RESEARCH ETHICS AND CONSENT ON THE COLLECTION AND USE OF HUMAN BIOLOGICAL MATERIALS: A SINGAPORE PERSPECTIVE Chan Tuck Wai B.Sc (Pharmacy), NUS MBA, GGU A THESIS SUBMITTED FOR THE DEGREE OF DOCTOR OF PHILOSOPHY NUS CENTRE FOR BIOMEDICAL ETHICS YONG YOO LIN SCHOOL OF MEDICINE NATIONAL UNIVERSITY OF SINGAPORE 2015 i DECLARATION I hereby declare that this thesis is my original work and it has been written by me in its entirety, with inputs and advices from my supervisors I have duly acknowledged all the sources of information that have been used in this thesis This thesis has also not been submitted for any degree in any university previously Chan Tuck Wai June 2015 i ACKNOWLEDGEMENTS To complete the PhD programme by the age of 50 has always been part of my dream However, with a full-time job, suffering from several medical conditions and a list of learning disabilities, it would have been impossible to achieve this dream Despite genuine concerns from friends and colleagues, I went on to enrol into this program in 2009 I have thoroughly enjoyed my journey, even with a heart attack in the 2nd year of the program There are many people whom I like to thank for this miraculous learning journey My gratitude goes to my supervisors, Prof Leonardo De Castro and Dr Calvin Ho, who provided inputs and comments to multiple draft versions of my thesis Special acknowledgements to my Thesis Advisory Committee – AP Chong Siew Meng, AP Jacqueline Chin and PhD Examiners – AP Anita Ho, Prof Graeme Laurie, Prof Chia Kee Seng and Dr Tamra Lysaght; Prof Desley Hegney, Prof Vicky Drury, Dr Grace Zeng, Dr Azhar Bin Ali, Ms Chia Chiu Yuin, Ms Iris Wee An-Li for their kind assistances, supports and advices in this thesis I would like to thank Prof Lee Hin Peng and colleagues in NUS Institutional Review Board for all their hard work to help my work duties during my course and study leave I would like to express my appreciation to NUH Department of Pathology, NUH Tissues Repository, and NUS Centre for BioMedical Ethics for supporting this thesis and with great gratitude to all patients who had patiently and willingly participated in this study Thank you all and I am overwhelmed with gratitude Chan Tuck Wai June 2015 ii TABLE OF CONTENTS Declaration……………………………………………………………………………………………………………………… i Acknowledgement……………………………………………………………………………………… ………………… ii Table of Content…………………………………………………………………………………………………………… iii Summary…………………………………………………………………………………………………….………….……… v List of Publications………………………………………………….…………………………………………………… vii List of Tables…………………………………………………………………………………………………… ………… viii List of Figures………………………………………………………………………………………………… ……………… ix List of Appendices……………………………………………………………………………………….……………….… x Main body of thesis………………………………………………………………………………….………………….… Chapter Introduction 1.1 The need for Human Biological Materials for research 1.2 Description of residual HBMs in Research 11 1.3 Sources of HBMs 13 1.4 Informed consent for Biobanking of residual HBMs for research 18 1.5 Current Guidelines on Biobanks in Singapore 23 1.2.1 1.4.1 1.5.1 1.5.2 1.5.3 1.5.4 1.5.5 What are residual human biological materials? 11 Types of Consent 19 BAC Guidelines on Tissue Banking 23 BAC - An outright gift model for tissue donation 24 Recommendation on Governance and regulations 26 Where are we now in terms of Biobank governance? 27 Role of the Institutional Review Board (IRB) in tissue research 29 Chapter Research? Human Biological Materials: Abandonment, Donation or Participation in ……………………………………………………………………………………………………………… 32 2.1 Consent Regimes in NUH for Biobanking 35 2.2 Abandonment in Property Law 40 2.3 Legacy Tissue and the Rejection of Implied Consent 48 2.4 Rights-based Jurisprudence 51 2.5 ‘Donation’: Beyond Abandonment and Fundamental Rights 56 2.6 The Illusion of ‘Fully’ Informed Consent 58 2.1.1 2.1.2 2.1.3 NUH – A Singapore example 35 Consent-taking for storage and use of residual HBMs from surgeries 35 Consent-taking for the banking of residual HBMs and medical information with NUH TR 37 2.7 Informed Consent is an Inadequate Safeguard – the importance of statutory governance in biobanking 66 iii Chapter Research on donation of residual biological samples and consent given for secondary use ……………………………………………………………………………………………………………… 70 3.1 Background 70 3.2 Research Objective 74 3.3 Methodology 75 3.4 Ethics Approval for qualitative interview 82 3.5 Review of Results and Findings 83 3.6 SOME CONCLUSIONS FROM THE RESEARCH 134 3.3.1 3.5.1 3.5.2 3.5.3 3.6.1 3.6.2 3.6.3 3.6.4 Overview of mixed method research design 76 PHASE 1: Systematic Literature Review 83 PHASE 2: Analysis of Consent for Residual Surgical HBMs from 2002 – 2011 97 PHASE 3: Qualitative Study involving NUH Patients 109 Motivations, Attitudes and Perceptions of Singaporean in Tissue banking 134 Altruism and Trust: Why patients donate their residual tissues 136 Lack of consensus on informed consent regime for Tissue banking 141 Presupposition of Good Governance at various stages of tissue banking 144 Chapter Discussions and Recommendations on Trust and Governance 146 4.1 Broad Consent as the Preferred Choice in tissue banking 147 4.2 Tissue Repository and its institution as Stewards of residual HBMs 154 4.3 Good Governance 159 4.4 Transparency and Mediated Communication in tissue banking 168 Chapter Prologue Conclusion 177 ……………………………………………………………………………………………………………….185 Implications for research 185 Implications for Practice 186 Bibliography ……………………………………………………………………………………………………………….187 Appendices …………………………………………………………………………………………………… 206 iv SUMMARY Biobanking of residual human biological materials (HBMs), usually obtained from surgeries, is crucial for the advancement of science and public health and improves current treatment of various diseases However, biobanking of residual HBMs comes with ethical, social and legal implications (ELSI) that require attention This thesis will focus on residual HBMs tissue repository, which is considered as a biobank The current ethical paradigm and academic debates have focused on informed consent and ownership of residual HBMs, and subsequent discussion on the rights of patients through benefits sharing, returning of results from the research and profit sharing when the residual HBMs are commercialised In this thesis, I will attempt to critique this paradigm and its’ application in the Singapore context A key aim of this thesis is to contribute to the knowledge with regards to patients’ knowledge, attitudes, preferences and expectations in donating residual HBMs for research This study will also examine the current approach to consent in a major healthcare institution in Singapore compared with other consent regimes, in relation to preferences expressed by patients when contributing their tissues The outcome of a 3-part explanatory sequential research using mixed methods design is a main component of this thesis It comprises of a systematic literature review, a quantitative research using consent forms for a period of ten years (from 2002 to 2011) in a major Singapore hospital and a qualitative interview of 100 patients who had contributed HBMs to the hospital’s tissue repository The empirical results have been analysed in comparison with previous reports in academic publications on ethical issues of tissue repositories and v biobanking, with primary focus on informed consent and the relationship between residual HBMs repositories and patients I defend in this thesis that specific informed consent is neither morally meaningful nor important to the donors of residual HBMs A regime of general consent with mediated communication and respecting donor intent is proposed, together with the establishment of a moral institution with proper governance, safeguards and control for the collection, storage, distribution and use of HBMs in tissue repositories vi LIST OF PUBLICATIONS This dissertation is based on the following original publications: Chan TW, Mackey SJ, Hegney D 2011 Patients’ experiences towards the donation of their residual biological samples and the impact of these experiences on the type of consent given for secondary use: A systematic review JBI Library of Systematic Reviews 08 Aug 2011; 9(42): 1714-1781 Chan TW, Mackey SJ, Hegney D 2012 Patients’ consent and donation of their residual biological samples: A systematic review International Journal of EvidenceBased Healthcare - International Journal of Evidence Based Healthcare 2012; 10: 926 Chan TW 2012 The Closure of the National Bio-bank in Singapore Asia-Pacific Biotech News Journal Vol 16, No 4, April 2012: 40-43 Chan TW, Mackey SJ, Hegney D 2012 Donation of residual biological samples and consent given for secondary use The Joanna Briggs Institute, Vol 15, No 9, Page 1-4, 09/12/2011 vii LIST OF TABLES TABLE 1: SUMMARY OF GENDER AND CONSENT RATE FOR THE DONATION OF RESIDUAL TISSUES IN NUH FROM 2002 TO 2011 99 TABLE 2: SUMMARY OF ETHNIC GROUP AND CONSENT RATE FOR THE DONATION OF RESIDUAL TISSUES IN NUH FROM 2002 TO 2011 100 TABLE 3: SUMMARY OF RELIGION AND CONSENT RATE FOR THE DONATION OF RESIDUAL TISSUES IN NUH FROM 2002 TO 2011 101 TABLE 4: SUMMARY OF AGE GROUP AND CONSENT RATE FOR THE DONATION OF RESIDUAL TISSUES IN NUH FROM 2002 TO 2011 102 TABLE 5: SUMMARY OF FEE SCHEDULE AND CONSENT RATE FOR THE DONATION OF RESIDUAL TISSUES IN NUH FROM 2002 TO 2011 103 TABLE 6: SUMMARY OF YEARLY ANNUAL CONSENT RATE FOR THE DONATION OF RESIDUAL TISSUES IN NUH FROM 2002 TO 2011 104 TABLE 7: SUMMARY CONSENT RATE STRATIFIED BY DEPARTMENT FOR THE DONATION OF RESIDUAL TISSUES IN NUH FROM 2002 TO 2011 105 TABLE 8: SUMMARY OF GENDER OF PARTICIPANTS (N=100) 109 TABLE 9: SUMMARY OF ETHNIC GROUPS OF PARTICIPANTS (N=100) 110 TABLE 10: SUMMARY OF RELIGION OF PARTICIPANTS (N=100) 110 TABLE 11: SUMMARY OF PARTICIPANTS STRATIFIED BY AGE GROUP (N=100) 111 TABLE 12: SUMMARY ON REASONS GIVEN FOR DONATING HBMS 114 TABLE 13: REASONS FOR DONATING HBMS IN CSR AND QUALITATIVE RESEARCH 115 TABLE 14: SUMMARY ON COMMENTS ON PRIVACY AND CONFIDENTIALITY 127 TABLE 15: SUMMARY ON PERCEIVED GOVERNANCE 128 TABLE 16: SUMMARY ON “WHO CAN USE MY HBMS FOR RESEARCH?” 129 TABLE 17: PROPOSED ‘STEWARDSHIP’ OF RESIDUAL HBMS 161 viii LIST OF FIGURES FIGURE 1: SAMPLE OF NUH CONSENT FORM 36 FIGURE 2: SYNTHESIZED THEMATIC FINDING - CATEGORIES AND STUDY FINDINGS 84 FIGURE 3: SYNTHESIZED THEMATIC FINDING - CATEGORIES AND STUDY FINDINGS 91 FIGURE 4: SYNTHESIZED THEMATIC FINDING - CATEGORIES AND STUDY FINDINGS 93 FIGURE 5: SYNTHESIZED THEMATIC FINDING 4, CATEGORIES AND STUDY FINDINGS 97 ix Chi-Square Tests b 79 831 Co ntinuity Lik eliho od Ra tio 00 Ex act Sig (1- sided) 00 78 843 Co rrect ion a 79 504 Pea rson Chi-Square Ex act Sig (2- sided) Asy mp Sig (2- sided) df Value 00 Fisher's Exact T est 00 00 Lin ear-by-Lin ear Assoc iation 79 826 N o f Valid Ca ses 165 32 00 a Com puted only for a 2x2 table b cells (.0 %) have exp ected count less t han The m inim um ex pected coun t is 15 75.54 Crosstabs Case Processing Summary Cases Valid N religion * resp onse 724 78 Missing Per cent N 100 0% T o tal Per cent N 0% 724 78 Per cent 100 0% rel igion * response Crosstabul ation response yes no T o tal oth ers T o tal 181 590 69 2% 30 8% 100 0% Co unt 495 40 170 29 665 69 % within religion hin duism 409 % within religion religion 74 4% 25 6% 100 0% Co unt Co unt 536 30 188 48 724 78 % within religion 74 0% 26 0% 100 0% 30 Chi-Square Tests b 76 341 Co ntinuity Lik eliho od Ra tio 00 Ex act Sig (1- sided) 00 73 854 Co rrect ion a 76 071 Pea rson Chi-Square Ex act Sig (2- sided) Asy mp Sig (2- sided) df Value 00 Fisher's Exact T est 00 00 Lin ear-by-Lin ear Assoc iation 76 340 N o f Valid Ca ses 724 78 00 a Com puted only for a 2x2 table b cells (.0 %) have exp ected count less t han The m inim um ex pected coun t is 15 36.64 Crosstabs Case Processing Summary Cases Valid N religion * resp onse Missing Per cent 168 29 N 100 0% T o tal Per cent 0% Per cent N 168 29 100 0% rel igion * response Crosstabul ation response yes religion isla m no T o tal 494 165 72 70 2% 29 8% 100 0% 189 68 257 % within religion T o tal 116 27 % within religion rom an c atholicism Co unt 73 5% 26 5% 100 0% Co unt 118 16 501 168 29 % within religion 70 2% 29 8% 100 0% Co unt 31 Chi-Square Tests b 1.3 83 Co ntinuity Lik eliho od Ra tio 26 Ex act Sig (1- sided) 24 1.4 14 Co rrect ion a 1.2 26 Pea rson Chi-Square Ex act Sig (2- sided) Asy mp Sig (2- sided) df Value 23 Fisher's Exact T est 13 27 Lin ear-by-Lin ear Assoc iation 1.3 83 N o f Valid Ca ses 168 29 24 a Com puted only for a 2x2 table b cells (.0 %) have exp ected count less t han The m inim um ex pected coun t is 76 55 Crosstabs Case Processing Summary Cases Valid N religion * resp onse 171 51 Missing N Per cent 100 0% T o tal Per cent N 0% 171 51 Per cent 100 0% rel igion * response Crosstabulation response yes no T o tal sik hism T o tal 11 627 49 45 16 572 70 2% 29 8% 10 0.0% 40 17 57 % within religion isla m Co unt % within religion religion 70 3% 29 7% 10 0.0% Co unt 12 034 51 17 17 151 % within religion 70 2% 29 8% 10 0.0% Co unt 32 Chi-Square Tests b 00 Co ntinuity Lik eliho od Ra tio 98 Ex act Sig (1- sided) 94 00 Co rrect ion a 00 Pea rson Chi-Square Ex act Sig (2- sided) Asy mp Sig (2- sided) df Value 94 Fisher's Exact T est 49 96 Lin ear-by-Lin ear Assoc iation 00 N o f Valid Ca ses 94 171 51 a Com puted only for a 2x2 table b cells (.0 %) have exp ected count less t han The m inim um ex pected coun t is 17 2.74 Crosstabs Case Processing Summary Cases Valid N religion * resp onse Missing Per cent 271 95 N T o tal Per cent 100 0% 0% Per cent N 271 95 100 0% rel igion * response Crosstabul ation response yes religion isla m no T o tal 494 165 72 70 2% 29 8% 100 0% 803 258 106 23 % within religion T o tal 116 27 % within religion non den omina tiona l Co unt 75 6% 24 4% 100 0% Co unt 196 61 753 271 95 % within religion 72 3% 27 7% 100 0% Co unt 33 Chi-Square Tests b 96 630 Co ntinuity Lik eliho od Ra tio 00 Ex act Sig (1- sided) 00 97 631 Co rrect ion a 96 357 Pea rson Chi-Square Ex act Sig (2- sided) Asy mp Sig (2- sided) df Value 00 Fisher's Exact T est 00 00 Lin ear-by-Lin ear Assoc iation 96 626 N o f Valid Ca ses 271 95 00 a Com puted only for a 2x2 table b cells (.0 %) have exp ected count less t han The m inim um ex pected coun t is 29 42.96 Crosstabs Case Processing Summary Cases Valid N religion * resp onse 831 41 Missing N Per cent 100 0% T o tal Per cent 0% N 831 41 Per cent 100 0% rel igion * response Crosstabulation response yes religion isla m no T o tal 49 45 16 572 70 2% 29 8% 10 0.0% Co unt 49 540 17 029 66 569 % within religion T o tal 11 627 % within religion oth ers Co unt 74 4% 25 6% 10 0.0% Co unt 61 167 21 974 83 141 % within religion 73 6% 26 4% 10 0.0% 34 Chi-Square Tests b 123 752 Co ntinuity Lik eliho od Ra tio 00 Ex act Sig (1- sided) 00 121 392 Co rrect ion a 123 533 Pea rson Chi-Square Ex act Sig (2- sided) Asy mp Sig (2- sided) df Value 00 Fisher's Exact T est 00 00 Lin ear-by-Lin ear Assoc iation 123 750 N o f Valid Ca ses 00 831 41 a Com puted only for a 2x2 table b cells (.0 %) have exp ected count less t han The m inim um ex pected coun t is 43 79.95 Crosstabs Case Processing Summary Cases Valid N Per cent 836 religion * resp onse Missing N 100 0% T o tal Per cent 0% N Per cent 836 100 0% rel igion * response Crosstabul ation response yes religion rom an c atholicism Co unt % within religion sik hism Co unt % within religion T o tal Co unt % within religion no T o tal 189 68 257 73 5% 26 5% 100 0% 407 172 579 70 3% 29 7% 100 0% 596 240 836 71 3% 28 7% 100 0% 35 Chi-Square Tests b 91 Co ntinuity Lik eliho od Ra tio 38 Ex act Sig (1- sided) 33 92 Co rrect ion a 76 Pea rson Chi-Square Ex act Sig (2- sided) Asy mp Sig (2- sided) df Value 33 Fisher's Exact T est 19 36 Lin ear-by-Lin ear Assoc iation 91 N o f Valid Ca ses 836 33 a Com puted only for a 2x2 table b cells (.0 %) have exp ected count less t han The m inim um ex pected coun t is 73 78 Crosstabs Case Processing Summary Cases Valid N religion * resp onse Missing Per cent 108 80 N T o tal Per cent 100 0% Per cent N 0% 108 80 100 0% rel igion * response Crosstabul ation response yes religion rom an c atholicism Co unt % within religion non den omina tiona l Co unt % within religion T o tal Co unt % within religion no T o tal 189 68 257 73 5% 26 5% 100 0% 803 258 106 23 75 6% 24 4% 100 0% 822 265 108 80 75 6% 24 4% 100 0% 36 Chi-Square Tests b 59 Co ntinuity Lik eliho od Ra tio 48 Ex act Sig (1- sided) 44 58 Co rrect ion a 48 Pea rson Chi-Square Ex act Sig (2- sided) Asy mp Sig (2- sided) df Value 44 Fisher's Exact T est 24 46 Lin ear-by-Lin ear Assoc iation 59 N o f Valid Ca ses 44 108 80 a Com puted only for a 2x2 table b cells (.0 %) have exp ected count less t han The m inim um ex pected coun t is 62 76 Crosstabs Case Processing Summary Cases Valid N religion * resp onse Missing Per cent 668 26 N 100 0% T o tal Per cent 0% Per cent N 668 26 100 0% rel igion * response Crosstabul ation response yes religion rom an c atholicism T o tal 68 257 73 5% 26 5% 100 0% Co unt 495 40 170 29 665 69 % within religion T o tal 189 % within religion oth ers Co unt no 74 4% 25 6% 100 0% Co unt 497 29 170 97 668 26 % within religion 74 4% 25 6% 100 0% 37 Chi-Square Tests b 10 Co ntinuity Lik eliho od Ra tio 80 Ex act Sig (1- sided) 74 10 Co rrect ion a 06 Pea rson Chi-Square Ex act Sig (2- sided) Asy mp Sig (2- sided) df Value 74 Fisher's Exact T est 40 77 Lin ear-by-Lin ear Assoc iation 10 N o f Valid Ca ses 74 668 26 a Com puted only for a 2x2 table b cells (.0 %) have exp ected count less t han The m inim um ex pected coun t is 65 75 Crosstabs Case Processing Summary Cases Valid N religion * resp onse Missing Per cent 112 02 N T o tal Per cent 100 0% 0% Per cent N 112 02 100 0% rel igion * response Crosstabul ation response yes religion sik hism Co unt % within religion non den omina tiona l Co unt % within religion T o tal Co unt % within religion no T o tal 407 172 579 70 3% 29 7% 100 0% 803 258 106 23 75 6% 24 4% 100 0% 844 276 112 02 75 4% 24 6% 100 0% 38 Chi-Square Tests b 8.4 14 Co ntinuity Lik eliho od Ra tio 00 Ex act Sig (1- sided) 00 8.0 87 Co rrect ion a 8.1 29 Pea rson Chi-Square Ex act Sig (2- sided) Asy mp Sig (2- sided) df Value 00 Fisher's Exact T est 00 00 Lin ear-by-Lin ear Assoc iation 8.4 13 N o f Valid Ca ses 112 02 00 a Com puted only for a 2x2 table b cells (.0 %) have exp ected count less t han The m inim um ex pected coun t is 14 2.71 Crosstabs Case Processing Summary Cases Valid N 671 48 religion * resp onse Missing Per cent N 100 0% T o tal Per cent N 0% 671 48 Per cent 100 0% rel igion * response Crosstabulation response yes no T o tal oth ers T o tal 17 57 70 3% 29 7% 10 0.0% Co unt 49 540 17 029 66 569 % within religion sik hism 40 % within religion religion 74 4% 25 6% 10 0.0% Co unt Co unt 49 947 17 201 67 148 % within religion 74 4% 25 6% 10 0.0% 39 Chi-Square Tests b 5.1 27 Co ntinuity Lik eliho od Ra tio 02 Ex act Sig (1- sided) 02 4.9 65 Co rrect ion a 4.9 13 Pea rson Chi-Square Ex act Sig (2- sided) Asy mp Sig (2- sided) df Value 02 Fisher's Exact T est 01 02 Lin ear-by-Lin ear Assoc iation 5.1 27 N o f Valid Ca ses 671 48 02 a Com puted only for a 2x2 table b cells (.0 %) have exp ected count less t han The m inim um ex pected coun t is 14 8.32 Crosstabs Case Processing Summary Cases Valid N religion * resp onse Missing Per cent 771 92 N T o tal Per cent 100 0% 0% N Per cent 771 92 100 0% rel igion * response Crosstabul ation response yes religion non den omina tiona l no T o tal 258 106 23 75 6% 24 4% 100 0% Co unt 495 40 170 29 665 69 % within religion T o tal 803 % within religion oth ers Co unt 74 4% 25 6% 100 0% Co unt 575 74 196 18 771 92 % within religion 74 6% 25 4% 100 0% 40 Chi-Square Tests Value b 7.0 68 Lik eliho od Ra tio Ex act Sig (1- sided) 00 Ex act Sig (2- sided) 00 7.1 23 Co rrect ion a 7.0 04 Pea rson Chi-Square Co ntinuity Asy mp Sig (2- sided) df 00 Fisher's Exact T est 00 Lin ear-by-Lin ear Assoc iation 7.0 68 N o f Valid Ca ses 00 771 92 00 a Com puted only for a 2x2 table b cells (.0 %) have exp ected count less t han The m inim um ex pected coun t is 26 99.79 total yes % lower 95% CI upper 95% CI BUDDHISM 35563 26543 74.64 74.18 75.09 CHRISTIANITY 12156 9002 74.05 73.27 74.83 5909 4090 69.22 68.04 70.39 16572 11627 70.16 69.46 70.86 ROMAN CATHOLICISM 257 189 73.54 68.15 78.93 SIKHISM 579 407 70.29 66.57 74.02 NONDENOMINATION 10623 8034 75.63 74.81 76.44 OTHERS 66569 49540 74.42 74.09 74.75 HINDUISM ISLAM Slide 34 age trend (ignoring the > 100 age group) 41 Coefficientsa Sta ndardized Co efficients Un standardiz ed Co effic ients Mo del B Std Erro r (Co nsta nt) 70 576 50 Be ta 23 Lo wer Bound Up per Bound 48 078 t 00 67 191 73 961 2.1 27 1.4 68 age _gro up 95 % Co nfide nce I nterv al for B 06 -.0 42 1.0 49 60 Sig a Dep enden t Variable: percen t trend = 0.5% (95% -0.4% to 1.05%),p = 0.066 slide 35 comparison by fee fee * response Cross tabulation response yes private fee no T o tal 123 39 514 25 76 0% 24 0% 100 0% Co unt 702 89 264 31 967 20 % within fee oth ers 390 86 % within fee subsidise d Co unt 72 7% 27 3% 100 0% 57 26 83 68 7% 31 3% 100 0% Co unt % within fee T o tal Co unt 109 432 387 96 148 228 73 8% % within fee 26 2% 100 0% Chi-Square Tests Value Asy mp Sig (2- sided) df Pea rson Chi-Square a 194 181 00 Lik eliho od Ra tio 195 903 00 Lin ear-by-Lin ear Association 194 161 00 N o f Valid Ca ses 148 228 a cells (.0 %) have exp ected count less t han The m inim um ex pected coun t is 1.72 42 fee * response Crosstabulation response private T o tal no yes fee Co unt 514 25 76 0% 24 0% 100 0% Co unt 702 89 264 31 967 20 % within fee T o tal 123 39 % within fee subsidise d 390 86 72 7% 27 3% 100 0% Co unt 109 375 387 70 148 145 73 8% 26 2% 100 0% % within fee Chi-Square Tests Value b 193 054 Co rrect ion a Lik eliho od Ra tio 192 882 Ex act Sig (1- sided) 00 Ex act Sig (2- sided) 00 194 806 Pea rson Chi-Square Co ntinuity Asy mp Sig (2- sided) df 00 Fisher's Exact T est 00 Lin ear-by-Lin ear Assoc iation N o f Valid Ca ses 193 053 00 00 148 145 a Com puted only for a 2x2 table b cells (.0 %) have exp ected count less t han The m inim um ex pected coun t is 13 458.0 fee * response Crosstabul ation response no yes fee private T o tal 39 086 12 339 51 425 % within fee oth ers Co unt 76 0% 24 0% 10 0.0% 57 26 83 68 7% 31 3% 10 0.0% Co unt % within fee T o tal Co unt 39 143 12 365 51 508 % within fee 76 0% 24 0% 10 0.0% 43 Chi-Square Tests b 2.4 41 Co ntinuity Lik eliho od Ra tio 15 Ex act Sig (1- sided) 11 2.2 97 Co rrect ion a 2.0 56 Pea rson Chi-Square Ex act Sig (2- sided) Asy mp Sig (2- sided) df Value 13 Fisher's Exact T est 07 12 Lin ear-by-Lin ear Assoc iation 2.4 41 N o f Valid Ca ses 515 08 11 a Com puted only for a 2x2 table b cells (.0 %) have exp ected count less t han The m inim um ex pected coun t is 19 92 fee * response Crosstabulation response yes fee subsidise d no T o tal 264 31 967 20 72 7% 27 3% 100 0% 57 26 83 % within fee 68 7% 31 3% 100 0% Co unt 703 46 264 57 968 03 % within fee T o tal 702 89 % within fee oth ers Co unt 72 7% 27 3% 100 0% Co unt Chi-Square Tests Value b 66 Lik eliho od Ra tio 42 66 Ex act Sig (1- sided) 48 Ex act Sig (2- sided) 41 64 Co rrect ion a 48 Pea rson Chi-Square Co ntinuity Asy mp Sig (2- sided) df 41 Fisher's Exact T est 46 Lin ear-by-Lin ear Assoc iation N o f Valid Ca ses 24 968 03 a Com puted only for a 2x2 table b cells (.0 %) have exp ected count less t han The m inim um ex pected coun t is 22 68 total yes % lower 95% CI Private 51425 39086 76.01 75.64 76.37 Subsidised 96720 70289 72.67 72.39 72.95 83 57 68.67 58.70 78.65 Others upper 95% CI 44 ... recommendation on ? ?Research on biological materials of human origin” 7, the National Bioethics Advisory Commission (USA) in its report on Research Involving Human Biological Materials: Ethical Issues... taking or accepting any HBMs for research, and must ensure confidentiality of the contributor''s personal information during collection, storage, and use of human biological materials for research. .. for diagnostic purposes, they are presumed to have consented to research participation Precautionary consent The term ‘precautionary consent? ?? was used by the Council of Europe and the German Ethics