A systematic review of ethnic diversity in clinical trial participation in Aotearoa

The lasting effects of colonisation continue to negatively affect the health status of Indigenous populations worldwide.¹ In Aotearoa New Zealand, Te Tiriti o Waitangi/the Treaty of Waitangi establishes the Crown’s obligation to ensure equity in health outcomes for Māori (the Indigenous people of New Zealand), yet systemic inequities persist in access to healthcare, workforce representation and exposure to the determinants of health. This continues to be a significant cause of ongoing injustice, with the economic costs of Indigenous health inequities estimated at NZ$863.3 million annually, while the Waitangi Tribunal’s Hauora report found that underfunding for Māori primary healthcare alone exceeds NZ$1 billion per year when unmet need is considered.^2–4

A randomised controlled trial (RCT) is the gold-standard method to determine the efficacy of an intervention. Ensuring diversity in participants recruited to RCTs is essential in ensuring the external validity of data and to best represent the characteristics of those with the disease being researched. Despite recognition of this, adequate representation of gender, demographics, minority and vulnerable populations is rarely achieved, impacting the external validity of clinical trial results, and propagating a barrier to optimal translation of research findings.^5–7

Two commonly used, demographic terms to categorise clinical trial participants are “race” and “ethnicity”, defined by the Oxford English Dictionary as “a group of people belonging to the same family and descended from a common ancestor” and “status in respect of a group regarded as ultimately of common descent, or having a common national or cultural tradition” respectively.^8,9

Standards for the reporting of race and ethnicity in published research varies by region and journal, with many reports omitting this information altogether.^6,10

In New Zealand, an ethnicity standard classification is published by Stats NZ Tatauranga Aotearoa (Stats NZ).^11,12 This is a hierarchical system comprising four levels, each of which involves more detailed ethnic categorisation. In health-related data presentation, level one is most commonly used and comprises six categories: 1) European, 2) Māori, 3) Pacific peoples, 4) Asian, 5) Middle Eastern/Latin American/African (MELAA) and 6) Other ethnicity. Users self-identify and can report multiple categories to best reflect their cultural, ancestral and geographic origins. Self-identified categories are then categorised into one of these six categories.

New Zealand has a vibrant clinical trials presence, contributing research findings of international importance through strong academic and commercial networks. However limited data exist to describe ethnic representation in clinical studies undertaken in New Zealand, despite being critical to ensure research priorities align with the health needs of the community and that the study conduct meets Te Tiriti obligations of partnership, protection and participation for Māori communities.

Here we report the findings of a systematic review of ethnic representation, with a particular focus on Māori and Pacific peoples, in all published RCTs undertaken in New Zealand between 2010 and 2020 and registered on the Australia New Zealand Clinical Trials Registry (ANZCTR). The hypothesis was that structured reporting of ethnicity and representation in clinical trials was inadequate.

Methodology

We conducted a systematic review using the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, the protocol for which is registered in the international prospective register of systematic reviews (PROSPERO) database (Ref: CRD42020210764).¹³

Search strategy

We searched the ANZCTR for interventional, randomised controlled trials undertaken in New Zealand, registered between 12 October 2010 and 12 October 2020. Additional parameters were studies marked as complete and with ethical approval.

Eligibility criteria

Results were screened and included for analysis if a linked publication was available in the PubMed database. Where multiple publications for a single study were present, the one reporting ethnicity data was included, or in the event of no ethnicity data reporting the main publication was used. Published protocols were excluded. This screening process was undertaken by two reviewers in duplicate, with conflicts arbitrated by a third.

Data extraction

All data were extracted using standardised forms created in REDCap electronic data capture tools hosted at the Medical Research Institute of New Zealand.¹⁴ Publication details recorded included title, first author, digital object identifier (DOI), study phase, country(ies) of recruitment, single- or multi-centre, funding source and principal investigator host-organisation type. Given the disparity in use of the terms “race” and “ethnicity” across the reported studies, the number of participants were recorded by ethnicity using Stats NZ level one—1) European, 2) Māori, 3) Pacific peoples, 4) Asian, 5) Middle Eastern/Latin American/African (MELAA) and 6) Other ethnicity—and level two codes where available or defined in free-text fields. The classification “residual” is used where responses do not fit into these specified categories.

The primary outcome was the proportion of each Stats NZ level one ethnicity code, for all participants recruited in RCTs conducted in New Zealand, in which ethnicity data were provided. Secondary outcomes included the mean proportion of each Stats NZ level one ethnicity code, per study; study characteristics reported for phase, funding source and sponsor type; study categorisation to “race”, “ethnicity”, “race and ethnicity” or “missing”.

Results

One thousand and forty trials were identified from the ANZCTR search, of which 342 met our inclusion criteria (Figure 1). Of these 342 studies, 103 (38%) published no ethnicity data at all, with the remaining 239 included in the analyses. General descriptors of the extracted studies are described in Table 1.

View Figure 1–2, Table 1–4.

Study phases, their funding source and type of sponsor for the 239 RCTs are described in Table 1.

Race and ethnicity categorisation

Of the publications that categorised participants, 112/259 (46.9%) categorised participants under a heading of “race”, 95 (39.7%) under a heading of “ethnicity”, 31 (13.0%) under both race and ethnicity and 1 (0.4%) study had no definition (Table 2).

Participant representation by ethnicity

There were 295,254 participants enrolled across all 239 RCTs analysed. The proportion of each Stats NZ level one ethnicity code for all participants are presented in Table 3.

Ethnicity reporting per trial

The mean proportions of participations per RCT, by ethnicity, are presented in Table 4.

Discussion

This analysis of RCTs recruiting participants in New Zealand between 2010 and 2020, highlights inconsistent and inadequate demographic reporting, with 38% of studies publishing no ethnicity/race data at all. Of the studies that reported ethnicity or race data in some form, 70.6% of all participants could not be classified according to Stats NZ level one codes.

When combining all 295,254 participants across these RCTs, the reported ethnic representation was 6.1% European, 2.9% Māori, 7.5% Asian, 1.4% Pacific peoples, 2.5% MELAA, 9% Other and 70.6% residual in which responses did not fit into these specified ethnic categories. The mean study enrollment proportion, across all 239 studies that reported ethnicity or race data, was 23.2% European, 2.7% Māori, 9.2% Asian, 1.8% Pacific peoples and 2.3% MELAA. Differences between these figures are explained by the influence of very large RCTs and targeted ethnicity studies on the pooled data description.

The 2023 Census reports figures of 67.8% European, 17.8% Māori, 17.3% Asian, 8.9% Pacific peoples and 1.9% MELAA respectively.¹⁵ This significant discrepancy between reported proportions of all ethnic groups and the census data is driven by a majority of participants placed in the Stats NZ residual category, comprising those data points unable to be defined within the official level one or two coding. For example those reported as “non-hispanic”, “white”, “don’t know”, “unable or willing to answer” or placed in combined groupings such as “Māori/Pacific” were classified as “residual”.

This gross disparity between ethnic proportions reported in RCTs and those derived from the census reinforces our major finding that reporting of ethnicity in RCTs is inadequate and mandates cautious interpretation of these data. However, potential under-representation of Māori in research is a concern, given the many health conditions that disproportionately affect Māori and obligations to Te Tiriti o Waitangi to ensure equitable participation in New Zealand–based RCTs. Several factors may contribute to this, including historical trauma and mistrust from health and research interactions, lack of cultural responsiveness in trial design, and anxieties about data sovereignty. Ensuring clarity around who controls research data, how they are used, and whether they serve Māori aspirations for Hauora (health and wellbeing) are fundamental to increasing representation in New Zealand research.

International efforts to increase equitable access to clinical trials are ongoing.⁷ Assessing progress toward equitable representation in New Zealand–based clinical trials requires a standardised, mandatory reporting mechanism.

Currently, every research team undertaking an RCT in New Zealand is required to submit their study for ethical review by the Health and Disability Ethics Committees (HDEC) and formally register their studies in the ANZCTR. HDEC requires that all research reports require ethnicity breakdown; however, as this is not explicitly stipulated at the review and approvals stage, it may not be prospectively implemented. Furthermore, the optional ethnicity classification fields do not align with any of the Stats NZ levels, making interpretation within an approved framework difficult (Figure 2).

The data presented reinforce the importance of structured, prospective collection of ethnicity data in clinical trials in order to gauge progress toward a goal of equitable participation. For New Zealand trials, consideration should be given to mandatory recording of ethnicity to HDEC at the final study report stage, aligning with Stats NZ level one codes as a minimum. For international multicentre trials that require protocolised ethnicity or race classifications locally relevant to the sponsor, this can be achieved as an additional, country specific, data collection. Extending this to the ANZCTR would further promote transparency in reporting, allowing open analysis of trial related ethnicity data to better track representation in specific specialist fields, trial phases or novel methodologies such as decentralised designs. Given the dominance of industry sponsored clinical trials (Table 1), including requirements at the regulatory stage will establish clear expectations for all research conducted in New Zealand.

Beyond this, consideration must be given to how whakapapa, or ancestral lineage, shapes a participant’s identity, including interaction with healthcare services and clinical research opportunities. This underlines the importance of adequately incorporating other cultural worldviews and context when designing and implementing clinical trials in New Zealand. For Māori, systemic efforts have been made to ensure responsiveness in research grant applications, study protocols and workforce representation, toward improving participation and health related outcomes.^16,17 To our knowledge, no previous overall reporting of Māori participation in New Zealand–based clinical trials has been undertaken, undermining these efforts toward equity and limiting opportunity for continuous improvement. We therefore recommend the mandatory reporting of trial participation according to Stats NZ level one ethnicity codes by regulatory bodies and registries such as HDEC and ANZCTR.

Conclusion

Ethnicity reporting in New Zealand–based clinical trials is inadequate and not standardised. Mandatory recording of ethnicity to Stats NZ codes should be considered during trial protocol development and reporting to the New Zealand HDEC, ANZCTR and peer reviewed journals. The lack of accurate data on Māori participation in clinical trials is undermining health equity goals and obligations under Te Tiriti o Waitangi.