Transcript Human Subjects Research: What is Required and Why David Ungar, MD Kathleen Hay, PhD, CIP, Assoc.

Human Subjects Research:
What is Required and Why
David Ungar, MD
Kathleen Hay, PhD, CIP, Assoc. Director
Human Subjects Protection Office (HSPO)
“It is essential that the research
community come to value the
ethics of research as central to
the scientific process.”
National Bioethics Advisory Commission
Requirements for Conducting
Human Subjects Research
at
Penn State Hershey
Requirements for Conducting Human Subjects
Research at Penn State Hershey
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Ethical Principles for Human
Subjects Research
IRB Review of Research
IRB Submission Process
IRB Required Training
Investigator Responsibilities
PHS Study of Untreated Syphilis
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‘Tuskegee Study’, began in1932
Recruited poor sharecroppers
No informed consent
 Deception
 Undue influence
Eventual RX of penicillin withheld
National Research Act - 1974
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Required regulations be put in place:
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protect human subjects of research
informed consent
independent review of research
Established a national commission:
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National Commission for the Protection of Human
Subjects of Biomedical and Behavioral Research
This group wrote the Belmont Report , in 1979,
embodying the ethical principles for protection of
research subjects
Principles of Human Subject Protection
The Belmont Report: Guiding Ethical Principles
 Respect for Persons
 Informed consent
 Protection for the vulnerable
 Beneficence
 Maximize possible benefits
 Minimize possible harms
 Justice
 Fair distribution of research burdens vs. benefits
Is It Research?
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Research means a systematic investigation,
including research development, testing
and evaluation, designed to develop or
contribute to generalizable knowledge
Case reports are not research (not
systematic)
Internal quality improvement activities are
not research (not designed to produce
generalizable knowledge)
Does It Involve Human Subjects?
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Access to private information
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Use of data or specimens
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Viewing records or using data from a
medical chart
If they can be linked to an individual
Interacting/interventions with
individuals
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Including non-invasive activities,
questionnaires/surveys, and procedures
Institution Review Board (IRB)
Review of Research
What is the IRB?
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Ethics review committee
Advocates for the rights, safety and
welfare of subjects
Includes physicians,
scientists and
non-scientists, and
representatives
of the community
Penn State Hershey IRB
Institutional
Review
Board
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Operates under federal regulations, state
law and institutional policy
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Authority to approve, require modification
in, or disapprove research
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IRB approval is needed for all human
research at Penn State Hershey
IRB Review of Research
IRB Review Criteria
 Informed Consent
(Respect for Persons)
 Will be sought prospectively
 Includes required elements of information
 Additional safeguards to protect vulnerable subjects
 Risk are Balanced and Minimized (Beneficence)
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Sound research not to unnecessarily expose subjects to risk
Risks are minimized (e.g. - use data or proc. already available)
Risk to subjects is reasonable vs. potential benefits
Safety provisions & monitoring are adequate
Privacy & confidentiality provisions are adequate
 Subject Selection is Equitable (Justice)
 Rationale for inclusion/exclusion criteria
 Involvement of vulnerable populations justified
What The IRB Wants To Know
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Do you understand ethical research?
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What are you doing?
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Procedures/Protocol
Who are you doing it to?
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Training requirement
Subject Population
Inclusion/Exclusion Criteria
What are the risks and benefits?
How will you ensure voluntary
participation?
Tips for Success in Navigating the
Human Subjects Protection System
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Start early
Read and follow directions
Understand the process
Ask for help
What Needs IRB Review
What is Human Research?
Department of Health & Human Services (DHHS)
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Research - a systematic investigation ..., designed to
develop or contribute to generalizable knowledge.
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Human subject - a living individual about whom an
investigator conducting research obtains:
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data through intervention or interaction with individual, or
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identifiable private information
– individually identifiable;
– reasonably expect not to be observed, recorded or made
public
(IRB is also the ‘Privacy Board’ at HMC/COM and privacy protection
requirements apply to health information of decedents)
What is Human Research?
FDA Clinical Research
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Clinical Investigation - any experiment that involves a test
article and one or more human subjects…
 Test article - any drug (including a biological product for
human use), medical device for human use, human food
additive, color additive, electronic product, or any other
article subject to regulation under the [Public Health
Service Act].
 Human subject - an individual who is or becomes a
participant in research, either as a recipient of the test
article or as a control. A subject may be either a healthy
human or a patient.
(…includes a human on whose specimen an investigational device is used.)
How do I determine if my project needs IRB
review?
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Determining What Needs IRB
Review
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Decision charts & FAQs on IRB website
Call the Human Subjects Protection
Office for a consultation
Request for a formal determination
 Use
Request for an IRB Determination form
What activities do not require IRB
review?
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Case report or case series
Quality improvement projects
Quality assessment projects
Medical practice and innovative
therapy
Public health practice (disease monitoring
or program evaluation)
What activities do require IRB review?
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Research involving existing or
prospectively collected human
specimens or data
Review of medical records
Educational research
Research involving surveys,
interviews or focus groups
Clinical trials of investigational drugs
and devices
What are the IRB review categories?
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Types of review
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Exempt from IRB review
Expedited IRB review
Full board (convened) IRB review
Affected by the level of risk and the
type of project
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Minimal risk
What is minimal risk?
Level of risk
A study is Minimal Risk when:
 both probability and magnitude
 of possible harm or discomfort
 are not greater than that ordinarily
encountered in daily life or during the
performance of routine physical or
psychological examinations or tests
IRB Review of Research
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Exempt – ‘no risk’ activities
● The IRB must certify the exemption
● Involves only activities from an exemption list:
- Research involving normal educa. practices
e.g., instructional strategies/curriculum evalu.
- Tests, surveys, interviews, or observation (e.g.,
data de-identified, or no harm if disclosure)
- Study of existing records or specimens
if not identifiable/linkable, or if from public source
IRB Review of Research
 Expedited – no more than ‘minimal risk’
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IRB Chair or IRB designee may approve
● Involves
only activities from an expedited list, such as:
- Data / materials collected solely for non-research purposes
- Non-invasive recordings in adults (e.g., MRI, EKG)
- Survey of indiv./group characteristics (if no manipulation)
- Collect samples non-invasively (e.g., saliva, sputum, excreta)
- Blood draws (e.g., finger/heel stick, limited venipuncture)
● Not
eligible if identification would expose subjects to
risk of damage or stigmatization
● Standard informed consent requirements apply
IRB Review of Research
 Convened Board Review
● Required
for research involving greater than
minimal risk
● Pre-review
● IRB
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– Insures submission is ready for IRB
primary reviewer may contact PI for clarifications
PIs invited to the meeting to answer question (optional)
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PI may provide phone # to call if IRB has questions
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PI excused for final deliberation and vote
PI receives copy of board minutes outlining IRB
requirements
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IRB Submission Process
IRB Submission Process
Submit 3 weeks in advance
Best to consult with HSPO staff first if unclear
Forms & Instructions on web www.hmc.psu.edu/irb
IRB submission should include:
 Application Form, and Addenda if applicable
 Research protocol
 Protocol summary abstract
 Informed consent process
 Recruitment methods/materials, if applicable
 Supporting materials, if applicable
IRB Submission Process
IRB Submission Process
Where to submit
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Human Subjects Protection Office and Staff
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Phone (717) 531-5687
Academic Support Bldg. #1140
Electronic Submissions
 Use electronic ‘IRB Submission Drop Box’ on server:
\\hersheymed.net\files\hspo
• ‘IRB Submit Instructions’ for e-submissions
• Also on IRB website under ‘Investigator Resources’
IRB Required Training
IRB Required Training - CITI
Collaborative Institutional Training Initiative
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CITI Course – Biomedical Research
at Penn State, COM & HMC
 Required for all investigators/key personnel
 Continuing education required every 3 years
 Investigators receive automatic CITI reminder
 Access instructions on IRB web site:
www.psu.edu/irb/education/tutorials/protecting.htm
IRB Required Training - CITI
Medical Student Research Projects
MSR Projects – Example #1
Example #1 –
 Med student designs a study
 Study will be conducted at HMC
and/or off-site
 Study involves human subjects
MSR Projects – Example #1
IRB Requirements for Example #1
 Study must be submitted to the Hershey IRB
for review using the standard IRB forms
 Student must complete the CITI Course training
 Hershey IRB reviews and approves study and
issues an approval or exemption determination
memo
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After receiving the IRB approval memo the student may
start the research
Student must provide a copy of the IRB approval memo to
the Director, Medical Student Research
MSR Projects – Example #2
Example #2
 Medical student plans to work on an
IRB-approved study here at Hershey
 Study has previously been confirmed
exempt or received IRB approval
MSR Projects - Example #2
IRB Requirements for Example #2
 Principal Investigator of the study must
submit a Modification Request Form to
add the student as a co-investigator
 Student must complete the CITI Course
 PI receives an IRB approval memo for the
addition of the student to the study
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After the PI receives this memo the student may
commence work on the project
Student must provide a copy of this memo to
the Director of Medical Student Research
MSR Project – Example #3
Example #3
 Medical student plans to work as a
co-investigator on a study off
campus
 Study has previously been confirmed
exempt or received approval from
another IRB
MSR Projects – Example #3
IRB Requirements for Example #3
 Student must submit the following to the
Hershey IRB office
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MSR proposal
Copy of the approval memo from the other IRB
Email or letter from the principal investigator at
the other institution stating that they agree to
supervise the student’s work on the project
Student must complete the CITI Course
MSR Projects – Example #3
IRB Requirements for Example #3 (cont.)
 IRB Chair reviews the information to decide if
review by the Hershey IRB is required.
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If review and approval by the Hershey IRB is required, the
study must be submitted to the Hershey IRB using the
standard IRB forms as in Example #1.
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Student will be notified if Hershey IRB review is required.
If the IRB Chair determines that Hershey IRB review is not
required, the student receives a memo stating that review
and approval by the Hershey IRB is not necessary.
 After this memo is received work may commence on the
project.
 Student must provide a copy of this memo to the Director
of Medical Student Research.
MSR Projects
REMEMBER:
 IRB approval must be obtained
prospectively
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Before you start your research.
The IRB does not grant retroactive
approval for research that has
already taken place.
Key Investigator Responsibilities
Key Responsibilities for Investigators
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The principal investigator has the ultimate
responsibility for the conduct of the study
The ethical performance of the project
 The protection of the rights and welfare of human
participants
 Strict adherence to the study protocol and any
stipulations imposed by the IRB
 Complying with applicable federal, state, and local
regulations and PSU policies
 Ensure key personnel are trained/qualified
 Obtaining legally effective informed consent
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Key Responsibilities for Investigators
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The principal investigator has the
ultimate responsibility for the conduct
of the study
Ensuring continuing review approval is obtained
within the timeframe stipulated
 Ensuring no changes in the approved research plan
are implemented without prior IRB approval, except
where necessary to eliminate apparent immediate
hazards to participants
 Notifying the IRB of unanticipated problems
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Key Responsibilities for Investigators
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Obtaining legally effective informed
consent from participants or their LAR
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Using only the currently approved, datestamped informed consent documents
Ensuring that only IRB-approved
investigators obtain informed consent
Informing subject of any new information
Key Responsibilities for Investigators
Continuing Review
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Continuing review approval must be
obtained within the stipulated timeframe
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Approval effective for a maximum of 1 year
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Failure to do so results in automatic
expiration of IRB approval
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PI receives e-mail reminder and progress
report form to complete
Key Responsibilities for Investigators
Modifications to Research
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Changes in the research plan must be
approved by IRB prior to implementation
IRB must review all changes
 Obtain IRB approval before implementing changes,
unless necessary to avoid immediate hazard
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Types of changes
 Protocol
amendments - permanent intentional action
 Protocol deviations - one-time, unintentional action
 Protocol exceptions - one-time, intentional action
Ongoing IRB Review Requirements
Unanticipated Problems
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Investigators must notify the IRB of any event or report
that describes a possible unanticipated problem involving
risks to participants or others
Definition:
 Unexpected (in nature, severity, or frequency) given the
research procedures and participant population
 Suggests that the research places participants or others at
a greater risk of harm or discomfort related to the research
than was previously recognized
– Physical, psychological, economic or social harm
Submit Problem Report Form & Accumulative Tracking Log
Ongoing IRB Review Requirements
Unanticipated Problems
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Investigator must report the following promptly to the IRB
 Adverse events (unexpected and related or likely related to the
research as determined by the PI
 Info that indicates a change in the risks or potential benefits
 Breaches in confidentiality
 Incarceration of subject in study not approved for prisoners
 Sponsor imposed suspensions for risk
 Unintentional protocol deviations that involved risks
 Emergency protocol changes (deviations)
 Complaints that indicate risks or can’t be resolved by the research staff
Are there other committees that must
review research?
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Conflict of Interest Review
Committee (CIRC)
Human Use of Radioisotopes
Committee
Institutional Biosafety Committee
Anatomic Pathology
Departmental scientific review
committees
Resources for Investigators
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Human Subjects Protection Office
Phone (717) 531-5687, Academic Support Bldg. #1140
 Individuals Consultations
 HSPO Update e-mails
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IRB/HSPO web site:
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www.hmc.psu.edu/irb
Investigator Resources
Instructions and Forms
QA Tools: Templates to help you manage research records
www.hmc.psu.edu/irb/qualityassurance/index.htm
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IRB Seminars
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IRB New Investigator Series online
http://media1.hmc.psu.edu/mediasite/Catalog/