Transcript Slide 1

Human Subjects Research Protection
February 12, 2010
James Riddle, MCSE, CNE, CIP
FHCRC Institutional Review Office
https://centernet.fhcrc.org/CN/depts/iro/index.html
History
Principles and Regulations
Institutional Review Boards
Responsibilities of Investigators
Informed Consent
Privacy and Confidentiality
Vulnerable Subjects
Practical Implications
At FHCRC, you need human subjects
training if…
Design: developing the research concept, scientific
method, and objectives that involve intervention with a
human subject or the use of data or tissue derived from a
human subject, or
Conduct: implementation and management of research
involving human subjects. Staff conducting research
include principal investigators, research staff working on
a research study, and others engaged in research activity
supporting the research study (e.g., conducting
interviews, surveys, data collection), or
Reporting: analyzing, summarizing, or preparing
manuscripts involving data derived from a research
study involving human subjects.
This training is good until February 11, 2013
19th C.
18th C.
20th C.
Nuremberg, 1946
THOSE NAZI DOCTORS
DID HORRIBLE THINGS!!
GOOD THING WE’RE NOT NAZIS!!
Willowbrook Hepatitis Study, 1956
Jewish Chronic Disease Hospital, 1963
PHS Syphilis Study, 1932-72
This examination is a very
special one and after it is
finished you will be given a
special treatment if it is
believed you are in a
condition to stand it.
REMEMBER THIS IS YOUR
LAST CHANCE FOR SPECIAL
FREE TREATMENT. BE SURE
TO MEET THE NURSE.
1.Respect for Persons
Informed consent
2. Beneficence
Risk/benefit assessment
3. Justice
Selection of subjects
Theory…
…and Practice
FDA
Regulations
• Food and Drug Administration (FDA)
– 21 CFR Parts 50 & 56
• Health and Human Services (HHS) – 45 CRF 46
(AKA: Common Rule)
– Office of Human Research Protections
(OHRP)
FDA
What is “human subjects research”?
Clinical investigation
means any experiment
that involves a test article
and one or more human
subjects ….
Human subject means an
individual who is or
becomes a participant in
research, either as a
recipient of the test
article or as a control. A
subject may be either a
healthy human or a patient.
21 CFR 50.3
Who are “investigators”?
Regulations – HHS -45 CFR part 46 (AKA: “Common Rule”) use
the term “investigator” to refer to an individual performing
various tasks related to the conduct of human subjects research
activities:
– Obtaining informed consent from subjects
– Interacting with subjects
– Communicating with the IRB.
OHRP interprets an “investigator” to be any individual who
is involved in conducting human subjects research studies.
Such involvement would include:
– Obtaining information about living individuals by intervening
or interacting with them for research purposes;
– Obtaining identifiable private information about living
individuals for research purposes;
– Obtaining the voluntary informed consent of individuals to
be subjects in research; and
– studying, interpreting, or analyzing identifiable private
information or data for research purposes.
What is AAHRPP
• Founded in 2001
• Responding to increased public concern for protecting
research participants
– seeks to ensure compliance with federal regulations
– raise the bar in human research protection by helping
organizations reach performance standards that
surpass the threshold of state and federal
requirements
• First institutions accredited in April 2003
• FHCRC received accreditation in March 2008, one of
approximately 80 institutions outside the VA to have
their HRPP accredited.
Break…
Theory…
…and Practice
Levels of IRB Review
1. Full Committee Review
2. Expedited Review
(a dramatization)
3. Review for Exemption Status
4. Determination of “Not Human Subjects”
Criteria of IRB approval
• Risks to subjects are minimized by using procedures which are
consistent with sound research design and resources which do
not unnecessarily expose subjects to risk.
• Risks to subjects are reasonable in relation to anticipated
benefits, if any, to subjects, and the importance of knowledge that
may reasonably be expected to result.
• Selection of subjects is equitable.
• Informed consent process and compensation will be sought
from each prospective subject or the subject's legally authorized
representative.
• Informed consent will be appropriately documented.
• Where appropriate, the research plan makes adequate provision for
monitoring the data collected to ensure the safety of subjects.
• Where appropriate, there are adequate provisions to protect the
privacy of subjects and to maintain the confidentiality of data.
• Appropriate safeguards for special populations.
Basic Elements of Informed Consent
1. A statement that the study involves research, an explanation of the purposes of
the research and the expected duration of the subject's participation, a description
of the procedures to be followed, and identification of any procedures which are
experimental;
2. A description of any reasonably foreseeable risks or discomforts to the subject;
3. A description of any benefits to the subject or to others which may reasonably be
expected from the research;
4. A disclosure of appropriate alternative procedures or courses of treatment, if any,
that might be advantageous to the subject;
5. A statement describing the extent, if any, to which confidentiality of records
identifying the subject will be maintained;
6. For research involving more than minimal risk, an explanation as to whether any
compensation and an explanation as to whether any medical treatments are
available if injury occurs and, if so, what they consist of, or where further
information may be obtained;
7. An explanation of whom to contact for answers to pertinent questions about the
research and research subjects’ rights, and whom to contact in the event of a
research-related injury to the subject; and
8. A statement that 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.
Additional Elements
of Informed Consent
1.
A statement that the particular treatment or procedure may involve risks to the
subject (or to the embryo or fetus, if the subject is or may become pregnant) which
are currently unforeseeable;
2.
Anticipated circumstances under which the subject’s participation may be
terminated by the investigator without regard to the subject's consent;
3.
Any additional costs to the subject that may result from participation in the
research;
4.
The consequences of a subject’s decision to withdraw from the research and
procedures for orderly termination of participation by the subject;
5.
A statement that significant new findings developed during the course of the
research which may relate to the subject's willingness to continue participation will
be provided to the subject; and
6.
The approximate number of subjects involved in the study.
FHCRC Model consent (template)
IRB may waive/alter consent if…
1. The research involves no more than minimal risk to
the subjects;
2. The waiver or alteration will not adversely affect
the rights and welfare of the subjects;
3. The research could not practicably be carried out
without the waiver or alteration; and
4. Whenever appropriate, the subjects will be provided
with additional pertinent information after
participation.
45 CFR 46.116(d)
Privacy
Confidentiality
T
Working with specimens/data
Identifiability
Gatekeeping
Access
Consent
OHRP Guidance on Research Involving Coded Private
Information or Biological Specimens (10/16/2008)
Obtaining identifiable private information or identifiable
specimens for research purposes constitutes human
subjects research.
OHRP considers private information or specimens to be
individually identifiable … when they can be linked to
specific individuals by the investigator(s) either directly or
indirectly through coding systems.
Not human subjects research if:
not collected specifically for the currently proposed
research project through an interaction or
intervention with living individuals
cannot readily ascertain the identity of the
individual
Vulnerable
Working with Vulnerable Populations
Repositories
How is consent obtained?
How are specimens labeled (how identifiable?)
Who is the gatekeeper of the repository?
Are confidentiality pledges used to confirm that
staff understand confidentiality obligations?
How do you confirm each new study involving
stored tissue receives IRB review and approval?
P Q
Emergency Treatment
Regulations do not prohibit an investigator from
using any investigational or approved drug/device
in an emergency situation for patient clinical care.
This use is not considered research. Prior IRB
review and approval is required to consider the
data as research.
Q
Investigational New Drug (IND): 21 CFR 312
Investigational Device Exemption (IDE): 21 CFR 812
15 Q
Practical Application
A look at the FHCRC IRB Application Form
Practical Application
Cancer Consortium Review System
Responsibilities of Investigators
and the research team
6. Obtain informed consent in accord with the federal
regulations and as approved by the IRB
7. Document the process
8. Report progress of the approved research to the IRB as
often and in the manner prescribed by the IRB
9. Report to the IRB any injuries, adverse events or other
unanticipated problems involving risk to the
participant
10. Retain IRB research records and signed consent
documents for at least 3 years past completion of the
study
Responsibilities of Investigators
and the research team.
1. Design and implement ethical research
consistent with the three ethical principles
outlined in the Belmont report
2. Comply with all applicable federal regulations
impacting the protection of human subjects
3. Ensure that all research involving human subjects is
submitted to and approved by the appropriate IRB
4. Comply with all applicable IRB policies, procedures and
decisions
5. Implement the research as approved and obtain prior
IRB approval of modifications
The success of clinical research lies on the element
of trust – trust in researchers, trust in hospitals,
and trust in the research process itself… Without
trust at all of these levels, research could not be
carried out. Potential subjects would be unwilling
to put themselves in harm’s way if they perceived
that they would be used by researchers,
institutions, or those who fund research, and
society at large would be unwilling to have its tax
dollars spent on an enterprise that neither
enjoyed nor deserved its trust.
Kahn and Mastroianni, 2001
Thanks:
Karen Hansen
CITI
Lee Hartwell
Scientific Directors, FHCRC
Protocol Office
Questions?
FDA
Repositories
Emergency treatment
https://centernet.fhcrc.org/CN/depts/iro/index.html