Several overall objectives, in addition to the goal of setting high ethical standards, guided formulation of the CIRM regulations.
Encourage research institutions and researchers to develop best practices for ethical conduct of hSC research. Research oversight is decentralized in the United States, in that Institutional Review Boards (IRBs) at each research institution take primary responsibility for reviewing all proposed projects involving human participants. hESC research, however, raises ethical issues that are beyond the mission or expertise of IRBs. Among these, for example, are the scientific justification for using oocytes and embryos to derive new hESC lines and concerns that transplantation of hSCs into the brains of animals might result in transfer of human characteristics. CIRM requires that a Stem Cell Research Oversight Committee (SCRO) be constituted at each institution with appropriate expertise to review, approve, and oversee CIRM-funded stem cell research. Institutions have considerable flexibility in coordinating the work of the SCRO and IRB.
The regulations recognize that hSC research is a rapidly advancing field and that there is little experience overseeing such research. To encourage SCRO committees to develop and adopt best practices, the CIRM regulations set performance standards rather than prescriptive standards. For example, the regulations require that those who donate oocytes for hESC research not only give consent, but show comprehension of what they have agreed to. The regulations do not specify how the assessment of comprehension is to be accomplished—this is left to researchers, with the approval of IRBs. The expectation is that with experience and evaluation, best practices for donor consent will be developed and broadly applied.
Avoid unnecessary regulatory burdens. US oversight of research with human participants has been criticized for requiring excessive documentation and procedures that add time and expense but do little to protect against ethical lapses. The CIRM regulations try to avoid unnecessary regulatory burdens. To avoid duplicative review, some specified human stem cell lines are acceptable for CIRM-funded research without further review: stem cell lines approved by the US National Institutes of Health, which were derived before August 2001, as well as cell lines approved by the United Kingdom Human Fertilisation and Embryology Authority, the UK Stem Cell Bank, or those meeting the Canadian Institutes of Health Research Guidelines for Human Pluripotent Stem Cell Research.
Some types of human stem cell research—such as research with adult and cord blood stem cells and in vitro research with embryonic stem cells—do not raise novel ethical concerns and therefore do not require in-depth review by the SCRO. However, in-depth SCRO review is required for research that raises complex ethical issues [1–6
], including research involving oocytes and embryos, the derivation of new pluripotent stem cell lines, and the introduction of human stem cells into humans and nonhuman animals.
Documentation is also tailored to the degree of ethical concern. A research institution must maintain a record of every donated egg or embryo and any products of somatic cell nuclear transfer that have been produced or used in CIRM-funded research. Such strict accounting helps prevent misappropriation of oocytes or the illegal use of somatic cell nuclear transfer for reproductive purposes. While burdensome reporting is not required, CIRM retains the power to conduct investigations and to penalize violations.
Involve the public in developing regulations. Given the public's role in providing the research funding and the level of interest in hESC research, public involvement in the formulation of the regulations was important. CIRM found various ways to engage the public during the process of drafting and revising the regulations. First, all SWG meetings were public meetings, at which the public had access to all written materials, such as briefing papers and draft guidelines, and were invited to comment on each topic discussed. These discussions often involved vigorous give-and-take discussions involving both working group members and members of the public. Second, CIRM held a series of meetings around the state at which the public was invited to offer input and comment on ethical issues related to stem cell research. The most frequent comments concerned the ethical use of human oocytes for nuclear transfer research. Finally, after the regulations were drafted, there was a 45-day period of formal public comment, during which CIRM responded in writing to all suggestions made. Many suggestions were incorporated into the final regulations. The extensive exchange with the public resulted in a stronger document that reflected both professional and public input.
Be consistent with existing laws, regulations, and ethical guidelines. The Working Group was very conscious of existing regulations and sought to harmonize the CIRM regulations with them, so that researchers and their institutions would not face contradictory requirements from different funding sources or regulatory bodies.
Facilitate collaboration to accelerate scientific progress.
To facilitate research cooperation, CIRM wanted to uphold international standards but also recognize and respect differences in detail. This issue arose most acutely in defining the requirements for hSC lines used by CIRM-funded researchers but derived with other funding. CIRM did not insist on exact conformity to CIRM standards, but defined core requirements for hSC lines that CIRM-funded researchers might use [6–8
]. For example, imported hESC lines need not meet CIRM's heightened consent requirements for oocyte donors. The question of whether oocyte donors should be paid is one issue on which there is extensive disagreement. In this case, the ballot measure authorizing the Institute, as well as other California laws, prohibit payment to donors of research oocytes beyond reimbursement for expenses.