Disparities based on sex, age, and race and ethnicity continue in both US and international clinical trial enrollment for primary liver cancer (PLC), according to study results published in Gastroenterology.

Investigators conducted a systematic search of the US ClinicalTrials.gov database from inception through July 2019 for all studies assessing treatment efficacy in adult patients with PLC. Data on trial phase, study location, therapeutic type, and funding source were extracted. Disparities in enrollment by sex, race, and ethnicity were explored using study-reported demographics. In a separate analysis, authors calculated an “enrollment fraction,” or the number of trial enrollees of a certain group divided by the estimated number of patients with liver cancer in that same group. The latter population was estimated using the US Cancer Statistics Database.

Sixty-three trials met inclusion criteria: 30 (47.6%) were sponsored by academic institutions; 21 (33.3%) were sponsored by industry; and 12 (19.1%) were sponsored by the National Institutes of Health. The majority of trials (n=44; 69.8%) were limited to US-only enrollment, though 19 (30.2%) were international. The sex of participants was reported by all trials, but just 26 (41.2%) and 21 (33.3%) trials reported enrollment data on race and ethnicity, respectively. Patient age was reported by 28 trials (44.4%). A greater proportion of US-based trials reported race and ethnicity data compared to international studies (45.4% vs 36.8%). The fraction of studies reporting race and ethnicity enrollment data increased over time, from 29.0% for publication years 1998-2008 to 54.2% for 2009-2018 (P =.04). The proportion of studies reporting age also increased between these periods, though not significantly (43.0% vs 48.5%; P =.66).


Continue Reading

Underrepresentation of racial and ethnic minority populations was observed across all trial subgroups, including subgroups defined by trial phase, trial funding source, and therapeutic type. Hispanic patients accounted for an estimated 14.8% of PLC cases in the US, but comprised just 8.3% of US-only trial participants. Black patients comprised 14.4% of participants in US-only trials and 1.6% of participants in international trials, despite accounting for significantly more PLC cases globally. Asian patients comprised 9.0% of US-only trial cohorts and the majority (54.4%) of international cohorts. Across all studies, the proportion of White patients increased between the periods 1998-2008 and 2009-2018 (27.3% vs 49.5%).

Sex-based disparities were also observed; women were estimated to account for 26.4% of PLC cases in the US, but comprised just 22.7% of US-based cohorts. This sex disparity was more pronounced in international cohorts, with women comprising 17.1% of enrollees. Women were particularly underrepresented in phase 3/4 trials, industry-sponsored trials, and trials of systemic therapies. Older adults (>65 years) were also underrepresented relative to adults aged 18 to 64 years, with enrollment fractions of 0.18% and 0.23%, respectively. However, the proportion of older enrollees increased over time, from 36.7% in 1998-2008 to 54.0% in 2009-2018.

Results from this study underline disparities in clinical trial enrollment across subgroups defined by age, sex, and race and ethnicity. Study limitations included the absence of data on race and ethnicity and age in a number of studies.

“…[T]here are persistent inequities in PLC clinical trial participation, with underrepresentation of racial and ethnic minority groups, women, and older adults despite disproportionate increases in the burden of PLC in these populations,” the investigators wrote. “While awareness of the problem is the necessary first step, targeted efforts are needed to ensure equity in PLC trial enrollment and improve outcomes for all patients.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

Reference

Jan J, Osho A, Murphy CC, Mazure CM, Singal AG, Rich NE. Gender, age, racial and ethnic disparities in clinical trial enrollment for primary liver cancer. Gastroenterology. Published online March 11, 2022. doi:10.1053/j.gastro.2022.03.015