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Risk stratification: an important tool in the special review of research using oocytes and embryos
  1. G Owen Schaefer,
  2. Teck Chuan Voo
  1. Centre for Biomedical Ethics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
  1. Correspondence to G Owen Schaefer, Centre for Biomedical Ethics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; medgos{at}nus.edu.sg

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Like all research, embryo research can take a variety of forms, some posing substantially more risks to persons than others. Savulescu et al argue persuasively that regulatory regimes specially designed for sensitive embryo research should differentiate between person-affecting and non-person-affecting embryo research, with substantial scrutiny only warranted for the former.1 Yet if we find Savulescu et al’s argument persuasive, what practical implications would it have?

In this commentary, we focus in particular on how such an argument might apply in Singapore, one of the jurisdictions with special regulations for embryo (and oocyte) research. We will summarise the way in which approval for oocyte and embryonic research operates in Singapore, and suggest that Savulesc et al’s distinction requires specification to be useful in such contexts. We propose adopting a risk-stratified framework similar to that employed with Institutional Review Boards (IRBs). This requires a wider view of risks than the focus by Savulescu et al on future persons. We then illustrate how such a framework would apply in five scenarios discussed in Savulescu et al.

Singaporean context

Research with embryos and oocytes is regulated in Singapore under the Human Biomedical Research Act.2 Enacted in 2015, this law sets out requirements for consent, IRB review and research oversight. By definition, all research involving gametes and embryos fall within the remit of the Act. Moreover, such research is defined as ‘restricted’; besides the Act, research involving oocytes and embryos is also subject to control under the Human Biomedical Research (Restricted Research) Regulations.3 In addition to an institution’s IRB approval, an advisory committee on restricted research appointed by the Ministry of Health (MOH) must recommend approval before such research can commence.

With regard to approval, two criteria, as stated in the regulations, are especially relevant: the scientific merits of the research proposal, and whether the research would raise ‘ethical issues and concerns with regard to conducting such a research at the wider societal level’.3

At present, the law and subsidiary regulation on restricted research do not distinguish between person-affecting and non-person-affecting research.

Savulescu et al’s approach can usefully inform any potential future revisions to the approach to oocyte and embryo research of jurisdictions like Singapore that require special approval for such research, but with some clarifications and specifications we will describe below.

Risk stratification

A standard approach to proportionate IRB review (including in Singapore) is risk stratification: studies that are potentially more risky or sensitive receive greater scrutiny. A ‘full board’ application is typically the highest level of scrutiny, where an entire IRB will meet and discuss an application. Studies that meet criteria such as being of ‘minimal risk’ (risks not greater than everyday life or routine clinical practice) may qualify for ‘expedited review’, where only one or two IRB members reviews a study and approval does not require meeting with the full IRB. Studies with almost no risks to participants, such as anonymous questionnaires, could qualify for ‘exempt review’. Despite its name, studies that are exempt still must submit documentation to IRBs for verification that they qualify, but approval of such submissions is typically quicker than the other categories.

The Human Biomedical Research (Restricted Research) Regulations do not permit expedited or exemption from IRB review for any form of restricted research.3 Nevertheless, regulations are silent on whether the advisory committee may conduct such expedited or exempt review. It may be appropriate for the committee to adopt a risk-stratified review process for oocyte and embryonic research, which aligns with the categorisations Savulescu et al identify. There is indeed a crucial difference in potential risks for studies where embryos or gametes will not be used for reproduction, and those where a resultant child may be affected by the study’s interventions. Just as IRBs might expedite or exempt the former but conduct full board review on the latter, so too could an advisory committee decide to assign one or more designated member(s) to review non-person-affecting studies in lieu of a full committee review.

Two other categories of review are worth mentioning. First, a study could be excluded from review entirely, such that an application for exemption would not even be necessary. This relates to the scope of restricted research in the first place, all of which must be presently approved by the MOH viz. the advisory committee on restricted research in Singapore.4 But if a study’s risks are not qualitatively different from other forms of research that do not require another committee’s approval above and beyond IRB review, then arguably scrutiny by an additional committee is redundant and unnecessary.

Second, some types of research are so controversial, risky and/or socially disruptive that a blanket policy of rejecting such studies is appropriate until certain conditions obtain. This is arguably the case with germline gene editing, where there is broad international agreement that the procedure is too risky to be justifiably applied to person-affecting research at this time.5

Scope of risks

A risk-stratified framework must be sensitive to all relevant forms of risk that can obtain from a study. Savulescu et al focus on one central form of risk–risk to future children, such as deleterious long-term health effects from manipulation of embryos.1 This risk indeed does not obtain for research where embryos or gametes would not be implanted. Nevertheless, two other sources of risk remain that are relevant to risk stratification and thus the question of appropriate level of committee review.

One, risks to future parents. Even if an embryo or gamete under study is not implanted, research could impact them negatively. Psychological distress related to their embryos or gametes being manipulated and destroyed is a possibility. Another is that of a conflict of interest. In cases where researchers are also involved in fertility care, there may be a concern that certain embryos or gametes are earmarked for being discarded in order to provide a greater supply of biological material available for the research.

Two, certain forms of research may have deleterious social effects. For example, those who hold that bioenhancement would be on net bad for society might object to basic research on discarded embryos or gametes that advanced the field and brings that world closer to reality. Such questions of social impact are naturally speculative and often quite controversial. This does not mean they should be outright banned, but it may be appropriate for committees providing additional scrutiny of oocyte and embryonic research to assess studies for their down-the-line social impact.

Applying a risk-stratified approach

The preceding is somewhat abstract, so in table 1 we have offered potential ways in which a risk-stratified review approach may be applied to the case studies provided by Savulescu et al.1 We add a fifth case study to explicitly cover the example of gene editing that they raise. This is not meant to be a full proposal, but indicative of how risk stratification can specify and clarify the import of the general considerations Savulescu et al raise. We hope that as relevant committees review their practices, these considerations may inform future iterations of their procedures.

Table 1

: Risk Stratification in 5 Case Studies

Ethics statements

Patient consent for publication

Ethics approval

Not applicable.

Acknowledgments

Dr Voo Teck Chuan is a member of the Advisory Committee on Restricted Research (ACRR) in Singapore. This commentary is written in his personal capacity and does not express the views and opinions of the MOH or the ACRR.

References

Footnotes

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Commissioned; internally peer reviewed.

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