Human Subject Protections in NIH SBIR STTR Applications

Report
Human Subjects Protections
in NIH SBIR/STTR Applications
Ann Hardy, DrPH
NIH Extramural Human Research Protection Officer
Office of Extramural Programs (OEP), OER
SBIR Conference October 21-23, 2014
Learning Objectives
After this presentation, you will:
• Understand the regulatory basis for human
subjects protection in research
• Define human subjects research and apply the
regulations to common research designs
• Distinguish exempt and non-exempt human
subjects research
• Understand the human subjects requirements
for NIH applications and awards
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HHS Regulations
• 45 CFR part 46: Protection of Human
Research Subjects
– Subpart A - Basic Requirements for Protection
– Subpart B, C, D – Additional protections for Pregnant
Women/Fetuses/Neonates; Prisoners; Children
– Subpart E – IRB Registration
Office for Human Research Protections (OHRP) is
responsible for ensuring compliance
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45 CFR 46 - Subpart A
Applicability
Key Definitions
Sponsoring Agency Responsibilities
Institutional Responsibilities
– Assurance (FWA)
– Institutional Review Board (IRB)
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Do The Regulations Apply to My Project?
Does activity involve Research?
Does research involve Human Subjects?
If yes, is human subjects research Exempt?
ASK QUESTIONS IN THIS ORDER!
Human Subject Regulations Decision Chart:
http://www.hhs.gov/ohrp/policy/checklists/decisioncharts.html
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Definition of Research
• Research – a systematic investigation
designed to develop or contribute to
generalizable knowledge
– includes research development, testing,
evaluation, pilot studies
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Definition of Human Subject
• … a living individual
• about whom an investigator (professional or
student) conducting research obtains
– Data through intervention or
interaction with the individual
OR
– Identifiable private information
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Definition Deconstructed
•
a living individual
– Regulations do NOT apply to
research involving materials from
deceased individuals
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Definition Deconstructed
• about whom an investigator
conducting research obtains
– Data through intervention or interaction
Examples:
Collect biological samples (blood)
Administer a questionnaire
Conduct MRI
Manipulating environment and
noting response
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OR
Collected
for THIS
Research
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Definition Deconstructed
–Identifiable Private Information
Identity of subjects can be readily ascertained by
ANY of the investigators
Name or Unique # linked to name
Collected
for
OTHER
purpose
- Who is an investigator?
- Anyone involved in conduct of the research (study,
analysis, interpretation of research data, coauthorship). Does NOT include providing info or
samples.
•
OHRP guidance on coded info and specimens
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Definition Examples
• PI will use materials from a brain bank;
donors consented prior to death for materials
to be used for research
Not human subjects research because the federal
regulations only apply to living persons
• PI will purchase tissue from commercial
vendor
Not human subjects research because not collected for
research and no identifiers
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Definition Examples
• At time of clinical blood draw, an extra tube
of blood is collected for research
– Yes, because this tube is being collected
specifically for research. This is different from
using left-over blood that was collected for
clinical reasons.
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Is the Human Subjects Research
Exempt?
Exempt
6 categories of human
subjects research
activities that are so low
risk, they are EXEMPT
from the regulations
Non-Exempt
All other human
subjects research is
classified as NONEXEMPT HUMAN
SUBJECTS
RESEARCH
About 13% of SBIR/STTR awards that involve
human subjects are exempt
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Categories of Exempt Human Subjects
Research
(1) Research in educational settings on educational practices
(2) Educational Tests, Surveys, Interviews… (not if ID and
info disclosure put subject at risk; parts not applicable to
research w/ children)
(3) Tests, Surveys, Interviews with public officials, or if federal
law requires confidentiality
(4) Collection/Study of existing data, specimens if recorded
by investigator in way subjects cannot be identified
(5) Research approved/conducted by Federal Agencies on
public benefit programs
(6) Evaluation of taste or food quality
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Exemption 1
Research conducted in educational settings on
educational practices such as instructional strategies,
techniques, curricula ….
• Examples:
– Study to determine effectiveness of on-line training as
supplement to regular instructional approach for teaching
anatomy to medical students.
– Study to determine effectiveness of planned activities to
increase the public’s awareness of oral health to be
delivered at a community science museum.
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Exemption 2
Research involving use of educational tests,
surveys, interviews or observation of public
behavior unless ID AND disclosure could harm
• Examples:
– Focus group to discuss general barriers to use of
community health centers
• Some parts not applicable to research with
children
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Exemption 4
• Research involving the study of existing
data, documents, records, specimens if
publicly available OR info recorded by the
investigator in manner that subjects
cannot be identified directly or indirectly
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Research Involving Coded
Data/Specimens
• OHRP Policy Guidance 2008: http://www.hhs.gov/ohrp/policy/cdebiol.html
• Research involving only use of coded data/spec from living
individuals is NOT human subjects research IF
– Info/spec not collected for proposed research
AND
– Investigator(s) cannot readily ascertain identity of subjects
• Provider will not to share ID w/ investigator
• Written policies prohibiting release of ID (repositories)
• Clarified that most research with existing data/specimens
– Not HS research (no one has ID’s) OR
– Non-exempt (investigator has ID’s)
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Tricky Issues in Applying Guidance
• Who is an “investigator”
– Anyone involved in any aspect of the research
• Only providing data/spec is not “involvement”
• Assisting w/ data analysis or interpretation,
authorship is involvement
• PI involved in primary collection or associated w/
repository
• NO circumstances where investigators could identify
• “Excess” clinical samples
• When is E4 applicable?
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Exemption 4
• Research involving the study of existing
data, documents, records, specimens if
publicly available OR info recorded by the
investigator in manner that subjects
cannot be identified directly or indirectly
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When is E4 Applicable?
• For E4
– Investigator initially obtains identifiable info/specimens
AND
– “Records the data in such a manner that subjects cannot
be identified” – break link
• Examples
– PI accesses identifiable data but extracts research data
w/o identifiers that can no longer be linked back.
– PI goes through set of existing excess clinical samples to
identify those of interest. She removes label with
identifiers and marks tubes with random number and basic
non-identifiable clinical info.
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Expert Advice and
Product Testing
• Using expert consultants to improve research
design or advise on research process – NOT
research
• Persons to test a new product to identify flaws –
NOT human subjects research
• Pilot test of new product
– May be human subjects research if collecting data
about individuals and/or identifiable private info
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Examples
• Computer design experts will review your
software product to identify flaws and overall
usability (colors, font, readability, navigation)
– Probably not research
• Conduct a small pilot study of your survey
system with end users.
– It Depends
• You ask patients to wear your new prosthetic
device and provide feedback
– Is HS research
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Is it Human Subjects Research?
• Ask Questions in THIS ORDER
1/Does it meet the definition of human
subjects research?
Data through intervention or interaction OR
Identifiable private information
Living
Subjects
• For secondary use of specimens/data
– Who are investigators; is provider an investigator?
– Who has access to identifiers or can link?
If No, NOT Human subjects research (STOP)
2/If Yes, do any of the Exemptions apply?
• Yes: Exemption #
• No: Non-exempt human subjects research
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Sponsoring Agency
Responsibilities
Regulations require
Agencies to evaluate
applications and
proposals involving
human subjects:
4.
1.
2.
Risks subjects
Adequacy of protections
3.
Benefits
Importance of knowledge to be gained
• NIH evaluates through peer review
• No funds expended unless regulatory requirements
are met; can withdraw funding for non-compliance
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Human Subjects Section of Grant
Application
• Risks to Human Subjects
– Human subjects involvement and characteristics
• Demographic and health characteristics
• Inclusion and exclusion criteria
• Rational for involvement of vulnerable populations
– Sources of materials
• What materials (specimens, records, data)
• How will materials be collected
• Who has access to information
– Potential Risks
• Physical, psychological, financial,
legal or other risks
• Alternative treatments/procedures
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Human Subjects Section (con’t)
• Adequacy of Protection Against Risks
– Recruitment
– Informed consent
• Children – assent; parental permission
• How consent will be obtained; info provided
– Protections against risk
• Procedures to minimize risk; protect privacy and
confidentiality
• Additional protections for vulnerable populations
• Ensure necessary medical/professional intervention
• Data and safety monitoring
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Human Subjects Section (con’t)
• Potential Benefits of Research to Human
Subjects and Others
– May not be direct benefit to subjects
– Compensation is not a benefit
– Discuss risks in relation to anticipated benefits
• Importance of Knowledge to be Gained
– Discuss in relation to risks
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Preparing the Human Subjects
Section
• All proposed research will fall into one of
six scenarios:
A. No Human Subjects
B. Non-Exempt Human Subjects Research
C. Exempt Human Subjects Research
D. Delayed-Onset of Human Subjects Research
E. Clinical Trial
F. NIH-defined Phase III Clinical Trial
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Scenario A: No Human Subjects
Are Human Subjects Involved? ___ Yes

____ No
• Provide clear justification if using human specimens
or data
• Only post-mortem samples will be used
• Samples will be purchased from a commercial vendor
and will be provided without identifiers
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Scenario B: Non-Exempt Research
Are Human Subjects Involved?
Research Exempt?
Clinical Trial?
NIH-Defined Phase III CT?

___ Yes
___ Yes
___ Yes
___ Yes
___ No
___ No
___ No
___ No



• Human Subjects Section- no page limitations
– Address 4 required points (risk, protections, benefits,
knowledge)
• Inclusion of Women and Minorities
• Planned Enrollment Tables
• Inclusion of Children
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Scenario C: Exempt Research
Are Human Subjects Involved?
Research Exempt
Exemption Number (mark all)
Clinical Trial?
NIH-Defined Phase III CT?


___ Yes
___ No
___ Yes
____No
__1 __2 __3 __4 __5 __6
___ Yes
___ No
___ Yes
___ No


• Human Subjects Section
– Justify selection of exemption(s)
– Sources of research materials
• Inclusion of Women and Minorities*
• Targeted/Planned Enrollment Tables*
• Inclusion of Children*
* Not required for Exemption 4
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Scenario D: Delayed Onset HS
Research
Are Human Subjects Involved?
Research Exempt?
Clinical Trial?
NIH-Defined Phase III CT ?

____ Yes ___No
____ Yes ___No
____ Yes ___No
____ Yes ___No
Mark as
applicable
• Delayed Onset: Human subjects research anticipated but
• Specific plans cannot be described (45 CFR 46.118)
• Human Subjects Section – explain why delayed onset
• If funded, you will have submit human subjects section, FWA
and IRB approval before involving human subjects
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Scenarios E & F: Clinical Trial
• Clinical Trial: Prospective research study designed to
answer questions about biomedical or behavioral
interventions
•
NIH Defined Phase III Trial: broad-based, prospective
trial, often to provide scientific basis for change in health
policy or standard of care
(Scenario F)
• All other Phases (Scenario E)
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Scenario E: Clinical Trial
(not Phase III)
Are Human Subjects Involved?
Research Exempt?
Clinical Trial?
NIH-Defined Phase III CT?


___ Yes
___ Yes
___ Yes
___ Yes
___ No
___ No
___ No
___ No


• Provide information required for Scenario B (NonExempt Human Subjects Research)
• Must have a Data and Safety Monitoring Plan
• May need Data and Safety Monitoring Board (DSMB)
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Scenario F: NIH-defined
Phase III Clinical Trial
Are Human Subjects Involved?
Research Exempt?
Clinical Trial?
NIH-Defined Phase III CT?



___ Yes
___ Yes
___ Yes
___ Yes
___ No
___ No
___ No
___ No

• Provide information required for Scenario E
• Generally requires Data and Safety Monitoring Board
(DSMB)
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Inclusion of Women,
Minorities, and Children
By law, Women and
Minorities must be
included in clinical
research studies; in Ph
III CT in numbers
adequate for valid
analysis
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By NIH policy, children should
also be included in human
subjects research unless
scientific/ethical reasons
(NOTE: Children are < 21
years)
NOTE: difference between
children according to HS
regulations and children
according to inclusion policy
NIH Uses Two Definitions for Children
• For purposes of human subjects
protection: Children are persons who have
not attained the legal age of consent for
research treatment/procedures where
research will be conducted.
• For the purposes of inclusion:
Children are individuals under
the age of 21.
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Inclusion of Women,
Minorities, and Children
• Cost or convenience is NOT an acceptable reason for
exclusion
• Inclusion should be tied to scientific goals of project
• Enrollment tables (recently revised)
http://grants.nih.gov/grants/funding/women_min/women_min.htm
http://grants.nih.gov/grants/funding/children/children.htm
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Planned Enrollment Report
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For Internal NIH Use Only
Peer Review of HS and Inclusion
• Each reviewer assesses human subjects
protections and inclusion
• Peer review group will determine overall rating of
“acceptable” or “unacceptable”. May affect overall
score
– 24% SBIR/STTR applications involving HS are
deemed Unacceptable vs 18% overall
• Summary Statement: will note Unacceptable on
front page; nacceptable for HS or inclusion is bar
to funding
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What Happens to Grants with Unacceptable
Code for Human Subjects?
• For grants in the fundable range:
– PI submits written response
– After Program Officer approves response,
submit request to OEP for review and code
change
– OEP reviews entire Human Subjects plan
• OEP concurs
• OEP may request additional information
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Common HS Concerns
• Source of existing specimens/data; missing or inadequate
justification for no human subjects research
• Risks -physical, psychological, reputation, employability,
financial, etc.
• Missing/inadequate Data & Safety Monitoring Plans for
Clinical Trials
• Confidentiality of data
• Inadequate protections for vulnerable populations
• Coercive recruitment
• Incidental findings not addressed
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Institutional Responsibilities:
FWA
• Documents institution’s
commitment to regulations
• Designate a registered
Institutional Review Board
(IRB)
IRB
Reviews/approves proposed
research and on-going
research at least annually
&
• FWA and IRB approval required for funded institutions
and sites engaged in human subjects research (just-in
time) (http://www.hhs.gov/ohrp/policy/engage08.html)
• For cooperative projects, may rely on single IRB
(http://www.hhs.gov/ohrp/assurances/forms/irbauthorizpdf.pdf)
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Additional NIH Award
Requirements
• Certification that Key Personnel have
completed appropriate human subjects
research education
– Protecting Human Research Participants
Tutorial: http://phrp.nihtraining.com/users/login.php
• Annual IRB approval
• Update Inclusion enrollment in annual
progress report
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Cumulative Inclusion Enrollment Report
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For Internal NIH Use Only
Human Subjects Resources
• Office of Extramural Research Human Subjects Web site:
http://grants.nih.gov/grants/policy/hs/index.htm
• OHRP Web site:
http://www.hhs.gov/ohrp/
• Coded Information/Specimens Resources
http://www.hhs.gov/ohrp/policy/cdebiol.html
http://www.youtube.com/watch?v=yp5GzAmXlPM (VIDEO)
– OER Flow Chart Code Specimen Guidance
http://grants.nih.gov/grants/policy/hs/PrivateInfoOrBioSpecimensDe
cisionChart.pdf
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Contact Information
Email: [email protected]
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