We are all individuals, who are of a certain demographic group based on, for example, age, gender, ethnicity, genetic make-up, vulnerable state, or rare disease. When treated with an intervention, our responsiveness can differ in significant ways.
Traditionally, clinical trials have not been representative of the full population spectrum and have excluded minorities, enrolling majority Caucasian patients to participate in clinical trials. Thus, because of under-representation of other racial groups, we still have medicines that require further investigation into their potential effectiveness and efficacy in other populations. We need to understand how the effectiveness of a medicine may potentially vary based on its use in different patient populations, such as those with differences in genetics.
In many disease indications, notably in the US, certain types of cancers and heart disease are recorded to be higher in African American men than in their counterparts. Yet historically, these men have not been participants in trials that could have been of benefit to them and would have allowed more informed understanding and obtaining of biological knowledge of the intervention across diverse populations.
Pharmacokinetics, which means the absorption and distribution of drugs in our bodies, metabolism, and excretion, must also be considered. This will provide us with insights into new biologics and targets that could be identified as potential pathways to cures in all disease indications, including rare and genetic abnormality diseases.
Insufficient attention has been paid to the diversity and equity of patients in clinical trials.”
Attitudes and structures create “health deserts”
The health authorities and health policy advocates are highlighting the importance of diversity and equity in clinical trials. But why has the major emphasis only been in the most recent years? Why not earlier?
- In the absence of statutory requirements and guidelines, clinical trials have not had to consider genetic, biological, or socio-economic differences in humans.
- The reasons for the lack of diversity and equity in clinical trials also lie in general attitudes and social structures.
In the past, trials have tended to exclude patients with genetic abnormalities, rare diseases or kidney failure, and pregnant women. Therefore, the possibility of interventions for these vulnerable groups have also been left out.
In the United States, for example, clinical research institutes are often located in geographical areas predominantly populated by educated Caucasian people who are able to access world renowned and established health services. This is representative of a recent cancer study by Kahn et al in 2022, which depicted that 40% of the country’s cancer population identifies as non-Caucasian, yet non-Caucasian participants only make up 15% of the cancer clinical trial population. This leaves room for a mismatch of representation, potential erroneous estimates of treatment efficacy and probable miscalculations of disease-free survival rates. It can also exacerbate health disparities.
It is more difficult for other ethnic groups to participate in trials because most of them live in areas with no research institutes. I call such areas health deserts. In addition, because of the weight of history, minority groups may be sceptical of doctors and clinical trials. For understandable reasons, they don’t believe that the intentions are good, or that they will be taken care of throughout the trial and beyond.
Identifying the problem marks the beginning of change.”
Diversity and equity now also on the regulators' agenda
The US Food and Drug Administration (FDA) has begun to address the growing need for diversity, by developing a “Race and Ethnicity Diversity Plan”. The FDA published draft guidelines in April 2022 under the title “Enhancing Diversity and Equity in Clinical Trials.”
- The guidelines present recommendations and strategies to improve the participation of different demographic groups in clinical trials.
- The guidelines focus in particular on increasing the participation of under-represented groups, such as ethnic and racial minorities, women, the elderly and children.
- In its guidelines, the FDA requires that diversity and equity must be considered in every clinical trial conducted in the United States.
- Pharmaceutical companies must provide the authorities with a plan on how they will ensure that the medicine being studied is effective and safe in all relevant demographic groups.
- In practice, a pharmaceutical company must provide the authorities with demographic data on its trial patients and justify the choices made for inclusion of minority and other ethnic groups that are to participate.
Continuous improvement is necessary
Continuous improvements in the design, recruitment and implementation of clinical trials are essential to achieve more comprehensive, diverse and equal healthcare and to ensure that all population groups receive equitable care.
It is important that research centres are established in areas where diverse demographic groups live and/or solutions must be provided, such as cultural and language support and concrete assistance with travel costs and schedules, to facilitate the participation of under-represented groups in clinical trials.
The misconduct of past decades must be remedied through efforts to educate historically vulnerable groups of people about the importance of clinical trials, so that they can participate with greater confidence. Training is also needed for researchers and research staff to enable them to include diversity and equity in their own work.
I’m glad that the importance of diversity and equity in clinical trials is now being recognised. Identifying the problem marks the beginning of change. What we need now is close cooperation with the authorities, patient organisations, research institutes, pharmaceutical companies and healthcare providers to turn the course of history.
It’s in all our interests that the results of clinical trials genuinely and equitably reflect all the people of the world.
Catherine Akello-Opio
Assistant Director, Pain Therapy Area USA, New York City
CV:
- Founded and ran Otino International, a non-profit organisation that provides access to healthcare in post-conflict sub-Saharan Africa.
- Has worked for more than 15 years in international innovative research and development programmes, achieving significant clinical and medical results for diverse populations.
- Has overseen strategy, planning, implementation, reporting and data analysis to implement inclusive decisions that improve the protocol and research design.
- Catherine’s biomedical research and insights on research feasibility, real-world evidence (RWE), demographic analysis and therapeutic geography have been used to develop new therapeutic innovations worldwide, particularly in under-represented regions in Southeast Asia, Latin America, the Middle East and Eastern Europe.
