A discussion of how an IRB can face liability in particular scenarios in the clinical trial arena, including a discussion of best practices for IRBs.

1. Guilty „Til Proven Innocent:
A Look at IRB Liability
Felix A. Gyi, Pharm.D., M.B.A.
CEO, Founder
Chesapeake Research Review, Inc.
Dennis J. LaCroix, Esq.
Vice President, Legal
Genzyme Corporation
Linda G. Strause, PhD
Founder & Past Chair, Institute of Palliative Medicine & San Diego Hospice IRB
Executive Director & Head, Clinical Operations
Vical Incorporated
Michael A. Swit, Esq.
Vice President
The Weinberg Group Inc.

2. Standard Disclaimers
• Views expressed here are solely our own and do not
necessarily reflect those of our firms or any of our
clients or customers.
• These slides support an oral briefing and may not be
relied upon solely on their own to support any
conclusion of law or fact.
• No panelist has a relevant financial relationship to this
educational activity.
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3.  IRB Scenario: Michael
 IRB Liability: Dennis
 IRB Responsibility/Best Practices:
 Linda & Felix, IRB Chairpersons
A Look at IRB Responsibility & Liability
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4. SCENARIO
 We could have created a fictional
scenario
 However, thanks to the Government
Accountability Office (GAO), fact has
become stranger than fiction.
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5.  GAO conducted undercover sting operations of central IRBs.
 Fictitious medical device company
 Phony protocol based on an actual high-risk study
 Submitted to 3 central IRBs
 2 IRBs firmly rejected however Toast IRB approved
unanimously
 Established a fake IRB, with a website and online
advertising
 Registered the IRB with OHRP
 Obtained a DHHS-approved assurance
Government Accountability Office Sting:
2009
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13. Premise
The purpose of IRB review is to assure, both in
advance and by periodic review, that appropriate
steps are taken to protect the rights and welfare
of humans participating as subjects in the
research. To accomplish this purpose, IRBs use
a group process to review research protocols and
related materials. . .to ensure protection of the
rights and welfare of human subjects of research.
Source: FDA Guidance for IRBs and Investigators (1998 Update)
IRB Responsibility/Liability
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14.  The purpose of an IRB is to assure
that appropriate steps are taken to
protect the rights & welfare of
humans participating as subjects in
research studies. . .
Can We Agree As Follows?
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15.  Two keys to this protection of such
participants are:
(a) an effective assessment by the
IRB of the risks, benefits, and
design of the protocol. . .
Can We Agree As Follows?
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16.  and (b) providing sufficient
information to potential participants
to allow them to make an informed
decision around particiaption.
Can We Agree As Follows?
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17.  The IRB must protect the rights & welfare of
subjects. . .
 The IRB must effectively assess protocol
design, risk, & benefit. . .
 The IRB must ensure provision of sufficient
information to potential participants to allow an
informed decision around participation.
So, We Agree That:
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18. The purpose of IRB review is to assure, both in
advance and by periodic review, that appropriate
steps are taken to protect the rights and welfare
of humans participating as subjects in the
research. To accomplish this purpose, IRBs use
a group process to review research protocols and
related materials. . .to ensure protection of the
rights and welfare of human subjects of research.
Source: FDA Guidance for IRBs and Investigators (1998 Update)
Premise
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19.  Let’s look at your IRB’s review process. . .
 Evaluate study design & scientific quality –
How? Training. . .? Checklists. . .?
 Review the ICF - sufficient info? informed
decision around participation? How. . .?
 One and Done. . .?
So, How Does That Happen?
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20.  Adopt and follow written procedures
 Initial and continuing reviews
 Evaluate degree of risk and changes
 Review and document AEs and SAEs
 Document, document, document
IRB Best Practices
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21. • Continuing Review
– Written progress reports from P.I.
• # of subjects
• Summary description of subject experiences
(benefits, AEs)
• # of withdrawals & reasons
• Current risk/benefit ratios
– Compare current I.C. form to one cleared
– Frequency & nature of review a factor of the study,
but must be based on a written SOP
IRB Best Practices
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22.  Continuing Review
– IND – duty to compare IND filings to info given the IRB?
• Not articulated in IRB guide sheets
• Might have caught some of the Gelsinger problems
– AEs
• Must have a procedure to get these
– PIs – need to know of IRB procedures for continuing
review
• How do you do that?
– Major Protocol Changes - Handle in a formal meeting
IRB Best Practices
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23.  Always a process – not just a paper
Informed Consent Best Practices
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24.  Consider reading level of the potential
participants
 Use simple language – 8th grade, at most
 If scientific terms used, define them
Best Practices: Preparing ICDs
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25.  Avoid abbreviations or acronyms unless
they are spelled out first
 Consider the age of the volunteer
 Version control, numbered pages and a
very readable font size
Best Practices: Preparing ICDs
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26.  Be concise
 Number the pages
 Spell it all correctly & use correct grammar
[A common error is to misspell principal
investigator: it’s principal, not principle.]
 Use “you” consistently throughout to refer to
the subject/participant
Best Practices: Preparing ICDs
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27.  When risk/benefit ratio changes
 New information becomes available
 The Investigator decides, but needs
OK from Sponsor
Best Practices: Revising ICDs
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28.  Investigator’s involvement
 Signatures & initials & dates
 Witnesses
 Documentation
 Setting
 Enrollment goals
 Training on human subject protection
Best Practices:
IC: How, What, When & Where
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29. Best Practices
The IC Process
 Those involved in the informed consent
process must be trained in the areas of
human subject protection
 Ultimately, it is the Investigator’s regulatory
responsibility to ensure IC is obtained and
all regulations, laws, SOPs are followed
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30. Best Practices:
The IC Process
 Information exchange between and among
investigators, study coordinators, subjects
 Subjects read and sign the ICD
 ICD copy given to each subject
 Informed Consent = Ongoing Process. . .!!!
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31. Best Practices:
The IC Process
 During the IC discussion, SC measures the
subject’s comprehension / understanding
by asking study specific questions
 Investigator to review with subjects any
questions they may have as to the study
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32. Best Practices:
The IC Process
 If subject is willing to participate, ask subject to
sign/date ICD
 Have person obtaining IC sign/date form (if
applicable)
 Have witness sign/date ICD (if applicable)
 Provide subject copy of the consent form
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33. Best Practices:
The IC Process
 Should there be a waiting period? [6 days in
Ireland]
 Retain original consent in separate study
binder or regulatory binder
 Put copy of signed consent form in subject’s
source documents
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34. Best Practices:
The IC Process
 Note in source documentation that consent
was administered BEFORE initiation of
study procedures
 Remember IC is an ongoing process
 At follow-up visits, document subjects’ desire
to remain on study 34

35. Best Practices:
The IC Process
 Investigator discusses with his/her potential
participant the nature of the study
 If subject appears to meet eligibility requirements
and is interested in participating in the study, the
patient can be referred to the study coordinator
(SC)
 SC reviews the ICD with the subject and
addresses any questions within SC’s scope of
knowledge
 SC provides the subject with the ICD and time to
read the ICD
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36. How long does it take to obtain IC
for a “routine clinical study”?
45 - 60 minutes. . .
Source: Christine K. Pierre, Immediate Past Chair, ACRP
Personal observation in clinical research setting
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37.  Guidelines and regulations are the base
 Know the regulations:
• 21 CFR 50 & 21 CFR 56
• 45 CFR 46
 FDA Information Sheets
 Protect your committee:
• Errors and Omissions Insurance
• Directors and Officers Insurance
Raise the Bar
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38. “Research participation is a gift and
contribution by the subject.”
Jay Katz, 1994
As presented by Dale Hammerschmidt
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39. Call or e-mail:
Felix A. Gyi, Pharm.D., M.B.A.
410.884.2900
felix@irbinfo.com
Dennis J. LaCroix, Esq.
617.768.6313
dennis.lacroix@genzyme.com
Linda G. Strause, Ph.D.
858.646.1156
lstrause@vical.com
Michael A. Swit, Esq.
760.452.6568
michael.swit@weinberggroup.com
Questions?
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40. Appendices
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