Post on 27-Jun-2020
transcript
Dawn Corbett (NIH/OER)
Protection of Human Participants in NIH Research
Goals
• Understand the regulatory basis and requirements for human subjects
protection and inclusion in research
• Define human subjects research and understand exempt and non-exempt
research involving human subjects
• Gain clarity about which requirements apply to different types of human
subjects studies;
• Recognize NIH post award reporting requirements for research involving
human participants
SLIDE | 2
HHS Regulations
45 CFR part 46: Protection of Human Research Subjects
• Subpart A (“Common Rule”) – Basic Requirements for Protection**
• Subpart B, C, D – Additional protections for Pregnant Women/Fetuses/Neonates; Prisoners; & Children
• Subpart E – IRB Registration
• The Office for Human Research Protections (OHRP) is responsible for ensuring compliance.
• Revisions to the Common Rule were published on 1/19/17, with a general implementation date of 1/19/18. After subsequent delays, general compliance date: 1/21/2019
3
Three Pillars of Human Subjects Protections Under the Common Rule
1. Institutional Assurance of Compliance (Federalwideassurance – FWA)• Documents institution’s commitment to protecting the
rights and welfare of research subjects2. Institutional Review Boards (IRB) Review
• Oversees and reviews research by an independent committee with diverse knowledge and perspectives
• Reviews and approves non-exempt human subjects research according to criteria laid out in the regulations
3. Informed Consent• Respects research subjects’ autonomy to participate or
not• Helps protect subjects’ interests
4
When Do the Regulations Apply?
To determine if your project is non-exempt human subjects research…
Ask these questions in this order:1) Does the activity involve research?
2) Does the research involve human subjects?
3) Is the research with human subjects exempt?
5
Human Subjects Research
ResearchA systematic investigation, including research development, testing, and evaluation, designed to develop or contribute to generalizable knowledge
Does not include: Certain scholarly and journalistic activities; certain public health
surveillance activities, collection and analysis of information, specimens, or records, by or for a criminal justice agency for certain criminal justice or investigative purposes, and certain authorized operational activities for national security purposes
A living individual about whom an investigator conducting research(1) Obtains information or biospecimens through intervention or
interaction with the individual, and uses, studies, or analyzes the information or biospecimens; or
(2) Obtains, uses, studies, analyzes, or generates identifiableprivate information or identifiable biospecimens
6
Unpacking the Definition of a Human Subject
• a living individual
• Regulations do NOT apply to research
involving materials from deceased individuals
7
7
Who is An Investigator?Anyone involved in the conduct of the research (study, analysis, interpretation of research data, co-authorship).
**Does NOT include simply providing info or samples.
OHRP guidance on coded info and specimens
8
Do The Regulations Apply to My Project?
Does the activity involve Research?
Does the 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
9
Currently, about 10% of NIH awards are considered exempt.
Exempt Human Subjects Research
8 Exemptions
Meets the definition of human subjects research.Exempt studies involve human subjects research: research involving a living individual about whom
data or biospecimens are obtained/used/studied/analyzed through interaction/intervention, or identifiable, private information is used/studied/analyzed/generated
1
Meets the criteria of one of the following exemptions:2
Exemption 1: conducted in an educational setting using normal educational
practices*
Exemption 2: uses educational tests, surveys,
interviews, or observations of public behavior*
*Limited IRB review may be required
Exemption 3: uses benign behavioral interventions
*Limited IRB review may be required
Exemption 4: involves the collection or study of data or
specimens if publicly available or information
recorded such that subjects cannot be identified
Exemption 5: public service program or demonstration
project
Exemption 6: taste and food quality
Exemption 7: storage of identifiable information or
biospecimens for secondary research use. Broad consent is and limited IRB review are
required.
Exemption 8: secondary research use of identifiable
information or biospecimens. Broad consent and limited IRB review are required.
*Cannot include any other procedures, such as collection of clinical data or biospecimens
Exemption 1 addition: Cannot adversely impact student learning
of required content or
assessment of educators
Exemption 2 addition: NEW
concept- limited IRB review for privacy/
confidentiality when identifiable info is
recorded.
NEW Exemption 3:Replaces exemption for
specific types of research on public
officials & candidates. Includes verbal, written
or audiovisual data.
Must be brief in duration, harmless,
painless, not physically invasive, unlikely to
have adverse effect or be offensive and/or embarrassing to the subjects. Limited IRB
review required when identifiable info is
recorded.
Exemption 4 expanded:
No longer includes only existing
data/specimens. Added HIPAA-
regulated use as exempt. Exemption 5
expanded: Includes federally
supported research.
Requires list of E5 projects to be
published.
NEW exemptions 7 and 8. Includes new
concepts- broad consent and limited
IRB review
Consider
NIH Requirements:•HS education•Inclusion tracking for all except 4
45 CFR 46 Requirements:•Limited IRB review for 7 & 8, and some study designs under 2 & 3.•Broad consent for 7 & 8
Cannot involve prisoners, unless includes a broader population that happens to include prisoners.
Cannot involve children in:•Exemption 2 if investigators participate in the activity being observed or includes identifiable info. OR •Exemption 3.
For more information see the OER website for Research Involving Human Subjects.
Send questions/comments to OER-HS@nih.gov.
Exemption 1
Research conducted in educational settings on normal educational practices such as instructional strategies, techniques, curricula ….
May not be likely to adversely impact:
• Students’ opportunity to learn required educational content, or
• Assessment of educators who provide instruction
• 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.
11
Exemption 2
• Research that only includes use of educational tests, surveys,
interviews or observation of public behavior
• Limited IRB review required if sensitive or identifiable
• Children can included only in observation of public behavior if
investigators not participating in activities
Examples
• Focus group of adult community members to discuss access to dental
care
• Questionnaire about outdoor exercise, including collection of
participants’ age and zip code (with limited IRB review)12
Research involving benign behavioral interventions with adults who
prospectively agree, when information collection is limited to verbal
or written (including data entry) or audiovisual recording
• Limited IRB review required if identifiable
• Intervention must be brief in duration, harmless, painless, not physically
invasive, not likely to have a significant adverse lasting impact on the subjects,
AND investigator has no reason to think the subjects will find the interventions
offensive or embarrassing
• Includes authorized deception research
13
Exemption 3 (New)
Exemption 3 (Continued)
Examples
• Study among young adults evaluating preferred snack foods following
a television program.
• Study investigating text vs. voice message appointment reminders on
self-reported annual physical appointment attendance.
SLIDE | 14
Exemption 4
Research involving the study of existing data, documents, records, specimens if publicly available,
information recorded by the investigator in manner that subjects cannot be identified directly or
indirectly, or identifiable and regulated under HIPAA or conducted by federal agency under federal
privacy standards
• Investigator does not contact or re-identify the subjects
• No longer has to be existing under Revised Common Rule
• Examples
• PI accesses information from medical records. He records information for the study without recording identifiable info.
• PI goes through set of existing excess blood samples to identify those of interest. She removes label with identifiers and marks tubes with random number and basic non-identifiable clinical info.15
Do The Regulations Apply to My Project?
Does the activity involve Research?
Does the research involve Human Subjects?
If yes, is human subjects research Exempt?
45 CFR 46 applies to your research
16
Federalwide Assurance (FWA)
• Required when institutions are engaged in non-exempt human subject research conducted or supported by a federal department/agency
• Documentation of institution’s commitment
• to protecting the rights and welfare of human research subjects;
• comply with applicable regulations
• Designate the IRB(s) to be used to review applicable human subjects research
• IRB must be registered w/ OHRP
17
If you are awarded Federal funding, you must have your
own FWA
What Is An Institutional Review Board (IRB)?
A committee charged with the review of research involving human
subjects to assure that their rights and welfare are adequately
protected
An IRB will review submissions by:
• Full board review• Review by a fully convened IRB
• Expedited review• Review by IRB chair or experienced member(s)
• Meets one of categories eligible for expedited review
Options
• Set up own IRB
• Rely on other registered IRB
18
Many institutions have procedures for determining exempt human subjects research
Full Board
Expedited
IRB Review of Projects
• Initial Review BEFORE start of Research
• Continuing Review may be required
• Specific Criteria for IRB Approval
• Consider subparts B, C, D when applicable
19
Decision Tool: Am I Doing Human Subjects Research
SLIDE | 20 https://grants.nih.gov/policy/humansubjects/hs-decision.htm
NIH Human Subjects Research Policies
21
When do NIH Human Subjects Polices Apply?
•Apply to Human Subjects research as defined in 45 CFR part 46: Protection of Human Research Subjects Subpart A (aka the Common Rule)• Includes exempt and non-exempt research• Inclusion policies apply only to clinical research• Some policies apply only to clinical trials
•NIH policies complementary or in addition to the Common Rule
SLIDE | 22
NIH’s Role in Human Research Protections
•Evaluate applications/proposals involving human subjects for• Risks• Adequacy of protections• Benefits• Importance of knowledge to be
gained (45 CFR § 690.120)
•NIH delegates to peer review
SLIDE | 23
Single IRB Policy
• Multi-site domestic studies which involve non-exempt human subjects research must use a
single Institutional Review Board (siRB)
• Applies to applications submitted for due dates January 25, 2018 or later
• Exclusions:• Foreign sites
• Career development (K), institutional training (T), and fellowship awards (F)
• Applies to applications submitted for due dates January 25, 2018 or later
• Some exceptions apply :• When Federal, State, Tribal, local requirements require local review
• Time-limited exception for ancillary studies
• Other cases with a compelling rationale (rare)
24
Guide Notice: http://grants.nih.gov/grants/guide/notice-files/NOT-OD-16-
094.html
Certificates of Confidentiality (CoC)
• What is a Certificate of Confidentiality?
• Prohibits disclosure of names or information, documents, or
biospecimens containing identifiable sensitive information
As a result of 21st Century Cures Act:
• To persons not connected to the research
• In any Federal, State, or local civil, criminal,
administrative, legislative, or other proceeding, (unless
with participants’ consent)
• For any other purpose, with some exceptions
• See (NOT-OD-17-109) published September 7, 2017
CoC
SLIDE | 25
Key Changes to Certificates of Confidentiality
Issue Previous Authority Current Authority
How to get oneIssued upon approval of
application• NIH-funded – automatic
DisclosurePI/ Institution could voluntarily
disclose
Disclosure is prohibited unless specifically allowed by statute or
with consent
Admissibility as evidence
Information protected by a CoC could be used in a legal proceeding if disclosed
Protected information cannot be used in a legal proceeding even if it
is disclosed elsewhere
Copies of information
Unclear; typically advised to amend or extend
All information, including copies, is protected
Applies to ongoing research as of December 13, 2016
Inclusion of Women and Minorities in NIH Research
Public Law (42 U.S. Code § 289a–2) requires:
• Women and minorities be included in all NIH-funded clinical research studies unless there is a compelling rationale for exclusion
• Analyses by sex/gender, race and ethnicity for NIH-defined Phase III clinical trials
• Applicable* NIH-defined Phase III trials awarded December 13, 2017 or later must report results of “valid” analyses to Clinicaltrials.gov. See NOT-OD-18-104
*Applicable clinical trials are drug and device trials subject to Clinicaltrials.gov registration and results reporting requirements under Title VIII of the Food and Drug Administration Amendments Act (FDAAA) of 2007
SLIDE | 27
Inclusion Across the Lifespan
• Revision to Inclusion of Children Policy; effective for
applications submitted for due dates on or after January
25, 2019 (and for contract solicitations and intramural
studies issued after that date).
• See NOT-OD-18-116
• Requires individuals of all ages be included in NIH
human subjects research unless there are scientific or
ethical reasons not to do so
• Requires submission of individual-level data on
participant age at enrollment in progress reports
SLIDE | 28
How Does NIH Define a Clinical Trial?
A research study in which one or more
human subjects are prospectively
assigned to one or more
interventions (which may include
placebo or other control) to evaluate
the effects of those interventions
on health-related biomedical or
behavioral outcomes.
SLIDE | 29
Helpful resources: https://grants.nih.gov/policy/clinical-trials/definition.htm
Funding Opportunity Announcement (FOA) Policy
• Applications involving clinical trials must be submitted to
clinical-trial specific FOAs
• Purpose is to:
• Improve NIH’s ability to identify proposed clinical trials
• Ensure key pieces of trial-specific information are submitted with
each application
• Uniformly apply trial-specific review criteria
https://grants.nih.gov/policy/clinical-trials/specific-funding-opportunities.htm
SLIDE | 30
Registration & Results Reporting
NIH Policy Requires:
Submit a plan in the application that outlines compliance with the expectations of the policy
Register the clinical trial no later than 21 days after enrolling the first participant
Submit summary results no later than one year after primary completion date
SLIDE | 31
Good Clinical Practice Training (GCP)
• All NIH-funded clinical investigators and clinical trial staff involved in the design, conduct, oversight, or management of clinical trials should be trained in GCP
• GCP training can be achieved through :
class or course
academic training program
certification from a recognized clinical research professional organization
• Training should be refreshed every 3 years
Learn more at https://grants.nih.gov/policy/clinical-trials/good-clinical-training.htm
SLIDE | 32
• Clinical trials must submit a Data and Safety monitoring plan
• Address overall data and safety monitoring framework
• Describe procedures for adverse event reporting
• Identify responsible entity (e.g. PI, independent safety
monitor, DSMB, etc.)
• Data and safety monitoring board generally required for NIH-
defined phase III trials
33
Data and Safety Monitoring
33
Review IC-Specific Guidelines at https://humansubjects.nih.gov/data_safety
Human Subjects and Clinical Trials Information Form
SLIDE | 34
Main Landing Page
• Some information prepopulated from
R&R Other Project Information Form
Study Record(s)
• Add ‘Study Record’ or ‘Delayed Onset
Study Record’ for each study in
application
See the Application Guide for detailed instructions
Research Strategy
Overall strategy, methodology,
and analyses of your proposed
research
Human Subjects/Clinical Trial Form
Detailed study information (e.g.,
eligibility, inclusion, protection
and monitoring plans)
SLIDE | 35
Developing Your Application
In the Research Strategy:
• Refer to information from the Human Subjects/Clinical Trial Form as
needed
• Do not duplicate information presented in the Human Subjects/Clinical
Trial Form
How Many Studies Does My Application Have?
• In some cases how to group or split studies is a judgement call
• Consider:
• What will be most clear for reviewers
• Not necessarily based on how aims are separated
• May be best to group studies if many of the study details are the same between studies
• Study Records live with award for duration of funding and used for post-award reporting
SLIDE | 36
“No” Human Subjects Involved• If research involves use of human materials, a
justification for the claim of “No Human Subjects” is
needed
37
Key Points of Justification
• Material is NOT collected for your proposed research• Discuss source (repository, purchased commercially)
• NO investigator has access to ID, including access to code key)• Investigator = anyone involved in conduct of the research beyond providing
samples/data
Applying to a due date on/after January 25, 2018----------
Forms-E – PHS HS/CT Info Form; specific attachment to explain
Exempt Human Subjects Research
• Inclusion justification for the exemption in Protections of Human
Subjects attachment
• Be aware of changes to exemptions in Revised Common Rule
• Refer to current exemptions and definitions
• Described in section 46.101(b) of 45 CFR 46
• https://www.hhs.gov/ohrp/regulations-and-
policy/regulations/45-cfr-46/index.html#46.101
SLIDE | 38
Protection of Human Subjects Section (no page limits):
1. Risks
• Human subjects involvement and characteristics; meets regulary requirements for vulnerable populations
• Sources of materials – what, how, access to identifiers
• Potential Risks for ALL research interventions: physical, psychological, social, legal
2. Adequacy of Protection Against Risks
• The consenting process
• Procedures to minimize identified risks
• Additional protections for vulnerable subjects
39
Non-exempt Human Subjects Research
3. Potential Benefits of Research to Human Subjects and
Others
• In some cases, no direct benefit to subjects
• Should not include monetary compensation
4. Importance of Knowledge to be Gained
• Discuss in relation to risks
40
Non-exempt Human Subjects Research
3. Potential Benefits of Research to Human Subjects and Others
• May not be direct benefit to subjects
• Discuss risks in relation to anticipated benefits
• Should not include monetary compensation
4. Importance of Knowledge to be Gained
• Discuss in relation to risks
41
Non-exempt Human Subjects Research
Clinical Trial Questionnaire
Answers determine:
Appropriate FOA type
Application form requirements
Review criteria for evaluation
Requirement for registration and results reporting
Requirement for GCP training
Does the study involve human participants?
Are the participants prospectively assigned to an intervention?
Is the study designed to evaluate the effect of the intervention of the
participants?
Is the effect that will be evaluated a health-related biomedical or
behavioral outcome?
If YES to all questions, study is a clinical trial SLIDE | 42
Using the Human Subjects and Clinical Trial Form
Form SectionIf answered “No” to anyquestions in Clinical Trial
Questionnaire
If answered “Yes” to allquestions in Clinical Trial
Questionnaire
Section 1Basic Information
Required Required
Section 2Study Population Characteristics
Required Required
Section 3Protection and Monitoring Plans
Some fields required; some fields optional
Required
Section 4Protocol Synopsis
Not permitted Required
Section 5Other Clinical Trial-related Attachments
Not permitted Required only if specified in FOA
SLIDE | 43
Trainees & Fellows Proposing “Clinical Trial Research Experience”:
• Answer ‘Yes’ to all 4 questions in Clinical Trial Questionnaire
• Complete form Sections 1-3
• Not permitted to complete Section 4 or 5
• Statement from Mentor or Sponsor:
• Role of fellow/trainee in proposed clinical trial
• Source of funding for the trial
• Mentor’s relevant experience
• Assurance that the mentor/sponsor will be responsible for the clinical trial
SLIDE | 44
Peer Review of Human Subjects Section
• Each reviewer will assess human subjects involvement & protections
• Actual or potential unacceptable risks, or inadequate protections, or
insufficient information
• Peer review group will determine overall rating of “acceptable” or
“unacceptable”
• Summary Statement:
• PROTECTION OF HUMAN SUBJECTS: UNACCEPTABLE (Code 48)
• Code 48 is a restricted to award
45
45
Just-in-Time Requirements
After peer review, during just-in-time period:
• Provide Institution’s OHRP Federal-wide Assurance Number
(FWA)
• Certify:
• IRB approval (or exemption)
• Human subjects education for key personnel
46SLIDE | 46
Just-in-Time Requirements
• Work with Institute/Center staff to resolve unacceptable inclusion concerns
• Provide inclusion enrollment report(s) if missing or needs updated as a
result of peer review and/or programmatic adjustments
47SLIDE | 47
After the Award…Now What?
• Provide actual inclusion enrollment data in progress reports
• Provide required information for delayed onset studies
• For NIH-defined Phase III Clinical Trials – report
status/results of analyses by sex/gender, race, and ethnicity
• For applicable NIH-defined Phase III Clinical Trials, report
results by sex/gender and/or race/ethnicity in
Clinicaltrials.gov within 1 year of primary completion date
• Keep in mind you are expected to follow NIH single IRB policy
if site is addedSLIDE | 48
Useful Resources: Human Subjects Protections and Inclusion
• NIH OER Human Subjects Website https://grants.nih.gov/policy/humansubjects.htm
• Certificates of Confidentiality https://grants.nih.gov/policy/humansubjects/coc.htm
• Single IRB Policy https://grants.nih.gov/policy/humansubjects/single-irb-
policy-multi-site-research.htm
• Inclusion of Women and Minorities https://grants.nih.gov/grants/funding/women_min/women_min.htm
• Inclusion Across the Lifespanhttps://grants.nih.gov/grants/funding/lifespan/lifespan.htm
SLIDE |49
Useful Resources: Clinical Trials
• Clinical Trials Requirements website: https://grants.nih.gov/policy/clinical-trials.htm
• Clinical Trial FAQs: https://grants.nih.gov/policy/clinical-trials/faq-list.htm
• Video overview of Human Subjects and Clinical Trials form: https://www.youtube.com/watch?v=nz9NWFhYOG8&list=PLOEUwSnjvqBJeHcb4yai7_fDnFZFPEmQK&index=1
SLIDE | 50
Questions
SLIDE | 51
CONTACT US
Dawn Corbett dcorbett@mail.nih.gov