Human Genome Editing Science, Ethics, and Governance (2017) / Chapter Skim
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2 Oversight of Human Genome Editing and Overarching Principles for Governance
2 Oversight of Human Genome Editing and Overarching Principles for Governance
Pages 29-60
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It then provides an in-depth look at U.S. governance of gene transfer research and therapy, and a brief review of alternative governance approaches used in other countries (some of which are explored in greater depth in Appendix B)
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The Universal Declaration of Human Rights (UN, 1948) , adopted shortly after World War II, became the foundational document for many of the more particularized declarations, conventions, and treaties that followed.
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In the United States, the landmark 1979 Belmont Report of the National Commission for the Protection of Human Subjects in Biomedical and Behavioral Research (HHS, 1979) focused on avoiding infliction of harm, 3See http://www.cioms.ch (accessed January 5, 2017)
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Responsibilities that flow from adherence to this principle include (1) pursuing applications of human genome editing that promote the health and well-being of individuals, such as treating or preventing disease, while minimizing risk to individuals in early applications with a high degree of uncertainty; and (2)
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Responsibilities that flow from adherence to this principle include proceeding cautiously and incrementally, under appropriate supervision and in ways that allow for frequent reassessment in light of future advances and cultural opinions.
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REGULATION OF GENE THERAPY IN THE UNITED STATES Both somatic and germline human genome editing would be regulated in the United States within the framework for gene-transfer research and, once approved, for gene therapy, which applies to work with human tissues and cells from the early stages of laboratory research through preclinical testing, human clinical trials, approval for introduction into medical therapy, and postapproval surveillance. At the national level, regulation may be mandatory in all cases -- for example, when the work is to be submitted to the U.S.
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, whose focus is on protecting donors from the effects of being identified and on ensuring appropriate informed consent. Laboratory work using human embryos does not fall within IRB jurisdiction unless the progenitor-donors are identifiable, but this work may be overseen by voluntary oversight bodies, such as embryonic stem cell research oversight committees (ESCROs)
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-funded researchers must comply with NIH Guidelines for Human Stem Cell Research (certain uses of iPSC lines are prohibited) • NIH-funded researchers must comply with NIH Guidelines for Human Stem Cell Research (only human embryonic stem cell [hESC]
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Examples of Considerations Laboratory research in • Institutional embryonic Special ethical concerns human embryonic stem stem cell research oversight and regulations (federal cells or embryos committees (ESCROs) or and state)
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Once the tissue has been obtained, it is available for laboratory research, subject to the usual rules for oversight of recombinant DNA research by IBCs. This pattern of regulation is the same regardless of whether genome editing will be carried out on the tissues.
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Human Tissue Use and Institutional Review Boards Laboratory-based research using human tissue may also trigger certain human subjects protections, even though all the work is done in vitro. Two situations trigger this additional level of regulation.
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But if the donor's identity can be readily ascertained, the donor is considered a research subject, and IRB review is triggered unless the work is eligible for exemption or waiver of some or all elements of informed consent. The rules will change with respect to research using stored human specimens upon the effective date of the January 2017 revisions to the "Common Rule" that sets out the framework and requirements for human subjects research that is funded by most federal agencies and departments or is otherwise subject to its jurisdiction.6 Effective as of January 2018, the revised rule covering use of identifiable tissue Allows the use of broad consent (i.e., seeking prospective consent to unspecified future research)
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or from a legally authorized representative. Additional Rules Governing Laboratory Research on Human Gametes and Embryos Basic science research on genome editing may entail experimentation on human gametes and embryos, with no intention of performing intrauterine transfer to establish a pregnancy in a woman (see Chapter 3)
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. In the United States, the public policy issues surrounding laboratory research with human embryos were debated extensively by the 1994 NIH Human Embryo Research Panel, which was convened to provide recommendations to the Advisory Committee to the NIH Director.
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institutions housing embryonic stem cell research have put voluntary oversight measures in place (Devereaux and Kalichman, 2013) , and the International Society for Stem Cell Research recently adopted guidelines calling for expanding these oversight committees to almost all research involving human embryos, regardless of whether stem cells will be derived and regardless of funding source (ISSCR, 2016b)
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. Oversight in Other Nations for Research Using Human Embryos As noted earlier, in the United States, a handful of states have laws governing or forbidding research using human embryos (NCSL, 2016)
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. Clinical Trials of Human Genome Editing -- The Role of IRBs Clinical genome-editing trials -- that is, studies involving human subjects -- cannot commence without permission from the FDA, the details of which are discussed below.
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IRBs have the authority to approve or deny approval for research protocols, human subject recruitment plans, and informed consent documents. They also may require modifications to a protocol as a condition of approval.
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If the research holds the prospect of benefit only to the fetus and not to the pregnant woman herself, then paternal consent is also required, if feasible. Requiring voluntary and informed consent is one of the key protections for human subjects.
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. The NIH Guidelines are a term and condition of NIH funding, and are applicable to all recombinant DNA research that is conducted or sponsored by a public or private institution that receives NIH funding for any such research (NIH, 2013a)
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. With regard to in utero gene transfer, the NIH Guidelines state that NIH may be willing to consider such research, but only after significant additional preclinical and clinical studies satisfy criteria developed at a RAC conference.
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, protocol review by the RAC serves many functions (Corrigan-Curay, 2013) , including • optimizing clinical trial design and increasing safety for research subjects, and in some instances strengthening biosafety protections necessary for researchers, health care workers, and close contacts of research subjects; • improving the efficiency of gene therapy research by allowing scien tists to build on a common foundation of new knowledge emanating from a timely, transparent analytic process; and • informing the deliberations of the FDA, the NIH Office of Human Research Protections (OHRP)
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CBER regulates a range of biologics, including human gene therapy products, and certain devices related to gene transfer. The FDA defines gene therapy products as products that "mediat[e]
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In 2015 the FDA released "Considerations for the Design of Early-Phase Clinical Trials of Cellular and Gene Therapy Products" (FDA, 2015b)
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As a general rule, when reviewing IND submissions, the FDA balances potential benefits and risks to participants in the clinical trials (Au et al., 2012; Takefman and Bryan, 2012)
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. Federal regulations require that information about many clinical trials be posted at ClinicalTrials.gov, the government's database for information about a large proportion of clinical trials, or a similar site.
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This provision for accelerated review was expanded to include regenerative medicine and other cell therapy products in the 21st Century Cures Act,20 signed into law in December 2016. The act allows for approval of a "regenerative-medicine therapy" based on surrogate endpoints reasonably expected to predict clinical outcomes and on evidence provided by a wider range of sources, including those outside the realm of controlled clinical trials.
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. In contrast, the RAC is able to address broader scientific, social, and ethical issues raised by gene-transfer and gene therapy research, and -- unlike IRBs -- the RAC is permitted to address these broader issues in its review of individual protocols as well (NIH, 2016b, Sec.
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. The European Union has additional layers of quality control for "advanced therapy medicinal products," which would include some gene therapy products, although as in the United States, off-label use would be permissible (George, 2011)
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The U.K. Clinical Trials Regulations require that before clinical trials of gene therapy are conducted, approval must be obtained from the Medicines and Healthcare Products Regulatory Agency.
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The existing U.S. regulatory structures discussed in this chapter provide a starting framework for governance of laboratory research, preclinical testing, clinical trials, and potential medical uses involving human genome editing in the United States, as well as for an understanding of differences between the U.S.
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