Bridging the Gap: A Viewpoint on Including Underserved Communities in Clinical Research – Needs and Recommendations for Action

INTRODUCTION

Clinical research plays a key role in the healthcare continuum. Ensuring diversity, equity and inclusion is the key to enhancing quality. Health equity aims to eliminate unfair and preventable healthcare disparities arising from economic, environmental, or social disadvantages faced by different groups.¹ Diversity encompasses a multitude of ways individuals identify themselves, including factors such as race, gender, age, ethnicity, national origin, or socioeconomic status. In contrast, inclusion refers to a culture that fosters respect and acceptance, where all individuals experience a profound sense of community belonging and receive equitable treatment across all life domains. The absence of underserved communities widens inequalities in healthcare, making their inclusion a top public health concern. Food and Drug Administration (FDA) drug trial data indicate a stark disparity between African and European women. Specifically, non-Hispanic African American women in the United States face 41% higher breast cancer mortality and 98% higher uterine corpus cancer mortality.² This discrepancy persists despite substantial advancements in innovative cancer therapies.³ While socioeconomic factors might seem to explain this trend initially, deeper analysis revealed a more concerning key issue: Key cancer treatment studies predominantly enrolled European women, with non-Hispanic African American women severely underrepresented.^4,5 This raises a crucial question about the efficacy of treatments across diverse patient populations when clinical trial participants do not adequately reflect this diversity. How can we expect universal treatment success when the study cohorts fail to represent the full spectrum of patients?

Inadequate representation of underserved communities in the Severe Acute Respiratory Syndrome Coronavirus 2 vaccine trial led to diminished confidence regarding vaccine safety and effectiveness, ultimately affecting vaccine acceptance among crucial underserved groups who potentially had the most to gain.⁶ The exclusion of patients with neuromyelitis optica from the optic neuritis treatment study⁷ led to inadequate treatment for these groups for decades. Furthermore, the lack of variation in study subjects could potentially result in overlooking ethnicity-related pharmacokinetic differences, which have clinical significance. An illustration of such variability is demonstrated by the impact of Human Leucocyte Antigen haplotype on carbamazepine hypersensitivity risk.⁸ Pregnant women and newborns often face disproportionate effects during such outbreaks. During the H1N1 influenza pandemic of 2009–2010, pregnant individuals suffered from a high mortality rate, negative birth outcomes, and an elevated risk of severe illness.⁹ The Ebola virus disease led to increased maternal and neonatal mortality, while the Zika virus caused severe microcephaly in infants born to infected mothers.¹⁰ The importance of inclusivity extends beyond the therapeutic interventional studies. Non-inclusive observational and epidemiological research can also yield results that lack generalizability and restrict our core understanding of diseases. To exemplify this issue, a recent initiative calling for increased diversity, inclusion and equity in Parkinson’s disease research and care outlines the challenge.¹¹ There is a significant lack of understanding regarding the impact of ethnic background and socioeconomic factors on the occurrence, severity and fatality rates of Parkinson’s disease.

This calls for a re-evaluation of the entire paradigm on which clinical trials are built, and necessitates the diversification of inclusion criteria to adequately serve the underserved communities.

To effectively address, the issue requires identifying underserved groups, acknowledging their barriers and implementing strategies to overcome the obstacles.

WHO ARE UNDERSERVED GROUPS?

Underserved groups refer to the segments of the population that are underrepresented in health studies compared to their actual population estimates.¹² Underserved groups can be categorised based on various characteristics: Demographic factors (such as age, gender, race and educational background); socioeconomic elements (including employment status, caregiving duties, lack of digital access, social exclusion and geographical location); health related issues (for instance, multiple chronic conditions, cognitive deficits, developmental disabilities and sensory impairments) and disease-specific aspects (such as rare disorders). As a result, inclusivity is highly dependent on context and inherently intersectional. It varies based on the population, the health issue under investigation, the research objectives, the intervention being evaluated and the observations made. The concept of underserved groups is intricate and context-specific, making it challenging to formulate a single, all-encompassing definition that applies to every instance.¹³

WHAT ARE THE PARTICIPATION BARRIERS?

Unable to speak a particular language,^14-16 poor communication,^17,18 lack of trust,^14-16,18-22 lack of information about trials,^20,21,23 barriers to healthcare or research facility access,^19,23,24 competition for participant enrollment and insufficient recruitment staff,²⁵ disproportionate inclusion criteria,^23,25,26 stigmatisation of the studied condition,^16,22,27 concerns about taking experimental medication,^26,28 religious beliefs,²⁴ lack of social approval,^23,26 insufficient knowledge of clinical trial processes,^14,18,20,24 lack of transportation,^16,19,23-25 inadequate follow-up during the recruitment phase,²⁵ insufficient outreach efforts by study teams to local communities,²³ complex socio-structural factors affecting patients²² and unavailability of research staffs²⁸ are some of the barriers of inclusion, diversity and equity. There are several reasons for the exclusion of pregnant women from clinical trials, including the apprehension of sponsors and researchers about potential legal responsibilities arising from negative outcomes.^29,30 This caution in involving pregnant women in clinical trials mirrors the hesitance observed among manufacturers and institutional review boards. The manufacturers’ caution is largely influenced by two significant historical events, specifically the diethylstilbestrol and thalidomide legal cases.³¹ Shaikh et al.³² in the review article on inclusion of pregnant women in clinical trials give a detailed description of ethical issues in different demographic regions.

While various initiatives aimed at enhancing research inclusivity fail to address the core issue: Inadequate healthcare access in underserved populations. This lack of access impedes diagnosis and treatment, reducing participation in clinical settings that serve as gateways to research.

To improve inclusivity, addressing all the barriers along with addressing this core problem is imperative.

STRATEGIES TO OVERCOME BARRIERS

Various national entities are spearheading initiatives. Notably, the UK National Institute for Health and Care Research has developed the INCLUDE guidelines,¹² which offer valuable inquiries to assist researchers, funding bodies, evaluators and research implementation teams to improve inclusion, and can be used by all institutions while developing protocols for study. Simultaneously, the FDA has issued new directives to promote industry-wide changes aimed at diversifying trial participants.³³ In addition, initiatives like the OPTIMISE: MS study,³⁴ which systematically collects real-world data, are helping to bridge evidence gaps and improve trial participation. Ultimately, a unified approach is crucial to deliver better healthcare for all individuals.

RECOMMENDATIONS

After a series of literature searches, a series of 10 recommendations are proposed to improve inclusion and achieve health equity, diversity in clinical research [Table 1].

These recommendations provided are fundamental principles that can be broadly implemented across any clinical and healthcare settings. Executing these proposals could lead to better representation of underserved groups in clinical trials, ultimately enhancing the external validity of the findings. The absence of externally valid research-based treatments and services compromises the delivery of equitable, high-quality care across healthcare systems.

CONCLUSION

To effectively implement evidence-based practices, it is essential to minimise bias and inequality in the evidence generation process. The benefits and opportunities associated with clinical research should be accessible to all, not just a privileged few. This includes patients, researchers and clinicians. Ensuring such inclusivity is a shared, global ethical obligation.