Motivation to Clinical Trial Participation: Health Information Distrust and Healthcare Access as Explanatory Variables and Gender as Moderator.

: There is significant underrepresentation in clinical trials across diverse populations. Less is known about how health system-related factors, such as relationships and trust, mediate the motivation for clinical trial participation. We aimed to investigate whether health system-related factors explain the association between sociodemographic factors and motivation for participation. Additionally, we explored whether the mediating effects differ by gender. : We used the Health Information National Trends Survey 2020 cycle-4 data. Motivation for clinical trial participation, assessed through eight items, was the outcome variable (range 1-4). Predictors included age, race, ethnicity, education, general health, and depression. The health system-related explanatory variables were health information distrust, having a regular provider, and the frequency of healthcare visits. Gender was the moderator. A structural equation model (SEM) was used for the overall and gender-stratified analyses. : Among the 3865 participants (mean [SE] age of 48.4 [0.53] years, 51.4% women, and 24.3% non-White), older age (β = -0.170; < 0.001) and non-White race (β = -0.078; < 0.01) were negatively associated, and higher education (β = 0.117; < 0.001) was positively associated with motivation. Higher distrust (β = -0.094; < 0.01) decreased motivation, whereas having a regular provider increased motivation (β = 0.087; < 0.01). The gender-stratified SEM revealed that women, but not men, with higher distrust showed lower motivation (β = -0.121; < 0.01), and men, but not women, with a regular healthcare provider showed higher motivation (β = 0.116; < 0.01). : Our study found that women with higher distrust showed lower motivation, while men with a regular healthcare provider demonstrated higher motivation. These gender differences highlight the need for tailored recruitment approaches that account for their distinct relationships with the health system.