Conference on International Collaborative Research and Health Ethics

29 November 2005Jakarta, Indonesia

Research Ethics Review:The Regulatory Framework in Singapore

Terry Sheung-Hung KAANFaculty of Law, National University of Singapore

Bioethics Advisory Committee, Singaporeterry@nus.edu.sg

2

Regulatory Policy Regulations, regulations, regulations, and the

letter of the law – but contrary to expectations … Basic scheme similar to that of UK, multi-

pronged approach with checks and balances at many points through: Statutory law providing general framework, most often

concerned establishing regulatory jurisdiction, powers Assumption of dynamic common law filling interstices Professional, and institutional self-regulation Subsidiary legislation, Executive directives, policy

statements, professional codes, ethical codes and practice guidelines – quasi-law, because statutes require compliance with professional standards

3

The General Regulatory Framework Ministry of Health (MoH) has general oversight

of medical profession, tissue banks, hospitals, “clinics” (defined broadly), stem cell research (e.g. Private Hospitals and Medical Clinics Act, Medical Registration Act, Medicines Act, the Human Cloning & Other Prohibited Practices Act)

Health Sciences Authority (HSA) has general oversight of pharmaceutical / clinical trials, issues clinical trial licences (Medicines (Clinical Trials) Regulations / Singapore Guideline for Good Clinical Practice)

Singapore Medical Council (SMC) has general oversight of medical profession (Medical Registration Act) – applies professional standards

4

Statutory law provides general regulatory framework, confers regulatory jurisdiction and enforcement teeth

Common law principles & precedents provide further underpinnings (but does it?) – “seamless” body of law?

Leaving particular and interstitial details and implementation to institutional and professional self-regulation

Role of IRBs and statutory professional bodies Role of bodies such as the National Medical Ethics

Committee (NMEC), and the Bioethics Advisory Committee (BAC)

5

Clear preference for professional self-regulation and institutional self-regulation where practical – has worked well in past

General public acceptance, also preferred by professions

Leaves Government in high-level “gatekeeper” supervisory role through audit / accreditation / licensing (may prescribe licensing conditions), without getting involved in micro-management

6

Argument that in fields where state of ethical debate (let alone agreement on law) barely keeps pace with the state of the science, constantly evolving policy statements and practice directions crafted in consultation with public, community and professional groups often more realistic, flexible and substantively responsive than hard statutory law

Spirit as opposed to letter of the law: when in doubt, ask! consult! (Government, IRBs, professions)

Not reinventing the wheel: in absence of local direction, general assumption that starting point is best practice in major scientific jurisdictions (but if best practices differ?) Ditto policy and legislation

7

The System in Action Since establishment in 2000, four Reports issued by the

Bioethics Advisory Committee (BAC):

Ethical, Legal and Social Issues in Human Stem Cell Research, Reproductive and Therapeutic Cloning (“The Stem Cell Report”, June 2002)

Human Tissue Research (November 2002) Research Involving Human Subjects: Guidelines for

IRBs (November 2004) Genetic Testing and Genetic Research (November,

2005)

Full text of all Reports downloadable fromhttp://www.bioethics-singapore.org

8

General starting point: the public Consultation Paper (“White Paper”)

First used by the National Medical Ethics Committee in 1994 for the proposals leading to the Advance Medical Directive Act (living wills)

Extensive consultation with professional, civic, community, patient interests, religious groups

Aim is to come up with a set of recommendations / guidelines that takes into account as far as possible the views of all in the community, and not just professional groups

Groups and public are invited to submit written representations – all become part of the record when Reports are published

9

Record of representations offer valuable insights and a permanent record of perspectives and views of sections of the community, particularly where there is fundamental disagreement e.g. human embryonic stem cell research, pre-implantation genetic diagnosis

Of particular interest to ethicists looking for sources on Asian cultural and religious perspectives – Singapore is a plural society

Religious, professional views predominate

When concerns are crystallised into words and positions, easier to work out agreement and compromise instead of working on assumptions

10

After the Consultation:

If Report accepted by Government, recommendations (if in form of normative guidelines) have force as ethical guidelines to be applied as the considered and accepted practice and professional norms / best practice by professional groups, institutions, IRBs

Sometimes, however, statutory teeth is required – translation into law: e.g. the Human Cloning and Other Prohibited Practices Act

Public consultation before legislation approach also now widely used by Government in other areas, especially through the internet

11

Research Ethics Review If pharmaceutical / clinical trial, regulated by the Health

Sciences Authority (HSA) under the Medicines (Clinical Trials) Regulations: clinical trial licence, full ethics review required, full process described in the Research Involving Human Subjects Report

HSA also regulates medical devices, therapeutic use of experimental drugs

Human embryonic research, stem cell research regulated directly by MoH under Human Cloning and Other Prohibited Practices Act

12

Tissue banking (and indirectly research access to stored human tissue) by MoH regulatory jurisdiction over tissue banks under the Private Hospitals and Medical Clinics Act

Other kinds of biomedical research involving human subjects:

If by physicians (majority of biomedical researchers are), MoH under the Medical Registration Act

If carried out in or under auspices of hospitals and medical institutions (most trials), MoH under the Private Hospitals and Medical Clinics Act

If involving administration of drugs (but not pharmaceutical trials), MoH under the Medicines Act and the Medical Registration Act

13

Since 1998, all hospitals required to have IRBs (generally separate clinical ethics committees and research IRBs)

Most IRBs institutional, some organised along domain lines, some shared

No uniform guidelines for structure / constitution of IRBs until 2004 BAC Report

IRB approval required for all research involving human subjects (long required by principal funders) – separation into scientific review, then ethics review

Provision for exempted review (pre-approved categories of “routine” investigations involving minimal or remote risks

14

Provision for expedited review – similar to exempted review for low-risk, accepted categories (e.g. annual reviews of previously approved research in which there has been little or no change in on-going research)

IRBs and institutions must have clearly defined guidelines for exempted and expedited review categories e.g. writing up clinical results, review of clinical program, research using commercially available cell lines or commercially available anonymous DNAs, RNAs, fixed tissues)

Responsibilities of IRBs: Ethics review Continuing Review and Supervision Reporting and Feedback

15

“Lead IRB” concept for multinational, multi-loci / centre research projects – concept of “lead IRBs” for primary review, but each institution responsible for making final decision

Guidelines for SOPs, consent requirements, conflicts of interests, impartiality and independence of IRB members, fair review and documentation of decisions – but institution vary greatly in amount of research they undertake

IRBs as gateway control for access to research subjects, facilities, research material, collaboration, publication – efficacy?

16

Responsibilities of Researchers:Researchers have a “primary and central role

in ethics governance” – to not treat IRB approval as transfer of ethical and legal responsibilities, which are non-delegable

Researchers “primarily and ultimately responsible for making the first judgment” as to whether research is ethical – submission to IRB is assertion that it is

Continuing responsibilities, deviation and variation. Adverse events.

17

Researchers and attending physicians: should physicians have veto power over recruitment for trials? Or merely kept informed, if at all?

Responsibilities of appointing institutions – IRB reporting to top management, protected time, administrative support

Legal relationship between appointing institutions and IRBs – recommendation for statutory legal indemnity obligation

Accreditation of IRBs (MoH licensing requirements)

18

The Future More research being carried outside of traditional

setting – shifting paradigms Limits of self-regulation > public trust, statutory

teeth Different institutions, different challenges New laws needed to plug the gap – a omnibus

Regulation of Biomedical Research Bill was proposed and public feedback sought in 2003, but Human Cloning Act hived out of it for early enactment

Health, or research? A cautionary tale? But perhaps better

evolutionary than revolutionary. Stay tuned …

19

Resources Full text of Singapore Statutes:

http://www.statutes.agc.gov.sg or http://www.agc.gov.sg > click on “Statutes Online”

Full text of all Bioethics Advisory Committee Reports and Consultation Papers (including written representations): http://www.bioethics-singapore.org

Other biomedical research information: The Ministry of Health: http://www.moh.gov.sg Singapore Government portal: http://.www.gov.sg

Conference on International Collaborative Research and Health Ethics

29 November 2005Jakarta, Indonesia

Research Ethics Review:The Regulatory Framework in Singapore

Terry Sheung-Hung KAANFaculty of Law, National University of Singapore

Bioethics Advisory Committee, Singaporeterry@nus.edu.sg