'Oh pick me, pick me' - Selecting participants for xenotransplant clinical trials

Medical Law Review

Volumn 15, Issue 2, 2007, Pages 176-219

  Fovargue, Sara ^a  

^a LANCASTER UNIVERSITY   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ARTICLE; CLINICAL TRIAL; ETHICS; HUMAN; LEGAL ASPECT; MEDICAL RESEARCH; PATIENT SELECTION; UNITED KINGDOM; XENOGRAFT;

BIOMEDICAL RESEARCH; CLINICAL TRIALS; GREAT BRITAIN; HUMANS; PATIENT SELECTION; TRANSPLANTATION, HETEROLOGOUS;

EID: 34547118608     PISSN: 09670742     EISSN: 14643790     Source Type: Journal    
DOI: 10.1093/medlaw/fwm005     Document Type: Article

References (370)

1. H. Rosenau, 'Legal Prerequisites for Clinical Trials under the Revised Declaration of Helsinki and the European Convention on Human Rights and Biomedicine' (2000) 7 European Journal of Health Law 105 at 106.
2. See, for example, S. Boseley, 'Six Men in Intensive Care after Drug Trial Goes Wrong' The Guardian 15 March 2006.
3. Following the unexpected side effects of the trial the Medicines and Healthcare products Regulatory Agency (MHRA) conducted an investigation into the trial and published the results in May 2006: MHRA, Investigations into Adverse Incidents during Clinical Trials of TGN1412 (2006): http://www.mhra.gov.uk.
4. The Government also established an expert group to learn from the incident and its findings were published in December 2006: Expert Group on Phase One Clinical Trials, Final Report (2006): http://www.dh.gov.uk.
5. I. Sample and J. Maley, 'Interest Surges in Trials Despite Patients' Plight' The Guardian 18 March 2006.
6. Department of Health (DH), Xenotransplantation Guidance (2006) at 1: http://www.advisorybodies.doh.gov.uk/ukxira.
7. A table listing cardiac non-human to human animal xenotransplants to date can be found in M.J. Weiss, C.Y. Ng and J.C. Madsen, 'Tolerance, Xenotransplantation: Future Therapies' (2006) 86 Surgical Clinics of North American 1277.
8. In relation to the 1992 cardiac xenotransplant, see J. Czaplicki and B. Blońska, 'The Lack of Hyperacute Xenogeneic Heart Transplant Rejection in a Human - Letter' (1992) 11 The Journal of Heart and Lung Transplantation 393.
9. It was reported that a pig's heart was xenotransplanted into a human in India in 1996, but the results of this experiment have not been published: See K.S. Jayaraman, 'Pig Heart Transplant Surgeon Held in Jail' (1997) 385 Nature 378.
10. See, for example, A. Warrens, 'When Will We Be Able To Use Animal Organs in Human Transplantation?' presented at the British Association Festival of Science, Dublin on 9 September 2005: http://www1.the-ba.net/ presspapers/showtalk2.asp?TalkID=459
11. A.J.F. d'Apice, 'Seventh Congress of the International Xenotransplantation Association, Glasgow, 2003: "In vivo" highlights' (2004) 11 Xenotransplantation 228.
12. This information gap makes it questionable whether a potential xeno-recipient can give her 'informed' consent to the procedure, an issue which has been explored elsewhere. See, for example, S. Fovargue, 'Consenting to Bio-Risk: Xenotransplantation and the Law' (2005) 25 Legal Studies 404;
13. S.A.M. McLean and L. Williamson, Xenotransplantation - Law and Ethics (Ashgate 2005) at Ch. 7;
14. P.S. Florencio and E.D. Ramanathan, 'Legal Enforcement of Xenotransplantation Public Health Safeguards' (2004) 32 Journal of Law, Medicine and Ethics 117.
15. S. Welin, 'Starting Clinical Trials of Xenotransplantation - Reflections on the Ethics of the Early Phase' (2000) 26 Journal of Medical Ethics 231.
16. It was assumed that this type of patient might be involved in early xenotransplants in the two UK reports on the subject: A Report by the Advisory Group of the Ethics of Xenotransplantation, Animal Tissue into Humans (DH 1996) (the Kennedy Report) at paras 7.6 and 7.8;
17. Nuffield Council on Bioethics, Animal-to-Human Transplants - The Ethics of Xenotransplantation (Nuffield Council on Bioethics 1996) at para 7.11.
18. See, for example, Z. Ibrahim et al., 'Which Patients First? Planning the First Clinical Trial of Xenotransplantation: A Case for Cardiac Bridging' (2005) 12 Xenotransplantation 168;
19. D.K.C. Cooper et al., 'Report of the Xenotransplantation Advisory Committee of the International Society for Heart and Lung Transplantation: The Present Status of Xenotransplantation and Its Potential Role in the Treatment of End-Stage Cardiac and Pulmonary Diseases' (2000) 19 Journal of Heart and Lung Transplantation 1125.
20. See McLean and Williamson, supra, n. 7 at 29-30;
21. K. Reemtsma et al., 'Renal Heterotransplantation in Man' (1964) 160 Annals of Surgery 384;
22. T.E. Starzl et al., 'Renal Heterotransplantation from Baboon to Man: Experiences with 6 Cases' (1964) 2 Transplantation 752.
23. Expert Scientific Group on Phase One Clinical Trials, Interim Report (2006) at Ch. 9 recommendation 9: http://www.dh.gov.uk
24. Press Association, 'Stem Cell Research on Humans - Call' The Scotsman 27 December 2005.
25. A. Ravelingien et al., 'Proceeding with Clinical Trials of Animal to Human Organ Transplantation: A Way Out of the Dilemma' (2004) 30 Journal of Medical Ethics 92.
26. W.M. Kong, 'Legitimate Requests and Indecent Proposals: Matters of Justice in the Ethical Assessment of Phase I Trials Involving Competent Patients' (2005) 31 Journal of Medical Ethics 205.
27. Royal College of Physicians (RCP), Guidelines on the Practice of Ethics Committees in Medical Research Involving Human Subjects, 3rd edn. (1996) at paras A1.2-A1.3.
28. Supra, n. 13 at 206.
29. Ibid., 207.
30. Ibid.
31. D.K.C. Cooper and R.P. Lanza, Xeno - The Promise of Transplanting Animal Organs into Humans (Oxford University Press 2000) at 178.
32. For criticisms of RECs see, for example, C.G. Foster, 'The Development and Future of Research Ethics Committees in Britain' in A. Grubb (ed.) Choice and Decisions in Health Care (John Wiley and Sons 1993).
33. For non-genetically modified xenogeneic medicinal products, this review will be in addition to the ethical review conducted by the MHRA. For genetically modified xenogeneic medicinal products, ethical review will be conducted by the MHRA & the Gene Therapy Advisory Committee: Supra n. 4 at 2-3.
34. See, for example, Council of Europe, Recommendation Rec (2003)10 of the Committee of Ministers to member states on xenotransplantation : http://www.coe.int
35. World Health Organization (WHO), WHO Guidance on Xenogeneic Infection/ Disease Surveillance and Response: A Strategy for International Cooperation and Coordination WHO/CDS/CSR/EPH/2001.2: http://www.who.int/emc.
36. There may also be different liability and insurance issues if a procedure is defined as experimental treatment rather than medical research.
37. The assumption that the desperately ill with little or 'no other hope' are competent is questionable and I have discussed this elsewhere: See Fovargue, supra, n. 7.
38. Here I am assuming that they are competent and that only competent people will be included in the initial xenotransplants because of the post-xenotransplant regime which must be complied with: supra, n. 21.
39. See J. Katz, 'Human Experimentation and Human Rights' (1993) 38 Saint Louis University Law Journal 7;
40. M. Bassiouni et.al., 'An Appraisal of Human Experimentation in International Law and Practice: The Need for International Regulation of Human Experimentation' (1981) 72 The Journal of Criminal Law and Criminology 1597.
41. See, for example, Bassiouni et al., ibid.
42. DH, Research Governance Framework for Health and Social Care, 2nd edn. (2005) at para 1.10: http://www.dh.gov.uk.
43. C. Faulder, Whose Body Is It?: The Troubling Issue of Informed Consent (Virago Press 1985) at 65.
44. See also P.M. McNeill, The Ethics and Politics of Human Experimentation (Cambridge University Press 1993) at 11-12.
45. Katz, supra, n. 24 at 13.
46. Ibid., at 15-16.
47. W.M. Kong, 'The Regulation of Gene Therapy Research in Competent Adult Patients, Today and Tomorrow: Implications of EU Directive 2001/20/EC' (2004) 12 Med. L. Rev. 164 at 170-171.
48. I am grateful to José Miola for his patience in allowing me to work through my confusion over this distinction, and the implications thereof, with him.
49. For a discussion of this distinction see, for example, supra, n. 14 at paras 6.4-6.6.
50. See R.C. Fox and J.P. Swazey, The Courage to Fail - A Social View of Organ Transplants and Dialysis (Transaction Publishers 2002) at Ch. 3. They suggest that 'the experiment-to-therapy process is neither a simple, linear progression, totally conscious, entirely logical and rational, nor altogether biomedically determined', at 305.
51. The Medicines for Human Use (Clinical Trials) Regulations 2004, S.I. 2004 No. 1031, implementing Directive 2001/20/EC of the European Parliament and of the Council, On the Approximation of the Laws, Regulations, and Administrative Provisions of the Members States Relating to the Implementation of Good Clinical Practice in the Conduct of Clinical Trials on Medicinal Products for Human Use. The 2004 Regulations were amended in 2006: The Medicines for Human Use (Clinical Trials) Amendment Regulations 2006 - SI 2006/1928, implementing into UK law Directive 2005/28/EC laying down principles and detailed guidelines for good clinical practice as regards investigational medicinal products for human use, as well as the requirements for authorisation of the manufacturing or importation of such products, (the GCP Directive).
52. See T.K. Hervey and J.V. McHale, Health Law and the European Union (Cambridge University Press 2004) at 251.
53. Confusingly, the British Medical Association (BMA) uses the terms 'clinical trials' and 'experimental treatment' interchangeably in their Clinical Trials Internet Resource material, see 'Involving Patients: Participation Concerns' and 'End of Trial' (2004): http://www.bma.org.uk.
54. I. Kennedy and A. Grubb, Medical Law, 3rd ed. (Butterworths 2000) at 1686.
55. See, for example, J.K. Mason and G.T. Laurie, Mason & McCall Smith's Law and Medical Ethics (Oxford University Press 2006) at 651;
56. McNeill, supra, n. 27 at 12.
57. Mason and Laurie, ibid.
58. See also supra, n. 14 at note to para 6.5.
59. Mason and Laurie, ibid.
60. See also the definition provided by the Institute of Medical Ethics - 'innovative therapy consists in the performance of a new or non-standard intervention as all or part of a therapeutic activity and not as part of a formal research project': R.H. Nicholson (ed.) Medical Research with Children: Ethics, Law, and Practice - The Report of an Institute of Medical Ethics Working Group on the Ethics of Clinical Research Investigations on Children (Oxford University Press 1986) at 36, emphasis in original.
61. J.A. Harrington, 'Deciding Best Interests: Medical Progress, Clinical Judgment and the "Good Family"'[2003] 3 Web Journal of Current Legal Issues: http://webjcli.ncl.ac.uk.
62. Supra, n. 14 at note to para 6.5, emphasis supplied.
63. Mason and Laurie, supra, n. 37 at 668.
64. Mason and Laurie, supra, n. 37 at 651.
65. See, for example, Health Canada, Proposed Canadian Standard for Xenotransplantation (Health Canada 1999): http://www.hc-sc.gc.ca at 4
66. supra, n. 18 at 179;
67. A.S. Daar, 'Choosing Risk-Benefit Analysis or Precautionary Principle as Our Approach to Clinical Xenotransplantation' (2001) 4 Graft 164.
68. Nuffield Report, supra, n. 8 at paras 7.5-7.6.
69. Ibid., at paras 1.20-1.1.21.
70. See also J.M. Kress, 'Xenotransplantation: Ethics and Economics' (1998) 53 Food and Drug Law Journal 353 at 371: 'Given the poor survival rates of those receiving xenografts today, it would be fair to conclude that early recipients are being used primarily as experimental subjects for the development of xenotransplantation as a viable technology. Many of these patients willingly participate, with their motive being the contribution they are making to medical progress'.
71. See, for example, G.E. Pence, Classic Cases in Medical Ethics (McGraw-Hill 1990) at Ch. 12;
72. G.J. Annas, Judging Medicine (Humana Press 1990) at 384-421;
73. L.L. Hubbard, 'The Baby Fae Case' (1987) 6 Medicine and Law 385.
74. See, for example, E. Knoll and G.D. Lundberg, 'Informed Consent and Baby Fae' (1985) 254 Journal of the American Medical Association 3359;
75. A.L. Caplan, 'Ethical Issues Raised by Research Involving Xenografts' (1985) 254 Journal of the American Medical Association 3339.
76. Mason and Laurie, supra, n. 37 at 679.
77. Reemtsma, supra, n. 10.
78. G. Griffin and D. Muir, Infection Risks in Xenotransplantation (DH 2001).
79. M.J. Goddard et al., 'Histopathology of Cardiac Xenograft Rejection in the Pig-to-Baboon Model' (2002) 21 The Journal of Heart and Lung Transplantation 474.
80. Recently, 179 days survival was achieved in non-life supporting heart xenotransplants between pigs and baboons, but only one of the eight baboons survived this long with the median survival being 78 days: K. Kuwaki, 'Heart Transplantation in Baboons using α1,3-galactosyltransferase Gene-Knockout Pigs as Donors: Initial Experience' (2005) 11 Nature Medicine 29.
81. J.B. Cabezuelo, et al., 'Assessment of Renal Function During the Postoperative Period Following Liver Xenotransplantation From Transgenic Pig to Baboon' (2002) 34 Transplantation Proceedings 321.
82. K. Yamada et al., 'Marked Prolongation of Porcine Renal Xenograft Survival in Baboons through the use of α1,3-galactosyltransferase Gene-Knockout Donors and the Cotransplantation of Vascularized Thymic Tissue' (2005) 11 Nature Medicine 32.
83. See, for example, D.K.C. Cooper et al., 'Xenotranplantation - How Far Have We Come?' (2002) 9 Transplant Immunology 251;
84. B. Soin et al., 'Physiological Aspects of Pig-to-Primate Renal Xenotransplantation' (2001) 60 Kidney International 1592.
85. For further information see, for example, J.M. Dobson and J.H. Dark, The Physiology of Xenotransplantation (DH 2002);
86. P. Igaz, 'Recent Strategies to Overcome the Hyper-acute Rejection in Pig to Human Xenotransplantation' (2001) 74 Yale Journal of Biology and Medicine 329.
87. For further information, see supra, n. 51;
88. V. Specke et al., 'Virus Safety in Xenotransplantation: First Exploratory In Vivo Studies in Small Laboratory Animals and Non-Human Primates' (2002) 9 Transplant Immunology 281.
89. See, for example, supra, n 21;
90. US Department of Health and Human Services (DHHS), PHS Guideline on Infectious Disease Issues in Xenotransplantation (2001): http://www.fda.gov/cber
91. Health Canada, supra, n. 44;
92. UKXIRA, Draft Report of the Infection Surveillance Steering Group of the UKXIRA, (DH 1999): http://www.advisorybodies.doh.gov.uk/ukxira.
93. UKXIRA, ibid., at para A5.2.
94. McLean and Williamson, supra, n. 7 at 197.
95. Learning from Bristol : The Report of the Public Inquiry into Children's Heart Surgery at the Bristol Royal Infirmary 1984-1995 (The Stationery Office 2001) Cm 5207(I): http://www.bristol-inquiry.org.uk
96. The Royal Liverpool Children's Inquiry Report (The Stationery Office 2001): http://www.rlcinquiry.org.uk.
97. Supra, n. 33 at viii.
98. Ibid.
99. See, for example, Butler-Sloss P. in Simms v. Simms and another
100. PA v. JA and another [2002] EWHC 2734 at para 48.
101. [1995] 2 All ER 129 at 137, C.A.
102. The court was also asked particularly to consider the contentious issue of resource allocation.
103. Supra, n. 64.
104. Ibid. at para 48.
105. Ibid. at paras 57 and 61.
106. Ibid. at para 72, emphasis supplied.
107. M. Brazier, Medicine, Patients and the Law (Penguin 2003) at 405.
108. This treatment was subsequently further approved by Dame Elizabeth Butler-Sloss P. in An NHS Trust v. HM [2004] Lloyd's Law Reports 207;
109. EP v. Trusts A, B & C [2004] Lloyd's Law Reports 211, but still not within the context of formal clinical trials.
110. This conclusion is supported by a number of commentators including D. Price, 'Remodelling the Regulation of Postmodern Innovation in Medicine' (2005) 1 International Journal of Law in Context 121;
111. supra, n. 36 at 1686.
112. The RCP has also suggested that those involved in 'sensitive areas of innovative practice' should consider deeming their work as descriptive or qualitative research in order to be encompassed within the ethics committee regulatory scheme: supra, n. 14 at para 6.7.
113. Bristol Inquiry, supra, n. 61 at paras 100-101. More generally, statutory regulation of the ethics committees system was recommended by the Independent Review Group on Retention of Organs at Post Mortem, Final Report (Scottish Executive 2001) at para 99.
114. Some ethics committees are now on a statutory footing following the implementation of the EC Clinical Trials Directive into UK law via the 2004 Regulations, supra, n. 34 at Parts 2 and 3, as amended by the 2006 Regulations,
115. supra, n. 34 at Regulations 6-14.
116. See E. Jackson, Medical Law Text Cases and Materials (Oxford University Press 2006) at 459-463;
117. S.D. Pattinson, Medical Law and Ethics (Sweet and Maxwell 2006) at 339-340;
118. supra, n. 36 at 1707-1708, 1720-1721;
119. supra, n. 14 at para 6.12.
120. M. Fox,'Clinical Research and Patients: The Legal Perspective' in J. Tingle and A. Cribb (eds.) Nursing Law, and Ethics, 2nd ed. (Blackwell Science 2002) at 252-277, 253.
121. R. Gillon, "'Fully" informed Consent, Clinical Trials and the Boundaries of Therapeutic Discretion' in L. Doyal and J.S. Tobias (eds.) Informed Consent in Medical Research (BMJ Books 2001) at 257-265, 258.
122. Supra, n. 14 at para 7.7.
123. N. Shumway, 'Transplantation of an Unpaired Organ, The Heart' (1969) 63 Proceedings of the the National Academy of Science USA 1032 at 1033.
124. Supra, n. 40.
125. For a further discussion of the competing tensions doctors involved in experimental treatment or research may face see supra, n. 33 at 68.
126. Supra, n. 33 at 88.
127. Nuffield Report, n. 8 at para 7.6;
128. Kennedy Report, supra, n.8 at para 7.5.
129. Council of Europe, supra, n. 21 at Article 5 (1).
130. UKXIRA, Guidance on Making Proposals to Conduct Xenotransplantation on Human Subjects (DH 1998) at paras 5.3 and 4.3, respectively: http://www.advisorybodies.-doh.gov.uk/ukxira. The current UK regulation of xenotransplantation is considered in section IVC.
131. Other reaulators have also assumed that at the stage of clinical trials xenotransplantation will be therapeutic medical research see, for example, US DHHS, Secretary's Advisory Committee on Xenotransplantation (SACX), Informed Consent in Clinical Research involving Xenotransplantation - Draft (2004): http://www4.od.nih.gov/oba/SACX/ reports/IC&Rdbl;aft_030905.pdf
132. Swedish Committee on Xenotransplantation, From One Species to Another - Transplantation from Animals to Humans (1999) Ministry of Health and social Affairs, Swedish Government Official Report, No. 1999:120 at 4, section 5 of the Proposal for an Ordinance (32000:000) on clinical trials on humans involving the transfer of living biological material from animals (Xeno Licensing and Control Ordinance): http://www.oecd.org
133. McLean and Williamson, supra, n. 7 at 208.
134. Supra, n. 64 at para 57.
135. Supra, n. 30 at 168,
136. referencing Re F (Mental Patient: Sterilisation) [1990] 2 AC 1
137. and Re S (Sterilisation: Patient's Best Interests) [2000] 2 FLR 389.
138. Supra, n. 30 at 168.
139. N King, 'Defining and Describing Benefit Appropriately in Clinical Trails (2000) 28 Journal of Law, Medicine and Ethics 332 at 336.
140. [199] PIQR 53 at 59, supporting the judgment of Lord Browne-Wilkinson in Bolitho v. City and Hackney HA [1997] 4 All ER 771, HL.
141. McLean and Williamson, supra, n. 7 at 92.
142. Supra, n. 33 at 105.
143. L.K. Christopherson and D.T. Lunde, 'The Selection of Cardiac Transplant Recipients and Their Subsequent Psychological Adjustment' (1971) 3 Seminars in Psychiatry 36 at 40,
144. as cited ibid at 105.
145. Supra, n. 76 at 253, reference removed.
146. See also supra, n. 33 at Ch. 3;
147. M. Little, Research, Ethics and Conflicts of Interest' (1999) 25 Journal of Medical Ethics 259;
148. McNeill, supra, n. 27 at 10 and Ch. 7.
149. For a discussion of the lobbying which preceded a baboon-to-human Done marrow transplant in the USA in the 1990s see A.S. Daar, 'Animal-to-Human Organ Transplants - A Solution Or A New Problem?' (1999) 77 Bulletin ofthe World Health Organization 54.
150. For an example of unsuccessful lobbying see supra, n. 64.
151. See, for example, supra, n. 64 at paras 32, 36, 64;
152. A. Coghlan, 'Trial of Treatment for vCJD to Launch' (2004) New Scientist 4: http://www.newscientist.com
153. J. Meikle, 'Cautious Go-ahead for vCJD Treatment' The Guardian 15 December 2004.
154. For a discussion of the parental lobbying see supra, n. 40.
155. A lot of this has been played out in the media and can be traced in, for example, articles in The Guardian during 2005-06. The lobbying culminated in the Court of Appeal decision, R (On the Application of Rogers) v. Swindon NHS Primary Care Trust and another [2006] EWCA Civ 392. The cancer 'lottery' and lobbying for treatment has also been in evidence in articles in The Observer during the summer of 2006.
156. Supra, n. 40.
157. See supra, n. 76 at 268;
158. supra, n. 33 at Ch. 3;
159. Mason and Laurie, supra, n. 37 at 654.
160. M. Fox, 'Research Bodies: Feminist Perspectives on Clinical Research' in S. Sheldon and M. Thomson (eds.) Feminist Perspectives in Health Care Law (Cavendish 1998) at 123.
161. See also BMA, The Medical Profession and Human Rights - Handbook for a Changing Agenda (Zed Books 2001) at Ch. 9.
162. A.J. Pinching, 'The Impact of AIDS on Medical Ethics - 1' (2000) 26 Journal of Medical Ethics 3.
163. For a discussion of patient's motivations for participating in research see N.E. Kass et al., 'Trust - The Fragile Foundation of Contemporary Biomedical Research' (1996) 26 Hastings Center Report 25.
164. Nuffield Report, supra, n. 8 at para 7.7. See also para 7.4.
165. Ibid. at para 7.5.
166. Mason and Laurie, supra, n. 37 at 654.
167. See, for example, Council for International Organizations of Medical Sciences (CIOMS) and World Health Organization (WHO), International Ethical Guidelines for Biomedical Research Involving Human Subjects (2002) at Guidelines 2 and 3: http://www.cioms.ch
168. General Medical Council (GMC), Research: The Role and Responsibilities of Doctors (2002) at paras 5 and 11: http://www.gmc-uk.org.
169. World Medical Association, Declaration of Helsinki, Ethical Principles for Medical Research Involving Human Subjects, adopted by the 18th WMA, Helsinki, Finland, June 1964. Amended in 1975, 1983, 1989, 1996, 2000 and clarifications added in 2002 and 2004: http://www.wma.net/ e/policy/b3.html, emphasis supplied.
170. GMC, supra, n. 103 at para. 4.
171. Supra, n. 14 at paras. 6.5-6.6.
172. Supra, n. 73.
173. Bristol Inquiry, supra, n. 74.
174. An 'interventional procedure' is 'one used for diagnosis or treatment that involves incision, puncture, entry into a body cavity, electromagnetic or acoustic energy': HSSC 2003/011, The Interventional Procedures Programme - Working with the National Institute for Clinical Excellence to promote safe clinical innovation at para 15: http://ww.dh.gov.uk. 'An interventional procedure should be considered new if a doctor no longer in a training post is using it for the first time in his or her NHS clinical practice', at para 16, emphasis in original.
175. For more information on the Interventional Procedures Programme see NICE, The Interventional Procedures Programme - Programme Manual (2004): http://www.nice.org.uk.
176. HSC 2003/011, ibid. at para. 1.
177. Ibid. at paras. 2 and 12.
178. Ibid. at para. 4.
179. Ibid. at para. 4.
180. The doctor must have met externally set standards of training, patients should, among other things, be made aware of the procedure's special status, and the proposed arrangements for clinical audit must be sound and capture data on clinical outcomes that can be used to review its continued use: ibid. at para 8.
181. Ibid. at para 10.
182. NICE, The Legal Implications of NICE Guidance, at 3: http://www.nice.org.uk.
183. Ibid.
184. 'A doctor is not guilty of negligence if he has acted in accordance with a practice accepted as proper by a responsible body of medical men skilled in that particular art': Bolam v. Friern Hospital Management Committee [1957] 2 All ER 118 at 121 per McNair J.
185. M. Jones, Medical Negligence (Sweet and Maxwell 2003) at para 3-053.
186. (1955) SLT 213 at 217.
187. Ibid.
188. Mason and Laurie, supra, n. 37 at 669, reference removed.
189. Supra n. 90.
190. Mason and Laurie, supra, n. 37 at 669 and 317-318.
191. See, for example, Simms v. Simms supra, n. 64 though not R. v. Cambridge Health Authority ex p. B supra, n. 65.
192. Supra, n. 104.
193. CIOMS and WHO, supra, n. 103 at Commentary on Guideline 13.
194. Ibid.
195. Ibid at Guideline 12.
196. Ibid at Commentary on Guideline 12.
197. Infra, section III D.
198. Mason and Laurie, supra, n. 37 at 668.
199. Supra, n. 112.
200. NICE also produces specific guidance about consent in this area: NICE, Consent - Procedures for which the Benefits and Risks are Uncertain (2003): http://www.nice.org.uk.
201. Capacity was determined by the Court of Appeal's two stage test in Re MB [1997] 8 Med. L. R. 217. From 1 April 2007, sections 2 and 3 of the Mental Capacity Act 2005 apply.
202. Chatterton v. Gerson [1981] 1 All ER 257 at 265 per Bristow J.
203. R v. Brown [1993] 2 All ER 75 at 79 per Lord Templeman, and at 103 per Lord Mustill, HL.
204. See also Law Commission, Consent in the Criminal Law, Consultation Paper No 139 (HMSO 1995) at para 8.51.
205. Jackson, supra, n. 75 at 460.
206. See supra, n. 64.
207. vCJD is part of a group of rare and fatal neurodegenerative disorders and, when infected, abnormal prion proteins are deposited in the brain, multiply and cause neurological damage.
208. Supra, n. 64 at para 20, emphasis supplied.
209. Dr Knight also acknowledged the limitations of research on non-human animals, ibid. at para 31.
210. Ibid. at para 22, emphasis supplied.
211. Ibid.
212. Ibid. at para 30.
213. Ibid. at para 31, emphasis supplied.
214. Ibid.
215. Ibid. at para. 33, emphasis supplied.
216. Ibid. at para 32, emphasis supplied.
217. Ibid. at para 36, emphasis supplied.
218. For a discussion of the role of families in such cases see supra, n. 93.
219. Ibid. at para. 38.
220. Ibid. at para. 40. See also paras 53-54.
221. The involvement of those without capacity in xenotransplants was considered by the Nuffield and Kennedy Reports, with both concluding that they should not be involved in 'the first xenotransplantation trials' (Nuffield, para 7.25) or until 'initial concerns about safety and efficacy have been satisfactorily resolved' (Kennedy, para 7.7): See paras 7.25-7.26 and para 7.7, respectively. For further information on involving those without capacity in research, see sections 30-34 Mental Capacity Act 2005; 2004 Regulations, supra, n. 34 at Schedule 1, Part 3;
222. K. Liddell, et al., 'Medical Research Involving Incapacitated Adults: Implications of the EU Clinical Trials Directive 2001/20/EC' (2006) 14 Med. L. R. 367.
223. Supra, n. 64 at para 57, emphasis supplied. Furthermore, '[a] patient who is not able to consent to pioneering treatment ought not to be deprived of the chance in circumstances where he would have been likely to consent if he had been competent'.
224. Supra, n. 69.
225. Supra, n. 64 at paras 42-46. Four questions need to be answered: (a) are they with capacity, (b) is the treatment within the Bolam test, (c) is it in their best interests to have it and (d) if (b)-(c) are positively answered, is the NHS capable of providing it?
226. Ibid. at paras 46, 48-51.
227. Ibid. at para 48.
228. Ibid.
229. Ibid.
230. Ibid, emphasis supplied.
231. Ibid. at para 49.
232. Supra, n. 40.
233. Supra, n. 64 at para 51.
234. Ibid. at para 56.
235. ibid. at para 57.
236. J. Laing, 'Incompetent Patients, Experimental Treatment and the 'Bolam Test' - JS v. An NHS Trust; JA v. An NHS Trust' (2003) 11 Med. L. Rev 237 at 240.
237. Supra, n. 86.
238. Supra, n. 64 at para 58.
239. See supra, n. 71.
240. Supra, n. 40.
241. Supra, n. 79.
242. See, for example, supra, n. 104 at para A4;
243. GMC, supra, n. 103 at para 1;
244. Medical Research Council (MRC), Good Research Practice (MRC 2005);
245. supra, n. 14 at paras 1.6 and 1.8.
246. Supra, n. 104 at paras B16-B18;
247. CIOMS and WHO, supra, n. 103 at Guideline 8;
248. The European Agency for the Evaluation of Medicinal Products, ICH Topic E6 - Guideline for Good Clinical Practice, Note for Guidance on Good Clinical Practice (CPMP/ICH/135/95))(1996), para 2.2: http://www.emea.eu.int
249. GMC, supra, n. 103 at para 5;
250. MRC, MRC Guidelines for Clinical Practice in Clinical Trials (MRC 1998) at para 2.2;
251. supra, n. 14 at para 1.10 and section 7.
252. Supra, n. 104 at para B13;
253. CIOMS and WHO, n. 103 at Comment on Guideline 1 and Appendix 1;
254. ICH, supra, n. 173 at para 2.5 and section 6;
255. GMC, supra, n. 103 at paras 11-12;
256. MRC, supra, n. 172 at para 2.2.
257. Supra, n. 104 at para B13;
258. CIOMS and WHO, supra, n. 103 at Guidelines 2-3;
259. ICH, supra, n. 173 at para 2.6 and section 3;
260. GMC, supra, n. 103 at para 5;
261. MRC, supra, n. 172 at para 2.6.
262. Generally see supra, n. 14.
263. Supra n. 104 at para B15;
264. CIOMS and WHO, supra, n. 103 at Commentary on Guideline 1;
265. ICH, supra n. 173 at paras 2.7-2.8;
266. MRC, supra, n. 172 at paras 2.7-2.8
267. Supra, n. 104 at para B18.
268. CIOMS and WHO, supra, n. 103 at Guideline 8.
269. Supra, n. 14 at para 7.3.
270. Ibid at para 7.2.
271. Supra, n. 104 at paras C.28-32.
272. Ibid at paras. C28, C29.
273. Ibid at para C32.
274. CIOMS and WHO, supra, n. 103 at Guideline 8;
275. GMC, supra, n. 103 at para 5.
276. For the definitions of 'clinical trial' and 'medicinal product' see 2004 Regulations, supra, n. 34 at Regulation 2.
277. Ibid at Regulation 12(3)(a). For further information on ethics committees see Regulation 5-16 and Schedules 2-4.
278. These have been amended by the 2006 Regulations. supra, n. 34 at Regulations 6-10 28-30.
279. Regulations, supra n. 34 at Regulation 12(3)(b).
280. See further Regulations 12 and, 17-27. These have been amended by the 2006 Regulations, supra, n. 34 at Regulations 11-14.
281. For the ethics committee timetable see 2004 Regulations, supra, n. 34 at Regulation 15(10), and for the MHRA at Regulations 18-20.
282. Ibid at Regulation 20(1)(a)(ii).
283. For further discussion, see S. Fovargue, 'A Leap Of Faith? Sanctioning Xenotransplant Clinical Trials' (2005) 26 Liverpool Law Review 125.
284. Pattinson has disagreed with this analysis see supra, n. 75 at 466
285. and D. Beyleveld, T. Finnegan, S.D. Pattinson, "The Regulation of Hybrids and Chimeras in the UK", report produced for CHIMBRIDS (Chimeras and Hybrids in Comparative European and International Research), a co-ordinated project run by the University of Mannheim, funded by the EC Sixth Framework.
286. Regulations, supra, n. 34 at Regulation 3.
287. This has been amended by the 2006 Regulations, supra, n. 34 at Regulation 3.
288. Regulation, supra n. 34 at Regulation 28.
289. See further Regulations 29-31, Schedule 1 and 5.
290. Supra, n. 34.
291. Regulations, supra, n. 34 at Schedule 1, Part 2, paras 3 and 6, as amended by 2006 Regulations, supra, n. 34 at Regulation 27(2).
292. Regulations, supra, n. 34 at Regulation 27(2), paras 5 and 10.
293. Ibid. at para 12.
294. Supra, n. 104 at paras B20, B22-B23;
295. CIOMS and WHO, supra, n. 103 at Guidelines 4-6;
296. ICH, supra, n 173 at paras 2.9 and 4.8;
297. GMC supra n. 103 at paras 5, 15-22;
298. MRC, supra, n. 172 at paras 2.9 3.1.10, 5.4;
299. supra n. 14 at paras 1.15, 7.5 7.31-7.49.
300. Supra, n. 104 at para B22;
301. CIOM and WHO, supra, n. 103 at Commentary on Guideline 4, Guideline 6;
302. ICH, supra, n 173 paras 1.28 and 4.8.8;
303. MRC, supra, n. 172 at para 5.4.2;
304. supra, n 14 at para 7.41.
305. Supra, n. 104 at para A8.
306. See, for example, supra, n. 104 at paras B22, B24-B26.
307. See supra, n. 127-130.
308. CIOMS and WHO, supra, n. 103 at Guideline 13.
309. ICH, supra, n. 173 at para 3.1.1.
310. Ibid. at para 1.61.
311. GMC, supra, n. 103 at para 43.
312. Supra, n. 14 at Ch. 8.
313. Ibid. at para 8.18.
314. Supra, n. 175.
315. Supra, n. 104 at para B13;
316. CIOMS and WHO, supra, n. 103 at Appendix 1;
317. ICH, supra, n. 173 at paras 3.1.2 and 6.5;
318. GMC, supra, n. 103 at para 12.
319. CIOMS and WHO, supra, n. 103 at Commentary on Guideline 8.
320. Supra, n. 104 at para B22;
321. CIOMS and WHO, supra, n. 103 at Guideline 5, para 10;
322. ICH, supra, n. 173 at para 4.8.10 h,
323. GMC, supra, n. 103 at para 20;
324. MRC, supra, n. 172 at para 3.1.9.
325. Supra, n. 104 at para C31.
326. Ibid. at B23.
327. See also CIOMS and WHO, supra, n. 103 at Commentary on Guideline 6.
328. Supra, n. 104 at para B22;
329. CIOMS and WHO, supra, n. 103 at Guideline 5, para 10;
330. ICH, supra, n. 173 at paras 4.8.10 g-h;
331. GMC, supra, n. 103 at para 20;
332. MRC, supra, n. 172 at para 3.1.9.
333. CIOMS and WHO, supra, n. 103 at Guideline 5, para 22.
334. Supra, n. 14 at paras 6.33-6.34.
335. Ibid. at para 6.34.
336. Regulations, supra, n. 34 at Regulations 12(2)
337. and 12(3)(a), as amended by 2006 Regulations, supra, n. 34 at Regulation 27(2).
338. Regulations, supra, n. 34 at Schedule 1, Part 2, para 7, as amended by 2006 Regulations,
339. supra, n. 34 at Regulation 29(2).
340. Regulations, supra, n. 34 at Schedule 1, Part 2, para 9.
341. Schedule 1, Parts 3-5 of the 2004 Regulations apply to those who are unable to consent for themselves and remain, although amended, following the 2006 Regulations, supra, n. 34 at Regulation 27(3).
342. Regulations, supra, n. 34 at Regulation 27(2).
343. Supra, n. 134-136.
344. For a discussion of this see, for example, supra, n. 64.
345. UKXIRA, 'Background and terms of reference' (2005): http://www.advisorybodies.dh.gov.uk.
346. DH, (2006), supra, n. 4 at 1.
347. This replaces HSC 1998/126, Clinical Procedures Involving Xenotransplantation.
348. DH, (2006), ibid. at 1-2.
349. Ibid. at 2.
350. Directive 2003/63/EC amending Directive 2001/83/EC of the European Parliament and of the Council on the Community code relating to medicinal products for human use, at Annex I, Part IV defines xenotransplantation medicinal products as: 'any procedure that involves the transplantation, implantation, or infusion into a human recipient of either live tissues or organs retrieved from animals, or, human body fluids, cells, tissues or organs that have undergone ex vivo contact with live non-human animal cells, tissues or organs'.
351. See 2004 Regulations, supra, n. 34 at Regulations 5-10.
352. DH (2006), supra, n. 4 at 3.
353. Ibid at 4.
354. Supra, n. 82-83.
355. UKXIRA, supra, n. 84 at paras 4.6 and 7.5.
356. Ibid. at para 7.21.
357. Ibid. at para 7.22.
358. UKXIRA published its own draft scheme in 1999. This remains a draft 8 years on: UKXIRA, supra, n. 58.
359. Council of Europe, supra, n. 21 at Article 5(1).
360. Ibid. at Article 12.
361. UKXIRA, supra, n. 84 at para 7.17.
362. Ibid. at para 7.13.
363. For information on other regulatory body's approach to consent see, for example, US DHHS, SACX, Informed Consent in Clinical Research Involving Xenotransplantation - Draft (2004): http://www4.od.nih.gov/ oba/SACX/reports/IC_draft_030905.pdf.
364. UKXIRA, supra, n. 84 at para 7.15.
365. UKXIRA, supra, n. 58 at para A5.7.
366. UKXIRA, supra, n. 84
367. and HSC 1998/126, supra, n. 225.
368. S. Guest, 'Compensation for Subjects of Medical Research: The Moral Rights of Patients and the Power of Research Ethics Committees' (1997) 23 Journal of Medical Ethics 181 at 182.
369. NICE, About Interventional Procedures : http://www.nice.org.uk.
370. HSC 2003/011, supra, n. 109 at para 3.