
Amendments – 13,000
Adverse Events – 100
Other – 1,000
Total Actions – 22,000
We are the deciders!
IRBs are INDEPENDENT of Hospital
Departments, Medical School, Licensing,
Offices of Grants & Contracts, Clinical
Care/Oversight, etc.
Others can stop research if IRB approved,
Others cannot start if IRB disapproved.
HIPAA as it relates to research.
Conflict of Interest as it relates to research.
The IRB is a peer review
process, Not a computer.
Although we strive for consistency
Different reviewers
Different panels have different
opinions.
Guiding Regulations
Code of Federal Regulations (CFR) Title 45 Part
46 (45CFR46) 1981
– General statements open to interpretation
– OHRP (part of HHS) is the interpreter
– Specific guidance not always forthcoming
– Much based upon “case law”
National Research Act (IRB) 1974
FDA regulations (IND, IDE)
ICH Good Clinical Practice (GCP)
IRB Accreditation! AAHRPP
7 legal requirements for IRB approval
in the US
Risks to subjects must be minimized
– sound scientific protocol which does not
UNNECESSARILY expose subject to risk
Risks are reasonable with regard to potential benefit
or knowledge gained
Selection of subjects is equitable
Informed consent will be sought
7 Requirements, continued.
Adequate provisions for monitoring of data collected
to ensure subject’s safety.
Confidentiality must be maintained.
Vulnerable populations must be protected
– Children, prisoners, pregnant women/fetus,
mentally ill or incompetent, educationally,
economically or socially disadvantaged
– Special “subparts” of the regulations apply
Review Mechanisms
Expedited Review - Chair only
– Specified limited research activities only!
Full Review – Panel
Emergency uses of investigational drugs
and devices
Expedited - Minimal risk
Blood draw healthy adults
(limits!)
Observational studies
Study of data already
existing and collected for
other reasons.
Noninvasive “standard
clinical tests” Physical
Exam, Ultrasound, MRI,
History Taking
Moderate exercise
Studies of perception,
views, thoughts
Samples - buccal swab,
tooth scrapings, saliva,
urine
Phase IV post-marketing
studies of drugs/devices
At the meeting
Primary reviewer presents a 2-3 minute SUMMARY of
the study.
Reviewer present criticisms and concerns.
Discuss major consent form problems.
Secondary reviewer comments: focus on highlighting or
adding new points.
Open for discussion by panel.
Act on the study.
All this in about 13 minutes per study!
Actions of the committee
Approved
Requires modifications – Requests for alterations, usually with specific
directions
Deferred - not enough information to assess risks/benefits, substantive clarifications – Must return to the convened group when fixed
Disapproval - major scientific/ethical problems, not likely resolved
Guiding Principles
Hippocratic Oath (4th C BCE). Do no harm
Nuremberg Code (1947)
Declaration of Helsinki (1964, 2001, 2004)
Belmont Report (1979)
Nuremberg Code
Voluntary consent of the subject must be obtained.
Prior animal experimentation is needed to assess risks.
Human experimentation must be performed only by qualified medical personnel.
Belmont Report
Respect for persons as autonomous individuals with right to self determination
Beneficence
Justice
Please read it before you start clinical research. 3 pages on the ethical principles
Respect for Persons
Two major ethical convictions – Individuals are autonomous agents and can act
under the direction of such deliberation
– People with diminished autonomy are entitled
to protection
“Enter into the research voluntarily and with
adequate information”
Beneficence
Two major ethical convictions
– Do no harm
– Maximize possible benefits and minimize possible harms
Beneficence considers the particular research project and the entire research enterprise
Justice
Who receives the benefits of
research?
Who bears its burdens?
Who is equal and who is unequal?
What considerations justify departure
from equal distribution?
Justice - Historically
The burden of research subjects fell to the poor ward patients while the benefits of better medical care went the private patients
Experimentation of prisoners in the Nazi camps. Mengele twins
Tuskegee syphilis study
Informed Consent
It’s a process, not a form.
The form reflects the process.
Forms written for 13-14 year old reader.
Children assent.
Adults consent.
Surrogates consent for others
– Carefully considered.
– Risk/Benefit Assessment
– Legal issues
Informed Consent
Goals of informed consent process?
– Communicate to the subject what the study is
about
– Describe what a reasonable person would
want to know
– Not coercive
– Subject would understand the study so as to
make a choice to participate
Informed Consent
Informed Consent Process Protections
– Should not be coerced
– Therapeutic misconception
– It should not preclude getting standard care.
– What if the PI is the subjects own physician?
Capacity to give Informed Consent
How to assess Capacity to consent
MacArthur Competence Assessment Tool
for Clinical Research
– Takes about 15-20 minutes
– It is a semi structured interview tailored to the
research study
– Researchers can assess and rate the potential
subjects capacity to give informed consent
Capacity to give Informed Consent
MacArthur Competence Assessment Tool
for Clinical Research
– Understanding of disclosed information about
the research project and its procedures
– Appreciation of the effects of research
participation (or failure to participate) on
subjects own situations.
Capacity to give Informed Consent
MacArthur Competence Assessment Tool
for Clinical Research
– Reasoning in the process of deciding to
compare alternatives in light of their
consequences
– Expressing a choice about research
participation
What can you do to learn more about
human subject protection
Observe an IRB meeting
Join an IRB
Learn about your research project and IRB approval.
Work on the application
“Real Life” Case Studies
What would you say, if you
were on the IRB?
Case 1
A researcher wants to study a new drug used to treat brain swelling in patients admitted to the hospital, who have had a large stroke.
Many of these patients are sedated so are not able to give informed consent.
Case 1 The investigator wants to allow health care
proxies to give consent, instead of the
subject.
– What are the important issues for the IRB to consider
before allowing this?
– What is a health care proxy
– What guides the health care proxy in making decisions
for the subject.
Case 2
Another investigator wants to review the medical records of a group of adult patients who have Type 1 diabetes
It does not seem very dangerous just to look at a medical record.
Does the investigator need IRB review just for a medical record review?
Case 2
Yes, this is Medical Records Research.
Some wouldn’t allow if asked!
You CAN do this with IRB approval.
You CANNOT do it without such!
HIPAA
Case 3
An investigator wants to use a drug already
approved for use to treat asthma in adults,
in a study of children with asthma.
What does the IRB need to consider in
approving a drug study involving kids ages
10-17?
Case 3
Who provides consent?
What if the child hears about the study while sitting in the waiting room of the doctor's office but his parents won't let him be in the study?
Can he do it without his parent's permission?
Your Cases 4, 5, 6 …