Design Thinking For Clinical Trials

Historically, the importance of clinical trial diversity has been largely overlooked by researchers and health authorities at the expense of underrepresented groups. However, as evidence emerges, researchers are beginning to realise the importance of prioritising diversity and inclusion in medical research and its impact on human health.

Clinical trials are a cornerstone in medical innovation

In the field of medical research, clinical trials are a key tool that enable researchers to assess the safety, efficacy, and effectiveness of novel and emerging treatments, therapies, and preventative strategies against disease in human subjects, and according to National Institute for Health Research (NIHR)(1), are widely regarded as the gold standard method for evaluating healthcare interventions. Through well-structured and ethically conducted trials, researchers can explore the potential benefits and risks of cutting-edge treatments and are fundamental in the process of translating promising laboratory findings into real-world applications. In this context, the significance of clinical trials cannot be overstated as they form the bedrock of evidence-based medicine.

The importance of diversity in clinical trials

Ensuring appropriate representation of the target treatment population in clinical trials is imperative, although this has historically proven to be challenging. Inclusivity in trial design is essential to avoid the underrepresentation of various minority groups. It is widely acknowledged that different subgroups within the human population may respond differently to treatments and be more or less predisposed to certain health conditions. The lack of representation and misrepresentation of target populations can compromise the quality of research, as the trial results may not truly reflect the expected outcomes in the actual target population, leading to potential negative health consequences.

For instance, consider the case of clopidogrel, an anti-platelet medication used to reduce the risk of adverse cardiovascular events. Clinical trials testing its efficacy and safety were predominantly conducted on white populations, with a staggering 95.8% of participants being white, and 74.4% being male, as revealed by a meta-analysis of nine studies (2). However, this approach led to an oversight – the prevalence of a reduced function CYP2C19 genotype, which substantially increases the risk of major adverse cardiovascular events with clopidogrel use (2) , is significantly higher in East Asian and Pacific Islander populations (23-45% and 40-77%, respectively) compared to Caucasians (10-20%)(4). Consequently, the clinical trials indicated high effectiveness and wide prescription of the drug in predominantly white populations with low incidence of these genetic variants. This oversight had substantial consequences in places like Hawaii, which boasts a diverse demographic population comprising Caucasian, East Asian, and Pacific Islander individuals. Prior to alternate antiplatelet drugs being approved by the FDA, between 2007-2009, the cardiovascular death rate among Pacific Islanders was nearly double that of Caucasians (4.8% vs. 2.5%)(3).

Current initiatives in improving inclusion

Examples such as these really illustrate that prioritising the diversification of clinical trial recruitment is more than just a social debate that we can use to improve quota scores or improve our EDI image. It is essential to ensure that whole populations benefit from medical research. So, what is actually being done to improve inclusion? Several health governing bodies have released guidelines to enhance the diversity of clinical trial populations. In the UK, NIHR launched INLCUDE initiative, providing guidance on how to identify under-represented groups and increase their participation in clinical trials. INCLUDE defined the term ‘under-served’ groups. An under-served group is highly-context specific, but has the characteristic of having lower inclusion in research than expected from population estimates, a high healthcare burden not matched by the volume of research, and differences in how the group engages with healthcare services in comparison to other groups. The guidance highlights why inclusion of underserved groups is important in clinical research. The key reasons include: scientific robustness; ensuring that the treatment or intervention is effective and/or safe for a whole population. We cannot be sure that results are generalisable to a broad population if we haven’t tested in a broad range of participants. There is also a moral justification for ensuring that under-served groups are included in research. The evidence base necessary for decision making by clinicians and patients must be one generated by the participation of a broad range of groups in the research underpinning that evidence base. INCLUDE guidelines also provide a strategic framework for potential points of intervention to improve inclusion of under-served groups. Similarly, in the USA the FDA released their guidance on enhancing the diversity of clinical trial population. In both countries these guidelines highlight to researchers examples of underrepresented groups possible reasons for the exclusion of certain groups, possible solutions to removing these barriers and a framework to design more inclusive clinical trials.

Further improvements in increasing under-served group participation in research

These guidelines are an important first step in improving clinical trial inclusivity. They reflect a change in attitude towards diversity and inclusion from health authorities and encourage industry partners to be more considerate in their trial design. However, whilst this is a positive step in the right direction, we must be careful not to become complacent. Despite offering guidance on how to improve trial diversity and inclusion, neither health authority provided clear or objective goals on improving diversity. Consequently, measuring the success of implementation of these guidelines becomes difficult. Have they made any really impact, or has this become just another document to add to our EDI page to say we are meeting diversity quotas? We believe that if governments and health authorities really want to start seeing the benefits of increased inclusion and diverse representation in clinical trials, measurable goals and targets need to be set out, so that industry leads and researchers have something to strive for.

Conclusion

In conclusion, as the field of medical research progresses, it is incumbent upon us to uphold the principles of inclusivity and diversity in clinical trial recruitment. By designing trials that prioritise representation and inclusivity, we can generate evidence that better serves the entire population, leaving no one behind in the pursuit of improved health outcomes. As we embark on this collective journey, let us seize the potential of design thinking to drive innovation and change, ensuring that medical research benefits all and leaves no one overlooked or underserved. Only then can we truly realize the transformative power of clinical trials as the cornerstone of evidence-based medicine.