What is the question that the research addressed?
In the United States, some racial and ethnic groups experience worse health outcomes [1] and tend to be diagnosed later for certain conditions. This may also be true for PIDDs – a group of more than 500 rare, chronic, and often genetic disorders that impair the immune system, making individuals highly susceptible to recurrent, severe, or persistent infections. Present from birth, they affect approximately 500,000 people in the US, often causing debilitating health issues, poor growth, and, in severe cases, fatal infections [2]. Although it is suspected that there may be wide disparities amongst different ethnicities in how PIDDs are diagnosed and treated, there are few studies examining the issue and existing studies have conflicting results.
To understand whether differences in diagnosis or care might exist, we wanted to know which populations are actually included in research studies and how observational trials report race and ethnicity. If studies do not accurately record race and ethnicity, it is difficult to tell whether:
- Some groups are being underdiagnosed.
- Some conditions are more common in certain populations.
- Differences between groups are mainly due to access to healthcare.
The question that we set out to answer was how often and how well US studies of PIDDs report race and ethnicity and whether the people included in the studies reflect the US population.
What is the difference between race and ethnicity?
While the terms ‘race’ and ‘ethnicity’ are often (incorrectly) used interchangeably, they represent two distinct ways of categorising people.
Race is a social category based on visible physical markers, and ‘races’ may vary between countries. Examples of races included in the current FDA guidance [3] are Asian, Black or African American, Native Hawaiian or other Pacific Island, and White. In comparison, ethnicity is about shared culture; it describes a sense of belonging to a group that shares common ancestral, national or cultural experience. You can be the same ‘race’ as someone else but belong to a different ‘ethnicity’. For example, someone who identifies as Hispanic or Latino may have a Cuban, Mexican, Puerto Rican, or South/Central American ethnicity.
What type of study did we do?
We undertook a scoping review to map and describe a representative sample of the available research. The study involved:
- Searching MEDLINE for observational studies taking place in the US.
- Extracting the reported data on participant race and ethnicity from recent, large studies (from 2014 onwards) identified in the search.
- Comparing the race and ethnicity reporting in the studies with US Food and Drug Administration (FDA) recommendations [3].
- Comparing the racial makeup of study participants with the 2020 US Census to see whether study populations were representative of the wider US population.
How many studies were found?
126 studies were identified; all 126 studies were assessed to determine the proportion that reported the race and ethnicity of participants. 25 of the largest studies were analysed in further detail.
How was race and ethnicity reported in the studies?
Out of 126 eligible studies, only half (49%) reported any information on race or ethnicity. Of the 25 studies analysed in further detail, the majority (72%) did not follow current FDA-recommended standards at the time of publication:
- Many did not separate race and ethnicity.
- Some treated “Hispanic/Latino” as a race rather than an ethnicity.
- Some combined distinct categories that should be reported separately.
A few only reported the proportion of White participants, grouping all other races together.
This discrepancy makes it difficult to interpret or compare results across studies, which is important for scientific accuracy.
Who was included in the studies?
In every study, White participants were the largest group, often making up more than half of the sample. Black/African American participants were usually the second largest group, but in much smaller proportions.
Fewer than one-third of studies reported ethnicity separately. When ethnicity was reported, the proportion of Hispanic/Latino participants varied widely.
How does the population in the studies compare with the US population?
For every type of PIDD examined, the racial distribution of study participants was significantly different from the US population overall. In other words, the people included in these studies do not reflect the country’s overall demographics.
What are the implications of this?
Our study showed that participant race and ethnicity are often not reported by study authors, and that many studies on PIDDs appear not to be representative of the wider population. Where race and ethnicity are reported, it is often not reported in a standardised way. This means that it is currently very difficult to determine whether PIDDs are truly underdiagnosed in certain races and ethnicities, or whether there is a differing incidence of PIDDs within certain populations.
With the increased use of AI tools in healthcare, it is particularly important for clinical trial data to be as robustly representative of the population as possible; these future diagnostic systems can only ‘learn’ from the data that is available.
Is this likely to be case for other health conditions as well?
It is possible that similar issues relating to the collection and reporting of participant race and ethnicity may impact studies in other rare disease indications and geographical locations. However, additional work would be required to establish whether this is the case, and if so, which indications may be particularly impacted. The underrepresentation of minority groups in trial reporting in general has come under scrutiny in several reviews, with a recent UK-based study of 3 high-impact journals [4] finding that only around half the studies assessed reported some ethnicity data, and more than a third of these did not provide a detailed ethnicity breakdown. Although some journals have introduced mandatory requirements for reporting representation, researchers have called for more action earlier in the clinical trial pipeline to ensure that funders and trialists collaborate to enable trial teams to include ethnic minority participants as well as to capture detailed ethnicity data.
What did we conclude?
Improving the accuracy and consistency of data collection and reporting is essential for understanding who is affected by these diseases and for ensuring equitable access to diagnosis and care.
Read the research in full.
What is YHEC?
YHEC integrates advanced methodological expertise with a detailed understanding of the rare diseases space. The team is experienced in synthesising heterogeneous evidence sources to develop robust and transparent research. This approach is complemented by the systematic incorporation of patient-reported outcomes and lived experience, alongside explicit consideration of health equity and inclusion.
Visit our website for more information on our work in the rare diseases space.
