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Ethical Issues With Informed Consent From Potential Living Kidney Donors
Ethical Issues With Informed Consent From Potential Living Kidney Donors C. Petrini ABSTRACT Living organ donation and participation in clinical research trials have several features in common from an ethical perspective. The primary similarity is risk justification: the risk of harm to living organ donors and clinical research participants is justified by a resulting benefit to one or more other individuals. Some authors hold that organ donation and clinical trial participation are full-fledged duties. Such an implicit likening of the two leads to several considerations regarding informed consent in each situation. Informed consent raises ethical concerns in every medical context, and some of those concerns, such as competence, understanding, autonomy, and free or voluntary choice, are uniquely relevant to living organ donation and clinical trial participation. Most countries regulate informed consent procedures for living organ donation in great detail, and although informed consent procedures for clinical trial participation are somewhat less detailed, their rules are subject to review by ethics committees. It would be constructive for research participation informed consent procedures and living organ donation informed consent procedures to learn from one another. RGAN PROCUREMENT raises many ethical questions. Organ donation has been defined as a “moral,” “prima facie,” “de facto,” and “ordinary” obligation.1 According to some authors, living organ donation and voluntary clinical trial participation are comparable to one another and are both moral duties.2,3 Living organ donation resembles voluntary clinical research participation in several ways. First, the risks to both donors and research participants are justified by benefits to one or more other individuals. Moreover, the relationships between patient and clinician in both practices differ from the fiduciary professional relationship typical of clinical medicine. Are living organ donation and clinical trial participation real duties? Are the risks accepted in clinical trial participation and organ removal truly comparable? These are crucial questions; however, this article focuses on a related yet perhaps more important question: are the informed consent procedures for organ donation and clinical trial participation comparable?
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GENERAL ASPECTS OF INFORMED CONSENT FOR RESEARCH ON HUMAN SUBJECTS AND FOR LIVING ORGAN DONATION
Ethically justifiable living organ donation presupposes the voluntary decision of consent from a confirmed competent
donor on the basis of adequate information.4 From this, we can derive the three essential components of all types of informed consent: prerequisites, information, and decision.5 First, the two main prerequisites for informed consent must be met: competence, which comprises sufficient ability to understand and decision-making capacity, and voluntariness, or lack of constraint or undue pressure. Next, because information is essential, health care workers have the duty to provide complete information to subjects having met the prerequisites. Once complete information has been ensured, the final step of decision and authorization can occur. Unless participation is irrevocable once the medical procedure has begun, such as in the case of an organ removal operation, the subject should maintain the right to withdraw consent at any point and for any reason. Consent is also said to be related (ie, part of the physician–patient therapeutic alliance), informed (ie, expressed after the subject has been informed of all elements necessary for a
From the Bioethics Unit, Office of the President, Istituto Superiore di Sanità, Rome, Italy. Address reprint requests to Carlo Petrini, Bioethics Unit, Office of the President, Istituto Superiore di Sanità, Via Giano della Bella 34, 00162 Roma, Italy. E-mail: [email protected]
0041-1345/10/$–see front matter doi:10.1016/j.transproceed.2010.03.075
© 2010 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
1040
Transplantation Proceedings, 42, 1040 –1042 (2010)
ETHICAL ISSUES WITH INFORMED CONSENT
complete understanding of the situation), and detailed (ie, specific, referring to a real, definite situation).6 Truly informed consent may be difficult if not impossible to obtain.7 According to the Nuffield Council on Bioethics, “fully informed consent is . . . an unattainable ideal.”8 General ethical concerns about informed consent for living organ donation focus on the potential donor’s competence,9 level of understanding, and free and voluntary choice,10 whatever the relationship between the donor and the recipient may be.11 Yet when the candidate donor is related to the recipient, further specific concerns arise about the dangerous risks of undue pressure, coercion, and influence.12 These risks are present even when the donor is competent, has received adequate information, and appears to understand the information.13 Moreover, several studies show that most kidney donors decide to donate immediately upon learning of the need, and most do not change their minds after having received the appropriate information.14 In fact, with this in mind, some authors believe that a profound understanding of all of the technical and scientific aspects is not fundamental: they think that genuine donor consent is most important, meaning that the subject truly and freely wishes to donate.15 In this light, the problem comes back to determining what level of understanding is necessary to consider a person’s consent valid. NONMALEFICENCE, HARM, AND HIPPOCRATIC ETHICS
Living donor transplantation engenders a conflict between the duty to do no harm and the duty to respect the donor’s autonomy, both of which are fundamental pillars of medical ethics.16,17 If interpreted in a strict sense, the duty to do no harm would prevent surgeons from removing organs even if a person consented, because there would be no direct benefit for the subject being harmed. In fact, regardless of good success rates, recovery rates, and postoperative functionality with one less organ, organ removal causes definite though not incapacitating harm (cutting open the body and removing a healthy organ), and leaves the donor at risk of other complications associated with surgical interventions.18 Clearly, then, there is a need to clarify the meaning of harm in order to properly understand the duty to do no harm. It implausible to take a narrow view of harm as purely physical, particularly if organ donation is ever to be justified. Broadening the understanding of harm to the idea of a cost, the duty to do no harm should be weighed against the cost to the donor of foregoing donation,19 which may include psychological components. The comparison is not easy, and two main difficulties arise: first, how can costs and benefits be measured; second, who is the person entitled to weigh those costs and benefits? The latter is known as the problem of the best judge, and it is heavily debated in the ethical literature on medical paternalism.20 Ultimately, the ostensibly conflicting duties of doing no harm and respecting autonomy are not irreconcilable: doing no harm need not exclude organ donation, and respecting
1041
autonomy need not require it. Indeed, there are still other factors that can be taken into account in balancing these values. Despite the potential conflict of voluntary living organ donation with the principle of beneficence and nonmaleficence, it can be ethically justified based on various arguments, two of which include the benefits for the organ recipient (and therefore for the whole society) and the high moral value of donation and solidarity.21 INFORMED CONSENT AND THE PROBLEM OF AUTONOMY: DIFFERENCES BETWEEN LIVING ORGAN DONATION AND THE PARTICIPATION OF HUMAN SUBJECTS IN CLINICAL RESEARCH
Living organ donation and research on human subjects are only comparable if we consider the first phase of clinical experimentation, which involves healthy volunteers and therefore expects no physical benefits; subsequent phases instead apply to sick patients in whom a direct physical benefit is the goal, though oftentimes it is not achieved. In contrast, direct physical benefit is neither the goal nor an expectation for living organ donors: in fact, they necessarily undergo physical harm. Furthermore, living organ donor autonomy is much more ambiguous than research participant autonomy: while the knowledge or benefit derived from clinical research goes to third parties unrelated to the volunteer, organ recipients are to be strictly related to the donor in most countries. This leads to the concern that donor autonomy may be jeopardized by an undue sense of obligation: “pressures [to donate] may make it impossible for someone to choose freely . . . . Does anyone really think parents can say ’No’ when the option is certain death for their own son or daughter?”22 In other words, a potential organ donor may feel trapped and forced to donate for fear of damaging relationships with family members or with others who strongly desire the transplantation. Fortunately, transplant surgeons are conscious of this and often consider it acceptable to offer potential donors a medical excuse for donation refusal, alleviating pressure while safeguarding relationships with family and others desiring the donation.23 Although explicit pressures to donate are unusual, some studies have shown that kidney transplant candidates frequently attempt to recruit a donor.24 Situations of this nature are highly unlikely in clinical trials. DISCUSSION AND PROPOSALS
A comparative study of living organ donation and clinical trial participation may therefore be a helpful way of identifying improvements for the living organ donation informed consent process. At the least, a rigorous framework of rules to minimize risks, guarantee fairness, and promote high technical and organizational standards is crucial to the ethical acceptability of living organ donation.25,26 Although an absolutely free and informed consent is illusory, a continuous effort must be made to improve the procedures. Such effort is dutiful and commendable despite some of the major differences between living organ donation and clinical trial participation.
1042
Generally speaking, living organ donation is probably the field of medicine with the most regulated, detailed, and controlled process of informed consent. In fact, most countries have compulsory informed consent procedures involving demanding checks and verifications.27 Yet at the same time, organ removal and transplantation protocols are seldom submitted for review by ethics committees. On the other hand, submission of clinical trail protocols for review by an ethics committee is compulsory and tightly regulated in most countries, whereas the informed consent process is often hurried, neglected, and reduced to a bureaucratic formality.28 It therefore seems that living organ donation and clinical trial participation procedures should learn from one another. As a final thought, the strict controls on the validity of organ donor informed consent, which are necessary for an adequate protection of the person, also might have undesirable consequences: excessive informed consent controls might become burdensome and exasperating for the candidate donor and engender suspicion that living donor organ donation is a stain on the field of medicine requiring a sort of redemption.29 Given this, together with the comparisons between living organ donation and human subject participation, a final suggestion for both field is offered: evaluation by an ethics committee is highly recommendable, and verification of valid informed consent should be highly rigorous yet not overburdening. REFERENCES 1. Hester M: Why must we leave our organs to others. Am J Bioethics 6:W23, 2006 2. Schaefer GO, Emanuel EJ, Wertheimer A: The obligation to participate in biomedical research. JAMA 302:67, 2009 3. Miller FG, Joffe S: Limits to research risks. J Med Ethics 35:445, 2009 4. World Medical Association: Statement on human organ and tissue donation and transplantation. Adopted by the 52nd WMA General Assembly in Edinburgh, Scotland during October 2000 and Revised by the WMA General Assembly, Pilanesberg, South Africa, October 2006. Available at: www.wma.net/en/30publications/ 10policies/wma/index.html. Accessed October 10, 2009 5. Beauchamp T, Childress JF: Principles of Biomedical Ethics, 5th ed. Oxford: Oxford University Press; 2001, p 80 6. United Nations Educational, Scientific and Cultural Organization (UNESCO), Report of the International Bioethics Committee (IBC) on consent. Available at: unesdoc.unesco.org/images/ 0017/001781/178124E.pdf. Accessed October 10, 2009 7. Wilkinson TM: Living donor organ transplantation. In Ashcroft RE, Dawson A, Draper H, et al (eds): Principles of Health Care Ethics, 2nd ed. Hoboken: John Wiley; 2007 p 433 8. Nuffield Council on Bioethics: Human tissue: Ethical and legal issues. London: Nuffield Council on Bioethics, 1995, p 45. Available at: www.nuffieldbioethics.org/fileLibrary/pdf/human_ tissue.pdf. Accessed October 10, 2009 9. Wong JG, Clare CL, Gunn MJ, Holland AJ: Capacity to make health care decisions: its importance to clinical practice. Psychol Med 29:437, 1999
PETRINI 10. Schneewind KA: Psychological aspects in living organ donation. In: Collins GM, Dubernard JM, Persijn GG, et al (eds): In: Procurement and Preservation of Vascularized Organs. Dordrecht: Kluwer; 1997, p 325 11. Reese P, Abt P, Bloom R: Protecting live kidney and liver donors. In: Ravitsky V, Autumn F, Caplan AL (eds): The Penn Center Guide to Bioethics. New York: Springer; 2009, p 735 12. Truog RD: The ethics of organ donation by living donors. N Engl J Med 353:444, 2005 13. Veatch RM: Live-donor organ transplant: including the permanent unconscious and paired- and live-donor/cadaver exchanges. In: Transplantation Ethics. Washington: Georgetown University Press; 2000, p 182 14. Stothers L, Gourlay WA, Liu L: Attitudes and predictive factors for live kidney donation: a comparison of live kidney donors versus non donors. Kidney Int 67:1105, 2005 15. Fox RC, Swazey JP: Organ transplants, sociocultural aspects of. In: Post SG (ed): Encyclopedia of Bioethics, 3rd ed. New York: Macmillan Reference-Thomson Gale; 2003, p 1953 16. Levine RJ: The National Commission’s ethical principles, with special attention to beneficence. In: Childress JF, Meslin EM, Shapiro HT (eds): Belmont Revisited: Ethical Principles for Research With Human Subjects. Washington: Georgetown University Press; 2005, p 126 17. Cullity J: Beneficence. In: Ashcroft RE, Dawson A, Draper H, et al (eds): Principles of Health Care Ethics, 2nd ed. Hoboken: John Wiley; 2007, p 11 18. Glannon W: Underestimating the risk in living kidney donation. J Med Ethics 34:127, 2008 19. Ingelfinger JR: Risks and benefits to the living donor. N Engl J Med 353:447, 2005 20. Beauchamp TL: Paternalism. In: Post SG (ed). Encyclopedia of Bioethics, 3rd ed. New York: Macmillan Reference-Thomson Gale; 2003, p 2983 21. Council of Europe: Additional protocol to Convention on Human Rights and Biomedicine, on transplantation of organs and tissues of human origin (text and explanatory report). 22 January 2002. Available at: conventions.coe.int/treaty/EN/treaties/html/ 186.htm. Accessed October 10, 2009 22. Caplan A: Must I be my brother’s keeper? Ethical issues in the use of living donors as source of liver and other solid organs. Transplant Proc 25:1997, 1993 23. Cotler SJ, Cotler S, Gambera M, et al: Adult living donor liver transplantation: perspectives from 100 liver transplant surgeons. Liver Transpl 9:637, 2003 24. Reese PP, Shea JA, Berns JS, et al: Recruitment of live donors by candidates for kidney transplantation. Clin J Am Soc Nephrol 3:1152, 2008 25. World Health Organization: Guiding principles on human organ transplantation. Lancet 337:1470, 1991 26. World Health Organization: Guiding principles on human organ transplantation. Revised on 26 May 2008. Note EB123/5. Available at: www.who.int/transplantation/txgp08-en.pdf. Accessed October 10, 2009 27. Principes éthiques et législation comparées en Europe: le cas des transplatnations rénales: In: Collange JF: Éthique et transplantation d’organes. Paris: Ellipses; 2000, p 194 28. Palmer BW, Cassidy EL, Dunn LB, et al: Effective use of consent forms and interactive questions in the consent process. IRB Ethics Human Res 30:8, 2008 29. Reese PP, Shea JA, Berns JS, et al: Recruitment of live donors by candidates for kidney transplantation. Clin J Am Soc Nephrol 3:1152, 2008
O
GENERAL ASPECTS OF INFORMED CONSENT FOR RESEARCH ON HUMAN SUBJECTS AND FOR LIVING ORGAN DONATION
Ethically justifiable living organ donation presupposes the voluntary decision of consent from a confirmed competent
donor on the basis of adequate information.4 From this, we can derive the three essential components of all types of informed consent: prerequisites, information, and decision.5 First, the two main prerequisites for informed consent must be met: competence, which comprises sufficient ability to understand and decision-making capacity, and voluntariness, or lack of constraint or undue pressure. Next, because information is essential, health care workers have the duty to provide complete information to subjects having met the prerequisites. Once complete information has been ensured, the final step of decision and authorization can occur. Unless participation is irrevocable once the medical procedure has begun, such as in the case of an organ removal operation, the subject should maintain the right to withdraw consent at any point and for any reason. Consent is also said to be related (ie, part of the physician–patient therapeutic alliance), informed (ie, expressed after the subject has been informed of all elements necessary for a
From the Bioethics Unit, Office of the President, Istituto Superiore di Sanità, Rome, Italy. Address reprint requests to Carlo Petrini, Bioethics Unit, Office of the President, Istituto Superiore di Sanità, Via Giano della Bella 34, 00162 Roma, Italy. E-mail: [email protected]
0041-1345/10/$–see front matter doi:10.1016/j.transproceed.2010.03.075
© 2010 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
1040
Transplantation Proceedings, 42, 1040 –1042 (2010)
ETHICAL ISSUES WITH INFORMED CONSENT
complete understanding of the situation), and detailed (ie, specific, referring to a real, definite situation).6 Truly informed consent may be difficult if not impossible to obtain.7 According to the Nuffield Council on Bioethics, “fully informed consent is . . . an unattainable ideal.”8 General ethical concerns about informed consent for living organ donation focus on the potential donor’s competence,9 level of understanding, and free and voluntary choice,10 whatever the relationship between the donor and the recipient may be.11 Yet when the candidate donor is related to the recipient, further specific concerns arise about the dangerous risks of undue pressure, coercion, and influence.12 These risks are present even when the donor is competent, has received adequate information, and appears to understand the information.13 Moreover, several studies show that most kidney donors decide to donate immediately upon learning of the need, and most do not change their minds after having received the appropriate information.14 In fact, with this in mind, some authors believe that a profound understanding of all of the technical and scientific aspects is not fundamental: they think that genuine donor consent is most important, meaning that the subject truly and freely wishes to donate.15 In this light, the problem comes back to determining what level of understanding is necessary to consider a person’s consent valid. NONMALEFICENCE, HARM, AND HIPPOCRATIC ETHICS
Living donor transplantation engenders a conflict between the duty to do no harm and the duty to respect the donor’s autonomy, both of which are fundamental pillars of medical ethics.16,17 If interpreted in a strict sense, the duty to do no harm would prevent surgeons from removing organs even if a person consented, because there would be no direct benefit for the subject being harmed. In fact, regardless of good success rates, recovery rates, and postoperative functionality with one less organ, organ removal causes definite though not incapacitating harm (cutting open the body and removing a healthy organ), and leaves the donor at risk of other complications associated with surgical interventions.18 Clearly, then, there is a need to clarify the meaning of harm in order to properly understand the duty to do no harm. It implausible to take a narrow view of harm as purely physical, particularly if organ donation is ever to be justified. Broadening the understanding of harm to the idea of a cost, the duty to do no harm should be weighed against the cost to the donor of foregoing donation,19 which may include psychological components. The comparison is not easy, and two main difficulties arise: first, how can costs and benefits be measured; second, who is the person entitled to weigh those costs and benefits? The latter is known as the problem of the best judge, and it is heavily debated in the ethical literature on medical paternalism.20 Ultimately, the ostensibly conflicting duties of doing no harm and respecting autonomy are not irreconcilable: doing no harm need not exclude organ donation, and respecting
1041
autonomy need not require it. Indeed, there are still other factors that can be taken into account in balancing these values. Despite the potential conflict of voluntary living organ donation with the principle of beneficence and nonmaleficence, it can be ethically justified based on various arguments, two of which include the benefits for the organ recipient (and therefore for the whole society) and the high moral value of donation and solidarity.21 INFORMED CONSENT AND THE PROBLEM OF AUTONOMY: DIFFERENCES BETWEEN LIVING ORGAN DONATION AND THE PARTICIPATION OF HUMAN SUBJECTS IN CLINICAL RESEARCH
Living organ donation and research on human subjects are only comparable if we consider the first phase of clinical experimentation, which involves healthy volunteers and therefore expects no physical benefits; subsequent phases instead apply to sick patients in whom a direct physical benefit is the goal, though oftentimes it is not achieved. In contrast, direct physical benefit is neither the goal nor an expectation for living organ donors: in fact, they necessarily undergo physical harm. Furthermore, living organ donor autonomy is much more ambiguous than research participant autonomy: while the knowledge or benefit derived from clinical research goes to third parties unrelated to the volunteer, organ recipients are to be strictly related to the donor in most countries. This leads to the concern that donor autonomy may be jeopardized by an undue sense of obligation: “pressures [to donate] may make it impossible for someone to choose freely . . . . Does anyone really think parents can say ’No’ when the option is certain death for their own son or daughter?”22 In other words, a potential organ donor may feel trapped and forced to donate for fear of damaging relationships with family members or with others who strongly desire the transplantation. Fortunately, transplant surgeons are conscious of this and often consider it acceptable to offer potential donors a medical excuse for donation refusal, alleviating pressure while safeguarding relationships with family and others desiring the donation.23 Although explicit pressures to donate are unusual, some studies have shown that kidney transplant candidates frequently attempt to recruit a donor.24 Situations of this nature are highly unlikely in clinical trials. DISCUSSION AND PROPOSALS
A comparative study of living organ donation and clinical trial participation may therefore be a helpful way of identifying improvements for the living organ donation informed consent process. At the least, a rigorous framework of rules to minimize risks, guarantee fairness, and promote high technical and organizational standards is crucial to the ethical acceptability of living organ donation.25,26 Although an absolutely free and informed consent is illusory, a continuous effort must be made to improve the procedures. Such effort is dutiful and commendable despite some of the major differences between living organ donation and clinical trial participation.
1042
Generally speaking, living organ donation is probably the field of medicine with the most regulated, detailed, and controlled process of informed consent. In fact, most countries have compulsory informed consent procedures involving demanding checks and verifications.27 Yet at the same time, organ removal and transplantation protocols are seldom submitted for review by ethics committees. On the other hand, submission of clinical trail protocols for review by an ethics committee is compulsory and tightly regulated in most countries, whereas the informed consent process is often hurried, neglected, and reduced to a bureaucratic formality.28 It therefore seems that living organ donation and clinical trial participation procedures should learn from one another. As a final thought, the strict controls on the validity of organ donor informed consent, which are necessary for an adequate protection of the person, also might have undesirable consequences: excessive informed consent controls might become burdensome and exasperating for the candidate donor and engender suspicion that living donor organ donation is a stain on the field of medicine requiring a sort of redemption.29 Given this, together with the comparisons between living organ donation and human subject participation, a final suggestion for both field is offered: evaluation by an ethics committee is highly recommendable, and verification of valid informed consent should be highly rigorous yet not overburdening. REFERENCES 1. Hester M: Why must we leave our organs to others. Am J Bioethics 6:W23, 2006 2. Schaefer GO, Emanuel EJ, Wertheimer A: The obligation to participate in biomedical research. JAMA 302:67, 2009 3. Miller FG, Joffe S: Limits to research risks. J Med Ethics 35:445, 2009 4. World Medical Association: Statement on human organ and tissue donation and transplantation. Adopted by the 52nd WMA General Assembly in Edinburgh, Scotland during October 2000 and Revised by the WMA General Assembly, Pilanesberg, South Africa, October 2006. Available at: www.wma.net/en/30publications/ 10policies/wma/index.html. Accessed October 10, 2009 5. Beauchamp T, Childress JF: Principles of Biomedical Ethics, 5th ed. Oxford: Oxford University Press; 2001, p 80 6. United Nations Educational, Scientific and Cultural Organization (UNESCO), Report of the International Bioethics Committee (IBC) on consent. Available at: unesdoc.unesco.org/images/ 0017/001781/178124E.pdf. Accessed October 10, 2009 7. Wilkinson TM: Living donor organ transplantation. In Ashcroft RE, Dawson A, Draper H, et al (eds): Principles of Health Care Ethics, 2nd ed. Hoboken: John Wiley; 2007 p 433 8. Nuffield Council on Bioethics: Human tissue: Ethical and legal issues. London: Nuffield Council on Bioethics, 1995, p 45. Available at: www.nuffieldbioethics.org/fileLibrary/pdf/human_ tissue.pdf. Accessed October 10, 2009 9. Wong JG, Clare CL, Gunn MJ, Holland AJ: Capacity to make health care decisions: its importance to clinical practice. Psychol Med 29:437, 1999
PETRINI 10. Schneewind KA: Psychological aspects in living organ donation. In: Collins GM, Dubernard JM, Persijn GG, et al (eds): In: Procurement and Preservation of Vascularized Organs. Dordrecht: Kluwer; 1997, p 325 11. Reese P, Abt P, Bloom R: Protecting live kidney and liver donors. In: Ravitsky V, Autumn F, Caplan AL (eds): The Penn Center Guide to Bioethics. New York: Springer; 2009, p 735 12. Truog RD: The ethics of organ donation by living donors. N Engl J Med 353:444, 2005 13. Veatch RM: Live-donor organ transplant: including the permanent unconscious and paired- and live-donor/cadaver exchanges. In: Transplantation Ethics. Washington: Georgetown University Press; 2000, p 182 14. Stothers L, Gourlay WA, Liu L: Attitudes and predictive factors for live kidney donation: a comparison of live kidney donors versus non donors. Kidney Int 67:1105, 2005 15. Fox RC, Swazey JP: Organ transplants, sociocultural aspects of. In: Post SG (ed): Encyclopedia of Bioethics, 3rd ed. New York: Macmillan Reference-Thomson Gale; 2003, p 1953 16. Levine RJ: The National Commission’s ethical principles, with special attention to beneficence. In: Childress JF, Meslin EM, Shapiro HT (eds): Belmont Revisited: Ethical Principles for Research With Human Subjects. Washington: Georgetown University Press; 2005, p 126 17. Cullity J: Beneficence. In: Ashcroft RE, Dawson A, Draper H, et al (eds): Principles of Health Care Ethics, 2nd ed. Hoboken: John Wiley; 2007, p 11 18. Glannon W: Underestimating the risk in living kidney donation. J Med Ethics 34:127, 2008 19. Ingelfinger JR: Risks and benefits to the living donor. N Engl J Med 353:447, 2005 20. Beauchamp TL: Paternalism. In: Post SG (ed). Encyclopedia of Bioethics, 3rd ed. New York: Macmillan Reference-Thomson Gale; 2003, p 2983 21. Council of Europe: Additional protocol to Convention on Human Rights and Biomedicine, on transplantation of organs and tissues of human origin (text and explanatory report). 22 January 2002. Available at: conventions.coe.int/treaty/EN/treaties/html/ 186.htm. Accessed October 10, 2009 22. Caplan A: Must I be my brother’s keeper? Ethical issues in the use of living donors as source of liver and other solid organs. Transplant Proc 25:1997, 1993 23. Cotler SJ, Cotler S, Gambera M, et al: Adult living donor liver transplantation: perspectives from 100 liver transplant surgeons. Liver Transpl 9:637, 2003 24. Reese PP, Shea JA, Berns JS, et al: Recruitment of live donors by candidates for kidney transplantation. Clin J Am Soc Nephrol 3:1152, 2008 25. World Health Organization: Guiding principles on human organ transplantation. Lancet 337:1470, 1991 26. World Health Organization: Guiding principles on human organ transplantation. Revised on 26 May 2008. Note EB123/5. Available at: www.who.int/transplantation/txgp08-en.pdf. Accessed October 10, 2009 27. Principes éthiques et législation comparées en Europe: le cas des transplatnations rénales: In: Collange JF: Éthique et transplantation d’organes. Paris: Ellipses; 2000, p 194 28. Palmer BW, Cassidy EL, Dunn LB, et al: Effective use of consent forms and interactive questions in the consent process. IRB Ethics Human Res 30:8, 2008 29. Reese PP, Shea JA, Berns JS, et al: Recruitment of live donors by candidates for kidney transplantation. Clin J Am Soc Nephrol 3:1152, 2008