Ethical challenges of conducting and reviewing human genomics research in Malaysia: An exploratory study

Abstract

Even though there is a significant amount of scholarly work examining the ethical issues surrounding human genomics research, little is known about its footing in Malaysia. This study aims to explore the experience of local researchers and research ethics committee (REC) members in developing it in Malaysia. In-depth interviews were conducted from April to May 2021, and the data were thematically analysed. In advancing this technology, both genomics researchers and REC members have concerns over how this research is being developed in the country especially the absence of a clear ethical and regulatory framework at the national level as a guidance. However, this study argues that it is not a salient issue as there are international guidelines in existence and both researchers and RECs will benefit from a training on the guidelines to ensure genomics research can be developed in an ethical manner.

1.|. INTRODUCTION

Novel and emerging technologies in genomics are leading to better understanding of the etiology of diseases and enable new approaches to healthcare. Currently, clinical precision medicine in Malaysia is not yet mainstream, but human genomic research is actively ongoing in fields such as oncology^1,2 and genetic disorders such as Thalassaemia.^3,4 Malaysia is also a member of several global and regional genomics research consortia, such as the Human Variome Project,⁵ GenomeAsia100K Consortium,⁶ and South East Asia Pharmacogenomics Network (SEAPharm).⁷

Biobanks store a large collection of biospecimens and support many types of research, including genomic research. The largest biobank in the country, The Malaysian Cohort, stores samples from over 100,000 Malaysians⁸ and focuses on research on non-communicable diseases (NCD).^9,10 The biobank is also a member of the Asia Cohort Consortium, whose membership includes Japan, Taiwan, South Korea, China, India, Singapore, and the USA.¹¹ Other biobanks in the country include the Malaysian Oral Cancer Database and Tissue Bank System;¹² the Malaysian Breast Cancer Cohort; Universiti Kebangsaan Malaysia Medical Molecular Biology Institute Cancer Biobank; and Thalassaemia DNA Biobank.¹³

Notwithstanding its promising benefits, the unique nature of human genetic data brings about various ethical, legal, and social issues.¹⁴ The field of genetic and genomics is incredibly complex, thus making ethics review challenging. Also, delivering information in a comprehensible manner to research participants can be challenging, and therefore the validity of consent can be questioned.¹⁵ Another contentious issue is the risk of genetic discrimination particularly pertaining to individuals and their family members’ future employment and access to health insurance.¹⁶ Furthermore, globally, human genomic research is mostly carried out among population of European descent.¹⁷ It can be argued that the findings from these studies may not be applicable to other non-European populations. Another important ethical issue is the risk of exploitation of genetic resources¹⁸ and inequitable benefit sharing when the research project involves collaboration among researchers from different institutions and countries that requires data sharing.¹⁹

1.1. |. Regulation of genomics research at the international level

Firstly, the UNESCO has released several relevant regulatory instruments that can provide guidance in conducting human genomic research in an ethical manner:

• The Universal Declaration on the Human Genome and Human Rights in 1997 sets out the ethical principles and highlights human rights that are associated with human genomic research.²⁰

• The subsequent International Declaration on Human Genetic Data in 2003 emphasises heavily on the protection of human rights from the lens of using human genetic data in research.²¹

• The Universal Declaration on Bioethics and Human Rights 2005 expands from the previous two documents to serve as a comprehensive ethical guideline to guide scientific and technological advancement.²²

Other relevant international ethical guidelines that also promote ethical human genomic research include:

• The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Guideline E18 on Genomic Sampling and Management of Genomic Data, which provides a set of harmonised principles of genomic sampling and management of genomic data in clinical studies.²³

• The fourth edition of International Ethical Guidelines for Health-related Research Involving Humans by the Council for International Organizations of Medical Sciences (CIOMS) is an all-encompassing research ethics guideline that also includes considerations for fair research in low-resource settings.²⁴

• Global Alliance for Genomic Health (GA4GH) was established to promote a conducive environment for responsible, voluntary, and secure sharing of clinical and genomic data²⁵. The Alliance published a Framework for Responsible Sharing of Genomic and Health-related Data²⁶ and accompanying regulatory and ethics toolkit, including policies on consent,²⁷ data privacy and security,²⁸ ethics review recognition,²⁹ and genomic research results.³⁰

1.2. |. Existing regulation in Malaysia

There is a lack of regulatory framework for emerging technologies such as genetic testing, screening, and gene therapy to address ethical issues posed by these technologies. However, there are existing legislations that may be relevant in regulating human genomics research:

• The Personal Data Protection Act 2010 (PDPA 2010) regulates processing of personal data for commercial transactions.³¹ It exempts research activities in Malaysia from abiding many principles in the Act.^32,33 Usage of data by the state and federal government is also exempted.³⁴

• The Access to Biological Resources and Benefit Sharing (ABS) Act 2017 regulates access to all biological resources within Malaysia, including traditional and indigenous knowledge associated with the resources, and any benefits arising from their utilisation for research and development (R&D) for commercial or non-commercial purposes. Human genetic material is also regulated under this Act.³⁵

Besides that, there are also national guidelines on medical genetics and medical research. However, all these guidelines do not address issues specific to human genomics research.

• The Guideline on Ethical Issues in the Provision of Medical Genetics Services in Malaysia,³⁶ updated in 2019, is by far the most comprehensive guideline in the country focusing on clinical genetics.

• The Guidelines on the Use of Human Biological Samples for Research by the National Committee of Clinical Research³⁷ aims to harmonise the practice of the various RECs in Malaysia in research on human biological materials.

• The Malaysian Good Clinical Practice is an international ethical and quality standard for clinical trials, and are often referenced among Malaysian RECs.³⁸

Currently, there is no comprehensive study on the development of human genomics research in Malaysia that capture the challenges faced by key stakeholders in developing this technology in the country from both the practical and ethical point of view. Existing literature on ethical issues of genomic research in Malaysia only focus narrowly on specific issues such as genetic privacy³⁹ and informed consent,⁴⁰ or as a short commentary.⁴¹ Therefore, this study aims to provide a comprehensive overview of the human genomics research field in Malaysia; and explore the local researchers’ experience in conducting research and REC members in reviewing this highly complex and ethically controversial area.

2. |. METHODS

In-depth interviews were conducted with researchers and local REC members who are involved in human genomics research in Malaysia. Semi-structured interview guides were developed for both groups based on a narrative literature review. The following topics were explored: (a) current practice in conducting human genomics research or when reviewing such protocols; (b) ethical challenges that respondents may face; and (c) their opinions on the regulatory challenges of human genomics research in Malaysia. The same topics were explored with both groups with questions tailored to their background and expertise.

Prospective respondents from both the public and private research institutions were identified using purposive and snowball sampling. They were contacted through e-mail addresses obtained from websites and published journal articles. They were provided with the participation information sheet and informed consent form. In addition, the identified respondents were also requested for referrals of other potential respondents. Of all the identified respondents, only five researchers and three EC members, who are all affiliated with public higher education institutions in Malaysia, agreed to take part in this study. They were interviewed from April to May 2021. All interviews were conducted in English via video conferencing by the first author during the COVID-19 pandemic, and recorded with the respondents’ permission. Interviewees who were unable to attend the interview responded via email. Some of the respondents were also re-contacted via email for additional questions. All respondents were given a token of appreciation in the form of a food delivery voucher worth MYR 30 (~ USD 8).

Data collection and analysis were carried out simultaneously. The recorded interviews were transcribed verbatim immediately after each session. The obtained data was analysed thematically using the framework by Braun and Clarke⁴² facilitated NVivo 2021 software. An initial coding frame, developed based on literature review, was used to code the transcripts. Any information that did not fit in any of the codes in the initial coding frame was given a new code. Subsequently, all of the coding was reviewed multiple times and categorised into themes and sub-themes by all authors.

This study obtained ethical clearance from the Universiti Malaya Research Ethics Committee (UM.TNC2/UMREC_1249) and Ministry of Health Malaysia Medical Research Ethics Committee (NMRR-21-209-58136(IIR), reference number: KKM/NIHSEC/P21–438(12)).

3. |. RESULTS

Based on the findings obtained from the interviews, this study has identified four main themes as presented below.

3.1. |. Theme 1: Current development of human genomics research in Malaysia

Currently, respondents who are local researchers only focus on NCD such as type 2 diabetes mellitus and hypercholesterolemia, and cancer. There is also research work that focuses on pharmacogenomics of NCD. Researchers mainly obtain samples directly from patients in the hospital on top of samples sourced from local biobanks.

“We obtained the samples from [the hospital]. For other NCDs (hypercholesterolemia and diabetes) and cancer studies, the samples were obtained from [a biobank].”

– Researcher 4

Given most genomics research activities globally are carried out among populations of European ancestry, the respondents argued that the outcome of these research may not be applicable to the Asian population. As such, all researchers hope that their research work will be able to advance precision medicine in Malaysia using locally resourced genetics materials.

“… most genetic research […] is usually done in developed countries, where most of them are Caucasians[…]ethnicity does play a role in our genetic makeup, and Asians may have very different and unique genetic make-up compared to Caucasian. […] We are a multiracial country, so we have a very wide pool of genetic makeup […] I think [my study] will provide understanding of the genetic risk factors for the Malaysian population. We have collected samples from different ethnicities [such as] the Malay patients, Chinese patients, Indian patients. We also have samples from the Aborigines as well…”

– Researcher 2

“…we hope that the [research] projects could lead the path for precision and personalised medicine in Malaysia. In addition, early screening can be done for early detection, hence could reduce morbidity and mortality due to the disease.”

– Researcher 4

3.2. |. Theme 2: Practical challenges of conducting human genomics research in Malaysia

The primary obstacle faced by the researchers is insufficient local funding. Therefore, researchers have to rely on international funding or collaboration with their counterparts from developed countries.

“…if you look at much of the genome-related research [in Malaysia], the sample size is very small! […] the largest grant from [the government], I would put only at about 3 million [Ringgit Malaysia] […] you can’t do much [in genomics research] in terms of [sample size].”

– Researcher 3

“…if we [want to] continue to be able to contribute to a global genetics project, because of the cost issue, it’s very difficult to do it alone. But when it is funded, it is easier. And with this funding, we will be able to do whole genome sequencing for the samples…”

– Researcher 2

Limited local funding may also be due to lack of awareness of the significance of large-scale genomics research by funders from the public sector. They do not appear to believe that local scientific talents and the existing technology infrastructure can fulfil the ambitious goals of genomics research.

“…sometimes mega projects like this scare the [funding] panel. Many of our panellists, sometimes don’t believe we have the capability. Sometimes they were like, “[Is this possible?] Do we have the expertise?”

– Researcher 3

3.3. |. Theme 3: Ethical challenges faced by researchers and REC members

Unequal partnership and benefit sharing in international research collaboration

Several respondents expressed that Malaysia serves as a sample collecting ground. Local researchers are eager to share data and biological materials with their counterparts in the high income countries in exchange for authorship in prestigious journals. One respondent coined this phenomenon as “FedEx research”.

“[Local researchers] send [their] specimens [or research data] overseas, [to] a consortium, and then get [authorships] in Q1, Q2 [research publications]. Many researchers in Malaysia do FedEx research!”

– Researcher 3

Some of the respondents shared their concern over the sharing of genetic information with their foreign counterparts particularly with the uncertainty as to how the information will be used post sharing. They also expressed the issue of recognising the source of the genetic information as well as the contribution by the local researchers.

“…[these genetic information] are almost like the country’s property and assets, so to speak. So, when we transfer it to another country[…] how they’re going to use the data in future, and for what purpose, and do they then recognise contributions….”

– REC member 3

3.3.1. |. Data security, privacy, and possibility of stigmatisation and discrimination

According to all the respondents, data protection practices is an established practice among researchers to restrict access to sensitive data, such as by anonymising the data very early on before analysis, even though one can still argue whether the data is truly anonymous.

“The participants will be given ID numbers and [identifiers] will be encrypted. Only the Principal Investigator could access this data.”

— Researcher 4

“Genetic results are stored in a separate private datasheet, which is shared only with [key research staff] who are performing the genetic testing [and analysis].”

– Researcher 2

Instead, respondents are more concerned about the breach of data security and subsequent implications on study participants’ confidentiality.

“You hear about computer systems being breached all the time, don’t you? […] It’s not difficult apparently just to break through very complex password-protected computer systems.”

– REC member 2

Respondents are also aware that a violation in data privacy may also include unconsented disclosure of genetic data to third parties such as insurance companies and employers. Disclosing genetic information potentially leads to better healthcare management, but it may also have an unfavourable impact, such as the possibility of being discriminated against.

“At least [the employers] could take precaution or discuss with you your options and the plans for you to take extra coverage. But the problem is catch-22. The moment you know you are predisposed to cancer, would they be able to cover you on their insurance scheme?”

– Researcher 3

“…all these consent forms which are used by the insurance company, particularly they can discriminate against genetic disease…”

– Researcher 1

3.3.2 |. Returning individual genetic results

All respondents agree that the participants have the right to decide whether to know their genetic results. At the informed consent stage, research participants are given the choice to decide whether to know their results, including incidental findings.

“…the information sheet must say that often we find things which are new, are novel, and this result will be made known to you if you wish to know…”

– REC member 1

Our respondents who wear two hats as researcher and clinician agree that results that are confirmatory and have significance or utility to the research participants should be returned. This would be beneficial for their long-term plans should they be susceptible to any diseases. However, the respondents also shared their concern about oversharing of information, which can have a negative impact on participants especially if there is no certainty.

“…we will not disclose [genetic results to participants] unless there is a clinical need. Because a lot of genetic tests are not confirmatory, they are just exploratory in nature, so those exploratory studies, we don’t…whatever we find, we do not know for sure the pathogenicity of those genetic variants. And I think when you don’t know, it’s not good to share too much when you’re causing confusion. In this project where we have panel testing, […] [we’re] testing now for genes that are known pathogenicity […] it’s very important for the patient to know [the results], so that he or she can […] think about long-term plans…”

– Researcher 2

There was also a concern about the process of returning the results. It was argued that genetic counsellors who are trained to communicate genetic results tactfully and provide psychological support to patients should be made available. However, due to limited expertise, clinician-researchers are forced to take on the role of the genetic counsellor. (REC member 2 and Researcher 2 are from different institutions.)

“There should be the availability of a counsellor, maybe psychological support, if these [genetic] results are returned.”

– REC member 2

“We don’t have a genetic counsellor in our clinic […] I’m not certified to do genetic counselling, but I have to do it in a resource-limited setting.”

– Researcher 2

3.3.3 |. Informed consent process

Some respondents highlighted the use of medical jargon in information sheet, which is not useful to facilitate research participants’ understanding. Another respondent suggested that it is important to understand participants’ backgrounds so that the choice of language to be used during the informed consent process is appropriate to ensure their understanding.

“The subject information sheet itself is very hi-fi, with a lot of medical jargon.”

– REC member 1

“…we need to identify their educational level, so that we can explain complicated terms in a language which they understand.”

– Researcher 1

One respondent recommended researchers to separate the necessary information such as the right to withdraw, the secondary use of collected samples, and the measures in place to protect confidentiality from the explanation on the scientific aspects of the research. This is to ensure that participants are at least aware and informed of their rights in research including the right to withdraw their consent to participate.

“Let’s say you’ve got 10 pages of information, most people […] just flip [to the informed consent page and sign]. Our [REC’s informed consent] guidelines is one page […] if you want to know more about genetics then you put enclose [as an appendix], then [the participants] can read at their [own convenience]… you just give them the main things here [on the first page], about you can withdraw, the samples won’t be used for other purposes other than research, all that, the patients knows exactly what they’re in for, and the confidentiality part and so on…”

– REC member 1

There is also a concern over how informed consent is generally practiced in the country. Several respondents questioned the attitude of local researchers towards the practice of informed consent. For instance, some researchers failed to declare that privacy and confidentiality of the participants may not be absolute. The respondents also highlight the attitude among participants who would normally trust medical doctors.

“The informed consent itself is an issue here, whether it’s a valid consent, a genuine consent. How many of our researchers actually have given the right information to every participant before they understand and make an informed choice?”

– Researcher 3

“…[Researchers] don’t declare it to the participants that there is a risk that [the protection of participants’] privacy and confidentiality is not 100% […] Just invite [the participants] to read it and [they] just ‘ikut doktor’ [follow the doctor’s instructions] and the doctor is not even aware of what can happen and things do happen…”

– REC member 2

3.4. |. Theme 4: Challenges of RECs in evaluating ethical concerns in human genomics research

3.4.1 |. Ethical evaluation methods

All three REC members agreed that guidelines are helpful in ethical evaluation of human genomics research proposals. Guidelines are also useful to increase awareness among researchers about the ethical issues in genomic research.

“…guidelines guide us [to make decisions], so that there’s some consistency because as you know our committee is made up of a diverse group of people…”

– REC member 1

“All these researchers are coming to us, not knowing about the ethical issues. So we have provided them with guidelines so they have no excuse anymore not to know about the ethical issues around it.”

– REC member 2

One respondent highlighted the lack of expertise in genetics among the REC members and that they may not have the ability to critically analyse and address ethical concerns of genomics research objectively.

“[Our REC members] know the broad [ethical] principles but we are not “expert” in reviewing genetic studies […] [our REC has] a pathologist and … many pathologists need to look at the sequence of genetics, more as a treatment really. So, I think it would be good to have some marrying the research ethics expertise with genomics.”

– REC member 3

One respondent commented that REC members evaluate human genomics research just like clinical drug trials. Therefore, this reviewing method may not confer sufficient protection to research participants and their family members.

“[Genomics research is] not the same as a drug trial […] You cannot use the same approach [in evaluating ethical issues] for a drug trial, for a genomic research, because it has an impact not just for the patient but for the relatives…”

– Researcher 1

3.4.2. Absence of specific and actionable guidelines in protecting research participants

Respondents with experience being in the REC raised the issue that REC members lack competency in ensuring research participants are protected due to a lack of clear guiding rules. For instance, one respondent shared that REC members are not fully aware as to how genetic data is being shared and protected based on the existing law.

“…ethics committee review the data sharing plan of a research protocol […] eventually how [the data is] being shared we also don’t know. We don’t go around checking. Then, it’s up to the researchers to share, right? How do we make sure that they are shared properly? So, at the moment, we do not have the guidelines to go through that. We do have site visits, but that’s done in a very ad hoc manner. So, how we do it then, to ensure that these are being done to protect individuals or even community or national interest.”

– REC member 3

Another account shared by a respondent further highlights the lack of competency of the REC members. The respondent questioned the ethical approval given to a research project involving samples that are taken from the local indigenous peoples which are now stored in different biobanks in other countries.

“There are many of our patients’ DNA sitting in repositories overseas […] including those from the Orang Asli (Indigenous Peoples’) […] If this were to happen in Australia, the Aborigines, our researchers can be brought to court for breaching ethical principles. But, how did our local researchers manage to get approval from our ethics committee?”

– Researcher 3

Some respondents argued that there is a need for regulation on material transfer and data sharing to be established at the national level. This is to ensure clarity among stakeholders particularly the REC members. Moreover, the guiding rules would not only facilitate stakeholders to conduct their work in an ethical manner but also protect them from being sanctioned.

“There must be national guidelines for material transfer, data transfer, that one especially for genetic research. Then the local [ethics] committee can refer to that […] I’m sure local institutions also would want to see a national guideline or an Act governing this, so that they want themselves to be protected and they don’t want to be accused of breaching any rules or policies.”

– Researcher 3

Such regulation can also dictate the terms of the collaboration which can encourage fair collaboration between local researchers and their collaborators. Benefits can be distributed evenly, resulting in a win-win situation for all.

“…there’s a need for [national regulation in data transfer] […] not only the DNA is not exportable, but that we keep and control of our own data and we want to work together with [other countries] and we want to share but as partners not as just, ‘Ok, here is the data, do what you want and if you publish, you publish by yourself and we just get an acknowledgement section’…”

– REC member 2

4. |. DISCUSSION

Based on the ethical challenges highlighted in the preceding section, one could argue that these are not new issues and have been widely discussed.^{43, 44, 45, 46} Several international instruments are available to address these issues.^47,48 However, this paper attempts to highlight some of the issues in the Malaysian context.

4.1. |. Development of genomic research in Malaysia

Unequal ethnic representation in genomics research can exacerbate existing healthcare disparities.⁴⁹ A disproportionate majority of participants in published GWAS are of European ancestry.^50,51 The results may not be helpful for individuals of non-European descent, who may be more likely to receive ambiguous test results from genetic screening and inaccurate diagnoses due to scarce information in genetic variation,⁵² thus leading to inadequate clinical management. The same can also be said for pharmacogenetics.⁵³ To ensure that genetic research is broadly applicable to all populations, including people with different genetic ancestries in genetic research is important.

Based on the findings reported, it can be seen that Malaysia is heading towards the right direction in terms of addressing the unequal representation, whereby local scientists are working towards capturing genetic data from the local samples to ensure that any genetic-based therapy in the future would be meaningful for the local people. This is a positive development and should be supported by the government.

4.2. |. Benefit sharing to promote equity in international health collaboration

The desired outcome from a collaboration between a low- and middle-income nations such as Malaysia and high-income countries would be a long-term and equal partnership where benefits from such research are shared,⁵⁴ and to build and sustain research capacity in the developing country,⁵⁵ ultimately reduce reliance on developed countries.⁵⁶ However, such collaborations also have a high possibility of incurring inequity. One pertinent example of this scenario would be local researchers are not involved in the creative or decision-making process of the research, but merely treated as field workers.^57,58

Biopiracy occurs when biological materials native to a particular country are appropriated or commercially exploited without providing fair compensation to the local people.⁵⁹ When samples and data are anonymised and then exported or shared, the contributing country will then have less control over their subsequent uses.⁶⁰ Without proper tracking, benefits from the usage of these samples may not reach the original contributors.⁶¹ This has occurred in other parts of the world,⁶² and it will not be a surprise that this will happen in Malaysia too if no necessary measures are introduced to address this issue.

In recognising the issue of benefit sharing involving biological resources, Malaysia has introduced the Access to Biological Resources and Benefit Sharing (ABS) Act. According to the Act, researchers are required to obtain informed consent from the community before commencing data collection. If there are any plans or potential for commercialisation, a legally-binding benefit sharing agreement needs to be negotiated with the local communities before accessing the samples.⁶³ These benefits are not limited to monetary form⁶⁴ and should be in accordance with the needs, values, priorities, and cultural expectations of the community.^65,66 Such an agreement would allow researchers and the local community to work together as partners, thus ensuring the ethical and social value of the research project⁶⁷ while also remaining relevant to and acceptable by the community.

Distributive justice is paramount in benefit sharing. Researchers have the responsibility of being culturally sensitive and socially responsible when interacting with local communities. Their duty goes beyond scientific inquiry to reduce exploitation and promote equitable distribution of benefits to the local communities. Negotiation for fair benefit sharing can be challenging,⁶⁸ especially when it is difficult to predict future challenges and benefits.⁶⁹ If researchers hold true to the duty of social responsibility, and RECs to provide accountability watch on the researchers, such practice can ensure sustainability of the research efforts and win-win situation for both parties.

Researchers need to obtain a permit from the national authority,⁷⁰ who will then monitor the usage of biological samples, including application of patents within and outside Malaysia derived from the use of these samples. However, non-commercial R&D activities conducted by Malaysian public institutions or government agencies are exempted from applying for said permit (informed consent from the community is still required).⁷¹ The Act also does not mention the need to obtain ethics approval for research on human subjects. There is also little mention of equal partnerships between researchers, as what is emphasised in several international instruments.⁷² These exemptions mean that REC members and researchers in public institutions have a bigger responsibility in protecting research participants.

4.3. |. Data security and possibility of stigmatisation and discrimination

Many respondents showed great concerns over data security and genetic discrimination. Internationally, there is consensus that genetic discrimination should be prevented,^73,74 but only a handful of countries globally, have regulatory framework to address genetic discrimination.⁷⁵ The only country in Asia which has legislation to address genetic discrimination is South Korea⁷⁶. In Malaysia, the only document that specifically mentions genetic discrimination is the MOH medical genetic guideline,⁷⁷ which is not legally binding.

The relevant existing law in Malaysia is the Personal Data Protection Act 2010. However, as highlighted earlier, only activities that involve commercial transactions will fall within the ambit of the PDPA 2010. Commercial transactions are defined as “any transaction of a commercial nature, whether contractual or not, which includes any matters relating to the supply or exchange of goods or services, agency, investments, financing, banking and insurance, but does not include a credit reporting business…”.⁷⁸ By this definition, data sharing for research purposes does not come under the purview of PDPA 2010. The PDPA is also not applicable to institutions such as public higher academic institutions, which are under the purview of the Federal government.⁷⁹

Under the PDPA, genetic data, being “related to a person’s physical or mental condition”,⁸⁰ can be regarded as sensitive personal data, which can only be collected, processed, or used for certain purposes such as medical and employment, legal obligation, and any other purposes conferred under any Malaysian law.⁸¹ However, it does not seem this clause can be relied on to prevent the use of genetic information for differential treatment. Notwithstanding, in view of “damage or distress”, the law provides that data subjects will have to make the initiative to contact the data users to prevent further processing of such data.⁸² However, one would argue that when damage is done, the processing of data may have been so extensive that it would be difficult to know where things start and end. Therefore, it can be argued that a clear legal protection against discrimination involving genetic data should be established, especially given the fact that it is uncertain as to whether data generated from a whole genome sequencing are truly anonymous.

4.4. |. Return of results

All respondents in this study support research participants’ rights not to know their genetic results, consistent with the local⁸³ and international regulatory instruments.^84,85,86 Respondents also agreed that returned genetic results should be valid, confirmatory, and of certain significance or utility. Globally, there are discrepancies on what type of results should be returned to participant, from “clinical significance” and “actionable”;^87,88 to urgency;⁸⁹ to utility of the results towards the persons beyond the individual, such as family members.⁹⁰ The local guideline only emphasised on confirmatory and reliability and not the possible implication of results.⁹¹

Internationally, there is significant debate on how to handle the questionable analytic and clinical validity of research findings.⁹² Even though international⁹³ and local guidelines⁹⁴ recommend that the applied assay and its level of validation should be taken into consideration, no further elaboration about the standards to adhere to was specified.

Despite the uncertain and varying interpretation of disclosure policies, researchers and global community alike agree that a justified disclosure of results is the way to go.⁹⁵ Such policy aims to reduce the distress towards research participants, while still maximising the benefits that they can get from participating in genomic research. Researchers bear the responsibility of mitigating the distress that research participants might encounter during this process.

One way to mitigate the distress is by employing a genetic counsellor or clinical geneticist to return the genetic results. Local guideline⁹⁶ requires returning of results conducted by a genetic counsellor or clinical geneticist, but our study showed that this is not the case. All the respondents in this study acknowledge the role of genetic counsellors, but human resource is a limitation. In 2018, there were only 14 medical geneticists and two certified genetic counsellors in the country.⁹⁷ Therefore, there is a need to develop human capacity in this profession.

4.5. |. Challenges of RECs in evaluating human genomics research protocols

The sheer scale of human genomic research and its novelty makes evaluating such research challenging to RECs.^98,99 It may be unrealistic to expect the ethics committee to be expert in the particular scientific field, but it is reasonable to expect them to constantly enhance their knowledge in research ethics^100,101 and subsequently their ethical reasoning skills, to appropriately safeguard research participants. Our findings, however, highlighted the lack of such formal training for local REC members. According to See et al., many committee members, in general (and not specific to genomics research), learn to conduct reviews mostly through observation, which may lead to inadequate ethical reasoning ability.¹⁰² This might result in poor decision-making during ethical review and, as a result, inadequate protection of research participants. One would argue that this challenge can be overcome with a training provided to REC members on the existing international guidelines on genomics research.

4.6. |. The lack of clear guiding rules

The available local medical genetic guideline¹⁰³ place heavier emphasis on clinical ethics instead. Another issue raised is that the existing laws do not cover biomedical research on human subjects. For instance, the PDPA 2010 is not specific to protecting health data used in research settings that do not involve commercial transactions, let alone preventing genetic discrimination. Furthermore, even though the ABS Act provides some form of benefits sharing to local communities, it does not address the issue of inequity between local and international research partners. Notwithstanding, as mentioned above, one could argue that there are international guidelines that can be used by both RECs and researchers. The reason of non-existence of clear guiding rules at the national level should not be an obstacle for providing protection to research participants. For whatever that is lacking from the local regulation, RECs and researchers could refer to the internationally established guidelines. Both parties should keep themselves abreast with the latest updates. A proper training for the REC members in interpreting the guidelines and regulations, and researchers on operationalisation of these documents.

4.7. |. Strengths and limitations of the study

This study provides an overview on the ethical landscape of human genomics research in Malaysia from the perspectives of stakeholders on-the-ground, i.e., the REC and researchers who are involved in genomics research, mainly from the public sector. The small sample size is due to the limited number of stakeholders who are actively involved in genomics research. Notwithstanding, all of the respondents raised similar issues, suggesting data saturation. Invitations to participate in this study were sent to researchers and REC members from private institutions, however none of them responded to the invitation. As such, perspectives and opinions in this study may not be shared by the stakeholders in the private sector. This study also does not address ethical issues among vulnerable populations, or in specific medical fields within human genomics. Furthermore, given the exploratory nature of this study, the reported findings may not be substantial to be relied as a guide to develop or propose an ethical framework for conducting human genomics research in the country. Nonetheless, this study has laid the groundwork for a more in-depth work in the future.

5. |. CONCLUSION

Due to insufficient local funding, Malaysian researchers rely on international funding and collaboration to carry out impactful genomics research. As such, the ethical concerns of unequal partnership and benefit sharing in international collaboration emerge, where local researchers and communities may not benefit equally from the fruit of the research. Nationally, clear regulation for human genomics research is lacking, existing national regulatory instruments are insufficient to guide researchers and RECs in navigating these ethical issues. This is compounded by the lack of training in international guidelines making it potentially challenging in addressing the ethical concerns and challenges that were raised in this study. It is hopeful that the discourse offered by this study, albeit its exploratory in nature, demonstrates the importance of advancing this promising research in an ethical manner.

Biographies

Teong Win Zee, MHR, is presently a research pharmacist in Clinical Research Centre, an integral part of the Institute for Clinical Research network under the National Institutes of Health, Malaysia. In 2021, she successfully earned her Master of Health Research Ethics from Universiti Malaya. Her primary research focus centres on special populations, particularly patients receiving palliative care.

Mohammad Firdaus Bin Abdul Aziz, PhD, is a senior lecturer and a Deputy Dean of Research, Value Creation and Enterprise at the Faculty of Law, Universiti Malaya in Malaysia. His research interests are in the areas of legal and ethical issues of emerging technologies such as stem cell technology, biobanking, genomics, and AI in healthcare. He is a co-investigator in a collaborative research group supported by The Wellcome Trust to establish the Southeast Asia Bioethics Network (SEABioN) to bring underrepresented SEA voices to the forefront in the contemporary Bioethics discourses.

Phan Chia Wei, PhD, serves as a senior lecturer within the Faculty of Pharmacy at Universiti Malaya (UM), and has been instrumental in shaping the future of pharmaceutical education in Malaysia. Additionally, Dr Phan is the Head of the Clinical Investigation Centre at Universiti Malaya Medical Centre, leading groundbreaking research initiatives. His commitment to advancing research ethics is exemplified through his faculty membership in the Master of Health Research Ethics program. Dr Phan also plays an active role in the Academic Research Organization Alliance for ASEAN and East Asia (ARISE) program, strengthening clinical research collaborations across the ASEAN and East Asian regions.