Why Equity Needs to Become Obligatory

When Sadia Haqnawaz went in for her 20-week scan, she heard words that no pregnant woman wants to hear.

“It was quite quiet for a long time and the sonographer said that he’s having trouble looking at the scan because there’s no fluid, there’s no amniotic fluid. And as soon as he said that, I said, ‘I think I know what this is,’” she recalled.

At this point, her sister had already lost two babies to a genetic condition called autosomal recessive polycystic kidney disease, but no one had read anything into it.

“We always assumed it was an issue with her and her husband, never assumed that it was the wider family and that [it] was our limited understanding of genetics and how this works,” said Sadia.

Tests revealed that Sadia, a British-born Pakistani Muslim, had inherited the faulty gene, although her husband—who is her first cousin—did not have it. Her parents, who are also first cousins, both carried it as well but had been lucky enough to have seven healthy children.

Sadia decided to continue with her pregnancy even though she knew the chances of survival were slim. “To get to 20 weeks was such a big thing for me,” she said, remembering the six years of fertility struggles that followed the birth of her first son. Sadia’s daughter sadly died at 32 weeks and her treatment—albeit nearly 20 years ago now—has shaped Sadia’s feelings around the U.K. healthcare system.

“As soon as you say I’m married to a cousin, that’s it. Everyone kind of loses that sympathy for you. It’s your own fault. You feel like you are blamed,” she explained.

“I was forced into a marriage at 16, in school, but I feel like that’s overlooked sometimes,” she continued. “Yes, I’m still with my husband. I feel like I was lucky in that sense because we kind of both wanted that freedom from our family, so we connected. But it’s not always like that. There’s horror stories out there … There’s not that trust with authority, with healthcare, with governments,” she continued, highlighting skepticism over vaccines and treatments rolled out during the COVID-19 pandemic.

“There’s a lot of work that needs to be done to build that trust. And I think part of that is to do with showing the benefits of genetic testing. So, having some good case studies to show that this is a positive story of genetic testing and genomic medicine, having stories like that, that actually you can relate to,” can help, she said.

Medical mistrust has been identified as a key barrier in a major U.K. report on ethnic inequalities in genomics and precision medicine, released earlier this year by the NHS Race and Health Observatory.

Its chief executive Habib Naqvi, PhD, said that the pandemic shined a spotlight on pre-existing inequalities in health, with stark differences in outcomes based on race and ethnicity.

”What we’ve seen so vividly, particularly over the COVID years, has been a breakdown in levels of trust and confidence amongst our diverse communities with regards to not just healthcare, but more widely around other aspects of society and structures within society,” he maintained.

“And trust is fast becoming a determinant of health. It’s determining people’s choices as to whether they take up a medical intervention or whether or not they take part in clinical research associated with genomics or genetics.”

This mistrust has not been misplaced in the past. The Observatory’s senior clinical advisor Veline L’Esperance, PhD, pointed to the infamous Tuskegee Experiment of 1932, in which hundreds of Black men with syphilis were deceived into thinking they were receiving treatment for their “bad blood” but only received placebos so that full disease progression could be studied.

The experiment continued until 1972, almost 30 years after effective antibiotics became available, with many participants going blind, becoming insane, or dying in the interim.

“It is important to understand, acknowledge, and address the historical wrongs experienced by Black and ethnic minority groups through participation in clinical trials,” said L’Esperance, who calls for research to be done in partnership with patients from diverse groups.

“Diverse representation amongst researchers, senior leaders, and clinicians which reflect the communities they serve is essential in rebuilding this trust,” she added.

The situation remains imperfect more than 50 years later, with medical devices and assessments still being designed, developed, and rolled out in a way that can leave some communities behind. The NHS Race and Health Observatory’s seminal report in 2021 highlighted racial bias in estimating blood oxygen levels using a pulse oximeter, which remains commonly used throughout the British healthcare system. The device may lead to delays in identifying dangerously low oxygen levels in patients with darker skin tones, which would usually trigger referral to more intensive care. The Observatory’s report drove the U.K. government to commission an independent review into equity in medical devices.

Similarly, the Apgar score that is used to check a baby’s health shortly after birth still includes a measure for skin colour and can miss jaundice or cyanosis in Black babies or those of Asian origin.

“Judging the health of a baby minutes after its birth partly based upon the colour of its skin was not right in 1952 when the Apgar score was rolled out and is certainly not right today in 2024,” said Naqvi, whose organisation commissioned a review on the topic.

“And that score is still being used in maternal units across the country, not just in this country but in parts of Africa as well.”

The vast majority of research used to understand risk factors and treatments remains rooted in populations with predominantly European ancestry, particularly for genomics where around 90% of advanced genetic data is sourced from European ancestry populations.

This lack of variety affects our understanding of genetic variation and can contribute to health inequalities, warned Raghib Ali, MD, CEO and chief executive of Our Future Health U.K., the U.K.’s largest health research program.

“Whether you’re looking at risk factors or treatments or preventative interventions, if we haven’t got data from ethnic ancestry populations—we can’t really call them minorities in a global context, but non-European—then it’s very difficult to prove that either the risk factors operate in the same way or that treatments operate in the same way or side effects or efficacy, et cetera,” he explained.

Efforts are being made to redress the situation. In China, the Kadoorie Biobank has collected information from over half a million people from a mix of urban and rural settings, making it one of the world’s largest prospective cohort studies.

Although the Middle East has generally lagged in this field, the Iranome Genomic Database has sequenced the exomes of hundreds of Iranian citizens from eight major ethic groups. Last year, the United Arab Emirates unveiled a 10-year national genome strategy to collect a million samples from its population to hasten the development of personalized, preventive, and precision medicines to combat chronic and genetic diseases.

Similar studies have also begun in India, Pakistan, Singapore, and Malaysia. The U.K.’s South Asia Biobank is aiming to recruit 100,000 people of South Asian origin across the country. In Africa, the Wellcome Trust has been funding the Africa Genome Variation Project, which aims to map 2.5 million genetic variants from 10 sub-Saharan ethnic groups, sampling 100 people from each group.

“The biggest imbalance just by sheer population numbers and data is probably still South Asia, then possibly Southeast Asia, then Sub-Saharan Africa,” said Ali.

“They’re all well behind where they need to be. So until we get more data from those populations, we’ll always have a lack of understanding.”

Essential metrics taken for granted when calculating risks for heart disease, diabetes, and cancer are mostly based on European descendants. This can have consequences when attempting to extrapolate to other populations.

“Even for something very simple like smoking and lung cancer, it doesn’t operate in the same way for a European ancestry population versus a Chinese population,” said Ali.

“BMI and diabetes—again, there’s data that they don’t operate in the same way, cholesterol and heart disease.”

The same problems extend to treatments. “There’s data that not all medicines work in the same way in very different ethnic groups. There’s been some recent evidence for clopidogrel, which is widely used in heart disease, that it doesn’t work as well in people of South Asian origin.”

For these patients, who tend to be at high risk of heart disease and diabetes, such issues can exacerbate the health disparities they face compared with their White counterparts.

“There are more examples than that, but just as a general principle you’ll never have good evidence—or a good evidence base—for these ethnic groups until they’re included in large numbers in research,” said Ali.

Our Future Health U.K. is in the unique position of being able to collect information from a diverse multi-ethnic population within a single healthcare system, with linked NHS records. This enables the organization to not only test risk factors but also carry out clinical trials in the U.K. population. Recruitment began about 20 months ago and the study has collected questionnaire data from around a million volunteers, alongside 300,000 genomes and 600,000 linked NHS data points. Participants are eligible from the age of 18, allowing the study to run far longer than others that recruit in middle age.

Ali anticipates that it could continue for a century.

He called the approach “precision prevention or precision public health” in its attempts to use measures such as polygenic risk scores to identify people at higher risk based on their susceptibility.

“Of course, it’s primarily a U.K. study, but it has an importance internationally as well,” he maintained. “Our intention and our aim is to make it not just the largest study in the U.K., which it already is, not just the largest in the world by absolute numbers, but the largest in the world by being multi-ethnic as well.” The aim is to recruit five million people altogether, of whom 10% will be from a non-European ancestry background.

“That’d be 500,000 people, which would be by far the biggest multi-ethnic cohort in the world. The biggest ones in the world currently are I think around 100,000. So this would really be much, much bigger.”

The findings will hopefully provide greater information on risk factors and treatments for the seven big minority groups in the U.K.: Indian, Pakistani, Bangladeshi, Black African, Black Caribbean, Chinese, and Eastern European. The last group is underrepresented in global databases as well.

Commercial pharma is also getting in on the act, working to better understand primary risk factors for chronic conditions across the globe. Boehringer Ingelheim was first to invest in the Precision Health Research, Singapore (PRECISE) initiative, which provides insights into underrepresented Asian populations.

“This diverse clinical research is crucial for the advancement of precision medicine, leading to new treatment approaches, novel therapies, and earlier diagnoses for individuals at greater risk for certain diseases,” said Boehringer’s SVP global head of translational medicine and clinical pharmacology Vittoria Zinzalla, PhD.

“Other companies like AbbVie, Bayer, and Novo Nordisk have followed suit in funding PRECISE.”

Nonetheless, there remains another vital element that lies outside, but is intertwined with, race and ethnicity that determines health across the globe and needs to be considered.

“For many diseases, I mean for nearly every disease, people from poorer backgrounds certainly do worse than those from richer backgrounds,” Ali pointed out.

His study is making determined efforts to include volunteers from all socioeconomic groups by working with clinics all over the country, including some in more deprived rural and coastal areas.

“In terms of the disease picture as a whole, social determinants of health are by far the biggest contributor to inequalities, much more so than genetics,” he stressed. “That’s not just in the U.K., but globally as well. Poverty basically.”

The NHS Race and Health Observatory also acknowledges the role of these social determinants of health and points to their underlying causes.

“Ethnic inequality is affected by deeply ingrained systemic inequalities in employment, housing, justice, education,” said Naqvi. “We must therefore focus on the ‘causes of the causes’ of health inequities if we are to achieve meaningful outcomes.”

Anita Chakraverty is a U.K.-based journalist who has been writing about medicine and health across several international publications for more than 20 years. In her spare time, she enjoys reading, films, and walks in the countryside.