HUMAN SUBJECT
RESEARCH COMPLIANCE
PRESENTED BY BRIAN WEIMER
TULANE UNIVERSITY RESEARCH COMPLIANCE OFFICER
July 23, 2013
Objectives of Presentation
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What is the role of the Research Compliance
Officer?
What is noncompliance?
What should I expect during an audit?
Why does it matter if human subjects research is
involved?
Does my research involve human subjects?
Is IRB review of my research required?
What are the different levels of IRB Review?
Role of Research Compliance Officer
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Compliance role on the following committees:
Institutional Review Board (IRB):
http://tulane.edu/asvpr/irb/index.cfm
 Institutional Animal Care and Use Committee (IACUC):
http://tulane.edu/asvpr/iacuc/index.cfm
 Institutional Biosafety Committee (IBC):
http://tulane.edu/asvpr/biosafety/committee/index.cfm
 Radiation Safety Committee:
http://tulane.edu/oehs/radiation/radiationsafety.cfm
 Conflicts of Interest Committee:
http://tulane.edu/counsel/conflict-of-interest-policy.cfm
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Role of Research Compliance Officer
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Resource to Tulane community regarding compliance with
regulations and university policies that relate to the
conduct of research
Policy development, training, and auditing
Open-door policy for questions from university community
Role on IRB:
Review proposals for compliance with SOPs and regulations
 Assist with questions regarding regulations and policies
 Review and investigate research noncompliance
 Conducts for-cause and not-for-cause audits
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Noncompliance
Definition:
 Failure to comply with or adhere to rules,
regulations, policies and standards of conduct that
govern human subject research;
 Failure to follow the determinations of the IRB;
 Failure to follow institutional policies.
Noncompliance may be minor or serious, or it may
be sporadic or continuing.
Serious Noncompliance
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Noncompliance which increases risks to participants,
decreases potential benefits, or compromises the
integrity of the human research protection program;
generally a reckless or intentional disregard for
human subject regulation and policies.
Research being conducted without prior IRB
approval is always considered serious
noncompliance.
Continuing noncompliance
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A pattern of noncompliance that suggests a
likelihood that without intervention, instances of
noncompliance will continue - three instances of the
same type of noncompliance, without adequate
explanation, is generally considered continuing
noncompliance.
Failure to respond to a request to resolve an
episode on noncompliance.
Noncompliance
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The IRB makes the determination about whether the compliance
is serious or is part of a pattern of noncompliance (continuing
noncompliance).
The IRB then makes a determination about what action is
warranted, including any additional action it deems necessary
to protect the rights and welfare of research subjects
participating in the study.
The IRB must report all determinations of serious or
continuing noncompliance to the federal Office for Human
Research Protections (OHRP), the FDA (if the study is FDA
regulated), and the study’s sponsor (if the project is
sponsored)
Noncompliance
Possible actions:
 Detail corrective action plan
 Education/Re-education
 Modification to the research and/or protocol
 Increased monitoring
 Informing study subjects
 Refer to the Tulane University Research Compliance
Officer for investigation and/or audit.
 Suspension or termination of research
Audits – what to expect
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The Tulane Research Compliance Office conducts not-forcause audits, which means that no specific issue or action
prompted the audit, and for-cause audits as directed by the
IRB. For-cause audits are occur when the IRB has determined
that problems occur on the study necessitating an audit.
Not-for-cause audits can be totally random or targeted.
Examples of studies where a targeted audit my be
appropriate are investigator-initiated studies (due to a lack
of a sponsor, as sponsors provide additional oversight),
high-risk studies, an inexperienced principal investigator, or
a principal investigator with a history of noncompliance.
Audits – what to expect
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Review of Regulatory Binder to ensure that all
necessary documents are included and are up to
date, including:
 Current
training certificates for research staff
 Curriculum Vitae for research staff
 All IRB approved documents, including protocol(s),
informed consent documents, and approval letters
 Delegation of Authority Logs
 Updated Form 1572 (for FDA regulated studies)
Audits – what to expect
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Review of Regulatory Binder (continued):
 All
correspondence to and from the IRB
 Protocol Deviation Report(s) and Unanticipated Problem
Reports(s) (the auditors will be checking to see that such
reports were timely submitted to the IRB in accordance
with SOP Sections 8 and 9)
 All correspondence to and from the sponsor
 All correspondence resulting from site visit by a monitor
(the auditors will be checking that all actions
recommended by the site visitors have been completed)
Audits – what to expect
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Review of participant files:
 Review
that informed consent procedures performed
correctly
 If documentation of informed consent was required by
the IRB, review that the informed consent documentation
was completed correctly and that a copy of the signed
informed consent was provided to the participant
 Documentation that informed consent process was
completed prior to any study specific procedures
 Documentation that participant was provided approved
compensation for participation in the research
Audits – what to expect
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Review of drug and/or device accountability logs
At the end of the interview, the auditors will conduct
and exit interview to review the findings. If you can
correct any deficiencies immediately found by the
auditors, do so (for example, placing missing items
into the regulatory binder).
You will then get a letter from the auditors with the
findings and required follow-up action items, as well
as whether your audit findings will be presented to
the convened IRB for further consideration.
Audits – what to expect
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Audit finding are presented to the convened IRB in
the case of all for-cause audits and all not-forcause audits if significant and/or numerous issues
are found by the auditors.
If the audit findings will be presented to the
convened IRB, you will receive an IRB action letter
regarding whether any further corrective measures
are necessary to correct deficiences.
Regulation of human subjects research
– why is it needed?
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People imprisoned in Nazi Germany during Holocaust
were forced to participate in human experiments – no
informed consent.
Total deaths uncertain, but death toll was very high.
For example, experiments on twins resulted in 1,300
deaths out of 1,500 forced to participate.
Other experiments: freezing point of the human body,
malaria, mustard gas, sterilization, and effects of high
altitude.
Led to the passage of the Nuremberg Code: guidance
(non-binding) on informed consent, minimization of risk
and harm, and the freedom to withdraw.
Regulation of human subjects research
– why is it needed?
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Tuskegee Syphilis Study (1932-1972):
 No
informed consent
 Participants not informed of all known dangers.
 Participants were never told that Penicillin was an
effective treatment for Syphilis, even though Penicillin
became widely known as an effective treatment
beginning in 1947.
 Public outcry following an exposé led to the passage in
1974 of the National Research Act, which contained the
first mandatory human subject protection provisions.
Human Subjects Research Regulations
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5 CFR 46: known as the “Common Rule”. Main body
of regulations for protection of human subjects
participating in research
FDA Regulations:
 21
CFR 50: protection of human subjects
21 CFR 56: FDA IRB Regulations
21 CFR 312: FDA Investigational Drug Regulations
21 CFR 812: FDA Investigational Device Regulations
45 CFR 164.508-514: HIPAA Regulations
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State-specific regulations
Human Research Protection at Tulane
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Tulane’s Human Research Protection Program (“HRPP”)
includes SOPs that incorporate state and federal
regulations, including the “Common Rule”, FDA regulations,
state regulations, and the standards of the IRB’s accrediting
body, AAHRPP. These regulations and standards:
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govern all aspects of human subject research protections
mandates use of IRB to review research proposals and the
composition of the IRB
Tulane HRPP SOPs are published at:
http://tulane.edu/asvpr/irb/policies.cfm
The Tulane Human Research Protection Office (“HRPO”)
administers the IRB
Role of the IRB
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The university has charged the IRB with initial and
continuing review of all human subjects research
occurring under the auspices of the university.
In order for investigators at Tulane to receive
federal funding, the IRB must file a “FederalWide Assurance” (FWA) stating that the IRB is
complying with federal regulations regarding
human subjects research and obligating the IRB to
enforce human subjects protection regulations.
Role of the IRB
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Investigators are responsible for the initial
determination of whether the planned activity
comprises human subjects research (Tulane SOPs
3.3). However, the university, as well as sponsors,
hold the investigator accountable for wrong
determinations.
Investigators should err on the side of caution and
contact the HRPO (irbmain@tulane.edu) for
guidance regarding whether the activity constitutes
human subjects research before commencing their
research.
Role of the IRB
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Possible Repercussions for failure to obtain IRB
approval of human subjects research:
 Prohibition
from using data;
 Prohibition from publishing;
 Reporting to federal oversight agencies
 Subject to filing of a research misconduct
allegation, which can lead to a range of penalties,
including expulsion.
 The
research misconduct policies are located in the
faculty handbook in Part III(H):
(http://tulane.edu/provost/upload/Faculty-Handbook2011-12.pdf )
2-Step process for review of research
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Step 1: Does the activity constitute human subjects
research?
 Look
to prospective intent of the investigator and the
definition of research
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Step 2: If so, does the research qualify for exempt
review, expedited review, or convened (i.e., full)
board review?
Definition of Human Subjects Research
(45 CFR 46 & Tulane SOPs 1.4) :
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Any systematic investigation (including research
development, testing, and evaluation)
On a living individual about whom the investigation is
being conducted
Where the investigator obtains
 Data through intervention or interaction with the
individual; or
 Individually identifiable private information
That is designed to develop or contribute to
generalizable knowledge
Practical Interpretations
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A “systematic investigation” is an activity that involves a
prospective research plan that incorporates data collection,
either quantitative or qualitative, and data analysis to
answer a research question
“Generalizable knowledge” involves studies that are
designed to draw general conclusions (i.e., knowledge
gained from a study may be applied to populations outside
the specific study population), inform policy, or generalize
findings
Federal regulations do not provide a definition for either
“systematic investigation” or “generalizable” knowledge, so
decisions are made on a case-by-case basis
What is Individually Identifiable
Information? (SOP 3.8.5)
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Information where the identity of the subject is or may
be readily ascertained by the investigator, such as:
Name
 Address
 SSN
 Phone No.
 Email address
 Full Face Photo
 Finger Print
 Account Number or any other unique identifying number,
characteristic, or code
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Essential Questions
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Ask yourself the following:
 Am
I trying to answer a research question?
 Am I collecting data through intervention or
interaction with a living individual or collecting
identifiable private information about a living
individual?
 Am I using systematic methods to collect my data?
 Will I write up the results?
 Will the results be readily available to others?
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If yes to all, then the activity likely involves
human subjects research subject to
review/oversight by Tulane’s IRB
Who can serve as Principal Investigator?
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Faculty, Staff, Residents, and Postdocs
Students if a faculty member has agreed to serve
as the students’ faculty advisor for submission to IRB
 It
is the faculty advisor’s responsibility to
 assure
that the research is conducted consistent with
regulations and Tulane SOPs; and
 assure closeout of the study
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CITI training must be taken prior to submission to the
IRB
CITI Training
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All associated with Tulane are eligible for CITI
Training.
Before a submission may be made to the IRB, you
must complete CITI Training:
 https://www.citiprogram.org/
 Biomedical
researchers should complete the
“Biomedical (group 1) Research for Investigators and
Key Personnel” module
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CITI Training modules for responsible animal care
and use and financial conflicts of interest are also
available.
Case Examples
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Now we will look at examples. As you will see, it is not
always a clear cut answer.
The answers to each of these questions depends upon the
facts and whether the researcher is engaging in a
systematic investigation on a living individual about whom
the investigation is being conducted where the investigator
obtains data through intervention or interaction with the
individual or individually identifiable private information
that is designed to develop or contribute to generalizable
knowledge
Is it human subjects research?
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A study comparing cognitive behavior therapy
to medication in treating depression?
 Yes,
this is research, unless the investigator is not
doing anything with the data.
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Focus group study of parenting practices?
 Maybe.
What is the planned use of the data? If
it is a systematic investigation and designed for
generalizable knowledge, then yes. If presented
solely in class, then no. If conducted for quality
improvement within the group, then no.
Is it human subjects research?
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Biomedical research on cadavers?
 No,
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as this would not involve living human subjects.
Study that counts the number of Hispanic surnames in
the voter registry in Orleans Parish?
 No.
Counting names in the voter registry is not a
“systematic investigation”, i.e., an activity that involves a
prospective research plan that incorporates data
collection, either quantitative or qualitative, and data
analysis to answer a research question.
What is not research?
Training exercises that do not produce
generalizable results
 Activities designed for educational purposes
only
 Results of class projects that will not be
published outside the classroom
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 Examples
of publishing outside of the classroom:
magazine articles, master’s thesis, doctoral
dissertation, poster session, abstract, or any other
publication or public presentation.
Quality Improvement studies
 Research involving dead people
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What is publishing?
Look to intent to make the results public.
 Information used only within a class and not
provided outside of the class setting does not
constitute publishing.
 Sharing the information openly with individuals
outside the classroom likely constitutes
publishing, therefore necessitating review.
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Is this publishing?
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As part of a class project, a School of Medicine class collects
data from 10 human subjects to answer a research question.
The results are not intended to be shared outside the
classroom, is this publishing?
 No
If the results are shared via the department’s intranet that is
password protected, does this constitute “publishing?”
 Generally, if the results are confined to limited audience,
this is not considered a systematic investigation that is
designed to develop or contribute to generalizable
knowledge
Example: Research Practica
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Question: A course requires students to undertake projects in
which other people are interviewed, observed, or otherwise
serve as participants. The purpose of these course projects is
to train students and provide them with a closer view of
social, educational, or psychological processes, and an
opportunity to practice various research methods. Is this
human subjects research?
Answer: No. The purpose of the activity is to train students to
conduct research, not for generalizable knowledge. Research
practica are designed to offer students opportunities to learn
various research methodologies through practice.
Example: Thesis or Dissertation
Question: Is research for a thesis or dissertation
considered human subjects research?
 Answer: It depends. A thesis ordinarily
involves a systematic investigation that is
published or made generally available. The
analysis turns on whether data is obtained
through intervention or interaction with
individuals or whether individually identifiable
private information is obtained on a living
person.
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Example: Pilot Studies
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Question: An investigator plans to undertake a preliminary
investigation of the feasibility of a study on a small scale (i.e.,
fewer than 10 subjects), which will be exploratory in nature. It
is designed to help the investigator refine data collection
procedures and instruments to prepare a better, more precise
research design. Is this research?
Answer: No. This study focuses on data collection procedures
and research design. This is akin to quality improvement and is
not human subject research. However, pilot studies intended to
lead to generalizable knowledge are considered human subjects
research.
Example: Video Interviews
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Question: Are video recordings of interviews with
Hurricane Katrina survivors created to preserve or
describe individual experiences to be viewed at a
museum considered “human subject research”?
Answer:
No. The creation of the video recording does NOT intend to
draw conclusions, inform policy, or generalize findings.
 The sole purpose is to create a historical record of specific
personal events related to experiencing the hurricane and
to provide a venue for survivors to tell their stories.
 What if the purpose of the interviews is to create an archive
for future research? Since the intent is to collect data for
future research, IRB review would be needed.
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Assuming Human Subjects Research
Exists, three levels of IRB review
Exempt Review; Expedited Review; Full-Board
Review (as provided for in federal regulations).
 Each level requires a different application.
 Application forms are available on
www.IRBNet.org, the IRB’s electronic submission
system.
 If unsure of what level is required for your
activity, submit query to irbmain@tulane.edu
prior to submitting your application to the IRB.
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What is exempt research?
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Minimal risk studies that fall within set categories listed
in Tulane SOPs 3.5.2.
Shortened application – exempt from further review
Exempt studies do not require convened IRB review and
are reviewed by the IRB chair (or designee).
Exempt research can not include research involving
children or prisoners [Tulane SOPs 3.5.1].
Approval period can be for up to three years, unlike
expedited or full-board review approval periods, which
are for a maximum of one year.
Common exempt studies (SOP 3.5.2)
1. Research involving the collection or study of existing data,
documents, or records where the sources are publicly available.
2. Research 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.
Common exempt studies (continued)
3. Research involving the use of educational tests, survey
procedures, interview procedures, or observation of public
behavior, unless:
 Information obtained is recorded in such a manner that
human subjects can be identified directly or through
identifiers linked to the subjects; and
 Any disclosure of the human subjects responses outside the
research could reasonably place the subjects at risk
What is expedited research?
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Research that is no more than minimal risk to subjects
and that meets the categories listed in Tulane SOPs
3.5
The identification of participants will not place them
at risk of criminal or civil liability or be otherwise
damaging
Review is conducted by the IRB Chair or the Chair’s
designee
Approval period is for up to one year
Categories of expedited research
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The research must fit into one of several specific categories to
qualify as expedited research (see Tulane SOPs 3.6.1).
Common categories include:
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Collections of blood samples by finger stick, heel stick, ear stick, or
venipuncture
Prospective collection of biological specimens for research purposes by
noninvasive means.
Collection of data from voice, video, digital, or image recordings made
for research purposes
Research on individual or group characteristics or behavior (including
research on perception, cognition, motivation, identity, language, cultural
beliefs, social behavior, etc.)
Categories of expedited research
(continued)
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Clinical studies of Drugs and Medical Devices only
when condition (a) or (b) is met.
a)
b)
Research on Drugs for which an IND [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.
Research on Medical Devices for which (i) an IDE [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.
How long does the IRB take to review a
submission?
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Exempt Review:
 1-2 weeks
Expedited Review:
 2-3 weeks
Full Board Review:
 4-5 weeks if approved as submitted
 6-8 weeks if modifications are required by the board and
the PI timely submits the appropriate modifications
The IRB approval letter will contain an expiration date for IRB
approval of the research. Be sure to submit your continuing
review application well in advance of the expiration date.
Critical Points to Remember
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Register with IRBNet in order to submit a protocol to IRB
(all submissions are via IRBNet)
Complete CITI training prior to submission to IRB. All
personnel involved in the project must complete CITI
training.
Be cognizant of the lead time needed for review by the
IRB.
Students need a faculty advisor in order to submit a
protocol.
Do not begin research until you receive the IRB approval
letter (MOST IMPORTANT!).
Critical Points to Remember (cont.)
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Be cognizant of expiration dates for approval of the
study and for approval of the informed consent document.
Most studies are approved for a maximum of one year.
A continuing review application must be submitted far
enough in advance of the expiration date to allow for IRB
review of the continuing review application.
File an amendment if any changes are made to the study.
If activity originally does not involve human subjects
research but your intent changes to include human subjects
research, then make a submission to IRB.
Contact Information
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Research Compliance (Brian Weimer): 504.988.1147;
bweimer1@tulane.edu; Room 2425 of Tidewater Bldg;
http://tulane.edu/asvpr/research-compliance.cfm
Tulane’s Human Research Protection Office (HRPO):
504.988.2665; irbmain@tulane.edu;
http://tulane.edu/asvpr/irb/index.cfm
Tulane human subjects protection policies:
http://tulane.edu/asvpr/irb/policies.cfm
Instructions for taking CITI Training:
https://tulane.edu/asvpr/irb/index.cfm