The U.S. and global pharmaceutical industries have faced a persistent challenge over the past several decades: the lack of diversity in clinical trials. While efforts to increase the representation of historically underrepresented groups have gained traction in recent years, the reality remains—racial and ethnic minorities, women, older adults, and rural populations are still underrepresented in the trials and studies that shape how therapies are approved, reimbursed, and delivered.

In the realm of Health Economics and Outcomes Research, Real World Evidence, and Market Access, this issue is not simply about ethics—it’s about validity, applicability, and value. Without a diverse trial population, the evidence base used to guide coverage decisions, health technology assessments (HTAs), pricing negotiations, and inform policy decisions risks being incomplete at best, and inequitable at worst.

This argument echoes themes we explored in our previous blog, “Beyond the Averages: Addressing Health Equity in an Unequal World.” In that piece, we discussed how standard HEOR models, grounded in population averages, often fail to capture disparities created by social determinants of health (SDOH). Clinical trial diversity sits at the other end of the evidence spectrum: unless studies include a diverse and comprehensive study population, representative of the various demographics reflected in the current global patient population, the downstream models and policies built upon that evidence will continue to perpetuate these disparities.

What’s at Stake: Why Clinical Trial Diversity Matters

When trial participants don’t reflect the real-world patient population, the ripple effects are profound:

• Clinical Effectiveness: Drugs may behave differently across genetic backgrounds, comorbidities, or cultural contexts. A therapy tested primarily in white patients may not perform the same in Black, Hispanic, or Indigenous populations.
  
  
• Safety Signals: Adverse events may be underreported or missed altogether if key subgroups are absent from trials. For example, higher incidence of hypertension among African American patients or metabolic differences among Asian populations can influence both efficacy and safety.
  
  
• Market Access: Payers and HTA bodies increasingly demand subgroup evidence. Without it, sponsors face uncertainty in demonstrating value for broad patient populations.
  
  
• Health Equity: Lack of inclusion perpetuates disparities in who benefits from innovation. Communities most burdened by chronic disease are often least represented in evidence generation.
  
  

In short, clinical trial diversity is not just a regulatory checkbox. It’s central to building a credible value narrative, ensuring equitable access, and strengthening the bridge between RWE and market access.

Policy Pressure: Regulators Are Raising the Bar

The regulatory environment is evolving rapidly, placing additional pressure for reform.

• FDA: In 2020, the U.S. Food and Drug Administration issued guidance calling for greater inclusion of underrepresented groups in clinical research. By 2022, the agency began requiring Race and Ethnicity Diversity Plans for pivotal trials, effectively forcing sponsors to explain how they will recruit more representative cohorts.
  
  
• Congress: The Food and Drug Omnibus Reform Act (FDORA) of 2022 made these diversity plans mandatory. Sponsors who fail to comply now face increased scrutiny, and in some cases, trial delays.
  
  
• International Momentum: Agencies like the EMA and Health Canada are also exploring frameworks to ensure diversity, recognizing the global implications of unrepresentative data.
  
  

For HEOR and market access teams, this regulatory push signals a critical shift: diversity is becoming a prerequisite for credibility. Subgroup analyses, stratified cost-effectiveness estimates, and culturally relevant patient-reported outcomes (PROs) are likely to become standard expectations from payers and HTAs.

The Role of RWE in Closing the Gap

Clinical trials, by design, are selective. But RWE offers a powerful complement by capturing outcomes in populations often underrepresented in these trials. Utilizing electronic health records, claims databases, patient registries, and digital health tools, RWE helps validate whether clinical trial findings apply to broader, more diverse groups. For instance, it can determine if a new treatment provides the same survival benefits among Medicaid patients or in rural hospital settings as it does for those located in an area of higher affluence where patients don’t rely heavily on state and federally funded care plans. Moreover, RWE allows for subgroup analyses by race, ethnicity, age, socioeconomic status, and geography, enhancing the generalizability of findings and strengthening negotiations with payers. 

By incorporating surveys, wearables, and digital health platforms, RWE ensures that patient-reported outcomes across various demographics are captured, thus making value assessments more reflective of real-world experiences. Health technology assessments (HTAs) and payers are increasingly receptive to incorporating RWE into cost-effectiveness models, as this inclusion ensures that the models are more representative and persuasive. However, RWE is not without its challenges, as biases can arise from claims data that may undercount uninsured populations and electronic health records that often lack standardized demographic fields. Addressing these limitations is crucial if RWE is to achieve its full potential in promoting equity.

Market Access Implications

From a market access perspective, the diversity of clinical and real-world data has become a competitive differentiator. Sponsors who can demonstrate that their product works across all relevant subgroups are in a stronger position to secure favorable coverage and formulary placement.

• ICER and HTA bodies: These organizations increasingly highlight evidence gaps in underrepresented groups as a weakness in value assessments. Sponsors that address these gaps proactively strengthen their credibility.
  
  
• Payers: Insurers and PBMs are attentive to evidence that reflects the populations they cover. For Medicaid-focused therapies, for instance, subgroup analyses in lower-income and racially diverse cohorts are critical.
  
  
• Value-Based Contracts: Outcomes-based agreements rely on evidence that drugs deliver consistent value in the real world. If trial data fails to reflect patient diversity, payers may be reluctant to enter such agreements—or may negotiate steeper rebates.
  
  

Ultimately, trial diversity is not just an ethical imperative. It’s a market access strategy.

Barriers to Progress

Despite advancements, several systemic challenges continue to hinder progress in achieving diversity in clinical trials. Recruitment for clinical trials remains a challenge due to persistent lack of trust between underrepresented communities and the research community, a consequence of past abuses, which continues to impede participation. Logistical hurdles also pose significant issues, with trials often conducted at academic centers, typically located far from rural or underserved communities. Furthermore, strict inclusion and exclusion criteria can unintentionally exclude diverse participants who have comorbidities. 

The cost and burden of participation, such as travel, time off work, and childcare, remain practical barriers for many patients. These burdens of participation often disproportionally affect underrepresented populations for all of the previously listed challenges. For example, women who live far from an academic center that are also responsible for child rearing have to travel far, find care for their children, all while confronting a system that has shown discrimination against them in the past. Without directly addressing these obstacles, efforts to mandate diversity can be seen as being more symbolic than substantive…not ideal when you’re trying to build better trust with these patients. 

Best Practices and Emerging Solutions

The industry is beginning to adopt strategies to improve representation and build that trust between researchers and patients:

• Community Partnerships: Collaborating with local clinics, advocacy groups, and faith-based organizations to build trust and awareness.
  
  
• Decentralized Trials: Leveraging telemedicine, mobile sites, and digital monitoring to reach patients outside major research hubs.
  
  
• Flexible Design: Loosening eligibility criteria to better reflect real-world patients with multiple comorbidities.
  
  
• Incentives and Support: Offering transportation, stipends, or flexible scheduling to reduce participation barriers.
  
  
• Data Infrastructure: Improving demographic capture in EHRs and claims, ensuring researchers can stratify outcomes more effectively.
  
  

For HEOR teams, incorporating these practices into trial design and evidence-generation plans will not only strengthen regulatory compliance but also improve downstream value demonstration.

Linking Back to Equity in HEOR

This is where the connection to “Beyond the Averages” becomes clear. Just as traditional cost-effectiveness models risk overlooking disparities when relying on population averages, clinical trials that lack diversity risk setting the wrong foundation for those models. Diversity in trials ensures the raw data itself is more representative; equity-focused HEOR frameworks like distributional cost-effectiveness analysis (DCEA) then ensure that interpretation and policy decisions account for differences in who benefits.

In other words: diverse evidence + equity-focused models = more just and effective healthcare decision-making.

Looking Ahead: A Call to Action

As payers, regulators, and patients demand more representative evidence, clinical trial diversity is no longer optional—it’s a strategic imperative. For HEOR, RWE, and market access professionals, this shift creates both challenges and opportunities:

• Evidence plans must now anticipate payer and HTA scrutiny of subgroup outcomes.
  
  
• RWE must be leveraged to supplement trial findings and demonstrate broad applicability.
  
  
• Market access strategies must foreground equity as part of the value narrative.
  
  

If done well, diversity in trials and evidence generation can lead to more credible science, fairer pricing negotiations, and, most importantly, improved health outcomes across all populations.

The message is clear: diverse evidence is stronger evidence. And in the evolving landscape of healthcare policy, that strength will define not just who gains market access, but who ultimately benefits from innovation.