Ethical challenges in obtaining informed consent for the genomic study of Rheumatic Heart Disease: a qualitative study A research dissertation in fulfilment for the requirement of the MSc Med in Bioethics at the University of Cape Town, South Africa BY FRANCIS MASIYE MSYFRA001 UniversitySUPERVISORS: of Cape Town DR JANTINA DE VRIES PROF BONGANI MAYOSI 1 The copyright of this thesis vests in the author. No quotation from it or information derived from it is to be published without full acknowledgement of the source. The thesis is to be used for private study or non- commercial research purposes only. Published by the University of Cape Town (UCT) in terms of the non-exclusive license granted to UCT by the author. University of Cape Town ACKNOWLEDGEMENTS I would like to thank my supervisors, Dr Jantina de Vries and Prof Bongani Mayosi for all their help and support throughout both the conduct of this research project and the writing of the thesis, and for providing such a valuable learning experience. I wish to thank Ms Peggy Mgwayi for her kind and calm assistance in data collection and transcription as well as in helping me to understand the cultural meanings behind what was said in the interviews. I also thank the Wellcome Trust through the RHDGen grant (WT09313MA) for funding this research project. I thank the staff and patients at the Groote Schuur Hospital and Vanguard Community Health Centre for participating in the study and members of the Heideveld Community in the Cape Flats for giving me their time and for their willingness to talk to me during the interviews. I also thank my family – my wife, Phoebe, for always encouraging me to take the next step despite some family commitments and hurdles; my parents for always believing in me; and two boys, Orama and Mwisho for their patience and support. Lastly, I would like to thank the Mayosi Research Group and the RHDGen research team in particular for their support and being such a pleasure to work with; and the RHDGen cases and controls who were the inspiration for the study and to whom this thesis is dedicated. 2 DECLARATION I, Francis Masiye, hereby declare that the work on which this thesis is based is my original work (except where acknowledgements indicate otherwise) and that neither the whole work nor any part of it has been, is being, or is to be submitted for another degree in this or any other university. I empower the university to reproduce for the purpose of research either the whole or any portion of the contents in any manner whatsoever. Signature: Date: 13th May 2016 Department of Medicine, Faculty of Health Sciences 3 Table of Contents 1 INTRODUCTION .................................................................................................... 12 1.1 A background of the Genomics of Rheumatic Heart Disease Network (RHDGen) Study ........................................................................................................ 13 2 LITERATURE REVIEW .......................................................................................... 14 2.1 Ethical challenges in obtaining informed consent in biomedical research ........ 16 2.2 Ethical challenges in obtaining informed consent in genetic and genomic research ..................................................................................................................... 18 2.3 Problem statement and justification ................................................................. 21 2.4 AIM AND OBJECTIVES ................................................................................... 22 2.4.1 AIM ............................................................................................................ 22 2.4.2 OBJECTIVES ............................................................................................ 22 3 METHODOLOGY ................................................................................................... 23 3.1 INTRODUCTION .............................................................................................. 23 3.2 RESEARCH DESIGN ...................................................................................... 23 3.3 LOCATION OF THE RHDGEN PROJECT ...................................................... 23 3.3.1 RHDGen recruitment at Groote Schuur Hospital ....................................... 24 3.3.2 RHDGen recruitment at Vanguard Community Health Centre ................... 25 3.3.3 RHDGEN recruitment at Heideveld Community ........................................ 26 3.4 RESEARCH PARTICIPANTS .......................................................................... 27 3.4.1 RHDGen cases .......................................................................................... 27 3.4.2 RHDGen controls ...................................................................................... 27 4 3.4.3 RHDGen staff as key informants ............................................................... 28 3.5 DATA COLLECTION METHODS ..................................................................... 28 3.5.1 IN-DEPTH INTERVIEWS (IDIs) ................................................................. 28 3.5.2 PARTICIPANT OBSERVATIONS (POs) ................................................... 32 3.6 DATA PROCESSING AND MANAGEMENT.................................................... 35 3.7 ANALYSIS OF INTERVIEW DATA .................................................................. 35 3.8 METHODOLOGICAL CHALLENGES AND STUDY LIMITATIONS ................. 36 3.9 ETHICAL CONSIDERATIONS ......................................................................... 38 3.10 SUMMARY ................................................................................................... 39 4 OUTCOMES OF PARTICIPANT OBSERVATIONS OF THE CONSENT PROCESS OF RHDGEN CASES AND CONTROLS ...................................................................... 39 4.1 Introduction ...................................................................................................... 39 4.2 Different recruitment contexts of RHDGen cases and controls ............................ 40 4.2.1 Recruitment and consent process of RHDGEN cases in the Cardiac Clinic and the Clinical Research Centre at the Groote Schuur Hospital ......... 40 4.2.2 Recruitment and consent process of RHDGen controls at the Clinical Research Centre of the Groote Schuur Hospital..................................................... 41 4.2.3 Recruitment and consent process of RHDGen controls at the Vanguard Community Health .................................................................................................. 43 4.2.4 Recruitment and consent process of RHDGen controls at the Heideveld Community ............................................................................................................. 45 4.3 Specific ethical challenges with the informed consent process of RHDGen cases and controls in the different recruitment sites .................................................. 46 5 4.3.1 Fear of giving blood ....................................................................................... 46 4.3.2 Trust and familiarity with research staff ......................................................... 47 4.3.3 Diagnostic misconception among prospective research participants ............. 47 4.3.4 Privacy and confidentiality ............................................................................. 48 4.3.5 Pressure during the recruitment process ....................................................... 48 4.3.6 Undue inducement to participate in the RHDGen research project ............... 49 4.3.7 Refusal to disclose names and sign consent documents .............................. 50 4.3.8 Security and safety of research staff .............................................................. 50 4.4 Conclusion ........................................................................................................... 51 5 FINDINGS FROM INDEPTH INTERVIEWS WITH RHDGEN RESEARCH PARTICIPANTS ............................................................................................................ 52 5.1 DIAGNOSTIC AND THERAPEUTIC MISCONCEPTION IN THE RHDGEN STUDY ....................................................................................................................... 52 DIAGNOSTIC AND THERAPEUTIC MISCONCEPTION: DISCUSSION ............... 59 5.2 ALTRUISM IN THE RHDGEN STUDY................................................................. 60 ALTRUISIM: DISCUSSION .................................................................................... 63 5.3 SAFETY AND INSECURITY OF RESEARCH STAFF IN THE RHDGEN STUDY ................................................................................................................................... 64 SAFETY AND INSECURITY: DISCUSSION .......................................................... 68 5.4 FEAR OF GIVING BLOOD IN THE RHDGEN STUDY ........................................ 69 FEAR OF GIVING BLOOD: DISCUSSION ................................................................... 74 5.5 COMPREHENSION OF INFORMATION ABOUT THE RHDGEN STUDY .......... 76 6 COMPREHENSION: DISCUSSION .............................................................................. 87 6 DISCUSSION OF THE FINDINGS ......................................................................... 90 7 CONCLUSION AND RECOMMENDATIONS ......................................................... 98 8 REFERENCES ....................................................................................................