THURSDAY, 20 JANUARY 2022It is thought that the majority of medicines available today are only effective in a minority of people. The efficacy of therapies such as vaccines or medicines can be influenced by interactions between the drug and an individual’s genetics or environmental factors (such as HIV status). To address this, medical practice is evolving away from the traditional “one-size fits all” approach, towards more individualistic treatments known as “personalised-” or “precision medicine”.
Precision medicine aims to use treatments that take into account individual variability in genes, environment and lifestyle. Clinical trials help physicians to identify which groups of people respond to a new treatment and which don’t. Yet despite this growing appreciation for the interactions between genetics and medicine, there is evidence of ongoing disparity in the representation of some ethnic groups in both international and UK clinical trials. This lack of representation could lead to the safety and effectiveness of new therapies being incorrectly estimated for the underrepresented groups.
Blinded, randomised and controlled clinical trials are used to determine the safety and efficacy of any new vaccine or medicine. Clinical trials involve several phases which usually take years to complete. Prior to human trials, a drug is tested in animals to see if it produces the expected response. In phase I clinical trials, a few dozen people are given the therapy to test its safety in humans. In phase II trials the therapy is tested in hundreds of people to further investigate the physiological response to the drug. Phase III trials involve thousands of people and aim to measure the efficacy of the therapy compared with current standard therapy or a placebo. If the preliminary data suggest that the therapy is safe and effective, authorization may be provided for roll-out in the wider population. However, recipients will continue to be monitored carefully for adverse side effects.
Small variations in our DNA, called polymorphisms, can have a dramatic effect on the way our body responds to drugs. Polymorphisms in genes encoding enzymes involved in drug metabolism, such as P450 enzymes, can change how quickly a drug is metabolised by an individual and hence their risk of side effects. While most genetic variation in humans occurs between individuals rather than between individuals of different ethnicities, certain polymorphisms are associated with populations from certain geographies and ethnic groups. Importantly, differences in physiological responses to drugs between people of different ethnicities have been observed, highlighting the need to include people from diverse genetic backgrounds in all drug and vaccine trials.
Clinical trials are notoriously expensive and consequently, the market is dominated by a small number of pharmaceutical giants. Low-income countries are less likely to be chosen by funders to host clinical trials. Despite around 16% of the world’s population inhabiting the African continent, only 2% of vaccine trials take place in African nations. This means that for many new vaccines and medicines, genetic and environmental factors relevant to populations living in low-income countries are not being considered.
The non-profit AstraZeneca/Oxford vaccine was developed with global equity of access in mind; however, early phase I/II trial cohorts may have an underrepresentation of some non-white ethnicities. Of the four trials being conducted by AstraZeneca (in the UK, Brazil, and South Africa), the interim trial report for the UK and Brazil trials revealed that 82.7% of the cohort were white. These cohorts with 23 848 participants were significantly larger than the South Africa trial cohort which consisted of 70.5% black-African, 14.9% mixed-race and 12.8% white but had just 2,026 participants. A bias towards running larger trials in certain countries is likely contributing to the underrepresentation of certain groups in global trial data.
In the United Kingdom, there is also evidence of underrepresentation of some ethnicities among clinical trial cohorts. A recent review found that in the UK, despite South Asians representing just over 11% of the type-2 diabetes population, only 5% out of 12 trial cohorts was of South Asian descent. This problem is compounded by a pervasive lack of ethnicity recording in medical research. Despite early data suggesting that COVID-19 was disproportionately affecting non-white ethnicities in Western countries, a review of the literature found that of 1,106 COVID-19 research papers and pre-prints only 51 included information about ethnicity in their reports. The link between early COVID-19 hospitalisations and patient ethnicity was later attributed to factors such as disproportionately working in public-facing roles and a higher prevalence of comorbidities such as type-2 diabetes in these populations. Insights such as these are crucial for directing public health policy, yet this analysis was impeded by the lack of ethnicity recording in research publications. Unlike in the US, there is currently no legal obligation to record ethnicity in research studies in the UK. Some of these issues are starting to be addressed by the Innovations in Clinical Trial Design and Delivery project for disadvantaged groups (INCLUDE) from the UK’s National Institute for Health Research. This project aims to widen the inclusion of many underserved groups, including certain ethnic groups, in the field of research.
Reasons for the under-representation of certain groups in UK trials are multifaceted. Some communities lack access to nearby hospitals that are running trials. Others may face cultural barriers such as trial information only being available in English. A lack of trust between certain communities and the medical profession may also be playing a role.
Mistrust in the medical community stems from both historic and ongoing mistreatment of people by the medical profession. The most famous example is the Tuskegee experiment between the 1930s-70s, in which hundreds of black men with syphilis were denied life-saving penicillin treatment in the name of medical research. Another is that in the 1960’s Puerto Rican women were exploited in the testing of the oral contraceptive pill and were subject to compulsory surgical sterilisation. Incidents of unethical practices by the medical profession continue to harm certain communities more recently. In 2012, American doctors pretended to give Hepatitis-B vaccinations to people in Pakistan in a ploy to obtain the DNA of relatives to Osama Bin Ladin. In 2020, the World Health Organisation was criticised for the lack of consent in its pilot study of a Malaria vaccine which was linked to a 10-fold increase in meningitis cases among recipients. Ongoing incidents such as these fail to assert a healthy exchange of honesty and trust between communities and the Western medical profession. As such, there may be an understandable lack of trust from some communities.
In order to achieve control of infectious diseases, we need equitable access to vaccines and medicines globally. Researchers and research funders need to focus on addressing the psychosocial barriers to the recruitment of ethnically diverse cohorts both globally and in the UK. Having cohorts that reflect our communities is the first step in ensuring that everyone can benefit from new therapies.
Lauren Lee is a third-year PhD student at Lucy Cavendish College studying tubercolsis pathogenesis.