Strategies to improve representativeness when recruiting patients for clinical trials

An interesting article was published in October that talks about ways to make cardiology clinical trials more inclusive.? The authors talk about how cardiovascular clinical trials continue to under-represent children, older adults, females and people from ethnic minority groups relative to population disease distribution.?The authors note that despite years of data on the under-representation of older adults, females and people from racial or ethnic minority groups in clinical trial populations, trends have not improved substantively.?

This is not a problem unique to this therapeutic area, and finding ways to include representative patients is something that will continue to become more and more important as regulatory authorities and ethics committees around the world include diversity expectations and targets in their guidelines.?

The strategies highlighted are relevant to many therapeutic areas, and are outlined below.

The importance of representativeness

The paper talks about why representativeness in clinical trials matters.

“Trials lacking participants similar to those in routine clinical practice may not yield appropriate efficacy or safety estimates that reflect those in real-world clinical settings. In addition to the impaired generalizability of study results, there is the ethical obligation of ensuring that under-represented groups benefit from inclusion in clinical trials.

The efficacy and safety of an intervention may be affected by sex, ancestry, ethnicity, cultural and behavioural norms, comorbidities, baseline usual care standards, access to care, socioeconomic status and healthcare systems.

Clinical trials are commonly conducted in a very small proportion of eligible patients, with little evidence to guide uptake in excluded patient groups.? Subgroups may be imbalanced and subgroup analysis may lack adequate statistical power for meaningful results. Post-approval real-world data have the potential to provide generalizable evidence, but these data do not have the methodological rigour to make causal inferences; they also take a long time to accrue evidence.”

How can representativeness be improved?

At a high level, these include:

·???????? Creating broad recruitment strategies

·???????? Streamlined and justifiable inclusion and exclusion criteria

·???????? Cultural competency training of investigators (including for consent processes)

·???????? Efficient trial processes that minimize research burden on participants

·???????? Broad representation on trial committees of both investigators and patients

·???????? Interim analyses to monitor the representativeness of participants

Recruitment of representative patient populations in clinical trials

In relation to patient recruitment strategies, the paper talks about several approaches that can be used including:

• Meaningful patient and community engagement to building trust, especially for groups that have experienced mistreatment or ethical violations in the past. Factors such as culture, language, socioeconomic status, and past healthcare experiences influence whether patients trust, understand, and participate in trials. ?This could include engaging patients and community leaders in advisory boards during trial design to increase trial representativeness .? Clear, co-designed trial documents can also build trust and ensure transparency and understanding.
• Using Digital Technologies such as social media platforms to offer a broad reach to recruit diverse trial participants and engaging with community leaders and advocacy groups, using AI and machine learning algorithms to analyze online data and predict disease trajectories, and using health data from routine healthcare settings like EHRs to broaden trial recruitment pools and help mitigate clinician biases.
• Site selection is crucial for recruiting a diverse sample, as clinical trials often focus on research-intensive centres, leading to a limited and unrepresentative population. Including rural and underserved areas can better reflect disease distribution. Collaborating with local communities can help identify barriers to participation.

The paper also discusses the importance of the design of clinical trials and education to improve population-based health and research readiness across all groups at the societal level.? Again, patient engagement is important, with a key approach being in co-designing studies and education strategies with representative patients and healthcare professionals.

Whether patient engagement occurs within communities, through patient panels / boards, at an individual patient level through interviews or by designing and executing relevant surveys, having patients involved as active participants, is an important foundation throughout R&D to improve representativeness, speed up recruitment and increase patient access.

To read the paper in full, please go to:? https://doi.org/10.1038/s41591-024-03273-3

About me: Having started my career in academic research and teaching at Guys Hospital, London over 30 years ago, I then moved into the commercial world of Clinical Research Organisations and Healthcare Consultancies. I have a strong interest in looking at ways to more effectively and efficiently use real-world data to better support and involve patients, both during the development of new treatments and once launched. I am part of the leadership team at DontBePatient Intelligence, which focuses on the design of patient and healthcare research and in accessing patients both quickly and in appropriate numbers to enable decisions to be made using scientifically robust methods on representative data. Follow me or the DBPi page for more insights every week.