A roadmap for improving representation in clinical trials

Abstract

Clinical trials continue to struggle with recruiting diverse participants that include historically underrepresented and minoritized patients, who are typically patients in non-white racial and ethnic groups and have low income (Medicaid). Enrolling diverse participants will benefit the health sciences by providing more generalizable findings. The Cancer Financial Experience project (CAFÉ) study sought to improve financial distress by providing financial navigation for newly diagnosed cancer patients, and intentionally recruited diverse participants. All diverse participants consented at slightly higher rates than non-diverse participants (21.3 % vs. 20.1 %). Spanish-speaking patients consented at a much higher rate than non-Spanish speakers (36.4 % vs. 20.2 % respectively). Here we discuss how we increased our recruitment of diverse participants. Obtaining diverse participation is achievable and will provide more meaningful findings.

1. Background

Lack of diverse participant representation in research trials is often a critical shortcoming of the clinical trial enterprise in the United State (U.S). Clinical trial participants should reflect the racial/ethnic, age, socioeconomic, sex/gender identity, disability, and other characteristics of the population with the underlying disease of interest. Yet, that is not the case, even though several federal agencies, including the National Institute of Health (NIH) and the Food and Drug Administration (FDA), have prioritized diversity in clinical trials [1]. An FDA summary report found that non-Hispanic whites composed 78% of participants enrolled in U.S. drug trials conducted between 2015 and 2019 [2]. Even though non-Hispanics whites represent less than 60% of the U.S. general population during this time interval.

A 2022 report from the National Academies of Sciences, Engineering, and Medicine (NASEM) notes that lack of representation from diverse populations may reduce the generalizability of research findings, hinder innovation, impede equitable access to new and effective interventions, contribute to health disparities, undermine trust in both medical research and the medical establishment, and cost society hundreds of billions of dollars [3].

Researchers commonly attribute under representation in clinical trials to mistrust, particularly among Black and Hispanic populations. Although there is no doubt that such mistrust exists—understandably so, given the history of abuses in medical research in these populations—mistrust alone does not explain the gaps in participation in clinical trials [3]. Patients, particularly those from under represented communities, may not participate due to other factors such as lack of trial awareness, lack of access to trials, and perceived discrimination and racism [4].

Regardless of race or ethnicity, patients may want to participate in clinical trials for many reasons that may outweigh their misgivings. These may include the assurance of receiving high-quality medical care, usually at reduced or no cost; the possibility of benefitting from an experimental treatment; and the desire to contribute to science and help others within their communities [5].

According to the NASEM report, investigators must approach recruitment of diverse populations with intentionality. This involves setting recruitment goals and considering access barriers for study participants in the research design, within appropriate infrastructure resources to support recruitment of participants in diverse settings. Flexibility in recruitment techniques, may include modifying patient identification to target diverse groups. Flexibility and data collection are also key to achieving diverse study enrollment and retention. It also is important to have a diverse study team, at all levels, including diverse leadership.

Enabling a culture of shared learning within the U.S. clinical trial infrastructure may help bridge the representation gap. With many clinical trials available across various diseases and conditions, it is imperative that researchers share successes in recruitment techniques and approaches that improve participation in underrepresented and minoritized individuals.

2. Methods

Cancer Financial Experience (CAFÉ) is a randomized controlled trial of a financial navigation intervention addressing cancer-related financial hardship among people newly diagnosed with cancer of any type (excluding nonmelanoma skin cancer) or stage (n = 371) at two integrated health systems that serve patients in the Pacific Northwest, U.S [6]. Cancer-related financial hardship is having to choose between paying for treatment or other household expenses, as cancer patients often face high out of pocket costs and reduction in income [7,8]. Financial hardship is associated with adverse health outcomes, including poor quality of life, treatment non-adherence, and lower survival. Communication about financial concerns and out-of-pocket (OOP) costs early in the treatment trajectory and in partnership with the care team, through patient navigation, could help to prevent or lessen financial hardship [[8], [9], [10]].

CAFÉ participants randomized to the intervention group received a written list of financial assistance resources plus 6 months of personalized outreach and assistance to address financial concerns. Participants randomized to the control group (enhanced usual care) received the written list of financial assistance resources that the intervention group participants received, but did not receive financial navigation.

When designing the CAFÉ trial, the study team made recruitment of a diverse study population a central goal. The team prioritized recruitment of diverse populations in what we call an equity-informed enrichment sampling of underrepresented populations, whereby Spanish-speaking individuals, people from racial or ethnic minoritized groups (i.e., non-White and/or Hispanic), and people with Medicaid insurance were oversampled. The study goal set a high goal of 50 % for the underrepresented sample, aiming to try to recruit at least of the study population from a historically under represented population.

3. Findings

At the conclusion of recruitment, the overall consent rate among the underrepresented sample patients (158/742 (21.3%) Table 1) was slightly but not significantly (p = 0.54) higher than the non-underrepresented patients (213/1059 (20.1 %), Fig. 1.) Fig. 2. shows the Spanish-speaking patients who consented after being asked to participate in the trial was significantly higher (p = 0.01) than that of English speakers (15/41 (36.64%) vs. 356/1760 (20.2%) respectively). For comparison, in recent years, the percentage of Hispanics enrolled in clinical trials funded by the National Institutes of Health (NIH) has ranged between 6.7% to 11.3%, even though Hispanics make up 18% of the U.S. population [3]. The underrepresented sample made up 42.6% of all randomized patients.

Table 1.

Sample Characteristics (not mutually exclusive).

Underrepresented Characteristic	n(%)
Non-White	131 (83 %)
Hispanic	37 (23 %)
Medicaid Insurance	23 (15 %)
Spanish-speaking	15 (9 %)
Total:	158

Fig. 1.

Consented Diverse Participants.

Note: Percentages are based on the number of individuals who consented to participate in the CAFÉ trial among those who were approached to participate, stratified by whether it was they were from the under represented or general recruitment population. P-value = 0.54 based on chi-square test.

Fig. 2.

Consented Primary Spanish Speaking Participants

Note: Percentages are based on the number of individuals who consented to participate in the CAFÉ trial among those who were approached to participate, stratified by whether it was they were in the Spanish- or English-speaking population. P-value-0.01 based on chi-square test.

4. Discussion

The recruitment numbers from the CAFÉ study demonstrate that when researchers prioritize diverse recruitment and deploy strategies for increasing representation, groups that historically have been excluded from clinical trial participation will enroll and provide valuable insights to the research findings. Enrolling diverse patients in our sample improved what we know about Spanish-speakers’ experience with financial distress during a cancer diagnosis.

Despite the intentionality of the study design and recruitment techniques, the researchers found that they needed to devote resources to achieving their goals. They hired Spanish speakers outside the research institute for assistance with developing Spanish-language materials, prioritized translating recruitment materials and recorded phone messages, and retained Spanish-speaking team members and study interviewers from a centralized survey research program that hires and trains Spanish-speaking interviewers at one health system.

Attaining diverse study participation, particularly language-specific recruitment is achievable. The CAFÉ study experience shows that intentional goal setting, resource allocation, and planning can pay off, as greater trial diversity will deliver results that are more meaningful and more generalizable, allow more people to participate in trials, and contribute to improvements in health care and population health.

Investigators who want diverse participation in their trials can achieve it, even in less diverse populations by making intentional recruitment of diverse groups a top goal and implementing strategies that include specific recruitment targets, diverse research teams with appropriate training and expertise, and language-specific materials. Representation must be part of the research design from the very beginning, and strategies for increasing representation must be supported with adequate resources and staff.

Funding/support

Drs. Banegas and Hendrikson receive funding for the CAFÉ study from the National Institute of Health (NCI R01CA237322).

Role of the funder/sponsor

The funder had no role in the preparation, review, or approval of the manuscript and decision to submit the manuscript for publication.

Data Availability

The datasets generated during for this report are not publicly available due to the brevity of this brief, and a greater dataset will be available upon publication of the main outcomes from the Café study but are available from the corresponding author on reasonable request.

Ethics approval

This study was approved by the KPWA IRB.

Consent to participate

Informed consent was obtained from all individual participants in the Café study.

CRediT authorship contribution statement

Amanda F. Petrik: Writing – review & editing, Writing – original draft, Data curation, Conceptualization. Nora B. Henrikson: Writing – review & editing. Gloria D. Coronado: Writing – review & editing, Writing – original draft, Conceptualization. Erin Keast: Writing – review & editing, Formal analysis, Data curation. Matthew P. Banegas: Writing – review & editing, Writing – original draft, Data curation, Conceptualization.

Declaration of competing interest

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nora Henrickson and Mateo Banegas report financial support for this project was provided by National Cancer Institute. Gloria Coronado reports a relationship with Exact Sciences Corporation that includes: consulting or advisory. Other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Data availability

Data will be made available on request.