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Abstract

Objective

Quantify recruitment of Native Hawaiian and Pacific Islander (NHPI) participants from 22 Alzheimer's disease (AD) clinical trials over 5 years and utilize choropleth maps as a visual tool to identify where in the Hawaiian community recruited participants are located in order to better inform future recruitment efforts and improve equity and population diversity for future AD clinical trials.

Methods

A retrospective chart review was conducted at a dual-site origin clinical trial center in Hawai‘i. Inclusion criteria were a diagnosis of mild cognitive impairment and participation in one or more AD clinical trials conducted between 2020 and 2024. Demographic information of clinical trial participants was collected via chart review and included self-identified race/ethnicity, age, residence, and number of clinical trials the patient has participated in. Clinical trial participants were categorized by ZIP codes established by the US Census Bureau. Differences across race/ethnicity groups were assessed using either Pearson's Chi-squared test or Fisher's exact test.

Results

A total of 244 patients participated across the state of Hawai‘i in 22 AD clinical trials between 2020 and 2024. Of this total, 169 (69%) patients provided their race/ethnicity, and 75 (31%) did not provide their race/ethnicity. White patients had the highest percentage of participation (44%), followed by Asian patients (34%) and NHPI patients (15%). The population distribution visualized in this study's choropleth maps suggests that NHPI were under-recruited from the west side of O‘ahu.

Conclusions

Our retrospective study applied choropleth maps to visualize the recruitment data and patterns of AD clinical trials. By utilizing choropleth maps to analyze recruitment areas, the NHPI community and other underrepresented populations may benefit from targeted, culturally informed recruitment strategies.

Keywords

Alzheimer's disease clinical trials Native Hawaiians and Pacific Islanders choropleth maps recruitment strategies

Introduction

Alzheimer's disease (AD) is a neurocognitive disorder that continues to increase in prevalence worldwide.^1,2 As of 1 January 2024, the US National Library of Medicine clinical research registry, ClinicalTrials.gov, reported 164 clinical trials assessing 127 medications for AD (targeting the three stages: preclinical AD, mild cognitive impairment (MCI) due to AD, and Alzheimer's dementia), with 76% of the drugs as disease-modifying treatments.³ In addition, there are currently 427 AD clinical trials focusing on nonpharmacological treatments (e.g. exercise and neurostimulation), dementia care and caregiving, understanding disease processes, diagnostic tools, assessments, imaging studies, and treatments for neuropsychiatric symptoms.⁴

Native Hawaiian and Pacific Islanders (NHPI) are persons with origins from Hawaii, Guam, American Samoa, Fiji, the Marshall Islands, or other Pacific Islands. According to the State of Hawaii, there were 310,789 Native Hawaiians, 37,223 Samoans, 36,475 Micronesians, and 10,457 Tongans living in Hawaii in 2021.⁵ Other Pacific Islanders were not quantified. The number of people who identified as Asian was 987,423, White was 615,223, African American was 53,159, and American Indian or Alaskan Native was 34,910.⁵ Micronesians comprised the largest Pacific Islander population to have limited English proficiency within their race group (33.2%), followed by Tongan at 15.1%, Samoan at 9.3%, and Native Hawaiians at 2.1%.⁵ Among the ethnicities studied, Pacific Islanders earned the least, with 14% to 31% living in poverty, while Native Hawaiians earned below the median annual income of $41,200 with 12% living in poverty.⁵

The NHPI population has been found to have the highest proportion and youngest age of AD diagnosis.⁶ They are further characterized by the highest prevalence of hypertension, hyperlipidemia, and diabetes mellitus type II, comorbidities that serve as risk factors for AD.⁶ Various studies have observed that NHPI are underrepresented not only in clinical trials but also in AD clinical trials, despite their high prevalence of AD and comorbidities linked to AD.^7–9 Recent clinical trials for Donanemab and Lecanemab, two anti-amyloid monoclonal antibody therapies for AD, either did not report NHPI participation or excluded NHPI participants from their report due to the small number of participants.^8,9 Ethnic diversity in clinical trial research is necessary to reduce under inclusion, increase validity and generalizability of results, and improve the safety and effectiveness of medicine across diverse populations.⁷^10–13

The lack of information on clinical trials, difficulty coordinating transportation, and socioeconomic factors—geographic isolation, poverty, time, and opportunity costs—all serve as barriers to NHPI participation in clinical trials.^14,15 Previous studies have explored various methods to improve recruitment of these underrepresented populations (URPs). Establishing localized outreach, such as on-site, in-person clinics or screening events, has proven effective in improving URP recruitment and is suggested as a strategy to achieve adequate inclusion of the NHPI population in research.^7,10,14,15 Other potentially effective recruitment methods have included culturally informed social media advertisements, remuneration offers, and forms of community-engaged research.^7,^11–13 The implementation of these strategies into future AD clinical trials may help overcome the abovementioned barriers and increase NHPI participation. However, first understanding where current recruitment efforts are focused relative to the targeted population distribution is essential to determining where purposeful and culturally informed recruitment strategies could be directed.

We suggest that data visualization tools, such as choropleth maps, can be used to understand recruitment patterns in clinical trials by providing an at-a-glance map of various population densities. Visualization tools can simplify complex information into understandable data and recognizable patterns, which can aid in decision making.^16,17 For example, studies have used choropleth maps to analyze distribution of diseases and uncover associated risk factors.^18,19 Another study explored the use of geographic visualization to find and analyze the distribution of clinical trial recruitment sites.²⁰ In this retrospective study, we quantified recruitment of NHPI participants from 22 AD clinical trials over 5 years in Hawaii and utilized choropleth maps to compare participant location and population density. We propose that ZIP code-based choropleth maps may better inform future recruitment efforts and improve equity and population diversity, including NHPI inclusion and representation, for future AD clinical trials.

Methods

A retrospective chart review was conducted at Hawai‘i Pacific Neuroscience, a dual-site origin clinical trial center in Hawai‘i, where the main outpatient neurology referral site with a dedicated memory clinic is in Honolulu (96817) and a secondary outpatient clinic is in Waipahu (96797). The Honolulu site in focus is a major clinical research center for the Pacific region and serves a large and diverse population with patients drawn from across O‘ahu and other Hawaiian islands, which further served to potentially reduce bias. Inclusion criteria for this study were a diagnosis of MCI (ICD-10-G31.84) and participation in one or more of 22 AD clinical trials conducted between 2020 and 2024. Eligibility criteria for each of the 22 clinical trials can be found at the end of this manuscript as Supplemental Table 1.

Demographic information of clinical trial participants was collected via chart review and included self-identified race/ethnicity, age, alcohol use, site of residence, and number of clinical trials the patient has participated in. Those who self-identified as either Native Hawaiian or Pacific Islander in their medical records were categorized as “NHPI.” Those who self-identified as Asian or White were categorized as “Asian” and “White,” respectively. Those who self-identified as Black, Native American, Alaska Native, or Hispanic were defined as “Other.” Note that those with more than one race/ethnicity were categorized as only one race/ethnicity in the following priority: NHPI → Asian → Other → White. Thus, the NHPI, Asian, and Other groups may include mixed-race individuals (e.g. NHPI/White and NHPI/Asian), while the White group does not include mixed-race individuals. All patient details have been de-identified.

The clinical trial participants were categorized by ZIP Code Tabulation Areas (ZCTAs) established officially by the US Census Bureau, further potentially reducing bias. Clinical trial participant data were organized by location and race/ethnicity. Relative proportions were calculated for the following: NHPI participants and all participants of one area (percentage of recruited population that was NHPI), NHPI participants and overall NHPI population for the same area (NHPI recruited vs total NHPI in area), and overall NHPI and total population for a specific area (percentage populational constitution of NHPI). The demographics of the general population (e.g. median household income, education level, and population that was 55 years and older) of each ZIP code on O‘ahu were obtained from the US Census Bureau website, Census.gov, by searching “ZCTA5” with the corresponding ZIP code. ZIP code choropleth maps were then generated via Microsoft Excel and used to depict the distribution of the general population of O‘ahu and study participation by race in the AD clinical trials. A color scale was used to represent population density, from black to white, indicating high population density to low population density, respectively.

The study was approved by the University of Hawai‘i Institutional Review Board and classified as exempt research. The study was conducted in accordance with the Helsinki Declaration of 1975 as revised in 2024. The reporting of this study conforms to STROBE guidelines.²¹

Statistical analysis

Descriptive statistics were used to summarize patient characteristics. Categorical variables were reported as frequencies and percentages. Differences across race/ethnicity groups were assessed using either Pearson's Chi-squared test or Fisher's exact test, as appropriate. Statistical significance was defined as a two-sided p-value < 0.05. All analyses were conducted using R version 4.4.2.

Literature review

Literature review was conducted with employment of Google, university library resources, as well as artificial intelligence tool Elicit. Zotero was used for creating the references section.

Results

A total of 244 patients participated across the state of Hawai‘i in 22 AD clinical trials between 2020 and 2024 at the dual-site origin clinical trial center. Of this total, 169 (69%) patients provided their race/ethnicity and 75 (31%) did not provide their race/ethnicity. White patients had the highest percentage of participation (44%, 75 participants), followed by Asian patients (34%, 58 participants) and NHPI patients (15%, 25 participants). These patients participated in up to 6 of these 22 AD clinical trials. White participants appeared to participate more frequently than other race/ethnicity groups.

Of the 169 participants who provided their race/ethnicity, 142 participants (84%) resided on O‘ahu, 3 participants (2%) resided on Kaua‘i, 8 participants (5%) resided on Maui, and 16 participants (9%) resided on the Island of Hawai‘i. Since the majority of the study population resided on O‘ahu, this retrospective study will focus on analyzing the patient population from O‘ahu. Of the study population on O‘ahu, 57 participants reported as White (40%), 53 participants reported as Asian (37%), 21 participants reported as NHPI (15%), and 11 participants reported as Other (8%). The Kaneohe/Kailua resident area (encompassing ZIP codes 96744, 96730, 96863, 96734, and 96795) had the highest recruitment of 45 participants (32%). The ZIP codes 96797 and 96706 did not have much recruitment even though the United States Census Bureau indicates that O‘ahu's biggest populations reside in said ZIP codes. The full characterization of the patient demographics can be seen on Table 1.

Table 1.

Characterization by county and residential area of participants in AD clinical trials between 2020 and 2024.

Characteristics	Overall n = 169*	NHPI n = 25 (15%)*	White n = 75 (44%)*	Asian n = 58 (34%)*	Other n = 11 (6.5%)*	p-value**
County						0.3
Honolulu	142 (84.0%)	21 (84.0%)	57 (76.0%)	53 (91.4%)	11 (100.0%)
Hawaii	16 (9.5%)	2 (8.0%)	12 (16.0%)	2 (3.4%)	0 (0.0%)
Maui	8 (4.7%)	2 (8.0%)	4 (5.3%)	2 (3.4%)	0 (0.0%)
Kauai	3 (1.8%)	0 (0.0%)	2 (2.7%)	1 (1.7%)	0 (0.0%)
Residential area						<0.001
Central Honolulu	30 (17.8%)	2 (8.0%)	18 (24.0%)	9 (15.5%)	1 (9.1%)
East Honolulu	20 (11.8%)	4 (16.0%)	12 (16.0%)	3 (5.2%)	1 (9.1%)
Kaneohe/Kailua	45 (26.6%)	8 (32.0%)	20 (26.7%)	14 (24.1%)	3 (27.3%)
Pearl City/Aiea	12 (7.1%)	0 (0.0%)	2 (2.7%)	9 (15.5%)	1 (9.1%)
North Shore	5 (3.0%)	0 (0.0%)	2 (2.7%)	3 (5.2%)	0 (0.0%)
Ewa	8 (4.7%)	1 (4.0%)	1 (1.3%)	4 (6.9%)	2 (18.2%)
West Honolulu	18 (10.7%)	4 (16.0%)	2 (2.7%)	11 (19.0%)	1 (9.1%)
Waianae	4 (2.4%)	2 (8.0%)	0 (0.0%)	0 (0.0%)	2 (18.2%)
Hilo/North Hawaii	5 (3.0%)	0 (0.0%)	4 (5.3%)	1 (1.7%)	0 (0.0%)
Kona	9 (5.3%)	1 (4.0%)	7 (9.3%)	1 (1.7%)	0 (0.0%)
South Hawaii	2 (1.2%)	1 (4.0%)	1 (1.3%)	0 (0.0%)	0 (0.0%)
Molokai/Lanai/East Maui	4 (2.4%)	2 (8.0%)	1 (1.3%)	1 (1.7%)	0 (0.0%)
West & Central Maui	4 (2.4%)	0 (0.0%)	3 (4.0%)	1 (1.7%)	0 (0.0%)
East Kauai	1 (0.6%)	0 (0.0%)	0 (0.0%)	1 (1.7%)	0 (0.0%)
North & West Kauai	2 (1.2%)	0 (0.0%)	2 (2.7%)	0 (0.0%)	0 (0.0%)

*Mean (SD); n (%); Median (Q1, Q3).

**One-way analysis of means; Fisher's Exact Test for Count Data with simulated p-value (based on 2000 replicates); Pearson's Chi-squared test; Fisher's exact test; Kruskal–Wallis rank sum test.

AD: Alzheimer's disease; NHPI: Native Hawaiian and Pacific Islander.

The majority of NHPI resided in ZIP code 96792 (Waianae), while most of the NHPI participants came from ZIP code 96817 (Honolulu). Breakdown of residential areas of NHPI participants can be seen in Table 2. As visualized by the choropleth maps, White and NHPI had different patterns of recruitment to AD clinical trials. Substantially more NHPI patients enrolled from the eastern and western side of O‘ahu, while substantially more white participants enrolled from central and eastern regions of O‘ahu (Table 1).

Table 2.

Comparison of income, education, number of NHPI participants, and the relative percentages of NHPI participants and population by ZIP code from O‘ahu.

ZIP code	Median income	Education(bachelor's or higher)	Population that is 55 and older	Number of NHPI participants recruited	Percentage of recruited population that was NHPI*	Percentage populational constitution of NHPI**	NHPI recruited vs total NHPI in area***
96825 (Honolulu)	$149,757	59.50%	40.35%	1	10.00%	2.97%	0.11%
96730 (Kaaawa)	$112,237	56.20%	22.35%	1	100.00%	13.89%	0.45%
96734 (Kailua)	$131,554	53.40%	30.44%	2	8.70%	5.19%	0.08%
96816 (Honolulu)	$114,744	48.10%	37.88%	3	21.43%	7.45%	0.08%
96815 (Honolulu)	$75,020	46.90%	37.33%	2	18.18%	3.62%	0.19%
96744 (Kaneohe)	$129,263	39.50%	37.80%	3	11.11%	9.98%	0.05%
96707 (Kapolei)	$121,409	33.80%	24.67%	1	25.00%	11.96%	0.02%
96817 (Honolulu)	$74,690	29.90%	37.23%	4	30.77%	12.06%	0.06%
96795 (Waimanalo)	$118,365	21.80%	28.34%	2	33.33%	36.25%	0.05%
96792 (Waianae)	$83,927	15.80%	23.86%	2	40.00%	31.29%	0.01%

*Percentage of recruited population that was NHPI: This value was calculated by dividing the number of NHPI participants recruited (column 5) by the total number of AD clinical trial participants from that ZIP code area.

**Percentage populational constitution of NHPI: This value was calculated by dividing the number of NHPI in the ZIP code compared to the total population in that ZIP code.

***NHPI recruited versus total NHPI in area: This value was calculated by dividing the number of NHPI participants recruited (column 5) by the total NHPI in the ZIP code area (according to US census bureau data).

AD: Alzheimer's disease; NHPI: Native Hawaiian and Pacific Islander.

Table 2 is a comparison of income, education, number of NHPI participants, and the relative percentages of NHPI participants and population by ZIP code from the island of Oahu. Table 2 shows the differences in median income in different ZIP codes, which can be used as a proxy for socioeconomic status of participants from that region. The Honolulu area comprises 36 ZIP codes, 4 of which are included in Table 2 as those 4 ZIP codes had NHPI representation. The 96825 Honolulu ZIP code has a relatively high median income of $149,757, while the 96817 Honolulu ZIP code has a relatively low median income of $74,690. The Honolulu ZIP code with higher median income has less NHPI participation at 10%, while the Honolulu ZIP code with lower median income had more NHPI participation at 30.77%.

The majority of the study population came from ZIP codes with a median household income above the state of Hawai‘i's median of $95,322. This is also true for the individual White, Asian, and NHPI racial groups. 64% of White, 67% of Asian, and 52% of NHPI participants (Table 2) in this study resided in ZIP codes where the median household income exceeded the state median. Participants in these AD clinical trials followed the general expectation that those who participate in clinical trials tend to be wealthier than average.²²

Figure 1(b) shows that Ewa Beach (96706) and Waipahu (96797) census-designated places (CDPs) have a high general population. However, most participants of the clinical trials resided in Kaneohe (96744) and Kailua (96734) CDPs. We found that the distribution of White clinical trial participants was qualitatively comparable to distribution of the general White population (Figure 1(c) and (d)). The overlay of NHPI population choropleth maps highlighted west O‘ahu (Waianae, Waipahu, Kapolei, and Ewa Beach) as an area of high general NHPI population residence but of low NHPI participant recruitment (Figure 1(e) and (f)). The calculated percentage of NHPI participants recruited in the trial, compared to the total population of NHPI, was 0.01% for the Waianae CDP (96792) and 0.02% for the Kapolei CDP (96707). These were the lowest percentages out of all the ZIP codes of the recruited NHPI population.

Figure 1.

O‘ahu choropleth maps by ZIP code of (a) total participants (n = 142) who provided race/ethnicity in the AD clinical trials, (b) total population (all races), (c) White participants (n = 57) in the AD clinical trials, (d) the total White population, (e) NHPI participants (n = 21) in the AD clinical trials, and (f) the total NHPI population. AD: Alzheimer's disease; NHPI: Native Hawaiian and Pacific Islander.

Discussion

To better assess current NHPI study participation and determine future target areas for recruitment, we conducted a retrospective study on NHPI participation in 22 AD clinical trials between 2020 and 2024 from an O‘ahu memory clinic. We then created ZIP code-based choropleth maps of the total, White, and NHPI participants’ residences to visualize and compare population densities. Only patient data from O‘ahu was used to create choropleth maps, based on the factors that the research center was located on O‘ahu and 84% of the participant population were from O‘ahu (Table 1). ZIP code choropleth maps provided valuable insight; beyond identifying the location of participants in relation to location of AD clinical trials. They can directly inform and enhance future recruitment strategies for all types of clinical trials. The following discusses the potential application of this information, as summarized in Table 3.

Table 3.

Summary table: How choropleth map insights inform recruitment.

Insight from choropleth maps	Actionable recruitment strategy
High-density participant areas	Focus outreach/events in these locations
Low-density participant (“whitespace”) areas	Increase targeted outreach or address barriers
Proximity to research center	Temporary satellite locations or mobile unitsFree transportation
Demographic clusters by ZIP code	Tailor messages to specific communitiesCulturally informed digital campaigns/social media advertisements
Patterns of recruitment	Continue use of effective strategiesInnovate new techniques when current strategies are ineffectiveDetermine future target locations to achieve equitable representation

Improve diversity and reach

The NHPI population constitutes about 26% of the population on the island of O‘ahu.^5,23 Despite this, NHPI participants constituted 15% of the AD clinical trial population at our site. This aligns with previous research, in which NHPI were less likely to participate in clinical trials.^19,20 Understanding the underlying reasons for these discrepancies in clinical trial participation between different races is critical to obtaining reliable and generalizable results and ensuring equitable representation of minority populations. This allows for culturally appropriate and effective application, which is especially necessary for URPs, such as NHPI who experience existing health disparities and a disproportionate burden of dementia.⁶ Participating in community engagement and relationships is a strategy to increase the representation of URPs in clinical trials.¹¹ In the future, Hawai‘i Pacific Neuroscience can consider establishing a research team to investigate the community's needs and collaborate with community organizations, leaders, and members in ZIP codes with a high NHPI population. For example, approximately 28% of O‘ahu's older adults speak a foreign language at home.²³ Community organizations and leaders can be educated and tasked with passing on the importance and availability of clinical trials to older adults who do not speak English. Clinical trial advertisements can also be tailored to target corresponding NHPI languages—that is, Kalihi (96819), which has a large concentration of Tongan and Samoan populations.

Successful strategies

Previous research on cancer clinical trials in Hawaii has demonstrated success with recruiting NHPI along with other ethnic minorities. A research team at the University of Hawaii Cancer Center (UHCC) found that Asian and Native Hawaiian minority patients are enrolled at a similar or higher rate than Whites in their analysis of cancer patients.²⁴ UHCC had three main strategies that increased NHPI and minority recruitment to cancer clinical trials. The first strategy was to involve and hire minority healthcare providers and research staff. The second strategy was to provide minority patients with the same clinical trial opportunities as Whites. The third strategy was to obtain funding to specifically enhance recruitment of minorities. These three strategies can be practically implemented at Hawaii Pacific Neuroscience to aid in recruitment of NHPI in AD clinical trials.

Targeting recruitment efforts and expanding geographic coverage

Analysis and overlay of our choropleth maps highlight contrasting distributions among participant populations. CDPs with the highest clinical trial recruitment levels did not correspond to zip code level population density. This may be due to certain CDPs being in close vicinity to the main clinical trial center located in Honolulu (96817), which suggests that proximity to the research center is a strong driver of participation. This was also true for NHPI, where ZIP code 96817 had the highest NHPI recruitment for the clinical trials. NHPI participation in these AD clinical trials supports the findings that clinical trial engagement depends more on characteristics of the trial, such as site location, than the attitudes of the American minority populations.⁷ Thus, future outreach can be focused in the same or nearby areas of research centers for efficient recruitment. For instance, Hawai‘i Pacific Neuroscience should continue to participate in community events, such as the Walk to End Alzheimer's in ZIP code 96815, to recruit participants for AD clinical trials. However, it is still important to seek enrollment of patients from both urban and rural areas, that may be further from the clinical site, to protect the generalizability of results.²⁵ Although maintaining contact with patients who live away from a recruitment site, including rural areas, can be challenging, there are strategies to maintain contact. For example, previous clinical trials have provided telehealth opportunities which reduces the need for in person visits.²⁶ Previous research shows that distance between patient and trial site was an independent predictor of missed in-person visits but not with adherence to study treatment or preventive care.²⁵ Therefore, Hawaii Pacific Neuroscience could explore the possibility of “site-less” clinical trials conducted through telehealth. Such clinical trials could improve recruitment of NHPI who live in rural areas like the neighboring Hawaii islands.

The choropleth maps also revealed geographic “whitespaces”—areas with low or no participant density. These gaps can highlight communities that may have been overlooked or face barriers to participation, guiding recruiters to direct additional resources or tailored outreach to those regions. By identifying and acting on areas with low participation, researchers can broaden the geographic diversity of the sample, strengthening the generalizability of the research. For example, Hawai‘i Pacific Neuroscience can allocate additional resources to their West O‘ahu office to increase accessibility and thus recruitment from that location. Another possibility is to provide free transportation to potential patients from west O‘ahu or set up temporary research clinics that may address a barrier from areas distant from the trial center.

Optimize resource allocation and strategic planning for future studies

Knowing where recruitment is most effective allows trials to concentrate resources (e.g. advertising, community engagement, and event hosting) in high-yield areas, while also experimenting with new strategies in underrepresented ZIP codes. Future recruitment for White participants can be concentrated in Kailua and Kaneohe for an increased chance of success. Results further suggest that NHPI participants were under-recruited in West O‘ahu. New strategies should be thought of to improve future recruitment efforts for NHPI in the western area of O‘ahu. Overall, choropleth maps may suggest target locations for digital campaigns and in-person events or clinics to maximize accessibility for target populations that lead to better recruitment.

Long-term outreach

Choropleth maps are a helpful tool in providing an at-a-glance visualization of data, such as population density, which allows analysis and comparison of these choropleth maps to reveal patterns and direct actionable strategies.^16,17 Tracking changes with successive choropleth maps over time can reveal trends in participation, helping clinical researchers refine recruitment strategies for future studies or ongoing programs. By creating updated choropleth maps after implementing new recruitment strategies in target locations directed by prior analysis, researchers can assess the efficacy of their efforts and determine whether different strategies are needed or other locations should be the focus of culturally informed recruitment strategies. Further research would help to better understand the long-term utility of implementing choropleth maps in the ongoing improvement of clinical trials to achieve equitable participation.

While it is possible that certain clinical trials might be appealing to one particular group over another, review of the protocols offered indicates that the major eligibility factors—such as diagnosis of mild cognitive impairment, age range, and key safety exclusions—were broadly similar between studies and aligned with established standards in the field. Importantly, none of the trials employed selection criteria that would systematically favor or disadvantage recruitment from any particular racial or ethnic group. Requirements for participation, such as language proficiency, residency, or technological access, were uniform and did not selectively enhance or limit the attractiveness of these studies for specific populations. As a result, any differences observed in rates of participation or representation across racial and ethnic groups are unlikely to be attributable to the structure of the eligibility criteria themselves, but rather reflect broader community and sociodemographic factors. The inclusion and exclusion criteria for all 22 AD clinical trials analyzed in this study are summarized in Supplemental Table 1, while a summary of eligibility criteria is included in Table 4.

Table 4.

Summary of eligibility criteria for the 22 clinical trials.

Trials	Common inclusion criteria	Common exclusion criteria	Differences (generic)
DAYBREAK I8D-MC-AZET, ITI-007-201, CREAD 2, GENERATIONS 2, ADVANCE AXS-05-AD-301, MISSIONAD2, CLARITY AD BAN, 243HV101, 20-AVP-786-306, ANVS-12003, LIFT-AD ATH-1017-AD-0201, Evoke + NN6535-4725, Evoke NN6535-4730, Cyclerion C6463-202, PIONEER, AXS-05-AD-302, CELIA 247AD201,ENVISION 221AD305, ANVS-22002, PRX012-101, PRX012-103, Lightwave	Probable AD dementia or MCI due to AD per NIA-AA criteria	Other neurological diseases impacting cognition (e.g. Parkinson's, stroke, frontotemporal dementia)	Specific cardiac, genetic, or psychiatric exclusions vary (e.g. QT prolongation, APOE4 genetic risk disclosure)
	MMSE or cognitive scores consistent with mild to moderate impairment (usually ∼18–30)	Other neurological diseases impacting cognition (e.g. Parkinson's, stroke, frontotemporal dementia)	Variations in cognitive score cutoffs
	Biomarker evidence of amyloid pathology (PET/CSF)	Contraindications for MRI or lumbar puncture or abnormal MRI unrelated to AD	Treatment-naïve vs stable medication requirements
	Age usually between ∼50 and 90	Recent cancer history (3–5 years)	Some trials include agitation or neuropsychiatric symptom focus
	Availability of reliable study partner or caregiver	Substance abuse or suicidal ideation/behavior in recent months	Differences in additional recruitment criteria such as formal education or BMI or caregiver involvement
	Stable AD symptomatic treatment if applicable	Recent enrollment in other clinical trials	Differences in imaging or biomarker confirmation methods

AD: Alzheimer's disease; BMI: body mass index; CSF: cerebrospinal fluid; MCI: mild cognitive impairment; MMSE: Mini-Mental State Examination; MRI: magnetic resonance imaging; PET: positron emission tomography.

Limitations

This work had certain limitations. ZIP codes were used as a proxy for education and socioeconomic status. There is a possibility that the actual education and socioeconomic status of the individual coming from a ZIP code may differ from the average status of individuals coming from the same ZIP code. Also, the age distribution across the NHPI population in each ZIP code was not reflected in the choropleth maps used in this retrospective study, because the US Census Bureau analyzes the age distribution and ethnic composition of ZIP codes as distinct categories. Since AD becomes more prevalent with age progression, the assumption of normal age distribution may have affected the representative amount of recruitable NHPI individuals in each ZIP code.^1,27 For example, a ZIP code area with a small proportion of older adults relative to younger individuals would likely have less AD prevalence. Another limitation is that 75 patients out of the 244 clinical trial participants (31%) did not provide either their ethnicity or residency ZIP code, which potentially affected the patient population distribution in the choropleth maps. For example, if the reporting of racial and ethnic data varied by different racial and ethnic groups, the true participation rates of some groups may be inaccurately reflected on the choropleth maps. Additionally, the variable eligibility criteria in the 22 AD clinical trials may have also directly impacted participation of different races/ethnicities.

Conclusion and future directions

Our retrospective study applied choropleth maps to visualize the recruitment data and patterns of AD clinical trials on O‘ahu. The population distribution visualized in this study's choropleth maps may demonstrate that NHPI were under-recruited from the west side of O‘ahu, suggesting a possible area of focus for NHPI recruitment for future AD clinical trials. Taira et al. suggested that access to local, in-person clinical trial sites in NHPI-dense communities may improve NHPI recruitment.⁷ However, as this study suggests, under-inclusion of NHPI persists despite the presence of a local, in-person clinical trial site on O‘ahu. By utilizing choropleth maps to analyze recruitment areas, the NHPI community and other URPs may benefit from targeted, culturally informed recruitment strategies.^7,11 Future studies exploring the application of other culturally informed, community-engaged research strategies are needed to determine whether or not there are factors beyond lack of adequate information creating barriers to clinical trial participation for URPs.

Supplemental Material

sj-docx-1-sci-10.1177_00368504251411203 - Supplemental material for Utilizing ZIP code-based choropleth maps as a visual tool to analyze Native Hawaiian and Pacific Islander (NHPI) recruitment patterns in Alzheimer's disease clinical trials in Hawai‘i: A retrospective study

Supplemental material, sj-docx-1-sci-10.1177_00368504251411203 for Utilizing ZIP code-based choropleth maps as a visual tool to analyze Native Hawaiian and Pacific Islander (NHPI) recruitment patterns in Alzheimer's disease clinical trials in Hawai‘i: A retrospective study by Matthew Kobylinski, Nina Krupa, Hollis Tam, Linda Nguyen, Julia R Jahansooz, Kylie Herndon, Kaelyn Pacpaco, Masako Matsunaga, Samuel Toh Kim, Qi Zhi, Michael Sonson, Chathura Siriwardhana, Enrique Carrazana and Kore Liow in Science Progress

Supplemental Material

sj-pdf-2-sci-10.1177_00368504251411203 - Supplemental material for Utilizing ZIP code-based choropleth maps as a visual tool to analyze Native Hawaiian and Pacific Islander (NHPI) recruitment patterns in Alzheimer's disease clinical trials in Hawai‘i: A retrospective study

Supplemental material, sj-pdf-2-sci-10.1177_00368504251411203 for Utilizing ZIP code-based choropleth maps as a visual tool to analyze Native Hawaiian and Pacific Islander (NHPI) recruitment patterns in Alzheimer's disease clinical trials in Hawai‘i: A retrospective study by Matthew Kobylinski, Nina Krupa, Hollis Tam, Linda Nguyen, Julia R Jahansooz, Kylie Herndon, Kaelyn Pacpaco, Masako Matsunaga, Samuel Toh Kim, Qi Zhi, Michael Sonson, Chathura Siriwardhana, Enrique Carrazana and Kore Liow in Science Progress

Supplemental Material

sj-pdf-4-sci-10.1177_00368504251411203 - Supplemental material for Utilizing ZIP code-based choropleth maps as a visual tool to analyze Native Hawaiian and Pacific Islander (NHPI) recruitment patterns in Alzheimer's disease clinical trials in Hawai‘i: A retrospective study

Supplemental material, sj-pdf-4-sci-10.1177_00368504251411203 for Utilizing ZIP code-based choropleth maps as a visual tool to analyze Native Hawaiian and Pacific Islander (NHPI) recruitment patterns in Alzheimer's disease clinical trials in Hawai‘i: A retrospective study by Matthew Kobylinski, Nina Krupa, Hollis Tam, Linda Nguyen, Julia R Jahansooz, Kylie Herndon, Kaelyn Pacpaco, Masako Matsunaga, Samuel Toh Kim, Qi Zhi, Michael Sonson, Chathura Siriwardhana, Enrique Carrazana and Kore Liow in Science Progress

Footnotes

ORCID iDs

Matthew Kobylinski

Nina Krupa

Hollis Tam

Linda Nguyen

Samuel Toh Kim

Chathura Siriwardhana

Ethics approval

Our institution does not require ethical approval for reporting individual cases or case series.

Informed consent

Informed consent for patient information to be published in this article was not obtained because this was a retrospective study.

Author contributions

MK contributed to writing of manuscript, revisions, and generating choropleth maps. NK contributed to data collection, data analysis, writing of manuscript, revisions, and generation of choropleth maps. HT contributed to data analysis, writing of manuscript, and revisions. LN contributed to generation of choropleth maps and data tables, writing of manuscript, and revisions. JJ, QZ, MS, CS, EC, and KL contributed to writing of manuscript. KH, KP, and STK contributed to data collection. MM conducted statistical analysis and contributed to writing of manuscript.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The analytical work of this project was partially supported by the JABSOM Office of the Dean; U54MD007601 (Ola HAWAII) from the National Institutes of Health (NIH); and U54GM138062 (PIKO) from the NIH’s National Institute of General Medical Sciences (NIGMS). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or NIGMS.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Data availability statement

The data that support the findings of this study are available from the corresponding author on reasonable request.

Supplemental material

Supplemental material for this article is available online.

References

Alzheimer’s disease facts and figures. Alzheimers Dement 2023; 19: 1598–1695.

Langbaum

Zissimopoulos

, et al. Recommendations to address key recruitment challenges of Alzheimer’s disease clinical trials. Alzheimers Dement 2023; 19: 696–707.

Cummings

Zhou

Lee

, et al. Alzheimer’s disease drug development pipeline: 2024. Alzheimers Dement Transl Res Clin Interv 2024; 10: e12465.

NIA-Funded Active Alzheimer’s and Related Dementias Clinical Trials and Studies. National Institute on Aging. Accessed June 15, 2025. https://www.nia.nih.gov/research/ongoing-AD-trials.

Research and Economic Analysis Division (READ) of the Department of Business, Economic Development & Tourism (DBEDT), State of Hawaii. Demographic, Social, and Economic Characteristics of Hawaii’s Race Groups: 2017-2021, https://files.hawaii.gov/dbedt/economic/reports/Detailed-race-characteristics_ACS2021.pdf (May 2024, accessed 18 September 2025).

Smith

Van

Roberts

, et al. Disparities in Alzheimer disease and mild cognitive impairment among Native Hawaiians and Pacific Islanders. Cogn Behav Neurol 2021; 34: 200–206.

Taira

Ranken

Seto

, et al. Representation of Native Hawaiian and Pacific Islander individuals in clinical trials. JAMA Netw Open 2024; 7: e2442204.

Sims

Zimmer

Evans

, et al. Donanemab in early symptomatic Alzheimer disease: the TRAILBLAZER-ALZ 2 randomized clinical trial. JAMA 2023; 330: 512–527.

Grill

Flournoy

Dhadda

, et al. Eligibility rates among racially and ethnically diverse us participants in phase 2 and phase 3 placebo-controlled, double-blind, randomized trials of lecanemab and elenbecestat in early Alzheimer disease. Ann Neurol 2024; 95: 288–298.

10.

Varma

Jones

Oladele

, et al. Diversity in clinical research: public health and social justice imperatives. J Med Ethics 2023; 49: 200–203.

11.

Okonkwo

Rivera Mindt

Ashford

, et al. A protocol for the inclusion of minoritized persons in Alzheimer disease research from the ADNI3 diversity taskforce. JAMA Netw Open 2024; 7: e2427073.

12.

Smith

Porter

Biddle

, et al. The Arkansas minority barber and beauty shop health initiative: meeting people where they are. Prev Chronic Dis 2020; 17: 200277.

13.

Gabel

Denny

Llibre-Guerra

, et al. Remuneration and recruitment of study participants for AD cohort studies from the general public and from minority communities. Alzheimer Dis Assoc Disord 2023; 37: 107–112.

14.

Lee

Jahansooz

Guittu

, et al. Barriers to Alzheimer disease clinical trial participation in a minority population. Cogn Behav Neurol 2024; 37: 40–47.

15.

Benavente

Gimmen

Roberto

, et al. Oncology clinical trials and indigenous Native Hawaiian and other Pacific Islander erasure. In: Garvey

(ed.) Indigenous and tribal peoples and cancer. Springer Nature Switzerland, 2024, pp.343–347. doi:10.1007/978-3-031-56806-0_72

16.

Ofori

Lartey

Durneva

, et al. Visual communication of public health data: a scoping review. Front Digit Health 2025; 7: 1555231. Published 2025 Apr 24.

17.

Chishtie

Bielska

Barrera

, et al. Interactive visualization applications in population health and health services research: systematic scoping review. J Med Internet Res 2022; 24: e27534. PMID: 35179499; PMCID: PMC8900899.

18.

Nyadanu

Pereira

Nawumbeni

, et al. Geo-visual integration of health outcomes and risk factors using excess risk and conditioned choropleth maps: a case study of malaria incidence and sociodemographic determinants in Ghana. BMC Public Health 2019; 19: 514.

19.

Lin

Chen

Gong

, et al. Geographic distribution and epidemiology of lung cancer during 2011 in Zhejiang province of China. Asian Pac J Cancer Prev 2014; 15: 5299–5303.

20.

Luo

Chen

, et al. Systematic data ingratiation of clinical trial recruitment locations for geographic-based query and visualization. Int J Med Inform 2017; 108: 85–91.

21.

Von Elm

Altman

Egger

, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Ann Intern Med 2007; 147: 573–577.

22.

Kim

Florez

Botto

, et al. The influence of socioeconomic status on individual attitudes and experience with clinical trials. Commun Med (Lond) 2024; 4: 172.

23.

City and County of Honolulu. Four-year area plan on aging. The City and County of Honolulu’s Department of Community Services’ Elderly Affairs Division. https://www.honolulu.gov/dcs/wp-content/uploads/sites/24/2024/02/EAD-4-Year-Area-Plan.FINAL_.pdf (October 2023, accessed 15 June 2025).

24.

Acoba

Sumida

Berenberg

. Overcoming racial disparities in cancer clinical trial enrollment of Asians and Native Hawaiians. Contemp Clin Trials Commun 2022; 28: 100933. PMID: 36688088; PMCID: PMC9846448.

25.

Leira

Viscoli

Polgreen

, et al. Distance from home to research center: a barrier to in-person visits but not treatment adherence in a stroke trial. Neuroepidemiology 2018; 50: 137–143.

26.

Hilderbrand

Zangrilli

Stinson

. Decentralized clinical trial case study: five-stage process for recruiting and completing a site-less clinical study in less time and lower cost than traditional methods. Am J Health Res 2021; 9: 213–217.

27.

Brookmeyer

Gray

Kawas

. Projections of Alzheimer’s disease in the United States and the public health impact of delaying disease onset. Am J Public Health 1998; 88: 1337–1342.

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