The use of blood biomarkers in lung cancer screening in Aotearoa New Zealand: a cross-sectional survey of Māori perspectives and preferences

In Aotearoa New Zealand, Māori lung cancer incidence and mortality rates are substantially higher than those of non-Māori, contributing greatly to health inequities.¹ An equitably designed lung cancer screening (LCS) programme has the potential to enable stage shift and earlier diagnosis when curative intent treatment is more likely to be effective, which in turn has the potential to reduce Māori health inequities.^2,3 Although still a novel aspect of LCS programme development around the world, incorporating biomarker identification and analyses is promising as a non-invasive technique to enhance early detection of, and guide treatment decisions for, lung cancer. Within LCS programmes, biomarkers derived from blood samples have three potential purposes: 1) to identify those most at risk of lung cancer who may benefit from screening, 2) to improve ways of managing nodules that are identified by a low-dose computed tomography scan, including differentiating between malignant and benign nodules, and 3) to optimise treatment regimens for people with lung cancer in the treatment space, and to monitor responses to those treatments.^4–8 A number of circulating biomarkers have been identified, including germline gene variants, micro ribonucleic acid, epigenetic markers, autoantibodies, protein markers and circulating tumour deoxyribonucleic acid (DNA).⁶ However, only a small number have undergone validation, and none have been widely adopted for screening purposes.⁶ While biomarkers may soon play a key role in optimising LCS, not all population groups at high risk of developing lung cancer may be comfortable with blood collection and analysis.

Despite initiatives to enhance diversity in research studies, Indigenous populations continue to be significantly under-represented in genomic datasets.⁹ Unethical research, poor communication, disregard for cultural and spiritual beliefs, exploitation and failure to prioritise Indigenous interests have historically created mistrust between Indigenous communities and researchers and a hesitancy to engage in research.^9–12 For example, the 1990s Human Genome Diversity Project failed to consult with Indigenous communities or to be transparent over sample use, and the benefits to Indigenous communities were not identified.¹³ In response, the international movement of Indigenous Data Sovereignty has gained significant momentum among Indigenous scholars and activists, particularly following the adoption of the United Nations Declaration on the Rights of Indigenous Peoples in 2007.¹⁴ Indigenous communities globally have developed principles and guidelines for the management and use of their data.¹⁴ These communities expect that the use of blood samples will contribute insights into diseases (and their treatments) that affect their communities, and that the knowledge gained will benefit current and future generations.^9,11–17 Despite previous historical issues, Māori have, for a long time now, been proactively seeking to ensure the benefit of new technologies to do with tissue, genomics and biomarkers, and developing world-leading guidance, expectations and standards to establish best-practice trusted processes that are guided by mātauranga Māori (Māori knowledge), Māori rights and interest in tissue and data and are grounded in Te Tiriti.

Guidelines for genomic research with Māori, Te Mata Ira, were outlined in a 3-year research project. These guidelines were published after extensive consultation with iwi (tribes) and other stakeholders and draw on mātauranga and tikanga Māori (Māori protocols and practices).^15,16 While Māori views towards genomic research are not homogenous,¹⁵ the guidelines set out considerations ensuring: Māori rights and interests are protected; Māori health is prioritised; there is oversight of samples and data; appropriate consultation and consent is undertaken; and an open feedback loop is maintained.^15,16 A further set of guidelines, He Tangata Kei Tua, was developed to facilitate best practice in addressing Māori ethical concerns by guiding culturally informed policy and practice for biobanks in relation to governance, operational and community engagement activities.¹⁸ These guidelines categorise cultural and trust issues in three ways: 1) the level of comfort that participants and communities have in the research project, 2) the level of control that donors and communities have in relation to the use of tissue in biobanks, and 3) the level of integrity present within systems that contribute to the research endeavour.¹⁶ Additionally, there has been further development within the Rakaiora programme of work under the National Science Challenge, with new standards expected to be published soon.¹⁹

If Māori participants decline to participate in research, this may lead to under-representation, potentially exacerbating existing health inequities.^9,10 It is therefore essential to be aware of how Māori view biomarker collection and analysis to address concerns and ensure equitable participation. While New Zealand does not currently have a national LCS programme, research efforts are underway to understand how such a programme could be equitably implemented.^20,21 Planning for the future inclusion of blood biomarkers is an important implementation issue. Our research, Te Oranga Pūkahukahu: The Lung Cancer Screening Research Programme, is a Māori-led approach to ensure that a future national lung screening programme benefits Māori—the population group most in need of LCS—by providing policy- and programme-relevant evidence to inform future implementation of LCS in Aotearoa New Zealand.²⁰ One example of a specific biomarker that has shown potential in identifying participants who may benefit from LCS, which is of interest to our research group, is DNA methylation at CpG site cg05575921 in the aryl hydrocarbon receptor repressor (AHRR) gene, which is closely related to smoking intensity and duration.^22–26 An important challenge for LCS is that self-reported smoking data are often inaccurate due to factors such as recall bias, stigma, second-hand exposure and variation in smoking technique.²² Furthermore, the accuracy of smoking data in primary care has been shown to be underestimated,²⁷ potentially resulting in a substantial proportion of the target population missing out on screening. An assay to measure the level of AHRR methylation therefore has the potential to improve lung cancer prediction by accounting for second-hand smoke exposure and mitigating the impact of inaccurate self-reported smoking histories.²⁵

In 2020, we surveyed a cohort of Māori current or ex-smokers potentially eligible for a future LCS programme, and their whānau tautoko (self-identified family/support people), building on earlier exploratory qualitative work.²¹ The objectives of this survey were to determine the level of support of potentially eligible Māori and their whānau and to explore decision making and design preferences for an LCS programme.²⁸ The objective of this paper is to describe the acceptability of providing blood samples for the purpose of including biomarkers in an LCS programme for potentially eligible Māori and their whānau tautoko. The STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) checklist for cross-sectional studies was used to guide this study.²⁹

Methods

Study design

Two surveys were developed, one for potentially eligible LCS participants—“screenees”—and one for whānau tautoko. Whānau were included because decision making within Māori contexts is often collective, and whānau views may influence participation. This paper focusses on two specific questions from the broader surveys, exploring attitudes and options related to blood sample collection (Appendix). The surveys were developed in collaboration with a steering committee and underwent pilot testing with focus groups comprising potential screening participants. This pilot phase enabled the refinement of the surveys to enhance their readability and cultural sensitivity, ensuring their appropriateness for the target audience. There were some further minor wording updates for Te Tai Tokerau to improve question clarity based on provider feedback. The Health and Disability Ethics Committee (ref 19/CEN/90) approved this study in June 2019. Localities approvals were obtained from the Auckland (ref A+ 8276) and Waitematā (ref RM 14431) District Health Boards, which included Māori review. All participants provided informed consent to participate.

Setting

The two surveys were administered in Tāmaki Makaurau (the largely urban area of Auckland, New Zealand’s largest city) and Te Tai Tokerau (Northland, a mostly rural region, including remote and isolated populations). These regions have distinctly different demographics, with Māori comprising 36% of the population in Te Tai Tokerau versus 12% in Tāmaki Makaurau.³⁰ The regions were selected due to future LCS research that was planned to be implemented in those regions. Participants for this study were recruited from two districts within the Auckland Region: Te Toka Tumai Auckland and Waitematā, excluding Counties Manukāu. The recruitment for participants in Tāmaki Makaurau commenced in January 2020 but was temporarily halted due to the national COVID-19 lockdown in March. The recruitment process resumed in April and was completed by June 2020. In Te Tai Tokerau, recruitment began in May 2020 and was completed by August 2020.

Participants

The eligibility criteria for potential screenees consisted of: 1) self-identifying as Māori, 2) aged between 50 and 80 years, and 3) having a history of smoking at some point in their lives. Participants were excluded if they had a previous diagnosis of lung cancer or were unable to provide informed consent. Whānau tautoko, of any ethnicity, aged 16 and older who were able to provide informed consent were eligible to participate. The research team employed a range of recruitment strategies to reach potential participants. Due to COVID-19 lockdowns, the surveys in Tāmaki Makaurau were primarily completed using relevant clinical databases (e.g., Abdominal Aortic Aneurysm screening database) and recent hospital discharge information. The majority were completed over the phone with a trained researcher (who was either Māori or spoke te reo Māori [the Māori language]) instead of the originally intended in-person format. A small number of participants opted for alternative methods, including completing a mailed questionnaire or accessing an online link. In Te Tai Tokerau, the majority of participants completed paper surveys, which were distributed with the assistance of volunteer Māori health organisations. Others were opportunistically recruited by a medical receptionist at participating practices during routine medical clinic interactions. A smaller number of participants in Te Tai Tokerau completed the survey either over the phone or online. All participants received a $20 gift voucher at the completion of the survey, and kai (food) at the community hui (meeting) as koha (gift, offering) for their contribution. If required, participants were also supported with transport to address participation barriers.

Variables

The surveys aimed to explore and gain insight into the attitudes and perceptions of Māori participants and whānau tautoko regarding the acceptability and processes involved in a potential lung screening programme. Previous research has described the results relating to the acceptability and preferences for a lung screening programme.²⁸ This paper focusses on the two questions relating to blood sampling: the first question assessed participants’ comfort with providing a blood sample for use in future LCS, while the second question explored the factors that would be important to them if blood sample donation were an option within LCS (Appendix).

Demographic information included gender, age, ethnic group and region. Participants self-identified their gender as male, female, gender diverse, or prefer not to answer. Potential screenees were categorised into three age groups, 50–59, 60–69 and 70+, while whānau tautoko were divided into two categories, under 50 and 50+. These age groups were selected because they correspond to the age at which individuals would be either eligible or ineligible for LCS. Ethnicity was self-reported. When a participant identified multiple ethnicities, the recommended prioritisation process was used to determine their primary ethnicity (Māori>Pacific>Asian>Other).³¹ The region was either Te Tai Tokerau or Tāmaki Makaurau.

Study size

Our objective was to collect 300 surveys from screenee participants and 100 surveys from whānau tautoko, determined by the level of confidence in estimates when comparing responses across age group, gender and region.

Statistical methods

The two surveys (screenees and whānau tautoko) were analysed separately using R (version 4.3.1). For each question, frequencies and percentages were examined. Fisher’s exact tests were used to compare responses by region, age group and gender, with a p-value <0.05 considered statistically significant. For cases where Fisher’s exact test revealed significant differences, pairwise comparisons with a Bonferroni correction were conducted to identify which specific groups differed.

Results

Screenee survey

In total, 388 screenee participant surveys were completed; however, 11 were excluded because they did not self-identify as Māori at survey completion, despite initially being identified as Māori through recruitment lists, leaving a total of 377 surveys included in the analysis. Most Māori individuals who participated in the screenee survey resided in Tāmaki Makaurau (79.0%). The group consisted of slightly more females (54.9%) than males (45%). Most participants were in the 50–59 (38.7%) and 60–69 (44.0%) age brackets, with 17.0% over the age of 70 (Table 1).

Question one: comfort with blood donation

Most participants (61.9%) reported feeling “very comfortable” providing a blood sample, while an additional 21.5% felt “comfortable” with the process. A small proportion of participants indicated they were “uncomfortable” (4.4%) or “very uncomfortable” (2.7%), and 9.3% reported being neutral on the matter (Table 2). Ten participants did not respond to this question and were therefore excluded from analysis.

Significant regional differences in responses were observed (p<.001) (Table 2). Participants from Tāmaki Makaurau were significantly more likely to be “very comfortable” compared with those from Te Tai Tokerau (70.1% cf. 28.88% [p<.001]), while Te Tai Tokerau participants were more likely to be neutral (20.5% cf. 6.5% [p=.005]), uncomfortable (12.3% cf. 2.4% [p=.005]) or very uncomfortable (8.2% cf. 1.4% [p=.027]) with providing blood samples.

There were also significant differences by gender (p=.012); however, post hoc pairwise comparisons using the Bonferroni correction found no significant differences between the groups. Responses to this question did not vary significantly by age.

Question two: important factors regarding blood donation

When selecting from a list of factors “important” to them regarding blood sample provision, participants were able to select more than one response. The majority of participants (57.8%) selected “nothing, I’m fine with it anyway”. The next most important factor was “clear information about how it is going to be used” (35.0%), followed by “knowing how this might protect the health of future generations (tamariki/mokopuna)” (24.1%) and “being able to say yes or no to some uses” (23.6%) (Table 3).

There were significant regional differences in response to this question (p<.001). Participants from Tāmaki Makaurau were significantly more likely to select “nothing, I’m fine with it anyway” (63.0% cf. 39.2% [p<.002]). In contrast, almost all aspects of blood collection and storage were significantly more important to Te Tai Tokerau participants. For example, almost twice as many participants from Te Tai Tokerau identified “knowing how this might protect the health of future generations (tamariki/mokopuna)” as important (38.0% cf. 20.5% [p=.018]). Furthermore, almost one-quarter (22.8%) of Te Tai Tokerau participants indicated they would not participate in research if blood tests were involved, compared with only 2.4% of those from Tāmaki Makaurau (p<.001). There were no significant differences in response by age group or gender.

Whānau tautoko survey

A total of 134 whānau tautoko surveys were completed. Most resided in Tāmaki Makaurau (77.6%). The group had slightly more females than males (55.2% cf. 44.8%), and a larger number of participants over the age of 50 compared to those under (60.4% cf. 39.6%). There was also a substantial representation of Māori participants compared with non-Māori (79.9% cf. 20.1%) (Table 1).

Question one: comfort with blood donation

The majority of whānau tautoko (62.0%) reported they felt “very comfortable” providing a blood sample and an additional 19.4% indicated they were “comfortable” with the process. A smaller proportion of participants indicated they were “uncomfortable” (7.8%) or “very uncomfortable” (2.3%), and 8.5% remained neutral (Table 4). Five participants preferred not to answer this question and were therefore excluded from analysis.

Significant regional differences were observed for whānau tautoko (p<.001). While almost three-quarters (73.2%) of whānau tautoko participants from Tāmaki Makaurau reported being “very comfortable” providing a blood sample, less than one-quarter of Te Tai Tokerau participants reported feeling this way (21.4%) (p<.001). Significantly more participants from Te Tai Tokerau indicated they felt neutral (25.0% cf. 4.0% [p=.010]) compared with respondents from Tāmaki Makaurau.

Whānau tautoko responses also differed by age (p=.006). Almost three-quarters of participants over the age of 50 were “very comfortable” with donating blood (74.0%) compared with less than half of those under 50 (44.2%) (p=.004). There was no evidence of a statistical difference in responses by gender or ethnicity.

Question two: important factors regarding blood donation

When choosing from the list of factors that could influence their willingness to provide blood samples, over half of the whānau tautoko participants (54.5%) selected “nothing, I’m fine with it anyway”. The next most common response was “clear information about how it is going to be used” (35.8%), followed by “being able to say yes or no to some uses” (27.6%) and “knowing how this might protect the health of future generations (tamariki/mokopuna)” (23.8%). Less important factors included “knowing who makes decisions about its use” (15.7%), “return of samples if not used” (9.7%) and “iwi involvement in decisions about storage/use” (5.2%). Very few participants would not participate if blood tests were involved (4.8%) (Table 5).

A significant difference in responses was observed between whānau members in the under-50 age bracket and those 50 or over (p=.005) (Table 5). Post hoc comparisons did not identify any specific group differences after adjustment. There were no statistically significant differences in blood comfort factors between gender, region or ethnicity for whānau tautoko.

View Table 1–5.

Discussion

Both lung cancer screenees and their whānau tautoko were strongly supportive of the use of blood samples in LCS. The majority of screenees (82%) and whānau (79%) participants were either “very comfortable” or “comfortable” with blood donation. Although most did not report needing further information, those who did identified “clear information about how it would be used”, “being able to say yes or no to some uses” and “knowing how this might protect the health of future generations” as key determinants influencing their decision to donate blood. Results for each survey were heavily region-dependent, with the more northern and rural Te Tai Tokerau participants indicating relatively less comfort with blood donation and more caveats around its use than participants from the large urban centre of Tāmaki Makaurau. Some other statistically significant differences by demographic factors were noted. For example, among whānau tautoko participants, those aged over 50 years were significantly more likely to be “very comfortable” with donating blood. For screenees, males were also significantly more likely to be “very comfortable” with donating blood compared with females. While we did not find any significant differences between ethnic groups in the whānau tautoko survey, we note that in our sample non-Māori participants are not likely to be representative of the wider population of non-Māori, since whānau tautoko participants may share similar beliefs and attitudes to their Māori whānau members.

Māori support for donating blood within the context of an LCS programme is promising in terms of lending support to the use of biomarkers to help streamline future implementation of LCS, including better identification of at-risk individuals, diagnosis and work-up of tumours and informed treatment regimes. While the literature explicitly exploring the views of Indigenous communities is limited,¹⁰ our findings support the issues identified in international and local guidelines for best practice.^9–17,32 As per international and New Zealand–specific guidelines,^15,16 research involving blood samples needs to engage with communities and include them as partners in the research.¹⁵ The relationship between researchers and communities must be trusting¹⁶ and all blood samples must be treated respectfully with an open dialogue with communities about their use.¹⁵ It is vital that communities where blood is being taken feel comfort, control and integrity in these processes.¹⁶ This requires not just following guidelines, but also demonstrating trustworthiness through good governance, transparent processes and adherence to the standards of excellence identified by Indigenous people. In our survey, Māori potential screenees and their whānau valued being informed about how blood would be used and having the opportunity to say yes or no about some uses. These results reinforce the importance of the earlier work of Te Mata Ira. A very small proportion of participants stated they would not participate in an LCS programme if it included the taking of blood samples. There was some variation in wording for this question—in Te Tai Tokerau, responses were explicitly in the context of research, whereas in Tāmaki Makaurau, participants were asked about a “lung health check”, which could be interpreted as either a research setting or a national screening programme. Our programme is cognisant of these views and is aware that the inclusion of biomarkers in LCS may potentially discourage a very small number of people from participating. These views have implications for future programme messaging around biomarkers.

The regional differences observed for both screenees and whānau members have important implications for the collection of blood samples in LCS research and in the implementation of a future LCS programme. Researchers and programme developers will need to ensure that the issues identified as important considerations are appropriately addressed in project and programme design and in the information they provide to communities and participants.

Strengths and limitations

Provision of blood samples is an important issue within the context of barriers and facilitators to participation in a potential LCS programme. There is a clear gap in the literature specifically regarding potential participants’ perspectives of biomarkers within LCS programmes. A key strength of this research is that it provides insight into potential participant views on the use of blood biomarkers in LCS, and specifically into Indigenous views, a little-researched area internationally. Additionally, the two questions regarding Māori views about blood sampling were specifically designed to address the issue of blood sample provision within a wider survey that examined a range of views and perspectives on LCS. Limitations of this research include that due to COVID-19, the methods of data collection varied; therefore, there may have been differences in responses depending on whether participants completed the survey in-person or over the phone, or whether it was entirely self-administered or facilitated by a researcher. Another limitation was that the survey questions were solely quantitative in nature, restricting respondents to selecting pre-defined options without the opportunity to provide qualitative feedback. There was also some variation in the wording of the questions across regions (see Appendix), which could have influenced answers. Additionally, we did not explore participants’ perspectives on specific biomarkers versus future unspecified uses of their blood. Finally, the views captured were from potential participants and may differ to responses from participants who actually take part in an LCS programme.

Future directions

Our two survey questions are a first step towards understanding Indigenous Māori views regarding biomarker use in potential future LCS. More research is needed to understand the regional differences that we observed. A qualitative study specifically focussed on biomarker collection and use for LCS, one that seeks to include diverse rural and urban Māori voices, would shed further light on these regional variations. Further research could examine whether Māori attitudes differ towards the different ways that biomarkers can be used within LCS, such as identifying high-risk individuals versus determining treatment regimes. Additionally, research that examines existing programmes that involve blood collection could provide valuable feedback from participants who decline to take part, helping to identify their concerns. This could involve distinguishing between concerns related to specific biomarkers, such as those linked to smoking history, versus broader concerns about blood testing in general.

Conclusions

Māori participants were comfortable with the use of blood sampling for biomarkers in LCS although those from a more rural region were slightly less comfortable and had more caveats. Future research could usefully examine whether the use of biomarkers in determining LCS programme eligibility might be viewed differently than those used for improving screening or treatment outcomes, and whether Māori views are similar or different to other ethnic groups; it could also explore regional differences in-depth. Any future collection of blood samples for the purposes of LCS in New Zealand should apply the same principles and guidance as has been articulated for research purposes, including community partnership, ensuring return of benefit to whānau, management of potential harms and processes to ensure Indigenous data and tissue sovereignty.

View Appendix.