JECH Online First, published on February 10, 2015 as 10.1136/jech-2014-205215
Essay
Biobank research, informed consent and society. Towards a new alliance? Flavio D’Abramo Correspondence to Flavio D’Abramo, Charité Comprehensive Cancer Center, Charitéplatz 1, 10117, Berlin, Germany; fl[email protected] Received 7 November 2014 Revised 17 January 2015 Accepted 19 January 2015
To cite: D’Abramo F. J Epidemiol Community Health Published Online First: [please include Day Month Year] doi:10.1136/jech2014-205215
ABSTRACT With the rise of -omics disciplines and biobank research, personal data and biosamples crossing national borders pose new ethical questions. In this article, informed consent, as originally conceived, is shown as not being sufficient to address aims of research and interests of patients any more. Therefore the author has, after having scrutinised issues in biobanking, sketched a model of dynamic consent and a manner of scrutinising ethical issues through empirical data. During the past decades a revolution has taken place in science: productive methods and techniques from the industry have been transferred between medical and biological laboratories around the world. Omics disciplines such as genomics are possible thanks to high-throughput standards. The Human Genome Project, completed in 2001, was established on the new characteristics of biological laboratories being able to realise economies of scale. From the moment of its completion, genome researchers have been occupied with finding ways to analyse massive amounts of DNA in a faster, cheaper, easier and, at the same time, cost-reducing way, to expand productive capacities and to extract more information from the same amount of work.1 Nowadays, with technologies such as Genome Wide Association Studies, laboratories are consociated within consortia in processing huge amounts of genomic data to describe the common patterns of human genetic variation. The main goal of this enterprise consists in finding genes (eg, single nucleotide polymorphisms) or molecular characteristics associated with human diseases, related susceptibilities and response to pharmaceuticals. Human biological samples such as those made of blood, tissue, saliva, umbilical cord, placenta, etc, which are at the base of processes of data extraction, are collected in biobanks. These biorepositories, created for various reasons—for instance, pathology collections, repositories for specific diseases as cancer registries and population databases created to permit longitudinal studies of any disease or condition—are at the base of genomics and personalised medicine. To make sense of genetic and genomic data it is necessary to couple them with phenotypic, lifestyle and social information—for example, healthcare data such as disease histories, treatments received; lifestyle information such as nutrition, exercise, wealth, family background, genealogy and other kinds of identifying data. As has often been pointed out, a challenge to carrying out biobank research and taking informed consent is disclosing, to prospective participants,
research goals, risks and benefits. Informed consent, which was thought of as a tool to disclose information to research participants in order to allow them to take an autonomous decision, challenges biobank research as relevant information is not known or not clearly stated at the time of eliciting consent. That means information needed to fulfil informed consent procedures in biobank research is difficult to give. When biobank samples and related data are used to develop genomic research (or other kinds of projects based on -omics technologies), participants could be harmed by unscrupulous usage of their personal data. This informational risk is the main reason underlying the actual ethical debate. Among the risks, we can include genetic discrimination and stigmatisation. For instance, knowledge of a person’s genetic makeup can be used to justify unequal treatment— for example, a candidate for a job may be excluded on the grounds of her genetic disposition to a future disease or a person wishing to buy health insurance could be refused on genetic grounds.2 Moreover, those who undergo genomic research could be harmed by disclosure of information on their health status that they might not wish to know. This compulsory or forced provision of health information has been justified through arguments supporting the next generation’s well-being, for instance, to predict inherited disease susceptibility. Nevertheless, even if disclosure of genetic information could be useful in some contexts, the right not to know has been defended as a legitimate act to protect patients’ and individuals’ autonomy and psychological status.3 On the other hand, before the introduction of -omics technologies, important beneficial public health discoveries were carried out through biobank research such as the association between helicobacter pylori infection and the risk of gastric carcinoma4 or the causal relation between human papilloma virus (HPV) and cervical cancer.5 Therefore, medical research based on -omics techniques can easily exacerbate the tension between individual rights and bioethical principles versus a population outlook and objectives of biobank research.6 In 2004, Klaus Hoeyer held that informed consent in relation to tissue donation was not yet an established routine.7 As shown by the empirical literature,8 during the past few years an increasing number of socioempirical studies on public and patients’ perception of biobank research has been carried out, underlying the need of taking on the arduous task of informing research participants to obtain their consent. Despite informed consent in biobank research being a fairly novel issue, inability to recall risks spelled out during the consent
D’Abramo F. J Epidemiol Community Health 2015;0:1–4. doi:10.1136/jech-2014-205215
Copyright Article author (or their employer) 2015. Produced by BMJ Publishing Group Ltd under licence.
1
Essay process is a leitmotif—for example, within clinical trials.9 Being a dynamic process, risk understanding can depend on the recipient or on the medium utilised by groups or institutions—wellknown problems are a formulation of inherent risks. For instance, it is not easy to find a consent model stating risks derived from commercialisation of individual biosamples or data. Certainly, difficulties of understanding depend on the state of mind of the recipient. Indeed, when research participants experience a state of illness, this could determine the decision-making process of donation—as the illness progresses, patients understand less,10 as could happen in oncological cases where different patient symptoms such as pain, anxiety, fear and depression, linked to the type of cancer and the stage, will likely influence the consent process and its understanding.11 Despite the problems attached to the consent process tout court, there are other characteristics of informed consent utilised in biobanking, and not linked to recipients, which can explain both (1) the empirical evidence highlighting distrust of science, biobanks and industry,12 13 and patients’, and the public’s, concerns for personal and societal risks,14 15 and (2) the empirical evidence showing participants’ problems of comprehension.15 16
SOCIETAL RISKS ON THE INDIVIDUALS’ SHOULDERS The consent process in biobanking is of a unique nature, certainly different from that in other kinds of medical research enterprises. First of all, risks and benefits in biobanking are asymmetrically distributed: risks deriving from biobank research are of an individual and societal nature—discrimination can be produced at both, individual and group levels— whereas, most of the time, benefits are only for the society (biobank research seldom produces direct returns for participants, or benefits are produced only after several years). This risks/benefits asymmetry of biobank research connotes the consent process in a very unique manner. Indeed, the consent process, which is a process to defend the individualistic principle of autonomy, when applied to biobanking, refers necessarily to an evaluation of societal risks and benefits at the individual level. Is it right to give societal responsibilities to persons who remain seen solely as individuals? In this framework where, by requiring consent, individuals are loaded with societal responsibilities, a commune reaction could be an escape: what you do not know cannot be an object of your responsibility. There, an explanation for the lack of recall of information about the biobank projects and for the lack of interest in reading the consent sheets might be interpreted as a way of refusing an imposition of responsibility.7 In this respect, what has been named the ‘deficit model’ for the public understanding of science (roughly speaking this model holds that the public does not understand science as it is ignorant and anxious, and considered in need of information presented in a better or clearer manner) is useless in addressing the issue of consent in biobanking as well as detrimental as it avoids considering ethical themes other than autonomy of individuals. For instance, in the case of a UK biobank, the ‘openness’ and ‘transparency’ invoked for the project management was far from a real involvement of participants in shaping the overall aims of the biobank. Specifically, methods of the projects have not been explained, and proceedings and communications (written or oral) produced by the ethics Interim Advisory Group were handled as confidential and not to be disseminated among the media and other parties without prior agreement of the biobank’s founders.17 2
CASES OF AUTONOMY BREACHING IN BIOBANK RESEARCH Cases of biobank management causing public distrust are not rare; for instance, the case represented by the Swedish biobank established to detect the metabolic disease phenylketonuria (PKU), which contains blood samples from all children born in Sweden after 1975.18 It was one of the banks used to correlate HPV infection to cervical cancer, and it was used also in 2003 to solve the murder of the Swedish Minister for Foreign Affairs Anna Lindh. In that case, the police made exceptional use of the PKU Swedish biobank, even if legal representatives of children agreed to donate blood only for medical research purposes. In doing so, the consent taken from citizens was violated. The media highlighted the fact, and as a consequence many Swedish citizens decided to withdraw from it—they asked the biobank institutions to destroy their samples and to erase their data. In 2005, the Swedish parliament decided to use the biobank for other purposes than it had been intended for, ignoring the Swedish rules regulating informed consent—in this specific case the Swedish government decided to use the PKU biobank to identify those citizens who died in Thailand because of the 2004 tsunami. In this and other similar cases, the main ethical question posed is: “Would it be justified to hand over samples belonging in biobanks and/or genetic new-borns banks for forensic purposes, even without the consent of the donors or their legal representatives?”19 Another important issue on autonomy breaching regards the proper role of commercial interests within biobank research. Indeed, commercial interests that are pivotal in the success of pharmacogenomics (eg, the development of effective personalised treatments) pose the issue of commercial uses of publicly funded databases, registries and biobanks. To use a public biobank for commercial motives apparently clashes with national regulatory frameworks. However, at least for what concerns the body material—that is, biological samples—the ban on commercialisation is not as strict as it appears at first sight. A recent case of lack of transparency in commercialisation is the one represented by the University Medical Centre Hamburg-Eppendorf, where the chief of the pathology department, who also worked as a consultant for US enterprise Tristar, offered for worldwide sale via the US company, tissue samples originating from the normal diagnostic work of the hospital without the consent and knowledge of patients.20 According to the hospital, law of the Federal Estate of Hamburg provided that the samples were anonymised; the selling and the transfer of diagnostic tissue samples to other countries without the patient’s knowledge and informed consent was legal. There are known cases in which public founded biobanks and databases were commercially exploited, including in Iceland, Estonia, the UK, Latvia, Tonga, Canada, Singapore and Sweden.21 Many European countries’ signatories to documents affirming the noncommercialisation of the human body, regulate this issue, allowing various forms of buying and selling of human biological material.22 The issue of commodification of biological samples highlights the fact that public knowledge of the transfer of human tissue for commercial use is limited, and that within the consent process commercial aspects are very often not explained.
PUBLIC FEARS AND MISTRUST OF SCIENCE Scientific institutions can themselves be implicated in the problem of ‘public mistrust of science’, and currently we prefer to observe a ‘deficit model’ of what the experts regard as D’Abramo F. J Epidemiol Community Health 2015;0:1–4. doi:10.1136/jech-2014-205215
Essay understanding of the public.23 The institutional denial of citizens’ wishes and concerns about scientific research and the Hobbesian imperative for participation in medical research24 might increase the distrust towards science. Indeed, overall, when the scientific enterprise regards public health, public governance and biobanking, the use of informed consent has been conceived in a manner so as to provide an ethical basis especially for fostering public trust in scientific projects, as the public itself has the capacity to undermine scientific programmes.17 Even if participation in biobank research is very often elicited on the base of duties towards society, the benefit to the population is one of the critical issues in determining the justification for the study itself. This means that communicating to individuals and the population the benefits of biobank research, and gathering and implementing their points of view, are focal points to further develop medical projects. Furthermore, policies surrounding research projects often circumvent the indication of who should be responsible in case participants and communities are injured by the research. The choice of opting out from a project can be a way to avoid injury, but damage already caused to the participant(s) should be taken into consideration by institutional bodies in order to provide compensation.25 If autonomy and self-determination are at the core of the consent process, then researchers and scientific institutions are responsible for the (mis)understanding of participants for what is at stake in the research. However if misunderstanding and distrust of biobank research are public issues, then there is no way to address an ethical evaluation focusing solely on the consent process as it was conceived for traditional medical research where risks are mainly for individuals and of a physical nature. On the contrary, finding patterns of genes in a population can influence the entire community—patterns of disease susceptibility influence the manner in which individuals within the community are seen by others and how they see themselves. Also, the benefits derived from biobank research are frequently directed towards future generations. Issues such as “How medical research in itself could change cultural and social understanding of what is an individual?”, or “What means to be an autonomous individual?”, are beyond the core point of the consent process as it was conceived.26 Ethical committees that have been working fairly on protection of individual rights, mainly allowing the use of broad consent (broad consent authorises uses of samples and data for a large, vaguely defined, spectrum of aims), have seldom used their expertise to extend ethical assessments towards the interaction between science and society. Here it is central to go beyond the consent process and the related right of individual autonomy to instead focus on building and improving trustworthiness of scientific institutions. For instance, very few articles in the socioempirical literature on the public perception of biobank research show data from public consultations (ie, deliberative events), where participants were able to take part in the decision-making,14 27 denoting an escape from the need of considering the public’s points of view on biobank research. One of the ways to address the ethical challenges posed by biobank research could consist in conferring a societal relevance to such research, first of all giving a role to consultations within the communities involved. Involvement of specific communities, or groups of citizens within decision-making stages, and more general involvement of ‘active citizenship’, has been proposed as ethical prerequisites21—for example, public deliberations or consultation for patient organisations, patient groups and the public.28 29 Through these kinds of actions where the public can participate and where it can actively shape D’Abramo F. J Epidemiol Community Health 2015;0:1–4. doi:10.1136/jech-2014-205215
the project’s aims and processes, all the parties involved could discuss the project’s values and related implications so that mistrust and resistance towards biobanking might decrease.
TOWARDS A DYNAMIC CONSENT As medical research is heavily based on biobanks and data repositories, with a flux of personal information and biological samples travelling across national borders within research networks and consortia, new ethical norms, practices and standards are worth analysing and implementing, in the area of informed consent. One of the main aims of future research consists of sketching an operational trajectory to go beyond one-off static consent. For instance, dynamic consent is a patient-centred approach with mechanisms of governance engendered through IT solutions to allow participants to engage as much as they choose and to alter their consent choices over time.30 This approach should be contextualised within specific settings and harmonised with the centres part of research networks and consortia.31 Pros of this approach consist of improving public trust, in limiting participants’ withdrawal from research, in facilitating selection of participants to involve in research, in overcoming the perennial issue of consent form length and comprehension. Moreover, dynamic consent can improve transparency and accountability in the research processes: through continuous contact with patients, researchers can gather phonotypical information, reduce research biases and, by using an epigenetic model, the burden of social and environmental effects on health can become lighter.32 Finally, dynamic consent could be sought in a manner involving participants in a discussion on the handling of incidental findings discovered during medical research. The main cons of dynamic consent are its comparably greater management costs, which might not be feasible for less funded groups or may escalate for very large research collaborations. Nevertheless, even if such a dynamic consent fosters active participation of research subjects and patients, the risk of imposing ethical principles derived from theories detached from empirical socioempirical data without considering citizens’ thoughts is always around the corner. Specifically, here the issue can be focused on how to embed social values within scientific values (ie, epistemic norms) in a period in which political, social and cultural factors that created such a segregation have ended.33 The ‘social versus scientific values’ schism pertains to almost all the scientific disciplines and its solution could strengthen science in its function of social governance. Practically speaking, to mitigate the risk of overlooking social values, ethical assessments performed through theoretical/empirical methodologies can be of help (surveys and questionnaires to gather socioempirical data),34 especially to indicate normative arguments useful in planning consent processes that could answer what the parties involved in medical projects want to know, and to communicate and shape the project itself. For instance, participants’ preferences about uses of their personal data could be elicited and incorporated as meta-data within those data sets that travel among laboratories. Such actions that can be thought out and prepared by interdisciplinary teams involving researchers, clinicians, ethical committee members, patients, financing bodies and insurance providers, and can be a viable way to inform experts about public perceptions of medical research.23 Contributors This article was written by FDA after receiving ideas from and having helpful discussions with Dr Jan Schildmann. The COST Action IS 1303 “Chip Me” is the context through which FDA have been developing trajectories for the dynamic consent approach. 3
Essay Competing interests None.
16
Patient consent Obtained. Provenance and peer review Commissioned; externally peer reviewed.
REFERENCES 1
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Hilgartner S. Making maps and making social order. Governing American genome centers, 1988–93. In: Gaudilliere JP, Rheinberger HJ, eds. From molecular genetics to genomics: the mapping cultures of twenty-century genetics. London and New York: Routledge, 2004:113–28. Nationaler Ethikrat. Human biobanks for research. Berlin: The German National Ethics Council, 2010. Andorno R. The right not to know: an autonomy based approach. J Med Ethics 2004;30:435–9; discussion 9–40. Parsonnet J, Friedman GD, Vandersteen DP, et al. Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med 1991;325:1127–31. Dillner J, Lenner P, Lehtinen M, et al. A population-based seroepidemiological study of cervical cancer. Cancer Res 1994;54:134–41. Mauron A. Biobanks, genomic and research. A nightmare for public policy makers? In: Elger B, Biller-Andorno N, Mauron A, et al., eds. Ethical issues in governing biobanks global perspectives. Hampshire, UK: Ashgate, 2008:1–9. Hoeyer K. Ambiguous gifts. Public anxiety, informed consent and biobanks. In: Tutton R, Corrigan O, eds. Genetic databases socio-ethical issues in the collection and use of DNA. London: Taylor & Francis, 2004:97–116. D’Abramo F, Vollmann J, Schildmann J. Research participants' perception and views on consent for biobank research: A review of socio-empirical data and critical appraisal in light of the ethical debate. Under review 2015. Estey A, Wilkin G, Dossetor J. Are research subjects able to retain the information they are given during the consent process? Health Law Rev 1994;3:37–41. Cassileth BR, Zupkis RV, Sutton-Smith K, et al. Informed consent—why are its goals imperfectly realized? N Engl J Med 1980;302:896–900. Caenazzo L, Tozzo P, Pegoraro R. Biobanking research on oncological residual material: a framework between the rights of the individual and the interest of society. BMC Med Ethics 2013;14:17. Gaskell G, Gottweis H, Starkbaum J, et al. Publics and biobanks: Pan-European diversity and the challenge of responsible innovation. Eur J Hum Genet 2013;21:14–20. Hobbs A, Starkbaum J, Gottweis U, et al. The privacy-reciprocity connection in biobanking: comparing German with UK strategies. Public Health Genomics 2012;15:272–84. O’Doherty KC, Hawkins AK, Burgess MM. Involving citizens in the ethics of biobank research: informing institutional policy through structured public deliberation. Soc Sci Med 2012;75:1604–11. Oliver JM, Slashinski MJ, Wang T, et al. Balancing the risks and benefits of genomic data sharing: genome research participants’ perspectives. Public Health Genomics 2012;15:106–14.
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Mancini J, Pellegrini I, Viret F, et al. Consent for biobanking: assessing the understanding and views of cancer patients. J Natl Cancer Inst 2011;103: 154–7. Corrigan O, Petersen A. UK biobank. Bioethics as a technology of governance. In: Gottweis H, Petersen A, eds. Biobanks governance in comparative perspectives. UK: Routledge, 2008:143–58. Gottweis H. Biobanks in action. New strategies in the governance of life. In: Gottweis H, Petersen A, eds. Biobanks governance in comparative perspectives. Oxford, UK: Routledge, 2008:22–38. Tamburrini C. What’s wrong with forensic uses of biobanks? The public, the patient and the regulation. In: Lenk C, Sandor J, Gordijn B, eds. Biboank and tissue research. Dordrecht: Springer, 2011:127–42. Lenk C, Beier K. Is the commercialisation of human tissue and body material forbidden in the countries of the European Union? J Med Ethics 2011;38: 342–6. Corrigan O, Tutton R. Genetic databases: socio-ethical issues in the collection and use of DNA. Routledge, 2004. Petrini C. Between altruism and commercialisation: some ethical aspects of blood donation. Ann Ist Super Sanita 2013;49:412–16. Wynne B. Public engagement as a means of restoring public trust in science —hitting the notes, but missing the music? Community Genet 2006;9:211–20. Hofmann B. Broadening consent—and diluting ethics? J Med Ethics 2009;35:125–9. Prainsack B, Buyx A. A solidarity-based approach to the governance of research biobanks. Med Law Rev 2013;21:71–91. Brekke AO, Thorvald S. Population biobanks: the ethical gravity of informed consent. BioSocieties 2006;1:385–98. Hawkins AK, O’Doherty K. Biobank governance: a lesson in trust. New Genet Soc 2010;29:311–27. Dickert N, Sugarman J. Ethical goals of community consultation in research. Am J Public Health 2005;95:1123–7. Ganguli-Mitra A. Collective consent. In: Elger PB, Biller-Andorno N, Mauron A, et al, eds. Ethical issues in governing biobanks: global perspectives. Ashgate Pub. Limited, 2013:121–30. Terry SF, Shelton R, Biggers G, et al. The haystack is made of needles. Genet Test Mol Biomarkers 2013;17:175–7. Kaye J, Whitley EA, Lund D, et al. Dynamic consent: a patient interface for twenty-first century research networks. Eur J Hum Genet 2015;23:141–6. Loi M, Del Savio L, Stupka E. Social epigenetics and equality of opportunity. Public Health Ethics 2013;6:142–53. Douglas H. Science, policy, and the value-free ideal. University of Pittsburgh Press, 2009. Mertz M, Inthorn J, Renz G, et al. Research across the disciplines: a road map for quality criteria in empirical ethics research. BMC Med Ethics 2014;15:17.
D’Abramo F. J Epidemiol Community Health 2015;0:1–4. doi:10.1136/jech-2014-205215
Essay
Biobank research, informed consent and society. Towards a new alliance? Flavio D’Abramo Correspondence to Flavio D’Abramo, Charité Comprehensive Cancer Center, Charitéplatz 1, 10117, Berlin, Germany; fl[email protected] Received 7 November 2014 Revised 17 January 2015 Accepted 19 January 2015
To cite: D’Abramo F. J Epidemiol Community Health Published Online First: [please include Day Month Year] doi:10.1136/jech2014-205215
ABSTRACT With the rise of -omics disciplines and biobank research, personal data and biosamples crossing national borders pose new ethical questions. In this article, informed consent, as originally conceived, is shown as not being sufficient to address aims of research and interests of patients any more. Therefore the author has, after having scrutinised issues in biobanking, sketched a model of dynamic consent and a manner of scrutinising ethical issues through empirical data. During the past decades a revolution has taken place in science: productive methods and techniques from the industry have been transferred between medical and biological laboratories around the world. Omics disciplines such as genomics are possible thanks to high-throughput standards. The Human Genome Project, completed in 2001, was established on the new characteristics of biological laboratories being able to realise economies of scale. From the moment of its completion, genome researchers have been occupied with finding ways to analyse massive amounts of DNA in a faster, cheaper, easier and, at the same time, cost-reducing way, to expand productive capacities and to extract more information from the same amount of work.1 Nowadays, with technologies such as Genome Wide Association Studies, laboratories are consociated within consortia in processing huge amounts of genomic data to describe the common patterns of human genetic variation. The main goal of this enterprise consists in finding genes (eg, single nucleotide polymorphisms) or molecular characteristics associated with human diseases, related susceptibilities and response to pharmaceuticals. Human biological samples such as those made of blood, tissue, saliva, umbilical cord, placenta, etc, which are at the base of processes of data extraction, are collected in biobanks. These biorepositories, created for various reasons—for instance, pathology collections, repositories for specific diseases as cancer registries and population databases created to permit longitudinal studies of any disease or condition—are at the base of genomics and personalised medicine. To make sense of genetic and genomic data it is necessary to couple them with phenotypic, lifestyle and social information—for example, healthcare data such as disease histories, treatments received; lifestyle information such as nutrition, exercise, wealth, family background, genealogy and other kinds of identifying data. As has often been pointed out, a challenge to carrying out biobank research and taking informed consent is disclosing, to prospective participants,
research goals, risks and benefits. Informed consent, which was thought of as a tool to disclose information to research participants in order to allow them to take an autonomous decision, challenges biobank research as relevant information is not known or not clearly stated at the time of eliciting consent. That means information needed to fulfil informed consent procedures in biobank research is difficult to give. When biobank samples and related data are used to develop genomic research (or other kinds of projects based on -omics technologies), participants could be harmed by unscrupulous usage of their personal data. This informational risk is the main reason underlying the actual ethical debate. Among the risks, we can include genetic discrimination and stigmatisation. For instance, knowledge of a person’s genetic makeup can be used to justify unequal treatment— for example, a candidate for a job may be excluded on the grounds of her genetic disposition to a future disease or a person wishing to buy health insurance could be refused on genetic grounds.2 Moreover, those who undergo genomic research could be harmed by disclosure of information on their health status that they might not wish to know. This compulsory or forced provision of health information has been justified through arguments supporting the next generation’s well-being, for instance, to predict inherited disease susceptibility. Nevertheless, even if disclosure of genetic information could be useful in some contexts, the right not to know has been defended as a legitimate act to protect patients’ and individuals’ autonomy and psychological status.3 On the other hand, before the introduction of -omics technologies, important beneficial public health discoveries were carried out through biobank research such as the association between helicobacter pylori infection and the risk of gastric carcinoma4 or the causal relation between human papilloma virus (HPV) and cervical cancer.5 Therefore, medical research based on -omics techniques can easily exacerbate the tension between individual rights and bioethical principles versus a population outlook and objectives of biobank research.6 In 2004, Klaus Hoeyer held that informed consent in relation to tissue donation was not yet an established routine.7 As shown by the empirical literature,8 during the past few years an increasing number of socioempirical studies on public and patients’ perception of biobank research has been carried out, underlying the need of taking on the arduous task of informing research participants to obtain their consent. Despite informed consent in biobank research being a fairly novel issue, inability to recall risks spelled out during the consent
D’Abramo F. J Epidemiol Community Health 2015;0:1–4. doi:10.1136/jech-2014-205215
Copyright Article author (or their employer) 2015. Produced by BMJ Publishing Group Ltd under licence.
1
Essay process is a leitmotif—for example, within clinical trials.9 Being a dynamic process, risk understanding can depend on the recipient or on the medium utilised by groups or institutions—wellknown problems are a formulation of inherent risks. For instance, it is not easy to find a consent model stating risks derived from commercialisation of individual biosamples or data. Certainly, difficulties of understanding depend on the state of mind of the recipient. Indeed, when research participants experience a state of illness, this could determine the decision-making process of donation—as the illness progresses, patients understand less,10 as could happen in oncological cases where different patient symptoms such as pain, anxiety, fear and depression, linked to the type of cancer and the stage, will likely influence the consent process and its understanding.11 Despite the problems attached to the consent process tout court, there are other characteristics of informed consent utilised in biobanking, and not linked to recipients, which can explain both (1) the empirical evidence highlighting distrust of science, biobanks and industry,12 13 and patients’, and the public’s, concerns for personal and societal risks,14 15 and (2) the empirical evidence showing participants’ problems of comprehension.15 16
SOCIETAL RISKS ON THE INDIVIDUALS’ SHOULDERS The consent process in biobanking is of a unique nature, certainly different from that in other kinds of medical research enterprises. First of all, risks and benefits in biobanking are asymmetrically distributed: risks deriving from biobank research are of an individual and societal nature—discrimination can be produced at both, individual and group levels— whereas, most of the time, benefits are only for the society (biobank research seldom produces direct returns for participants, or benefits are produced only after several years). This risks/benefits asymmetry of biobank research connotes the consent process in a very unique manner. Indeed, the consent process, which is a process to defend the individualistic principle of autonomy, when applied to biobanking, refers necessarily to an evaluation of societal risks and benefits at the individual level. Is it right to give societal responsibilities to persons who remain seen solely as individuals? In this framework where, by requiring consent, individuals are loaded with societal responsibilities, a commune reaction could be an escape: what you do not know cannot be an object of your responsibility. There, an explanation for the lack of recall of information about the biobank projects and for the lack of interest in reading the consent sheets might be interpreted as a way of refusing an imposition of responsibility.7 In this respect, what has been named the ‘deficit model’ for the public understanding of science (roughly speaking this model holds that the public does not understand science as it is ignorant and anxious, and considered in need of information presented in a better or clearer manner) is useless in addressing the issue of consent in biobanking as well as detrimental as it avoids considering ethical themes other than autonomy of individuals. For instance, in the case of a UK biobank, the ‘openness’ and ‘transparency’ invoked for the project management was far from a real involvement of participants in shaping the overall aims of the biobank. Specifically, methods of the projects have not been explained, and proceedings and communications (written or oral) produced by the ethics Interim Advisory Group were handled as confidential and not to be disseminated among the media and other parties without prior agreement of the biobank’s founders.17 2
CASES OF AUTONOMY BREACHING IN BIOBANK RESEARCH Cases of biobank management causing public distrust are not rare; for instance, the case represented by the Swedish biobank established to detect the metabolic disease phenylketonuria (PKU), which contains blood samples from all children born in Sweden after 1975.18 It was one of the banks used to correlate HPV infection to cervical cancer, and it was used also in 2003 to solve the murder of the Swedish Minister for Foreign Affairs Anna Lindh. In that case, the police made exceptional use of the PKU Swedish biobank, even if legal representatives of children agreed to donate blood only for medical research purposes. In doing so, the consent taken from citizens was violated. The media highlighted the fact, and as a consequence many Swedish citizens decided to withdraw from it—they asked the biobank institutions to destroy their samples and to erase their data. In 2005, the Swedish parliament decided to use the biobank for other purposes than it had been intended for, ignoring the Swedish rules regulating informed consent—in this specific case the Swedish government decided to use the PKU biobank to identify those citizens who died in Thailand because of the 2004 tsunami. In this and other similar cases, the main ethical question posed is: “Would it be justified to hand over samples belonging in biobanks and/or genetic new-borns banks for forensic purposes, even without the consent of the donors or their legal representatives?”19 Another important issue on autonomy breaching regards the proper role of commercial interests within biobank research. Indeed, commercial interests that are pivotal in the success of pharmacogenomics (eg, the development of effective personalised treatments) pose the issue of commercial uses of publicly funded databases, registries and biobanks. To use a public biobank for commercial motives apparently clashes with national regulatory frameworks. However, at least for what concerns the body material—that is, biological samples—the ban on commercialisation is not as strict as it appears at first sight. A recent case of lack of transparency in commercialisation is the one represented by the University Medical Centre Hamburg-Eppendorf, where the chief of the pathology department, who also worked as a consultant for US enterprise Tristar, offered for worldwide sale via the US company, tissue samples originating from the normal diagnostic work of the hospital without the consent and knowledge of patients.20 According to the hospital, law of the Federal Estate of Hamburg provided that the samples were anonymised; the selling and the transfer of diagnostic tissue samples to other countries without the patient’s knowledge and informed consent was legal. There are known cases in which public founded biobanks and databases were commercially exploited, including in Iceland, Estonia, the UK, Latvia, Tonga, Canada, Singapore and Sweden.21 Many European countries’ signatories to documents affirming the noncommercialisation of the human body, regulate this issue, allowing various forms of buying and selling of human biological material.22 The issue of commodification of biological samples highlights the fact that public knowledge of the transfer of human tissue for commercial use is limited, and that within the consent process commercial aspects are very often not explained.
PUBLIC FEARS AND MISTRUST OF SCIENCE Scientific institutions can themselves be implicated in the problem of ‘public mistrust of science’, and currently we prefer to observe a ‘deficit model’ of what the experts regard as D’Abramo F. J Epidemiol Community Health 2015;0:1–4. doi:10.1136/jech-2014-205215
Essay understanding of the public.23 The institutional denial of citizens’ wishes and concerns about scientific research and the Hobbesian imperative for participation in medical research24 might increase the distrust towards science. Indeed, overall, when the scientific enterprise regards public health, public governance and biobanking, the use of informed consent has been conceived in a manner so as to provide an ethical basis especially for fostering public trust in scientific projects, as the public itself has the capacity to undermine scientific programmes.17 Even if participation in biobank research is very often elicited on the base of duties towards society, the benefit to the population is one of the critical issues in determining the justification for the study itself. This means that communicating to individuals and the population the benefits of biobank research, and gathering and implementing their points of view, are focal points to further develop medical projects. Furthermore, policies surrounding research projects often circumvent the indication of who should be responsible in case participants and communities are injured by the research. The choice of opting out from a project can be a way to avoid injury, but damage already caused to the participant(s) should be taken into consideration by institutional bodies in order to provide compensation.25 If autonomy and self-determination are at the core of the consent process, then researchers and scientific institutions are responsible for the (mis)understanding of participants for what is at stake in the research. However if misunderstanding and distrust of biobank research are public issues, then there is no way to address an ethical evaluation focusing solely on the consent process as it was conceived for traditional medical research where risks are mainly for individuals and of a physical nature. On the contrary, finding patterns of genes in a population can influence the entire community—patterns of disease susceptibility influence the manner in which individuals within the community are seen by others and how they see themselves. Also, the benefits derived from biobank research are frequently directed towards future generations. Issues such as “How medical research in itself could change cultural and social understanding of what is an individual?”, or “What means to be an autonomous individual?”, are beyond the core point of the consent process as it was conceived.26 Ethical committees that have been working fairly on protection of individual rights, mainly allowing the use of broad consent (broad consent authorises uses of samples and data for a large, vaguely defined, spectrum of aims), have seldom used their expertise to extend ethical assessments towards the interaction between science and society. Here it is central to go beyond the consent process and the related right of individual autonomy to instead focus on building and improving trustworthiness of scientific institutions. For instance, very few articles in the socioempirical literature on the public perception of biobank research show data from public consultations (ie, deliberative events), where participants were able to take part in the decision-making,14 27 denoting an escape from the need of considering the public’s points of view on biobank research. One of the ways to address the ethical challenges posed by biobank research could consist in conferring a societal relevance to such research, first of all giving a role to consultations within the communities involved. Involvement of specific communities, or groups of citizens within decision-making stages, and more general involvement of ‘active citizenship’, has been proposed as ethical prerequisites21—for example, public deliberations or consultation for patient organisations, patient groups and the public.28 29 Through these kinds of actions where the public can participate and where it can actively shape D’Abramo F. J Epidemiol Community Health 2015;0:1–4. doi:10.1136/jech-2014-205215
the project’s aims and processes, all the parties involved could discuss the project’s values and related implications so that mistrust and resistance towards biobanking might decrease.
TOWARDS A DYNAMIC CONSENT As medical research is heavily based on biobanks and data repositories, with a flux of personal information and biological samples travelling across national borders within research networks and consortia, new ethical norms, practices and standards are worth analysing and implementing, in the area of informed consent. One of the main aims of future research consists of sketching an operational trajectory to go beyond one-off static consent. For instance, dynamic consent is a patient-centred approach with mechanisms of governance engendered through IT solutions to allow participants to engage as much as they choose and to alter their consent choices over time.30 This approach should be contextualised within specific settings and harmonised with the centres part of research networks and consortia.31 Pros of this approach consist of improving public trust, in limiting participants’ withdrawal from research, in facilitating selection of participants to involve in research, in overcoming the perennial issue of consent form length and comprehension. Moreover, dynamic consent can improve transparency and accountability in the research processes: through continuous contact with patients, researchers can gather phonotypical information, reduce research biases and, by using an epigenetic model, the burden of social and environmental effects on health can become lighter.32 Finally, dynamic consent could be sought in a manner involving participants in a discussion on the handling of incidental findings discovered during medical research. The main cons of dynamic consent are its comparably greater management costs, which might not be feasible for less funded groups or may escalate for very large research collaborations. Nevertheless, even if such a dynamic consent fosters active participation of research subjects and patients, the risk of imposing ethical principles derived from theories detached from empirical socioempirical data without considering citizens’ thoughts is always around the corner. Specifically, here the issue can be focused on how to embed social values within scientific values (ie, epistemic norms) in a period in which political, social and cultural factors that created such a segregation have ended.33 The ‘social versus scientific values’ schism pertains to almost all the scientific disciplines and its solution could strengthen science in its function of social governance. Practically speaking, to mitigate the risk of overlooking social values, ethical assessments performed through theoretical/empirical methodologies can be of help (surveys and questionnaires to gather socioempirical data),34 especially to indicate normative arguments useful in planning consent processes that could answer what the parties involved in medical projects want to know, and to communicate and shape the project itself. For instance, participants’ preferences about uses of their personal data could be elicited and incorporated as meta-data within those data sets that travel among laboratories. Such actions that can be thought out and prepared by interdisciplinary teams involving researchers, clinicians, ethical committee members, patients, financing bodies and insurance providers, and can be a viable way to inform experts about public perceptions of medical research.23 Contributors This article was written by FDA after receiving ideas from and having helpful discussions with Dr Jan Schildmann. The COST Action IS 1303 “Chip Me” is the context through which FDA have been developing trajectories for the dynamic consent approach. 3
Essay Competing interests None.
16
Patient consent Obtained. Provenance and peer review Commissioned; externally peer reviewed.
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