Studies and Clinical Trials
Issues and Concerns
Revolving Gene Therapy
Introduction
Review and proper registration of Human Gene Transfer
protocols is very complex. A protocol goes through
rigorous review by multiple Committees both internally
and externally. Due to this complexity, we have
developed this guidance to assist researchers navigate
the process.
• FDA
• Hospital Service Lines
• Institutional Biosafety Committee (IBC)
• Recombinant DNA Advisory Committee (RAC)
• Committees on Human Research (IRB)
• NIH Office of Science Policy (OSP)
Investigator-Initiated
vs Industry Sponsored
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Investigator-Initiated - If this is an investigator-initiated
gene transfer project, then all of the requirements as
outlined in this power point are the local investigator’s
responsibility.
Industry-Sponsored - Some of the requirements as
outlined in this power point are to be completed by the
local investigator while some are to be completed by
the sponsor. We will address where there are
differences.
Obtain FDA Approval
FDA approval is required prior to submission for
institutional review. This will be the responsibility
of the local investigator for investigator-initiated
protocols and the sponsor for industry-sponsored
projects.
Obtain Approval from the
Following Hospital Services
Local Investigator is responsible to obtain feasibility
approvals from the following hospital services,
regardless of sponsorship:
• UVMMC Investigational Drug Pharmacy
• UVMMC Environmental Health and Safety Dept
• UVMMC Infectious Disease
• UVMMC Infection Prevention
Materials Required for Each
Service Review
Each service will require the following materials for review:
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Clinical Trial Protocol
Investigational Drug Brochure
Standard Operating Procedures for Drug Preparation
Standard Operating Procedures for Transport of Drug
Standard Operating Procedures for Handling of Drug by Clinical Staff
IBC REVIEW
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Local investigator is responsible for submission to the IBC.
Gene transfer protocols will require a full Committee review.
All Service Line reviews must be complete prior to submission to the
IBC.
A site risk assessment must be completed prior to submission to the
IBC. This would typically be done by the UVMMC Environmental
Health and Safety staff, UVM Biosafety, the UVMMC Research
Pharmacy Manager and the PI for the project.
IBC Committee will make the final determination regarding RAC
Review for the institution. This determination is separate and
distinct from an industry-sponsored determination.
Documents Required
for IBC Review
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IBC Protocol Form including
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Standard Operating Procedures for Drug Preparation, Transport, and
Handling as approved by the Service Lines
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Complete Human Subjects IRB Cover Form
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Draft of Human Subjects IRB Consent Form
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Clinical Protocol
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Investigational Drug Brochure
*Review of these materials satisfies the requirement to meet
the Points to Consider Section, M-I-A, of the NIH Guidelines.
Who Decides if RAC
Review Is Required?
• Investigator-Initiated Single-Site
• UVM’s IBC will determine if a protocol requires
RAC review based on the criteria presented in
previous slide.
• Industry-Sponsored Multiple Sites
• Often times, sponsors will make a study level
decision and approach RAC if they feel it meets
criteria. The local site, however still makes its
own determination of the need for RAC review.
The various sites’ determinations are provided
back to NIH for consideration.
IRB Review
• Local investigator is responsible for submission to the
IRB.
• Gene transfer protocols will require a full Committee
review.
• Initial IBC review has to be completed with an approvedtype status.
• IRB formally cedes the decision as to whether RAC review
will be required to the IBC Committee.
Serious Adverse Event Reporting
Requirements for Human Gene Therapy
Research
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Human gene transfer protocols have additional adverse event
reporting responsibilities. The NIH Guidelines require that any
significant problems, violations, or any significant research-related
accidents and illnesses” be reported to the NIH Office of Science
Policy (OSP) within 30 days.
https://osp.od.nih.gov/biotechnology/faqs-on-incident-reporting/
If the gene transfer study is supported by an external sponsor, this
reporting should be coordinated with the sponsor.
In addition to submitting a serious adverse event (SAE) to the OSP,
researcher must submit SAEs to the IBC and the IRB.
CONCLUSION
This presentation was designed to inform the audience
on the local and national requirements for review of gene
therapy experiments.