Clinical trials are evolving in response to growing expectations around diversity, accessibility and patient-centricity.

Improving diversity in clinical trials can help generate more representative evidence and strengthen confidence in treatment performance across different patient groups. However, building study populations that reflect real-world patients remains a significant challenge.

In this article, Julie Massicotte, Senior Director, Regulatory Affairs at Indero, explores how sponsors can address these issues earlier in the trial life cycle through more inclusive protocol design, patient-focused recruitment strategies and stronger statistical planning.

Clinical trials are the foundation of evidence-based medicine, generating the data needed to evaluate the safety and efficacy of new therapies before they reach patients.

However, many studies still struggle to enrol participants who accurately reflect the populations seen in routine clinical practice. Meanwhile, regulators are placing growing emphasis on diversity and inclusion, increasing pressure on sponsors to generate scientifically robust evidence across broader patient populations.

Achieving this requires more than wider recruitment campaigns alone. Protocol design, statistical strategy, site selection and patient engagement all play important roles in determining whether a trial can successfully recruit and retain a representative patient population.
Considerations around accessibility, participation burden and operational feasibility must therefore be incorporated as early as possible in study planning.

Historically, clinical trials have often struggled to recruit participants from under-represented populations.

Geographic limitations, financial pressures, limited access to specialist research centres and mistrust of pharmaceutical research can all discourage participation. At the same time, restrictive inclusion and exclusion criteria may unintentionally exclude real-world patients with common comorbidities, limiting how well trial results reflect routine clinical practice.

These challenges are particularly significant because disease presentation, treatment response and adverse event profiles can vary between patient populations.

In dermatology, for example, conditions such as atopic dermatitis, acne and melanoma may present differently across skin tones, potentially affecting diagnosis, endpoint assessment and treatment outcomes.

Factors such as Fitzpatrick skin type and endpoint assessments training must therefore be considered during protocol planning to ensure that efficacy and safety data accurately reflect a broader patient population.

Regulatory agencies are increasingly addressing this issue, with the FDA, EMA, MHRA and HRA all emphasising the importance of improving participant diversity and embedding inclusion strategies into study planning.

The EU Clinical Trial Regulation also encourages sponsors to justify non-representative enrolment approaches and consider broader accessibility during protocol development.

In the UK, new MHRA regulations that came into force on 28 April 2026 introduced further guidance to help researchers embed the patient voice into the design and conduct of trials.

Similarly, the US FDA finalised its guidance on enhancing participation in clinical trials in December 2025. The final guidance provides recommendations to increase enrolment of representative populations by considering both demographic and non-demographic characteristics.

These growing regulatory expectations are also driving industry groups and professional bodies to develop guidance that helps sponsors integrate patient feedback and reduce participant burden in protocol design.

Feedback from all interested parties is highlighting that excessive site visits, complex assessment schedules, lengthy procedures and unrealistic expectations can create substantial burdens for participants and sites alike.

These can be particularly significant in long-term conditions such as rheumatological diseases, where chronic symptoms, comorbidities and complex treatment histories may affect patients’ ability or willingness to enrol in trials.
Most immune-mediated inflammatory dermatological and rheumatological diseases also appear during working and childbearing years, meaning intensive trial schedules heavily disrupt professional and family responsibilities.

In addition, rheumatology patients often experience severe pain and active inflammation, particularly during the screening period and first few weeks of a trial. This severely reduces their physical independence, meaning they may need a caregiver or companion to travel to and attend site visits.

Factors such as realistic visit schedules, travel support and caregiver involvement are therefore playing an important role in encouraging both recruitment and retention.

Even scientifically robust protocols may struggle operationally if they fail to reflect the realities of patients’ daily lives.

While planning study designs, sponsors should consider logistical and participant-related factors that may create barriers to trial participation. Engaging with patients, investigators and site teams during protocol development can help sponsors identify these practical barriers before studies begin.

Improving representation also requires inclusion strategies to be integrated into protocol development from the start.

This includes carefully reviewing eligibility criteria to ensure exclusions are scientifically justified, as well as evaluating recruitment targets and stratification approaches that allow broader representation across demographic and clinical variables.

As these examples illustrate, sponsors must also consider non-clinical factors that may affect participation within different patient groups, including transportation difficulties, work commitments, language access, digital accessibility, socioeconomic factors and cultural sensitivities.

Clear communication remains equally important, particularly for informed consent forms, protocol summaries, study instructions and retention strategies. Using accessible language and offering information in multiple formats can help patients better understand trial expectations and build trust in the research process.

Flexible trial models are also helping to reduce participation barriers. Hybrid and decentralised approaches that incorporate remote monitoring, digital reporting tools and virtual visits can reduce the need for frequent travel and improve accessibility for patients in rural or underserved communities.

While fully decentralised models may not be appropriate in every therapeutic area, particularly where subjective or imaging-based assessments are required, incorporating flexibility wherever possible can improve recruitment and retention.