Prop 71 opens doors to stem cell research; IRBs look for guidance
Prop 71 opens doors to stem cell research; IRBs look for guidance
California’s $3 billion bond initiative re-energizes discussions
More IRBs are being drawn into the complex and controversial world of human embryonic stem cell research.
While the amount of research so far has been limited by the restrictions imposed on federally funded research by President Bush in 2001, it already has raised ethical and practical issues for review boards: Whose interests are the IRBs supposed to protect? When do those donating the materials — either eggs and sperm or embryos themselves — get treated as human subjects needing protection? And how do you put regulatory limits on a field of research whose scope may not be fully known yet?
Nowhere are these questions more pressing than in California, where voters last November approved Proposition 71, a $3 billion ballot initiative designed to provide state funding for embryonic stem cell research, and to attract it to the state. The state will sell general obligation bonds to cover the costs of the research.
By California law, institutional review boards must review all human stem cell research, and the proposition passed in November states that standards for review of research will be established, generally based on IRB standards promulgated by the NIH.
But some officials at research institutions in the state say they worry that the funding will come before more detailed guidelines do, leaving them scrambling for guidance.
"I communicate with other IRB directors at other [University of California] campuses," says Tony Perez, director of human research protections at the University of California, Davis. "We’re all pretty much in the same state in that we see something potentially coming down the pike that we’re definitely going to have to deal with, and it could be very large; but right now there’s a large unknown.
"We don’t know what guidelines to apply. We don’t know exactly what we’re supposed to review [stem cell research] for other than what’s required under the Common Rule; and we don’t know the volume yet until the dollars start getting doled out."
The state of California was to have developed a set of guidelines for reviewing stem cell research by Jan. 1. As of last month, members of an advisory committee designated to draw up those guidelines had just been chosen and were in the process of being notified, says Lea Brooks, chief of the public information section for the California Department of Health Services in Sacramento.
Meanwhile, the committee created by Proposition 71, the Independent Citizens Oversight Committee (ICOC), will create its own guidelines. Fiona Hutton, spokeswoman for the Emeryville, CA-based ICOC, says initial standards will be adopted based on existing NIH guidelines. Permanent guidelines will be developed later, based on a number of sources, including a set of guidelines that were to be released this past month from the National Academies of Science.
Issues are complex, intriguing’
R. Alta Charo, JD, professor of law and bioethics at the University of Wisconsin Law School in Madison, says there are many facets of human embryonic stem cell research that fit neatly within the IRBs’ existing experience — most notably the donation of biological materials for the stem cell lines.
"Most typically, that will be people donating excess embryos," she says. "It will less frequently be people donating eggs, sperm, or somatic cells so that you can deliberately make an embryo for research, whether by [in vitro fertilization] or by cloning."
She notes that IRBs have long experience in evaluating the recruitment of research subjects — in this case, the donors — to ensure they’ve been recruited ethically, that the medical and social risks have been explained, and that they haven’t been paid for the materials, although reimbursement of expenses is allowed.
"So the IRBs, with regard to recruitment of donors of biological materials, are in very familiar terrain," Charo says. "They’ve been doing it for years."
But she calls the situation involving donations of existing embryos "a little more complex and intriguing." If a couple has leftover embryos from in vitro fertilization efforts and a researcher approaches them to ask them to be donated, are the donors truly research subjects?
"This conversation [asking the couple for the donation] is really the only interaction that the researcher has with the donors — it’s a consent conversation only," she says. "There’s no physical interaction. We’re not taking new materials from them; we’re not poking or prodding them. In this situation, where the only interaction is the request to use the materials, the donors are not, in fact, considered research subjects. That’s the interpretation of OHRP."
Charo says the only situation in which the couple would technically be considered research subjects is if they are asked for private medical information, which triggers both research protections and privacy concerns under HIPAA.
She says the interpretation creates "a kind of weird world in which people are moving in and out of the category of research subjects. They can be a research subject in one moment and not in another because of the way the information’s being handled."
Despite this gray area of IRB responsibility, Charo says IRBs will always review such research, to err on the side of caution.
"In most cases, medical information does need to be collected from the donors so that the medical information can be connected to the embryos and the resulting stem cell lines," she says. "That’s especially true if you expect those stem cell lines to be eventually used to develop transplantable tissue, because the FDA regulates transplantation and it generally wants a complete medical profile of the tissue that’s going to be transplanted. That would mean that these people are research subjects — the HIPAA protections apply, the research protections apply, the IRB review applies."
She says that doesn’t mean that all subsequent work with those stem cell lines have to go to an IRB, since usually the information is coded in a way that effectively renders its origins anonymous. "The medical information stays, but the identity of the donors is dropped."
Aside from concerns of medical information from the donors, Charo says there currently is discussion as to whether IRBs also should look at the lab research itself, to ensure that it is being conducted ethically. She says some research falls through the cracks of the existing oversight committees — they’re not covered by institutional biosafety committees, or animal care committees.
"Here, some people have said that the IRBs need to look at the lab research, too," she says. "But keep in mind: The IRBs in this case really have no expertise. They look at the protection of human subjects, they don’t look at the science, except to the extent that it’s part of the analysis of the risks and benefits to research subjects. So this is an area in which bringing in the IRBs — if people want to do that — may require new areas of expertise."
One answer may be to require IRBs to create special committees that advise them on such issues. Another may be a completely new type of oversight committee, such as the kind created for recombinant DNA work, Charo says.
Preparing for new studies
So what should IRBs, particularly in California, do while all of these issues are being hashed out?
Currently, at UC Davis, officials have been taking what steps they can. Lynne Chronister, MPA, associate vice chancellor for research, says her institution has written a policy that specifically states all embryonic stem cell research must be reviewed by the IRB.
Perez says he’s talked in general terms about the situation with his IRB chairs. "Everybody knows something’s coming; and if we need to react fast, whether it’s to create another committee to handle the volume, or maybe designate some committee members for expedited review, we’re prepared to do that."
He plans to look for members who have specific expertise in stem cell research, and to consult with outside experts if necessary. Chronister notes that they’ll need to update training for all IRB members who have to deal with stem cell issues.
"The bigger problem I see is the volume — that we may not have enough experts to deal with it," Perez says. "We would like to keep it within the institution, but if we need to, we may have to turn outside if we need that level of expertise on a particular protocol."
Charo says other IRBs watching California and wondering what they’ll be asked to take on in the future would do well to beef up their understanding of an area they’re already responsible for — protocols that involve the collection of biological materials such as tissue, blood, and urine.
"Many IRBs are still very confused about how to analyze these situations, how to analyze the presence or absence of an actual human subject, how to evaluate the significance of the information being collected from the human beings and how it’s packaged and travels or doesn’t travel with the biological materials. This has been a source of confusion for many years," Charo says.
Charo served on President Clinton’s bioethics commission, which wrote a report with recommendations for IRBs on use of biological materials. She says there is significant federal guidance available to IRBs, but not every IRB has actually dealt with the issues.
"Until you’ve dealt with it, you don’t realize how confusing it can be," Charo says. "And yet the issues raised by work with human biological materials are very close to some of the issues having to do with recruitment of embryo, egg, sperm, and somatic cell donors.
"So if there’s one area where I would say IRBs need to get up to speed, it would be generally with the field of human biological materials," Charo says. "It will help them with the next generation of genetic epidemiology, a lot of which has to do with looking at tissue banks and scanning for mutations and frequencies. And it will help them in evaluating the recruitment process and the significance of the research that results from stem cell lines developed with recruited material."
More IRBs are being drawn into the complex and controversial world of human embryonic stem cell research.Subscribe Now for Access
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