Setting the Ethical Groundwork for a Knowledge Economy

Policymakers have been especially conscious of Singapore’s vulnerability as a tiny nation-state. The trauma of expulsion from the federation of Malaysia in the short space of about two years after achieving independence from colonial rule may have further etched this vulnerability into the national psyche. In an interview with a panel of journalists from the principal English-language newspaper in Singapore, Lee Kuan Yew (the architect of modern Singapore) was asked if the nation-state should be “always living in fear of a catastrophe.” Mr. Lee’s response is indicative of the mind-set of key policymakers:

Through what has been described as a developmental state model, the state-led industrialization of Singapore between the late 1960s and the 1990s capitalized on the nation-state’s locational and infrastructural strengths to attract transnational corporations. This strategy has been relatively successful in enabling Singapore’s capabilities in back-end manufacturing, consumer electronics, and a variety of financial and distributional services. The economic returns that this strategy generated have in turn been a crucial source of legitimacy for the state. The rule of law has often been regarded as intrinsic to this developmental strategy. The assurance that the state will stick to the law has been considered to be critical in securing stable relations with transnational corporations and ensuring continued foreign direct investment. By this formulation, the rule of law amounts in effect to the security of persons, property rights, and contract enforcement. Such a conception has attributed to the common law a spontaneous (rather than engineered) origin and a prioritization of the rule of law ahead of development. Reflecting on the development experiences of East Asian nations, Francis Fukuyama takes a different view in arguing that the rule of law is but a distinct dimension of development, and not a precondition.^{Footnote 2} Rather, the state must intentionally and systematically adopt the rule of law. This is perhaps most evident in his argument that the common law was intimately associated with the rise of the early English state and dependent on state power for its eventual dominance.^{Footnote 3}

Bioethics, particularly in its institutional varieties (as public policy, governance framework, and academic discipline), would not have had so prominent a character in Singapore without strong endorsement and support from the state. To understand biotechnology in Asia, Aihwa Ong emphasizes the need to take the role of the state seriously.^{Footnote 4} Although pharmaceutical companies and global health agencies have tremendous influence over biotechnology, nationalist states have increasingly shaped the flow of human tissues and biotech products. Consequently, important scientific breakthroughs in the field of biotechnology and biomedicine have occurred within political environments with robust sovereignty and paternalist rule. East Asian states are drawing on bioethics and biotechnologies, not only to achieve economic ends but also to shape national identity and gain prestige. Bioethics has been employed in the production of shared corporeal needs and vulnerabilities, to trigger a sense of belonging, and to create a blend of the rationalities of market and science with the “irrationalities” of feeling and identity.^{Footnote 5}

Unlike the industrial development of the past, investment in biotechnology—as Joseph Wong observed—involves “different kinds of bets,” in view of uncertainties as to technological viability, economic (and, particularly, commercial) value, and temporal range.^{Footnote 6} Singapore recognizes its own vulnerabilities, particularly its small economy and lack of experience with the development and commercialization of technological innovation.^{Footnote 7} Amid these developments, the state has not retreated into obscurity but has adapted its policy strategies to address and manage the uncertainties in the life sciences. This is a development that is inconsistent with neoliberalism, which puts forward the view that it is in the public interest to reduce government intervention and allow the operation of the market to benefit as many “consumers” as possible.^{Footnote 8} A neoliberal agenda directed at creating a “market society” could lead to a failure of public life^{Footnote 9} and is not necessarily consistent with the ideals of democratic society.^{Footnote 10} Neoliberal thinking has been recognized in the policies of Singapore in creating a knowledge economy.^{Footnote 11} Yet a critical feature has been the ability of the state to channel private initiatives into areas of state priority, and to structure and use state power for economic development.^{Footnote 12}

Another important observation advanced by Wong is the emergence of a “multiple stakeholder state,” responsible for promoting research and development, on the one hand, but also for the protection of human subjects that are involved in research, on the other.^{Footnote 13} As these competing goals immediately make clear, regulatory policies are contested among different actors, including within the government by different ministries. In moving a policy initiative forward, it is often necessary for the state to function as a mediator and broker by designating a mechanism toward this end. Quite aside from the presence of multiple stakeholders, the state itself has multiple roles. It functions as both a market and a premarket regulatory gatekeeper, especially because it shapes market access for biotechnological innovations. The state is also the monopsonistic purchaser of care, thereby affecting in some way the price of all healthcare products and services. In addition, it acts as entrepreneur in the provision of a technology infrastructure,^{Footnote 14} when engaging in activities such as establishing joint research ventures and research parks. On a number of key life sciences policies, the BAC served as one such mechanism for mediation, with the Cabinet as the ultimate decisionmaker.^{Footnote 15} Bioethics, at a policy level, has emerged as a means by which the state could perform its very different functions for the purposes of balancing different needs and reconciling competing commitments. The inherent uncertainties of regulatory policies relating to the life sciences, and the challenges of asymmetric information, limit the state’s ability to impose a single viewpoint or regulatory stance. Since 2000, the BAC has advanced the interests of the state in reconciling competing interests, values, and perspectives arising from biomedical research, and in establishing a framework for ethical governance more generally.^{Footnote 16}

Broadening the Governance Framework for Biomedical Research

Prior to 2000, ethical governance of biomedical research had been mainly confined to clinical trials. For other types of biomedical research, an ad hoc institutional review board (IRB) or similar body might be established within academic and healthcare institutions on a when-necessary basis. Although the systematization of an ethics governance framework was on the agenda of the BAC from the time of its inception, an incident in 2003 required the prioritization of this initiative. This matter concerned Dr. Simon Shorvon, who was appointed as director of the National Neuroscience Institute in 2000, having been recruited from the UK, where he already had a distinguished career as a researcher.^{Footnote 17} The essence of the case against Dr. Shorvon was that he failed to obtain informed consent from several of the subjects of his research, inappropriately obtained the names of potential participants (through bypassing their own doctors and going to pharmacy records), and failed to inform the relevant ethics committees of some of the crucial details of his research. Of particular significance here was a test that involved instructing patients with Parkinson’s disease to omit their medication the evening before coming to the clinic (on-off Levodopa testing) and then videotaping them to observe changes in their movements and coordination. It emerged in the disciplinary hearing that neither the patients nor the ethics committees were properly informed of these aspects of the research, and that patients were under the false impression that this was part of treatment. Following complaints from some patients and their doctors, a series of enquiries was launched, culminating in a hearing before the Disciplinary Committee of the Singapore Medical Council (SMC), which found him guilty of thirty charges of professional misconduct. Dr. Shorvon did not contest these charges, and he chose not to appear at the hearing, having requested deregistration from the SMC’s register. He returned to the UK, where he remains registered with the General Medical Council (GMC). The GMC considered whether it should also institute a case against Dr. Shorvon but decided not to proceed. A judicial appeal by the SMC against this decision of the GMC was dismissed by an English court.

For the BAC, the incident highlighted the pressure clinician researchers faced to recruit patients and produce research results as a serious ethical challenge. It also illustrated the difficulties of having to promote innovation, on the one hand, and to safeguard the welfare of patients and research subjects, on the other. Following the approach in major scientific jurisdictions, an effective regulatory regime was considered to be critical in striking a publicly acceptable (and ethically defensible) balance among the different stakeholders. Continuing state interest is considered to be important for other social and political objectives not immediately linked to science; state presence also signaled public interest, and that the research was taken up for the common good.^{Footnote 18}

The governance framework that was established has a number of features. First, it created a common normative platform so that all human biomedical research projects in Singapore, including research involving human tissue or medical information, are to be subject to ethics review by IRBs. This was done by building on the existing system of regulations for pharmaceutical trials and human biomedical research conducted by hospitals, private clinics, and other healthcare establishments under supervision of the MOH. The BAC also specified the constitution, accreditation, and operation of IRBs, as well as their roles and responsibilities, in addition to those applicable to research institutions and individual researchers. Here, high standards of ethical governance are regarded as vital to the progress of biomedical sciences in Singapore. Although the governance framework proposed by the BAC does not have any direct regulatory authority, it is in effect implemented by the state through the MOH and by the Agency for Science, Technology and Research (A*STAR), a principal public funder of biomedical research in Singapore. Should an ethical infraction occur, either or both of these government agencies could require initiation of a number of regulatory actions, including the commencement of disciplinary action and/or the cessation of research funding. In this way, the state retains for itself ultimate discretion as to the degree of regulatory control that is appropriate.

Second, a measure of risk is implicit in the framework, so that ultimate oversight by the state (either through the MOH, the A*STAR, and/or other regulatory bodies) is increased proportionately with the risk that the research presents. The notion of risk clearly encompasses potential harm to the physical and mental well-being of a research participant. For certain types of research, such as those relating to the human embryo, risk has been conceptualized to include risk of harm to society. There are at least two categories of research that are regarded as warranting significant regulatory control. Clinical trials continue to require specific regulatory approval. With the systematization of the ethics review process, ethical clearance is now an additional level of safeguard. Researchers must obtain ethical clearance from an IRB. Regulatory approval will also have to be obtained from the Health Sciences Authority before a clinical trial may commence. In contrast, embryonic stem cell research is considered to pose a more abstract, but no less significant, form of potential harm. This category of research will similarly require both regulatory and ethics approval. Interestingly, harm to science as a knowledge discipline, or concerns that are taken to relate to research integrity, are not regarded as immediate concerns of the state.^{Footnote 19} Rather, these are felt to be more appropriately addressed at an institutional level. Consequently, key research institutions in Singapore have policies on research integrity. They incorporate to varying degrees the key principles set out in the Singapore Statement on Research Integrity—honesty, accountability, professional courtesy, and fairness, and good stewardship of research on behalf of others—while also defining irresponsible research conduct as essentially falsification, fabrication, and plagiarism.^{Footnote 20}

Third, the regulatory reach is incremental in terms of depth and scope, and it is targeted. It is most extensive and comprehensive for research that poses a direct threat of harm to human participants and to particular moral viewpoints. In contrast, there is at best limited regulatory presence on matters of scientific integrity, including concerns over conflicts of interest that do not pose direct or immediate risk of harm to human participants. On the former, existing provisions on ethics governance have either been elaborated on or otherwise supplemented. In 2007, the MOH issued supplementary guidelines on the day-to-day workings of an IRB. These include guidelines on the composition of an IRB, a more elaborate discussion on the informed consent process, meeting requirements, and requirements relating to documentation.^{Footnote 21} In addition, it emphasized the “fundamental” ethical principles as respect for persons (encompassing autonomy), beneficence, and justice, as its primary focus was on research involving patients, rather than healthy individuals.

Growing Concern over Conflicts of Interest

Although an ethics governance framework for biomedical research is now in place, the work of the BAC is not over. In recent years, there has been renewed concern over COIs as industrial collaboration and translational medicine (which entails the commercialization of research) are being emphasized.^{Footnote 22} At least from a regulatory standpoint, the extent to which scientific advance can be reconciled with the goal of maximizing economic returns is unclear. For instance, is there any research for which industrial collaboration should be ruled out? Or is there any research for which commercialization should never be allowed? Over the years, Singapore has enjoyed strong linkages with multinational firms, including big pharmaceutical companies. Whereas the ethical validity of this relationship has been taken for granted, it is difficult to ignore ethical concerns associated with certain practices in the industry.^{Footnote 23} The nation-state’s economic interest in the subject further accentuates COI concerns.

In Singapore, the BAC defines COIs as circumstances that adversely affect impartiality, objectivity, and independence, and it encapsulates both actual and potential conflicts.^{Footnote 24} The independence and ethical integrity of IRBs are identified as fundamental underlying principles, and institutional hosts of IRBs must take reasonable steps to avoid and minimize conflicts. A recommendation put forward by the BAC is for an IRB to prepare a special report on all reviews of research programs in which there is an actual, potential, or apparent COI, for submission directly to the board of directors of its host institution.^{Footnote 25} On the part of researchers, the BAC indicates that it is important for researchers to take special care to avoid any form of COI, whether actual, potential, or merely an appearance of conflict as such. To ensure objectivity in the review process, researchers should not be involved in, or give the appearance of being involved in, the ethics review and approval process of any project in which they are involved.^{Footnote 26} In addition, similar conflicts could arise where a researcher is also the administrative custodian of patients’ medical information, or an attending physician. Transparency through disclosure as a means of addressing conflict situations has been emphasized by the BAC. It says that researchers have a duty to make a declaration of any conflict, to give full disclosure of the facts giving rise to such conflict, and to detail the steps proposed or taken to minimize or avoid the appearance of actual or potential COIs. On financial COIs, the BAC states that potential research subjects may need to be informed of any financial arrangements offered by corporate sponsors to researchers or their institutions (or both). This disclosure is understood as facilitating understanding and advancing the ethical goal of informed consent.

Relying on individual integrity alone is not likely to hold out any great hope of change. Regulatory guidance is only as effective as its commitment to monitoring and pinpointing responsibility for compliance. Even with guidance that identifies for clinician-researchers certain norms of responsible behavior, such as making financial disclosures and receiving only due compensation, there is evidence in social science research that individuals are not always conscious of their motives and often fail to act in ways they believe they would.^{Footnote 27} Expectations of reciprocity operate in powerful and subtle ways that have negative consequences for clinical care.^{Footnote 28} Disclosure may sanitize COIs and lead clinicians to pretend they have disappeared. Otherwise, the effort to avoid disclosure requirements may lead clinicians to be “creative” in their interpretation of what is or is not a COI.^{Footnote 29}

Achieving an Ethically Sound Balance

It has been argued that academic medical centers, rather than individual clinicians, have a role in leading efforts to address COIs in the current climate of undue influence on medical objectivity.^{Footnote 30} This is because the profession and industry look to academic medical centers for influential and independent advice, because independent research into the impact of new drugs and devices on population health is borne mainly by them, and because they have primary responsibility for training future clinicians in the habits of scientific objectivity and integrity.^{Footnote 31} To a large extent, this rationale appears to underlie the current ethical governance framework on COIs in Singapore. However, many questions that arise cannot be adequately answered at an institutional level. For instance, sustaining an ethical understanding of the relationship between researchers and research participants, as well as the scientific research enterprise, is an ongoing process that must necessarily include stakeholders aside from academic medical centers. In addition, even if investment in research is intended to benefit the public, broader discussion is necessary on what “benefits” mean (and to whom), and on the extent to which market-driven research prioritization (given the emphasis on industrial collaboration) is ethically appropriate.^{Footnote 32}

To be sure, broader measures beyond installing regulatory oversight have been taken up by the state. One such measure relates to capacity development in biomedical ethics. Under a grant from the National Research Foundation, the Centre for Biomedical Ethics (CBmE) in the Yong Loo Lin School of Medicine in the National University of Singapore conducts workshops and seminars for biomedical researchers, IRB members, and clinicians on a number of topics.^{Footnote 33} At the A*STAR, participation in such training workshops conducted by the CBmE has been made mandatory for researchers. The Capacity Building Programme has also engaged in broader public education efforts, through symposia, seminars, workshops, and performing arts for secondary and preuniversity students and their teachers. The CBmE has collaborated with the Singapore Science Centre in the use of performing arts to promote awareness of biomedical ethics issues and with the BAC and the Science Centre in establishing a bioethics exhibition.