developing world bs_bs_banner bioethics Developing World Bioethics ISSN 1471-8731 (print); 1471-8847 (online) Volume 15 Number 1 2015 pp 8–17 doi:10.1111/dewb.12030 ENGAGING DIVERSE SOCIAL AND CULTURAL WORLDS: PERSPECTIVES ON BENEFITS IN INTERNATIONAL CLINICAL RESEARCH FROM SOUTH AFRICAN COMMUNITIES OLGA ZVONAREVA, NORA ENGEL, ELEANOR ROSS, RON BERGHMANS, AMES DHAI AND ANJA KRUMEICH Keywords benefit sharing, bioethics, South Africa, clinical trials, culture, local perspectives ABSTRACT The issue of benefits in international clinical research is highly controversial. Against the background of wide recognition of the need to share benefits of research, the nature of benefits remains strongly contested. Little is known about the perspectives of research populations on this issue and the extent to which research ethics discourses and guidelines are salient to the expectations and aspirations existing on the ground. This exploratory study contributes to filling this void by examining perspectives of people in low-income South African communities on benefits in international clinical research. Twenty-four individuals with and without experience of being involved in clinical research participated in in-depth interviews. Respondents felt that ancillary care should be provided to clinical research participants, while a clinical study conducted in particular community should bring better health to its members through post-trial benefits. Respondents’ perspectives were grounded in the perception that the ultimate goal of international clinical research is to improve local health. We argue that perspectives and understandings of the respondents are shaped by local moral traditions rather than clinical research specificities and require attention as valid moral claims. It is necessary to acknowledge such claims and cultural worlds from which they emerge, thus building the foundation for equal and embracing dialogue to bridge different perspectives and handle contradicting expectations. INTRODUCTION Clinical research is expanding globally. The numbers of international clinical studies, conducted in lower-income countries and funded by organizations from wealthier countries, have been growing, accompanied by a proliferation of ethical debates which have focused on preventing exploitation, promoting social value of research and designing legitimate regulatory regimes.1 One of the most pronounced controversies arose around research benefits. At the heart of this controversy is the concern that populations of lower-income countries bear burdens of international clinical research, while benefits accrue to other parties, including researchers who achieve career enhancement, sponsors who are recognized for their scientific profile and may obtain financial profits and citizens of wealthier countries where more developed, although still imperfect, infrastructure exists for translating research results into health-care practices.2 Against 1 S. Benatar. Reflections and Recommendations on Research Ethics in Developing Countries. Soc Sci Med 2002; 54: 1131–1141; R. Macklin. After Helsinki: Unresolved Issues in International Research. Kennedy Inst Ethics J 2001; 11: 17–36; E.J. Emanuel et al. What Makes Clinical Research in Developing Countries Ethical? The Benchmarks of Ethical Research. J Infect Dis 2004; 189: 930–937. 2 S.R. Benatar, A.S. Daar & P.A. Singer. Global Health Challenges: The Need for an Expanded Discourse on Bioethics. PLoS Med 2005; 2: e143. doi:10.1371/journal.pmed.0020143; C. Hayden. Taking as Giving: Bioscience, Exchange, and the Politics of Benefit-sharing. Soc Stud Sci 2007; 37: 729–758. Address for correspondence: Olga Zvonareva, Department of Health, Ethics and Society, Maastricht University, Postbus 616, Maastricht Limburg 6200 MD, Netherlands, Email: o.zvonareva@maastrichtuniversity.nl. Conflict of interest statement: No conflicts declared © 2013 John Wiley & Sons Ltd 9 Olga Zvonareva et al. the background of wide recognition of the need to share benefits arising from international clinical research there is still no agreement over what exactly, if anything, is owed to those participating in international clinical research and their communities.3 This study brings in viewpoints and experiences of actual and potential participants in international clinical research and adds to the growing body of literature calling for their equal inclusion in this debate as well as in wider discussions about the ethics of international clinical research.4 This article starts by positioning the study in current debates on benefits in international clinical research. Following a description of the methodology, the results based on data obtained through in-depth interviews with low-income members of South African communities with and without experience of being involved in clinical studies, are presented in 3 steps: 1) the respondents’ views on clinical research; 2) the respondents’ perspectives on benefits in clinical research; 3) the views and experiences of the respondents who had been involved in clinical research and whose expectations regarding their involvement were not met. Further we discuss how perspectives and understandings put forward by the respondents are grounded in local moral traditions and argue against attributing their views to lack of knowledge about clinical research and its activities. Finally, the article elaborates on the normative significance of the local perspectives, speaking to wider debates on the design of regulatory regimes for international clinical research and the need for a greater dialogue between diverse socio-cultural worlds open to different framings. For the purpose of clarity, throughout this article the term ‘respondent’ refers to the individuals who participated in interviews for our study. The term ‘participant’ refers to hypothetical clinical research participants who are referred to by the respondents. 3 Participants in the 2001 Conference on Ethical Aspects of Research in Developing Countries. Fair Benefits for Research in Developing Countries. Science 2002; 298: 2133–2134; Participants in the 2001 Conference on Ethical Aspects of Research in Developing Countries. Moral Standards for Research in Developing Countries: from ‘Reasonable Availability’ to ‘Fair Benefits’. Hast Cent Rep 2004; 34: 17–27; Participants in the 2006 Georgetown University Workshop on the Ancillary-Care Obligations of Medical Researchers Working in Developing Countries. The Ancillary-Care Obligations of Medical Researchers Working in Developing Countries. PLoS Med 2008; 5: e90. doi:10.1371/journal. pmed.0050090; A.J. Ballantyne. How to Do Research Fairly in an Unjust World. Am J Bioeth 2010; 10: 26–35. 4 P. Tindana et al. Grand Challenges in Global Health: Community Engagement in Research in Developing Countries. PLoS Med 2007; 4: e273; C. Weijer & G. LeBlanc. The Balm of Gilead: Is the Provision of Treatment to those who Seroconvert in HIV Prevention Trials a Matter of Moral Obligation or Moral Negotiation? J Law Med Ethics 2006; 34: 793–808. BACKGROUND Providing benefits to international clinical research participants and their communities has been widely recognized as an important means to minimize exploitation and promote social value of research. One approach advocates post-trial access to an intervention shown to be effective in a clinical study and other benefits.5 It is endorsed by international research guidelines,6 including the Declaration of Helsinki, which stipulates that at the conclusion of the study research participants are entitled ‘to share any benefits that result from it, for example, access to interventions identified as beneficial in the study or to other appropriate care or benefits’7 and states that research protocol should describe ‘arrangements for post-study access by study subjects to interventions identified as beneficial in the study or access to other appropriate care or benefits’.8 Further, there is a wide agreement in the policy documents that not only research participants but also their communities should benefit from research.9 However, existing regulations leave important questions open, including who is responsible for ensuring that benefits are available as well as to whom exactly, when and which types of benefits should be provided. This uncertainty complicates realization of benefit sharing in practice.10 Within the academic debates the prominent topic has been the fairness of distribution of research benefits. The ‘fair benefits’ framework also considers various forms of research benefits, besides access to the developed intervention, for example the construction of health care facilities, public health measures and health services beyond those required as part of the research that should be made available to participants and their communities, and, importantly, emphasizes community engagement by offering that host populations themselves point to the benefits that are of value for them and are fair, taking into account burdens, relative contributions and benefits to others.11 However, disagreement persists about whether fairness of benefits should be determined based 5 D. Schroeder & E. Gefenas. Realizing benefit sharing – the case of post-study obligations. Bioethics 2012; 26(6): 305–14. 6 See, for example, UNESCO, Universal Declaration on Bioethics and Human Rights 2005, Article 15. 7 World Medical Association, Declaration of Helsinki 2008, Guideline 33. 8 World Medical Association, Declaration of Helsinki 2008, Guideline 14. 9 CIOMS, International Ethical Guidelines for Biomedical Research Involving Human Subjects 2002 Guideline 10, 51. See also World Medical Association, Declaration of Helsinki 2008, Guideline 17, stating that research is only justified ‘if there is a reasonable likelihood that [research] population or community stands to benefit from the results of the research’. 10 Participants, op. cit. note 3; D. Schroeder & E. Gefenas, op. cit. note 5. 11 Ibid. © 2013 John Wiley & Sons Ltd Benefits in International Clinical Research on the micro-level transactional justice or whether it should take the broader macro level disparities into account, as well as about how benefit-sharing should be organized in practice.12 Several counter-arguments focusing on benefit sharing as a key dimension of ethical research conduct have been articulated, cautioning against conflating research with other types of activities. Taken together these arguments essentially claim that research as ‘an activity designed to test a hypothesis, permit conclusions to be drawn, and thereby to develop or contribute to generalizable knowledge’13 does not have an aim to provide health care or restore global inequalities.14 This conflating of research with clinical care and/or development work, it is argued, leads to erroneous ethical judgments.15 Furthermore, within the regulatory field much attention is given to limiting ‘excessive’ offers that can possibly distort decision-making of potential research participants, thus constituting undue inducement.16 Paradoxically, strict prohibitions against undue inducements, especially when research is performed among low-income populations, limit benefit sharing possibilities and threaten the protection from exploitation as disproportional distribution of benefits.17 Finally, there is lack of examples of good practice in providing benefits to research participants and host communities.18 Several studies on the perspectives of research populations themselves on the issue of benefits in international clinical research have been published to date. Few studies were conducted on perceptions of and experiences with 12 A. London & J. Zollman J. Research at the Auction Block: Problems for the Fair Benefits Approach to International Research. Hast Cent Rep 2010; 40(4): 34–45; A.J. Ballantyne. op. cit. note 3; R. Macklin. Fair Benefits in Developing Countries: Maximin as a Good Start. Am J Bioeth 2012; 10(6): 36–37; U. Schuklenk. For-profit Clinical Trials in Developing Countries – Those Troublesome Patient Benefits. Am J Bioeth 2010; 10(6): 52–54; B. Pratt & B. Loff. Justice in international clinical research. Dev World Bioeth 2011; 11(2): 75–81. 13 The Belmont Report, 1978; 3. 14 P. Litton & F.G. Miller. A Normative Justification for Distinguishing the Ethics of Clinical Research from the Ethics of Medical Care. J Law Med Ethics 2005; 33(3): 566–574. 15 F.G. Miller. Research Ethics and Misguided Moral Intuition. J Law Med Ethics 2004; 32(1): 111–116; F.G. Miller & H. Brody. A Critique of Clinical Equipoise: Therapeutic Misconception in the Ethics of Clinical Trials. Hast Cent Rep 2003; 33(3): 19–28. 16 See, for example, CIOMS, International Ethical Guidelines for Biomedical Research Involving Human Subjects 2002; Guideline 7, 45, stating ‘The payments should not be so large, however, or the medical services so extensive as to induce prospective subjects to consent to participate in the research against their better judgment (“undue inducement”)’. 17 G. Arnason & A. Van Niekerk. Undue Fear of Inducements in Research in Developing Countries. Camb Q Healthc Ethics 2009; 18(2): 122–129. 18 E.R.M. Cohen et al. Reporting of Informed Consent, Standard of Care and Post-Trial Obligations in Global Randomized Intervention Trials: A Systematic Survey of Registered Trials. Dev World Bioeth 2008; 9(2): 74–80. © 2013 John Wiley & Sons Ltd 10 benefits in international clinical research among stakeholders in developing countries19 and even fewer explicitly focus on perspectives of research participants and their communities,20 while most of the latter are devoted to HIV-related studies.21 Consequently, little is known about the extent to which research ethics discourses and guidelines are salient to the expectations and aspirations existing on the ground. The debates described above have been taking place mainly among academics and scientists from the economically rich countries of the West.22 However, it is crucially important that research populations inform discussions on this key ethical question. Views of people from culturally diverse and lower-income settings, who are confronted with ethical complexities introduced by international clinical research in real life, can reframe the debate by exposing overlooked issues, showing which arguments are particularly relevant, as well as by switching focus away from concerns which appear to have little relevance in practice settings. This exploratory study contributes to filling this void by examining perspectives of people in low-income South African communities on benefits in international clinical research and arguing for their equal inclusion into related discussions. METHODS The qualitative exploratory study was conducted in South Africa, a country with increasing numbers of international clinical research sites23 and with about 50% of the population living below the national poverty line of $121 (PPP).24 The study, inspired by the methodology 19 G.M. Lairumbi et al. Forms of Benefit Sharing in Global Health Research Undertaken in Resource Poor Settings: A Qualitative Study of Stakeholders’ Views in Kenya. Philos Ethics Humanit Med 2012; 7: 7. 17 January 2012; S. Molyneux et al. Benefits and Payments for Research Participants: Experiences and Views from a Research Centre on the Kenyan Coast. BMC Med Ethics, 2012; 13: 13. 22 June 2012. 20 C. Grady et al. op cit. note 12. 21 D.N. Shaffer et al. Equitable treatment for HIV/AIDS clinical trial participants: A focus group study of patients, clinical researchers, and administrators in western Kenya. J Law Med Ethics 2006; 32: 55–60; C.R. Thiessen et al. Personal and community benefits and harms of research: views from Rakai, Uganda. AIDS 2007; 21(18): 2493–501; N. Barsdorf et al. Access to Treatment in HIV Prevention Trials: Perspectives from a South African Community. Dev World Bioeth 2010; 10(2): 78–87. 22 P.W. Geissler & R. Pool. Editorial: Popular Concerns about Medical Research Projects in Sub-Saharan Africa – A Critical Voice in Debates about Medical Research Ethics. Trop Med Int Health 2006; 11(7): 975– 982. 23 J. Karlberg. Sponsored Clinical Trial Globalization Trends. Clinical Trial Magnifier 2008; 1(2): 13–18; J. Karlberg. The establishment of Emerging Trial Regions. Clinical Trial Magnifier 2011; 4(1): 7–23. 24 M. Leibbrandt et al. Trends in South African Income Distribution and Poverty since the Fall of Apartheid. OECD Social, Employment and Migration Working Papers 2010; 101. 11 Olga Zvonareva et al. of grounded moral analysis, combined empirical and normative enquiry.25 The research process was open, responsive and organized in interaction with the respondents, permitting methodological decisions such as directing sampling strategy, selecting issues that required further exploration and determining the point of saturation to be taken along the way.26 Respondents The study involved 24 respondents (7 men and 17 women in the age range 22–62), 9 of whom had experience with participating in clinical research. Originally the cleaning staff at one of the South African universities was invited to participate. This decision was based on the rationale that it is relatively safe to assume a low economic status for them as their salaries do not exceed R2000 (240 US dollars) per month. 19 members of the cleaning personnel were included in the study, among whom only 4 had an actual experience in clinical research. This relative lack of lived experiences among the respondents directed the sampling further. 5 more individuals were included, who were enrolled in a Phase III randomized controlled trial designed to assess the safety and effectiveness of a vaginal microbicide in the prevention of a HIV Type 1 infection in women. Economic status of the trial participants was not assessed directly. However, according to the research staff involved in the trial the community where the trial was conducted has historically been underprivileged and is still rather poor. Instrument and procedure The first author conducted in-depth individual interviews. This allowed for an understanding of why respondents expressed certain opinions and for the exploration of values and worldviews behind these. In the course of interviews, the respondents were encouraged to bring in issues related to international clinical research which in their opinion were relevant. The original interview guide was informed by the available literature and involved the following topics: experiences in clinical research, views on purpose of clinical research, on role of participants in it and on appropriate benefits and monetary payments to participants. The perspectives, which emerged in the interviews with the respondents, were then used to refine the interview guide and direct further research, considering relevant theoretical arguments. Thus, the topics of motives for (non)participation and perceptions of possible risks for participants were 25 M. Dunn et al. Toward Methodological Innovation in Empirical Ethics Research. Camb Q Healthc Ethics 2012; 21: 466–480. 26 J. Ives & H. Draper. Appropriate Methodologies for Empirical Bioethics: It’s All Relative. Bioethics 2009; 23: 249–258. incorporated into the interview guide; within the original topic of benefits two main points of focus were suggested by the respondents: medical care in clinical research and post-trial benefits; finally, the originally prominent topic of monetary payments came to be a less substantial part of the interview. A pilot interview was conducted to adjust wording as English was not the first language of the respondents. All interviews were conducted by the first author over a 3 month period from May to July 2012. 10 interviews were conducted completely in English, the remaining fourteen required the involvement of a translator. The degree of the translator’s involvement varied from assisting with communicating difficult concepts such as risk, to the translation of the entire interview to the native languages of the respondents – isiZulu, isiXhosa, Sesotho and Sesotho sa Leboa. The interviews lasted between 30 and 60 minutes and were audiotaped and transcribed verbatim. Data analysis Over the course of data collection, data analysis and interpretation were continuously performed. The interviews were read and discussed by the members of the research team. The first author identified text units relevant for the study purpose and coded them using the concepts derived from the data and preexisting theoretical frameworks. The codes were checked for consistency by other members of the research team in order to obtain consistency and congruency was observed. Further, the themes were developed drawing from the codes of similar content and underlying meanings ‘that are theorized as underpinning what is actually articulated in the data’.27 All investigators participated in reviewing and refining data interpretation and analysis. During data collection, quality was ensured through continuous review of tapes and transcripts to improve interview methods. While analyzing the data, concepts and emerging patterns were continuously cross-checked within and across interviews to challenge or support the respondents’ and investigators’ accounts and interpretations. Ethical considerations The study was approved by the Human Research Ethics Committee – Medical (HREC) of the University of the Witwatersrand. Informed consent and permission to record the interview was obtained from all respondents. The confidentiality of the respondents was ensured by the separation of data from identifiable individuals, secure storage of the codes linking data to individuals and 27 V. Braun & V. Clarke. Using Thematic Analysis in Psychology. Qual Res Psychol 2006; 3: 77–101: 85. © 2013 John Wiley & Sons Ltd Benefits in International Clinical Research anonymizing individuals in this paper. No compensation was provided to the respondents. RESULTS ‘May be it will bring good results to our nation’: views on clinical research This section presents respondents’ attitudes towards international clinical research, perceptions of risks involved in participation, ideas about reasons to participate in clinical studies and, finally, perceptions of the relationship between researchers and participants. Respondents generally expressed a positive and welcoming attitude towards international clinical research. It was seen as a search for ways to address health problems prevalent in South African communities with the HIV/ AIDS epidemic being mentioned most often. Clinical research possessed a high social value for the respondents, which was firmly situated in the local health conditions. A woman who, not having the experience of participating in a clinical study, knows several individuals who had been involved in research, stated: ‘Here we’ve got a dangerous sickness, a virus . . . we haven’t got a medicine here to help. . . . But you can come and make this research, . . . may be it will bring back good results to help our nation.’ (A, 56-year-old). And a woman currently enrolled in the Phase III microbicide trial echoes this statement: ‘I just wanted to take part in this research because we all need medicines for HIV, so if we don’t test it, don’t research about it, we won’t know whether it is working or not. So that’s why I joined.’ (O, 37-year-old). The large majority of the respondents acknowledged the risks involved in clinical research participation. They presented clinical research as inherently unsafe for participants. To explain this position they most often referred to the novelty of the intervention and unpredictability of its effects. For example, when asked about how safe the enrolment in a medical study would be, a woman who described clinical research as being very beneficial for her community, replied: ‘I don’t know how it will be on me. It might be dangerous. I don’t know about it. Nobody knows.’ (E, 54-year-old, no personal experience in clinical research). Acknowledgement of risks did not seem to discourage participation. A woman enrolled in a clinical trial for the first time described procedures associated with participation and their possible negative consequences: ‘Then you have to insert gel and then afterwards they see that gel may react some other way in your body and they © 2013 John Wiley & Sons Ltd 12 will have to check and see that this gel may be is damaging.’ (P, 28-year-old female). Another woman (also involved in clinical research for the first time) refers to the process of weighing personal risks against societal benefits, with societal benefits overweighing personal risks: ‘I don’t see a problem because of I know that at that stage there will be risk. And if I do it and then I get sick or I get ill, I will be proud of that I will say ok I was doing it for people.’ (Q, 22-year-old female, has personal experience in clinical research). Moreover, the respondents often brought up the idea of participation in clinical research as a duty, although a potentially dangerous one. This was rooted in the view of clinical research as a process that produces results, which at the end bring better health to communities where research was conducted. The feeling of personal responsibility to make a contribution was expressed with varying degrees of explicitness. ‘You know, to be fair, if I say no, how do we know that this drug is working? I must say yes, because I want to know its working. Because it is also about our lives.’ (E, 54-year-old female, no personal experience in clinical research). Some respondents extended the duty to participate beyond themselves to others in the community as well: ‘I think that medication is good. Us, we need to participate, all, because of, you know, helping. So these projects I think is good.’ (T, 47-year-old female, no personal experience in clinical research). These statements point to the tendency to link closely clinical research and better health, but not through perceiving research procedures as directly beneficial for participants’ own health. Respondents linked clinical research and practice through the perception of clinical research results being translatable into advances in locally available health care and, thus, a healthier society. Besides presenting clinical research as locally relevant and beneficial, the respondents often stressed the equal importance of the input of clinical research participants and that of researchers. The respondents commonly referred to everyone involved in a process of clinical research as ‘we’, highlighting the presumed collaborative nature and common goals. Explaining why he would take part in a clinical study, a respondent said: ‘I can do it because I can see we want to help people and see if this thing is working’. (X, 53-year-old male, no personal experience in clinical research). The respondents constructed the relationship between researchers and participants in international clinical 13 Olga Zvonareva et al. studies as a form of collaborative partnership, within which the participants were thought of as active contributors. The respondents made sense of participation in international clinical research through envisioning a positive image of research as in a long run bringing better health to their communities. The vivid feature of respondents’ narratives was the perception of medical research as a public good to which responsible people should contribute. The perspectives presented in this section provide a background for understanding the respondents’ views on benefits in international clinical research. ‘Partnership and mutuality’: Perspectives on benefits When speaking of benefits in international clinical research the respondents focused on ancillary care and post-trial benefits as their core expectations. Their views in this regard are presented in this section. Although the respondents did not think that financial payments should be provided to research participants (and in ethics literature financial payments usually are not regarded as research benefits), the general ideas about payments in clinical research articulated by the respondents are presented at the beginning of this section to better illustrate their aspirations. Monetary payments Deliberating on what should be offered to clinical research participants, the respondents themselves did not put forward financial reward. The logic of their riskbenefit calculus somewhat departed from the logic of the established theoretical debate, which assumes that financial reward may constitute undue inducement, thus ‘blinding’ participants to risks. Acknowledging that clinical research entails risk, the respondents conveyed that the risk of damaging their health in a context of hardly accessible healthcare, decisively outweighed personal benefit of obtaining even a considerable sum of money: ‘I won’t go for money. Money can’t do anything. If my health is suffered, then what? I am going to eat that money?’ (O, 37-year-old female, has personal experience in clinical research). However, while money was not presented as a valid reason to take risks, health improvements for one’s community could well be such a reason. The common thread was that motivation of gain, including financial gain, was not appropriate for participation in clinical research. Since clinical research, according to the respondents, was intended to improve health in the communities where it was conducted, the respondents felt it was not right to want something in return for helping their own communities (including future generations). One respondent compared participation in clinical research with blood donation, claiming that one could accept a reward but should not be motivated by the prospect of its reception: ‘It’s like blood donation, it’s like you feel that you are doing blood donation, it is from your heart. And if you feeling to do it, if government can say that now all the people who are doing blood donation we are going to give them money. So much, what. Even that it is not a problem. But only if you feel to donate you can go.’ (G, 32-year-old male, no personal experience in clinical research). Overall the respondents expressed indifference towards monetary rewards. Ancillary care Most respondents mentioned healthcare as something they would welcome, accept and actually expect from researchers conducting clinical studies. The respondents currently enrolled in the clinical trial stressed the importance of ancillary care (health care beyond the measures to ensure scientific validity, prevent study-related harms or address study related injuries), in the context of hardly accessible medical help in the following way: ‘So the healthcare should be high. If they find that something is happening in my body, they don’t just taking me to the public hospital. Public hospitals . . . You’ll go and die there. They have to take you somewhere where they know you will be taken care of. That way it is fine.’ (O, 37-year-old female, has personal experience in clinical research). Within the perceived relationship of partners working together towards finding ways to improve local health, described in the previous section, researchers and participants were seen by the respondents as bound by mutual responsibilities towards each other. Respondents felt that clinical research participants made a valuable and important contribution by providing their bodies and risking health, while researchers, in turn, were expected to be concerned about the wellbeing of participants and, in the long run, the study population. This mutuality was summed up by one of the respondents: ‘I know if I help them, they will help me and the other people.’ (A, 56-year-old female, no personal experience in clinical research). It should be stressed that the described perception of the relationship between researchers and participants did not lead to the thinking that the purpose of research was to help research participants personally. The respondents © 2013 John Wiley & Sons Ltd Benefits in International Clinical Research were well aware of the ‘research’ nature of clinical studies; however it was important for them to know that those who conduct research were not indifferent towards participants’ wellbeing and would reciprocate by making an effort to assist when a participant needed health care. Post-trial benefits Unanimously expressed was the hope that the output of international clinical research would benefit the host community. In the bioethics literature and international guidelines this topic has been framed as the post-trial benefits. Some respondents stressed that an intervention shown effective in the course of a clinical study should be provided to the ones who participated in research: ‘If there is a cure [found in the course of a clinical study] they should give it to me.’ (G, 32-year-old male, no personal experience in clinical research). Most of the respondents assumed that the intervention shown effective in the clinical study would be available for wider communities. ‘If it [tested intervention] helps her, it means that most of our nation they will get help.’ (A, 56-year-old female, no personal experience in clinical research). At the same time many respondents did not focus on single clinical studies, taking instead a broader view of clinical research as a process consisting of multiple trials and errors that sooner or later would yield beneficial results, which would be used for the betterment of those who need them in host communities. ‘But about this kind of research. At the end it will be helping us, people on the ground.’ (I, 38-year-old male, no personal experience in clinical research). The respondents found it quite natural that some clinical research studies failed to deliver results or were very early-stage projects. However they still presented the totality of research processes and agendas as directed towards concrete outcomes such as new and better treatments. In the view of the respondents, any outputs of international clinical research must be used for the benefit of host communities, otherwise it exposes participants to risks for no good reason. It was important for the respondents to be able to conceive the participation in clinical research as a contribution to the common good. ‘No, I won’t agree to participate’: Facing realities of clinical research This section presents accounts of the respondents who hold a negative attitude towards clinical research and their experiences that shaped this attitude, illustrating the importance of engagement with research participants and their perspectives. © 2013 John Wiley & Sons Ltd 14 Two respondents in this study expressed a negative attitude towards clinical research as such. This attitude was shaped by their previous experiences in clinical research. As clinical research participants they expected to be fully informed about a clinical study, their contribution in it as well as study results, and would like to establish equal and reciprocal relationships with a research team. However, these expectations were not met. One of them explained his dissatisfaction with participating in a clinical study conducted after 2000: ‘So maybe you will take hair from me and you will never come back to explain that this helped you by this, this and this. Because they don’t come back to us and explain to us what really-really they are needing from us . . . So when they took blood from me and gave me little money it was not good, because those people they took blood from us and we don’t know why they are taking blood from us.’ (F, 28-yearold male, has personal experience in clinical research). The second respondent echoed this story, but referred to events which took place in the 1960s in a rural area of South Africa: ‘In the area where I grew up they used to come and take blood from people . . . In those old days they would just come and take blood and will never explain to us what they are doing.’ (D, 62-year-old male, has personal experience in clinical research). Consequently, the respondents did not perceive clinical research as locally beneficial and were suspicious about its goals: ‘No, I won’t not agree to participate. Because I do not understand why people want to test anything. And I would not allow my children to do that.’ (D, 62-year-old male, has personal experience in clinical research). For both respondents these experiences resulted in disappointment and a negative perception of clinical research and researchers, with a corresponding reluctance to take part in clinical research anymore. ‘I won’t do anything, even if they come and ask for blood I won’t go there. And not because I am afraid.’ (F, 28-year-old male, has personal experience in clinical research). ‘So if ever they are testing this medicine I will say no, even if they offer those thousands of rands or whatever they are offering.’ (D, 62-year-old male, has personal experience in clinical research). The willingness to participate in clinical research was rooted in perceived local beneficence of research, which also laid the crucial foundation for communication between researchers and participants. The views and experiences described in this last section show that doubts 15 Olga Zvonareva et al. about the beneficial nature of research resulting from unmet expectations of involvement and acknowledgement erodes the willingness to participate. MAKING SENSE OF INTERNATIONAL CLINICAL RESEARCH The results of this study show that the respondents redefined the meaning of being involved in clinical research, constructing it as a contribution towards achieving better local health. Underlying this interpretation was the implicit assumption that international clinical research was conducted in South Africa due to the poor local health status with the purpose of finding ways to improve it. Consequently the respondents perceived research as having high social value for their communities. Researchers and participants were thought to share concerns over the poor health in many South African communities and were expected to form partnerships to work together towards achieving the common goals. The indifference towards payments and expectations of ancillary care and post-trial benefits for the host communities were grounded in the described interpretation. The respondents held essentially a relational understanding of international clinical research and the corresponding benefits. For them the relationship between researchers and participants was not shaped by a study protocol and regulated through informed consent to uphold the distanced position of a researcher as contrasted with the personal character of the doctor-patient relationship and to safeguard autonomy of an individual research participant.28 The assumption that the way participants understand clinical research can be determined by means of the effective communication of research aims and procedures has been relatively prominent in research ethics.29 It is reasoned that, when discrepancies arise, this must be a matter of inefficient communication and general ignorance, and ways to address them would be limited to such measures as instrumental improvements in consent forms (simplifying language, shortening forms) and improvements in the process of obtaining consent (addressing power dynamics, repeated administration of informed consent procedures and the assessment of comprehension).30 28 O. Corrigan. Empty Ethics: The Problem with Informed Consent. Sociol Health Illness 2003; 25: 768–792; 13: 87–106; K. Stewart & N. Sewankambo. Okukkera Ng’omuzungu (Lost in Translation): Understanding the Social Value of Global Health Research for HIV/AIDS Research Participants in Uganda. Global Public Health 2010; 5: 164–180. 29 U. Felt et al. Refusing the Information Paradigm: Informed Consent, Medical Research, and Patient Participation. Health (London) 2009. 30 There is a vast bulk of the literature on ‘improving participant comprehension’, see, for example, E. Cohn & E. Larson. Improving Participant Comprehension in the Informed Consent Process. J Nurs Scholarship 2007; 39: 273–280. However, medical anthropologists and ethnographers have been skeptical of reducing diverging perspectives to mere misinterpretation or misunderstanding due to ineffective communication and participants’ ignorance of science and its processes, attributing them rather to more fundamental differences in how clinical research is framed and interpreted within particular cultural horizons and actor groups.31 Also ideas in support of this critique are presented in the works of science and technology scholars, who see science and its ways as embedded socio-cultural practices, as much (in)valid as any other ways of finding sense.32 The perspectives of the respondents in this study and their expectations regarding benefits were influenced heavily by the indigenous accounts of right and wrong, which have hardly been articulated in the field of research ethics as the local moralities do not speak the language of this field. Discussing African33 moral traditions, Tangwa34 says: ‘For the most part, of course, African philosophy is not set out in monographs and journals; rather, it is manifested in, held by, African peoples themselves’. Some scholars, drawing on anthropological inputs and their own cultural backgrounds as members of indigenous communities, have attempted to describe the rich and long standing ethical heritage of Africa with its diverse populations.35 They do not claim that cultures with ideas about morality ingrained in them exist for centuries in a static and unchanged manner and/or being held uniformly by all African people. This literature, nevertheless, provides a helpful context for understanding the perspectives and expectations put forward in this study. African moral traditions are relational in nature. Their cornerstone is Ubuntu, a traditional philosophy and way of life of communities in South Africa and Sub-Saharan Africa in general.36 It is commonly accepted that Ubuntu derives from the word muntu, which means a person, human being.37 It is Ubuntu that constitutes the very 31 Geissler & Pool, op. cit. note 22; J. Fairhead, M. Leach & M. Small. Public Engagement with Science? Local Understandings of a Vaccine Trial in the Gambia. J Biosoc Sci 2006; 38: 103–116; J. Fairhead, M. Leach & M. Small. Where Techno-Science Meets Poverty: Medical Research and the Economy of Blood in The Gambia, West Africa. Soc Sci Med 2006; 63: 1109–1120. 32 S. Jasanoff. Technologies of Humility. Nature 2007; 450: 33. 33 Speaking about African moral traditions we refer to thought, values and practices of people who culturally belong to indigenous communities of Sub-Saharan Africa. 34 G.B. Tangwa. The Traditional African Perception of a Person: Some Implications for Bioethics. Hast Cent Rep 2000; 30: 39–43: 41. 35 G.B. Tangwa. Bioethics: An African Perspective. Bioethics 1996; 10: 183–200; T. Metz. African and Western Moral Theories in a Bioethical Context. Dev World Bioeth 2010; 10: 49–58. 36 M. Munyaka & M. Motlhabi. 2009. Ubuntu and its Socio-moral Significance. In African Ethics. An Anthropology of Comparative and Applied Ethics. M.F. Murove, ed. Scottsville: University of KwaZuluNatal Press: 63–84. 37 Ibid. © 2013 John Wiley & Sons Ltd Benefits in International Clinical Research essence of being human, it is an inner state that makes one feel and behave as a true human being. And behaving according to human nature is identified with contributing to the wellbeing of others and the community and promoting harmonious relations within society.38 Achieving a state of being a human or having Ubuntu is possible only through relating positively with others as expressed in the widespread maxim ‘A person is a person through other persons’.39 Such mutuality in African moral traditions allows one to distinguish between more human and less human. That is the more one promotes harmonious relations, the more morally virtuous and the more of a person one is. To become personally complete as a human being one has to engage more and more deeply in community with others.40 Whereas if one harms others or is even just indifferent to them, then one lacks Ubuntu, literally becoming ‘not a person’. Reflecting on the fundamental value of harmonious (communal) relationships, Metz41 suggests that such relationships involve identifying and exhibiting solidarity with each other. He describes identity as ‘to think of themselves as members of the same group, that is, to conceive of themselves as a “we”, as well as for them to engage in joint projects, coordinating their behavior to realize shared ends’; while exhibiting solidarity would mean ‘to engage in mutual aid, to act for the sake of one another (ideally, repeatedly over time)’.42 Ethics not only regulates behavior, but construes it, through interpretive power which is rooted in culture.43 Accordingly, clinical research was interpreted by the respondents through the lens of local moral traditions. The value of identity was expressed by them through relating to researchers as their partners and a desire to help the community. Solidarity was seen in the conceptualization of clinical research as a common quest towards better health and in expectations of care and results sharing on the part of researchers. Such an interpretation was necessary for international clinical research to be judged as morally right; impartial transaction-like research, that did not contribute to the betterment of the host communities (beyond the mere purposes of research) had no chance of being accepted, since within described social and cultural worlds it would be viewed as lacking humanity, violating harmonious relations within society and, therefore, as morally wrong. 38 Ibid Metz, op. cit. note 35. 40 A. Shutte. 2001. Ubuntu: An Ethic for the New South Africa. Cape Town, South Africa: Cluster Publications. 41 Metz, op. cit. note 35. 42 Metz, op. cit. note 35, p 51. 43 N.A. Christakis. Ethics are Local: Engaging Cross-Cultural Variation in the Ethics for Clinical Research. Soc Sci Med 1992; 35: 1079– 1091. 39 © 2013 John Wiley & Sons Ltd 16 The few respondents in this study who viewed clinical research negatively confirmed this by pointing to the detached attitude of researchers and absence of engagement with and concern about participants and their communities, which led them to a moral conclusion that clinical research ‘is not a good thing’. CONCLUSION The voices of the respondents in the present study require serious attention. Their accounts were shaped not by clinical research specificities but by the broader indigenous moral systems and cannot be ‘corrected’ with more and/or differently presented information. Respondents’ perspectives stem from the local social and cultural worlds and represent legitimate and valid moral claims, which require equal engagement with research participants and their communities as well as provision of ancillary care and post-trial benefits in settings with hardly accessible medical care for international clinical research to be judged as morally right. These claims are consonant with a growing body of ethics literature advocating collaborative partnerships and social value as important aspects of international clinical research.44 It is necessary to acknowledge local moral claims and cultural worlds from which they emerge, thus building the foundation for equal and embracing dialogue to bridge different perspectives and handle contradicting ethical expectations. Awareness of and respect for the legitimate ethical expectations of participants and host communities in international clinical research are crucial for sustainability of clinical research in South Africa and other developing countries. The necessity of a dialogue was stressed by the respondents who developed antagonistic attitudes towards clinical research after experiencing a clash between their expectations and actual research practices. The present exploratory study confirmed the need for more research on local moral perspectives on benefits and other issues in international clinical research, which would lay a foundation for further broader engagement. Attention also needs to be given to further development of the mechanisms of inclusion and practices of engagement to ensure that these are not orchestrated in favour of powerful actors and that local needs and perspectives are truly heard and taken seriously. 44 E.J. Emanuel et al. op. cit. note 1; V.M. Marsh et al. Working with Concepts: The Role of Community in International Collaborative Biomedical Research. Public Health Ethics 2011; 4(1): 26–39; C.P. Gikonyo et al. Taking Social Relationships Seriously: Lessons Learned from the Informed Consent Practices of a Vaccine Trial on the Kenyan Coast. Soc Sci Med 2008; 67: 708–720. 17 Olga Zvonareva et al. Acknowledgements The authors are grateful to the people who took part in the interviews for this study and colleagues at the Steve Biko Centre for Bioethics and Maastricht University for their useful comments and suggestions during the conduct of this study and development of this manuscript. We thank Human Research Ethics Committee – Medical (HREC) of the University of the Witwatersrand, Setshaba Research Centre and personally Professor Peter Cleaton-Jones, Dr Khatija Ahmed, Dr Mookho Malahleha, Dr Itumeleng Funani and Dr David Buso for their invaluable assistance. We also thank the reviewers for their helpful and insightful comments. Biographies Olga Zvonareva is a Research Assistant at the Department of Health, Ethics and Society, Maastricht University, the Netherlands, and honorary research associate at the Steve Biko Centre for Bioethics, University of the Witwatersrand, South Africa. She holds the Kootstra Talent Fellowship and obtained MSc in Global Health from Maastricht University. Her research interests lie in research ethics. Nora Engel is an Assistant Professor at the Department of Health, Ethics and Society at Maastricht University, The Netherlands. Her research draws on Science and Technology Studies and Innovation Studies to examine innovation dynamics related to global health challenges. Eleanor Ross is a Professor of Social Work and a former Head of the Social Work Department at the University of the Witwatersrand (Wits). She was elected to serve on the South African Council for Social Service Professions and is currently affiliated to the Steve Biko Centre for Bioethics at Wits Medical School. Ron Berghmans, PhD, is an Assistant Professor at the Department of Health, Ethics and Society, CAPHRI School for Public Health and Primary Care at Maastricht University, The Netherlands. He was trained as a psychologist and bioethicist. His major areas of interest are psychiatric ethics, research ethics, ethics in elderly care and end-of-life decision-making. Amaboo Dhai is Director of the Steve Biko Centre for Bioethics, Head of Bioethics at the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg. She is also Co-Chair of the Human Research Ethics Committee (Medical) and Deputy Chair of the National Health Research Ethics Council. Anja Krumeich, PhD, is an Assistant Professor and Programme Director MSc Global Health at the Department of Health, Ethics and Society. She studied Cultural Anthropology at the University of Amsterdam, majoring in Medical Anthropology. Her research interests include social differentiation, health and diversity, health and culture, health and poverty, international health, health promotion, and dialogical ethnography. © 2013 John Wiley & Sons Ltd Copyright of Developing World Bioethics is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.