Published online Aug 27, 2020. doi: 10.4254/wjh.v12.i8.506
Peer-review started: April 13, 2020
First decision: April 29, 2020
Revised: July 9, 2020
Accepted: July 26, 2020
Article in press: July 26, 2020
Published online: August 27, 2020
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the United States and has a heterogeneous distribution across racial and ethnic groups, with a disproportionate burden among Hispanics. Although it remains unclear why Hispanics are at a higher risk of developing NAFLD and nonalcoholic steatohepatitis (NASH), there is likely an interplay of multifactorial causes including genetics, culture, socioeconomic status and environment. Despite this high burden of disease, there are currently no approved therapies for the treatment of NAFLD. Several promising therapies are currently being investigated in clinical trials but it is unknown if Hispanics are appropriately represented in these clinical trials.
Identifying possible racial disparities is the first step in improving targeted interventions for patient subgroups. The purpose of this systematic review and meta-analysis was to characterize the participation rate of different races and ethnicities in clinical trials investigating therapies for NAFLD.
The aim of this study was to evaluate the enrollment of Hispanics in NAFLD trials conducted in the United States and Canada. We hypothesized that the expected rate of Hispanics in NAFLD therapy trials should be proportionate to the burden of disease among Hispanics within the NAFLD population.
The literature search was performed using the PubMed (US National Institutes of Health, Bethesda, MD, United States) database from January 1, 2005 to March 31, 2019 using the following search terms: Nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, and fatty liver. Randomized controlled trials (RCTs) or prospective cohort studies conducted in the United States and Canada with human subjects aged 18 years or older were included. Descriptive statistics were performed with frequencies and proportions reported. Two-tailed z-test was performed to compare differences in proportions. All meta-analyses were performed using random effects models and results were pooled using the maximum likelihood estimation.
Of the 38 trials that met eligibility criteria, twenty-five reported racial information. Among these only 17 (68%) provided data on ethnicity (participation of Hispanic patients). Among the 2983 patients enrolled in all eligible trials, a total of only 346 (11.6%) Hispanic participants was reported. Among the 17 trials that reported Hispanic participation, there were 346 Hispanic patients out of 1577 total enrolled patients with a participation rate of 21.9% compared to 74.8% of Caucasian participants among those including data on Caucasian participation. A meta-analysis was then performed to estimate pooled prevalence while taking heterogeneity of included studies into consideration. The pooled prevalence was found to be 24.3% (95%CI: 16.6-32.0) with significant heterogeneity (I2 = 94.6%). To determine if rates of Hispanic enrollment changed over time, studies conducted before and after 2015 were compared. The pooled prevalence of Hispanic patients in studies from 2005-2014 was 15%, compared to 37% for studies from 2015-2019.
North American clinical trials of NAFLD from 2015-2019 did not consistently include data on Hispanic participation. Among trials that did include racial/ethnic demographic data, Hispanic patients may be underrepresented relative to the burden of NAFLD and NASH among this population.
Future efforts aimed at improving or standardizing reporting of race in clinical trials and at increasing enrollment of diverse and representative study populations are needed to address this disparity. It is not known whether the low rate of Hispanic participation in these trials is due to lack of collection of ethnic demographic data on behalf of the investigators, failure to report ethnicity by subjects, or true under-enrollment. Despite the benefits of diversity in trial enrollment, minority patients have historically been underrepresented in clinical trials. Barriers to minority participation in clinical trials include mistrust of providers/research, reduced access to healthcare, financial and time constraints, lack of education about clinical trials, and cultural or language differences impairing communication with trial recruiters or providers. Interventions such as provision of Spanish-speaking recruitment materials or personnel have been shown to improve enrollment of Hispanic patients in clinical trials and serve as potential targets for increasing diversity of study populations for NAFLD.