Strengthen stem cell research ethics now

Protect safety of clinical trial participants

The possibility of using embryonic stem cells to treat disease, a strategy known as regenerative medicine, is not yet being explored in clinical trials, but current ethical practices need to be strengthened — now — in preparation for this possibility, according to an advisory committee at the University of California at San Francisco (UCSF).

UCSF’s Campus Advisory Committee on Human Gamete, Embryo, and Stem Cell Research reports that current practices must be amended to promote both the safety and well-being of the patients who would participate in clinical trials and the confidentiality of people who donate the embryos, oocytes, and sperm that contribute to the development of embryonic stem cells.

The recommendations address issues not examined by the National Academy of Sciences, which issued guidelines in May 2005, and go substantially beyond those addressed by the U.S. Food and Drug Administration in its May 2005 report.

"The potential use of embryonic stem cells as medical therapies presents unique ethical challenges that must be addressed before clinical trials begin," says Bernard Lo, MD, UCSF professor of medicine and director of the UCSF Program in Medical Ethics, who was lead author of a paper on the committee’s findings. "Lack of attention to these concerns could lead to delays of clinical trials in some cases and inappropriate clinical practices in others. Such developments, in turn, could undermine or delay progress toward stem cell therapies."

The recommendations of the team, which includes leading stem cell scientists, are aimed at ensuring the safety of biological materials being donated for the development of human embryonic stem cell lines, protecting the privacy of the people who donate biomaterials, and promoting effective communication between clinician–researchers and patients about the nature of early stage, or Phase I, clinical trials.

Addressing these issues would require:

• seeking consent from donors of biological materials to allow scientists to recontact them over the years to update their medical records and rescreen them;

• implementing stringent measures to secure donors’ confidentiality;

• enhancing communication with prospective patients about the ethical decision of participating in a clinical trial involving the use of embryonic stem cells and the unlikelihood of receiving clinical benefit from participation in Phase I clinical trials, which focus on safety of the therapy and drug dosage.

Donated biological materials hold the key to enabling scientists to develop human embryonic stem cell (hESC) lines. However, transplanted hESCs and the proteins they produce could carry infectious diseases, such as Creutzfeldt–Jakob disease, and genetic-based diseases such as cancer, Parkinson’s, and amyotrophic lateral sclerosis (Lou Gehrig’s disease).

The FDA issued regulations in May 2005 for screening and testing for communicable diseases at the time of donation and for tracking transplanted materials back to the original donors. However, the UCSF team says that these regulations are insufficient.

It is critical, they say, that the consent process include asking prospective donors of biological materials to agree to be recontacted in the months or years following their donations, to provide updates on their medical history and participate, as deemed necessary, in further screenings.

Reestablishing contact is necessary, the team says, for determining if diseases that could have been latent at the time of donation subsequently emerged. The process would allow scientists to determine if a donor, or a number of members of the donor’s family, has developed a disease with a strong genetic component that could affect the safety of transplanted cells.

These measures are necessary because there could be a gap of years between the time biological material is donated for embryonic stem cell studies and the time embryonic stem cells or their proteins would be used for transplantation.

Notably, one embryonic stem cell line could be used to treat hundreds or thousands of patients. Thus, one cell line containing a pathogen or disease-causing genetic mutation could affect many patients.

Without permission to recontact and possibly rescreen donors, the advisory team writes, scientists would be invading donors’ privacy by recontacting them. In such circumstances, the donors might refuse to reveal their updated medical information, which would disqualify the cells for transplantation.

It is equally critical, the UCSF team writes, that stringent measures be implemented to ensure that donors’ medical records are secured. The authors advocate steps ranging from having computer files locked in a secure room and password-protected, with access limited to a minimum number of individuals on a strict "need-to-know" basis; to having files with identifiers copy-protected and double-encrypted with one of the keys held by a high-ranking institutional official who is not involved in stem cell research; to having the records protected from subpoena by having the scientists who receive the donated biomaterial obtain a federal Certificate of Confidentiality.

Finally, clinician–researchers should ensure that patients who are considering participation in Phase I clinical trials of hESC transplantation are fully counseled and able to give a truly informed consent.

Because of the ethical issues regarding the use of human embryonic stem cells, informed consent would include researchers making clear to prospective patients that their therapy would involve the use of cells obtained from embryos.

Clinician/researchers also must make clear to prospective patients that Phase I clinical trials are intended to begin the process of determining the safety of a given therapy and the appropriate dosage; such trials rarely lead to improvement in the patient’s condition.

"The crucial ethical issue about informed consent is not what researchers disclose in consent forms or discussions, but rather what the participants in clinical trials understand," the UCSF team writes.

Because consensus on informed-consent practices needs to be in place by the time Phase I clinical trials are proposed, meetings to develop such guidelines should be convened now, the team says.

A chain of events — including funding, basic science, and clinical trials — must take place for the potential of human embryonic stem cells to be fully explored, the team concludes. The ethical issues of embryonic stem cell research form another important link, they write, adding, "a chain is only as strong as its weakest link."

The UCSF advisory committee’s recommendation report, "A new era in the ethics of human embryonic stem cell research," is available in the Sept. 15, 2005, issue of the on-line journal Stem Cells, at stemcells.alphamedpress.org.