guilty ‘til proven innocent: a look at irb liability dennis j. lacroix, esq. senior counsel -...
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Gelsinger context Informed Consent focus Thesis: IC process is broken! Antithesis: IRB, defend thyself! Synthesis: Best Practices... A Look at IRB LiabilityTRANSCRIPT
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Guilty ‘Til Proven Innocent:Guilty ‘Til Proven Innocent:A Look at IRB LiabilityA Look at IRB Liability
Dennis J. LaCroix, Esq.Senior Counsel - Compliance, Clinical Research & Healthcare
Genzyme Corporation
Linda G. Strause, PhDExecutive Director, Oncology Clinical Operations
Vical Incorporated
Michael A. Swit, Esq.Vice President, Life Sciences
THE WEINBERG GROUP INC.
ACRP Annual Meeting 23 April 2007 Seattle, WA
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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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Gelsinger context
Informed Consent focus
Thesis: IC process is broken!
Antithesis: IRB, defend thyself!
Synthesis: Best Practices. . .
A Look at IRB Liability
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Gelsinger Allegations
IRB Ineffectual
What IC process. . .???
Subject Unprotected. . .!
IC Process Is Broken
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On Sept. 17, 1999, Jesse Gelsinger, an 18 yr. old young man, died while participating in a gene transfer experiment at the Institute for Human Gene Therapy (“IHGT”) at UPenn. . .
Jesse volunteered to participate in the experiment, knowing it would not benefit him in the least, because he was led to believe his participation had little risk and would directly benefit as yet unborn infants with OTC. . .
Cf. Gelsinger Complaint, paragraphs 1 & 2
Jesse Gelsinger
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Wilson, Genovo, UPenn, et al.
$20 million, 5% equity owner
Licenses to Genovo
Much benefit from RDAd vector
CISC knew of the conflicts. . .
Cf. Complaint, para. 10-36;
51-54
Confilct of Interest
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Documents & Discussions
Deceptive & Misleading
Minimal Risk
Enormous Benefit Cf. Complaint, para. 59-62
IC Process. . .???
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Toxic effects understated
Monkeys not mentioned
No SAEs mentioned
Treatment efficacy noted
COIs not adequately disclosed Cf. Complaint, para. 61
IC Process. . .???
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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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Jesse’s wrongful death. . . (Cf. Complaint, para. 84-89, esp. 87)
Subject unprotected. . .
IRB Ineffective. . .
IRB Defend Thyself. . .!
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IRB should adopt and follow writtenprocedures
Initial and continuing reviews Evaluation of degree of risk and changes Review and documentation of Adverse and Serious Adverse Events Document, document, document
IRB Best Practices
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• BEST PRACTICES – Continuing Review– Written progress reports from P.I.
• # of subjects in study• Summary description of subject experiences (benefits, AEs)• # of withdrawals & reasons• Current risk/benefit ratios
– Get current I.C. document and compare to one cleared
– Frequency and nature of review is a factor of the study; but must be based on a written SOP
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• BEST PRACTICES – Continuing Review – IND – what is duty to compare IND filings to info
provided to the IRB?• Not articulated in IRB guidesheets• Might have caught some of the Gelsinger problems
– AE’s• Must have a procedure to get these
– P.I.’s – have to be informed of your procedures for continuing review
• How do you do that?– Handling of major changes to the research –
convened meeting
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A process – not just paper
Informed Consent Form
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BEST PRACTICES – Informed ConsentPreparing ICD’s
Consider the reading level of the potential participants
Use simple language – 8th grade If you need to use scientific terms, define
them
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BEST PRACTICESPreparing ICDs
Avoid using abbreviations or acronyms unless they are spelled out first
Consider the age of the volunteer and the font size
Version control & number pages
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BEST PRACTICESICD Development
Be concise Use the pronoun “you” consistently throughout
to refer to the subject/participant Number the pages if the ICD is more than one
page Spell everything correctly and use correct
grammar. The most common error is the spelling of principal investigator: it is principal not principle
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BEST PRACTICESWhen to revise the ICD
When risk/benefit ratio changes New information becomes available The Investigator decides, but needs ok
from sponsor
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BEST PRACTICESHow, What, When & Where
of obtaining informed consent Investigator’s involvement Signatures & initial lines & dates Witnesses Documentation Setting Enrollment goals Training on human subject protection
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BEST PRACTICESThe I.C. Process
Those obtaining informed consent from subjects must be trained in the areas of human subject protection [Note: Ultimately it is the regulatory responsibility of the Investigator to ensure IC has been obtained and all regulations, laws, SOP’s followed]
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BEST PRACTICESThe I.C. Process
Exchange of information between clinical investigators/study coordinators and subject
Reading and signing the ICD Providing a copy to the subject Ongoing process of informed consent
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BEST PRACTICESThe I.C. Process
During the IC discussion, the SC will measure the subject’s comprehension and understanding by asking study specific questions
Have Investigator review with subject any questions they may have in regards to the study
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BEST PRACTICESThe I.C. Process
If subject is willing to participate, ask subject to sign/date ICD; if requested on form, person obtaining IC should sign/date form
Have witness sign/date ICD (if applicable)Provide subject copy of the consent form
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BEST PRACTICESThe I.C. Process
Should there be a waiting period? [in Ireland, it’s six days]
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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BEST PRACTICESThe I.C. Process
Note in source documentation that consentwas administered PRIOR to initiation ofstudy procedures
Remember IC is an ongoing processDocument at follow-up visits patients desire
to remain on study
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BEST PRACTICESThe I.C. Process
Investigator discusses with his/her potential participant the nature of the study
If subject appears to meet eligibility requirements and shows interest in participating in the study, the patient can be referred to the study coordinator (SC)
The SC reviews the ICD with the subject and addresses any questions within his/her scope of knowledge
The SC provides the subject with the ICD and time to read the ICD
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How long does it take to obtain IC for a “routine clinical
study”?45-60 minutes –
Source: Christine K. Pierre, personal observation in clinical research setting
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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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BEST PRACTICES – Are They Possible for the IRB?
The University of Pennsylvania should evaluate the function of its IRBs. Specifically, the workload of each IRB may need to be decreased, in order to allow ample opportunity to carefully evaluate and monitor each clinical trial. There are approximately three to four thousand protocols per year with about 80 adverse events reported per one hundred protocols. Secondly, an IRB should have expertise, or, at a minimum, access to expertise, in evaluating the use of novel therapies such as gene therapy. It might help if individual IRBs were to deal with specialized areas of research, or be enlarged, so that they might be staffed with people knowledgeable about the issues before them. Furthermore, the IRBs should facilitate the sharing of information, especially the occurrence of adverse events, between different trials using similar therapies, such as the same viral vector.
Source: April 25, 2000, Interim Report, U. of Penn. Internal Committee on Research Using Humans
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“Research participation is a gift and contribution by the subject.”
Jay Katz, 1994 As presented by Dale Hammerschmidt