Why are clinical trials struggling with diversity?
In the diverse world we live in, the products we produce, the services we create and the places we work should be as equally representative. In recent years this has seen diversity, equity, and inclusion (DEI) become a big focus for industries to get right.
Within pharma and healthcare, where greater representation has been proven to lead to better health outcomes for all patients and the pharmaceutical companies developing medicines, change is also happening.
Fair and timely access to efficacious medicine is one of the vital tenets of the healthcare industry and is a critical building block of the sector’s environmental, social and governance (ESG) objectives. But historically there are groups that are typically neglected due to the current systems in place. Racial disparities are still commonplace in many clinical trials with white-ethnic groups often overrepresented amongst trial participants.
Factors such as ethnicity, gender, sexual orientation and age can contribute to interindividual differences in treatment responses and risks of adverse events. Inadequate clinical trial representations of all populations can therefore leave underrepresented groups vulnerable due to the lack of subgroup-specific data.
While many pharma companies are actively working on initiatives to improve diversity in clinical trials, we still have a long way to go. The good news is that technology is being harnessed to promote a DEI-conscious agenda within the clinical trial space, making diversity more attainable than it ever has been.
To understand why improving diversity, mitigating bias, and reinforcing inclusion in clinical trials is such a big task, it’s important to understand the challenges currently at play.
Unpacking the status quo
Traditional Randomised Control Trials (RCTs) continue to form the backbone of clinical efficacy and safety data submitted to health authorities for regulatory review. A risk-benefit approach underpins the decision-making process to evaluate human drugs, drug/device combinations and advanced therapy medicinal products for licensing of human medicines.
It is well-established that safety and efficacy data is highly influenced by internal (intrinsic: ethnicity, sex, age, genetic background) and external (extrinsic: climate, education, access to healthcare) factors. The challenge for regulators and pharma companies is that safety and efficacy data from an RCT may not always translate to the real world ‘effectiveness’ of a medicine (how efficacious the drug is in patients once marketed) which is governed by these complex intrinsic and extrinsic factors.
To mitigate against potentially lower drug efficacy or a different drug safety profile in a wider population vs those findings evidenced in RCTs it is important for companies to include ‘patient-orientated’ outcomes (relief of symptoms) alongside traditional endpoints (blood pressure, glucose concentrations). The diversity of clinical trial patients in the context of disease prevalence is key to capturing ‘patient-orientated’ outcomes in populations. For example, with skin conditions, textbooks, studies, and trial photos often present lighter-skinned individuals' symptoms, which are bound to differ in darker skinned individuals.
The pandemic brought imbalances into sharp focus
The race to produce a vaccine which could protect the world against COVID-19 brought the topic of diversity in clinical trials, or lack of it, into sharp focus.
Vaccines approved for public use require comprehensive RCTs to establish their safety and efficacy. The demographics of vaccine trial participants should reflect the vulnerable groups to whom infection with the disease presents the greatest risk of harm and mortality. However, this did not happen to the extent it could have during trials for the COVID-19 vaccine.
Research has shown a disproportionately higher rate of COVID-19 infection and mortality among the elderly and minority ethnic groups who are more likely to be negatively impacted by social and economic deprivation linked to pre-existing health conditions. In the UK, during the first wave of the COVID-19 pandemic, ethnic minority groups (except for women in “Chinese” or “White Other” categories) had higher rates of death post-exposure compared with the “White British” population.
These issues are not confined to the UK; in the US, some minority groups including Black, Latino, Pacific Islander and Indigenous peoples have been shown to have twice the COVID mortality rate of Caucasian people.
Despite policies, guidelines, and regulations to promote the diversification of clinical trial groups by the European Medicines Agency (EMA) and FDA, the inclusion of key demographic populations within clinical research continues to be less than proportionate to their representation in society.
Why are certain ethnic groups underrepresented?
Redressing the imbalance in trial participation is not a simple task. Throughout the pandemic, the issue of vaccine hesitancy was compounded by ethnic disparities. This is underpinned by historical mistrust in healthcare organisations, governments, and clinical research, which is still prevalent in some communities.
Factors influencing trust vary between ethnic groups. Reported experiences of discrimination, perceived structural inequalities impacting the access to and quality of healthcare, and concerns of trial under-representation are likely to influence trust issues, of which the latter is within the remit of companies to acknowledge and address with appropriate measures to effect change. Without diverse participation in clinical research there is a lack of breadth in safety and efficacy data. Certain groups of individuals may then not trust that the medicines have been produced with them in mind and may be highly sceptical of the resulting evidence base and prescribing label of medicines.
In the second half of this article, we’ll look at how technology is being used to make clinical trials more diverse and consider some of the lessons learned during the COVID-19 pandemic.
About the authors
Tanya Chambers is an ex-MHRA (Medicine and Healthcare Regulatory Agency) Senior Assessor with over 15 years’ experience principally evaluating preclinical data packages (small molecules and biologics) accompanying clinical trial applications, EU & UK marketing authorization applications (MRP/DCP/Centralised submissions) and variations across all therapeutic areas. Most recently, Tanya led the preclinical rolling review for COVID anti-viral applications resulting in national roll-out, and was product lead for the review of a vast array of development programmes via UK innovative licensing pathways: iLAP and EAMs. In addition, Tanya has working knowledge of the collaborative review of promising oncology treatments alongside Australia (TGA), Canada (Health Canada), UK (MHRA), Singapore (HSA), Switzerland (Swissmedic) and Brazil (ANVISA): ‘Project ORBIS’.
Liam Johnstone has six years of toxicology experience working across regulators in the UK, developing expertise in medicine, consumer product and agrochemical safety whilst working at the MHRA, OPSS and HSE, respectively. As a Non-Clinical Assessor at MHRA he assessed non-clinical data packages for new and generic medicines. He has provided scientific advice to companies both nationally and as part of the Scientific Advice Working Party (SAWP) on the suitability of non-clinical data packages and study plans, as well as generating guidance for the European Medicines Agency (EMA)