Do we still need broad patient representation in breast cancer trials? Absolutely.

A critical question in a shifting global landscape

Expanding patient inclusion in breast cancer clinical trials is not only an ethical obligation but also a scientific and business necessity for producing reliable, applicable data that supports global approval, reimbursement, and market access. While regulatory guidance documents on diversity continue to develop, they differ by region, causing short-term uncertainty for sponsors.

Nevertheless, even without regulatory mandates, broad patient inclusion—beyond race and ethnicity—is crucial for long-term scientific integrity, a smooth regulatory process, and lasting commercial success. 

The scientific case: Homogeneous data is less generalizable 

Data from a narrowly defined patient population are less scientifically valid and less applicable to the broader, demographically diverse real-world population. In cancer trials, many patient groups are underrepresented, which may reduce the ability to generalize findings.¹  

For example, historically, breast cancer trials have excluded patients with lower performance status (PS) scores.² However, standard PS scales like Karnofsky Performance Status (KPS) and Eastern Cooperative Oncology Group (ECOG) PS—both of which assess a person’s ability to perform daily activities without assistance—are subjective and can vary among raters. Excluding patients with lower functioning (those with a PS score of 2 or 3 on a scale of 0 to 5, where 5 indicates death) does not accurately reflect the typical population of cancer patients. Evidence suggests that including patients with a broader range of PS scores could lead to faster enrollment rates and more representative trial populations without negatively affecting outcomes.³ 

Men are often overlooked in breast cancer trials, in part because male breast cancer is rare, comprising just one percent of cases in the United States.⁴ As a result, little is known about the clinical features and outcomes of male breast cancer. Some evidence indicates that men with triple-negative breast cancer fare worse than women.⁵ More research is needed on tumor biology, treatment, and adherence to improve therapies for men.⁶ However, increasing the number of men in clinical trials is an essential first step.

Many breast cancer trials occur at academic centers, making it hard for rural and underserved patients to participate. A recent study found significant geographic disparities, noting limited trial availability in rural, low-income, and less-educated areas with fewer cancer specialists.⁷ Using targeted site selection and hub-and-spoke models, in which academic centers support community sites, can increase rural patient participation.

Some aspects of breast cancer biology vary among populations due to differences in their molecular and genomic makeup. For example, there is a higher prevalence of triple-negative breast cancer in young, Black women.⁸ Women of Ashkenazi Jewish descent have a higher risk and incidence of BRCA1/2 mutations. For precision medicines, sponsors can more easily locate the necessary number of patients with specific biomarkers, such as ESR1 or PIK3CA, if they cast a wider net across a more diverse population. 

Older patients and those with comorbidities or other health conditions in addition to cancer have traditionally been excluded from trial participation by the eligibility criteria. This is despite the fact that nearly one-third of new breast cancer cases are diagnosed in women aged 70 and older, and up to 42 percent of women with breast cancer have at least one comorbidity, with the most common being hypertension, ischemic heart disease, heart failure, and depression.⁹ Sponsors can modify eligibility criteria when there is a scientific and medical rationale to do so, to enroll a more typical patient population.

To plan a clinically sound and representative development program, sponsors must analyze the demographics and unique physiologic characteristics of the target population, encompassing factors beyond race and ethnicity. The composition of the target population can then dictate the composition of the trial population.

The regulatory case: Compelling data supports approvals

Regulatory agencies expect sponsors to evaluate new products in populations that reflect the patients who will use them. Official guidelines may change over time, but there is a global consensus that diverse clinical trials expand access for patients and generate data that better characterize how new products work in subgroups. That trajectory is unlikely to change.

There is significant national and regional variability in regulatory guidelines and procedures for reporting patient demographic data, particularly between the United States and Europe.¹⁰ While the FDA has historically emphasized racial and ethnic diversity, the European Medicines Agency (EMA) and national regulatory bodies, such as the UK’s Medicines and Healthcare products Regulatory Agency (MHRA), have emphasized a broader range of parameters, including both demographic and non-demographic factors.
For example, the UK’s National Institute for Health and Care Research (NIHR) identifies certain groups as underserved in clinical research: minority ethnic groups, caregivers, individuals who belong to a faith or belief community, those who are neurodiverse or pregnant, highly mobile communities, and the youngest and oldest age groups (those under 18 and over 75). Additionally, it includes people living in remote or rural areas, with diverse sex characteristics, language barriers, learning disabilities, lower educational attainment, multiple health conditions, physical or mobility impairments, non-binary sexual orientations, and diverse socioeconomic backgrounds such as those who are unemployed, have low income, or are experiencing homelessness.¹¹ In May of 2025, the MHRA provided revised guidance for sponsors on how to submit an Inclusion and Diversity Plan for clinical research.¹² Although the plans are not mandatory, they are highly encouraged.

From a regulatory perspective, a key goal of diversity in clinical research is to determine whether treatment benefits and risks vary based on biological or physiological factors. Measuring these differences requires solid evidence. For example, studies show that various ethnic groups of Asian descent often metabolize drugs differently, which may influence drug effectiveness and the likelihood of adverse events.¹³ Phase 1 trials must take into account this genetic variability. Physiological differences, such as body weight between genders, also influence drug metabolism and clearance. 

Therefore, an optimal drug development program should include representative percentages of relevant population subgroups. Epidemiological desk research and literature reviews can determine disease prevalence across different groups. Sponsors can use this data to monitor patient recruitment and ensure trial targets are met. Proactively recruiting a diverse population into a clinical trial may require more effort and expense upfront, as sponsors must manage recruitment across numerous patient segments with varying needs. However, a lack of diversity can lead to delays in a drug’s approval or require post-marketing studies, potentially incurring additional costs. 

The business case: Inclusion accelerates development and demonstrates value 

Inclusive clinical trials can accelerate development timelines. For instance, by including new, underserved patient groups such as those from VA hospitals, community centers, and pharmacies like Walgreens and CVS, sponsors may achieve high enrollment targets more quickly. A data package that covers a wide range of patients is more robust and convincing to multiple stakeholders, including health technology assessment (HTA) agencies. Clinical trials are most valuable in an HTA setting if they include the population most likely to be treated in routine clinical practice. Having a diverse group of participants helps ensure fair and effective HTA decisions. 

In 2024, the U.S.-based Institute for Clinical and Economic Review (ICER) released its Clinical Trial Diversity (CDR) framework to assist HTA agencies, regulators, policymakers, journal editors, and researchers in assessing trial diversity in a consistent, transparent manner.¹⁴ All ICER reviews will now evaluate the diversity of registrational trials based on how well the mix of race/ethnicity, sex, and age aligns with the prevalence estimates for the disease being studied.¹⁵ Studies can be rated as good, fair, or poor.

A globally representative trial population can ease HTA submissions across various regions, including Europe and APAC. A drug that is proven effective and reimbursable across a broad patient group will have a stronger, more sustainable market position.

A strategic path forward for sponsors

Sponsors don't need regulatory mandates to design scientific and ethical clinical trials that gather relevant and representative data, thereby reducing their regulatory and commercial risks. To reach demographically diverse patient populations, they can partner with community health centers, retail pharmacies, and patient advocacy groups. They can implement decentralized clinical trials (DCTs), when feasible, or design hybrid studies that lessen the logistical burden on patients in remote or underserved areas or who are less mobile due to disabilities. They can also modify eligibility criteria to be more inclusive and select sites and investigators whose demographics reflect the target patient population.

A commitment to equitable, inclusive, and representative clinical trials will better serve the needs of every patient in a diverse global population. At Parexel, we bring a wide range of knowledge and experience to help sponsors facilitate this process.

Resources

1. Evaluating generalizability of oncology trial results to real-world patients using machine learning-based trial emulations, Nature Medicine (January 3, 2025).
2. Modernizing Clinical Trial Eligibility Criteria: Recommendations of the ASCO-Friends of Cancer Research Performance Status Work Group, Clinical Cancer Research (November 1, 2021).
3. Ibid.
4. Breast carcinoma in men, Cancer (May 24, 2004).
5. A Systematic Comparison of Overall Survival Between Men and Women with Triple Negative Breast Cancer, Clinical Breast Cancer (February 2022).
6. Ibid.
7. Geographic disparity in the distribution of cancer clinical trials in the United States and the associated factors, Journal of Managed Care and Specialty Pharmacy (March 31, 2024).
8. Triple-negative breast cancer in African-American women: disparities versus biology, Nature Reviews Cancer (February 12, 2015).
9. Eligibility criteria in clinical trials in breast cancer: a cohort study, BMC Medicine (July 3, 2023).
10. Diversity in clinical trials in Europe and the USA: a review of a pharmaceutical company’s data collection, reporting, and interpretation of race and ethnicity, Annals of Oncology (December 2023).
11. Improving inclusion of under-served groups in clinical research: Guidance from INCLUDE project, National Institute for Health and Care Research (August 2024).
12. Guidance for developing and submitting an inclusion and diversity plan second draft, Health Research Authority and Medicines and Healthcare products Regulatory Agency (May 13, 2025).
13. The variation landscape of CYP2D6 in a multi-ethnic Asian population, Nature (July 20, 2024).
14. A framework for evaluating the diversity of clinical trials, Journal of Clinical Epidemiology (May 2024).
15. ICER Debuts Clinical Trial Diversity Assessment Framework, The Pink Sheet (May 2, 2024).

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