Every new therapy relies on years of painstaking research, but what if that research overlooks the very people most in need?
The problem: a mismatch between trials and reality
Ethnic minorities, people living with deprivation, older adults, and women are disproportionately affected by chronic liver conditions, yet they are frequently missing from the trials examining new treatments.
One systematic review examining NAFLD studies in North America found that documentation of racial/ethnic demographic data occurred in less than half of the eligible studies. And in those, participation from minority patients remained low(1).
When clinical evidence stems from an unrepresentative group, its relevance crumbles. Safety, efficacy, or dosing may not translate to underrepresented populations, exacerbating health inequalities rather than reducing them.
The status quo also reflects structural issues in how trials are run. Too often, recruitment is confined to the same research-active hospitals and clinics, drawing repeatedly from patient pools that are already engaged and accessible. The result is a cycle of evidence that is scientifically narrow and ethically insufficient.
What can be done?
1. Widen eligibility, narrow disparities
Overly restrictive eligibility criteria, excluding patients with common comorbidities or advanced disease, shrink the participant pool and often eliminate those who need access most. Broadening criteria allows participation from real-world patient populations, improving both validity and fairness.
2. Use non-invasive diagnostics
Inclusion criteria that rely on liver biopsy exclude patients who can’t tolerate or don’t want invasive procedures. Non-invasive tests (NITs), such as ELF, elastography, and MRI, offer safer, more accessible alternatives and can perform well at detecting and staging disease(2)(3).
3. Engage the community
Evidence from other therapeutic areas shows that community outreach, through partnerships with local clinics, patient groups, and trusted local leaders, boosts awareness and trust. Direct engagement breaks down historical barriers of mistrust and ensures patients are aware of trial opportunities(4).
4. Ease practical barriers
Language, transport, and scheduling hurdles can edge out those without time, transportation, or flexibility. Trials that offer materials in multiple languages, flexible hours, and reimburse travel remove these barriers and widen access.
5. Case-finding as a gateway to inclusion
Case-finding means proactively identifying at-risk individuals using their existing health data, such as routine blood tests, imaging performed for other reasons, or primary care records, and inviting them into research or care pathways.
By doing this, trials move beyond familiar research site pipelines. They connect with real-world populations who may not yet be engaged with liver services or research. Case-finding expands the pool of potential participants to include those most affected, but often least visible, ensuring trials reflect the true disease burden.
The way forward
Unrepresentative trials are both scientifically weak and ethically precarious. Evidence and outcomes derived from narrow, homogeneous groups fail the broader patient population. To change this, we must:
- Broaden eligibility
- Use non-invasive diagnostics
- Engage communities proactively
- Remove practical hurdles
- Embed case-finding as a recruitment strategy
If research is meant to serve everyone living with liver disease, trials must reflect the diversity of disease burden.
References
1. https://www.wjgnet.com/1948-5182/full/v12/i8/506.htm
2. linkinghub.elsevier.com/retrieve/pii/S2468125323001413
3. EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis – 2021 update.
4. https://www.sciencedirect.com/science/article/pii/S0146280618301889?via%3Dihub