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a Program in Medical Ethics and Division of General Internal Medicine in the2 E8 v. |: \& I" W
; \4 u- i: ^* M$ {6 e9 _b Department of Medicine and Department of Obstetrics, Gynecology, and Reproductive Sciences;
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- G7 n* [ R: R3 C/ x, ~" s+ b4 _- ~c Program in Development and Stem Cell Biology and Department of Neurology at the University of California San Francisco, San Francisco, California, USA;
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% Q, p) D+ O# L& v# ?" a0 Kd School of Law at Santa Clara University, Santa Clara, California, USA;
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e Program in Human Embryonic Stem Cell Biology;
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f Human Subjects Protection Program;
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0 t5 Y+ D' I% { ?g Community member of the UCSF Committee on Gamete, Embryo, and Stem Cell Research, San Francisco, California, USA;0 k9 C& I$ \ Q
6 t2 m( P5 u7 n2 T7 z. Th Department of Cellular and Molecular Pharmacology at the University of California San Francisco, San Francisco, California, USA
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# k! x+ |. ^6 S4 y7 YKey Words. Human stem cells ? Ethics ? Consent1 b' U7 T3 N( ]$ N2 o7 h
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Correspondence: Bernard Lo, M.D., Room C 126, 521 Parnassus Avenue, San Francisco, California 94143-0903, USA. Telephone: 415-476-5370; Fax: 415-476-5020; e-mail: bernie@medicine.ucsf.edu, `) T O5 f4 T
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ABSTRACT
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Increased funding and continued scientific progress have opened a new era in the ethics of human embryonic stem cell (hESC) research. These developments will reframe the ethical debate, which to date has focused on the moral status of the embryo and the acceptability of using embryos for research purposes. Although such philosophical questions have not been resolved, the issue is no longer if hESC research should proceed, but rather how it should proceed. The rapid pace of research makes it imperative to look ahead to the ethical issues generated by the expected use of hESCs for transplantation. Some of these issues should be addressed now, even though phase I clinical trials of hESC transplantation are still in the future. Crucial issues concerning the safety of hESC transplantation and the need to recontact donors of materials used to derive new hESC lines are best resolved when these materials are donated. In addition, informed consent for hESC transplantation phase I clinical trials will present particular challenges, which will require a modification of the usual consent process for clinical trials. Failure to address these ethical issues may delay or preclude clinical trials that will test whether interventions based on hESCs are safe and effective.3 y- K3 {2 ^) s$ t& k7 ~& P
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THE CURRENT SCIENTIFIC, ETHICAL, AND POLICY CONTEXT OF HESC RESEARCH
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& x) N! l9 p" x1 PThe goal of phase I clinical trials is to assess the safety and feasibility of the investigational intervention and to determine dosages for subsequent clinical trials . Direct therapeutic benefit, although hoped for, is unlikely in early trials, particularly if the first participants receive low doses . The guiding ethical principle of phase I studies should be "Do no harm." This ethical responsibility to protect the subjects in phase I trials has important implications for the derivation of hESC lines.2 ^; U, s$ n4 k) Z$ M7 m6 P% L# l
6 j6 v+ r4 ?- F& ]1 |A major safety concern is transmission of infectious agents or serious genetic conditions through transplanted hESCs or their products. The public will expect strong protections against diseases transmitted through hESC transplantation, just as it demands that blood transfusions and solid organ transplants be tested for very rare, but serious, communicable diseases . The May 2005 FDA regulations addressed possible transmission of communicable diseases by cell-based therapies, setting standards for screening and testing at the time of donation and for tracking transplanted materials back to the original donors . HCT/P must be linked through an identification code to the donor and to pertinent donor medical records . Although these requirements are necessary to protect recipients, we contend that they are not sufficient to adequately protect them.' b# D" R) ]/ X
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A broader perspective on protecting recipients of transplanted hESC materials is needed because of several clinical features of hESC transplantation. First, there is likely to be a considerable time period between donation of biological materials used to derive hESC lines and clinical trials involving transplantation of hESCs or products from them. During this period, new risks may become apparent in the donors whose gametes were used to derive the hESC lines. Emerging infectious diseases with long latency periods, such as Creutzfeldt-Jakob Disease, may be identified, for which testing and screening were not available at time of donation. Polymorphisms and biomarkers associated with risk for specific diseases are being defined at a rapid pace. Second, in hESC transplantation, serious genetic conditions might also be transmitted , some of which may not have been apparent at the time the materials were donated. For instance, after donating, donors may develop cancer or discover a strong family history of cancer. Third, immunosuppressive drugs, which may be essential after cell transplantation to reduce rejection, will increase the risk of communicable diseases and cancer in recipients. Fourth, if hESC transplantation proves clinically effective, many patients may receive transplantation from a single hESC line over time. Hence, many recipients may be at risk for diseases transmitted from donors. To safeguard recipients of hESC transplantation, researchers need to recontact persons whose gametes were used to derive the hESC lines at the time of clinical hESC transplantation trials to update information and perhaps do additional testing. Furthermore, if hESC transplantation becomes a proven clinical treatment, periodic updating of the clinical status of donors would be prudent.
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How can screening and testing of donors of materials for hESC lines be updated in an ethically acceptable manner? The responsibility to protect hESC transplant recipients from harm must be balanced against a responsibility to respect donors and protect their confidentiality. To resolve these countervailing mandates, researchers will need to obtain permission to recontact donors if hESCs or hESC materials derived from their gametes or embryos will be used for transplantation. Researchers need to tell donors about the kinds of information or testing that might be requested later and the reasons the information is needed. Such permission for recontact needs to be obtained when materials are donated for research. Without this permission, it would be a serious invasion of privacy to later recontact the donors. Also, donors who had not agreed to be recontacted might object strongly to a subsequent contact or refuse to provide information about their interim medical history or undergo additional testing. Previous reports on the consent process for donating gametes and embryos for hESC research have not discussed the issue of recontact in depth . Obtaining permission to recontact will undoubtedly complicate the consent process for donating embryos for hESC research. However, permission for recontact will likely minimize the disqualification of hESC lines late in the development process for use in transplantation studies because of inadequate follow-up with donors. Recontacting donors presents logistical challenges because donors may move and contact may be lost. It would be desirable to ask donors to provide contact information for a relative or friends who will know their new address should they move.
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+ U6 Q' [$ T" h# gConfidentiality must be carefully protected because breaches might subject donors to unwanted publicity or even harassment. Concerns that their identities will not be kept confidential may deter some individuals from agreeing to be recontacted. Because of the intense public interest in and contentiousness over hESC research, it would be prudent for researchers and research institutions to develop stringent mechanisms, extending beyond those used in routine clinical care, to assure donors that their identity and contact information remain protected.' Q9 r+ R1 u& o
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Recently, confidentiality of personal health care information has been violated through deliberate breaches by staff, through break-ins by computer hackers, and through loss or theft of laptop computers . Files containing the identities of persons whose gametes were used to derive hESC lines should be protected against such breaches through additional security measures. Any computer storing such files should be locked down in a secure room and password-protected, with access limited to a minimum number of individuals on a strict "need-to-know" basis. Entry to the computer storage room should also be restricted by means of a card-key, or equivalent system, that records each entry. Audit trails of access to the information should be routinely monitored for inappropriate access. The files with identifiers should be 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. The computer storing these data should not be connected to the Internet. To protect information from subpoena, investigators should obtain a federal Certificate of Confidentiality . Human factors in breaches of confidentiality should also be considered. Personnel who have access to these identifiers might receive additional background checks, interviews, and training. The personnel responsible for maintaining this confidential database and contacting any donor should not be part of an hESC research team.9 s; h1 ^6 c2 K* s$ K
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Funders of hESC research and institutional review boards (IRBs) or ESCROs that oversee hESC research should ensure that appropriate provisions for recontact and confidentiality are in place. The IRB should review and approve any requests for recontact of donors. The ethical reasons for these provisions are sufficiently compelling that materials donated without explicit permission for recontact should not be used to develop hESC lines for transplantation, lest the safety of recipients or privacy of the donors be compromised.' d6 w! [" J9 d2 U$ ~' F7 q
" C6 m7 P+ \/ R% SINFORMED CONSENT FOR RECIPIENTS OF HESC TRANSPLANTATION IN PHASE I CLINICAL TRIALS
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This work was supported by the Greenwall Foundation. We are grateful to Julie R. Sachse for her expert editing assistance.. `* j4 k" q, J- L8 b/ u& l& ?
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DISCLOSURES
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% R1 [" E8 O4 B5 a0 I SThe authors indicate no potential conflicts of interest.% o( ~) k5 @7 s1 U1 y
! ` k1 w, n+ O; hFOOTNOTES
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发表于 2010-3-30 17:13
