by Shermian Koh Jin Hui & Dr. Voo Teck Chuan
Centre for Biomedical Ethics, Yong Loo Lin School of Medicine, National University of Singapore
Regulatory regimes for research such as the ‘Common Rule’ (US federal regulations governing research involving human subjects) and the CIOMS Ethical Guidelines for Biomedical Research are currently being revised, in view of shifts and innovation in research activities and ethics, with the goals of enhancing respect for research subjects and improving research efficiency. In line with these developments, and prompted by the growth of human biomedical research and the increasing involvement of healthcare and non-healthcare professionals in Singapore, the Singapore Parliament passed the Human Biomedical Research Act (HBRA) in August 2015. In setting out interrelated regulatory frameworks for conducting human biomedical research and for handling of human tissue, the HBRA aims to advance safeguards for research subjects and tissue donors, and to enhance Singapore’s international standing as a hub of biomedical activities. Strong emphasis on consent and the imposition of sanctions for serious research misconducts illustrates the government’s commitment to the responsible advancement of science.
This paper provides a broad overview of the regulatory regime established under the HBRA, where appropriate comparisons will be made with other research governance regimes and norms.
Human Biomedical Research Framework
HBRA is a complex piece of legislation that will significantly change the way human biomedical research  is conducted in Singapore. It establishes a wide-ranging set of regulations and standards for conduct and oversight of human biomedical research including requirements for appropriate consent of research subjects; requirements for protection of confidentiality; specifications of prohibited research; and penalties for failure to comply commensurate with the nature and seriousness of the offences.
The HBRA also regulates human biomedical research by delineating the interlocking roles and responsibilities of its key entities: research institution (RI), individual researcher and institutional review board (IRB). At the centre of this tripartite relationship is the RI, which is responsible for supervising and controlling human biomedical research conducted by its researchers, and in appointing and supporting at least one IRB of its own. The functions of the IRB are laid down in Section 17 of the HBRA. Generally, the IRB ethically reviews the research proposals of researchers from its RI. The relationship between the three entities is not adversarial. Instead, they form an interlinked system with checks and oversight that reduces the risks of unethical research to research subjects, and institutional risks and personal risks to the RI and its researchers respectively. Nevertheless, the independence of the ethics review process ensures that the IRB, while working with the RI and researchers, provides a strictly fair assessment of proposed research. This cooperative structure ensures self-accountability of the three key players in human biomedical research as regards protecting the safety and welfare of research subjects.
The HBRA imposes a set of standards and requirements (including reports and information provision to the Ministry of Health for the purpose of administering and enforcing the Act) that apply uniformly to all human biomedical research in Singapore, including those conducted in the private sector and by non-clinician researchers. (Prior regulations and guidelines such the Medicines Act and the Medicines (Clinical Trials) Regulations govern clinical trials for pharmaceuticals, while the requirement to comply with “Ethical Guidelines on Research Involving Human Subjects” issued by the National Medical Ethics Committee apply to hospitals and medical personnel.) The expansion of governmental oversight in the governance of research viz. the HBRA is consistent with the proposed change to the scope of the Common Rule to apply to any human subject’s research conducted at a US institution that receives federal funds from a Common Rule agency, regardless of the funding source for the research.
Power to Waive Consent under Certain Conditions
The HBRA also effects research efficiency by calibrating oversight to the level of risk. One of the key responsibilities of the IRB set out in the HBRA is determining waivers of consent. Section 13(2) of the HBRA allows for the IRB to waive the requirement to obtain the appropriate consent of at least one adult parent or guardian for participation of a minor (defined as a person below 21 years old and who has never been married) in the research if:
It is important to note that the Chair of the IRB alone does not have the authority to waiver consent: it is the IRB as a collective body that may make a decision to do so. When the abovementioned requirements are met, appropriate consent is obtained only from the minor.
- there is no more than minimal risk to research subjects;
- rights and welfare of research subjects will not be adversely affected; and
- proposed research may not be practicably carried out unless there is a waiver.
This provision appears to be consistent with the view of the Nuffield Council on Bioethics (an independent bioethics advisory body in the UK) in its report, Children and Clinical Research: Ethical Issues.  It argues that vulnerability is primarily present in situations rather than in individuals. The HBRA reflects a similar philosophy in its provision that minors with sufficient understanding and intelligence should have an active role in deciding on research participation. As the Nuffield Council has observed, a tendency for vulnerability is induced circumstantially; those involved in conducting or reviewing research ought to recognise that even adults with sufficient understanding and intelligence could become vulnerable when placed in an unfamiliar (research) setting. Arguably, this is in line with the HBRA’s attempt to create a safe research environment that minimizes risks to research subjects and upholding their right to informed consent. The HBRA presents a sound research governance framework – one that protects research subjects not from research, but towards safe and ethical research.
Impact of HBRA on international research collaborations
A concern to RIs would be the impact of the HBRA on their collaborations with other RIs to conduct multi-centre research. The Act does not prescribe that the local RI must be the lead RI, and allows the appointment of a common IRB, which may be an IRB appointed by the lead RI or another IRB as agreed by the partner institutions. In comparison, the Common Rule has been proposed to change from permitting to requiring reliance on a single IRB of record (i.e. an IRB that assumes IRB responsibilities for another institution) for multi-centre studies, with some exceptions such as projects involving research conducted at non-US sites.
With respect to the HBRA’s framework for international multi-centre research, if the proposed research has a portion (e.g. recruitment of research subjects) conducted in Singapore, the local RI will assume responsibility for that portion. In addition, its own IRB must review the entire protocol and not just the Singapore portion. It has been clarified by the Minister of State of Health during the second reading of the HBR bill in Parliament that for such research, the local RI’s IRB must be satisfied that “the international protocol complies with the national laws of all the participating institutions as well as internationally-accepted ethical principles”.  This helps ensure that those outside of Singapore who participate in the research, particularly those from a country with less advanced laws and ethical standards than Singapore, receive the same level of protections as the research subjects in Singapore.
Building on Ethical Guidelines in Human Tissue Regulation
Where tissue banking is concerned, the HBRA essentially builds on a system of ethical governance that has been instituted by the government, on the advice and recommendations of its Bioethics Advisory Committee (BAC). Where the conduct of human tissue banking and biomedical research using human tissue in Singapore are concerned, a set of ethical guidelines has been published by the BAC in its report on ‘Human Tissue Research’ in November 2002. The ethical principles embodied in the guidelines include the primacy of the welfare of tissue donors, the need for informed consent and confidentiality, respect for the human body and sensitivity towards the religious and cultural perspectives and traditions of tissue donors.
Under the HBRA, these ethical provisions are now mostly legal requirements applicable to any individual, body of persons (whether corporate or unincorporated) or organisation that carries on or conduct any tissue banking activity. Those are legislatively defined as “a structured and an organised activity involving human tissue for the purposes of facilitating current or future research or for public health or epidemiological purposes or any combination of such purposes including…(a) the collection, storage, procurement or importation of human tissue; [and] (b) the supply, provision or export of human tissue”. The BAC’s firm stance against the commercialisation of the human body (or any part thereof) is enshrined in the HBRA’s prohibition of the sale or supply of any human tissue for valuable consideration, as well as any advertisement to that effect. The ethical requirement of informed consent is also a legal requirement, and is supported by a further rule against compelling or deceiving a person to donate tissue. In addition, operational requirements are necessitated as specific legal duties of a regulated person or entity. These include the submission of a declaration of compliance with prescribed statutory and regulatory requirements, designation of a person who will be held accountable, and the formulation and implementation of appropriate standards, policies and procedures.
Comparison with the Proposed Revised CIOMS Guidelines
One of the key objectives of the HBRA is to ensure that participation by research subjects is voluntary and done so with informed consent. Section 12(1)(j) of the HBRA seems to indicate that there is no specific requirement for biological material to be used only for the primary research since research subjects can indicate if the material will be ‘destroyed, discarded or stored for future biomedical research’. However, the HBRA model of consent seems to depart from the position taken in the New Draft Revisions of the Council for International Organizations of Medical Sciences (CIOMS) . Under Guideline 9 of its consultation document, a renewal of consent is proposed only when there are ‘substantive changes’. In contrast with the HBRA requirements, the New Draft Revisions of CIOMS does not seek actively for the research subject’s consent regarding secondary uses of the biological materials; it is automatically presumed that consent is sufficient when there are not substantive changes. This departure from international recommendations indicates stringency in Singapore’s HBRA. This is in line with increased sanctions in the HBRA as Singapore aims to foster a safer and more ethical research environment.
About the Author
- The HBRA has a two-branch approach to its definition of human biomedical research: (i) an ‘intention’ branch i.e. what the research intends to study (e.g. prevention, prognostication, diagnosis or alleviation of any disease, disorder or injury affecting the human body); and, (ii) a ‘means’ branch i.e. what the research involves (e.g. interventions that produce a temporary or permanent physical, mental or physiological effect on an individual person’s body). See Section 3 and its subsections.
- Nuffield Council on Bioethics, Children and Clinical Research: Ethical Issues, 2015. Available at https://nuffieldbioethics.org/project/children-research/
- Singapore Minister of Health, ‘Human Biomedical Research Bill Second Reading – Closing Speech by Minister of State for Health Dr Lam Pin Min’, 18 August 2015.
- CIOMS Working Group on the Revision of CIOMS 2002 International Ethical Guidelines for Biomedical Research Involving Human Subjects. Available here: https://cioms.ch/index.php/guidelines-test
Shermian Koh is a Research Assistant at the Centre for Biomedical Ethics of Yong Loo Lin School of Medicine, National University of Singapore. She studied law at the University of Manchester (England) and has graduated recently in 2015. Currently, she is undergoing traineeship for her admission as an advocate and solicitor of the Supreme Court of Singapore. Shermian has an interest in biomedical law and ethics and has co-authored an advisory report to the World Health Organization and also for an article regarding the ethics of live organ donation in Transplantation Proceedings.
Dr. Voo Teck Chuan is Assistant Professor at the National University of Singapore, Centre for Biomedical Ethics, Yong Loo Lin School of Medicine. He has served for the World Health Organization in various capacities in the area of research ethics and epidemics. He also co-directs CENTRES (Clinical Ethics Network + Research Ethics Support)—an initiative of the Ministry of Health led by CBmE to provide a networking and training platform for clinical ethics committees and for institutional review boards. He is an appointed Member of the Pro-Tem Subcommittee for Restricted Human Biomedical Research under the Human Biomedical Research Act.