Developing a New, Digitally Integrated Research Infrastructure: Results of the Macau Biobank Survey

In 1553, with the permission of Ming Government officials, the Portuguese were able to set up their first settlement in the Far East,^[1] Macau/Macao, a small area within the Pearl River Delta. In 1987, China and Portugal reached a consensus about Macau’s reversion to China in 1999. After becoming a Special Administrative Region (SAR) of China, Macau experienced rapid economic development reflected in many areas, including in the educational field, and the development of its higher educational and research institutes.^[2] Under the SAR arrangement, Macau maintains separate government and economic systems from mainland China under the principle of “one country, two systems.” As such, the city enjoys a high degree of autonomy, having its own legislation, immigration and customs control, currency, taxation system, and public health laws. Furthermore, the city has one of the highest per capita incomes in the world and is the world’s second-highest GDP, which is attributed to its very active gaming industry.^[3]

Technological and pharmaceutical advancements of the past 20 years have facilitated biological research at scale with the introduction of “-omics” technologies, such as genomics, proteomics, and others.^[4] As a result, many countries and regions have established centralized storage infrastructures for human biospecimens and associated data. These infrastructures are collectively called biobanks and aim to support overall regional, national, and/or international research endeavors.^[5] Some examples of this research infrastructure emergence are as follows: the UK Biobank in the United Kingdom,^[6] the Integrated BioBank of Luxembourg in Luxembourg,^[7] the China National GeneBank in Shenzhen,^[8] the CU-Med Biobank in Hong Kong,^[9] and the International Agency for Research on Cancer/World Health Organization biobank in Lyon.^[10] Macau has established academic institutions as a critical step to diversify its economy^[11,12] and as the basis for developing biomedical research locally. It also promotes the digital integration of publicly funded activities as part of the “smart-city” development occurring across the entire Pearl River Delta region.^[13] Thus, it is inevitable that Macau will have to consider whether establishing its own research infrastructures, such as a biobank, would be a necessary precondition for future biomedical research development and how it can be integrated within the developing digital ecosystem.

The national development of biobanking in various regions of China has been aligned with the main international biomedical research trends of its time over the last two decades (ie, high-throughput analyses of tissues for “-omics”-based experimentation).^[14] Further alignment with international standards has been achieved through dedicated teaching and training courses by higher education institutions and professional associations.^[15,16] Currently, there are numerous small to large biobanks in the neighboring areas of Macau, such as Guangdong Province^[17,18] and Hong Kong SAR.^[19] Each biobank has its unique scientific mission supporting different functions, projects, and purposes.^[20] However, they address a rather homogeneous and static population. Macau has a diverse mix of local and transient populations compared with mainland China.^[21] As such, biobanks from neighboring regions might not represent the local population mix within Macau. Given the ease of Macau’s entry and exit policy, population fluidity is expected to increase further, bringing additional opportunities in public and personal health, education, and biomedical research. Furthermore, the local Macau population has some distinct healthcare attributes, such as the highest life expectancy in all of China^[22] and a comparatively high adult mental health burden against the reported Chinese national average.^[23] However, establishing research programs that scientifically interrogate these unique regional healthcare aspects may require creating a biobank containing samples and digitally integrating them into local healthcare services to serve as a research platform and provide new skills for the local researchers.

As per international common practice, the Macau Foundation funded a feasibility study for a potential Macau biobank. The feasibility study results presented here include a survey to understand broader needs and opportunities regarding biobanking in Macau. It will also inform future public health and biomedical research infrastructure investment and operations.

The current survey was developed based on previous biobanking feasibility assessments conducted by the Qatar Biobank^[24] and similar European studies.^[25–27] Such information was unavailable for biobank setup in mainland China or Southeast Asia. Specifically, a group of international biobanking advisors participated in biweekly virtual meetings to review available references and written materials in the international scientific literature, provide their expertise on operational biobanking needs, and develop the survey and eventually a biobank feasibility study. Particular focus was given to the alignment of regulatory and governance structures as well as possible healthcare data–integration requirements. Those meetings were especially helpful in articulating the reasons behind all such regulatory requirements and establishing a common understanding of the historic development of biobanking in the Pearl River Delta. The survey received ethical approval; completing and returning the questionnaires were considered tantamount to informed consent.

The first step in creating this survey involved determining the domains of interest the questionnaire would measure. We conceptualized relevant constructs (underlying theme or subject matter) from the existing literature and previously published questionnaires from which to develop an item pool.^[24,28–32]

The initial survey consisted of 27 questions divided into the following three domains: professional details, relative rating of aspects, and governance and challenges. It was then further refined to 12 questions in 3 iterative review sessions with local healthcare professionals (who volunteered through Wechat or Whatsapp), providing input on the questions (eg, clearly defining terms, such as “biobanking of high-quality specimens”). Based on these responses, the survey was revised and proceeded to assess for content validity. Assessing content validity was a nonstatistical examination of the survey content that determined the representativeness of the survey questions and whether they could assess the topics of interest. The content validation process involved a panel of experts familiar with the construct.^[33] Four experts with knowledge and expertise in biobanking within the wider Pearl River area were recruited for this study.

The final form of the survey (provided in Supplementary Material A, available online) contained minimal information on professional details (to maintain privacy) and challenges (as these were entirely speculative) and was distributed among the healthcare and scientific community of Macau through the Wechat and Whatsapp platforms, using a snowballing method, for 1 month. We estimate that it reached over 100 professionals, and 47 complete questionnaires were received and considered for this study.

The survey was published in both Chinese and English, with 47 respondents from local academic institutions, researchers, and medical personnel. The first set of questions focused on the initial reaction to different aspects of biobanking. The rest of the questions ranged from the initial reaction to creating a standardized regional biobank to rating the importance of operating/maintaining a biobank, including infrastructure, financial sustainability, proper training, education, awareness of the community and collaboration between health services, research, and biobanking personnel.

The profile of the survey participants is shown in Table 1. The majority identified as medical personnel with research activity, while nearly one-fourth self-designated as “other.” The “other” designations were primarily laboratory-based positions with many role overlaps, including diagnostics implementation, research, and healthcare service, and, as such, did not feel that a single designation was representative.

As shown in Figure 1, overall responses were positive/very positive (41/47; 87.3%) for the establishment of a regional, digitally integrated biobank. When asked to justify this answer, 39 free-text responses were provided stating that there is a need for a facility for precision medicine development supporting the advancement of scientific research in Macau (27/39; 69%) through the provision of high-quality biospecimens and data (6/39; 15.4%); and thus, enhancing the reproducibility of ongoing work (3/39; 7.7%). Of note, there were also three neutral responses stating that the feasibility study for a biobank in Macau was not available and could not respond, and one negative opinion, though this level of investment was not justified at all in the follow-up free-text response.

The responses to the remaining eight questions are summarized in Figure 2, highlighting the relative significance of a number of biobanking aspects, as voted on a scale of 1 to 5 (low to high significance, respectively). The highest-scoring aspects (ie, of highest significance to the responders) were the emphasis on appropriate governance and the oversight of operational resources, while the lowest-scoring aspects were the safety concern and the links with the overall healthcare infrastructure. However, the observed difference in relative importance was low. In other words, responders considered that most of the aspects called upon to evaluate were mostly equally as significant to the potential operation of a biobank in Macau.

The responses to the survey were aligned with similar studies in China^[34,35] and globally,^[36–38] where biobanks are recognized as necessary infrastructures supporting biomedical research and the development of precision medicine initiatives through their digital integration within a wider healthcare ecosystem. In mainland China, the example of China Kadoorie Biobank serves as a common reference point, with the electronic linkage of biological samples to death/disease registries and the national health insurance system, and might be applicable at least in part for Macau.^[39] The second-highest response relates to the provision of high-quality, research-ready samples and data, directly linked to the third-highest response being the reproducibility of research. This aligned with the views expressed in China^[34,40] and globally,^[41,42] where biobanking is seen as an essential component for the provision of high-quality tissues and data at scale for research purposes, thus supporting research reproducibility.

The relative distribution of survey participants reflects the two major local user groups (ie, medical staff who are active researchers and laboratory-based individuals who also carry additional research-related tasks).^[43,44] These staff have already achieved high levels of digital literacy, as evidenced during the current pandemic with the creation of the linked infrastructure and the transition to digital patient management workflows.^[45] They are likely to be equally as versed in the digital integration of a biobank within the wider healthcare system. As such, it is evident that a user base exists for a potential biobanking initiative in Macau, though the scale of this future “customer base” is not possible to ascertain through this survey and would require additional work. Of note, contrary to global settings,^[46,47] there are no responses related to pharmaceutical-driven research (as a core component of precision medicine). It is unclear if this is due to the limited pharmaceutical-driven research within Macau or governance/regulatory reasons that relate to the SAR itself. It is also interesting to see that there is relatively low importance attributed to the integration of a potential biobank into other existing research infrastructures. This probably points to either an anticipation that this is a precondition (ie, practical inevitability) or an underlying siloed view for biobanking, though it would need to be further investigated. The experience from neighboring Hong Kong SAR and mainland China regarding the very high digital integration of healthcare services^[48] likely points to the former rather than the latter. The safety concern is not unexpected as Macau has often experienced epidemics through the movement of people and/or animals; however, it has not been the place of origin of any. As such, the perception of the local safety record on biological samples is likely to be high and deprioritized relative to other aspects that require a stronger focus.

Regional differences in a country as geographically vast as China present challenges for calculating generalizable and accurate estimates of country-level responses or ongoing knowledge and attitudes on specific topics, such as biobanking. Therefore, regional studies, such as the current one, are needed to identify opportunities and perceived challenges, including the public and private healthcare domains. This is true for Macau specifically but also for many other regions of China, where biobanking has enjoyed rapid development over the past decades.^[40] However, regional, context-driven granularity on biobanking activities, opportunities, and challenges might still be missing. Thus, investing in the possible creation of a digitally integrated biobanking infrastructure in Macau should become part of highlighting its unique role and purpose and how such an infrastructure can contribute to the greater good in the research community, as well as add value to existing operations in hospitals and primary healthcare units. For example, as biobanks include physical samples and data, laboratory staff would need to develop skills to handle and even interrogate large volumes of healthcare data.^[49] Furthermore, as a SAR, such a research investment proposal should also include how it may eventually collaborate/partner with its Pearl River Delta neighbors and internationally, creating the framework for data transfer and supporting wider educational and economic opportunities.

Limitations of this study include the potential online-driven inherent bias of the responders in such studies, as interested staff are more likely to provide the link to such studies to other colleagues; they are aware of sharing the same/similar interests. Thus, positive responses might be overrepresented in the sampled respondent population. Additionally, the sample size is relatively small compared with other similar studies. Macau is a comparatively small area with a small pool of potential responders. Therefore, the anticipation of much larger sample sizes could only materialize if primary and secondary education staff were also asked to participate en masse. Finally, this survey included only a small number of questions, sufficient to benchmark the initial responses of a potential customer base. Demonstrating the sustainability of a research infrastructure, such as a biobank, would require a more detailed feasibility study.

Biobanks represent significant investments in biomedical research and precision medicine development. However, they also require a good understanding of the potential user-base needs and expectations to be able to survive and thrive in the longer term. This research presents the first time that opinions on the potential creation of a digitally integrated biobank in Macau were surveyed among clinical, academic, and laboratory researchers in the area. As demonstrated by the current survey results, the emerging consensus opinion is that establishing a regional, digitally integrated biobank is much needed to support the advancement of research in Macau and enhance the reproducibility of ongoing research. Additionally, the survey demonstrates that the questionnaire developed is suitable for benchmarking the regional context and can identify areas of challenges and opportunities for the development of a biobank facility. It is anticipated that the outcomes of this work will inform the creation of a regional framework for biobanking in Macau as part of a comprehensive feasibility study on the subject.

The authors acknowledge Jasper Hoi Chun Luong (Smoke-Free & Healthy Life Association of Macau, Macau SAR, China) for assistance in proofreading and editing the manuscript.