11/9/2015
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Do I need IRB review for this?
Understanding the IRB ladder.
Galen Basse, Compliance Analyst Manager
UW Human Subjects Division (HSD)
November 2015
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Goals for today
 What
am I learning?
What is research with human subjects?
 Different levels of review
 Human subjects regulations basics

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 Why
am I learning it?
 How
will I know when I’ve learned it?
 How
will I use it in the future?
Huge caveat to a lot of what I’m
about to say
 The
Office for Human Research Protections (OHRP)
released a Notice of Proposed Rulemaking (NRPM)
in October 2015 that outlines changes to the federal
regulations that govern human subjects 45 CFR 46,
aka “The common Rule”
 Lots
 We’ll
and lots of non-trivial changes
return to this later, time permitting
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“The Big Four”
45 CFR 46
HIPAA
FDA
WA State
“The Big Four”
HIPAA
45 CFR 46
WA State
FDA
Our focus: The Common Rule (HHS/OHRP)
• 45 CFR 46: The set of federal regulations that govern research with human subjects.
• FDA, HIPAA, RCW: Non‐IRB
IRB
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Why are the regulations they way they are?
‘Monster’ study 1939
Milgram Studies 1960s
Tearoom Trade Study 1970s
Willowbrook Hepatitis Study 1950s
Nuremberg Trials/Nuremberg Code* 1947
National Research Act 1974
Thalidomide Experiment 1962
Declaration of Helsinki* 1964
Beecher “Ethics and clinical research” (1966)
National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research
Tuskegee Syphilis Study 1930s‐70s
The Belmont Report 1978
(*Foundational documents to the OHRP regs)
• Respect for Persons
– Protect autonomy
– Treat people with courtesy and respect – Obtain consent
– Be truthful
• Beneficence
Ethical code of conduct for research that helps inform how and why the regulations were written – Do no harm
– Maximize benefits
• Justice
– Fair distribution of costs and benefits
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HHS/OHRP:
The Common Rule (45 CFR 46)
Human Subjects Research
45 CFR 46
Is it full board?
Is it expedited?
Is my institution engaged?
Is it exempt?
Is it research with human subjects?
Is it research?
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The IRB ‘Ladder’
IRB
Review
Full board review
Is it expedited?
Is my institution engaged?
Is it exempt?
Is it research with human subjects?
Is it research?
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Seriously, how do I
know if I need IRB
review?
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You need IRB review if your
institution is engaged in non-exempt
human subjects research
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Walk up the IRB ladder
 Is it research?
 If not, IRB review is not required.
 Is it research with human subjects?
 If not, IRB review is not required
 Is it exempt?
 If so, IRB review is not required
 Is my institution engaged?
If not, IRB review is not required
 Does the application qualify for expedited review?
If not, review by the convened IRB
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Is it research? 45 CFR 46.102(d)
 Research
is “a systematic investigation,
including research development, testing
and evaluation, designed to develop or
contribute to generalizable knowledge.”
 Usually
the researcher makes this
determination. Call your IRB office!
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Publication
 Q:
Does the intent to publish or present the
information make it “generalizable”?
 A:
No. “Generalizable” does not refer to where or
how the information is shared.
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Is it research under
45 CFR 46.102(d)?
Program evaluation
Quality assurance project w/ plan to
publish results
 Case reports
 Oral histories
 Class projects
 Dancing like a robot on the street
and talking to passersby


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Is it research with human subjects?
45 CFR 46.102(f)
 Human subject = a living individual about
whom an investigator conducting research
obtains:
1) Data through interaction or intervention;
or
2) Private, identifiable information
 Usually the IRB office makes this
determination
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Is it research with human subjects?
Why or why not?
 Interview
with university president. Questions are
about the number of undergraduates enrolled,
budgeting, and how the university attracts faculty.
 Obtaining
data that is publicly posted online (e.g. FB,
Twitter, etc.).
 Interviewing
individuals about the health issues of
their now-deceased spouses.
 Medical
records review (no contact with patients)
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Is it exempt?
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Exemptions
45 CFR 46.101
 This
is human subjects research but it doesn’t
require IRB review
 IRB
6
office makes this determination
categories of research
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Types of exempt research
 Category
1: Research on normal educational practices
in normal educational settings
 Category
2: Surveys and interviews with very low risks
to subjects.
 Disqualified from exemption if the survey/interview
data are sensitive and identifiable
 Existing
records where identifiers are not extracted
(cat. 4). Does not include medical records in WA state.
 Category
6: Food/taste evaluations with healthy foods
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Engagement
Is your
institution
engaged?
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Engagement
Comes
into play for multi-site studies
Certain
types of involvement do not
require IRB review (i.e. the institution is
‘not engaged’)
Resource:
Call
OHRP guidance
your IRB office!
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If your institution is engaged in nonexempt human subjects research…
Full board review
IRB
Review
Is it expedited?
Is my institution engaged?
Is it exempt?
Is it research with human subjects?
Is it research?
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IRB review
 Expedited
aka ‘minimal risk’ IRB review
 Minimal
risk: probability and magnitude of harm or
discomfort anticipated are not greater than those ordinarily
encountered in daily life or during the performance of
routine physical or psychological examinations or tests
7
categories (mostly method-based, some topic-based)
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IRB review continued…
 Greater
than Minimal Risk
IRB review by convened IRB (“full board review”)
 Board must have at least 5 voting members with
varying backgrounds (race, gender, culture) and
appropriate expertise

 IRB
can:
Approve
 Conditionally Approve
 Defer
 Disapprove
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Criteria for IRB approval*
 Risks
are minimized
are reasonable in relation to anticipated
benefits
 Selection of subjects is equitable
 Informed consent will be obtained or waived
 Informed consent will be documented (unless
documentation of consent is waived)
 Protect privacy and confidentiality
 Provisions for monitoring of data to ensure safety
 Extra protections for vulnerable populations (those
with decreased autonomy)
 Risks
+Belmont Principle
Criteria for approval




Respect
for Persons
Obtain informed consent
Document informed consent
Protect privacy/confidentiality
Additional protections for vulnerable
populations
Beneficence
 Minimize risks
 Balance risks and benefits
 Monitor data to ensure safety
Justice
 Equitable selection of subjects
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Protected Populations
Subjects
with diminished autonomy:
Pregnant women, fetuses
Non-viable neonates; neonates of
uncertain viability
Prisoners
Children
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Consent basics
 Written
documentation of consent
 Standard
 Waiver
of documentation of consent
 Consent
 Waiver
 Omitting
 Waiver
 No
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process, no signature
of elements of consent
certain pieces of information
of consent
consent at all
Waiver of documentation of consent
(1)
Study does not involve more than minimal risk; and
(2)
Study does not involve any procedures for which written
consent is normally required outside the research context
(1)
The only record linking the subject and the research would be
the consent document; and
(2)
The principal risk would be potential harm resulting from a
breach of confidentiality. (Each subject must be asked
whether the subject wants documentation linking the subject
with the research; the subject's wishes will govern.)
- or -
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Waiver of (elements of) consent
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.
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General tips

Make sure the application is complete and consistent! For
example: identify any necessary waivers and include
them in your submission; ensure that the consent form
contains all required elements.

Understand the level of review required

Include a complete description of the procedures

Answer every question, even if the answer is ‘NA’ or
‘Zero’

Avoid too much technical jargon – use plain language.

Plan ahead, leave enough time for review
Back to the enormous caveat
Date
Event
1974
US regulations published
Early 1980s Revision
1991
Revision
2015
Proposed Revision
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Goals
Respect for persons
Beneficence
Justice
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Major changes
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De-identified biospecimens will be considered
“human subjects”
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Exclude classes of activities from regulations
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Exempt categories increased
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New consent requirements (info, process)
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Single IRB for multi-site clinical trials
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Status reports not required for minimal risk studies and
completed studies doing only data analysis
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Many others…
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Revision timetable
Date
Event
Sept 8, 2015
NPRM: Proposed revisions published
December 7, 2015
Public comment period ends
Unknown
(months, years)
Publication of the Final Rule
(official revised regulations)
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Implementation timetable
Date
Unknown
90 days later
1 year later
3 years later
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Event
Publication of the Final Rule
Voluntary implementation allowed
Goal: Reduce regulatory burden as soon as possible
General effective date
(see exceptions below)
Later effective date for:
 Biospecimens regulations
 Single IRB for multi-site clinical trials
So what do I do now?
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NPRM, cont.
 Required:
Nothing
 Optional
 Learn
more about the changes
 OHRP: http://www.hhs.gov/ohrp/humansubjects/regulations/nprmhome.html
 Summaries
from professional organizations
Webinars
 Submit a comment to OHRP. Why not, right?
 Stay informed!
 OHRP
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