MASH Clinical Trials Historically Underrepresent Certain Groups

Racial and ethnic minority populations continue to be underrepresented in randomized controlled trials (RCTs) of metabolic dysfunction–associated steatohepatitis (MASH), although inclusion of female and Hispanic/Latino populations has increased over time, a meta-analysis published in the journal Liver International found.¹ The findings are important because they suggest the results of trials may have limited applicability for racial and ethnic minorities.

The study authors explained that MASH involves a complicated “systematic metabolic milieu.” Insulin resistance and metabolic dysfunction contribute to the disease, which can cause cirrhosis, hepatocellular carcinoma, and extrahepatic complications like cardiovascular disease and chronic kidney disease.

The authors explained that underrepresentation of certain groups and countries in MASH clinical trials can be addressed through better collaboration and novel methodologies. | Image credit: Jo Panuwat D - stock.adobe.com

As such, they said, there is a pressing need to better understand how the disease occurs and to diagnose the disease in its earliest stages to reverse its progression and diminish the risk of associated comorbidities. On the pharmaceutical front, progress has been made. Most notably, the Food and Drug Administration approved resmetirom (Rezdiffra; Madrigal Pharmaceuticals) based on results of a double-blind, placebo-controlled trial that found the therapy led to resolution of MASH or an improvement in liver scarring in many patients.²

Yet, as more and more research is conducted examining potential therapies and strategies for treating MASH, the authors noted it is important for investigators to ensure their work is reflective of the diversity of the MASH patient population.³

The systematic review and meta-analysis aimed to better understand the degree to which existing research is representative of patients with MASH and to see whether the degree of representation has changed over time.¹

The investigators searched 2 scientific databases in search of RCTs of MASH pharmacotherapies that were published through December 13, 2024. They found a total of 109 studies that met their inclusion criteria. Those studies involved data from 112 RCTs (the latter number exceeds the number of published studies because 3 studies each reported data from 2 trials). Together, the studies included 19,516 participants with MASH.

Overall, 33 of the trials were multi-continental, but most were conducted on a single continent (most commonly North America, where 41 trials were conducted). Most (69.4%) of the 49 countries in which trials took place qualify as high-income countries according to World Bank classifications, the authors noted.

The investigators found females made up 54.23% of the total pooled trial population (95% CI, 51.31-57.12). Notably, the investigators said female participation was significantly higher in trials in which pharmaceutical companies were involved, compared with trials where drug developers were not involved.

While all but one of the 112 trials reported participants’ sex, only 69 trials (61.6%) included participants’ race. The investigators said the percentage of trials reporting participants’ race increased greatly over time.

Race data showed the vast majority (87.63%) of participants in trials were White (95% CI, 85.37-89.58). Asian participants made up about 5% of the pooled trial populations (4.95%; 95% CI, 3.42-7.10), and Black participants made up just 2.27% of the pooled population (95% CI, 1.89-2.71). Slightly less than one-third of participants were Hispanic or Latino (31.42%; 95% CI, 26.61-36.66). As with female participation, the investigators noted the proportion of Hispanic/Latino patients increased over time.

The authors explained that underrepresentation of certain groups and countries in clinical trials can be addressed through better collaboration and novel methodologies. They added that more work should be done to identify and guard against implicit bias or unconscious discrimination within the healthcare system.

From a clinical standpoint, more diverse trials would help better clarify potential differences in disease and therapeutic outcomes among different racial and ethnic groups, the authors noted. They added that social determinants of health should also be included in future studies alongside more robust demographic information. The heterogeneity of MASH, along with the role of genetic factors in the disease, show that broad representation in clinical trials must be a top priority.

“MASH is a heterogeneous disease with a complex interplay of genetic factors, environmental exposures, and social determinants of health,” the authors concluded. “Hence, the inclusion of different patient populations in research has important clinical implications.”

References

1. Souza M, Al-Sharif L, Diaz I, et al. Representation of sex, race and ethnicity in mash randomised controlled trials: a systematic review and meta-analysis. Liver Int. 2025;45(4):e70029. doi:10.1111/liv.70029
2. Harrison SA, Bedossa P, Guy CD, et al. A phase 3, randomized, controlled trial of resmetirom in NASH with liver fibrosis. N Engl J Med. 2024;390(6):497-509. doi:10.1056/NEJMoa2309000
3. Knepper TC, McLeod HL. When will clinical trials finally reflect diversity?. Nature. 2018;557(7704):157-159. doi:10.1038/d41586-018-05049-5