Transcript Slide 1

Understanding Our HRPP and Your Role
in the Accreditation Process
Introduction
Eugene Oddone, MD, Vice Dean for Research
What is AAHRPP?
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Association for the Accreditation of Human
Research Protection Programs
Gold standard for Human Research
Protections programs is participation in a
voluntary accreditation process.
Independent, non-profit accrediting body
that incorporates a voluntary, peer-driven,
educational model to ensure that Duke’s
Human Research Protection Program (HRPP)
meets rigorous standards for quality and
protection
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Why is Duke Seeking
Accreditation?
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The accreditation process allows us to take a
comprehensive look at our HRPP in order to
identify and address any weaknesses and build
upon our strengths.
It helps to ensure:
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The highest possible standards & protections
An assurance of quality
Improved efficiency & effectiveness
A competitive edge
Government recognition
Public trust & confidence
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What is My Role in the Process?
Investigators and their study teams are an
important component of an HRPP
 Prepare for the site visit:
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Familiarize yourself with Duke’s HRPP
 Review Duke’s policies
 Know what resources are available to assist you
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If identified as a contact on the consent
form, you may be called to determine if you
are prepared to answer questions & if you
respond in a reasonable amount of time.
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Overview of AAHRPP Accreditation
Wesley Byerly, PharmD, Associate Dean,
Research Support Services
Your Clinical Research
Environment
Good Clinical Practice: Regulations, Guidance,
Policies & SOPs
Human Research Protection Programs (HRPP)
Duke HRPP
Institutional (Duke) Policy
Site Based Research
• AAHRPP
• Research
Administration
Offices
Your Human Subjects
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Good Clinical Practice (GCP)
“Good Clinical Practice (GCP) is an international ethical
and scientific quality standard for designing, conducting,
recording and reporting trials that involve the
participation of human subjects. Compliance with this
standard provides public assurance that the rights, safety
and well-being of trial subjects are protected, consistent
with the principles that have their origin in the
Declaration of Helsinki, and that the clinical trial data are
credible”
ICH HARMONISED TRIPARTITE GUIDELINE ,
GUIDELINE FOR GOOD CLINICAL PRACTICE , E6
(http://www.ich.org/LOB/media/MEDIA482.pdf)
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Good Clinical Practice
Goal
Protect Subjects
Laws
Prescribes obligations
Regulations
ICH Guidelines
Mandatory requirements
Guidances
Standard Operating
Procedures
Standards of Care
Suggested ways to comply
Detailed directions
Professional Expectations of
Practice
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Which Regulations
do you Follow?
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Department Health and Human Services (HHS)
FDA Regulated
21 Code of Federal Regulations (CFR)
21 CFR Parts 50: Human Subject Protection
21 CFR PART 54: Financial Disclosure
21 CFR 56: Institutional Review Boards
21 CFR 312: Investigational New Drug
Application
21 CFR 803,812: Devices
Federally Funded
45 CFR 46, “Common Rule”
The Federal Policy for the protection of
human subjects and is codified by a number
of federal agencies. 2
45 CFR subpart B: Protection for Pregnant
Women, Human Fetuses & Neonates
45 CFR subpart C: Protection for
Prisoners
45 CFR subpart D: Protection for Children
• Health Insurance Portability and Accountability Act (HIPAA) – Office of Civil Rights
• National Coverage Decision (NCD) –Office of Inspector General (OIG)
• VA Policies & Procedures
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Human Research Protections
Program (HRPP)
An integrated process where all the various
components of an organization involved in
the conduct of human research work together
to protect the rights and welfare of
participants
The HRPP is not an office.
The HRPP is the collective effort of all who
participate in the Conduct, Review, Approval
and Facilitation of Clinical Research at Duke.
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Goals of an HRPP
 Improve the systems that protect the rights and
welfare of individuals who participate in research
 Communicate to the public the strength of an
organization's commitment to the protection of
human research participants
 Improve the overall quality of research by
consistently applying high standards and practices,
raising the global benchmark for human research
protection
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Conduct
Where?
• Duke University Hospital
• Durham Regional Hospital
• Duke Raleigh Hospital
By Whom?
• Investigators and Study Teams
Sponsorship and Finance
• Office of Research Administration (ORA)
• Office of Corporate Research and Collaboration
(OCRC)
• Office of Sponsored Programs (OSP)
• PRMO Clinical Trials Billing Office
• Research Costing & Compliance (RCC)
Review and Oversight
• Site-Based Research Units (SBRs)
• Institutional Review Board (IRB) and
Subcommittees
• Clinical Research Support Office (CRSO)
• Clinical Trials Quality Assurance (CTQA)
• Privacy Office
• Research Integrity Office
• Information Security Office
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Association for the Accreditation of
Human Research Protection
Programs (AAHRPP)
Step 1
Institution prepares and submits application with detailed policies,
procedures, tools
Step 2
A team of experts reviews the materials and sends report of changes to
be made by institution to meet accreditation standards
Step 3 (Currently at this step)
Institution makes changes, AAHRPP schedules Site Visit to look at
institution's HRPP performance with respect to accreditation standards
Step 4
Site Visit occurs: A report is received in 30 days and there
is a response period
Step 5
AAHRPP’s Council on Accreditation reviews the application, Site Visit
Report and institution’s response and determines site’s accreditation
status
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AAHRPP Accreditation Domains
(What will be reviewed)
 Organization The entity that assumes responsibility for the Human
Research Protection Program and applies for accreditation
 Research Review Unit Refers to the arrangements that the
Organization has made for an independent review of ethical and scientific
aspects of each research protocol involving human participants
 Investigator Includes the various arrangements that the Organization
has made for assuring that individuals who plan to conduct research —
whether as a principal investigator, co- investigator, or other member of a
research team — understand and fulfill their responsibilities
 Sponsored Research Includes the Organization’s arrangements for
structuring its relationships with those who fund or initiate research
external to the Organization, such as federal agencies, foundations,
individual donors, and corporations
 Participant Outreach Refers to the arrangements the Organization
has made for understanding the social, psychological, and physical needs
and concerns of research participants and their communities
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What Happens During
the Site Visit?
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Twelve study team groups will be interviewed as
representatives of our research community
The interviews will last 45 minutes
Groups will be either PI groups or coordinator groups
Investigators will meet separately with the site visitors from the
coordinators
The CRSO will meet with these representatives of our study
teams to assist them in preparing for the visit
Site visitors will ask questions regarding our training resources,
practices, procedures and processes
For more information on the site visit, go to the CRSO’s webpage
on AAHRPP:
http://crso.som.duke.edu/modules/crso_home/index.php?id=6
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Duke’s HRPP
Jennifer Holcomb, Director of Operations, CRSO
Research Administration Offices
CRSO
 IRB
 RIO
 OCRC
 ORA
 OSP
 PRMO
 CTBO
 IDS
 CTQA
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Clinical Research Support Office
Institutional Review Board
Research Integrity Office
Office of Corporate Research Collaboration
Office of Research Administration
Office of Sponsored Programs
Patient Revenue Management Organization
Clinical Trials Billing Office
Investigational Drug Service
Clinical Trials Quality Assurance
DUHS Compliance Duke University Health System Compliance
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Site-Based Research Units
(SBRs)
Department
Chair
Faculty
Advisory Board
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CRSO
SBR Medical Director
Unit Business
Manager
Financial
Manager
Lead CRCs
PIs
CRCs
Research Staff
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What Role do SBRs and Study Teams
Play in our HRPP?
 Policies, practices and procedures at the
institutional (Duke), Site-Based Research Unit
(SBR) and Study Team levels respectively,
must be followed and reviewed, evaluated
and revised regularly
 Communication between the Study Team and
Research Administration is essential to
Compliance with Regulations and
Institutional Policies
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SBR Functions
 Responsible for the integrity, financial
accountability, regulatory compliance, quality, and
academic productivity of the projects conducted
in their groups
 Provide day-to-day management of site-based
research activities including:
 Feasibility assessment of potential studies
 Study selection decisions
 Personnel management (hiring/supervision) of nonfaculty research staff
 Protocol-specific training and study execution
 Financial management
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Site Based Research
Investigator Responsibilities
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In addition to regulatory and DUHS requirements,
Investigators are responsible for:
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Identifying and proposing studies
Participating in the development of the Schedule of
Events, budget, and billing grid
Participating in negotiation with sponsors
Following SBR Standard Operation Procedures (SOPs)
The academic productivity of research
Compliance with Duke HRPP training requirements - new
on-line training modules taking effect Jan. 1, 2009
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Study Conduct and
Management
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Managing Approved Studies:
Documentation – What & Why
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Source Data (Documentation) All information in original records
and certified copies of original records…” (ICH GCP 1.51)
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Includes
 Clinical findings
 Observations
 Other study activities
Necessary for:
 The reconstruction and evaluation of the study
 Confirmation of subject existence and observations
 Substantiation of study data integrity
Source Document: A record which contains ORIGINAL source
data (e.g. Medical records, Lab reports, X-rays, ECGs, Intake/
Screening forms, Telephone contact records, faxes, e-mails, Subject
diaries, Informed consent forms, CRFS)
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Managing Approved Studies:
Documentation – What & Why
Note/Memo to File
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Used to clarify missing or inaccurate data or procedures.
Store memo in the appropriate regulatory binder and with
the source documentation.
Not a panacea for all things that have gone wrong.
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Document problem –Not enough.
Document problem -> document corrective action identified for
preventing recurrence -> institute corrective action
Examples:
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An assessment is missed or completed out of sequence
Are unable to obtain a blood sample at a visit
A subject failed to initial one page of a consent document
If an original document is destroyed and only a copy remains
A subject is lost to follow-up
A subject is dropped from the study
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Managing Approved Studies:
Record Retention – Quick Takes
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Drugs/Biologics: 2 years following the date of market
application approval, market application non-approval or
discontinuation of the investigation (21 CFR 312.62[c])
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Devices: For a period of 2 years after the latter of the
following investigation termination/completion date , or date
that records no longer required to support premarket approval
application (21 CFR 812.140[d])
FYI - ICH Guidelines: 2 years after the last approval of a
marketing application in an ICH region and until there are no
pending or contemplated marketing applications in an ICH
region or at least 2 years have elapsed since the formal
discontinuation of clinical development of the investigational
product. (ICH GCP (E6), 4.9.5)
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Study Conduct & Subject Protection
How do Privacy and Confidentiality
Differ?
Privacy is about protecting the person
 Confidentiality is about protecting the
private information (DATA) you
have access to
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Study Conduct & Subject Protection:
How do I Maintain the Privacy of my
Subjects?
 Do
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not “cold contact” subjects
When designing the recruitment process, remember that
the study must be introduced by healthcare personnel
known to the potential subject. If the subject indicates
interest in the study, then research personnel may
approach the subject to discuss the study further.
 Ensure
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interviews are convened in a private setting
If others are present, ensure that their presence is
appropriate
 Consider
how the subject might like to be treated
given their age, ethnicity, or gender
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Study Conduct & Subject Protection:
Protecting Confidentiality
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Refers to the protections that you provide for
private information
Expectation that data will not be divulged
except in ways previously agreed upon
It's about DATA
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verbal
written
electronic
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Study Conduct & Subject Protection:
Protecting Confidentiality
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Does your subject have an expectation that
information provided will be kept confidential?
How do you identify potential subjects?
What data are you collecting?
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Is the information you are recording of a personal
nature?
Are you recording information about a third party?
How are the data going to be stored?
Who is going to have access to the data?
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Study Conduct & Subject Protection:
Protecting Confidentiality
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There are tools to protect it both inside and
outside of Duke
HIPAA: Set of tools (and rules) for maintaining
confidentiality now and after disclosure
(commonly referred to as the “Privacy Rule”)
7 Certificate of Confidentiality: Allows you to
keep the data away from outsiders; even from a
court order (Applies to any research, not just
NIH funded)
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Study Conduct & Subject Protection:
Recruitment – The Foundation of
Informed Consent
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How is equitable selection operationalized?
Who has first contact with prospective
participants?
When is it appropriate to approach a family
member or friend first?
Is it acceptable to leave a consent with the
medical provider to pass on?
How is first contact made?
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Study Conduct & Subject Protection:
Do You Have Informed Consent?
When does Informed consent
begin…end?
 What do you assess to determine the
individual's capability to provide legally
effective informed consent?
 What criteria should be in place to
ensure you have informed consent?
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Study Conduct & Subject Protection:
Diminished Capacity/Cognitive Impairment
*Indications of potentially diminished capacity are:
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A diagnosis of dementia or cognitive impairment
Presenting for an evaluation of dementia
A report, in medical records or from a family member or person well
acquainted with the subject, that the subject has symptoms of cognitive
impairment or dementia
An abnormal degree of confusion, forgetfulness, or difficulties in
communication that is observed in the course of interacting with the subject
Psychotic symptoms, bizarre or abnormal behavior exhibited by the subject
For research that may involve subjects with diminished capacity to
make an informed decision, you need to inform the IRB of:
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What special protections will you ensure are in place?
Who will assess for decisional capacity?
When will this occur?
Under what circumstances will reassessment occur?
What provisions will be made to obtain the consent of the research subject
if the period of diminished capacity is temporary?
*UC Davis Alzheimer's Disease Center
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Study Conduct & Subject Protection:
Diminished Capacity/Cognitive Impairment
Considerations for the Informed Consent Process
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Determining extent of cognitive impairment
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Will the individual have enough information to make an
informed decision?
Will the individual be able to make a decision?
Will the individual understand the consequences of the
decision?
Will the individual be able to communicate the decision?
Will the subject need a legally authorized representative to act
on behalf of the subject?
Will assent be sought?
Circumstances under which the subject’s failure to assent can
be overridden by the subject’s legally authorized representative
Periodic reassessment of the subject’s cognition – will it be
necessary? If yes, when it will occur, and by whom?
Will the subject will be asked to consent for continued study
participation if the subject’s decisional capacity improves, and if
not, why not?
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Study Conduct & Subject Protection:
N.C. Order of Authority for Serving as a
Legally Authorized Representative (LAR)
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Court-approved guardian
Health care agent
Spouse
Adult son and/or daughter
Parent
Adult brother and/or sister
Uncle and/or aunt
Other adult kin
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Study Conduct & Subject Protection:
Assent – Diminished Capacity & Children
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Subjects with Diminished Capacity/Cognitive Impairment – IRB
does not have specific policies regarding assent for this
population
Children
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In NC residents under 18 years of age are considered minors in
unless they are "emancipated" by court order
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In determining whether children are capable of assenting, the IRB
will take into account the ages, maturity, and psychological state
of the children involved. This judgment may be made for all
children to be involved in research under a particular protocol, or
for each child, as the IRB deems appropriate
Age related IRB consent requirements
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> 6 years of age should be involved in the decision to participate in a
research project
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≥ 12 years of age must sign assent after the parent or legal guardian
has given consent (for exceptions consult IRB manual)
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Study Conduct & Subject Protection:
Documenting Informed Consent
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Document that the Subject was given a (signed) copy of the ICF
in the case history
If subject is a patient, DUHS requires a copy of the consent form
in the subject’s DUHS medical record (JCAHO requirement)
Best Practice:
 Document the consent process in the case history & the medical
record
 Include:
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IRB approval obtained prior to subject consenting
How subject was informed (read consent, discussion, Q&A, video)
Who participated in the consent process and how (investigator, study
coordinator, legal authorized representative, family, etc.)
How subject’s understanding of the information was assessed
Disposition of the signed consent form (original and copies)
Special or unusual circumstances (e.g. Illiterate subject –how did you
ensure the subject was informed and that your process met regulatory
requirements?)
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Study Conduct & Subject Protection:
Unanticipated Problems vs. Adverse
Events
SAE’s
Adverse Events
Unanticipated
Problems (including
SAE’s and AE’s)
involving new or
increased risk
Unanticipated
Problems
Require prompt reporting to the IRB, and
sponsor, if applicable, and the FDA, if
applicable.
• Most adverse events are not unanticipated problems
• Unanticipated problems include other incidents, experiences, and
outcomes not considered adverse events
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Study Conduct & Subject Protection:
Medical Devices, Adverse Events and
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Effects
Investigator Reporting Requirements
Device Related
Adverse Effect
Record & Document
21 CFR 812.140(a)(3)(ii)
Serious &
Unanticipated
Unreasonable
Risk
(Sponsor Obligation)
Report to sponsor & IRB within 10 days
812.150(a)(1)
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Managing Approved Studies: Protocol
Departures, a.k.a. “Noncompliance”
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Types of Departures
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Departures must be reported when the following are
impacted:
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Deviation – Unintentional
Violation – Intentional
Rights, welfare or safety of subject
Integrity of the research data
Subject’s willingness to continue study
Forms to use
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“Notification of Protocol Deviation/Violation”
If departure is both unanticipated and meets above criteria, the
“Notification of a Problem or Event requiring Prompt reporting to
the IRB as a New or Increased Risk” must also be submitted to
IRB
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