Transcript Controversies at the IRB - LLU Research Affairs

HOW TO PREPARE FOR IRB
SUBMISSION
Micheal A. Kuhn, MD
Vice Chair, Loma Linda University
Institutional Review Board
What type of
research needs
IRB review?
Anything and everything
that involves human subjects
Navigating the IRB process
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Application process
IRB submission and review
Revision
Initial approval
On going monitoring
Yearly renewal
http://researchaffairs.llu.edu/
Start Here
Research Affairs Forms and Documents
• Click on IRB link or scroll down
– Four printed pages of options
– Include:
• Applications
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Full board
Expedited
Retrospective
Humanitarian use device application
Checklists
Consents
How to prepare
Experimental Bill of Rights
Abstract/protocol outlines
Radiation Safety applications
Recruitment forms
Emergency use of investigational device
HIPAA forms
Waivers/assents
Conflict of interest forms
Applicant Checklist
I. GUIDE TO ASSEMBLY OF APPLICATION PACKET
Convened (Full Board) Review: Submit original and three
hardcopies in the order described below:
1.Smith_LymphomaStudy_application.pdf
2.Smith_LymphomaStudy _abstract.pdf
3.Smith_LymphomaStudy _billofrights_icd_hipaa.pdf
4. Smith_LymphomaStudy _protocol.pdf
5.Smith_LymphomaStudy _IB.pdf (if applicable)
6.Smith_LymphomaStudy _flyer.pdf
7.Smith_LymphomaStudy _questionnaire1.pdf
8.Smith_LymphomaStudy _ctc_feasibility.pdf
9.Smith_LymphomaStudy _device_worksheet.pdf (if applicable)
10.Smith_LymphomaStudy _ind_decision.pdf
11.Smith_LymphomaStudy _clinicaltrialreg.pdf
12.Smith_LymphomaStudy _bri.pdf
Additional Requirements
• Resource utilization
– Services outside instituion
– Services inside institution
– Clinical Trials Center
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Patient billing & reimbursement
Device studies
Research conflict of interest
Contract with external sponsor/institution
IRB fee
Clinical trial registration
Are you dizzy yet????
Or rethinking your career?
• It is not as daunting as it
seems
• Most is straight forward
– Follow the instructions
• Important areas
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Protocol
Consent
Support personnel
Multi-center trials
General Considerations
• Understanding of medical knowledge/jargon will
be varied
– The IRB is made up of physicians, nurses, ancillary
personnel and lay people
– Keep protocols simple and easy to understand
• Know what you are submitting
– As the PI, you have the final review before submitting.
– REVIEW EVERYTHING
• Do not rely on others to do it for you
General Considerations
• As a rule, your consenting population will have
little medical education.
– Keep explanation simple
• Using hospital resources for research needs to
be cleared by individual entities
– eg. Nursing, OR, cath lab, etc.
• The Clinical Trials Center is an invaluable
resource for assisting in multi-center trials
Application
Informed Consent
Quick Tips
• Know your audience
– Lay people
– Different socioeconomic backgrounds
– Varying level of education
– Potential language barriers
• Keep language in consent to a 6th grade level
• Minimize abbreviations
1. Why are we doing this study?
• The first thing in the consent should be the
study purpose
• Be clear, concise and to the point
2. How will you be involved?
• Section where the protocol is written
• Keep concise and explain in lay person’s terms
• Explain in clear terms the type of study
– Especially important in randomized controlled
studies
– Make clear that placebo group is a possibility
• Be mindful of canned language especially in
corporate sponsored studies
3. What are the reasonably
foreseeable risks or discomforts?
• Explain the degree of risk
• Use lay terminology
– e.g. vomiting for emesis, bruising for ecchymosis
• Describe in terms of varying risk
– Most common to rarest
– Mildest to most severe
• Table format very useful in organizing risk
– very common in drug studies
• Do not explain standard of care risks
• Do not rely on manufacturer terminology
4. Will there be any benefit to me or
others?
• Explain direct benefit to patient
– Important in studies with high risk groups
– Can impact approval if no benefit/higher risk
• Benefit to society in general
Other parts
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What are your rights as a subject?
Will you be informed of significant new findings?
What other choices do you have?
How will information be kept confidential?
What costs are involved?
Will you paid to participate in the study?
Will study staff receive payment?
Who do you call if you are injured as a result of
the study?
Who do you call if you have questions?
• Who is handling the study?
• Who can be reached 24/7?
• Appropriate phone numbers/pagers
Guarantees of Patient Protection
• You are required by law to
protect patient
information
• Need to supply secure
form of data storage
• Need to supply secure
form of data transmission
• Need to inform patient of
what patient information
will be published
• Provide HIPAA form to
patient and in application
for review
Failure to comply can cause serious problems
Genetic information
• The practice of storing DNA information very
common in industry
• Can be limited to the specific study or planned for
use in future study
• DNA storage must be disclosed in the consent
• Best done in a separate section with its own
signature line
Recruitment/Reimbursement
• All brochures, flyers and other recruitment
information must be provided to the IRB for review
• Reimbursement for visits is reasonable if financially
appropriate
• You must avoid coercing patient
with financial reward
Reimbursement
• Reasonable forms of
reimbursement:
– Small cash payment
– Gift cards
• Food
• Gas
Other items
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California Bill of Rights
Assents for underage subjects
HIPAA authorization form
Consent in second language
Consult website for the IRB submission checklist
• So what happens if you get the application
filled out correctly, have a well written
consent, and provide all the appropriate
information?
Controversies at the IRB
Travis Losey, MD
Chair, Loma Linda University IRB
What is the IRB?
Research Ethics
• In 1932 the "Tuskegee Study of Untreated
Syphilis in the Negro Male” was initiated.
• Initial plan was for a 6 month study.
• Enrolled 600 black men – 399 with syphilis, 201 who did
not have the disease.
• The study was conducted without patients' informed
consent. Researchers told the men they were being treated
for "bad blood," a local term used to describe several
ailments, including syphilis, anemia, and fatigue.
• In exchange for taking part in the study, the men received
free medical exams, free meals, and burial insurance
Research Ethics
• In 1945 PCN was shown to be the
treatment of choice for syphilis,
however for study purposes subjects were not
told their
true diagnosis and were not provided treatment.
• CDC and local chapter of AMA supported the
study.
• 127 medical students rotated through the study.
• In 1972 (40 years after initiation) news articles
about the study appear and it is terminated.
Research Ethics
• Three basic ethical principles:
– Respect for persons
– Beneficence (maximize benefit & minimize harm)
– Justice
What standards does the IRB use?
What are the common questions
asked at IRB meetings?
• Is the study ethical (respect for persons,
beneficence, and justice)?
• Are subjects appropriately informed of the
nature of the study as well as its risks and
benefits?
• Are appropriate federal regulations addressed
(i.e. IND)?
• Are institutional policies followed (billing,
collaboration with support services)?
What are the common questions
asked at IRB meetings?
What is the IRB not focused on
• The IRB is not an editorial service.
• The IRB is not a scientific journal club.
• The IRB is not the Office of Legal Counsel.
Controversy: QI project or research?
• An investigator proposes five evidence-based
procedures recommended by the CDC as having
the greatest effect on the rate of catheter-related
bloodstream infection and the lowest barriers to
implementation (hand washing, using full-barrier
precautions during the insertion of central venous
catheters, cleaning the skin with chlorhexidine,
avoiding the femoral site and removing
unnecessary catheters).
• All hospitalized patients will receive all
interventions.
Controversy: QI project or research?
• These interventions reduced the rate of
catheter associated bloodstream infections by
66%.
• This study was published in the New England
Journal of Medicine and cited in >2500
publications.
Controversy: QI project or research?
• A complaint was filed with OHRP due to the
fact that this federally funded project was
conducted without IRB review or subject
consent.
• JHU contended that it did not qualify as
research and was a QI project.
• OHRP rejected this contention and demanded
a corrective action plan from Johns Hopkins
University.
Does the project involve the
collection of data through
intervention, interaction with an
individual or the use of
identifiable private information?
YES
Is the project planned in
advance, and does it use data
collection and analysis to
answer a question?
YES
NO
Are any of the following present?
ON
• The project includes randomization to enhance
confidence in differences that might be obscured by
nonrandom selection
•The project tests issues that are beyond current
science and experience, such as new treatments
•The project involves investigators who have no
ongoing commitment to improvement of the local care
situation
•Feedback from implementing changes is delayed or
altered as part of the project
• Project receives funding from an outside organization
with a commercial interest in the results
YES
NO
This is not human subjects
research and IRB review is not
needed.
Is the project expected to
yield information that
expands the knowledge base
of a scientific discipline or
other scholarly field of study?
The project may be human
subjects research. Advise
contacting Research Protection
Programs for a formal
determination.
This project meets criteria for
human subjects research and
requires IRB review.
Controversy: Ethics in studies
performed by corporations
Controversy: Risk for studies involving
“standard of care”
Controversy: Risk for studies involving
“standard of care”
Controversy: Risk for studies involving
“standard of care”
Draft Guidance:
For subjects randomized between different “standards of care”, the
reasonably foreseeable risks of each of the potential treatments should
be disclosed to potential subjects and considered in assigning the risk of
the study.
• The risks of the research do not include the risks that are created by
the medical condition for which the person is being treated, or the
risks associated with treatment that they would receive for that
condition outside of the research.
• Thus, if an observational study compares two standards of care that
are chosen by individuals with a given medical condition in
consultation with their clinical care providers, and the research plan
does not assign subjects to any specific standard of care, then the
risks of the standards of care are not risks of research.
Controversy: Risk for studies involving
“standard of care”
• What are the risks for subjects in the study?
A: Minimal risk. As all treatments are “standard of
care” the only risk is loss of confidentiality.
B: Greater than minimal risk. In addition to A, there
is a risk of seizures of 25-50% with all treatments.
C: Greater than minimal risk. the risks of each of the
study medications should be disclosed to potential
subjects as different subjects might be
concerned
about different side effects.
D: All of the above
Practical Advice
• What to do when things go wrong.
Tips for IRB submissions
Tips for IRB submissions
• Protocols should be clearly written, direct and
internally consistent. The scientific rational should be
included in the protocol, references should be cited for
reviewers who have additional questions but critical
findings from these references should be included in
the protocol. Risks should be clearly and directly
addressed.
• Informed consent documents should avoid medical
jargon, completely and honestly discuss risks of the
study and explain how treatments in the study differ
from standard care. A person who does not have a
medical background should be able to understand the
study after reading the consent.
Tips for IRB submissions
• Protocol deviations:
– Should be requested in advance if possible as a
one time change request.
• Serious Protocol Violations:
– Should be clearly acknowledged with a thoughtful
plan to prevent recurrence.
• Minor Protocol Violations
– Should be recorded in a excel spreadsheet which
should be attached the annual renewal request.
Emergency Research
• In emergent situations, access to
investigational drugs or devices may be
required. Contact:
– IRB chair ( Dr Travis Losey) or Vice Chair (Dr
Michael Kuhn or Dr Andrea Rey) for ethics
approval.
– Research Coordinator (though department, Lila
Dalton or Amy Casey at CTC can help to identify).
– If institutional signature is needed, Dr Anthony
Zuccarelli or Dr Michael Kirby.