Oversight and Review of Clinical Gene Transfer Protocols Assessing the Role of the Recombinant DNA Advisory Committee (2014) / Chapter Skim
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4 Evolution of Oversight of Emerging Clinical Research
4 Evolution of Oversight of Emerging Clinical Research
Pages 77-94
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From page 77... ...
The charge for this independent review is to determine whether the RAC remains critical to the oversight of clinical gene transfer protocols and, if so, to provide criteria to guide when those protocols should be reviewed. LIMIT PUBLIC REVIEW OF SELECTED GENE TRANSFER PROTOCOLS Today, gene transfer research has matured to a state that has reduced some of the early concerns and uncertainty regarding risks; much has been learned about these technologies' safety and possible adverse events.
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From page 78... ...
Although patient safety is always paramount, regulatory oversight should not be required unless it provides a benefit; regulation without benefit is unnecessary and burdensome and should be eased. Therefore, the committee concluded that individual gene transfer protocols should not be subject to additional public review by the RAC except in exceptional circumstances, such as when human subjects research involves novel technologies and treatment strategies or when the protocols cannot be adequately performed by other oversight and regulatory bodies.
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From page 79... ...
The committee expects that allowing the NIH director, in consultation with IRBs and IBCs, to select protocols for review will eliminate the role of the RAC as a selfperpetuating body both selecting protocols to review and performing the review. The expertise and authority of the RAC is best utilized to provide additional oversight for exceptional circumstances, such as when human subjects research involves novel technologies and treatment strategies.
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From page 80... ...
an exemption from RAC review because none of the criteria is met. When the RAC performs public reviews of gene transfer protocols, the goal will be to advise prospective research participants, the investigator, the Office of the NIH Director, FDA, IRBs, and the public.
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From page 81... ...
Although these may be important questions generally, with regard to the individual protocol, other agencies are well-equipped to evaluate these issues. Furthermore, it is possible that the Office of the NIH Director will provide a platform for general discussion, beyond a single protocol, of more wide-ranging issues, such as societal impact.
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From page 82... ...
This information should assist the investigator, IRB, IBC, and FDA in the development of a treatment plan that optimizes safety and assists the research participant in making an informed decision about whether to participate. In addition, when considering which protocols are chosen for additional public review, the NIH director, in consultation with the other oversight and regulatory bodies, should consider broader societal issues that may warrant a public forum.
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From page 83... ...
Even if the protocol does not meet the foregoing criteria listed in items 1 and 2, the NIH director in consultation with appropriate regulatory and/or oversight authorities should have the flexibility to select protocols for review that may present significant societal or ethical concerns. Illustrative Case Studies In order to illustrate how the new criteria should be used to limit the number of protocol reviews that are selected by the Office of the NIH Director, three historical cases are provided below that compare the outcomes that could be reached by using the proposed framework versus the present-day RAC review (see Boxes 4-1, 4-2, and 4-3)
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From page 84... ...
Decision and Rationale for RAC Review Under Current Guidelines This study was chosen for in-depth review and public discussion by the RAC because a trial involving the intratumoral administration of Toca 511 was associated with detection of viral RNA sequences in the blood. An other study involving intracranial administration of Toca 511 resulted in one subject experiencing a dose-limiting toxicity, with 193,000 copies of virus/uL in the blood at the time of cough and fever and partial lung collapse
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From page 85... ...
This study will primarily evaluate whether the gene transfer product is safe, and secondarily include clinical assess ment of motor and sensory function and effect on disease pathology in sub jects' peripheral nerves. Eligibility Study subjects will be children over 4 years of age with a genetic diagno sis of GAN, a neurodegenerative disease generally associated with pro gressive loss of motor and sensory function over time and with death by age 30.
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From page 86... ...
. Decision and Rationale for RAC Review Under Current Guidelines This study was chosen for in-depth review and public discussion by the RAC because it is the first time this agent had been used in a U.S.
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From page 87... ...
SPECIAL REVIEW OF OTHER EMERGING SCIENCES AND TECHNOLOGIES Evolution of Oversight of Emerging Clinical Research The RAC was established to respond to an emerging technology of great public interest and with risks and benefits only barely understood. The RAC has successfully provided oversight for a complex technology for almost 40 years, providing exceptional service to NIH, the scientific community, and the public.
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From page 88... ...
However, different areas of emerging sciences are often at different stages of development, and therefore differ in their materials characterization and understanding, process development, understanding of uncertainties and establishment of safety to research participant, close contacts, community, and environment, in addition to raising different societal concerns. For example, technology creating chimeras raises different societal concerns than nanomedicine, and embryonic stem cell research raises still others.
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From page 89... ...
The committee recommends exploration of the potential for a new process that would have ad hoc capacity to review the full breadth of emerging areas of research supporting human clinical intervention that may have special risks and that could not be adequately assessed under the existing regulatory processes for clinical research. To be clear, the criteria presented in Recommendation 4-1 are meant to be used to select gene transfer protocols that require an exceptional level of review and are not meant to apply in whole or in part to other technologies.
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From page 90... ...
There are many options to be considered for implementation of an expanded process to evaluate and advise on new technologies that are anticipated for use in clinical interventions and which pose uncertain risk and consequences to individual and/or public health. The committee acknowledges that this process should leverage scientific knowledge sharing and commitment to advancing novel technologies.
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From page 91... ...
director should convene an ad hoc working group that will be responsible for considering whether additional oversight and a venue for public deliberation are indicated for other applications of emerging technologies, and if so, to explore procedural options, including the possibility of an integrated oversight body. In this task, the focus should be on those human clinical applications that may be of particular interest to the public, or that feature uncertain risk, may pose harms to individuals or to the public's health, and which could not otherwise be adequately assessed by existing regulatory and oversight processes.
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From page 92... ...
For the present, however, the RAC should continue to review individual gene transfer protocols but use the criteria set forth in Recommendation 4-1 to help limit review and focus resources on exceptional cases. This expanded process could take a number of forms.
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From page 93... ...
In the interim, all gene therapy protocols should continue to be registered with the NIH director, but should only be selected for public review according to the three criteria detailed above, in order to help make the process less burdensome and more efficient. The suggested continued registration and newly recommended criteria for review will maximize efficiency by removing duplication in the regulatory process and will optimize scientific advancement while providing rigorous human subjects protection.
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From page 94... ...
2013. NIH guidelines for research involving recombinant or synthetic nucleic acid molecules.
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