Workshop on the Protection of Human
Subjects in Research
Texas Christian University
August 24, 2012
Brian Gladue, PhD, CIP
Director, Office the Protection of Human Subjects (OPHS)\
Chair, Institutional Review Board (IRB)
Human Research Subject Protection
Human Research Protection
Program:
an organization-wide system to
assure comprehensive and farranging protection of human
subjects in research
•
Human Research Subject
Protection…Why is it important?
• Historical Basis/Core Principles of Ethical Research
• Federal Regulations and Laws Protecting Human
Subjects
• University Commitment to Sound Ethical Practices and
Research
Ethical Research = Quality Research
Federal Regulation & Law
In USA, human subject protection regulated by Federal Law
(CFR)
• FDA:
21 CFR 50, 56• Drug & device rules (IND, IDE, HDE, etc.)
• OHRP: 45 CFR 46 –
• Rules for review of studies, Education of IRB members
• Adequate IRB staff, appropriate investigator training
• Implementation of Belmont Report Principles
At the “local level” the IRB is mandated by federal law
to oversee human subject research
Roles of an IRB…
• Protect Human Subjects
• Assure that the Institution (and its investigators,
students and staff) are “in compliance” with
federal human subject research regulations /
state law / university policies
• Assist Investigators to
Enhance the Research Enterprise
• “The IRB (and IRB Office) is Your Friend”
University Commitment and Policy
ALL research projects involving human subjects require a priori review by the
Department Review Board (DRB), and subsequently, by the university’s
Institutional Review Board (IRB).
FWA (FederalWide Assurance)…an agreement by TCU with the federal
government to comply with the requirements of the Department of Health and
Human Services (HHS) Protection of Human Subjects regulations, 45 CFR part
46 when conducting human subject research.
University’s FWA and commitment to human subject protection includes all
university personnel (students, staff, faculty) … no matter where they are
conducting research (on or off-campus).
Is it Research involving Human Subjects?
• Research
A systematic investigation, including research development, testing and
evaluation, designed to develop or contribute to generalizable knowledge.
• Human subjects
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.
• Benefit: A valued or desired outcome; an advantage.
• Risk: The probability of harm or injury (physical, psychological, social, or
economic) occurring as a result of participation in a research study. Both the
probability and magnitude of possible harm may vary from minimal to significant.
Federal regulations define only "minimal risk.."
• Vulnerable Populations: Populations, such as children, prisoners, pregnant women,
mentally
disabled persons, or economically or educationally disadvantaged persons.
How do I know if what I am doing is “Research” and
needs IRB review and Approval ?
1. Publish If you plan to publish your inquiry (even if it is 10 years from now), IRB
review and approval is required.
2. Present If you think you will present your data at a professional meeting,
conference, or setting, including local research presentation events now
or in the future, IRB review and approval is required.
3. Recognition or Promotion If you want your research or achievements as an
investigator) recognized by someone such as your Department Head,
Dean, or Major Professor, IRB review and approval is required.
4. Graduation If your project will be used for a degree program (Masters,
Dissertation, Honors project, etc.) or to meet the requirements of a
residency program, IRB review and approval is required.
WHO decides what is / isn’t “Research” that would
need IRB review and Approval ?
The investigator is not the “final decision maker" as to whether or
not something is research...
Departmental Review Boards can assess the scientific merit,
attention to regulatory aspects, operational issues and general
“do-ability” of a project…
TCU policy and procedures (and good ethical practice) is for an
independent group to make the overall “research”
determination…in this case, the IRB is that group
General “rules of thumb”:
• If you think your project is (research)...then it probably is...
• If you are not sure...it probably still is (research)…
• and if you think it is NOT...confirm that with the IRB
In any case, the IRB makes the call
So, if we decide it is research…what is the
harm?
Determining if a study is “minimal risk”…
Federal Definition:
Minimal Risk: "the probability and magnitude of harm or discomfort
anticipated in the research are not greater in and of themselves than
those ordinarily encountered in daily life or during the performance of
routine physical or psychological examinations or tests" (from 45 CFR
46.102(i)
When making a decision about minimal risk of research:
Two Kinds of “Risk” to be Managed:
• Procedural Risk – associated with the actual process or procedures
associated with the study
• Informational Risk: breach of privacy, confidentiality risk, document
access, risk of embarrassment and other “risks” related to how
sensitive information is stored, accessed, managed.
Why is determining “minimal risk” important?
Regulations specify that EXEMPT category projects must be
minimal risk…also
EXPEDITED category projects must be “minimal risk”…
If it is more than minimal risk…then it goes to a convened meeting
of the IRB.
On
Once again: Minimal Risk: "the probability and magnitude of harm or discomfort
anticipated in the research are not greater in and of themselves than those
ordinarily encountered in daily life or during the performance of routine physical or
psychological examinations or tests" (from 45 CFR 46.102(i)
Evaluating Scientific Merit and
Research Design
• 45 CFR 46 §46.111 Criteria for IRB approval of research.
(a) (1) Risks to subjects are minimized: (i) by using procedures which
are consistent with sound research design and which do not
unnecessarily expose subjects to risk
Currently, OHRP determinations rule that the IRB is the ONLY body
authorized to make this evaluation for a given protocol.
A departmental or college level “scientific review committee” may “OK” a
research study or design…but if the IRB determines that study
design is an issue or concern, it must be addressed prior to approval.
Review of Human Subjects Research
 Exempt
 Expedited
 Full Board
 Continuing Review
 Amendments
Exempt Category Research
Language can be tricky…“Exempt” does NOT mean what
you think it does…
In the language of the IRB (and the Federal government) Exempt category research
means that the project is “Exempt from Full Board Review”, but at most institutions
(including UNTHSC and TCU) the protocol
STILL HAS TO BE REVIEWED AND CERTIFIED BY A INSTITUTIONALLY
DESIGNATED GROUP (USUALLY THE IRB) THAT THE PROJECT MEETS
FEDERAL CRITERIA FOR “EXEMPT” STATUS…
• Minimal risk
• Falls under of the categories listed by the Federal Regulations
…once approved, the project is then EXEMPT from further IRB surveillance and
consideration
Some Examples of Exempt Research
• Secondary analysis of de-identified data (e.g., publically
available databases, vital statistic records, student records,
etc.)
• Anonymous surveys or interviews
• Analyses of discarded pathological specimens without
patient identifiers (retrospective analyses)
• Retrospective Record or Chart Review (no use of a master
list of identifiers)
“Expedited” Research
In IRB parlance , “Expedited” does NOT mean fast, streamlined or
quickly reviewed (although it can be).
EXPEDITED research refers to protocols that are no more than minimal
risk and are also not exempt category research, but can be reviewed
by an “Expedited Review Procedure”…where one or more
experienced IRB members designated by the IRB Chair review the
protocol
AND from a list of specially (9) designated categories of research
published in the Federal Register
Some Examples of Expedited Research
• Studies involving the collection of hair, saliva, or
dental plaque samples,
• Studies of blood samples from healthy subjects,
• Studies of existing pathological specimens with
subject identifiers
• Focus group studies
• Retrospective Chart Reviews with a master list
• Prospective Chart Reviews
• Analysis of audio or video recordings
Full Board Review
• Everything else…and all research that is “more
than minimal risk”
IRB Protocol Review process…
Departmental review (if offered)
Pre-Consultation with the IRB Office (where available)
Submit IRB Application
• IRB Form
• Protocol Synopsis
• Consent Document(s)
• Related documents: recruiting materials, ads, survey
questionnaires, etc,
Pre-review by IRB Staff (time permitting)
IRB Review : Chair (Exempt/Expedited), convened Board (“Full”)
Determination / Approval
IRB Full Board Review…Determination
Discussion by IRB members: summary and Pre-review
Principal Investigator Presentation / Discussion / Q & A
Follow-Up Discussion by IRB Members
• Level of Risk
• Special Findings
• Technical Findings
Determination:
•
•
•
•
APPROVAL with no changes
APPROVAL CONTINGENT on minor (technical) modifications
DEFER (many modifications / significant changes needed)
DISAPPROVE (study not do-able in present form)
After the Approval…
Continuing Review … protocols can only be approved for one year (or
less)…often called “Progress Reports”
Final Report (Close-Out)…submitted at any time
Amendments / Modifications to a protocol…any change to the IRBApproved protocol (or consent forms, or any aspect of the research
project) must be approved by the IRB prior to implementation
Protocol Exception (requests)…seeking IRB approval for a “onetime”/rare deviation from the protocol BEFORE implementing it
Protocol Violations (Deviations)… an unauthorized change in protocol
or documentation [ AVOID – but report to IRB immediately if it
happens].
Unanticipated Problems / Serious Adverse Event (SAE) Reports
Being the Principal Investigator
Key Responsibilities…
 Research Project Manager: Direct initiation and coordination,
supervision of all aspects of the research project
 Personnel Manager: Training, supervision and management of all
personnel associated with the research project, especially
student projects
 Compliance Manager: Need to meet all university, state and federal
laws, policies and regulations.
In a phrase: “The Principal Investigator is responsible for
Everything!”
Being the Principal Investigator
Other Responsibilities
Need to “think through and develop” an effective and ethical
Research Protocol
Record retention (especially consent forms)
Hold for a minimum of 3 years after project ENDS
Crafting “correct” Consent Form(s)
Subject recruiting schemes, ads, flyers, documents
Discussion Items:
Subject Fees and Incentives
• Fair and Balanced (a good thing)
• Coercive / Unduly Influential ( NOT a good thing)
• Follow institutional policy (ALWAYS a smart thing)
Changes to Protocols must be approved by IRB
prior to implementation … watch out for
ambitious / creative students and staff
ambitious
Tips and Suggestions on
working with an IRB
Key Points for IRB Submissions…
Tips for Successful reviews (minimizing approval delays):
1. Write clearly and accurately – step by step process, listing, bullet
points, flow charts, etc.
2. Think of research needs first before fitting the design to a “standard”
protocol template
3. Include all needed documentation – approval from recruitment sites,
ads, web links, letters of support from key stakeholders (sample
providers, affiliated agencies, etc.)
4. Allow enough time for review…build in time for a possibly higher level of
review, modification or design changes
Key Points for IRB Submissions…
When drafting your protocol ask yourself…
WHO?
WHAT?
WHEN?
WHERE?
WHY?
AND
HOW?
Additional Tips
• Discuss materials, recruitment flyers, and instruments in the Protocol,
Application, and Consent Form!
• Describe study variables and identifiers data security/ confidentiality
& management…if it’s de-identified, describe de-identification process
• Use simple language (at 8th grade reading level) in the consent form
• Use consistent “person” in the consent form.
• Watch for grammar and typographical errors that affect
comprehension (& avoid jargon and awkward prose).
Additional Tips (cont.)
• Provide enough information about the study so that IRB staff and
IRB members (who may not be experts in your field) will know what
the investigators want to do.
• Provide all needed signatures (student, faculty, etc.)
• Obtain a Pre-review /Approval from DRBs before sending to the IRB
Take Home Message # 1
Doing Human Subject Research? Whatever is planned, it’s going to
need IRB REVIEW
TCU’s FWA and commitment to human subject protection includes all
university personnel (students, staff, faculty)…no matter where they
are conducting research (on or off-campus).
Failure (of ALL personnel) to submit
protocols to IRB for evaluation jeopardizes the
entire University!
Take Home Message # 2
(The End All Be All)
“The Principal Investigator is Responsible for
Everything...”
Take Home Message # 3
The IRB is your friend…and is a key component in
enhancing the research enterprise while protecting
human subjects (as well as investigators) …