FormalPara Key Points

  • Cancer patients who participate in clinical trials typically experience better outcomes, including increased survival and improved emotional and spiritual wellbeing.

  • Diverse representation in clinical trials is a matter of health equity, fairness, and public trust.

  • Trial participants should reflect the population affected by the disease.

  • Raising awareness, providing education, improving access, and allowing people to remain in their communities are essential for improving clinical trial diversity.

  • Community visits to raise awareness and build relationships of trust and safety are important first steps in recruiting Indigenous people to clinical trials.

Cancer patients who participate in clinical trials typically experience better outcomes. They receive early access to new treatments, increased survival, and improved wellbeing. Clearly, clinical trial participants should represent the population affected by the disease being studied. In addition, people experiencing the disease should have equal access to trials, regardless of their location, culture, or socioeconomic background. However, equal access is rarely the reality. This chapter considers Indigenous peoples’ access to clinical trials in Australia, the USA, and Aotearoa New Zealand.

The Australian Context

The Australian Government is committed to conducting clinical trials and ensuring that Australia remains at the forefront of cancer research, including its origins and treatment. Clinical trial participants currently do not represent the country’s diverse population. While little is known about the participation of Aboriginal and Torres Strait Islander people owing to under-reporting of Indigenous status, they are thought to be under-represented in clinical trials [1].

Over 100 clinical trials in Australia are known to have focused on Aboriginal and Torres Strait Islander people. When invited, Aboriginal and Torres Strait Islander people generally participate. However, only about 1.5% of all trials in Australia focus specifically on Indigenous health, and very few of these focus on cancer. Given the disparities in cancer outcomes experienced by Aboriginal and Torres Strait Islander people, their involvement in clinical trials is critical for reasons of equity and social justice. In addition, evidence suggests that cancer patients who participate in clinical trials typically experience better survival and wellbeing outcomes. This underscores the critical importance of ensuring equity in access to critical trials.

Cancer Trial Recruitment in the Northern Territory

The Alan Walker Cancer Care Centre in Darwin (Northern Territory—NT) has a clinical trial unit, which, in 2023, had 23 ongoing clinical trials (43% of all clinical trials in the NT).

Approximately one-third of the NT population identifies as Aboriginal and/or Torres Strait Islander. However, only 15 patients (6%) in the 23 clinical trials identify as such. Clinical trial staff experience several barriers to Indigenous enrollment, including consent processes; language and literacy difficulties; communication between patients, families, and providers; and geographical remoteness.

To overcome these barriers, staff focus on improving health literacy and working with sponsors to create opportunities for local clinical trial enrollment. For example, one recent trial offered a teletrials option, designed to improve participation among the rural and remote population, including Aboriginal and Torres Strait Islander people. To help address health literacy, staff develop resources designed to create meaning in a way that makes sense within individuals’ lived experiences and worldviews, often linked with local analogies. For example, vines growing over a fig tree are a useful metaphor for tumor cell growth in the body, and pandanus seed falling from a tree into a creek is a metaphor for cancer metastasis.

Cancer Trial Recruitment in Northern New South Wales

The Regional, Rural and Remote (R3) Clinical Trails Enabling Program was established in 2023, with four-year funding from the Australian Government. This program is designed to increase clinical trial participation among Indigenous people in northern New South Wales. It aims to establish a strong, sustainable, local clinical trials support infrastructure and workforce; develop and implement systems and partnerships; and increase clinicians’ participation in clinical trials. Its goal is to provide a virtual clinical trials support unit and deliver increased and more equitable access to clinical trials for patients in regional, rural, and remote areas.

A key focus of the program is increasing Aboriginal and Torres Strait Islander participation, primarily through a community engagement strategy. Staff engage with local communities, visit Aboriginal Medical Services, and initiate conversations about health and clinical trials. Future plans include creating a network of Aboriginal managers across New South Wales tasked with improving clinical trial recruitment and retention, opening up access in remote locations, and increasing participant diversity.

The US Context

In the USA, participation in clinical trials by American Indians and Alaska Natives (AI/AN) is an ongoing concern. Recruitment and retention are difficult, and trial findings may not be shared in ways that are relevant to participants. A key problem is that AI/AN people cannot see themselves in the data. Trials frequently report breakdowns for Caucasian, African American, and Hispanic populations, and label all remaining racial groups as “other.” There are no benefits to participation for Indigenous communities who are invisible in the data.

In 1977, the US Office of Management and Budget released Statistical Policy Directive No. 15, identifying required racial groups to be included in all documents [2]. It specified that AI/AN must be included and identified as a separate population of interest. All clinical trials are required to report findings for all racial groups. To achieve this, studies often combine data from multiple years, so that results remain anonymous.

Many AI/AN people currently lack best-practice cancer treatments, and treatment may be both prolonged and require extensive travel. Most trials compare current recommended treatments with new experimental arms (perhaps adding a medication to improve patient outcomes). Therefore, a key advantage of clinical trial participation is, at a minimum, the current best-practice recommended treatment. According to Native American Cancer Education for Survivors (NACES) study data, few AI/AN patients who are not clinical trial participants receive recommended treatments [3].

Walking Forward, at Monument Health Hospital, Rapid City, South Dakota seeks to address this. Although AI/ANs have access to cancer services at Monument Health, for many this involves extensive travel, with a median distance of 140 miles. Walking Forward has had significant success recruiting and retaining Indigenous patients in clinical trials. In 2020, it recruited more than 4500 patients, with the participation of Indigenous patients equal to that of all other facilities combined [4]. It reports increased cancer treatment compliance and has recruited patients for a genetic study exploring increased incidence of side effects among American Indians receiving external beam radiation compared with non-native patients. The strategies used by Walking Forward to recruit and retain trial participants are summarized elsewhere in this volume.

The Aotearoa New Zealand Context

Aotearoa New Zealand is in the process of restructuring its approach to clinical trials. Currently, Māori experience inequitable access to clinical trials, and contemporary research tools and measures are incompatible with Māori worldviews and methodologies. The Enhancing Aotearoa New Zealand Clinical Trials report [5] proposed a model and roadmap for national clinical trials and networks for the general population. iNZight Analytics were contracted to provide a Māori analysis of the data giving insight into the unique Indigenous experience and the investments required to achieve a more equitable clinical trial ecosystem [6].

Research with 130 non-Māori researchers found that while some sought to improve their cultural research skills, others continued with inadequate consultation processes and methodologies or reverted to narrow methods of not consulting with Māori regarding the relevance and suitability of research protocols [6]. The study found that 31% used Kaupapa Māori methodology (i.e., research practices that follow Māori processes from inception to dissemination). Of note, many non-Māori researchers requested further training on topics such as Kaupapa Māori methodology, Māori data sovereignty, and data governance, indicating they want to understand the priorities of Māori researchers.

Māori workforce development continues to be a significant issue in Aotearoa New Zealand. Only 4% of the workforce is Māori. Clinical trials need qualified Māori leadership to guide and develop appropriate methodologies and research agendas. Māori communities remain under-funded and under-resourced, and racism continues to interfere with recruitment and retention in clinical trials.

The Harti Clinical Trial in New Zealand

The Harti clinical trial was designed to develop a culturally safe model of cancer care for children and their families. It included 965 participants (56% were Māori; >50% were less than one year old); half were randomized to the Harti intervention and the rest to regular hospital care.

The intervention included a Māori Model of Care, with culturally appropriate, modified internal clinic culture protocols to create a safe, culturally aligned, racism-free space. Patients and whānau (extended family) reported feeling valued, respected, and awarded dignity and gained confidence in navigating the system. Based on feedback, staff continued to revise protocols guided by expert advisors, whānau, clinical staff, and evidence reviews, and to track improvements.

Based on this success, program staff expanded the Māori Model of Care to adult and elder cancer patients through the Whānau Hauora Integrated Response Initiative (WHIRI) clinical trial. Individuals who have been referred to Waikato Hospital with a high suspicion of cancer are eligible for participation. The trial involves three phases: (1) review of clinical notes and interviews with Māori cancer patients and their whānau, (2) project co-design guided by the He Pikinga Waiora Framework (Māori implementation framework), and (3) pilot testing with Māori patients and their families.

Key Issues Relevant to Indigenous Participation in Clinical Trials

  1. 1.

    Racism: Racism in a cancer facility offering clinical trials results in few or no Indigenous participants. Racism manifests in at least three ways [7, 8]: (1) institutional racism, leading to clinical trial information not being shared with Indigenous patients; (2) interpersonal racism, which may manifest as bias about Indigenous patients’ likelihood to comply with clinical trial protocols, rude or disrespectful treatment by service providers and co-workers, or service refusal; and (3) internal racism, which may involve Indigenous people accepting negative racial characterizations and demonstrating lack of respect for other Indigenous peoples [8, 9].

  2. 2.

    Implicit or explicit eligibility bias: Some physicians assume Indigenous patients will not comply with clinical trial protocols and decide not to discuss the topic. However, Indigenous cancer patients typically say they are willing to do whatever is necessary to survive the disease.

  3. 3.

    Distrust of research: A history of unethical research has created distrust among Indigenous people. For example, in the USA, members of the Havasupai Tribe consented to blood sampling to understand a genetic link to type 2 diabetes. Years later, participants learned that these blood samples had been shared, without their consent, with other researchers to study other diseases [10, 11].

  4. 4.

    Lack of consideration for cultural aspects of Indigenous life:

    1. (a)

      Indigenous people may perceive health differently from non-Indigenous people and may have different perceptions of health and wellbeing that are conceptualized through beliefs about life, land, and community.

    2. (b)

      Many Indigenous people have limited or no awareness and understanding of cancer and clinical trials.

    3. (c)

      Indigenous people within and across countries speak many Indigenous languages and dialects [12, 13]. Creating information materials in all the Indigenous languages spoken in the world is not feasible. Similarly, each Indigenous culture has its own icons and symbols, with unique connotations, and these cannot be simply dropped into materials in an attempt to be inclusive.

    4. (d)

      Communication gaps are most pronounced in remote areas, where cultural and linguistic differences are the greatest. Language and culture are closely related, amplifying these gaps [14].

  5. 5.

    Trial information is often in medical language: Trial materials, especially informed consent, are often long and complex. If information is not communicated in an understandable way, or if physicians explain options too quickly or using unfamiliar language, patients are more likely to say no.

  6. 6.

    Demands or costs of participation can limit access: Trial participants may face challenges related to costs (e.g., time off work, fees), transport difficulties (magnified by increased distance from trial sites), and support requirements (emotional or physical). Due to these factors, clinical trial participation may not be feasible even for those who want to participate.

  7. 7.

    Systemic barriers:

    1. (a)

      There are often insufficient trials for cancers common among Indigenous people.

    2. (b)

      Few Indigenous people are involved in the development, implementation, and analysis of cancer clinical trial research.

    3. (c)

      Non-Indigenous methodologies ignore Indigenous cultures and strengths, contributing to inequities and low clinical trial participation. There often are insufficient Indigenous healthcare staff to help bridge this problem.

    4. (d)

      Large clinical trials may take 10 years or longer before findings are available. While participants are not expected to personally benefit from participation, they need to be informed of the findings.

    5. (e)

      Strict inclusion and exclusion criteria can create barriers to Indigenous participation. Indigenous peoples are over-represented in adverse health conditions and chronic diseases which may lead to clinical trial ineligibility [15].

    6. (f)

      Funding is frequently limited to specific trial activities and may not extend to activities such as hosting meetings to enable partnerships and establish trust with Indigenous communities.

    7. (g)

      Many clinical trials are based in universities and hospitals, which may not be safe spaces for Indigenous peoples.

  8. 8.

    Poor recruitment and retention strategies: Many trials recruit participants using advertisements in traditional media or social media and these rarely result in Indigenous people requesting information. Face-to-face discussions are most appropriate for recruiting Indigenous peoples to clinical trials.

  9. 9.

    Language and communication barriers: Many words integral to clinical trials can alienate and/or confuse potential clinical trial participants. Some Indigenous participants may believe they will receive the placebo and not the actual treatment. Time and effort are required to redress misconceptions. Researchers must take such communication needs seriously in order to avoid less-optimal healthcare outcomes, lack of trust and engagement with healthcare settings, and non-compliance with treatment plans [16].

  10. 10.

    Insufficient participation information: Researchers require more information concerning when, where, and how Indigenous peoples can participate in clinical trials, and why participants do not continue or are dropped from clinical trials.

Solutions and Key Components of Success

  1. 1.

    Overcome and address racism:

    1. (a)

      Treat patients with dignity, respect, and value; this will lead to further positive engagement with services.

    2. (b)

      Build trusting relationships with Indigenous communities and services.

    3. (c)

      Involve Indigenous people in leadership and decision-making roles.

    4. (d)

      Involve staff, providers, Indigenous leaders, communities, and families in identifying problems and co-designing solutions, including system-wide modifications.

  2. 2.

    Improve communication [17]:

    1. (a)

      Utilize medical and cultural interpreters.

    2. (b)

      Use diagrams and illustrations.

    3. (c)

      Demonstrate procedures first where possible.

    4. (d)

      Use plain language and avoid idioms.

    5. (e)

      Allow extra time for Indigenous patients to respond or tell their stories.

    6. (f)

      Seek culturally meaningful analogies that make sense within the patient’s lived experience and worldview.

  3. 3.

    Recruitment and retention:

    1. (a)

      Re-examine recruitment and retention protocols.

    2. (b)

      Ensure inclusion of Indigenous populations.

    3. (c)

      Create programs such as Walking Forward to guide recruitment and retention.

    4. (d)

      Design trials with more time and increased resources to engage Indigenous communities.

    5. (e)

      Conduct trials in regional and remote locations. Bringing clinical trials to the community (rather than the community to the trial) will increase awareness and understanding.

  4. 4.

    Navigation: Employ trained patient navigators to work with patients and clinical trial recruiters. Indigenous navigators support in-person, one-on-one contact; can discuss clinical trials with patients and families; and support patients throughout their participation. They can help to bridge the gap between services and patients/families [18].

  5. 5.

    Community engagement and partnerships: Strong community engagement and Indigenous leadership are key components of success. Trusting partnerships need to be established and supported across countries, states, Tribal nations, and Indigenous organizations.

  6. 6.

    Education, materials, and resources: Quality resources can create meaningful local analogies that support depth of meaning and build cancer and clinical trial literacy in ways that are meaningful to patients’ lived experiences. Education activities should focus on:

    1. (a)

      Improving the health literacy of individuals and their communities.

    2. (b)

      Communicating specific clinical trial recruitment resources and the value of participation.

    3. (c)

      Collaborating with others to develop specific and relevant resources.

    4. (d)

      Providing presentations for staff at health facilities and for communities, starting small and local, and expanding.

    5. (e)

      Drawing on successful programs such as Clinical Trials Education for Native Americans (designed to help Indigenous cancer patients and their families make informed choices about clinical trial participation) [19] and materials such as those available on the Psycho-Oncology Co-operative Research Group website (https://www.pocog.org.au/).

    6. (f)

      Sharing resources and services and updating them to meet patient and family needs.

Conclusion

Indigenous participation in clinical trials is important, and researchers need to implement specific strategies to ensure Indigenous peoples are represented in trials. Achieving this requires trust, engagement, commitment to genuine partnerships, and willingness to understand people and their communities. Most importantly, it requires time and commitment to work in culturally appropriate and sensitive ways and a workforce dedicated to ensuring that Indigenous peoples are fully represented in clinical trials.